OBJECTIVES: This study investigated whether the lower extremity muscle mass index (LMI) mediates the relationship between general obesity, central obesity, and knee osteoarthritis in middle-aged and elderly women in Korea. METHODS: Data of 2,843 women aged ≥50 years were collected from the Korean National Health and Nutrition Examination Survey conducted between 2009 and 2011. General obesity and central obesity were evaluated based on body mass index (BMI) and waist circumference (WC), calculated through anthropometric measurements and body composition assessments. LMI was calculated by dividing the muscle mass in both legs—measured using the dual-energy X-ray absorptiometry—by body weight. Knee osteoarthritis was defined as a Kellgren-Lawrence scale (KL) grade of ≥2 as assessed through radiographic images. RESULTS: Knee osteoarthritis prevalence, indicated by KL grades, was significantly higher in the general obesity and central obesity groups compared to the normal group, and conversely, lower with varying LMI levels. Using mediation analysis with bootstrapping and adjusting for covariates, we found that LMI mediated the relationship between BMI and KL (β, 0.005; 95% confidence interval [CI], 0.000 to 0.010) and WC and KL grade (β, 0.002; 95% CI, 0.001 to 0.003), explaining 4.8% and 6.7% of the total effects of BMI and WC on KL grade, respectively. CONCLUSIONS The study suggested that LMI partially mediates the link between general obesity and/or central obesity and knee osteoarthritis, proposing that a higher proportion of lower limb muscle mass relative to body weight can alleviate the increased risk of knee osteoarthritis caused by obesity.

Hypothalamic hamartomas (HHs) are nonneoplastic mass lesions located in the hypothalamus that can cause central precocious puberty (CPP) and/or gelastic seizures. Seckel syndrome 5 (OMIM210600, SCKL5) is a rare autosomal recessive genetic spectrum disorder characterized by intrauterine growth retardation, proportionate osteodysplastic primordial dwarfism, a wide range of intellectual disability, "bird-headed" facial features, and microcephaly with various structural brain abnormalities. Two siblings presented with short stature and small head circumference and were diagnosed with SCKL 5. The younger sister had HH with CPP and experienced a slipped capital femoral epiphysis during treatment. The 2 siblings had the same genetic variant but showed different phenotypes, which has not been reported previously; this study also as presents the first cases of SCKL5 diagnosed by genetic confirmation in Korea.

Methods: Adolescent idiopathic scoliosis (AIS) patients ages 10 to 19 years completed the Korean version of the Quality of Life Profile for Spinal Deformities (K-QLPSD), the Scoliosis Research Society-22 self-image subscale (K-SRS-22-si), Korean version of the Spinal Appearance Questionnaire (K-SAQ), Korean version of the Body Image Disturbance Questionnaire-Scoliosis (K-BIDQ-S), and Korean version of the Italian Spine Youth Quality of Life (K-ISYQOL). Four body image questionnaires were compared with K-ISYQOL and radiographic major curve magnitude, coronal balance, and sagittal balance. Spearman’s correlation was performed to compare the four body image questionnaires. Results: The study included 84 AIS patients, with a mean age of 12.6 years and a major Cobb angle of 29.4°. The four surveys were correlated with major curve magnitude and K-ISYQOL. K-SAQ and K-BIDQ-S were correlated better than K-QLPSD, and K-SRS-22-si was correlated with K-ISYQOL. The four surveys were moderately correlated with major curve magnitude, but there was no correlation with age, coronal balance, and sagittal balance. Conclusions K-SAQ and K-BIDQ-S correlate better with K-ISYQOL than K-QLPSD and K-SRS-22-si.

Background: Cross-talk between mitogen-activated protein kinase and estrogen has been reported; however, the role of BRAFV600E in the estrogen responsiveness of thyroid cancer is unknown. We elucidated the effect of BRAFV600E on the estrogen-induced increase in metastatic potential in thyroid cancer. Methods: Using a pair of cell lines, human thyroid cell lines which harbor wild type BRAF gene (Nthy/WT) and Nthy/BRAFV600E (Nthy/V600E), the expression of estrogen receptors (ERs) and estrogen-induced metastatic phenotypes were evaluated. Susceptibility to ERα- and ERβ-selective agents was evaluated to confirm differential ER expression. ESR expression was analyzed according to BRAFV600E status and age (≤50 years vs. >50 years) using The Cancer Genome Atlas (TCGA) data. Results: Estradiol increased the ERα/ERβ expression ratio in Nthy/V600E, whereas the decreased ERα/ERβ expression ratio was found in Nthy/WT. BRAFV600E-mutated cell lines showed a higher E2-induced increase in metastatic potential, including migration, invasion, and anchorage-independent growth compared with Nthy/WT. An ERα antagonist significantly inhibited migration in Nthy/V600E cells, whereas an ERβ agonist was more effective in Nthy/WT. In the BRAFV600E group, ESR1/ESR2 ratio was significantly higher in younger age group (≤50 years) compared with older age group (>50 years) by TCGA data analysis. Conclusion Our data show that BRAFV600E mutation plays a crucial role in the estrogen responsiveness of thyroid cancer by regulating ER expression. Therefore, BRAFV600E might be used as a biomarker when deciding future hormone therapies based on estrogen signaling in thyroid cancer patients.

Background: Measuring accurate and reliable scores of quality of life in patients with ankylosing spondylitis (AS) is important in both decision-making and treatment planning for the disease. Questionnaire, The ankylosing spondylitis quality of life (ASQoL), is one of the representative tools for assessing how seriously AS patients view their disease severity, activity, as well as their overall health. To make these types of questionnaires readable and understandable, local language translation of surveys should be required. A Korean version of the ASQoL questionnaire has accordingly been developed. This study assessed the Korean version of the ASQoL survey to evaluate the reliability and validity of it. Methods: Translation and reverse translation of the English ASQoL survey were conducted. A total of 120 consecutive AS patients received a mail including the Korean-translated 36-Item Short Form Survey (SF-36), the ASQoL survey, and the visual analog scale (pain). The coefficient of intraclass correlation and Cronbach’s alpha were computed, and factor analysis, as well as reliability assessments utilizing the kappa agreement statistics for each item, was undertaken. By analyzing the responses to SF-36 and ASQoL questionnaire utilizing Pearson’s correlation coefficient, construct validity was calculated. Results: Factor analysis was performed regarding pain, physical function, and mental function. The kappa statistic of agreement was larger than 0.6 for all items. The ASQoL questionnaire had adequate test and re-test reliability (0.814). Furthermore, Cronbach’s α, the internal consistency, was very good (0.877). The Korean-translated ASQoL questionnaire demonstrated a significantly strong correlation between the single domain and total SF-36 scores. Conclusions The Korean version of the ASQoL questionnaire showed acceptable properties of measurement and successful translation. Thus, it can be said that the questionnaire is appropriate for evaluating the outcomes of Korean patients with AS.

Background: Tuberculous meningitis (TBM) is the most severe form of tuberculosis, but differentiating between the diagnosis of TBM and viral meningitis (VM) is difficult. Thus, we have developed machine-learning modules for differentiating TBM from VM.Material and Methods: For the training data, confirmed or probable TBM and confirmed VM cases were retrospectively collected from five teaching hospitals in Korea between January 2000 - July 2018. Various machine-learning algorithms were used for training. The machinelearning algorithms were tested by the leave-one-out cross-validation. Four residents and two infectious disease specialists were tested using the summarized medical information. Results: The training study comprised data from 60 patients with confirmed or probable TBM and 143 patients with confirmed VM. Older age, longer symptom duration before the visit, lower serum sodium, lower cerebrospinal fluid (CSF) glucose, higher CSF protein, and CSF adenosine deaminase were found in the TBM patients. Among the various machinelearning algorithms, the area under the curve (AUC) of the receiver operating characteristics of artificial neural network (ANN) with ImperativeImputer for matrix completion (0.85; 95% confidence interval 0.79 - 0.89) was found to be the highest. The AUC of the ANN model was statistically higher than those of all the residents (range 0.67 - 0.72, P <0.001) and an infectious disease specialist (AUC 0.76; P = 0.03). Conclusion The machine-learning techniques may play a role in differentiating between TBM and VM. Specifically, the ANN model seems to have better diagnostic performance than the non-expert clinician.

Background: Tuberculous meningitis (TBM) is the most severe form of tuberculosis, but differentiating between the diagnosis of TBM and viral meningitis (VM) is difficult. Thus, we have developed machine-learning modules for differentiating TBM from VM.Material and Methods: For the training data, confirmed or probable TBM and confirmed VM cases were retrospectively collected from five teaching hospitals in Korea between January 2000 - July 2018. Various machine-learning algorithms were used for training. The machinelearning algorithms were tested by the leave-one-out cross-validation. Four residents and two infectious disease specialists were tested using the summarized medical information. Results: The training study comprised data from 60 patients with confirmed or probable TBM and 143 patients with confirmed VM. Older age, longer symptom duration before the visit, lower serum sodium, lower cerebrospinal fluid (CSF) glucose, higher CSF protein, and CSF adenosine deaminase were found in the TBM patients. Among the various machinelearning algorithms, the area under the curve (AUC) of the receiver operating characteristics of artificial neural network (ANN) with ImperativeImputer for matrix completion (0.85; 95% confidence interval 0.79 - 0.89) was found to be the highest. The AUC of the ANN model was statistically higher than those of all the residents (range 0.67 - 0.72, P <0.001) and an infectious disease specialist (AUC 0.76; P = 0.03). Conclusion The machine-learning techniques may play a role in differentiating between TBM and VM. Specifically, the ANN model seems to have better diagnostic performance than the non-expert clinician.

Purpose: This study aimed to evaluate the safety of biologics and small molecules for the treatment of inflammatory bowel diseases (IBD) in patients receiving antirejection therapies after organ transplants. Materials and Methods: We reviewed the medical records of patients with IBD who received organ transplants at the Asan Medical Center between January 1989 and December 2021. We compared the parameters of patients receiving biologics or small molecules to those of patients without those therapies. Results: This study included a total of 53 patients (ulcerative colitis, 41; Crohn’s disease, 6; and gastrointestinal Behçet’s disease, 6). Among them, 15 patients were receiving biologics or small molecules and 38 were not. During a mean follow-up of 119 months, the proportion of patients experiencing severe infections was significantly higher in those treated with biologics or small molecules than in those not treated. However, other safety outcomes (e.g., malignancies, adverse events, including organizing pneumonia or hepatic failure, and death) were not different between the two groups. Kaplan–Meier curve analysis revealed no significant difference in the safety outcome rate related to the use of biologics or small molecules. During follow-up, eight patients underwent bowel resections for IBD. The rate of bowel resection was not different between the two groups. Conclusion The use of biologics or small molecules for patients with IBD who received organ transplants did not show a significant difference in safety outcomes. However, the possibility of severe infections must be considered.