SCI 발표논문

전체 4,588편

23082017

제1저자 김미화 · 교신저자 오도연

, , , , ,
Resistance Mechanism against Trastuzumab in HER2-Positive Cancer Cells and Its Negation by Src Inhibition.
Mol Cancer Ther. 2017;16(6):1145-1154.

Abstract
Trastuzumab in combination with chemotherapy is the standard of care for patients with human epidermal growth factor receptor 2 (HER2)-positive breast and gastric cancers. Several resistance mechanisms against anti-HER2 therapy have been proposed. Src activation has been suggested to be responsible for the resistance of HER2-positive breast cancer. In our study, we generated four trastuzumab-resistant (HR) cancer cell lines from HER2-amplified gastric and biliary tract cancer cell lines (SNU-216, NCI-N87, SNU-2670, and SNU-2773). Elevated Src phosphorylation was detected in SNU2670HR and NCI-N87HR cell lines, but not in SNU216HR or SNU2773HR cell lines. In SNU216HR and SNU2773HR cell lines, phospho-FAK (focal adhesion kinase) was elevated. Bosutinib as a Src inhibitor suppressed growth, cell-cycle progression, and migration in both parental and HR cell lines. Specifically, Src interacted with FAK to affect downstream molecules such as AKT, ERK, and STAT3. Bosutinib showed more potent antitumor effects in Src-activated HR cell lines than parental cell lines. Taken together, this study suggests that Src inhibition may be an effective measure to overcome trastuzumab resistance in HER2-positive cancer. Mol Cancer Ther; 16(6); 1145-54. ©2017 AACR.
PubMed IF 6.9 혈액종양내과
23072017

제1저자 김형우 · 교신저자 황진혁

, , , , , , , ,
Adjunctive role of preoperative liver magnetic resonance imaging for potentially resectable pancreatic cancer.
Surgery. 2017;161(6):1579-1587.

Abstract
BACKGROUND The adjunctive role of magnetic resonance imaging of the liver before pancreatic ductal adenocarcinoma has been unclear. We evaluated whether the combination of hepatic magnetic resonance imaging with multidetector computed tomography using a pancreatic protocol (pCT) could help surgeons select appropriate candidates and decrease the risk of early recurrence.
METHODS We retrospectively enrolled 167 patients in whom complete resection was achieved without grossly visible residual tumor; 102 patients underwent pCT alone (CT group) and 65 underwent both hepatic magnetic resonance imaging and pCT (magnetic resonance imaging group).
RESULTS By adding hepatic magnetic resonance imaging during preoperative evaluation, hepatic metastases were newly discovered in 3 of 58 patients (5%) without hepatic lesions on pCT and 17 of 53 patients (32%) with indeterminate hepatic lesions on pCT. Patients with borderline resectability, a tumor size >3 cm, or preoperative carbohydrate antigen 19-9 level >1,000 U/mL had a greater rate of hepatic metastasis on subsequent hepatic magnetic resonance imaging. Among 167 patients in whom R0/R1 resection was achieved, the median overall survival was 18.2 vs 24.7 months (P = .020) and the disease-free survival was 8.5 vs 10.0 months (P = .016) in the CT and magnetic resonance imaging groups, respectively (median follow-up, 18.3 months). Recurrence developed in 82 (80%) and 43 (66%) patients in the CT and magnetic resonance imaging groups, respectively. The cumulative hepatic recurrence rate was greater in the CT group than in the magnetic resonance imaging group (P < .001).
CONCLUSION Preoperative hepatic magnetic resonance imaging should be considered in patients with potentially resectable pancreatic ductal adenocarcinoma, especially those with high tumor burden.
PubMed IF 3.2 소화기내과
23062017

제1저자 김윤기 · 교신저자 서정원

, , , , , , , , , ,
A laboratory association between hemoglobin and VerifyNow P2Y12 reaction unit: A systematic review and meta-analysis.
Am Heart J. 2017;188:53-64.

Abstract
BACKGROUND VerifyNow P2Y12 assay is used widely to evaluate residual platelet reactivity in patients taking P2Y12 receptor antagonists. However, a laboratory association between VerifyNow P2Y12 reaction unit (PRU) and hemoglobin, which might lead to wrong interpretation of the data, is reported. We performed these systematic review and meta-analysis to clearly define the relationship between PRU and hemoglobin and to elucidate whether the relationship, if any, is a true biological association or is just a laboratory error.
METHODS Through a comprehensive electronic and manual search, 10 studies were selected for the cohort level meta-analysis. Among 10 studies, we were able to retrieve the raw data of 5 studies, and a patient-level meta-analysis was performed. Potential publication bias was searched by funnel plot analysis and was actively adjusted, if present, by trim and fill method.
RESULTS The pooled analysis revealed a significant inverse correlation between PRU and hemoglobin (r=-0.349; P<.001; 10 studies with 4,793 patients). VerifyNow P2Y12 base unit, which reflects off-drug platelet reactivity, was also inversely correlated with hemoglobin (r=-0.526; P<.001; 8 studies with 4,395 patients). % Inhibition (r=0.081; P=.059; 6 studies with 3,832 patients) and ΔPRU (r=-0.037; P=.188; 5 studies with 3,521 patients) were not associated with hemoglobin. A significant inverse association between PRU and hemoglobin was also observed in the patient-level meta-analysis (3,533 patients pooled from 5 studies; r=-0.335; P<.001). Light transmission aggregometry (r=0.160; P=.072; 4 studies with 1,144 patients) and multiple electrode platelet aggregometry (r=-0.029; P=.394; 3 studies with 7,645 patients) showed no significant association with hemoglobin.
CONCLUSIONS A significant inverse association was observed between PRU and hemoglobin which is likely to be a laboratory error. Clinicians should be aware that this association might lead to wrong interpretation of the data.
PubMed IF 3.4 순환기내과
23052017

제1저자 박경택, 김학령 · 교신저자 조주희

, , , , , , , ,
Association between reduced arterial stiffness and preserved diastolic function of the left ventricle in middle-aged and elderly patients.
J Clin Hypertens (Greenwich). 2017;19(6):620-626.

Abstract
The aim of this study was to investigate whether arterial stiffness plays a role in retaining normal diastolic function in a middle-aged and elderly Korean population. A total of 267 patients without documented cardiovascular disease, 50 years and older (mean age, 57.3±6.3 years; 69.8% men) were retrospectively analyzed. All patients underwent both transthoracic echocardiography and brachial-ankle pulse wave velocity measurement on the same day. Patients with septal annular peak velocity (e') ≥8 cm/s and left atrial volume index <34 mL/m² were considered as having normal diastolic function. Ninety-eight patients (36.7%) had normal diastolic function. Low brachial-ankle pulse wave velocity (<1314 cm/s) was an independent factor for determining normal diastolic function even after controlling for potential confounders in multiple logistic regression analysis (odds ratio, 2.58; 95% confidence interval, 1.46-4.57; P=.001). Our results suggest that compliant arteries may play an important role in maintaining normal left ventricular diastolic function in middle-aged and elderly patients without documented cardiovascular disease.
PubMed IF 2.9 순환기내과
23042017

제1저자 이진우 · 교신저자 박영식

, , , , , , , ,
The additional role of Xpert MTB/RIF in the diagnosis of intrathoracic tuberculous lymphadenitis.
J Infect Chemother. 2017;23(6):381-384.

Abstract
BACKGROUND Diagnosis of intrathoracic tuberculosis (TB) lymphadenitis remains a challenge because of difficulties in obtaining adequate tissue and the lack of a sensitive test. Recently, Xpert MTB/RIF assay is being used for rapid diagnosis of pulmonary TB, but it has not yet been widely validated in intrathoracic TB lymphadenitis. The aim of this study was to assess the additional role of Xpert MTB/RIF in diagnosing intrathoracic TB lymphadenitis using endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) specimen.
METHODS Consecutive patients who underwent Xpert MTB/RIF assay using EBUS-TBNA specimen from January 2012 and November 2013 at a tertiary referral hospital were recruited. Among them, the cases with malignant lymph nodes were excluded.
RESULTS Among 73 patients, 13 (17.8%) cases were diagnosed with intrathoracic TB lymphadenitis. In detail, 10 patients were diagnosed using conventional methods only (histology or AFB culture) and 3 patients were additionally diagnosed when adding Xpert MTB/RIF assay. The median time to diagnosis using Xpert MTB/RIF (1 day) was shorter than conventional methods (3 days for histology, 14 days for AFB culture). Rifampin resistance was not detected in any patients.
CONCLUSION In patients with enlarged intrathoracic lymph nodes and low suspicion of malignancy, combination of conventional diagnostic methods with Xpert MTB/RIF could lead to additional and rapid diagnosis of intrathoracic TB lymphadenitis.
PubMed IF 1.7 호흡기내과
23032017

제1저자 이소령 · 교신저자 최의근

, , , ,
Trends in the incidence and prevalence of atrial fibrillation and estimated thromboembolic risk using the CHA2DS2-VASc score in the entire Korean population.
Int J Cardiol. 2017;236:226-231.

Abstract
BACKGROUND Data on the epidemiology of atrial fibrillation (AF) and temporal trends are not well established in the Korean population. We aimed to estimate the incidence and prevalence of AF in Korea between 2008 and 2015.
METHODS Using the National Health Insurance Service database, we analyzed as a nationwide cohort the entire Korean adult population from 2008 to 2015 (n=41,505,679 in 2015). AF was identified by using diagnostic codes.
RESULTS During an 8-year period representing 314,311,360 person-years of follow-up, 496,341 individuals were newly diagnosed with AF. The incidence of AF increased to >1.12-fold as follows: from 15.34 to 17.14 per 10,000 person-years (p<0.001). We also found a 1.68-fold increase in the prevalence of AF, from 0.46% in 2008 to 0.67% in 2015 (p<0.001). The incidence and prevalence of AF increased with advancing age. The median age of the AF patients increased from 68 to 71years (p<0.001). The prevalence of diabetes and heart failure in AF subjects increased (p<0.001). The percentage of patients with a CHA₂DS₂-VASc score of ≥2, who were strongly recommended for anticoagulation treatment, increased from 80.2% to 86.8% (p<0.001).
CONCLUSION The incidence and prevalence of AF gradually increased from 2008 to 2015. The proportion of AF patients who were candidates for anticoagulation therapy also significantly increased owing to population aging and increasing comorbidities (i.e., heart failure and diabetes). These findings may provide a framework to understand the actual disease burden and establish the optimal management strategy for AF.
PubMed IF 3.3 순환기내과
23022017

제1저자 박석우 · 교신저자 이정표, 김영훈

, , , , , , , , , , , , ,
Metabolic Acidosis and Long-Term Clinical Outcomes in Kidney Transplant Recipients.
J Am Soc Nephrol. 2017;28(6):1886-1897.

Abstract
Metabolic acidosis (MA), indicated by low serum total CO₂ (TCO₂) concentration, is a risk factor for mortality and progressive renal dysfunction in CKD. However, the long-term effects of MA on kidney transplant recipients (KTRs) are unclear. We conducted a multicenter retrospective cohort study of 2318 adult KTRs, from January 1, 1997 to March 31, 2015, to evaluate the prevalence of MA and the relationships between TCO₂ concentration and clinical outcomes. The prevalence of low TCO₂ concentration (<22 mmol/L) began to increase in KTRs with eGFR<60 ml/min per 1.73 m² and ranged from approximately 30% to 70% in KTRs with eGFR<30 ml/min per 1.73 m² Multivariable Cox proportional hazards models revealed that low TCO₂ concentration 3 months after transplant associated with increased risk of graft loss (hazard ratio [HR], 1.74%; 95% confidence interval [95% CI], 1.26 to 2.42) and death-censored graft failure (DCGF) (HR, 1.66; 95% CI, 1.14 to 2.42). Cox regression models using time-varying TCO₂ concentration additionally demonstrated significant associations between low TCO₂ concentration and graft loss (HR, 3.48; 95% CI, 2.47 to 4.90), mortality (HR, 3.16; 95% CI, 1.77 to 5.62), and DCGF (HR, 3.17; 95% CI, 2.12 to 4.73). Marginal structural Cox models adjusted for time-varying eGFR further verified significant hazards of low TCO₂ concentration for graft loss, mortality, and DCGF. In conclusion, MA was frequent in KTRs despite relatively preserved renal function and may be a significant risk factor for graft failure and patient mortality, even after adjusting for eGFR.
PubMed IF 9.7 신장내과
23012017

제1저자 곽민선 · 교신저자 김동희

, , , ,
The preventive effect of sustained physical activity on incident nonalcoholic fatty liver disease.
Liver Int. 2017;37(6):919-926.

Abstract
BACKGROUND & AIMS Physical activity (PA) is inversely associated with nonalcoholic fatty liver disease (NAFLD) prevalence. However, few studies evaluated the effect of PA on NAFLD incidence in regard to visceral adipose tissue (VAT) and insulin resistance (IR). We investigated whether PA at baseline and change in PA during follow-up have any effect on incident NAFLD.
METHODS We enrolled subjects who underwent health screenings between 2007 and 2008 and participated in voluntary follow-up between 2011 and 2013 (median 4.42 years). Incident NAFLD was defined as NAFLD absence at baseline and presence at follow-up by ultrasonography. PA was measured using a detailed questionnaire-based metabolic equivalent at baseline and follow-up; the difference during follow-up was calculated.
RESULTS Of the 1373 subjects enrolled, 288 (21.0%) developed NAFLD. Both total and leisure-time PA at baseline were inversely associated with incident NAFLD (P for trend=.005 and .003 respectively). Decreased PA at follow-up was associated with increased incident NAFLD risk after adjusting for age, gender, body mass index, smoking, hypertension, diabetes and diet [hazard ratio (HR) 1.45, 95% confidence interval (CI) 1.04-2.02, 4th (most decreased PA) vs 1st quartile (increased PA), P=.028]. This relationship was attenuated but remained statistically significant after adjustment for VAT(HR 1.48, 95% CI 1.06-2.06, 4th vs 1st quartile) and IR(HR 1.59, 95% CI 1.11-2.27, 4th vs 1st quartile).
CONCLUSIONS This study shows an independent protective effect of PA at baseline on incident NAFLD after 4-year follow-up. Furthermore, sustained or increased PA had a preventive effect on incident NAFLD independent of VAT and IR.
PubMed IF 6.2 소화기내과
23002017

제1저자 김유림 · 교신저자 이연주

, , , , , , , , , , , , ,
Effectiveness Analysis of a Part-Time Rapid Response System During Operation Versus Nonoperation.
Crit Care Med. 2017;45(6):e592-e599.

Abstract
OBJECTIVES To evaluate the effect of a part-time rapid response system on the occurrence rate of cardiopulmonary arrest by comparing the times of rapid response system operation versus nonoperation.
DESIGN Retrospective cohort study.
SETTING A 1,360-bed tertiary care hospital.
PATIENTS Adult patients admitted to the general ward were screened. Data were collected over 36 months from rapid response system implementation (October 2012 to September 2015) and more than 45 months before rapid response system implementation (January 2009 to September 2012).
INTERVENTIONS None.
MEASUREMENTS AND MAIN RESULTS The rapid response system operates from 7 AM to 10 PM on weekdays and from 7 AM to 12 PM on Saturdays. Primary outcomes were the difference of cardiopulmonary arrest incidence between pre-rapid response system and post-rapid response system periods and whether the rapid response system operating time affects the cardiopulmonary arrest incidence. The overall cardiopulmonary arrest incidence (per 1,000 admissions) was 1.43. Although the number of admissions per month and case-mix index were increased (3,555.18 vs 4,564.72, p < 0.001; 1.09 vs 1.13, p = 0.001, respectively), the cardiopulmonary arrest incidence was significantly decreased after rapid response system (1.60 vs 1.23; p = 0.021), and mortality (%) was unchanged (1.38 vs 1.33; p = 0.322). After rapid response system implementation, the cardiopulmonary arrest incidence significantly decreased by 40% during rapid response system operating times (0.82 vs 0.49/1,000 admissions; p = 0.001) but remained similar during rapid response system nonoperating times (0.77 vs 0.73/1,000 admissions; p = 0.729).
CONCLUSIONS The implementation of a part-time rapid response system reduced the cardiopulmonary arrest incidence based on the reduction of cardiopulmonary arrest during rapid response system operating times. Further analysis of the cost effectiveness of part-time rapid response system is needed.
PubMed IF 7.5 호흡기내과
22992017

제1저자 장민정 · 교신저자 박종선, 이재호

, , , , , , , , , , , ,
Population pharmacokinetics of moxifloxacin, cycloserine, p-aminosalicylic acid and kanamycin for the treatment of multi-drug-resistant tuberculosis.
Int J Antimicrob Agents. 2017;49(6):677-687.

Abstract
Control of multi-drug-resistant tuberculosis (MDR-TB) requires extensive, supervised chemotherapy because second-line anti-TB drugs have a narrower therapeutic range than first-line drugs. This study aimed to develop population pharmacokinetic (PK) models for second-line drugs in patients with MDR-TB, evaluate the recommended dosage regimens and, if necessary, suggest new dosage regimens. A prospective, single-centre PK study was performed on second-line anti-TB drugs in patients with MDR-TB. Moxifloxacin, cycloserine, p-aminosalicylic acid (PAS), kanamycin and other second-line drugs were administered to the patients. Plasma concentrations were analysed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Population PK models were developed using non-linear mixed effect modelling (NONMEM, Version 7.30; ICON Development Solutions, Ellicott City, MD, USA). Simulations were performed using the calculated PK parameters. The respective absorption rate constant, apparent clearance and apparent volume of distribution values were as follows: 0.305/h, 9.37 L/h and 56.7 L for moxifloxacin; 0.135/h, 1.38 L/h and 10.5 L for cycloserine; 0.510/h, 30.8 L/h and 79.4 L for PAS; and 1.67/h, 3.75 L/h and 15.2 L for kanamycin. The simulations showed that the following dosage regimens were more likely to be within the recommended concentration ranges than the raw data in this study: 200 mg of moxifloxacin once daily (QD) (patient weight <50 kg) and 400 mg of moxifloxacin QD (patient weight ≥50 kg), 500-750 mg of cycloserine QD, 4.95-6.6 g of PAS twice daily and 750-1000 mg of intramuscular kanamycin QD. These findings indicate that the recommended doses should be revised to improve the clinical outcomes of MDR-TB treatment.
PubMed IF 5 호흡기내과
22982017

제1저자 백우현 · 교신저자 박도현

, , , , , , , , , ,
Conversion of external percutaneous transhepatic biliary drainage to endoscopic ultrasound-guided hepaticogastrostomy after failed standard internal stenting for malignant biliary obstruction.
Endoscopy. 2017;49(6):544-548.

Abstract
Background and study aim Percutaneous transhepatic biliary drainage (PTBD) is a rescue procedure after a failed endoscopic retrograde cholangiopancreatography. As PTBD causes patient discomfort, conversion of the PTBD to internal biliary stenting (PTBDS) may be required; however, PTBDS is sometimes difficult because of the tight stricture. We evaluated the efficacy and safety of conversion of external PTBD to endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) after failed PTBDS. Patients and methods A total of 16 patients with malignant distal biliary obstruction who underwent conversion of external PTBD to EUS-HGS after failed PTBDS were enrolled from two institutions in Korea and Japan. Data were analyzed retrospectively. Results The technical and clinical success rates were 100 % and 81 %, respectively. Early adverse events developed in two patients: proximal stent migration (n = 1), and cholecystitis (n = 1). Stents were occluded or migrated distally in five patients. The mean duration of stent patency was 402 days. Conclusions Conversion of external PTBD to EUS-HGS may be a good rescue option after failed PTBDS.
PubMed IF 11.8 소화기내과
22972017

제1저자 이은봉 · 교신저자 이은봉

, , , , , , ,
Disease-Drug Interaction of Sarilumab and Simvastatin in Patients with Rheumatoid Arthritis.
Clin Pharmacokinet. 2017;56(6):607-615.

Abstract
INTRODUCTION Elevated interleukin (IL)-6 occurs in patients with active rheumatoid arthritis (RA), which has been shown to lead to a decrease in cytochrome P450 (CYP) enzyme activity and alterations in drug concentrations metabolized by CYP. IL-6 signaling blockade by IL-6 receptor (IL-6R) antagonists may reverse this effect of IL-6 and restore CYP activity. This study evaluated the pharmacokinetic profile of simvastatin (a CYP3A4 substrate) before and 1 week after a single dose of sarilumab (a human monoclonal antibody [mAb] blocking the IL-6Rα) in patients with RA, to assess potential interaction.
METHODS Nineteen patients with active RA received oral simvastatin 40 mg 1 day before and 7 days after subcutaneous injection of sarilumab 200 mg. The pharmacokinetic parameters of simvastatin and its primary metabolite, β-hydroxy-simvastatin acid, were calculated using noncompartmental analysis.
RESULTS Compared with simvastatin alone, single-dose simvastatin administration 7 days after single-dose sarilumab administration in patients with RA resulted in reduced simvastatin and β-hydroxy-simvastatin acid exposure in plasma. Mean effect ratios (90 % confidence interval) for simvastatin peak plasma concentration (C _max) and area under the concentration-time curve extrapolated to infinity (AUC_∞) were 54.1 % (42.2-69.4 %) and 54.7 % (47.2-63.3 %), respectively. No changes occurred in time to C _max or half-life for either simvastatin or β-hydroxy-simvastatin acid after sarilumab administration.
CONCLUSIONS Sarilumab treatment resulted in a reduction in exposure of simvastatin, consistent with reversal of IL-6-mediated CYP3A4 suppression in patients with active RA, as was reported for tocilizumab with simvastatin and for sirukumab with midazolam.
CLINICAL TRIAL REGISTRATION NUMBER NCT02017639.
PubMed IF 4 류마티스내과
22962017

제1저자 박성열 · 교신저자 오도연

, , , , , , ,
Prospective Evaluation of Changes in Tumor Size and Tumor Metabolism in Patients with Advanced Gastric Cancer Undergoing Chemotherapy: Association and Clinical Implication.
J Nucl Med. 2017;58(6):899-904.

Abstract
A change in tumor size is a well-validated and commonly used value for evaluating response to chemotherapy in cancer. Metabolic changes induced by chemotherapy are related to prognosis in several tumor types. However, the clinical implication of metabolic changes in patients with advanced gastric cancer (AGC) undergoing chemotherapy remains unclear. We aimed to evaluate response of tumor size and metabolism in AGC during chemotherapy and to reveal the relationship between them in view of their impact on patient survival. Methods: We prospectively enrolled patients with AGC before the initiation of first-line palliative chemotherapy. Using baseline and follow-up contrast-enhanced CT and ¹⁸F-FDG PET, we assessed the tumor diameter, SUV_max, and total lesion glycolysis in each lesion and their changes during chemotherapy at the same time. We included all lesions with the maximal longest diameters over 1 cm on CT, and each lesion was evaluated by matched ¹⁸F-FDG PET. We analyzed the association between changes in tumor metabolism and tumor size and performed outcome analysis on overall survival (OS) and progression-free survival (PFS). Results: Seventy-four patients were enrolled, and the number of all lesions included in this study was 620. Compared with adenocarcinomas, poorly cohesive carcinomas demonstrated lower SUV_max irrespective of tumor size (P < 0.001). Human epidermal growth factor receptor 2 (HER2)-positive tumors showed higher SUV_max than HER2-negative tumors (P = 0.002). The changes in SUV_max due to chemotherapy had a linear correlation with the changes in tumor size of each lesion, and a 30% tumor size reduction was associated with a 50% SUV_max reduction (P < 0.001). Total lesion glycolysis changes also correlated with tumor size changes (P < 0.001). Better OS and PFS were obtained in patients with both tumor size and SUV_max reduction than in patients with either size or SUV_max reduction only (OS, P = 0.003; PFS, P = 0.038). Conclusion: Changes in tumor metabolism induced by chemotherapy correlated with changes in tumor size in AGC. Considering both changes in metabolism and size could help predict a more accurate prognosis for AGC patients undergoing chemotherapy.
PubMed IF 9.6 혈액종양내과
22952017

제1저자 이현우 · 교신저자 이창훈

, ,
The impact of olodaterol on the risk of mortality and serious adverse events: a systematic review and meta-analysis.
Br J Clin Pharmacol. 2017;83(6):1166-1175.

Abstract
AIMS Olodaterol is a novel inhaled long-acting β₂ -agonist (LABA) that showed efficacy as a bronchodilator for patients with chronic obstructive pulmonary disease (COPD) and asthma. However, it is unclear whether olodaterol reduces mortality; the safety issues of olodaterol have not been fully evaluated.
METHODS Randomized controlled trials comparing olodaterol with placebo for patients with COPD or asthma, which evaluated mortality or serious adverse events, were included. Eighteen trials reporting mortality and 26 trials reporting nonfatal serious adverse events were included.
RESULTS Inhaled olodaterol did not reduce the risk of mortality (Peto fixed OR 1.31; 95% CI 0.90-1.89) and had no significant impacts on nonfatal serious adverse events (Peto fixed OR 1.03; 95% CI 0.91-1.15).
CONCLUSIONS Inhaled olodaterol has no impact on mortality risk in clinical trials conducted on patients with COPD and asthma. However, the interpretation is limited by a high OR (1.31) and a wide CI that includes the hazardous effect. We could not find any relationship between inhaled olodaterol use and nonfatal serious adverse events.
PubMed IF 3 호흡기내과
22942017

제1저자 김정현 · 교신저자 이창훈

, , , , , , , , , , , , , , ,
Which bronchodilator reversibility criteria can predict severe acute exacerbation in chronic obstructive pulmonary disease patients?
Respir Res. 2017;18(1):107.

Abstract
BACKGROUND It is unclear whether various bronchodilator reversibility (BDR) criteria affect the prognosis of chronic obstructive pulmonary disease (COPD). The aim of this study is to evaluate the impact of positive BDR defined according to various BDR criteria on the risk of severe acute exacerbation (AE) in COPD patients.
METHODS Patients from four prospective COPD cohorts in South Korea who underwent follow-up for at least 1 year were enrolled in this study. The assessed BDR criteria included the Global Initiative for Chronic Obstructive Lung Disease (GOLD), American Thoracic Society (ATS), American College of Chest Physicians, (ACCP), major criteria of the Spanish definition of asthma-COPD overlap syndrome (ACOS), criteria compatible with ACOS in the Global Initiative for Asthma (GINA), and European Respiratory Society (ERS). The rate of patients with severe AE who required hospitalization within 1 year due to BDR results according to each set of criteria was analyzed using logistic regression models.
RESULTS Among a total of 854 patients, the BDR-positive cases varied according to the criteria used. There was a 3.5% positive BDR rate according to GINA and a 29.9% rate according to the ATS criteria. Positive BDR according to the GOLD criteria was significantly associated with a decreased risk of severe AE (adjusted odds ratio (aOR) = 0.38; 95% Confidence interval (CI) = 0.15-0.93). This result remained statistically significant even in a sensitivity analysis that included only participants with a smoking history of at least 10 pack-years and in the analysis for the propensity score-matched participants.
CONCLUSIONS Among different criteria for positive BDR, the use of the GOLD ones was significantly associated with a decreased risk of severe AE in COPD patients. Increase use of ICS/LABA may have affected this relationship.
PubMed IF 5.7 호흡기내과
22932017

제1저자 박미영 · 교신저자 이춘택

, , , , , , , , , , , ,
Generation of lung cancer cell lines harboring EGFR T790M mutation by CRISPR/Cas9-mediated genome editing.
Oncotarget. 2017;8(22):36331-36338.

Abstract
Tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib are effective against lung adenocarcinomas harboring epidermal growth factor receptor (EGFR) mutations. However, cancer cells can develop resistance to these agents with prolonged exposure; in over 50% of cases, this is attributable to the EGFR T790M mutation. Moreover, additional resistance mutations can arise with the use of new drugs. Cancer cell lines with specific mutations can enable the study of resistance mechanisms. In this study, we introduced the EGFR T790M mutation into the PC9 human lung cancer cell line-which has a deletion in exon 19 of the EGFR gene-by clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas)9-mediated genome editing. EGFR pyrosequencing and peptide nucleic acid clamping revealed that PC9 cells with EGFR T790M generated by CRISPR/Cas 9 had a higher T790M mutation rate than those with the same mutation generated by long-term exposure to gefitinib (PC9-G); moreover, resistance to gefitinib in these clones was higher than that in PC9-G cells. The clones were also highly sensitive to the 3rd-generation EGFR TKI AZD9291, which is cytotoxic to lung cancer cells with EGFR T790M. The CRISPR/Cas9 programmable nuclease system can be used to generate various cancer cell lines with specific mutations that can facilitate studies on resistance mechanisms and drug efficacy.
PubMed IF 5.008 호흡기내과
22922017

제1저자 김정주 · 교신저자 유철규

, , , , , , , , , , , ,
Inhaled indacaterol for the treatment of COPD patients with destroyed lung by tuberculosis and moderate-to-severe airflow limitation: results from the randomized INFINITY study.
Int J Chron Obstruct Pulmon Dis. 2017;12:1589-1596.

Abstract
BACKGROUND AND OBJECTIVE Pulmonary tuberculosis (TB) is a risk factor for chronic obstructive pulmonary disease (COPD); however, few clinical studies have investigated treatment effectiveness in COPD patients with destroyed lung by TB. The Indacaterol effectiveness in COPD patients with Tuberculosis history (INFINITY) study assessed the efficacy and safety of once-daily inhaled indacaterol 150 µg for the treatment of Korean COPD patients with destroyed lung by TB and moderate-to-severe airflow limitation.
METHODS This was a multicenter, double-blind, parallel-group study, in which eligible patients were randomized (1:1) to receive either once-daily indacaterol 150 µg or placebo for 8 weeks. The primary efficacy endpoint was change from baseline in trough forced expiratory volume in 1 s at Week 8; the secondary endpoints included changes in transition dyspnea index score and St George's Respiratory Questionnaire for COPD score at Week 8. Safety was evaluated over 8 weeks.
RESULTS Of the 136 patients randomized, 119 (87.5%) completed the study treatment. At Week 8, indacaterol significantly improved trough forced expiratory volume in 1 s versus placebo (treatment difference [TD] 140 mL, P<0.001). Statistically significant improvement in transition dyspnea index score (TD =0.78, P<0.05) and numerical improvement in St George's Respiratory Questionnaire for COPD score (TD =-2.36, P=0.3563) were observed with indacaterol versus placebo at Week 8. Incidence of adverse events was comparable between the treatment groups.
CONCLUSION Indacaterol provided significantly superior bronchodilation, significant improvement in breathlessness and improved health status with comparable safety versus placebo in Korean COPD patients with destroyed lung by TB and moderate-to-severe airflow limitation.
PubMed IF 4.1 호흡기내과
22912017

제1저자 최지민 · 교신저자 김상균

, , , , , , , , ,
Clinical implications of pre-existing adenoma in endoscopically resected early gastric cancers.
PLoS One. 2017;12(5):e0178419.

Abstract
BACKGROUND Although gastric adenoma is widely accepted as a precursor of gastric cancer, pre-existing adenoma is not always detected in gastric cancer patients.
OBJECTIVE To investigate the clinical characteristics of early gastric cancer (EGC) arising from adenoma, compared with those of EGC without pre-existing adenoma.
METHODS Patients who underwent endoscopic resection for EGC at a single tertiary hospital were divided into two groups based on the presence (ex-adenoma group) or absence (de novo group) of pre-existing adenoma on pathologic specimens. Clinicopathologic characteristics, endoscopic features and long-term outcomes were analyzed.
RESULTS Of 1,509 patients, 236 (15.6%) were included in the ex-adenoma group. Mean age (P = 0.003) and Helicobacter pylori infection rate (P = 0.040) were significantly higher in the ex-adenoma than in the de novo group. Mean endoscopic size was significantly larger, elevated lesions were more prevalent (both P < 0.001), and carcinomas were more differentiated in the ex-adenoma group than in the de novo group (P = 0.037). The degree of atrophy (P = 0.025) or intestinal metaplasia (P < 0.001) was more advanced in the ex-adenoma group. Synchronous gastric neoplasia was significantly more prevalent in the ex-adenoma group (P < 0.001), whereas metachronous cancer recurrence rate was not significantly different between the two groups.
CONCLUSIONS EGCs with pre-existing adenoma show a greater association with H. pylori-related chronic inflammation than those without, which could explain the differences in the characteristics between groups. Potential differences in carcinogenic mechanisms between the groups were explored.
PubMed IF 2.8 소화기내과
22902017

제1저자 이상언 · 교신저자 이해영

, , , , , , , , , , , , , , , , , ,
Clinical Characteristics and Outcome of Acute Heart Failure in Korea: Results from the Korean Acute Heart Failure Registry (KorAHF).
Korean Circ J. 2017;47(3):341-353.

Abstract
BACKGROUND AND OBJECTIVES The burden of heart failure has increased in Korea. This registry aims to evaluate demographics, clinical characteristics, management, and long-term outcomes in patients hospitalized for acute heart failure (AHF).
SUBJECTS AND METHODS We prospectively enrolled a total of 5625 consecutive subjects hospitalized for AHF in one of 10 tertiary university hospitals from March 2011 to February 2014. Descriptive statistics were used to determine the baseline characteristics of the study population and to compare them with those from other registries.
RESULTS The mean age was 68.5±14.5 years, 53.2% were male, and 52.2% had de novo heart failure. The mean systolic and diastolic blood pressures were 131.2±30.3 mmHg and 78.6±18.8 mmHg at admission, respectively. The left ventricular ejection fraction was ≤40% in 60.5% of patients. Ischemia was the most frequent etiology (37.6%) and aggravating factor (26.3%). Angiotensin converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers, and aldosterone antagonists were prescribed in 68.8%, 52.2%, and 46.6% of the patients at discharge, respectively. Compared with the previous registry performed in Korea a decade ago, extracorporeal membrane oxygenation (ECMO) and heart transplantation have been performed more frequently (ECMO 0.8% vs. 2.8%, heart transplantation 0.3% vs. 1.2%), and in-hospital mortality decreased from 7.6% to 4.8%. However, the total cost of hospital care increased by 40%, and one-year follow-up mortality remained high.
CONCLUSION While the quality of acute clinical care and AHF-related outcomes have improved over the last decade, the long-term prognosis of heart failure is still poor in Korea. Therefore, additional research is needed to improve long-term outcomes and implement cost-effective care.
PubMed IF 3.4 순환기내과
22892017

제1저자 구본권 · 교신저자 구본권

What Is the Clinical Relevance of the Discordance Between Fractional Flow Reserve and Coronary Flow Reserve?
JACC Cardiovasc Interv. 2017;10(10):1008-1010.

PubMed IF 12.7 순환기내과
22882017

제1저자 이정훈, 탁원영 · 교신저자 김윤준, 배영수

, , , , , , , , , , , ,
Adjuvant immunotherapy with autologous dendritic cells for hepatocellular carcinoma, randomized phase II study.
Oncoimmunology. 2017;6(7):e1328335.

Abstract
Our previous phase I/IIA study showed that autologous dendritic cells (DCs) pulsed with tumor-associated antigens are well tolerated in patients with hepatocellular carcinoma (HCC). In this randomized, multicenter, open-label, phase II trial, we investigated the efficacy and safety of this DC-based adjuvant immunotherapy with 156 patients, who treated for HCC with no evidence of residual tumor after standard treatment modalities. Patients were randomly assigned to immunotherapy (n = 77; injection of 3 × 10⁷ DC cells, six times over 14 weeks) or control (n = 79; no treatment). The primary end point was recurrence-free survival (RFS), and the secondary endpoints were immune response and safety. The RFS between the immunotherapy and control groups was not significantly different (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.60-1.56; p = 0.90). However, post-hoc subgroup analyses revealed that DC immunotherapy significantly reduced the risk of tumor recurrence of non-radiofrequency ablation (non-RFA) group patients (n = 83, HR, 0.49; 95% CI, 0.26-0.94; p = 0.03), whereas unexpectedly increased the risk of recurrence in RFA group (n = 61, p = 0.01). Tumor-specific immune responses were significantly enhanced (both p < 0.01) in the immunotherapy group. Baseline serum interleukin (IL)-15 was statistically correlated with RFS prolongation (HR, 0.16; 95% CI, 0.03-1.58; p = 0.001) within the immunotherapy groups. Overall adverse events were more frequent in the immunotherapy group (p < 0.001) but were mainly mild to moderate in severity. In conclusion, adjuvant immunotherapy with DC vaccine reduces the risk of tumor recurrence in HCC patients who underwent standard treatment modalities other than RFA. Baseline IL-15 might be a candidate biomarker for DC-based HCC immunotherapy.
PubMed IF 7.719 소화기내과
22872017

제1저자 백주영 · 교신저자 정숙향

, , , , , , , , ,
Prevalence and Incidence of Depression during Interferon-Based Antiviral Therapy in Chronic Hepatitis C Patients in the Republic of Korea.
Gut Liver. 2017;11(3):426-433.

Abstract
BACKGROUND/AIMS The association between depression and chronic hepatitis C virus (HCV) infection or pegylated interferon α and ribavirin therapy (PR therapy) has not been extensively studied in Korea. We aimed to clarify the prevalence of depression and its incidence during PR therapy in chronic hepatitis C (CHC) patients.
METHODS In this prospective, multicenter study, 114 CHC patients were screened for depression using two self-reported scales, the Beck Depression Inventory-I (BDI-I) and the Hospital Anxiety and Depression scale (HADS). The incidence of depression during PR therapy was evaluated in 62 patients who underwent PR therapy during the study period.
RESULTS The prevalence of baseline depression was 17.5% according to the BDI-I score ≥10 criterion and 4.4% according to the HADS-D score ≥8 criterion in the 114 CHC patients, and it was significantly associated with an unmarried state. During PR therapy, depression developed in 34.6% according to the BDI-I scale and 29.5% according to the HADS-D, which negatively affected sustained virologic response (SVR).
CONCLUSIONS The prevalence of depression in Korean CHC patients appears to be low compared to that in Western patients; however, its incidence during PR therapy (approximately 30%) was similar to that of other populations, which led to a lower SVR rate. Active screening and multidisciplinary management of depression during PR therapy is warranted.
PubMed IF 4.1 소화기내과
22862017

제1저자 임수경, 고성준 · 교신저자 고성준

, , , , , , , , ,
Stress and sleep quality in doctors working on-call shifts are associated with functional gastrointestinal disorders.
World J Gastroenterol. 2017;23(18):3330-3337.

Abstract
AIM To investigate the role of sleep quality and psychosocial problems as predictors of functional gastrointestinal disorders (FGIDs) in doctors that work 24 hour-on-call shifts.
METHODS In this cross-sectional observation study, using the Rome III Questionnaire and Pittsburgh Sleep Quality Index (PSQI), we analyzed 170 doctors with 24 hour-on-call shifts.
RESULTS Among the participants that had experienced a 24 hour-on-call shift within the last 6 mo, 48 (28.2%) had FGIDs. Overall prevalence of irritable bowel syndrome (IBS) and functional dyspepsia (FD) were 16.5% and 17.1%, respectively, with 5.3% exhibiting both. Sleep scores (PSQI) (8.79 ± 2.71 vs 7.30 ± 3.43, P = 0.008), the presence of serious psychosocial alarm (83.3% vs 56.6%, P = 0.004), and the proportion of doctors who experienced over two months of recent on-call work (81.2% vs 68.9%, P = 0.044) were significantly different between individuals with or without FGIDs. Multivariate analysis revealed that presenting serious psychosocial alarm was an independent risk factor for prevalence of FD (OR = 5.47, 95%CI: 1.06-28.15, P = 0.042) and poor sleep quality (PSQI ≥ 6) was a predictor of IBS (OR = 4.17, 95%CI: 1.92-19.02, P = 0.016).
CONCLUSION Physicians should recognize the role of sleep impairment and psychological stress in the development of FGIDs and a comprehensive approach should be considered to manage patients with FGIDs.
PubMed IF 7.7 소화기내과
22852017

제1저자 한미연 · 교신저자 오윤규, 김영훈

, , , , , , , , , , , ,
Early onset hyperuricemia is a prognostic marker for kidney graft failure: Propensity score matching analysis in a Korean multicenter cohort.
PLoS One. 2017;12(5):e0176786.

Abstract
It remains inconclusive whether hyperuricemia is a true risk factor for kidney graft failure. In the current study, we investigated the association of hyperuricemia and graft outcome. We performed a multi-center cohort study that included 2620 kidney transplant recipients. The patients were classified as either normouricemic or hyperuricemic at 3 months after transplantation. Hyperuricemia was defined as a serum uric acid level ≥ 7.0 mg/dL in males or ≥ 6.0 mg/dL in females or based on the use of urate-lowering medications. The two groups were compared before and after propensity score matching. A total of 657 (25.1%) patients were classified as hyperuricemic. The proportion of hyperuricemic patients increased over time, reaching 44.2% of the total cohort at 5 years after transplantation. Estimated glomerular filtration rate and donor type were independently associated with hyperuricemia. Hyperuricemia was associated with graft loss according to multiple Cox regression analysis before propensity score matching (hazard ratio [HR] = 1.56, 95% confidence interval [CI] = 1.14-2.13, P = 0.005) as well as after matching (HR = 1.65, 95% CI = 1.13-2.42, p = 0.010). Cox regression models using time-varying hyperuricemia or marginal structural models adjusted with time-varying eGFR also demonstrated significant hazards of hyperuricemia for graft loss. Cardiovascular events and recipient survival were not associated with hyperuricemia. Overall, hyperuricemia, especially early onset after transplantation, showed an increased risk for graft failure. Further studies are warranted to determine whether lowering serum uric acid levels would be beneficial to graft survival.
PubMed IF 2.8 신장내과
22842017

제1저자 변자민 · 교신저자 고영일

, , , , , , , , , , , , , , , , , , ,
BCR-ABL translocation as a favorable prognostic factor in elderly patients with acute lymphoblastic leukemia in the era of potent tyrosine kinase inhibitors.
Haematologica. 2017;102(5):e187-e190.

PubMed IF 8.2 혈액종양내과
22832017

제1저자 심성훈, 김소연 · 교신저자 김태민, 전윤경

, , , , , , , , , ,
Novel JAK3-Activating Mutations in Extranodal NK/T-Cell Lymphoma, Nasal Type.
Am J Pathol. 2017;187(5):980-986.

Abstract
Inhibition of the Janus kinase (JAK)-STAT pathway has been implicated as a treatment option for extranodal natural killer/T-cell lymphoma, nasal type (NTCL). However, JAK-STAT pathway alterations in NTCL are variable, and the efficacy of JAK-STAT pathway inhibition has been poorly evaluated. JAK3 mutation and STAT3 genetic alterations were investigated by direct sequencing and immunohistochemistry in 84 patients with newly diagnosed NTCL. Five of 71 patients with NTCL (7.0%) had JAK3 mutations in the pseudokinase domain: two JAK3^A573V, two JAK3^H583Y, and one JAK3^G589D mutation. Proliferation of Ba/F3 cells transduced with novel JAK3 mutations (JAK3^H583Y and JAK3^G589D) was independent of IL-3 and was inhibited by the JAK3 inhibitor tofacitinib (means ± SD drug concentration causing a 50% inhibition of the desired activity, 85 ± 10 nmol/L and 54 ± 9 nmol/L). Ribbon diagrams revealed that these JAK3 pseudokinase domain mutations were located at the pseudokinase-kinase domain interface. Although phosphorylated STAT3 was overexpressed in 35 of 68 patients with NTCL (51.4%), a STAT3 mutation (p.Tyr640Phe; STAT3^Y640F) at the SRC homology 2 domain was detected in 1 of the 63 patients (1.5%). A STAT3 inhibitor was active against STAT3-mutant SNK-6 and YT cells. Novel JAK3 mutations are oncogenic and druggable in NTCL. The JAK3 or STAT3 signal was altered in NTCL, and pathway inhibition might be a therapeutic option for patients with JAK3- or STAT3-mutant NTCL.
PubMed IF 4.9 혈액종양내과
22822017

제1저자 안창호 · 교신저자 박경수

, , , , , , , , , , , , , , , , , , , , ,
Efficacy and safety of gemigliptin, a dipeptidyl peptidase-4 inhibitor, in patients with type 2 diabetes mellitus inadequately controlled with combination treatment of metformin and sulphonylurea: a 24-week, multicentre, randomized, double-blind, placebo-controlled study (TROICA study).
Diabetes Obes Metab. 2017;19(5):635-643.

Abstract
AIMS To assess the efficacy and safety of gemigliptin, a dipeptidyl peptidase-4 inhibitor, added to metformin and sulphonylurea in patients with type 2 diabetes (T2DM).
MATERIALS AND METHODS We conducted a randomized, double-blind, placebo-controlled trial in 219 Korean patients inadequately controlled with metformin and glimepiride. Participants were randomized to gemigliptin 50 mg once daily or placebo added to metformin and glimepiride. The primary endpoint was change in glycated haemoglobin (HbA1c) level from baseline to week 24.
RESULTS The baseline HbA1c was 8.2% in both groups. The addition of gemigliptin to metformin and glimepiride significantly reduced HbA1c levels at week 24 compared with placebo (between-group difference in adjusted mean change -0.87%, 95% confidence interval [CI] -1.09% to -0.64%). Fasting plasma glucose level was also significantly reduced with gemigliptin (-0.93 mmol/L, 95% CI -1.50 to -0.35 mmol/L), and a higher proportion of participants achieved an HbA1c level of <7% (39.3% vs 5.5%; P <.001) in the gemigliptin group than in the placebo group. Total cholesterol and LDL cholesterol were modestly but significantly reduced in the gemigliptin group compared with the placebo group (-0.21 mmol/L, 95% CI -0.38 to -0.03 mmol/L for total cholesterol, -0.18 mmol/L, 95% CI -0.34 to -0.01 mmol/L for LDL cholesterol). The incidence of hypoglycaemia was 9.4% in the gemigliptin group and 2.7% in the placebo group.
CONCLUSIONS Gemigliptin significantly improved glycaemic control in patients with T2DM inadequately controlled with metformin and sulphonylurea. The incidence of hypoglycaemia was higher with gemigliptin than with placebo, which highlights the importance of optimal dose adjustment for sulphonylurea.
PubMed IF 6.1 내분비대사내과
22812017

제1저자 문신제, 송영신 · 교신저자 박영주

, , , , , , , ,
Effects of Coexistent BRAFV600E and TERT Promoter Mutations on Poor Clinical Outcomes in Papillary Thyroid Cancer: A Meta-Analysis.
Thyroid. 2017;27(5):651-660.

Abstract
BACKGROUND The presence of a telomerase reverse transcriptase (TERT) promoter mutation has been suggested as a potential prognostic marker for thyroid cancer, and a synergistic association with the BRAF^V600E mutation has been demonstrated. The aim of this study was to verify the role of this genetic duet in papillary thyroid cancer (PTC).
METHODS Studies of the association of BRAF^V600E and TERT promoter mutations with clinicopathologic features, recurrence, or PTC-related mortality were included from PubMed and Embase databases (inception to September 2016).
RESULTS Thirteen eligible studies incorporating 4347 patients with PTC were included, and 283 (median 8.3%) of these patients had coexistent BRAF^V600E and TERT promoter mutations. The coexistence of the two mutations was far more strongly associated with high-risk clinicopathologic features than either mutation alone was, including advanced TNM stage (vs. BRAF^V600E: odds ratio [OR] = 4.19 [confidence interval (CI) 3.07-5.71]; vs. TERT: OR = 4.66 [CI 2.67-8.13]), extrathyroidal extension (vs. BRAF^V600E: OR = 3.1 [CI 2.2-4.37]; vs. TERT: OR = 5.66 [CI 3.02-10.6]), lymph node metastasis (vs. BRAF^V600E: OR = 1.59 [CI 1.16-2.17]; vs. TERT: OR = 2.03 [CI 1.22-3.38]), and distant metastasis (vs. BRAF^V600E: OR = 11.76 [CI 5.63-24.58]). The coexistence of the mutations showed the highest risk of recurrence (coexistence vs. no mutations: hazard ratio [HR] = 6.60 [CI 3.82-11.40]; BRAF^V600E vs. no mutations: HR = 1.31 [CI 0.49-3.46]; TERT vs. no mutations: HR = 3.38 [CI 0.85-13.35]). Moreover, PTC-related mortality was significantly higher with coexistent mutations than in the presence of BRAF^V600E alone (HR = 20.07 [CI 8.37-48.09]).
CONCLUSIONS Coexistent BRAF^V600E and TERT promoter mutations have a synergistic effect on clinical outcomes in PTC, whereas each mutation alone has a modest effect. Therefore, molecular testing of BRAF^V600E and TERT promoter mutations together is useful in assessing risk stratification of PTC.
PubMed IF 6.6 내분비대사내과
22802017

제1저자 이지현, 김정희 · 교신저자 신찬수

, , , ,
Skeletal effects of vitamin D deficiency among patients with primary hyperparathyroidism.
Osteoporos Int. 2017;28(5):1667-1674.

Abstract
UNLABELLED Little is known about the association between vitamin D deficiency and the skeletal phenotypes in primary hyperparathyroidism (PHPT) patients. A low 25-hydroxyvitamin D level was associated with a low bone mineral density and deteriorated hip geometry in women with PHPT in an Asian population where vitamin D deficiency is prevalent.
INTRODUCTION Few studies have examined the effect of vitamin D deficiency on the bone health of primary hyperparathyroidism (PHPT) patients.
METHODS We investigated the skeletal effects of vitamin D deficiency in 79 PHPT patients by assessing bone mineral density (BMD), the trabecular bone score (TBS), and hip geometry, which were measured using dual-energy X-ray absorptiometry (27 men with median age 60 years [53;69]; 52 postmenopausal women with median age of 57 years [53;67]). Cross-sectional data were collected from subjects enrolled in an ongoing PHPT cohort study at Seoul National University Hospital from March 2008 to December 2015.
RESULTS We classified PHPT patients according to 25-hydroxyvitamin D (25(OH)D) levels (<20 vs. ≥20 ng/ml). After adjusting for age and body mass index, women with vitamin D deficiency had lower BMDs at the lumbar spine (LS) and femur neck (FN) than women who had sufficient levels of vitamin D (LS, 0.903 ± 0.138 vs. 0.998 ± 0.184 g/cm²; FN, 0.715 ± 0.084 vs. 0.791 ± 0.113 g/cm²; P < 0.05). However, the total hip BMD and the TBS were not significantly different between the two groups. In the hip geometry analysis, the cross-sectional area, cross-sectional moment of inertia, and section modulus were also significantly lower in women with vitamin D deficiency than in those without. No significant difference was found in the BMD, TBS, or hip geometry according to 25(OH)D levels in men.
CONCLUSION Vitamin D deficiency may be associated with a low BMD and deteriorated hip geometry in postmenopausal women with PHPT.
PubMed IF 5.4 내분비대사내과
22792017

제1저자 공성혜 · 교신저자 김정희

, , , , ,
Dietary potassium intake is beneficial to bone health in a low calcium intake population: the Korean National Health and Nutrition Examination Survey (KNHANES) (2008-2011).
Osteoporos Int. 2017;28(5):1577-1585.

Abstract
UNLABELLED Dietary potassium may neutralize acid load and reduce calcium loss from the bone, leading to beneficial effect on bone mineral density. In this nationwide Korean population study, dietary potassium intake was associated with improved bone mineral density in older men and postmenopausal women.
INTRODUCTION Nutrition is a major modifiable factor that affects bone health. The accompanying anion in dietary potassium may act as an alkaline source by neutralizing the acid load and reducing calcium loss from the bone. We aimed to evaluate the association between dietary potassium intake and bone mineral density (BMD) in the Korean population.
METHODS We analyzed a total of 3135 men aged >50 years and 4052 postmenopausal women from the Korean National Health and Nutrition Examination Survey (KNHANES). Lumbar spine, total hip, and femur neck BMD were measured using dual energy X-ray absorptiometry. The daily food intake was assessed using a food frequency questionnaire.
RESULTS When we divided the participants into tertiles based on the intake of potassium intake, the highest potassium intake tertile group showed a significantly higher total hip and femur neck BMD as compared to lower tertile groups (0.914 ± 0.004, 0.928 ± 0.003, 0.925 ± 0.004 mg/day across the tertiles, P = .014 for total hip; 0.736 ± 0.003, 0.748 ± 0.003, 0.750 ± 0.004 mg/day, P = .012 for femur neck). Postmenopausal women in the highest potassium intake tertile group showed significantly higher lumbar, total hip, and femur neck BMD as compared to those in lower potassium intake tertile groups (0.793 ± 0.004, 0.793 ± 0.003, 0.805 ± 0.004 mg/day across the tertiles, P = .029 for lumbar spine; 0.766 ± 0.003, 0.770 ± 0.002, 0.780 ± 0.003 mg/day, P = .002 for total hip; 0.615 ± 0.003, 0.619 ± 0.002, 0.628 ± 0.003 mg/day, P = .002 for femur neck).
CONCLUSIONS Dietary potassium intake was positively associated with BMD in men aged >50 years and postmenopausal women, indicating the beneficial effects of dietary potassium intake on bone health.
PubMed IF 5.4 내분비대사내과

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