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Choi, Jung Won,Son, Sung Min,Mook-Jung, Inhee,Moon, Youn Joo,Lee, Ji Yeoun,Wang, Kyu-Chang,Kang, Hyun-Seung,Phi, Ji Hoon,Choi, Seung Ah,Chong, Sangjoon,Byun, Jayoung,Kim, Seung-Ki Journal of Neurosurgery Publishing Group 2018 Journal of neurosurgery Vol.129 No.5
<B>OBJECTIVE</B><P>Moyamoya disease (MMD) is a unique cerebrovascular disorder characterized by the progressive occlusion of the bilateral internal carotid arteries. Endothelial colony-forming cells (ECFCs), previously termed “endothelial progenitor cells,” play an important role in the pathogenesis of MMD. In this study, the authors performed morphological and functional studies of the mitochondria of ECFCs from patients with MMD to present new insights into the pathogenesis of the disease.</P><B>METHODS</B><P>The morphology of ECFCs from 5 MMD patients and 5 healthy controls was examined under both a transmission electron microscope and a confocal laser scanning microscope. The oxygen consumption rates (OCRs), mitochondrial membrane potentials (MMPs), intracellular Ca<SUP>2+</SUP> concentrations, mitochondrial enzyme activities, and reactive oxygen species (ROS) levels were measured. Functional activity of the ECFCs was evaluated using a capillary tube formation assay.</P><B>RESULTS</B><P>The ECFCs from the MMD patients displayed a disrupted mitochondrial morphology, including a shorter and more circular shape. The ECFC mitochondria from the MMD patients exhibited functional abnormalities, which were assessed as a decreased OCR and an increased intracellular Ca<SUP>2+</SUP> concentration. Moreover, the ECFCs from MMD patients showed increased ROS levels. Interestingly, treatment with an ROS scavenger not only reversed the mitochondrial abnormalities but also restored the angiogenic activity of the ECFCs from the MMD patients.</P><B>CONCLUSIONS</B><P>The mitochondria of ECFCs from MMD patients, as compared with those from healthy patients, exhibited morphological and functional abnormalities. This finding suggests that the mitochondrial abnormalities may have a role in the pathogenesis of MMD.</P>
( Won-mook Choi ),( Jonggi Choi ),( Danbi Lee ),( Ju Hyun Shim ),( Kang Mo Kim ),( Young-suk Lim ),( Han Chu Lee ),( Changhoon Yoo ),( Sook Ryun Park ),( Min-hee Ryu ),( Baek-yeol Ryoo ) 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1
Aims: Nivolumab showed durable response and safety in patients with hepatocellular carcinoma (HCC) in the previous trials. However, real-world data of nivolumab in HCC patients, especially those with Child-Pugh class B, is lacking. We aimed to investigate the efficacy and safety of nivolumab in a real- world cohort of patients with advanced HCC. Methods: This study retrospectively evaluated 203 patients with HCC who were treated with nivolumab between July 2017 to February 2019. Radiologic evaluation was based on mRECIST. Survival outcomes were estimated by Kaplan-Meier method and Cox proportional hazard model. Logistic regression model was used to identify the predictive factors of treatment response. Results: Of 203 patients, 132 patients were within Child-Pugh class A and 71 patients were within Child-Pugh class B. Objective response rate was lower in patients with Child-Pugh class B than A (2.8% vs. 15.9%; P=0.010 by unweighted analysis and P=0.034 by weighted analysis) and Child-Pugh class was an independent predictor for objective response (Odds ratio, 0.21; 95% confidence interval; 0.05-0.93; P=0.040). Median overall survival was shorter in Child-Pugh B patients (11.3 vs. 42.9 weeks; P<0.001 by both unweighted and weighted analyses). However, other efficacy outcomes including disease control rate, time to progression, and progression-free survival were comparable between Child-Pugh A and B patients by unadjusted, adjusted, matched, and weighted analyses. There was no significant difference in terms of safety between Child-Pugh A and B patients. Conclusions: Given the limited treatment options for advanced HCC in Child-Pugh B patients, nivolumab may be a viable option despite lower response in these patients. Further studies are needed in this patient population.
( Won-mook Choi ),( Jonggi Choi ),( Danbi Lee ),( Ju Hyun Shim ),( Young-suk Lim ),( Han Chu Lee ),( Young-hwa Chung ),( Young-sang Lee ),( Sook Ryun Park ),( Min-hee Ryu ),( Baek-yeol Ryoo ),( So Jun 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1
Aims: Regorafenib and nivolumab are drugs approved for second-line treatment of patients with hepatocellular carcinoma (HCC) after sorafenib failure. However, the effectiveness of regorafenib and nivolumab following sorafenib has not been directly compared. Methods: This study retrospectively evaluated 373 patients with HCC who were treated with regorafenib (n=223) or nivolumab (n=150) after sorafenib failure between July 2017 and February 2019. Results: Progression-free survival (PFS; hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.69-1.06; P=0.150), time to progression (TTP; HR, 0.95; 95% CI, 0.77-1.19; P=0.680), and overall survival (OS; HR, 0.83; 95% CI, 0.64-1.07; P=0.154) did not differ significantly between groups of patients treated with regorafenib and nivolumab, findings consistently observed by multivariable-adjusted, propensity score-matched, and inverse probability treatment weighting (IPTW) analyses. However, the objective response rate was significantly higher in the nivolumab than in the regorafenib group (13.3% vs, 4.0%; P=0.002). When the effectiveness of regorafenib and nivolumab was compared in non-progressors to treatment, defined as patients who achieved complete response, partial response, or stable disease after first response evaluation, PFS (HR, 0.50; 95% CI, 0.33-0.75; P=0.001), TTP (HR, 0.48; 95% CI, 0.31-0.73; P<0.001), and OS (HR, 0.51; 95% CI, 0.31-0.87; P=0.013) were significantly longer in the 59 non-progressors to nivolumab than in the 104 non-progressors to regorafenib, findings also observed by multivariable-adjusted and IPTW analyses. Conclusions: Survival outcomes in patients treated with regorafenib and nivolumab after sorafenib failure did not differ significantly. However, nivolumab may be more effective than regorafenib in non-progressors.
Pathophysiology of liver fibrosis and liver immunity
( Won-mook Choi ),( Won-il Jeong ) 대한간학회 2015 임상연구방법론워크숍 Vol.2015 No.1
Various types of chronic liver disease cause liver fibrosis. Hepatic stellate cells (HSCs) are known as the key cell type by producing a large amount of extracellular matrix, profibrotic cytokines and chemokines. Recently, emerging evidence suggests that the liver is not only a metabolic organ but also an immunologic organ due to enrichment of diverse types of innate and adaptive immune cells. Moreover, the cell-to-cell interactions between HSCs and various types of immune cells are closely associated with the pathogenesis of liver fibrosis. Especially, the liver is known to play a key role in innate immune defenses against pathogens. Indeed, various innate immune cells such as Kupffer cells, macrophages/monocytes, neutrophils, and dendritic cells play an important role in accelerating or ameliorating liver fibrosis directly or indirectly via interactions with HSCs. Moreover, unlike other organs, innate lymphocytes such as natural killer (NK), NKT, and γδ T cell are abundant in the liver comprising up to 50% of whole liver lymphocytes. Although still controversial in their roles (i.e. profibrotic vs. antifibrotic), these innate lymphocytes are also deeply involved in the pathogenesis of liver fibrosis. Especially, NK cells seem to play a negative regulatory role in liver fibrosis via inhibiting or suppressing activated HSCs. In addition, increasing evidences have suggested that adaptive immune cells are no longer a ‘bystander’, but contribute considerably to liver fibrosis. In this review, we summarize the updated concept of pathophysiology of liver fibrosis and liver immunity.
( Won-mook Choi ),( Jonggi Choi ),( Young-suk Lim ) 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1
Aims: Tenofovir disoproxil fumarate (TDF) and entecavir are recommended as first-line treatments for chronic hepatitis B virus (HBV) infection. However, there is debate over the comparative effectiveness of these drugs in preventing hepatocellular carcinoma (HCC). We performed a systematic review and meta-analysis of the effectiveness of TDF vs entecavir in reducing the incidence of HCC among patients with chronic HBV infection. Methods: We performed a systematic review of the MEDLINE, EMBASE, Web of Science, and Cochrane Library from 2010 through 2019 for full-text articles and conference abstracts on studies of effects of TDF vs entecavir in patients with HBV infection. Extracted data were analyzed with the random effects model. Potential sources of heterogeneity were investigated using sensitivity, meta-regression, and subgroup analyses. Results: Our final analysis comprised 15 studies (61,787 patients; 16,101 patients given TDF and 45,686 given entecavir). TDF treatment was associated with a significantly lower risk of HCC than entecavir (hazard ratio, 0.80; 95% CI, 0.69-0.93; P=.003; I<sup>2</sup>=13%). The lower risk of HCC in patients given TDF compared with entecavir persisted in sensitivity and subcohort analyses performed with propensity score-matched cohorts and cirrhosis subcohorts. Inclusion of patients with decompensated cirrhosis and the sample size were the factors with the largest effects on between-study heterogeneity in meta-regression analyses. There were no statistical differences in the incidence of death or transplantation (hazard ratio, 0.93; 95% CI, 0.73-1.17; P=.519; I<sup>2</sup>=6%) between patients given TDV vs entecavir. Conclusions: In a meta-analysis of studies of patients with chronic HBV infection, we found that TDF treatment was associated with a significantly lower (20%) risk of HCC than entecavir treatment. Randomized trials are needed to support this finding.
Choi, Kyung Mook,Park, Hye Soon,Han, Jee Hye,Lee, Jee Sung,Lee, Juneyoung,Ryu, Ok Hyun,Lee, Kye Won,Cho, Kyung Hwan,Yoon, Dokyong,Baik, Sei Hyun,Choi, Dong Seop,Kim, Seon Mee Lippincott Williams Wilkins, Inc. 2006 Journal of hypertension Vol.24 No.8
OBJECTIVE: The present study aimed to determine the prevalence of prehypertension and hypertension, and their association with the risk factors in a Korean population. DESIGN: The Korean Nation Health and Nutrition Survey 2001, a cross-sectional survey, was a nationally representative survey in which a stratified multistage sampling design was used. METHODS: Data from a comprehensive questionnaire, together with a physical examination and blood sample, were obtained from 6074 Korean adults (2620 men and 3454 women) aged ≥ 20 years, and analysed. RESULTS: The estimated age-adjusted prevalence of hypertension and prehypertension was 22.9% (26.9% in men, 20.5% in women) and 31.6% (41.9% in men, 25.9% in women), respectively, in the Korean population according to Joint National Committee 7 criteria. Multivariate analysis revealed that age, gender, body mass index, fasting plasma glucose, total-cholesterol and alcohol consumption were significantly associated with hypertension. Overall, only 30.2% of the hypertensive individuals had been previously diagnosed. Furthermore, 22.9% of the hypertensive individuals were being treated with antihypertensive medication, but only 10.7% had their blood pressure adequately controlled. The rates of awareness, treatment and control were higher for the women than for the men, and these rates increased with age. CONCLUSION: Hypertension and prehypertension are common in Korea, and more than one-half of the hypertensive patients have not been diagnosed. These results place great emphasis on the urgent need for a public health program to improve the detection, prevention and treatment of hypertension and prehypertension.