1.Exploring orthostatic hypotension in patients with multiple system atrophy by a non-invasive cardiac output system
Ke-Vin Chang ; Ruey-Meei Wu ; Ssu-Yuan Chen ; Hsiu-Yu Shen ; Ching Lan ; Yen-Ho Wang
Neurology Asia 2012;17(4):311-318
Objective: To detect early subclinical signs of autonomic dysfunction in the cardiovascular system
and explore the mechanism of orthostatic hypotension (OH) in patients with multiple system atrophy
(MSA). Methods: Eighteen male patients with possible MSA and 10 healthy men were recruited.
The hemodynamic responses to head-up tilt and tilt-reversal were studied by an electrically-powered
tilt table and a non-invasive cardiac output measurement (NICOM) system. Results: At supine, there
was no signifi cant difference in blood pressure, heart rate (HR), stroke volume, cardiac output and
total peripheral resistance between MSA patients and healthy controls. During tilting upright, OH
developed in 5 MSA patients, with a 23.7±4.8 mmHg drop in systolic blood pressure. Patients with
OH were older and exhibited higher scores in unifi ed Multiple System Atrophy Rating Scale part I
than patients without OH. The stroke volume, cardiac output and total peripheral resistance did not
differ between groups. The controls had the most signifi cant HR elevation (6.5±2.5 bpm) during tiltup,
followed by patients without OH (2.8±1.6 bpm) and those with OH (-0.2±2.2 bpm). A similar
trend of HR decrease was observed during return to supine posture. The process of tilt-reversal altered
HR more signifi cantly than head-up tilt in controls (8.0±2.9 vs 6.5±2.5 bpm; P=0.031) and patients
without OH (4.2±2.1 vs 2.8±1.6 bpm; P=0.032), but not in patients with OH (1.2±1.5 vs -0.2±2.2
bpm; P=0.380).
Conclusions: The HR change during postural challenge showed signifi cant difference between MSA
patients and healthy controls. Impaired HR responsiveness contributed to OH in MSA. Monitoring HR
during the tilt table test may be a practical and useful method to detect early autonomic dysfunction
in patients with MSA.
2.Type 2 Diabetes Mellitus Increases Peritonsillar Abscess Susceptibility: Real-World Evidence
Ching-Lung WU ; Ming-Shao TSAI ; Ta-Jen LEE ; Yun-Ting WANG ; Chia-Yen LIU ; Yao-Hsu YANG ; Yao-Te TSAI ; Cheng-Ming HSU ; Ching-Yuan WU ; Pey-Jium CHANG ; Geng-He CHANG
Clinical and Experimental Otorhinolaryngology 2021;14(3):347-354
Objectives:
. Type 2 diabetes mellitus (T2DM) is a risk factor for deep neck infection (DNI) and leads to complications and poor outcomes. Our study aimed to investigate the risk, prognosis, and complications of peritonsillar abscess (PTA) in patients with T2DM.
Methods:
. We extracted data of patients newly diagnosed as having T2DM between January 2000 and December 2011 from Taiwan’s National Health Insurance Research Database. These patients were matched with patients without T2DM, and PTA incidence was compared between both cohorts.
Results:
. In total, 67,852 patients with and 135,704 patients without T2DM were enrolled. PTA incidence was significantly higher in patients with T2DM (incidence rate ratio, 1.91; P<0.001); moreover, PTA incidence was higher at 1 to 5 years after T2DM diagnosis than at <1 and >5 years after T2DM diagnosis. Cox regression analysis showed that patients with T2DM had an approximately 2-fold higher PTA risk (adjusted hazard ratio [aHR]: 1.89, P<0.001). Patients with a higher adapted Diabetes Complications Severity Index (aDCSI) had higher PTA risk than those with a lower aDCSI (aHRs: 2.17 for aDCSI ≥1, P=0.006 and 1.81 for aDCSI=0, P=0.002). T2DM patients with a high aDCSI (≥1) had a nonsignificantly longer hospitalization duration and a higher rate of DNI complications than did those with a low aDCSI (=0).
Conclusion
. In patients with T2DM, PTA incidence was relatively high, and it increased with T2DM severity. Moreover, T2DM patients should be particularly careful about PTA within 1 to 5 years after the diagnosis, and physicians should keep in mind that the prognosis of PTA was correlated with T2DM severity.
3.Type 2 Diabetes Mellitus Increases Peritonsillar Abscess Susceptibility: Real-World Evidence
Ching-Lung WU ; Ming-Shao TSAI ; Ta-Jen LEE ; Yun-Ting WANG ; Chia-Yen LIU ; Yao-Hsu YANG ; Yao-Te TSAI ; Cheng-Ming HSU ; Ching-Yuan WU ; Pey-Jium CHANG ; Geng-He CHANG
Clinical and Experimental Otorhinolaryngology 2021;14(3):347-354
Objectives:
. Type 2 diabetes mellitus (T2DM) is a risk factor for deep neck infection (DNI) and leads to complications and poor outcomes. Our study aimed to investigate the risk, prognosis, and complications of peritonsillar abscess (PTA) in patients with T2DM.
Methods:
. We extracted data of patients newly diagnosed as having T2DM between January 2000 and December 2011 from Taiwan’s National Health Insurance Research Database. These patients were matched with patients without T2DM, and PTA incidence was compared between both cohorts.
Results:
. In total, 67,852 patients with and 135,704 patients without T2DM were enrolled. PTA incidence was significantly higher in patients with T2DM (incidence rate ratio, 1.91; P<0.001); moreover, PTA incidence was higher at 1 to 5 years after T2DM diagnosis than at <1 and >5 years after T2DM diagnosis. Cox regression analysis showed that patients with T2DM had an approximately 2-fold higher PTA risk (adjusted hazard ratio [aHR]: 1.89, P<0.001). Patients with a higher adapted Diabetes Complications Severity Index (aDCSI) had higher PTA risk than those with a lower aDCSI (aHRs: 2.17 for aDCSI ≥1, P=0.006 and 1.81 for aDCSI=0, P=0.002). T2DM patients with a high aDCSI (≥1) had a nonsignificantly longer hospitalization duration and a higher rate of DNI complications than did those with a low aDCSI (=0).
Conclusion
. In patients with T2DM, PTA incidence was relatively high, and it increased with T2DM severity. Moreover, T2DM patients should be particularly careful about PTA within 1 to 5 years after the diagnosis, and physicians should keep in mind that the prognosis of PTA was correlated with T2DM severity.
4.Doxorubicin Promotes Migration and Invasion of Breast Cancer Cells through the Upregulation of the RhoA/MLC Pathway
Chien Liang LIU ; Ming Jen CHEN ; Jiunn Chang LIN ; Chi Hsin LIN ; Wen Chien HUANG ; Shih Ping CHENG ; Shan Na CHEN ; Yuan Ching CHANG
Journal of Breast Cancer 2019;22(2):185-195
PURPOSE: Cancer cells develop acquired resistance induced by chemotherapeutic drugs. In this study, we investigated the effects of brief treatment with cytotoxic drugs on the phenotype of breast cancer cells. METHODS: Breast cancer cells MCF7 and BT-474 were briefly treated with paclitaxel or doxorubicin. Clonogenic, migration, and invasion assays were performed on the treated cells. Western blot analysis and RhoA activity assay were also performed. RESULTS: Breast cancer cells when briefly treated with paclitaxel or doxorubicin showed reduced clonogenic ability. Doxorubicin, but not paclitaxel, augmented cell migration and invasion. The invasion-promoting effects of doxorubicin were lost when the two drugs were sequentially used in combination. Myosin light chain (MLC) 2 phosphorylation and RhoA activity were upregulated by doxorubicin and downregulated by paclitaxel. Pretreatment with RhoA inhibitors abolished the migration- and invasion-promoting effects of doxorubicin. CONCLUSION: Doxorubicin activates the RhoA/MLC pathway and enhances breast cancer cell migration and invasion. Therefore, this pathway might be explored as a therapeutic target to suppress anthracycline-enhanced tumor progression.
Blotting, Western
;
Breast Neoplasms
;
Breast
;
Cell Movement
;
Doxorubicin
;
Myosin Light Chains
;
Paclitaxel
;
Phenotype
;
Phosphorylation
;
Up-Regulation
5.Safety and Efficacy of Adalimumab for Patients With Moderate to Severe Crohn's Disease: The Taiwan Society of Inflammatory Bowel Disease (TSIBD) Study.
Chen Wang CHANG ; Shu Chen WEI ; Jen Wei CHOU ; Tzu Chi HSU ; Chiao Hsiung CHUANG ; Ching Pin LIN ; Wen Hung HSU ; Hsu Heng YEN ; Jen Kou LIN ; Yi Jen FANG ; Horng Yuan WANG ; Hung Hsin LIN ; Deng Cheng WU ; Yen Hsuan NI ; Cheng Yi WANG ; Jau Min WONG
Intestinal Research 2014;12(4):287-292
BACKGROUND/AIMS: Only moderate to severe Crohn's Disease (CD) patients without a satisfactory conventional therapy effect are eligible to get reimbursement from the National Health Insurance of Taiwan for using adalimumab. These are more stringent criteria than in many Western countries and Japan and Korea. We aim to explore the efficacy of using adalimumab in CD patients under such stringent criteria. METHODS: A retrospective analysis was conducted in nine medical centers in Taiwan and we collected the results of CD patients receiving adalimumab from Sep 2009 to Mar 2014. The clinical characteristics, response measured by CDAI (Crohn's Disease Activity Index), adverse events and survival status were recorded and analyzed. CR-70, CR-100, and CR-150 were defined as attaining a CDAI decrease of 70, 100 or 150 points compared with baseline. RESULTS: A total of 103 CD patient records were used in this study. Sixty percent of these patients received combination therapy of adalimumab together with immunomodulators. CR-70 was 68.7%, 74.5% and 88.4% after week 4, 8 and 12 of treatment, respectively. The steroid-free rate, complications and survival were 47.6%, 9.7% and 99% of patients, respectively. In considering the mucosal healing, only 25% patients achieve mucosal healing after treatment for 6 to12 months. Surgery was still needed in 16.5% of patients. Combination treatment of adalimumab with immunomodulators further decreased the level of CDAI at week 8 when compared with the monotherapy. CONCLUSIONS: Even under the stringent criteria for using adalimumab, the response rate was comparable to those without stringent criteria.
Adalimumab
;
Crohn Disease*
;
Humans
;
Immunologic Factors
;
Inflammatory Bowel Diseases*
;
Japan
;
Korea
;
National Health Programs
;
Retrospective Studies
;
Taiwan*
6.Cis-3-O-p-hydroxycinnamoyl Ursolic Acid Induced ROS-Dependent p53-Mediated Mitochondrial Apoptosis in Oral Cancer Cells.
Ching Ying WANG ; Chen Sheng LIN ; Chun Hung HUA ; Yu Jen JOU ; Chi Ren LIAO ; Yuan Shiun CHANG ; Lei WAN ; Su Hua HUANG ; Mann Jen HOUR ; Cheng Wen LIN
Biomolecules & Therapeutics 2019;27(1):54-62
Cis-3-O-p-hydroxycinnamoyl ursolic acid (HCUA), a triterpenoid compound, was purified from Elaeagnus oldhamii Maxim. This traditional medicinal plant has been used for treating rheumatoid arthritis and lung disorders as well as for its anti-inflammation and anticancer activities. This study aimed to investigate the anti-proliferative and apoptotic-inducing activities of HCUA in oral cancer cells. HCUA exhibited anti-proliferative activity in oral cancer cell lines (Ca9-22 and SAS cells), but not in normal oral fibroblasts. The inhibitory concentration of HCUA that resulted in 50% viability was 24.0 µM and 17.8 µM for Ca9-22 and SAS cells, respectively. Moreover, HCUA increased the number of cells in the sub-G1 arrest phase and apoptosis in a concentration-dependent manner in both oral cancer cell lines, but not in normal oral fibroblasts. Importantly, HCUA induced p53-mediated transcriptional regulation of pro-apoptotic proteins (Bax, Bak, Bim, Noxa, and PUMA), which are associated with mitochondrial apoptosis in oral cancer cells via the loss of mitochondrial membrane potential. HCUA triggered the production of intracellular reactive oxygen species (ROS) that was ascertained to be involved in HCUA-induced apoptosis by the ROS inhibitors YCG063 and N-acetyl-L-cysteine. As a result, HCUA had potential antitumor activity to oral cancer cells through eliciting ROS-dependent and p53-mediated mitochondrial apoptosis. Overall, HCUA could be applicable for the development of anticancer agents against human oral cancer.
Acetylcysteine
;
Antineoplastic Agents
;
Apoptosis Regulatory Proteins
;
Apoptosis*
;
Arthritis, Rheumatoid
;
Cell Line
;
Elaeagnaceae
;
Fibroblasts
;
Humans
;
Lung
;
Membrane Potential, Mitochondrial
;
Mouth Neoplasms*
;
Plants, Medicinal
;
Reactive Oxygen Species
7.Association Between Exposure to Particulate Matter and the Incidence of Parkinson’s Disease: A Nationwide Cohort Study in Taiwan
Ting-Bin CHEN ; Chih-Sung LIANG ; Ching-Mao CHANG ; Cheng-Chia YANG ; Hwa-Lung YU ; Yuh-Shen WU ; Winn-Jung HUANG ; I-Ju TSAI ; Yuan-Horng YAN ; Cheng-Yu WEI ; Chun-Pai YANG
Journal of Movement Disorders 2024;17(3):313-321
Objective:
Emerging evidence suggests that air pollution exposure may increase the risk of Parkinson’s disease (PD). We aimed to investigate the association between exposure to fine particulate matter (PM2.5) and the risk of incident PD nationwide.
Methods:
We utilized data from the Taiwan National Health Insurance Research Database, which is spatiotemporally linked with air quality data from the Taiwan Environmental Protection Administration website. The study population consisted of participants who were followed from the index date (January 1, 2005) until the occurrence of PD or the end of the study period (December 31, 2017). Participants who were diagnosed with PD before the index date were excluded. To evaluate the association between exposure to PM2.5 and incident PD risk, we employed Cox regression to estimate the hazard ratio and 95% confidence interval (CI).
Results:
A total of 454,583 participants were included, with a mean (standard deviation) age of 63.1 (9.9) years and a male proportion of 50%. Over a mean follow-up period of 11.1 (3.6) years, 4% of the participants (n = 18,862) developed PD. We observed a significant positive association between PM2.5 exposure and the risk of PD, with a hazard ratio of 1.22 (95% CI, 1.20–1.23) per interquartile range increase in exposure (10.17 μg/m3) when adjusting for both SO2 and NO2.
Conclusion
We provide further evidence of an association between PM2.5 exposure and the risk of PD. These findings underscore the urgent need for public health policies aimed at reducing ambient air pollution and its potential impact on PD.
8.Sofosbuvir/velpatasvir plus ribavirin for Child-Pugh B and Child-Pugh C hepatitis C virus-related cirrhosis
Chen-Hua LIU ; Chi-Yi CHEN ; Wei-Wen SU ; Chun-Jen LIU ; Ching-Chu LO ; Ke-Jhang HUANG ; Jyh-Jou CHEN ; Kuo-Chih TSENG ; Chi-Yang CHANG ; Cheng-Yuan PENG ; Yu-Lueng SHIH ; Chia-Sheng HUANG ; Wei-Yu KAO ; Sheng-Shun YANG ; Ming-Chang TSAI ; Jo-Hsuan WU ; Po-Yueh CHEN ; Pei-Yuan SU ; Jow-Jyh HWANG ; Yu-Jen FANG ; Pei-Lun LEE ; Chi-Wei TSENG ; Fu-Jen LEE ; Hsueh-Chou LAI ; Tsai-Yuan HSIEH ; Chun-Chao CHANG ; Chung-Hsin CHANG ; Yi-Jie HUANG ; Jia-Horng KAO
Clinical and Molecular Hepatology 2021;27(4):575-588
Background/Aims:
Real-world studies assessing the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) plus ribavirin (RBV) for Child-Pugh B/C hepatitis C virus (HCV)-related cirrhosis are limited.
Methods:
We included 107 patients with Child-Pugh B/C HCV-related cirrhosis receiving SOF/VEL plus RBV for 12 weeks in Taiwan. The sustained virologic response rates at off-treatment week 12 (SVR12) for the evaluable population (EP), modified EP, and per-protocol population (PP) were assessed. Thesafety profiles were reported.
Results:
The SVR12 rates in the EP, modified EP and PP were 89.7% (95% confidence interval [CI], 82.5–94.2%), 94.1% (95% CI, 87.8–97.3%), and 100% (95% CI, 96.2–100%). Number of patients who failed to achieve SVR12 were attributed to virologic failures. The SVR12 rates were comparable regardless of patient characteristics. One patient discontinued treatment because of adverse events (AEs). Twenty-four patients had serious AEs and six died, but none were related to SOF/VEL or RBV. Among the 96 patients achieving SVR12, 84.4% and 64.6% had improved Child-Pugh and model for endstage liver disease (MELD) scores. Multivariate analysis revealed that a baseline MELD score ≥15 was associated with an improved MELD score of ≥3 (odds ratio, 4.13; 95% CI, 1.16–14.71; P=0.02). Patients with chronic kidney disease (CKD) stage 1 had more significant estimated glomerular filtration rate declines than patients with CKD stage 2 (-0.42 mL/min/1.73 m2/month; P=0.01) or stage 3 (-0.56 mL/min/1.73 m2/month; P<0.001).
Conclusions
SOF/VEL plus RBV for 12 weeks is efficacious and well-tolerated for Child-Pugh B/C HCV-related cirrhosis.
9.Sofosbuvir/velpatasvir plus ribavirin for Child-Pugh B and Child-Pugh C hepatitis C virus-related cirrhosis
Chen-Hua LIU ; Chi-Yi CHEN ; Wei-Wen SU ; Chun-Jen LIU ; Ching-Chu LO ; Ke-Jhang HUANG ; Jyh-Jou CHEN ; Kuo-Chih TSENG ; Chi-Yang CHANG ; Cheng-Yuan PENG ; Yu-Lueng SHIH ; Chia-Sheng HUANG ; Wei-Yu KAO ; Sheng-Shun YANG ; Ming-Chang TSAI ; Jo-Hsuan WU ; Po-Yueh CHEN ; Pei-Yuan SU ; Jow-Jyh HWANG ; Yu-Jen FANG ; Pei-Lun LEE ; Chi-Wei TSENG ; Fu-Jen LEE ; Hsueh-Chou LAI ; Tsai-Yuan HSIEH ; Chun-Chao CHANG ; Chung-Hsin CHANG ; Yi-Jie HUANG ; Jia-Horng KAO
Clinical and Molecular Hepatology 2021;27(4):575-588
Background/Aims:
Real-world studies assessing the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) plus ribavirin (RBV) for Child-Pugh B/C hepatitis C virus (HCV)-related cirrhosis are limited.
Methods:
We included 107 patients with Child-Pugh B/C HCV-related cirrhosis receiving SOF/VEL plus RBV for 12 weeks in Taiwan. The sustained virologic response rates at off-treatment week 12 (SVR12) for the evaluable population (EP), modified EP, and per-protocol population (PP) were assessed. Thesafety profiles were reported.
Results:
The SVR12 rates in the EP, modified EP and PP were 89.7% (95% confidence interval [CI], 82.5–94.2%), 94.1% (95% CI, 87.8–97.3%), and 100% (95% CI, 96.2–100%). Number of patients who failed to achieve SVR12 were attributed to virologic failures. The SVR12 rates were comparable regardless of patient characteristics. One patient discontinued treatment because of adverse events (AEs). Twenty-four patients had serious AEs and six died, but none were related to SOF/VEL or RBV. Among the 96 patients achieving SVR12, 84.4% and 64.6% had improved Child-Pugh and model for endstage liver disease (MELD) scores. Multivariate analysis revealed that a baseline MELD score ≥15 was associated with an improved MELD score of ≥3 (odds ratio, 4.13; 95% CI, 1.16–14.71; P=0.02). Patients with chronic kidney disease (CKD) stage 1 had more significant estimated glomerular filtration rate declines than patients with CKD stage 2 (-0.42 mL/min/1.73 m2/month; P=0.01) or stage 3 (-0.56 mL/min/1.73 m2/month; P<0.001).
Conclusions
SOF/VEL plus RBV for 12 weeks is efficacious and well-tolerated for Child-Pugh B/C HCV-related cirrhosis.
10.Comedications and potential drug-drug interactions with direct-acting antivirals in hepatitis C patients on hemodialysis
Po-Yao HSU ; Yu-Ju WEI ; Jia-Jung LEE ; Sheng-Wen NIU ; Jiun-Chi HUANG ; Cheng-Ting HSU ; Tyng-Yuan JANG ; Ming-Lun YEH ; Ching-I HUANG ; Po-Cheng LIANG ; Yi-Hung LIN ; Ming-Yen HSIEH ; Meng-Hsuan HSIEH ; Szu-Chia CHEN ; Chia-Yen DAI ; Zu-Yau LIN ; Shinn-Cherng CHEN ; Jee-Fu HUANG ; Jer-Ming CHANG ; Shang-Jyh HWANG ; Wan-Long CHUANG ; Chung-Feng HUANG ; Yi-Wen CHIU ; Ming-Lung YU
Clinical and Molecular Hepatology 2021;27(1):186-196
Background/Aims:
Direct‐acting antivirals (DAAs) have been approved for hepatitis C virus (HCV) treatment in patients with end-stage renal disease (ESRD) on hemodialysis. Nevertheless, the complicated comedications and their potential drug-drug interactions (DDIs) with DAAs might limit clinical practice in this special population.
Methods:
The number, class, and characteristics of comedications and their potential DDIs with five DAA regimens were analyzed among HCV-viremic patients from 23 hemodialysis centers in Taiwan.
Results:
Of 2,015 hemodialysis patients screened in 2019, 169 patients seropositive for HCV RNA were enrolled (mean age, 65.6 years; median duration of hemodialysis, 5.8 years). All patients received at least one comedication (median number, 6; mean class number, 3.4). The most common comedication classes were ESRD-associated medications (94.1%), cardiovascular drugs (69.8%) and antidiabetic drugs (43.2%). ESRD-associated medications were excluded from DDI analysis. Sofosbuvir/velpatasvir/voxilaprevir had the highest frequency of potential contraindicated DDIs (red, 5.6%), followed by glecaprevir/pibrentasvir (4.0%), sofosbuvir/ledipasvir (1.3%), sofosbuvir/velpatasvir (1.3%), and elbasvir/grazoprevir (0.3%). For potentially significant DDIs (orange, requiring close monitoring or dose adjustments), sofosbuvir/velpatasvir/voxilaprevir had the highest frequency (19.9%), followed by sofosbuvir/ledipasvir (18.2%), glecaprevir/pibrentasvir (12.6%), sofosbuvir/velpatasvir (12.6%), and elbasvir/grazoprevir (7.3%). Overall, lipid-lowering agents were the most common comedication class with red-category DDIs to all DAA regimens (n=62), followed by cardiovascular agents (n=15), and central nervous system agents (n=10).
Conclusions
HCV-viremic patients on hemodialysis had a very high prevalence of comedications with a broad spectrum, which had varied DDIs with currently available DAA regimens. Elbasvir/grazoprevir had the fewest potential DDIs, and sofosbuvir/velpatasvir/voxilaprevir had the most potential DDIs.