Purpose: Vascular endothelial growth factor tyrosine kinase inhibitors (TKIs) have been the standard of care for advanced and metastatic clear cell renal cell carcinoma (ccRCC). However, the therapeutic effect of TKI monotherapy remains unsatisfactory given the high rates of acquired resistance to TKI therapy despite favorable initial tumor response. Materials and Methods: To define the TKI-resistance mechanism and identify new therapeutic target for TKI-resistant ccRCC, an integrative differential gene expression analysis was performed using acquired resistant cohort and a public dataset. Sunitinib-resistant RCC cell lines were established and used to test their malignant behaviors of TKI resistance through in vitro and in vivo studies. Immunohistochemistry was conducted to compare expression between the tumor and normal kidney and verify expression of pathway-related proteins. Results: Integrated differential gene expression analysis revealed increased interferon-induced transmembrane protein 3 (IFITM3) expression in post-TKI samples. IFITM3 expression was increased in ccRCC compared with the normal kidney. TKI-resistant RCC cells showed high expression of IFITM3 compared with TKI-sensitive cells and displayed aggressive biologic features such as higher proliferative ability, clonogenic survival, migration, and invasion while being treated with sunitinib. These aggressive features were suppressed by the inhibition of IFITM3 expression and promoted by IFITM3 overexpression, and these findings were confirmed in a xenograft model. IFITM3-mediated TKI resistance was associated with the activation of TRAF6 and MAPK/AP-1 pathways. Conclusions These results demonstrate IFITM3-mediated activation of the TRAF6/MAPK/AP-1 pathways as a mechanism of acquired TKI resistance, and suggest IFITM3 as a new target for TKI-resistant ccRCC.

Objectives: ：The high lifetime prevalence of depression in Korea is related to problems such as suicide and decreased productivity, as well as the cost of disease due to increased use of medical services, which can cause great socioeconomic loss. Therefore, in this study, the burden of disease of depression and the importance of managing mental health diseases, which are increasing day by day, are suggested to be helpful in determining priorities in health policy establishment. Methods: ：In this study, the socio-economic cost of depression was calculated by dividing it into direct cost and indirect cost. For statistical data, data from the National Health Insurance Service of the public and statistics on diseases of national interest were mainly used. Results: ：As a result, the socio-economic cost of depression in 2019 estimated in this study was calculated to be a total of KRW 4.83 trillion, with direct costs 692.9 billion won and indirect costs 4.13 trillion won. Among them, the cost due to decrease in work performance accounted for the largest portion, accounting for 65.5%. Conclusions ：As the socio-economic burden due to depression is expected to increase in the future, it is necessary to establish a systematic funding plan for the treatment and management of depressed patients in daily life.

Purpose: High incidence of osteoporosis has been reported in breast cancer patients due to early menopause triggered by adjuvant treatment and temporary ovarian function suppression. In this study, we sought to determine whether long-term breast cancer survivors had an elevated risk of low bone density compared to the general population. Methods: Long-term breast cancer survivors who had been treated for more than 5 years were selected for this study. Data were obtained from medical records and using a questionnaire from the Korea National Health and Nutrition Examination Survey (KNHANES). An agematched non-cancer control group was selected from the KNHANES records. Incidence of fracture and bone mineral density (BMD) were compared between the two groups. Results: In total, 74 long-term breast cancer survivors and 296 non-cancer controls were evaluated. The incidence of fracture did not differ between the two groups (P=0.130). No differences were detected in lumbar BMD (P=0.051) following adjustment for body mass index, while hip BMD was significantly lower in breast cancer survivors (P=0.028). Chemotherapy and endocrine treatment were not related to low BMD in breast cancer survivors. In more than half of the survivors, the 10-year risk of osteoporotic fracture was less than 1%. Conclusion Long-term breast cancer survivors had low bone density but a comparable risk of fracture compared to non-cancer agematched controls. Further studies on the factors related to low bone density in long-term breast cancer survivors are required.

Objectives: The purpose of our study was to investigate medical care utilization behavior and the conceptions of disease treatment among spine disease patients.Summary of Literature Review: Analyzing the medical care utilization behavior and conceptions of disease treatment among spine disease patients is important. Materials and Methods: A survey was administered to 500 first-time patients who visited the spine center of a tertiary educational hospital from May 2017 to August 2019. Results: A total of 479 valid responses were analyzed. A minority of patients (16.1%) visited the tertiary educational hospital without having previously visited a private hospital. Spinal procedures and surgery were considered negatively by 52.6% of respondents, and 14.8% of patients reported negative perceptions of orthopedic drugs. Conclusions Extensive efforts will be required to improve unreasonable medical utilization behavior by changing patients’ incorrect knowledge and beliefs about hospitals, diseases, and treatments.

BACKGROUND/AIMS: The aim of this study was to compare the sleep quality between rheumatoid arthritis (RA) patients and healthy controls; and to evaluate the relationship between RA disease activity and sleep quality in Korea. METHODS: A total of 130 RA patients and 67 age- and sex-matched healthy controls were enrolled in a comparative study of sleep quality using the Pittsburgh Sleep Quality Index (PSQI). Age, gender, concomitant medication, erythrocyte sedimentation rate, serum C-reactive protein, Beck Depression Inventory second edition (BDI-II), 28 joints disease activity score (DAS28), pain visual analog scale (VAS), and PSQI were analyzed as covariates. We also analyzed the sleep quality of RA patients according to the disease activity (DAS28 < or = 3.2, 3.2 < DAS28 < 5.1, and DAS28 > or = 5.1, respectively). RESULTS: The total PSQI score and the frequency of poor sleep quality, were higher in the RA patients (5.62 +/- 4.19, 38.5%) than in the control subjects (3.57 +/- 2.17, 13.4%). The patients with poor sleep quality (PSQI > 5) were older and had a higher BDI-II and VAS score than the patients without sleep disturbance (PSQI < or = 5). The score in subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance, daytime dysfunction, total PSQI, and frequency of poor sleep quality were increased when RA activity was high. CONCLUSIONS: Sleep disturbance was observed in RA patients (38.5%), and high RA disease activity was associated with poor sleep quality in Korea.
Adult ; Aged ; Aged, 80 and over ; Arthritis, Rheumatoid/diagnosis/ethnology/*physiopathology ; Asian Continental Ancestry Group ; Case-Control Studies ; Cross-Sectional Studies ; Depression/diagnosis/ethnology ; Female ; Humans ; Male ; Middle Aged ; Predictive Value of Tests ; Republic of Korea/epidemiology ; Risk Factors ; Severity of Illness Index ; *Sleep ; Sleep Wake Disorders/diagnosis/ethnology/*physiopathology ; Surveys and Questionnaires ; Young Adult

OBJECTIVE: To evaluate the prevalence of sleep disturbance in Korean patients with ankylosing spondylitis (AS), and its association with disease activity and depression. METHODS: Forty patients with AS and eighty healthy controls were included in this study. Sleep quality was assessed using the Korean version of Pittsburgh sleep quality index (PSQI). Depression was assessed by the Korean version of Beck depression inventory second edition (BDI-2). Ankylosing spondylitis disease activity score-C-reactive protein (ASDAS-CRP) was used to evaluate disease activity. Patients were dichotomized into a good sleeper group (PSQI< or =5) and a poor sleeper group (PSQI>5). RESULTS: The mean total PSQI score of patients with AS was 7.23+/-3.84. It was higher than that of the control subjects. AS patients had higher scores in all of the PSQI components, except for the use of sleep medication. Sixty percent of the AS patients were classified as poor sleepers. The mean BASDAI, ASDAS-CRP, and BDI-2 scores of the poor sleeper group were higher than that of the good sleeper group. Significantly, higher disease activity according to ASDAS-CRP was associated with poor sleep quality and depression. Multiple regression analysis revealed that the duration of morning stiffness and depression were independent risk factors that influenced poor sleep quality. CONCLUSION: Sleep disturbances are prevalent amongst Korean patients with AS. Lower quality of sleep is significantly associated with higher disease activity and depression. Therefore, optimal management to improve sleep quality in patients with AS is important.
Depression ; Humans ; Prevalence ; Risk Factors ; Spondylitis, Ankylosing*

OBJECTIVES: Idiopathic REM sleep behavior disorder (RBD) is by far the strongest clinical predictor of neurodegenerative disease available. Several potential early diagnostic markers of neurodegenerative disease including autonomic symptoms have been proposed, but they have generally not been tested in presymptomatic neurodegenerative disease. So the authors investigated autonomic symptoms and their associated factors in idiopathic RBD patients. METHODS: 52 idiopathic RBD patients and 52 controls participated in the study. Autonomic symptoms were evaluated by applying the unified multiple system atrophy rating scale (UMSARS) and measuring orthostatic systolic blood pressure drop. RESULTS: Idiopathic RBD patients showed significantly higher UMSARS subscale scores and sharper drop of orthostatic systolic blood pressure than controls. In multiple linear regression analysis, all autonomic symptoms and measured orthostatic systolic blood pressure drop were associated with RBD. In addition, orthostatic symptoms were associated with medication and age, urinary function was associated with benign prostatic hyperplasia, and measured orthostatic systolic blood pressure drop was associated with hypertension. CONCLUSION: In this study, idiopathic RBD patients showed more autonomic symptoms than controls. However, other autonomic symptoms-related factors also influenced some autonomic symptoms. Prospective studies should be performed to evaluate autonomic symptoms as a potential predictor of neurodegenerative diseases.
Aged* ; Blood Pressure ; Humans ; Hypertension ; Linear Models ; Multiple System Atrophy ; Neurodegenerative Diseases ; Prostatic Hyperplasia ; REM Sleep Behavior Disorder* ; Sleep, REM*

BACKGROUND/AIMS: This study evaluated the clinical outcomes of balloon-occluded retrograde transvenous obliteration (BRTO) for the treatment of hemorrhage from gastric varices (GV) in Korean patients with liver cirrhosis (LC). METHODS: We retrospectively analyzed data from 183 LC patients who underwent BRTO for GV bleeding in 6 university-based hospitals between January 2001 and December 2010. RESULTS: Of the 183 enrolled patients, 49 patients had Child-Pugh (CP) class A LC, 105 had CP class B, and 30 had CP class C at the time of BRTO. BRTO was successfully performed in 177 patients (96.7%). Procedure-related complications (e.g., pulmonary thromboembolism and renal infarction) occurred in eight patients (4.4%). Among 151 patients who underwent follow-up examinations of GV, 79 patients (52.3%) achieved eradication of GV, and 110 patients (72.8%) exhibited marked shrinkage of the treated GV to grade 0 or I. Meanwhile, new-appearance or aggravation of esophageal varices (EV) occurred in 54 out of 136 patients who underwent follow-up endoscopy (41.2%). During the 36.0+/-29.2 months (mean+/-SD) of follow-up, 39 patients rebled (hemorrhage from GV in 7, EV in 18, nonvariceal origin in 4, and unknown in 10 patients). The estimated 3-year rebleeding-free rate was 74.8%, and multivariate analysis showed that CP class C was associated with rebleeding (odds ratio, 2.404; 95% confidence-interval, 1.013-5.704; P=0.047). CONCLUSIONS: BRTO can be performed safely and effectively for the treatment of GV bleeding. However, aggravation of EV or bleeding from EV is not uncommon after BRTO; thus, periodic endoscopy to follow-up of EV with or without prophylactic treatment might be necessary in LC patients undergoing BRTO.
Adult ; Aged ; Asian Continental Ancestry Group ; *Balloon Occlusion/adverse effects ; Endoscopy, Gastrointestinal ; Esophageal and Gastric Varices/*complications ; Female ; Follow-Up Studies ; Gastrointestinal Hemorrhage/etiology/prevention & control/*therapy ; Humans ; Liver Cirrhosis/*complications ; Male ; Middle Aged ; Odds Ratio ; Pulmonary Embolism/etiology ; Recurrence ; Republic of Korea ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

PURPOSE: The need for surgical excision in patients with ultrasound-guided core needle biopsy (CNB)-diagnosed atypical ductal hyperplasia (ADH) remains an issue of debate. The present study sought to validate a scoring system (the U score, for underestimation) that we have previously developed for predicting malignancy in CNB-diagnosed ADH. METHODS: The study prospectively enrolled 85 female patients with CNB-diagnosed ADH who underwent subsequent surgical excision. Underestimation was defined as a surgical specimen having malignant foci. RESULTS: The overall underestimation rate was 37% (31/85). Multivariate analysis showed that a clinically palpable mass, microcalcification on imaging, size >15 mm and a patient age of > or =50 years were independently associated with underestimation. When applied to the scoring system, the validation score was significant (p<0.001; area under the curve, 0.852). No patient with a U score <3.5 had an underestimated lesion. CONCLUSION: The present study successfully validated the efficacy of our scoring system for predicting malignancy in CNB-diagnosed ADH. A U score of < or =3.5 indicates that surgical excision may not be necessary.
Biopsy, Large-Core Needle ; Biopsy, Needle ; Breast Neoplasms ; Diagnostic Errors ; Female ; Humans ; Hyperplasia ; Multivariate Analysis ; Prospective Studies

BACKGROUND: Single-nucleotide polymorphism (SNP) analysis is a powerful strategy for large-scale molecular population studies examining phylogenetic relationships among bacterial strains. Mycobacterial interspersed repetitive units-variable number of tandem repeats (MIRU-VNTR) can be easily digitized to share data among laboratories. This study applied SNP and MIRU-VNTR analyses for molecular strain typing of Mycobacterium tuberculosis isolates collected throughout Korea. METHODS: We studied 102 clinical M. tuberculosis isolates, including 6 paired strains, collected from 11 university hospitals in Korea in 2008 and 2009. SNPs were detected using hairpin primer assays, and then, MIRU-VNTR analysis was performed. RESULTS: Thirty-five SNPs contained polymorphisms that helped differentiate the 96 tested isolates. The isolates were classified into 15 clusters. The Beijing family strains were distributed within closely related clusters in the SNP dendrogram. For MIRU-VNTR analysis, the 96 isolates were divided into 12 groups. The discriminatory index in 8 of these groups (MIRU-10, -23, -26, and -31; ETR-A, -B, -C, and -F) was high (Hunter-Gaston diversity index > 0.6). Unlike the SNP method, MIRU-VNTR analysis did not identify any notable localizations of Beijing or non-Beijing family isolates in specific clusters. CONCLUSIONS: SNP and MIRU-VNTR analyses are surrogate molecular strain-typing methods for M. tuberculosis in Korea where Beijing family isolates are predominant.
Cluster Analysis ; DNA Primers/chemistry ; Interspersed Repetitive Sequences ; *Minisatellite Repeats ; Mycobacterium tuberculosis/*classification/genetics/isolation & purification ; Phylogeny ; *Polymorphism, Single Nucleotide ; Republic of Korea