No abstract available.
Lymphoma, B-Cell, Marginal Zone* ; Orbit* ; Orbital Diseases*

BACKGROUND: A standardized systematic approach to grade evidence and the strength of recommendations is important for guideline users to minimize bias and help interpret the most suitable decisions at the point of care. The study aims to identify and classify determinants used to make judgement for the strength of recommendations among 56 Korean clinical practice guidelines (CPGs), and explore strong recommendations based on low quality of evidence. METHODS: Determinants used in the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach among 34 CPGs which have reported both strength of recommendations and level of evidence were reviewed. RESULTS: Five of 34 CPGs (14.7%) considered quality of evidence, benefits and harms, patients' values and preferences, and costs. And 24 of 34 CPGs (70.6%) considered both magnitude of effect and feasibility as additional determinants. Judgement table was not widely provided for use to translate evidence into recommendations. Eighty-two of 121 recommendations (67.8%, ranged 20.0% to 100.0%) among 11 CPGs using the same judgement scheme showed ‘strong’ strength of recommendations based on low or very low quality of evidence. Among 5 paradigmatic situations that justify strong recommendations based on low or very low evidence, situation classified as ‘potential equivalence, one option clearly less risky or costly’ was 87.8% for 82 strong recommendations. Situation classified as ‘uncertain benefit, certain harm’ was 4.9%. CONCLUSION: There is a need to introduce and systematize an evidence-based grading system. Using judgement table to justify the strength of recommendations and applying the 5 paradigmatic situations mentioned above is also recommended in the near future.
Bias (Epidemiology) ; Point-of-Care Systems

BACKGROUND/AIMS: The fatigue, resistance, ambulation, illnesses, and loss of weight (FRAIL) scale is a screening tool for frailty status using a simple 5-item questionnaire. The aim of this study was to evaluate the clinical feasibility and validity of the Korean version of the FRAIL (K-FRAIL) scale. METHODS: Questionnaire items were translated and administered to 103 patients aged ≥ 65 years who underwent a comprehensive geriatric assessment at the Seoul National University Bundang Hospital. In this cross-sectional study, the K-FRAIL scale was compared with the domains and the multidimensional frailty index of the comprehensive geriatric assessment. We also assessed the time required to complete the scale. RESULTS: The participants' mean age was 76.8 years (standard deviation [SD], 6.1), and 55 (53.4%) were males. The mean overall frailty index was 0.19 (SD, 0.17). For K-FRAIL-robust, prefrail, and frail patients, the mean frailty indices were 0.09, 0.18, and 0.34, respectively (p for trend < 0.001). A higher degree of impairment in the K-FRAIL scale was associated with worse nutritional status, poor physical performance, functional dependence, and polypharmacy. The number of items with impairment in the K-FRAIL scale was positively associated with the frailty index (B = 3.73, p < 0.001). The K-FRAIL scale could differentiate vulnerability from robustness with a sensitivity of 0.90 and a specificity of 0.33. Of all patients, 75 (72.8%) completed the K-FRAIL scale within < 3 minutes. CONCLUSIONS: The K-FRAIL scale is correlated with the frailty index and is a simple tool to screen for frailty in a clinical setting.
Aged* ; Cross-Sectional Studies ; Diagnosis ; Fatigue ; Geriatric Assessment ; Humans ; Male ; Mass Screening ; Nutritional Status ; Polypharmacy ; Sensitivity and Specificity ; Seoul ; Walking

PURPOSE: Peripheral neuropathy (PN) is known as a major contributor of the worsening of ischemic symptoms and the foot ulceration in patients with peripheral arterial occlusive disease (PAOD). However, there are few studies reporting the prevalence and risk factors for PN in PAOD. This study aimed to evaluate these issues for PN and to establish the importance of screening as additional treatment target for PN in PAOD. MATERIALS AND METHODS: A total of 52 limbs with PAOD were enrolled from January 2011 to December 2012. PN was divided into radiculopathy, ischemic PN (IPN), and diabetic PN (DPN), based on electromyographic findings. We investigated the prevalence of overall PN and subtypes of PN and then analyzed the risk factors. RESULTS: The prevalence of overall PN in PAOD was 43 of 52 limbs (82.7%). In terms of subtypes of PN, the prevalence rate of radiculopathy and IPN was 30.8% and 23.1%, respectively. DPN showed in 22 limbs (73.3%) among 30 diabetic limbs. There was no significant correlation between each type of PN and ischemic symptoms. Our analysis showed that coronary artery disease (CAD) was a significant risk factor (P=0.01) for IPN, however, did not identify any significant risk factors for DPN. CONCLUSION: This present study indicated that most patients with PAOD had PN and CAD was a risk factor for IPN. In particular, PAOD with diabetes represented a higher prevalence for DPN. Our study suggests that PN should be evaluated and considered as another treatment target in patients with PAOD.
Arterial Occlusive Diseases* ; Coronary Artery Disease ; Extremities ; Foot Ulcer ; Humans ; Mass Screening ; Peripheral Nervous System Diseases* ; Prevalence* ; Radiculopathy ; Risk Factors*

Cytochrome P450 2E1 (CYP2E1) is a member of the cytochrome P450 superfamily, and it is a key enzyme responsible for the metabolic activation of many smallmolecular-weight compounds such as alcohol, which is classified as a human carcinogen. In this study, we identified 19 single nucleotide polymorphisms (SNPs) in CYP2E1 in Korean population. In these SNPs, we examined possible genetic association of CYP2E1 polymorphisms with HBV clearance and the risk of hepatocellular carcinoma (HCC). Five common polymorphic sites were selected, CYP2E1 polymorphisms at rs381-3867, rs3813870, rs2070673, rs2515641 and rs2480257 , considering their allele frequencies, haplotype-tagging status and LDs for genotyping in larger-scale subjects (n=1,092). Statistical analysis demonstrated that CYP2E1 polymorphisms and haplotypes show no significant association with HBV clearance, HCC occurrence and onset age of HCC (p>0.05). Previous studies, however, have shown contradictory findings on associations of CYP2E1 polymorphisms with CYP2E1 activities and HCC risk. Comparing the contrasting results of previous researches suggest that CYP2E1 polymorphism is associated with CYP2E1 activity induced by ethanol, but is not directly associated with HCC risk. CYP2E1 variation/haploype information identified in this study will provide valuable information for future studies on CYP2E1.
Age of Onset ; Biotransformation ; Carcinoma, Hepatocellular ; Cytochrome P-450 CYP2E1 ; Cytochrome P-450 Enzyme System ; Ethanol ; Gene Frequency ; Haplotypes ; Humans ; Polymorphism, Single Nucleotide

Purpose: The purpose of this study was to investigate the concordance rate of PIK3CA mutations between primary and matched distant metastatic sites in patients with breast cancer and to verify whether there are differences in the frequency of PIK3CA hotspot mutations depending on the metastatic sites involved. Materials and Methods: Archived formalin-fixed paraffin-embedded (FFPE) specimens of primary breast and matched distant metastatic tumors were retrospectively obtained for 49 patients. Additionally, 40 archived FFPE specimens were independently collected from different breast cancer metastatic sites, which were limited to three common sites: the liver, brain, and lung. PIK3CA mutations were analyzed using droplet digital PCR, including hotspots involving exons 9 and 20. Results: After analysis of 49 breast tumors with matched metastasis sites, 87.8% showed concordance in PIK3CA mutation status. According to PIK3CA hotspot mutation testing in 89 cases of breast cancer metastatic sites, the proportion of PIK3CA mutations at sites of metastasis involving the liver, brain, and lung was 37.5%, 28.6%, and 42.9%, respectively, which did not result in statistical significance. Conclusion The high concordance of PIK3CA mutation status between primary and matched metastasis sites suggests that metastatic sites, regardless of the metastatic organ, could be considered sample sources for PIK3CA mutation testing for improved therapeutic strategies in patients with metastatic breast cancer.

Objective: Disruptive behavior disorder (DBD) adversely impacts children and adolescents. However, a comprehensive and cost-effective scale to assess DBD is lacking in Korea. Therefore, this study translated the Disruptive Behavior Disorders Rating Scale (DBDRS) into Korean and analyzed its psychometric properties. Methods: Parents and primary caregivers of non-clinical (n=429) and clinical (n=28) children and adolescents aged 6–15 years were included in the analysis. Confirmatory factor analysis was conducted; further, concurrent validity and internal consistency were investigated using correlation analysis and Cronbach’s alpha, respectively. Furthermore, discriminative capacity was estimated using receiver operating characteristic curve analysis. Results: The four-factor model of K-DBDRS showed good model fit indices and factor loadings, which supported the construct validity of the scale. Strong correlations between K-DBDRS and related measurements were observed, and a robust level of Cronbach’s alpha was confirmed (0.891–0.933). The discriminative capacity of the scale was good, based on the area under the curve values (0.933–0.953). Conclusion This study indicated that the K-DBDRS is an appropriate screening tool for Korean children and adolescents. Thus, this scale can be applied in clinical and community settings to identify children and adolescents with disruptive behavior disorders.

BACKGROUND: Thyroid function depends on ethnic and environmental factors. North Korean refugees have the same genetic background as South Koreans, but they have been exposed to different environments. This study examines the prevalence and pattern of thyroid disorders in North Korean women living in South Korea, focusing on subclinical hypothyroidism (SCH). METHODS: The intended sample was a total of 327 North Korean women residing in Seoul. Health questionnaires and medical examinations, including serum thyrotropin (thyroid stimulating hormone, TSH), free thyroxine, and thyroid autoantibodies, were conducted. RESULTS: The prevalence of SCH was 9.4%. In logistic regression analysis, smoking, menopause, length of stay in South Korea, body mass index, history of thyroid disease, and metabolic syndrome were not associated with the risk of SCH. Whereas, the positivity of autoantibodies were associated with a high risk for SCH (odds ratio [OR], 4.840; 95% confidence interval [CI], 1.80-13.017; P = 0.002), and age was associated with a low risk for SCH (OR, 0.94; 95% CI, 0.888-0.994; P = 0.031). The serum TSH levels also decreased with increasing age, and in particular, there was significant difference between 30-39 years, and over 60 years (2.33 +/- 1.51 microIU/mL vs. 1.54 +/- 0.73 microIU/mL, P = 0.028). CONCLUSION: In North Korean women, the positivity of autoantibodies was associated with a high risk for SCH. But interestingly, a younger age was associated with a high risk for SCH. Considering that they suffered from severe famine at the period of growth, and this led to malnutrition, their thyroid dysfunction might be associated with the peculiar environment that they experienced.
Autoantibodies ; Body Mass Index ; Female ; Humans ; Hypothyroidism ; Length of Stay ; Logistic Models ; Malnutrition ; Menopause ; Prevalence ; Refugees ; Republic of Korea ; Smoke ; Smoking ; Starvation ; Thyroid Diseases ; Thyroid Gland ; Thyrotropin ; Thyroxine ; Surveys and Questionnaires

Purpose: NUT carcinoma (NC) is a solid tumor caused by the rearrangement of NUTM1 that usually develops in midline structures, such as the thorax. No standard treatment has been established despite high lethality. Thus, we investigated whether targeting the junction region of NUTM1 fusion breakpoints could serve as a potential treatment option for NC. Materials and Methods: We designed and evaluated a series of small interfering RNAs (siRNAs) targeting the junction region of BRD4-NUTM1 fusion (B4N), the most common form of NUTM1 fusion. Droplet digital polymerase chain reaction using the blood of patients was also tested to evaluate the treatment responses by the junction sequence of the B4N fusion transcripts. Results: As expected, the majority of NC fusion types were B4N (12 of 18, 67%). B4N fusion-specific siRNA treatment on NC cells showed specific inhibitory effects on the B4N fusion transcript and fusion protein without affecting the endogenous expression of the parent genes, resulting in decreased relative cell growth and attenuation of tumor size. In addition, the fusion transcript levels in platelet-rich-plasma samples of the NC patients with systemic metastasis showed a negative correlation with therapeutic effect, suggesting its potential as a measure of treatment responsiveness. Conclusion This study suggests that tumor-specific sequences could be used to treat patients with fusion genes as part of precision medicine for a rare but deadly disease.

Integrins are transmembrane receptor proteins that mediate cell-cell adhesion and cell-extracellular matrix (ECM) adhesion. The deregulation of cell-ECM adhesion and the abnormal expression of beta1 (beta1) integrins (ITGB1s) are involved in tumor development and metastasis. In the liver, the expression of integrins and ECM proteins can be a cause of hepatocellular carcinoma (HCC) development. We performed direct DNA sequencing of 24 individuals, and identified 23 sequence variants of ITGB1 polymorphisms. Among these 23 variants, 7 common variants were selected based on frequencies and linkage disequilibrium, and then genotyped in a larger-scale group of subjects (n=1,103). The genetic associations of ITGB1 polymorphisms with the clearance of HBV and HCC outcome of HBV patients were analyzed using logistic regression models and Cox relative hazard models. Although there was no significant association observed between the polymorphisms and the HCC outcome of HBV patients, the second most common haplotype (ITGB1 haplotype-2 [C-C-C-C-T-C-T]) was putatively associated with HBV clearance (OR=0.75, p=0.008 and P(corr)=0.05). The minor allele frequency (MAF) of ITGB1 haplotype-2 of the spontaneously recovered (SR) group was significantly higher than that of the chronic carrier group (CC) (freq. = 0.248 vs. 0.199). The information derived from this study could be valuable for understanding the genetic factors involved in the clearance of HBV.
Carcinoma, Hepatocellular ; Gene Frequency ; Haplotypes ; Humans ; Integrins ; Linkage Disequilibrium ; Liver ; Logistic Models ; Neoplasm Metastasis ; Proportional Hazards Models ; Proteins ; Sequence Analysis, DNA