Purpose: There are clinical unmet needs in predicting therapeutic response and precise strategy for the patient with advanced biliary tract cancer (BTC). We aimed to identify genomic alterations predicting therapeutic response and resistance to gemcitabine and cisplatin (Gem/Cis)-based chemotherapy in advanced BTC. Materials and Methods: Genomic analysis of advanced BTC multi-institutional cohorts was performed using targeted panel sequencing. Genomic alterations were analyzed integrating patients’ clinicopathologic data, including clinical outcomes of Gem/Cis-based therapy. Significance of genetic alterations was validated using clinical next-generation sequencing (NGS) cohorts from public repositories and drug sensitivity data from cancer cell lines. Results: 193 BTC patients from three cancer centers were analyzed. Most frequent genomic alterations were TP53 (55.5%), KRAS (22.8%), ARID1A (10.4%) alterations, and ERBB2 amplification (9.8%). Among 177 patients with BTC receiving Gem/Cis-based chemotherapy, ARID1A alteration was the only independent predictive molecular marker of primary resistance showing disease progression for 1st-line chemotherapy in the multivariate regression model (odds ratio, 3.12; p=0.046). In addition, ARID1A alteration was significantly correlated with inferior progression-free survival on Gem/Cis-based chemotherapy in the overall patient population (p=0.033) and in patients with extrahepatic cholangiocarcinoma (CCA) (p=0.041). External validation using public repository NGS revealed that ARID1A mutation was a significant predictor for poor survival in BTC patients. Investigation of multi-OMICs drug sensitivity data from cancer cell lines revealed that cisplatin-resistance was exclusively observed in ARID1A mutant bile duct cancer cells. Conclusion Integrative analysis with genomic alterations and clinical outcomes of the first-line Gem/Cis-based chemotherapy in advanced BTC revealed that patients with ARID1Aalterations showed a significant worse clinical outcome, especially in extrahepatic CCA. Well-designed prospective studies are mandatory to validate the predictive role of ARID1Amutation.

Background/Aims: The aim of this study was to investigate long-term post-discontinuation outcomes in patients with rheumatoid arthritis (RA) who had been treated with tumor necrosis factor-α inhibitors (TNF-αi) which was then discontinued. Methods: Sixty Korean patients with RA who participated in a 5-year GO-BEFORE and GO-FORWARD extension trials were included in this retrospective study. Golimumab was deliberately discontinued after the extension study (baseline). Patients were then followed by their rheumatologists. We reviewed their medical records for 2 years (max 28 months) following golimumab discontinuation. Patients were divided into a maintained benefit (MB) group and a loss-of-benefit (LB) group based on treatment pattern after golimumab discontinuation. The LB group included patients whose conventional disease-modifying antirheumatic drug(s) were stepped-up or added/switched (SC) and those who restarted biologic therapy (RB). Results: The mean age of patients at baseline was 56.5 years and 55 (91.7%) were females. At the end of follow-up, 23 (38.3%) patients remained in the MB group. In the LB group, 75.7% and 24.3% were assigned into SC and RB subgroups, respectively. Fifty percent of patients lost MB after 23.3 months. Demographics and clinical variables at baseline were comparable between MB and LB groups except for age, C-reactive protein level, and corticosteroid use. Restarting biologic therapy was associated with swollen joint count (adjusted hazard ratio [HR], 1.90; 95% confidence interval [CI], 1.01 to 3.55) and disease duration (adjusted HR, 1.12; 95% CI, 1.02 to 1.23) at baseline. Conclusions Treatment strategies after discontinuing TNF-αi are needed to better maintain disease control and quality of life of patients with RA.

Objective: To determine the effects of an integrated training device for strength and balance on extremity muscle strength, postural balance, and cognition in older adults using a combination with various rehabilitation training games, in which balance, strength, and cognitive training were configured in a single device. Methods: This prospective study included 20 healthy participants aged 65–85 years. Participants trained for 30 minutes daily, 3 days weekly, for 6 weeks with an integrated training device for strength and balance (SBT-120; Man&Tel Inc., Gumi, Korea). Main outcomes were measured using the Korean Mini-Mental State Examination (K-MMSE), Korean version of the Montreal Cognitive Assessment (K-MoCA), Timed Up and Go Test (TUG), Functional Reach Test (FRT), Berg Balance Scale (BBS), and Manual Muscle Test. Measurements were taken at three time points: T0 (pretreatment), T1 (immediately after treatment), and T2 (4 weeks after treatment). Results: All 20 patients completed the training, and TUG, FRT, and BBS scores significantly improved at T1 and T2 compared to T0. Mean TUG scores decreased by 0.99±2.00 at T1 and 1.05±1.55 at T2 compared to T0. Mean FRT scores increased by 6.13±4.26 at T1 and 6.75±4.79 at T2 compared to T0. BBS scores increased by 0.60±0.94 at T1 and 0.45±1.15 at T2 compared to T0. Moreover, muscle strength and cognition (K-MMSE and K-MoCA scores) increased after training. Conclusion Our findings suggest that an integrated training device for strength and balance can be a safe and useful tool for older adults.

Background/Aims: To examine the prevalence and clinical characteristics of apparent treatment-resistant hypertension among ambulatory hypertensive patients. Methods: We enrolled adult ambulatory hypertensive patients at 13 well-qualified general hospitals in Korea from January to June 2012. Apparent resistant hypertension was defined as an elevated blood pressure > 140/90 mmHg with the use of three antihypertensive agents, including diuretics, or ≥ 4 antihypertensives, regardless of the blood pressure. Controlled hypertension was defined as a blood pressure within the target using three antihypertensives, including diuretics. Results: Among 16,915 hypertensive patients, 1,172 (6.9%) had controlled hypertension, and 1,514 (8.9%) had apparent treatment-resistant hypertension. Patients with apparent treatment-resistant hypertension had an earlier onset of hypertension (56.8 years vs. 58.8 years, p = 0.007) and higher body mass index (26.3 kg/m2 vs. 24.9 kg/m2, p < 0.001) than those with controlled hypertension. Drug compliance did not differ between groups. In the multivariable analysis, earlier onset of hypertension (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.97 to 0.99; p < 0.001) and the presence of comorbidities (OR, 2.06; 95% CI, 1.27 to 3.35; p < 0.001), such as diabetes mellitus, ischemic heart disease, heart failure, and chronic kidney disease, were independent predictors. Among the patients with apparent treatment-resistant hypertension, only 5.2% were receiving ≥ 2 antihypertensives at maximally tolerated doses. Conclusions Apparent treatment-resistant hypertension prevalence is 8.9% among ambulatory hypertensive patients in Korea. An earlier onset of hypertension and the presence of comorbidities are independent predictors. Optimization of medical treatment may reduce the rate of apparent treatment-resistant hypertension.

Objective: To determine the effects of an integrated training device for strength and balance on extremity muscle strength, postural balance, and cognition in older adults using a combination with various rehabilitation training games, in which balance, strength, and cognitive training were configured in a single device. Methods: This prospective study included 20 healthy participants aged 65–85 years. Participants trained for 30 minutes daily, 3 days weekly, for 6 weeks with an integrated training device for strength and balance (SBT-120; Man&Tel Inc., Gumi, Korea). Main outcomes were measured using the Korean Mini-Mental State Examination (K-MMSE), Korean version of the Montreal Cognitive Assessment (K-MoCA), Timed Up and Go Test (TUG), Functional Reach Test (FRT), Berg Balance Scale (BBS), and Manual Muscle Test. Measurements were taken at three time points: T0 (pretreatment), T1 (immediately after treatment), and T2 (4 weeks after treatment). Results: All 20 patients completed the training, and TUG, FRT, and BBS scores significantly improved at T1 and T2 compared to T0. Mean TUG scores decreased by 0.99±2.00 at T1 and 1.05±1.55 at T2 compared to T0. Mean FRT scores increased by 6.13±4.26 at T1 and 6.75±4.79 at T2 compared to T0. BBS scores increased by 0.60±0.94 at T1 and 0.45±1.15 at T2 compared to T0. Moreover, muscle strength and cognition (K-MMSE and K-MoCA scores) increased after training. Conclusion Our findings suggest that an integrated training device for strength and balance can be a safe and useful tool for older adults.

Objective: Central nervous system involvement in coronavirus disease 2019 (COVID-19) has been increasingly reported. We performed a systematic review and meta-analysis to evaluate the incidence of radiologically demonstrated neurologic complications and detailed neuroimaging findings associated with COVID-19. Materials and Methods: A systematic literature search of MEDLINE/PubMed and EMBASE databases was performed up to September 17, 2020, and studies evaluating neuroimaging findings of COVID-19 using brain CT or MRI were included. Several cohort-based outcomes, including the proportion of patients with abnormal neuroimaging findings related to COVID-19 were evaluated. The proportion of patients showing specific neuroimaging findings was also assessed. Subgroup analyses were also conducted focusing on critically ill COVID-19 patients and results from studies that used MRI as the only imaging modality. Results: A total of 1394 COVID-19 patients who underwent neuroimaging from 17 studies were included; among them, 3.4% of the patients demonstrated COVID-19-related neuroimaging findings. Olfactory bulb abnormalities were the most commonly observed (23.1%). The predominant cerebral neuroimaging finding was white matter abnormality (17.6%), followed by acute/subacute ischemic infarction (16.0%), and encephalopathy (13.0%). Significantly more critically ill patients had COVID-19-related neuroimaging findings than other patients (9.1% vs. 1.6%; p = 0.029). The type of imaging modality used did not significantly affect the proportion of COVID-19-related neuroimaging findings. Conclusion Abnormal neuroimaging findings were occasionally observed in COVID-19 patients. Olfactory bulb abnormalities were the most commonly observed finding. Critically ill patients showed abnormal neuroimaging findings more frequently than the other patient groups. White matter abnormalities, ischemic infarctions, and encephalopathies were the common cerebral neuroimaging findings.

Background/Aims: To examine the prevalence and clinical characteristics of apparent treatment-resistant hypertension among ambulatory hypertensive patients. Methods: We enrolled adult ambulatory hypertensive patients at 13 well-qualified general hospitals in Korea from January to June 2012. Apparent resistant hypertension was defined as an elevated blood pressure > 140/90 mmHg with the use of three antihypertensive agents, including diuretics, or ≥ 4 antihypertensives, regardless of the blood pressure. Controlled hypertension was defined as a blood pressure within the target using three antihypertensives, including diuretics. Results: Among 16,915 hypertensive patients, 1,172 (6.9%) had controlled hypertension, and 1,514 (8.9%) had apparent treatment-resistant hypertension. Patients with apparent treatment-resistant hypertension had an earlier onset of hypertension (56.8 years vs. 58.8 years, p = 0.007) and higher body mass index (26.3 kg/m2 vs. 24.9 kg/m2, p < 0.001) than those with controlled hypertension. Drug compliance did not differ between groups. In the multivariable analysis, earlier onset of hypertension (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.97 to 0.99; p < 0.001) and the presence of comorbidities (OR, 2.06; 95% CI, 1.27 to 3.35; p < 0.001), such as diabetes mellitus, ischemic heart disease, heart failure, and chronic kidney disease, were independent predictors. Among the patients with apparent treatment-resistant hypertension, only 5.2% were receiving ≥ 2 antihypertensives at maximally tolerated doses. Conclusions Apparent treatment-resistant hypertension prevalence is 8.9% among ambulatory hypertensive patients in Korea. An earlier onset of hypertension and the presence of comorbidities are independent predictors. Optimization of medical treatment may reduce the rate of apparent treatment-resistant hypertension.

Objective: Frontal alpha asymmetry (FAA) of electroencephalography (EEG) has been studied to differentiate patients with major depressive disorder (MDD) from healthy controls (HC). However, inconsistent results have been obtained thus far. Suicidal ideation (SI) has been known to alter frontal lobe activity, and could be an important covariate in FAA studies. This study aimed to explore the influence of FAA on the relationship among MDD patients with SI and without SI, and HC. Methods: Sixty-seven patients with MDD (44 without and 23 with SI) and 60 HCs were recruited. Resting state EEG was recorded with their eyes open, and FAA as a lateralized index of alpha power was calculated in the frontal brain region. Hamilton Rating Scale for Anxiety and Depression scores were estimated. Results: FAA was higher (increased alpha power in the left frontal region) in the MDD group than in the HC group. The FAA was lower (reduced alpha power in the left frontal region) in MDD patients with SI than in MDD patients without SI. The severity of depression and anxiety symptoms were significantly correlated with FAA only in MDD patients with SI. SI moderated the effects of depressive symptom on FAA in the MDD group. Conclusion Our results suggest that SI is a clinically important moderator of frontal alpha asymmetry in patients with MDD.

To examine the effects of Populus tomentiglandulosa (PT) extract on the expressions of antioxidant enzymes and neurotrophic factors in the cornu ammonis 1 (CA1) region of the hippocampus at 5 min after inducing transient global cerebral ischemia (TGCI) in gerbils, TGCI was induced by occlusion of common carotid arteries for 5 min. Before ischemic surgery, 200 mg·kg PT extract was orally administrated once daily for 7 d. We performed neuronal nuclear antigen immunohistochemistry and Fluoro-Jade B staining. Furthermore, we determined in situ production of superoxide anion radical, expression levels of SOD1 and SOD2 as antioxidant enzymes and brain-derived neurotrophic factor (BDNF) and insulin-like growth factor I (IGF-I) as neurotrophic factors. Pretreatment with 200 mg·kg PT extract prevented neuronal death (loss). Furthermore, pretreatment with 200 mg·kg PT extract significantly inhibited the production of superoxide anion radical, increased expressions of SODs and maintained expressions of BDNF and IGF-I. Such increased expressions of SODs were maintained in the neurons after IRI. In summary, pretreated PT extract can significantly increase levels of SODs and protect the neurons against TGCI, suggesting that PT can be a useful natural agent to protect against TGCI.
Animals ; Brain-Derived Neurotrophic Factor ; genetics ; metabolism ; CA1 Region, Hippocampal ; drug effects ; metabolism ; Gerbillinae ; Humans ; Insulin-Like Growth Factor I ; genetics ; metabolism ; Male ; Neuroprotective Agents ; administration & dosage ; Plant Extracts ; administration & dosage ; Populus ; chemistry ; Pyramidal Cells ; drug effects ; metabolism ; Reperfusion Injury ; drug therapy ; genetics ; metabolism ; Superoxide Dismutase ; genetics ; metabolism ; Up-Regulation ; drug effects

BACKGROUND: Meniscus surgeries are frequently performed in orthopaedics. However, their current status is not well known in many countries, including Korea. This study aimed to investigate the national trends of meniscus surgery in Korea. METHODS: Information from the national database was acquired through the Korean Health Insurance Review and Assessment Service from 2010 to 2017. All cases coded as meniscectomy or meniscus repair were included. The total number and incidence of cases of meniscus surgery per 100,000 persons were determined, and the results were stratified by age and gender. The meniscus repair ratio for the total number of meniscus surgeries was evaluated. RESULTS: The total number and incidence of meniscectomy cases were 65,752 and 137, respectively, in 2010, which increased to 74,088 and 154, respectively, in 2017. The number of meniscectomies increased by 12.67% in 8 years. The total number and incidence of meniscus repair cases were 9,055 and 18, respectively, in 2010, which increased to 14,947 and 31 in 2017. The number of meniscus repairs increased by 65.04%. The meniscus repair ratio was 12.1% in 2010, which increased to 16.8% in 2017. The highest peak was noted for patients who underwent meniscus surgeries in their 50s and 60s. Meniscectomy was performed more frequently in women (57%) than in men (43%), whereas repair was performed more frequently in men (54%) than in women (46%) over the study period. CONCLUSION: The total number and incidence of meniscus surgeries increased from 2010 to 2017; the number and incidence of meniscus repair procedures increased more rapidly than those of meniscectomy, with the peak treatment age for both surgeries being in the 50s and 60s. The current study will contribute to understanding the epidemiology of meniscus surgery, its prevention, and cost-saving measures in Korea.
Epidemiology ; Female ; Humans ; Incidence ; Insurance, Health ; Korea ; Male