SCI 발표논문

1. 272019

   제1저자 유민수 · 교신저자 류지곤

   You MS, Ryu JK, Choi YH, Choi JH, Huh G, Paik WH, Lee SH, Kim YT

   Therapeutic outcomes and prognostic factors in unresectable gallbladder cancer treated with gemcitabine plus cisplatin.

   BMC Cancer. 2019;19(1):10.

   Abstract

   BACKGROUND Gallbladder cancer (GBC) is likely to be diagnosed at progressive stages and shows a very poor prognosis. Combination therapy with gemcitabine and cisplatin (GEMCIS) has been widely used as first-line palliative chemotherapy for advanced GBC. This study was designed to investigate the efficacy of GEMCIS and identify prognostic factors in patients with unresectable GBC.

   METHODS Patients with GBC who were treated with GEMCIS from January 2008 to June 2017 in a single tertiary hospital were included. All cases of GBC were diagnosed by pathologic findings and extent of the tumour was assessed by imaging tests. Combination chemotherapy consisted of cisplatin 25 mg/m² and gemcitabine 1000 mg/m² intravenously on days 1 and 8 every 3 weeks. To determine factors affecting prognosis, Kaplan-Meier survival analysis, log-rank test and the Cox proportional hazard regression linear model were used. All variables with P < 0.1 in univariable analysis were included in the multivariable model.

   RESULTS A total of 173 patients received a median of 5.3 ± 4.4 cycles of chemotherapy over 3.8 ± 3.9 months. Most of the patients (94.8%) were stage IVB at the time of diagnosis and the most common site of metastasis was the liver (42.8%). Disease control rate was 59.5%: 2 (1.2%) patients with complete response, 26 (15.0%) patients with partial response and 75 (43.4%) patients with stable disease. Overall survival (OS) and progression-free survival were 8.1 (95% confidence interval [CI], 7.1-10.2) and 5.6 (95% CI 4.5-6.8) months, respectively. Multivariable regression model indicated that metastasis to liver (hazard ratio [HR] = 1.63, 95% CI 1.11-2.40; P = 0.013), neutrophil-to-lymphocyte ratio (NLR) ≥3 (HR 1.65, 95% CI 1.09-2.49; P = 0.017), CEA ≥ 5 ng/mL (HR 1.50, 95% CI 1.02-2.19; P = 0.038), and CA19-9 ≥ 500 U/mL (HR 1.59, 95% CI 1.01-2.50; P = 0.043) were significantly associated with OS.

   CONCLUSIONS GEMCIS demonstrated a high disease control rate in patients with unresectable GBC. Factors independently related to OS were metastasis to liver, NLR ≥ 3, CEA ≥ 5 ng/mL and CA19-9 ≥ 500 U/mL.

   PubMed IF 4.1 소화기내과
2. 262019

   제1저자 김병근 · 교신저자 박흥우

   Kim BK, Lee HS, Sohn KH, Lee SY, Cho SH, Park HW

   Different Biological Pathways Are Up-regulated in the Elderly With Asthma: Sputum Transcriptomic Analysis.

   Allergy Asthma Immunol Res. 2019;11(1):104-115.

   Abstract

   BACKGROUND Elderly asthma (EA) is increasing, but the pathogenesis is unclear. This study aimed to identify EA-related biological pathways by analyzing genome-wide gene expression profiles in sputum cells.

   METHODS A total of 3,156 gene probes with significantly differential expressions between EA and healthy elderly controls were used for a hierarchical clustering of genes to identify gene clusters. Gene set enrichment analysis provided biological information, with replication from Gene Expression Omnibus expression profiles.

   RESULTS Fifty-five EA patients and 10 elderly control subjects were enrolled. Two distinct gene clusters were found. Cluster 1 (n = 35) showed a lower eosinophil proportion in sputum and less severe airway obstruction compared to cluster 2 (n = 20). The replication data set also identified 2 gene clusters (clusters 1' and 2'). Among 5 gene sets significantly enriched in cluster 1 and 3 gene sets significantly enriched in cluster 2, we confirmed that 2 were significantly enriched in the replication data set (OXIDATIVE_PHOSPHORYLATION gene set in cluster 1 and EPITHELIAL MESENCHYMAL TRANSITION gene set in cluster 2').

   CONCLUSIONS The findings of 2 distinct gene clusters in EA and different biological pathways in each gene cluster suggest 2 different pathogenesis mechanisms underlying EA.

   PubMed IF 4.3 알레르기내과
3. 252019

   제1저자 강지훈 · 교신저자 박경우, 김효수

   Kang J, Park KW, Palmerini T, Stone GW, Lee MS, Colombo A, Chieffo A, Feres F, Abizaid A, Bhatt DL, Valgimigli M, Hong MK, Jang Y, Gilard M, Morice MC, Park DW, Park SJ, Jeong YH, Park J, Koo BK, Kim HS

   Racial Differences in Ischaemia/Bleeding Risk Trade-Off during Anti-Platelet Therapy: Individual Patient Level Landmark Meta-Analysis from Seven RCTs.

   Thromb Haemost. 2019;119(1):149-162.

   Abstract

   BACKGROUND Prolonged dual anti-platelet therapy (DAPT) is intended to reduce ischaemic events, at the cost of an increased bleeding risk in patients undergoing percutaneous coronary intervention (PCI). In this study, we evaluated whether race influences the ischaemia/bleeding risk trade-off.

   METHODS We searched for randomized clinical trials (RCTs) comparing DAPT duration after PCI. To compare the benefit or harm between DAPT duration by race, individual patient-level landmark meta-analysis was performed after discontinuation of the shorter duration DAPT group in each RCT. The primary ischaemic endpoint was major adverse cardiac events (MACEs), and the primary bleeding endpoint was major bleeding events (clinicaltrials.gov NCT03338335).

   RESULTS Seven RCTs including 16,518 patients (8,605 East Asians, 7,913 non-East Asians) were pooled. MACE occurred more frequently in non-East Asians (0.8% vs. 1.8%, p < 0.001), while major bleeding events occurred more frequently in East Asians (0.6% vs. 0.3%, p = 0.001). In Cox proportional hazards model, prolonged DAPT significantly increased the risk of major bleeding in East Asians (hazard ratio [HR], 2.843, 95% confidence interval [CI], 1.474-5.152, p = 0.002), but not in non-East Asians (HR, 1.375, 95% CI, 0.523-3.616, p = 0.523). East Asians had a higher median probability risk ratio of bleeding to ischaemia (0.66 vs. 0.15), and the proportion of patients with higher probability of bleeding than ischaemia was significantly higher in East Asians (32.3% vs. 0.4%, p < 0.001).

   CONCLUSION We suggest that the ischaemia/bleeding trade-off may be different between East Asians and non-East Asians. In East Asians, prolonged DAPT may have no effect in reducing the ischaemic risk, while significantly increases the bleeding risk.

   PubMed IF 5.2 순환기내과
4. 242019

   제1저자 박세훈,백충희 · 교신저자 이하정

   Park S, Baek CH, Cho H, Yu MY, Kim YC, Go H, Kim YH, Lee JP, Min SI, Ha J, Moon KC, Kim YS, Ahn C, Park SK, Lee H

   Glomerular crescents are associated with worse graft outcome in allograft IgA nephropathy.

   Am J Transplant. 2019;19(1):145-155.

   Abstract

   The prognosis of patients with allograft IgA nephropathy (IgAN) requires further investigation. We performed a bicenter retrospective cohort study on kidney transplant recipients diagnosed with IgAN in allograft biopsy. Recipients without allograft IgAN but with known IgAN before transplantation were included as the control group. We investigated the associations between clinicopathological characteristics, including allograft crescents, and the risk of death-censored graft failure. In total, 1256 IgAN patients in both pre- and posttransplant stages were included. Among them, 559 were diagnosed with allograft IgAN, which was a time-dependent risk factor for worse prognosis (adjusted hazard ratio = 5.009 [3.610-6.951]; P < .001) during a median of 8.1 years of follow-up. Of the patients with allograft IgAN, 88 (15.9%) had glomerular crescents, including 40 patients (7.2%) with >10% crescent formation in the total biopsied glomeruli. The presence of glomerular crescents in IgAN was associated with a worse graft prognosis, and the association was still valid with the C scores of the current Oxford classification. In conclusion, allograft IgAN is a time-dependent event and is associated with worse graft outcomes. The pathological characteristics of allograft, particularly the degree of glomerular crescent formation, may represent important risk factors for a poor prognosis.

   PubMed IF 8.1 신장내과
5. 232019

   제1저자 이정규, 이지연 · 교신저자 임재준

   Lee JK, Lee JY, Kim DK, Yoon HI, Jeong I, Heo EY, Park YS, Jo YS, Lee JH, Park SS, Park JS, Kim J, Lee SM, Joh JS, Lee CH, Lee J, Choi SM, Park JH, Lee SH, Cho YJ, Lee YJ, Kim SJ, Kwak N, Hwang YR, Kim H, Ki J, Lim JN, Choi HS, Lee M, Song T, Kim HS, Han J, Ahn H, Hahn S, Yim JJ

   Substitution of ethambutol with linezolid during the intensive phase of treatment of pulmonary tuberculosis: a prospective, multicentre, randomised, open-label, phase 2 trial.

   Lancet Infect Dis. 2019;19(1):46-55.

   Abstract

   BACKGROUND Linezolid improves the treatment outcomes of multidrug-resistant tuberculosis substantially. We investigated whether use of linezolid instead of ethambutol increases the proportion of sputum culture conversion at 8 weeks of treatment in patients with pulmonary tuberculosis.

   METHODS We did a phase 2, multicentre, randomised, open-label trial for patients with pulmonary tuberculosis at the three affiliated hospitals to Seoul National University and National Medical Center (Seoul-Seongnam, South Korea). Patients, aged 20-80 years, with a positive sputum for pulmonary tuberculosis, but without resistance to rifampicin, and current treatment administered for 7 days or fewer, were randomly assigned at a 1:1:1 ratio into three groups. The control group received ethambutol (2 months) with isoniazid, rifampicin, and pyrazinamide. The second group used linezolid (600 mg/day) for 2 weeks and the third group for 4 weeks instead of ethambutol for 2 months. We used a minimisation method to randomise, and stratified according to institution, cavitation on chest radiographs, and diabetes. The primary endpoint was the proportion of patients with negative culture conversion of sputum in liquid media after 8 weeks of treatment. The results of this trial were analysed primarily in the modified intention-to-treat population. The trial is registered with ClinicalTrials.gov, number NCT01994460.

   FINDINGS Between Feb 19, 2014, and Jan 13, 2017, a total of 429 patients were enrolled and 428 were randomly assigned into either the control group (142 patients), the linezolid 2 weeks group (143 patients), or the linezolid 4 weeks group (143 patients). Among them, 401 were eligible for primary efficacy analyses. In the modified intention-to-treat analyses, negative cultures in liquid media at 8 weeks of treatment were observed in 103 (76·9%) of 134 control patients, 111 (82·2%) of 135 in the linezolid 2 weeks group, and 100 (75·8%) of 132 in the linezolid 4 weeks groups. The difference from the control group was 5.4% (95% CI -4·3 to 15·0, p=0·28) for the linezolid 2 weeks group and -1·1% (-11·3 to 9·1, p=0·83) for the linezolid 4 weeks group. Numbers of patients who experienced at least one adverse event were similar across the groups (86 [62·8%] of 137 in control, 79 [57·2%] of 138 in the linezolid 2 weeks group, and 75 [62·0%] of 121 in the linezolid 4 weeks group). Resistance to linezolid was not identified in any patient.

   INTERPRETATION Higher rates of culture conversion at 8 weeks of treatment with short-term use of linezolid were not observed. However, safety analyses and the resistance profile suggested the potential role of linezolid in shortening of treatment for drug-susceptible tuberculosis.

   FUNDING Ministry of Health and Welfare, South Korea.

   PubMed IF 29.4 호흡기내과
6. 222019

   제1저자 신중곤 · 교신저자 김윤준

   Shin JG, Cheong HS, Kim JY, Lee JH, Yu SJ, Yoon JH, Cheong JY, Cho SW, Park NH, Namgoong S, Kim LH, Kim YJ, Shin HD

   Identification of additional EHMT2 variant associated with the risk of chronic hepatitis B by GWAS follow-up study.

   Genes Immun. 2019;20(1):1-9.

   Abstract

   Chronic hepatitis B (CHB) is a precursor to liver cirrhosis and hepatocellular carcinoma, caused by a Hepatitis B viral infection. Genome-wide association studies (GWASs) have been conducted to find genes associated with CHB risk. In previous GWAS, EHMT2 was identified as one of the susceptibility genes for CHB. To further characterize this association and discover possible causal variants, we conducted an additional association study. A total of 11 EHMT2 single-nucleotide polymorphisms (SNP) were selected and genotyped in 3902 subjects (1046 CHB patients and 2856 controls). An additional eight imputed SNPs were also included in further analysis. As a result, rs35875104 showed a strong association with the CHB, along with the previously reported genetic marker for CHB risk, rs652888 (odds ratio (OR) = 0.53, P = 2.20 × 10^-8 at rs35875104 and OR = 1.58, P = 9.90 × 10^-12 at rs652888). In addition, linkage disequilibrium and conditional analysis identified one SNP (rs35875104) as a novel genetic marker for CHB susceptibility. The GRSs (genetic risk scores) were calculated to visualize the combined genetic effects of all known CHB-associated loci, including EHMT2 rs35875104, which was additionally identified in this study. The findings from the present study may be useful for further understanding of the genetic etiology of CHB.

   PubMed IF 4.2 소화기내과
7. 212019

   제1저자 김광일 · 교신저자 김광일

   Kim KI, Kang MG, Yoon SJ, Choi JY, Kim SW, Kim CH

   Relationship between Within-Visit Blood Pressure Variability and Skeletal Muscle Mass.

   J Nutr Health Aging. 2019;23(1):79-83.

   Abstract

   Sarcopenia, defined as loss of skeletal muscle mass and function with age, is an important health issue in aging society. We tried to investigate the relationship between blood pressure variability and skeletal muscle mass in nation-wide large population cohort. This cross-sectional study was based on data acquired in the Korea National Health and Nutrition Examination Survey (KNHANES), conducted from 2009 to 2011 by the Korean Centers for Disease Control and Prevention. We included 14,481 participants (age ≥ 20 years, male 6,302) for the analysis who had both blood pressure and whole-body dual energy X-ray absorptiometry (DXA) scan data. As an intra-individual within-visit blood pressure variability index, we calculated standard deviation (SD), coefficient of variation (CV), and maximum minus minimum BP difference (MMD) of systolic and diastolic blood pressure, which was measured 3 times. Appendicular skeletal muscle mass (ASM) was the sum of lean masses of both arms and legs. We adjusted ASM by body mass index. Significant inverse relationship was observed between blood pressure variability index (SD, CV, and MMD) and adjusted ASM. Blood pressure variability index were significantly higher in the lowest ASM quintile group both in male and female participants (p<0.001). In multivariate analysis, blood pressure variability index were significantly associated with ASM, even after adjusting confounding factors (p<0.001). In conclusion, hemodynamic influence may play an important role in the development of sarcopenia.

   PubMed IF 5 노인병내과
8. 202019

   제1저자 김미소 · 교신저자 김태민

   Kim M, Kim TM, Keam B, Kim YJ, Paeng JC, Moon KC, Kim DW, Heo DS

   A Phase II Trial of Pazopanib in Patients with Metastatic Alveolar Soft Part Sarcoma.

   Oncologist. 2019;24(1):20-e29.

   Abstract

   LESSONS LEARNED Pazopanib shows a modest efficacy in metastatic alveolar soft part sarcoma.Clinical outcomes were comparable to those in previous studies using antiangiogenic drugs.Further prospective studies evaluating the benefit of pazopanib in alveolar soft part sarcoma with a larger sample are warranted to validate results.

   BACKGROUND Alveolar soft part sarcoma (ASPS) is a rare mesenchymal malignant tumor characterized by an unbalanced translocation, t(X;17)(p11.2;q25), which leads to the fusion of ASPSCR1 to the TFE3 transcription factor. Because this results in the upregulation of angiogenesis-related transcripts, antiangiogenic drugs have been used in ASPS patients.

   METHODS This open-label, single-arm, multicenter, investigator-initiated phase II trial was designed to evaluate efficacy and safety of pazopanib 800 mg once daily in patients with metastatic ASPS. The primary endpoint was investigator-assessed overall response rate (ORR), and secondary endpoints were toxicity, progression-free survival (PFS), and overall survival (OS). ⁶⁸Ga-RGD (Arg-Gly-Asp) positron emission tomography (PET) scan and gene expression profiling using NanoString platform were performed for biomarker analysis.

   RESULTS Six patients with histologically confirmed metastatic ASPS were enrolled between December 2013 and November 2014. Among six patients, one achieved a partial response (PR) (ORR 16.7%) and five patients showed stable disease (SD). With a median follow-up of 33 months (range 18.7-39.3 months), median PFS was 5.5 months (95% confidence interval [CI] 3.4-7.6 months), and median OS was not reached. There were no severe toxicities except one patient with grade 3 diarrhea.

   CONCLUSION Pazopanib showed modest antitumor activity with manageable toxicities for patients with metastatic ASPS.

   PubMed IF 4.7 혈액종양내과
9. 192019

   제1저자 Ahsan Azhar, 김유정 · 교신저자 Eduardo Bruera

   Azhar A, Kim YJ, Haider A, Hui D, Balankari VR, Epner MC, Park M, Liu DD, Williams J, Frisbee-Hume SE, Allo JA, Bruera E

   Response to Oral Immediate-Release Opioids for Breakthrough Pain in Patients with Advanced Cancer with Adequately Controlled Background Pain.

   Oncologist. 2019;24(1):125-131.

   Abstract

   BACKGROUND There is limited evidence about the response of breakthrough pain (BTP) to the most commonly used oral immediate-release (IR) opioids. Our aim was to determine response rate to oral IR opioids for BTP control in patients with advanced cancer.

   MATERIALS AND METHODS In this prospective study, palliative care outpatients, with advanced cancer and adequately managed background pain, were asked to complete a self-administered survey. We assessed patients' baseline demographics, pain characteristics, alcoholism (CAGE questionnaire), tobacco and substance abuse, and Edmonton Symptom Assessment Scores (ESAS). We determined the effectiveness of oral IR BTP opioids by using a 7-point Likert scale ranging from "very ineffective" to "very effective." "Effective" and "very effective" were defined a priori as a good response to IR opioids for BTP.

   RESULTS Of 592 evaluable patients, 192 (32%) had background pain of ≤3 (ESAS pain scale 0-10). Among these 192 patients, 152 (79%) reported BTP, 143/152 (94%) took oral IR opioids for BTP, and 127/143 (89%) responded to a median dose of 10% of the total morphine equivalent daily dose. In univariate logistic regression analysis, younger age (odds ratio [OR], 0.94 per year; p = .008), higher ESAS scores for pain (OR, 1.32; p = .012), anxiety (OR, 1.24; p = .017), and dyspnea (OR, 1.31; p = .007) had statistically significant association with poor response to IR opioids for BTP. In multicovariate logistic regression, adjusted for age, a higher ESAS dyspnea score was significantly associated with poor response to oral IR opioids (OR, 1.44; p = .002).

   CONCLUSION The vast majority of patients with advanced cancer with adequately controlled background pain reported a good response to oral IR opioids for BTP, supporting their use in clinical practice.

   IMPLICATIONS FOR PRACTICE Oral immediate-release opioids are standard treatment for cancer breakthrough pain. However, information regarding treatment response to these commonly used opioids is limited. This study provides information that the vast majority of patients with advanced cancer, with adequately controlled background pain, reported good response to oral immediate release opioids for managing their breakthrough pain episodes. Results of this study support the use of conventional oral immediate release opioids that are relatively inexpensive and readily available for management of breakthrough pain in patients with advanced cancer.

   PubMed IF 4.7 혈액종양내과
10. 182019

    제1저자 박현경, 정창욱 · 교신저자 김인호, 곽철

    Park H, Jeong CW, Yuk H, Ku JH, Kim HH, Kwak C, Kim I

    Influence of Tumor Thrombus on Occurrence of Distant Venous Thromboembolism and Survival in Patients With Renal Cell Carcinoma After Surgery.

    Clin Appl Thromb Hemost. 2019;25:1076029618823288.

    Abstract

    Tumor thrombus is a unique characteristic of renal cell carcinoma (RCC). However, only a few studies have reported its clinical influence on the occurrence of venous thromboembolism (VTE). This study aimed to clarify the influence of tumor thrombus and other risk factors for VTE and to elucidate the impact of tumor thrombus on survival outcomes. We retrospectively reviewed data from patients with RCC who underwent radical or partial nephrectomy from September 1999 to August 2015 at Seoul National University Hospital. A total of 2762 patients were enrolled. The 1- and 5-year cumulative incidences of VTE were 0.5% ± 0.1% and 1.5% ± 0.3%, respectively. During a median follow-up of 39.0 months (95% confidence interval [CI], 37.1-41.0 months), deep vein thrombosis occurred in 13 patients and pulmonary embolism in 15 patients. Patients with tumor thrombus (diagnosed by surgical pathology findings) had a significantly higher incidence of VTE than those without thrombus (odds radio 8.160, 95% CI, 1.480-45.004). Older age (≥60 years) and higher preoperative C-reactive protein (>0.5 mg/dL) were also significant risk factors for VTE. Additionally, tumor thrombus was independently associated with worse progression-free survival (PFS) but not with overall survival (OS) in multivariable analysis (hazard ratio [HR] 1.916, 95% CI, 1.295-2.834 for PFS; HR 1.164, 95% CI, 0.755-1.793 for OS). In conclusion, the incidence of VTE was relatively low in patients who underwent surgery for RCC. Nevertheless, patients with tumor thrombus had an increased risk of VTE and should be closely monitored for VTE.

    PubMed IF 2.1 혈액종양내과
11. 172019

    제1저자 송영신 · 교신저자 조선욱, 박영주

    Song YS, Kim MJ, Sun HJ, Kim HH, Shin HS, Kim YA, Oh BC, Cho SW, Park YJ

    Aberrant Thyroid-Stimulating Hormone Receptor Signaling Increases VEGF-A and CXCL8 Secretion of Thyroid Cancer Cells, Contributing to Angiogenesis and Tumor Growth.

    Clin Cancer Res. 2019;25(1):414-425.

    Abstract

    PURPOSE Thyroid-stimulating hormone (TSH) suppression is widely used to treat well-differentiated thyroid cancer, whereas its role in poorly differentiated thyroid cancer (PDTC) is undetermined. Besides thyrocytes, TSH also binds to stromal cells, comprising tumor microenvironments. This study aimed to investigate the effects of TSH on tumor microenvironments in PDTC.

    EXPERIMENTAL DESIGN An ectopic tumor model using PDTC cells (BHP10-3SCp and FRO), which exhibit TSH/cAMP-independent cell growth, was treated with TSH. IHC was performed using tissue microarrays from 13 PDTCs.

    RESULTS TSH treatment significantly enhanced tumor growth of PDTCs with increased vascularity but not that of breast cancer cells, suggesting this effect is unique to thyroid cancer cells, not stromal cells. TSH significantly upregulated VEGF-A and CXCL8 expressions in BHP10-3SCp cells via AKT and ERK signaling, resulting in higher concentrations of VEGF-A and CXCL8 in conditioned medium of TSH-treated BHP10-3SCp cells (TSH-CM) compared with controls. TSH-CM treatment enhanced tube formation potentials of endothelial cells, and blocking VEGF and/or CXCL8 reduced them. Blocking VEGF and/or CXCL8 also reduced TSH-dependent tumor growth with reduced tumor vasculature in vivo. TSH-treated tumors showed increased macrophage densities, and macrophage inhibition reduced TSH-dependent tumor growth in vivo. In human PDTCs, preoperative TSH levels were positively associated with VEGF-A and tumor size, and the expression of VEGF-A was positively correlated with CD31, CD163, and CXCL8, and their clinical poor prognosis.

    CONCLUSIONS Aberrant TSH receptor signaling modulates tumor angiogenesis by stimulating VEGF-A and CXCL8 secretion from PDTC cells and enhances tumor growth; thus, TSH suppression is beneficial for treating PDTCs.

    PubMed IF 10.9 내분비대사내과
12. 162019

    제1저자 강버들, 김유정 · 교신저자 박혜연

    Kang B, Kim YJ, Suh SW, Son KL, Ahn GS, Park HY

    Delirium and its consequences in the specialized palliative care unit: Validation of the Korean version of Memorial Delirium Assessment Scale.

    Psychooncology. 2019;28(1):160-166.

    Abstract

    OBJECTIVES Delirium is highly prevalent in patients with advanced cancer. This study aimed to investigate delirium rates and potential associated factors such as mortality in patients admitted to an acute palliative care unit (APCU). Our second aim was to validate the Korean version of the Memorial Delirium Assessment Scale (K-MDAS).

    METHODS A total of 102 patients with advanced cancer, and who were admitted to the APCU, were assessed. Demographic data were collected alongside clinical diagnosis, Eastern Cooperative Oncology Group (ECOG) performance status, clinical symptoms according to the Edmonton Symptom Assessment System, history of smoking, alcohol use, hypnotic use, and daily dose of morphine were collected. The Confusion Assessment Method, the Delirium Rating Scale-Revised 98, and the K-MDAS were measured at admission and 1 week later.

    RESULTS Twenty-four patients (23.52%) were diagnosed with delirium, and associated factors were old age (P = 0.007), higher ECOG (P = 0.011), and drowsiness (P < 0.001). The presence of delirium was an independent predictor of 1-month mortality; male gender, higher body mass index, and hypnotic use were also related to 1-month mortality. The K-MDAS had reliable internal consistency (α = 0.942) and showed sensitivity of 0.958 and specificity of 0.921 at the optimal cutoff score for diagnosing delirium of 9.

    CONCLUSIONS Delirium was prevalent in patients admitted to the APCU and was associated with 1-month mortality. The K-MDAS showed acceptable reliability and validity and can be used to screen for delirium in a palliative care setting.

    PubMed IF 3.9 혈액종양내과
13. 152019

    제1저자 박세훈,조현정 · 교신저자 이하정

    Park S, Cho H, Park S, Lee S, Kim K, Yoon HJ, Park J, Choi Y, Lee S, Kim JH, Kim S, Chin HJ, Kim DK, Joo KW, Kim YS, Lee H

    Simple Postoperative AKI Risk (SPARK) Classification before Noncardiac Surgery: A Prediction Index Development Study with External Validation.

    J Am Soc Nephrol. 2019;30(1):170-181.

    Abstract

    BACKGROUND Researchers have suggested models to predict the risk of postoperative AKI (PO-AKI), but an externally validated risk index that can be practically implemented before patients undergo noncardiac surgery is needed.

    METHODS We performed a retrospective observational study of patients without preexisting renal failure who underwent a noncardiac operation (≥1 hour) at two tertiary hospitals in Korea. We fitted a proportional odds model for an ordinal outcome consisting of three categories: critical AKI (defined as Kidney Disease Improving Global Outcomes AKI stage ≥2, post-AKI death, or dialysis within 90 days after surgery), low-stage AKI (defined as PO-AKI events not fulfilling the definition of critical AKI), and no PO-AKI.

    RESULTS The study included 51,041 patients in a discovery cohort and 39,764 patients in a validation cohort. The Simple Postoperative AKI Risk (SPARK) index included a summation of the integer scores of the following variables: age, sex, expected surgery duration, emergency operation, diabetes mellitus, use of renin-angiotensin-aldosterone inhibitors, baseline eGFR, dipstick albuminuria hypoalbuminemia, anemia, and hyponatremia. The model calibration plot showed tolerable distribution of observed and predicted probabilities in both cohorts. The discrimination power of the SPARK index was acceptable in both the discovery (c-statistic 0.80) and validation (c-statistic 0.72) cohorts. When four SPARK classes were defined on the basis of the sum of the risk scores, the SPARK index and classes fairly reflected the risks of PO-AKI and critical AKI.

    CONCLUSIONS Clinicians may consider implementing the SPARK index and classifications to stratify patients' PO-AKI risks before performing noncardiac surgery.

    PubMed IF 9.7 신장내과
14. 142019

    제1저자 변자민 · 교신저자 변자민

    Byun JM, Kim D, Shin DY, Kim I, Koh Y, Yoon SS

    Combination of Genetic Aberration With International Staging System Classification for Stratification of Asian Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation.

    In Vivo. 2019;33(2):611-619.

    Abstract

    BACKGROUND/AIM The aim of the study was to contribute to the development of adaptive risk stratification methods specific to Asian multiple myeloma (MM) patients undergoing autologous stem cell transplantation (ASCT).

    PATIENTS AND METHODS We conducted this study to evaluate the prognostic impact of genetic abnormalities detected by fluorescent in situ hybridization (FISH) on survival outcomes in combination with the International Staging System (ISS) classification in 161 MM patients. This was a single-center retrospective longitudinal cohort study of newly diagnosed MM patients undergoing ASCT within 12 months from initial diagnosis. A single-center retrospective cohort study of newly diagnosed MM.

    RESULTS Patients were divided into 3 groups according to risk stratification: 1) low-risk, patients without del(17p13) nor t(14;16) or t(4;14) and ISS I/II; 2) high-risk, patients with t(4;14), regardless of ISS stage; 3) intermediate-risk, all remaining patients. The median PFS for the low-risk group was 18 months versus 13 months for the intermediate group (p=0.047, HR=1.527, 95%CI=1.006-2.316) versus 10 months for the high-risk group (p<0.001, HR=2.656, 95%CI=1.572-4.490).

    CONCLUSION An ISS/FISH-based prognostication strategy was developed that can predict PFS for Asian MM patients undergoing ASCT.

    PubMed IF 1.8 혈액종양내과
15. 132019

    제1저자 윤혁 · 교신저자 양석균

    Yoon H, Yang SK, So H, Lee KE, Park SH, Jung SA, Choh JH, Shin CM, Park YS, Kim N, Lee DH

    Development, validation, and application of a novel tool to measure disease-related knowledge in patients with inflammatory bowel disease.

    Korean J Intern Med. 2019;34(1):81-89.

    Abstract

    BACKGROUND/AIMS The Crohn's and Colitis Knowledge (CCKNOW) score does not reflect updated knowledge relating to inflammatory bowel disease (IBD). The aim of this study was to develop, validate, and apply a novel tool to measure disease-related knowledge in IBD patients.

    METHODS A questionnaire composed of 24 items regarding knowledge of IBD was developed: Inflammatory Bowel Disease Knowledge (IBD-KNOW). Discriminate ability of IBD-KNOW was validated in three occupational groups (14 doctors, 20 nurses, and 19 clerks). The CCKNOW and IBD-KNOW were administered to IBD patients. Factors affecting the level of IBD-related knowledge were analyzed.

    RESULTS The median Inflammatory Bowel Disease Knowledge (IBD-KNOW) score was significantly different among the three groups for validation (22 doctors, 20 nurses, and five clerks; p < 0.001). The IBD-KNOW showed excellent internal consistency (Cronbach α = 0.952) and high correlation with CCKNOW (Spearman ρ = 0.827, p = 0.01). A total of 200 IBD patients (120 Crohn's disease, 80 ulcerative colitis) completed questionnaires. Multivariate analysis showed that a higher IBDKNOW score than the median was associated with hospitalization history (odds ratio [OR], 2.625; p = 0.003), high education level (OR, 2.498; p = 0.012), and information acquired from patient organization (OR, 3.305, p = 0.035).

    CONCLUSION The IBD-KNOW demonstrated excellent test characteristics. Hospitalization history, education level, and information acquired from patient organization play an important role in correct IBD-related knowledge.

    PubMed IF 2.2 소화기내과
16. 122019

    제1저자 이윤규 · 교신저자 김인호

    Lee YG, Kim I, Oh S, Shin DY, Koh Y, Lee KW

    Small RNA sequencing profiles of mir-181 and mir-221, the most relevant microRNAs in acute myeloid leukemia.

    Korean J Intern Med. 2019;34(1):178-183.

    Abstract

    BACKGROUND/AIMS To evaluate and select microRNAs relevant to acute myeloid leukemia (AML) pathogenesis, we analyzed differential microRNA expression by quantitative small RNA next-generation sequencing using duplicate marrow samples from individual AML patients.

    METHODS For this study, we obtained paired marrow samples at two different time points (initial diagnosis and first complete remission status) in patients with AML. Bone marrow microRNAs were profiled by next-generation small RNA sequencing. Quantification of microRNA expression was performed by counting aligned reads to microRNA genes.

    RESULTS Among 38 samples (32 paired samples from 16 AML patients and 6 normal marrow controls), 27 were eligible for sequencing. Small RNA sequencing showed that 12 microRNAs were selectively expressed at higher levels in AML patients than in normal controls. Among these 12 microRNAs, mir-181, mir-221, and mir-3154 were more highly expressed at initial AML diagnosis as compared to first complete remission. Significant correlations were found between higher expression levels of mir-221, mir-146, and mir-155 and higher marrow blast counts.

    CONCLUSION Our results demonstrate that mir-221 and mir-181 are selectively enriched in AML marrow and reflect disease activity. mir-3154 is a novel microRNA that is relevant to AML but needs further validation.

    PubMed IF 2.2 혈액종양내과
17. 112019

    제1저자 양민석 · 교신저자 강혜련

    Yang MS, Kim JY, Kang MG, Lee SY, Jung JW, Cho SH, Min KU, Kang HR

    Direct costs of severe cutaneous adverse reactions in a tertiary hospital in Korea.

    Korean J Intern Med. 2019;34(1):195-201.

    Abstract

    BACKGROUND/AIMS There are only a few reports on the direct costs of severe cutaneous adverse reactions (SCARs), including drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), despite the tremendous negative impact these reactions can have on patients. We estimated the direct costs of treating SCARs.

    METHODS Patients admitted to a tertiary teaching hospital for the treatment of SCARs from January 1, 2005 to December 31, 2010 were included. Patients who had experienced SCARs during their admission for other medical conditions were excluded. The direct costs of hospitalization and outpatient department visits were collected. Inpatient and outpatient care costs were calculated, and factors affecting inpatient care costs were analyzed.

    RESULTS The total healthcare cost for the management of 73 SCAR patients (36 with DRESS, 21 with SJS, and 16 with TEN) was 752,067 US dollars (USD). Most of the costs were spent on inpatient care (703,832 USD). The median inpatient care cost per person was 3,720 (range, 1,133 to 107,490) USD for DRESS, 4,457 (range, 1,224 to 21,428) USD for SJS, and 8,061 (range, 1,127 to 52,220) USD for TEN. Longer hospitalization significantly increased the inpatient care costs of the patients with DRESS (by 428 USD [range, 395 to 461] per day). Longer hospitalization and death significantly increased the inpatient care costs of the patients with SJS/TEN (179 USD [range, 148 to 210] per day and an additional 14,425 USD [range, 9,513 to 19,337] for the deceased).

    CONCLUSION The management of SCARs required considerable direct medical costs. SCARs are not only a health problem but also a significant financial burden for the affected individuals.

    PubMed IF 2.2 알레르기내과
18. 102019

    제1저자 송경호, 정숙인 · 교신저자 이신원

    Song KH, Jung SI, Lee S, Park S, Kim ES, Park KH, Park WB, Choe PG, Kim YK, Kwak YG, Kim YS, Jang HC, Kiem S, Kim HI, Kim HB, Korea INfectious Diseases (KIND) study group

    Inoculum effect of methicillin-susceptible Staphylococcus aureus against broad-spectrum beta-lactam antibiotics.

    Eur J Clin Microbiol Infect Dis. 2019;38(1):67-74.

    Abstract

    Scarce information concerning the inoculum effect (InE) of methicillin-susceptible Staphylococcus aureus (MSSA) against broad-spectrum β-lactam antibiotics is available. We investigated the InE of MSSA against ceftriaxone, cefepime, meropenem, ampicillin/sulbactam and piperacillin/tazobactam. The bacteraemic MSSA isolates were collected at ten Korean general hospitals from Sep 2013 to Mar 2015. The InE was defined if MICs of antibiotics at high inoculum (HI, ~5 × 10⁷ CFU/ml) increased beyond the susceptible range compared to those at standard inoculum (SI, ~5 × 10⁵ CFU/ml). All isolates were sequenced for blaZ gene typing. Among 302 MSSA isolates, 254 (84.1%) were positive for blaZ; types A, B, C and D were 13.6%, 26.8%, 43.4% and 0.3%, respectively. Mean HI MICs of all tested antibiotics were significantly increased and increases in HI MIC of piperacillin/tazobactam (HI, 48.14 ± 4.08 vs. SI, 2.04 ± 0.08 mg/L, p < 0.001) and ampicillin/sulbactam (HI, 24.15 ± 1.27 vs. SI, 2.79 ± 0.11 mg/L, p < 0.001) were most prominent. No MSSA isolates exhibited meropenem InE, and few isolates exhibited cefepime (0.3%) and ceftriaxone (2.3%) InE, whereas 43.0% and 65.9% of MSSA isolates exhibited piperacillin/tazobactam and ampicillin/sulbactam InE, respectively. About 93% of type C blaZ versus 45% of non-type C exhibited ampicillin/sulbactam InE (p < 0.001) and 88% of type C blaZ versus 9% of non-type C exhibited piperacillin/tazobactam InE (p < 0.001). A large proportion of MSSA clinical isolates, especially those positive for type C blaZ, showed marked ampicillin/sulbactam InE and piperacillin/tazobactam.

    PubMed IF 3.2 감염내과
19. 92019

    제1저자 김경아/정완교 · 교신저자 정숙향

    Kim KA, Chung W, Choi HY, Ki M, Jang ES, Jeong SH

    Cost-effectiveness and health-related outcomes of screening for hepatitis C in Korean population.

    Liver Int. 2019;39(1):60-69.

    Abstract

    BACKGROUND/AIM In the era of direct-acting antivirals (DAA), active screening for hidden hepatitis C virus (HCV) infection is important for HCV elimination. This study estimated the cost-effectiveness and health-related outcomes of HCV screening and DAA treatment of a targeted population in Korea, where anti-HCV prevalence was 0.6% in 2015.

    METHODS A Markov model simulating the natural history of HCV infection was used to examine the cost-effectiveness of two strategies: no screening vs screening and DAA treatment. Screening was performed by integration of the anti-HCV test into the National Health Examination Program. From a healthcare system's perspective, the cost-utility and the impact on HCV-related health events of one-time anti-HCV screening and DAA treatment in Korean population aged 40-65 years was analysed with a lifetime horizon.

    RESULTS The HCV screening and DAA treatment strategy increased quality-adjusted life years (QALY) by 0.0015 at a cost of $11.27 resulting in an incremental cost-effectiveness ratio (ICER) of $7435 per QALY gained compared with no screening. The probability of the screening strategy to be cost-effective was 98.8% at a willingness-to-pay of $27 205. Deterministic sensitivity analyses revealed the ICERs were from $4602 to $12 588 and sensitive to screening costs, discount rates and treatment acceptability. Moreover, it can prevent 32 HCV-related deaths, 19 hepatocellular carcinomas and 15 decompensated cirrhosis per 100 000 screened persons.

    CONCLUSIONS A one-time HCV screening and DAA treatment of a Korean population aged 40-65 years would be highly cost-effective, and significantly reduce the HCV-related morbidity and mortality compared with no screening.

    PubMed IF 6.2 소화기내과
20. 82019

    제1저자 김은기 · 교신저자 조영민

    Kim EK, Kwak SH, Jung HS, Koo BK, Moon MK, Lim S, Jang HC, Park KS, Cho YM

    The Effect of a Smartphone-Based, Patient-Centered Diabetes Care System in Patients With Type 2 Diabetes: A Randomized, Controlled Trial for 24 Weeks.

    Diabetes Care. 2019;42(1):3-9.

    Abstract

    OBJECTIVE This study evaluated the efficacy of a smartphone-based, patient-centered diabetes care system (mDiabetes) for type 2 diabetes that contains comprehensive modules for glucose monitoring, diet, physical activity, and a clinical decision support system.

    RESEARCH DESIGN AND METHODS We conducted a 24-week, multicenter, randomized controlled trial with adult patients with inadequately controlled type 2 diabetes. The patients were randomly assigned to the mDiabetes group or the paper logbook (pLogbook) group. The primary end point was the difference of the change in HbA_1c from baseline between the two groups.

    RESULTS HbA_1c reduction from baseline was greater in the mDiabetes group (-0.40 ± 0.09%, n = 90) than in the pLogbook group (-0.06 ± 0.10%, n = 82). The difference of adjusted mean changes was 0.35% (95% CI 0.14-0.55, P = 0.001). The proportion of patients whose HbA_1c fell below 7.0% (53 mmol/mol) was 41.1% for the mDiabetes group and 20.7% for the pLogbook group (odds ratio [OR] 2.01, 95% CI 1.24-3.25, P = 0.003). The percentage of patients who attained HbA_1c levels below 7.0% (53 mmol/mol) without hypoglycemia was 31.1% in the mDiabetes group and 17.1% in the pLogbook group (OR 1.82, 95% CI 1.03-3.21, P = 0.024). There was no difference in the event numbers of severe hyperglycemia and hypoglycemia between the two groups.

    CONCLUSIONS The implementation of the mDiabetes for patients with inadequately controlled type 2 diabetes resulted in a significant reduction in HbA_1c levels, with tolerable safety profiles.

    PubMed IF 22.6 내분비대사내과
21. 72019

    제1저자 Mecoli, 박진균 · 교신저자 Chrisropher-Stine

    Mecoli CA, Park JK, Alexanderson H, Regardt M, Needham M, de Groot I, Sarver C, Lundberg IE, Shea B, de Visser M, Song YW, Bingham CO, Christopher-Stine L

    Perceptions of Patients, Caregivers, and Healthcare Providers of Idiopathic Inflammatory Myopathies: An International OMERACT Study.

    J Rheumatol. 2019;46(1):106-111.

    Abstract

    OBJECTIVE Patient-reported outcome measures (PROM) that incorporate the patient perspective have not been well established in idiopathic inflammatory myopathies (IIM). As part of our goal to develop IIM-specific PROM, the Outcome Measures in Rheumatology (OMERACT) Myositis special interest group sought to determine which aspects of disease and its effects are important to patients and healthcare providers (HCP).

    METHODS Based on a prior qualitative content analysis of focus groups, an initial list of 24 candidate domains was constructed. We subsequently conducted an international survey to identify the importance of each of the 24 domains to be assessed in clinical research. Patients with IIM, their caregivers, and HCP treating IIM completed the survey.

    RESULTS In this survey, a total of 638 respondents completed the survey, consisting of 510 patients, 101 HCP, and 27 caregivers from 48 countries. Overall, patients were more likely to rank "fatigue," "cognitive impact," and "difficulty sleeping" higher compared with HCP, who ranked "joint symptoms," "lung symptoms," and "dysphagia" higher. Both patients and providers rated muscle symptoms as their top domain. In general, patients from different countries were in agreement on which domains were most important. One notable exception was that patients from Sweden and the Netherlands ranked lung symptoms significantly higher compared to other countries including the United States and Australia (mean weighted rankings of 2.86 and 2.04 vs 0.76 and 0.80, respectively; p < 0.0001).

    CONCLUSION Substantial differences exist in how IIM is perceived by patients compared to HCP, with different domains prioritized. In contrast, patients' ratings across the world were largely similar.

    PubMed IF 3.7 류마티스내과
22. 62019

    제1저자 김진원 · 교신저자 이근욱

    Kim JW, Kim JG, Kang BW, Chung IJ, Hong YS, Kim TY, Song HS, Lee KH, Zang DY, Ko YH, Song EK, Baek JH, Koo DH, Oh SY, Cho H, Lee KW

    Treatment Patterns and Changes in Quality of Life during First-Line Palliative Chemotherapy in Korean Patients with Advanced Gastric Cancer.

    Cancer Res Treat. 2019;51(1):223-239.

    Abstract

    PURPOSE The purpose of this study was to evaluate chemotherapy patterns and changes in quality of life (QOL) during first-line palliative chemotherapy for Korean patients with unresectable or metastatic/recurrent gastric cancer (GC).

    MATERIALS AND METHODS Thiswas a non-interventional, multi-center, prospective, observational study of 527 patients in Korea. QOL assessments were conducted using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires (QLQ)-C30 and QLQ-STO22 every 3 months over a 12-month period during first-line palliative chemotherapy. The specific chemotherapy regimens were selected by individual clinicians.

    RESULTS Most patients (93.2%) received combination chemotherapy (mainly fluoropyrimidine plus platinum) as their first-line palliative chemotherapy. The median progression-free survival and overall survival were 8.2 and 14.8 months, respectively. Overall, "a little" changes (differences of 5-10 points from baseline)were observed in some of the functioning or symptom scales; none of the QOL scales showed either "moderate" or "very much" change (i.e., ≥ 11 point difference from baseline). When examining the best change in each QOL domain from baseline, scales related to some aspects of functioning, global health status/QOL, and most symptoms revealed significant improvements (p < 0.05). Throughout the course of first-line palliative chemotherapy, most patients' QOL was maintained to a similar degree, regardless of their actual response to chemotherapy.

    CONCLUSION This observational study provides important information on the chemotherapy patterns and QOL changes in Korean patientswith advanced GC. Overall, first-line palliative chemotherapy was found to maintain QOL, and most parameters showed an improvement compared with the baseline at some point during the course.

    PubMed IF 4.2 혈액종양내과
23. 52019

    제1저자 김동완 · 교신저자 허대석

    Kim DW, Kim HG, Kim JH, Park K, Kim HK, Jang JS, Kim BS, Kang JH, Lee KH, Kim SW, Ryoo HM, Kim JS, Lee KH, Kwon JH, Choi JH, Shin SW, Hahn S, Heo DS

    Randomized Phase III Trial of Irinotecan Plus Cisplatin versus Etoposide Plus Cisplatin in Chemotherapy-Naïve Korean Patients with Extensive-Disease Small Cell Lung Cancer.

    Cancer Res Treat. 2019;51(1):119-127.

    Abstract

    PURPOSE This randomized phase III study was designed to compare the efficacy and safety of irinote-can plus cisplatin (IP) over etoposide plus cisplatin (EP) in Korean patients with extensive-disease small-cell lung cancer (SCLC).

    MATERIALS AND METHODS Patients were randomly assigned to receive IP, composed of irinotecan 65 mg/m2 intravenously on days 1 and 8+cisplatin 70 mg/m2 intravenously on day 1 every 3 weeks, or EP, composed of etoposide 100 mg/m2 intravenously on days 1, 2, 3+cisplatin 70 mg/m2 intravenously on day 1, every 3 weeks for a maximum of six cycles, until disease progression, or until unacceptable toxicity occurred. The primary endpoint was overall survival.

    RESULTS A total of 362 patients were randomized to IP (n=173) and EP (n=189) arms. There were no significant differences between IP and EP arms for the median overall survival (10.9 months vs. 10.3 months, p=0.120) and the median progression-free survival (6.5 months vs. 5.8 months, p=0.115). However, there was a significant difference in response rate (62.4% vs. 48.2%, p=0.006). The pre-planned subgroup analyses showed that IP was associated with longer overall survival in male (11.3 months vs. 10.1 months, p=0.036), < 65 years old (12.7 months vs. 11.3 months, p=0.024), and Eastern Cooperative Oncology Group performance status 0/1 (12.4 months vs. 10.9 months, p=0.040) patient groups. The severity of treatment-related adverse events such as grade 3/4 anemia, nausea and diarrhea was more frequent in patients treated with IP.

    CONCLUSION The IP chemotherapy did not significantly improve the survival compared with EP chemotherapy in Korean patients with extensive-disease SCLC.

    PubMed IF 4.2 혈액종양내과
24. 42019

    제1저자 박준원 · 교신저자 이은영

    Park JW, Kim MJ, Lee JS, Ha YJ, Park JK, Kang EH, Lee YJ, Song YW, Lee EY

    Impact of Tumor Necrosis Factor Inhibitor Versus Nonsteroidal Antiinflammatory Drug Treatment on Radiographic Progression in Early Ankylosing Spondylitis: Its Relationship to Inflammation Control During Treatment.

    Arthritis Rheumatol. 2019;71(1):82-90.

    Abstract

    OBJECTIVE To investigate the impact of tumor necrosis factor inhibitor (TNFi) treatment and inflammation control on radiographic progression in early ankylosing spondylitis (AS) over 4 years.

    METHODS We included a total of 215 patients with early AS (symptom duration <10 years) treated with TNFi (the TNFi group; n = 135) or with nonsteroidal antiinflammatory drugs (NSAIDs) (the control group; n = 80). Two blinded readers assessed radiographic progression using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Inflammation control was inferred from C-reactive protein (CRP) levels time-averaged between 2 radiologic assessments. Linear mixed modeling was used to estimate mSASSS changes over radiographic intervals as well as the impact of clinical factors on outcomes.

    RESULTS The TNFi group had longer disease duration, a higher baseline CRP level, and a higher Bath Ankylosing Spondylitis Disease Activity Index than did controls. The time-averaged CRP level over radiographic intervals was lower with TNFi treatment than with NSAID treatment (mean ± SD 0.27 ± 0.30 mg/dl versus 0.61 ± 0.68 mg/dl; P < 0.001). Overall, mean ± SD mSASSS change over the 2-year interval was 1.30 ± 2.97 units. In the multivariable model adjusted for age, smoking status, baseline CRP level, and the presence of syndesmophytes at baseline, the TNFi group showed less mSASSS change over the 2-year interval (β = -0.90 [95% confidence interval {95% CI} -1.51, -0.29]). However, when a time-averaged CRP level was additionally included, it significantly influenced the mSASSS change (β = 1.02 [95% CI 0.32, 1.71]), decreasing the estimated group difference (β = -0.52 [95% CI -1.17, 0.14]). NSAID indices of both groups were not associated with either time-averaged CRP levels or mSASSS changes.

    CONCLUSION Effective suppression of inflammation by TNFi treatment decreases radiographic progression in early AS.

    PubMed IF 9.9 류마티스내과
25. 32019

    제1저자 이진용 · 교신저자 고성준,박현선

    Lee JY, Kang S, Bae JM, Jo SJ, Koh SJ, Park HS

    Psoriasis increases the risk of concurrent inflammatory bowel disease: A population-based nationwide study in Korea.

    Indian J Dermatol Venereol Leprol. 2019;85(2):145-152.

    Abstract

    BACKGROUND The epidemiology of the association between psoriasis and inflammatory bowel disease is poorly defined and remains controversial.

    AIM To evaluate the prevalence of inflammatory bowel disease in patients with psoriasis compared with the general population.

    METHODS We searched the nationwide health claims database between 2011 and 2015 and evaluated the prevalence of inflammatory bowel disease, including Crohn's disease and ulcerative colitis.

    RESULTS Prevalence of inflammatory bowel disease, Crohn's disease and ulcerative colitis in patients with psoriasis vs the general population in 2011 were 0.16, 0.05 and 0.12% vs 0.08, 0.03 and 0.06%, respectively, which increased significantly with time between 2011 and 2015. Patients with psoriasis consistently revealed higher standardized prevalence (age and sex adjusted) of inflammatory bowel disease, Crohn's disease and ulcerative colitis compared with the general population. Subgroup analysis revealed the highest risk of prevalent inflammatory bowel disease in patients younger than 19 years (crude odds ratio 5.33, 95% confidence interval 3.74-7.59). Severe psoriasis demonstrated higher odds of inflammatory bowel disease (odds ratio 2.96, 95% confidence interval 2.54-3.45) than mild psoriasis (odds ratio 1.68, 95% confidence interval 1.51-1.88).

    LIMITATIONS Limited data for doing adjustment and cross-sectional study design.

    CONCLUSIONS Psoriasis patients revealed higher risk of inflammatory bowel disease. In particular, young patients and those with severe psoriasis may require closer monitoring and comprehensive management.

    PubMed IF 3.4 소화기내과
26. 22019

    제1저자 손대원 · 교신저자 손대원

    Sohn DW, Park JB, Lee SP, Kim HK, Kim YJ

    Clinical implication of right-sided augmentation pressure in patients with pulmonary hypertension.

    Pulm Circ. 2019;9(1):2045894019833352.

    Abstract

    Similar to left ventricular and aortic pressure waveforms, augmentation pressure (AugPr) in the right ventricular (RV) pressure waveform is also frequent in patients with pulmonary hypertension (PH). This study sought to evaluate whether the degree of AugPr in RV pressure waveform has prognostic value. Forty-one patients (13 men; mean age = 50.7 ± 16.1 years) with group 1 PH (mean pulmonary artery pressure [mPAP] ≥ 25 mmHg) who underwent cardiac catheterization as part of their work-up were retrospectively enrolled. Patients were divided into three groups. Group A: AugPr/RV systolic pressure < 25%; group B: AugPr/RV systolic pressure ≥ 25%; and group C: no discernible AugPr but showing peaked RV pressure waveform. Ten patients were included in group A (male-to-female ratio 3:7; mean age = 45.9 ± 12.1 years), 12 in group B (4:8, 53.8 ± 14.6 years), and 19 in group C (6:13, 51.8 ± 18.7 years). No differences in mPAP were seen between the three groups. Pulse pressure was significantly higher in group C compared to group A. Eight patients died during the mean follow-up period of 35.9 ± 30.7 months; the incidence of death was significantly higher in group C than in the other groups (one patient in group A and seven patients in group C). AugPr in RV pressure waveform has prognostic value in patients with PH. Therefore, additional attention should be given to the RV pressure waveform in patients with PH undergoing invasive pressure measurements as a part of their work-up.

    PubMed IF 2.4 순환기내과
27. 12019

    제1저자 강성호 · 교신저자 김범석,안용운

    Kang SH, Keam B, Ahn YO, Park HR, Kim M, Kim TM, Kim DW, Heo DS

    Inhibition of MEK with trametinib enhances the efficacy of anti-PD-L1 inhibitor by regulating anti-tumor immunity in head and neck squamous cell carcinoma.

    Oncoimmunology. 2019;8(1):e1515057.

    Abstract

    Major histocompatibility complex (MHC) class I downregulation is the primary immune evasion mechanism associated with failure in anti-PD-1/PD-L1 blockade therapies for cancer. Here, we examined the role of MEK signaling pathway inhibition in head and neck squamous cell carcinoma (HNSCC) both in vitro and in vivo. We found that trametinib, a small molecule inhibitor of MEK, significantly enhanced MHC class I and PD-L1 expression in human HNSCC cell lines, and this occurred via STAT3 activation. Trametinib also further upregulated the increase in CXCL9 and CXCL10 expression caused by IFN-γ in HNSCC cells, which is associated with T cell infiltration in tumor tissues. Finally, we evaluated the therapeutic efficacy of trametinib combined with an anti-PD-L1 monoclonal antibody in vivo, using SCCVII mouse syngeneic tumor model for HNSCC. While neither PD-L1 blockade nor trametinib treatment alone affected tumor growth, the combined therapy significantly delayed tumor growth. Our results indicate that in the combined therapy trametinib increases CD8⁺ T cell infiltration in the tumor site and upregulates antigen presentation, and this may be associated with enhanced PD-L1 blockade efficacy. Furthermore, our results suggest that this combination would therapeutically benefit patients with HNSCC.

    PubMed IF 5.503 혈액종양내과

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