Displaying all 12 publications

  1. Wu WH, Kuo TC, Lin YT, Huang SW, Liu HF, Wang J, et al.
    PLoS ONE, 2013;8(12):e83711.
    PMID: 24391812 DOI: 10.1371/journal.pone.0083711
    Enterovirus 71 (EV71), a causative agent of hand, foot, and mouth disease can be classified into three genotypes and many subtypes. The objectives of this study were to conduct a molecular epidemiological study of EV71 in the central region of Taiwan from 2002-2012 and to test the hypothesis that whether the alternative appearance of different EV71 subtypes in Taiwan is due to transmission from neighboring countries or from re-emergence of pre-existing local strains. We selected 174 EV71 isolates and used reverse transcription-polymerase chain reaction to amplify their VP1 region for DNA sequencing. Phylogenetic analyses were conducted using Neighbor-Joining, Maximum Likelihood and Bayesian methods. We found that the major subtypes of EV71 in Taiwan were B4 for 2002 epidemic, C4 for 2004-2005 epidemic, B5 for 2008-2009 epidemic, C4 for 2010 epidemic and B5 for 2011-2012 epidemic. Phylogenetic analysis demonstrated that the 2002 and 2008 epidemics were associated with EV71 from Malaysia and Singapore; while both 2010 and 2011-2012 epidemics originated from different regions of mainland China including Shanghai, Henan, Xiamen and Gong-Dong. Furthermore, minor strains have been identified in each epidemic and some of them were correlated with the subsequent outbreaks. Therefore, the EV71 infection in Taiwan may originate from pre-existing minor strains or from other regions in Asia including mainland China. In addition, 101 EV71 isolates were selected for the detection of new recombinant strains using the nucleotide sequences spanning the VP1-2A-2B region. No new recombinant strain was found. Analysis of clinical manifestations showed that patients infected with C4 had significantly higher rates of pharyngeal vesicles or ulcers than patients infected with B5. This is the first study demonstrating that different EV 71 genotypes may have different clinical manifestations and the association of EV71 infections between Taiwan and mainland China.
  2. Lee YM, Wang SF, Lee CM, Chen KH, Chan YJ, Liu WT, et al.
    BMC Res Notes, 2009;2:86.
    PMID: 19426542 DOI: 10.1186/1756-0500-2-86
    From October 2006 to February 2007, clinical specimens from 452 patients with symptoms related to respiratory tract infection in the northern region of Taiwan were collected. Real-time PCR and direct immunofluorescent antibody tests showed that 145 (32%) patients had influenza B virus infections. Subsequently, nucleotide sequence analyses of both hemagglutinin (HA) and neuraminidase (NA) genes of 39 isolates were performed. Isolated viruses were antigenically characterized using hemagglutinin inhibition (HI) test.
  3. Lim CH, Lin CH, Chen DY, Chen YM, Chao WC, Liao TL, et al.
    PLoS ONE, 2016;11(11):e0166339.
    PMID: 27832150 DOI: 10.1371/journal.pone.0166339
    OBJECTIVE: To investigate the risk of tuberculosis (TB) among rheumatoid arthritis (RA) patients within 1 year after initiation of tumor necrosis factor inhibitor (TNFi) therapy from 2008 to 2012.

    METHODS: We used the 2003-2013 Taiwanese National Health Insurance Research Database to identify RA patients who started any RA-related medical therapy from 2008 to 2012. Those who initiated etanercept or adalimumab therapy during 2008-2012 were selected as the TNFi group and those who never received biologic disease-modifying anti-rheumatic drug therapy were identified as the comparison group after excluding the patients who had a history of TB or human immunodeficiency virus infection/acquired immune deficiency syndrome. We used propensity score matching (1:6) for age, sex, and the year of the drug index date to re-select the TNFi group and the non-TNFi controls. After adjusting for potential confounders, hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to examine the 1-year TB risk in the TNFi group compared with the non-TNFi controls. Subgroup analyses according to the year of treatment initiation and specific TNFi therapy were conducted to assess the trend of 1-year TB risk in TNFi users from 2008 to 2012.

    RESULTS: This study identified 5,349 TNFi-treated RA patients and 32,064 matched non-TNFi-treated controls. The 1-year incidence rates of TB were 1,513 per 105 years among the TNFi group and 235 per 105 years among the non-TNFi controls (incidence rate ratio, 6.44; 95% CI, 4.69-8.33). After adjusting for age, gender, disease duration, comoridities, history of TB, and concomitant medications, TNFi users had an increased 1-year TB risk (HR, 7.19; 95% CI, 4.18-12.34) compared with the non-TNFi-treated controls. The 1-year TB risk in TNFi users increased from 2008 to 2011 and deceased in 2012 when the Food and Drug Administration in Taiwan announced the Risk Management Plan for patients scheduled to receive TNFi therapy.

    CONCLUSION: This study showed that the 1-year TB risk in RA patients starting TNFi therapy was significantly higher than that in non-TNFi controls in Taiwan from 2008 to 2012.

  4. Lim CH, Tseng CW, Lin CT, Huang WN, Chen YH, Chen YM, et al.
    SAGE Open Med, 2018;6:2050312118781895.
    PMID: 29977547 DOI: 10.1177/2050312118781895
    Objective: To examine the clinical utility of tumor markers in dermatomyositis/polymyositis patients in Taiwan.

    Method: Data were collected retrospectively from the database of Taichung Veterans General Hospital in Taiwan from 1998 to 2014. Patients who fulfilled Bohan and Peter criteria of dermatomyositis/polymyositis were recruited. Serum level of tumor markers including carcinoembryonic antigen, alpha-fetoprotein, carbohydrate antigen 125, carbohydrate antigen 19-9 and carbohydrate antigen 15-3 were measured. The occurrence of malignancies and interstitial lung disease was identified. The association of tumor markers with malignancies and interstitial lung disease was examined using Chi-square test or Fisher's exact test.

    Results: Among the enrolled 151 patients, 98 (64.9%) dermatomyositis and 53 (35.1%) polymyositis, a total of 15 malignancies were detected: breast ductal carcinoma (n = 4), bladder transitional cell carcinoma (n = 2), lung adenocarcinoma (n = 2), cervical intraepithelial neoplasia 3 and papillary squamous cell carcinoma (n = 2), colorectal (colon and rectal adenocarcinoma) (n = 2), uterine adenocarcinoma (n = 1), nasopharyngeal carcinoma (n = 1) and hematological malignancy (myelodysplastic with excess blast cells) (n = 1). Among the patients with malignancies, 13 (86.7%) had dermatomyositis, 2 (13.3%) polymyositis and 3 (20%) interstitial lung disease. The mean duration from dermatomyositis/polymyositis diagnosis to the occurrence of malignancies was 6.05 ± 5.69 years. There was no significant association of raised tumor markers with the occurrence of malignancies (p > 0.085), while a significant association was observed between the elevated levels of carbohydrate antigen 15-3 and the presence of interstitial lung disease (p = 0.006).

    Conclusion: Tumor markers were not useful in malignancy screening or dermatomyositis/polymyositis patients in this tertiary center. The evaluation of the occurrence of malignancy in dermatomyositis/polymyositis patient should include a multidimensional approach. A raised level of carbohydrate antigen 15-3 may be a potential indicator of the presence of interstitial lung disease in dermatomyositis/polymyositis patients.
  5. Wang CT, Huang YS, Sangeetha T, Chen YM, Chong WT, Ong HC, et al.
    Bioresour. Technol., 2018 May;255:83-87.
    PMID: 29414177 DOI: 10.1016/j.biortech.2018.01.086
    Photosynthetic microbial fuel cells (PMFCs) are novel bioelectrochemical transducers that employ microalgae to generate oxygen, organic metabolites and electrons. Conventional PMFCs employ non-eco-friendly membranes, catalysts and phosphate buffer solution. Eliminating the membrane, buffer and catalyst can make the MFC a practical possibility. Therefore, single chambered (SPMFC) were constructed and operated at different recirculation flow rates (0, 40 and 240 ml/min) under bufferless conditions. Furthermore, maximum power density of 4.06 mW/m2, current density of 46.34 mA/m2 and open circuit potential of 0.43 V and low internal resistance of 611.8 Ω were obtained at 40 ml/min. Based on the results it was decided that SPMFC was better for operation at 40 ml/min. Therefore, these findings provided progressive insights for future pilot and industrial scale studies of PMFCs.
  6. Higuchi A, Kao SH, Ling QD, Chen YM, Li HF, Alarfaj AA, et al.
    Sci Rep, 2015 Dec 14;5:18136.
    PMID: 26656754 DOI: 10.1038/srep18136
    The tentative clinical application of human pluripotent stem cells (hPSCs), such as human embryonic stem cells and human induced pluripotent stem cells, is restricted by the possibility of xenogenic contamination resulting from the use of mouse embryonic fibroblasts (MEFs) as a feeder layer. Therefore, we investigated hPSC cultures on biomaterials with different elasticities that were grafted with different nanosegments. We prepared dishes coated with polyvinylalcohol-co-itaconic acid hydrogels grafted with an oligopeptide derived from vitronectin (KGGPQVTRGDVFTMP) with elasticities ranging from 10.3 to 30.4 kPa storage moduli by controlling the crosslinking time. The hPSCs cultured on the stiffest substrates (30.4 kPa) tended to differentiate after five days of culture, whereas the hPSCs cultured on the optimal elastic substrates (25 kPa) maintained their pluripotency for over 20 passages under xeno-free conditions. These results indicate that cell culture matrices with optimal elasticity can maintain the pluripotency of hPSCs in culture.
  7. Chen YM, Chen LH, Li MP, Li HF, Higuchi A, Kumar SS, et al.
    Sci Rep, 2017 03 23;7:45146.
    PMID: 28332572 DOI: 10.1038/srep45146
    Establishing cultures of human embryonic (ES) and induced pluripotent (iPS) stem cells in xeno-free conditions is essential for producing clinical-grade cells. Development of cell culture biomaterials for human ES and iPS cells is critical for this purpose. We designed several structures of oligopeptide-grafted poly (vinyl alcohol-co-itaconic acid) hydrogels with optimal elasticity, and prepared them in formations of single chain, single chain with joint segment, dual chain with joint segment, and branched-type chain. Oligopeptide sequences were selected from integrin- and glycosaminoglycan-binding domains of the extracellular matrix. The hydrogels grafted with vitronectin-derived oligopeptides having a joint segment or a dual chain, which has a storage modulus of 25 kPa, supported the long-term culture of human ES and iPS cells for over 10 passages. The dual chain and/or joint segment with cell adhesion molecules on the hydrogels facilitated the proliferation and pluripotency of human ES and iPS cells.
  8. Lai EL, Huang WN, Chen HH, Hsu CY, Chen DY, Hsieh TY, et al.
    Lupus, 2019 Jul;28(8):945-953.
    PMID: 31177913 DOI: 10.1177/0961203319855122
    The Fracture Risk Assessment Tool (FRAX) has been used universally for the purpose of fracture risk assessment. However, the predictive capacity of FRAX for autoimmune diseases remains inconclusive. This study aimed to compare the applicability of FRAX for autoimmune disease patients. This retrospective study recruited rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and primary Sjögren syndrome (pSS) patients with bone mineral density (BMD) tests. Patients with any osteoporotic fractures were identified. Taiwan-specific FRAX with and without BMD were then calculated. In total, 802 patients (451 RA, 233 SLE and 118 pSS) were enrolled in this study. The cumulative incidences of osteoporotic fractures in the RA, SLE and pSS patients were 43.0%, 29.2% and 33.1%, respectively. For those with a previous osteoporotic fracture, T-scores were classified as low bone mass. Overall, the patients' 10-year probability of major fracture risk by FRAX without BMD was 15.8%, which then increased to 20.3% after incorporation of BMD measurement. When analyzed by disease group, the fracture risk in RA patients was accurately predicted by FRAX. In contrast, current FRAX, either with or without BMD measurement, underestimated the fracture risk both in SLE and pSS patients, even after stratification by age and glucocorticoid treatment. For pSS patients with major osteoporotic fractures, FRAX risks imputed by RA were comparable to major osteoporotic fracture risks of RA patients. Current FRAX accurately predicted fracture probability in RA patients, but not in SLE and pSS patients. RA-imputed FRAX risk scores could be used as a temporary substitute for SLE and pSS patients.
  9. Oyomopito RA, Li PC, Sungkanuparph S, Phanuphak P, Tee KK, Sirisanthana T, et al.
    J. Acquir. Immune Defic. Syndr., 2013 Mar 1;62(3):293-300.
    PMID: 23138836 DOI: 10.1097/QAI.0b013e31827a2e8f
    HIV-1 group M viruses diverge 25%-35% in envelope, important for viral attachment during infection, and 10%-15% in the pol region, under selection pressure from common antiretrovirals. In Asia, subtypes B and CRF01_AE are common genotypes. Our objectives were to determine whether clinical, immunological, or virological treatment responses differed by genotype in treatment-naive patients initiating first-line therapy.
  10. Oyomopito RA, Chen YJ, Sungkanuparph S, Kantor R, Merati T, Yam WC, et al.
    Kaohsiung J. Med. Sci., 2015 Sep;31(9):445-53.
    PMID: 26362956 DOI: 10.1016/j.kjms.2015.07.002
    Human immunodeficiency virus (HIV)-1 epidemics in Asian countries are driven by varying exposures. The epidemiology of the regional pandemic has been changing with the spread of HIV-1 to lower-risk populations through sexual transmission. Common HIV-1 genotypes include subtype B and circulating recombinant form (CRF) 01_AE. Our objective was to use HIV-1 genotypic data to better quantify local epidemics. TASER-M is a multicenter prospective cohort of HIV-infected patients. Associations between HIV exposure, patient sex, country of sample origin and HIV-1 genotype were evaluated by multivariate logistic regression. Phylogenetic methods were used on genotypic data to investigate transmission relationships. A total of 1086 patients from Thailand, Hong Kong, Malaysia and the Philippines were included in analyses. Proportions of male patients within countries varied (Thailand: 55.6%, Hong Kong: 86.1%, Malaysia: 81.4%, Philippines: 93.8%; p 
  11. Lim CH, Chen HH, Chen YH, Chen DY, Huang WN, Tsai JJ, et al.
    PLoS ONE, 2017;12(6):e0178035.
    PMID: 28570568 DOI: 10.1371/journal.pone.0178035
    The objective of this study is to determine the risk of tuberculosis (TB) disease in biologics users among rheumatoid arthritis (RA) patients in Taiwan from 2000 to 2015. This retrospective cohort study enrolled adult RA patients initiated on first biologics at Taichung Veterans General Hospital. TB risks were determined as hazard ratio (HR) with 95% confidence interval (CI) using cox regression. A total of 951 patients were recruited; etanercept (n = 443), adalimumab (n = 332), abatacept (n = 74), golimumab (n = 60), tocilizumab (n = 31) and tofacitinib (n = 11). Twenty-four TB cases were identified; 13 in etanercept and 11 in adalimumab group with the TB incidence rate of 889.3/ 100,000 and 1055.6/ 100,000 patient-years respectively. There was no significant difference in TB risk between adalimumab and etanercept users with an incidence rate ratio of 1.27 (p = 0.556 by Poisson model). Significant 2-year TB risk factors included elderly patient >65 year-old (HR: 2.72, 95% CI: 1.06-6.99, p = 0.037), history of TB (HR: 6.24, 95% CI: 1.77-22.00, p = 0.004) and daily glucocorticoid use ≥5mg (HR:5.01, 95% CI: 1.46-17.21, p = 0.010). Sulfasalazine treatment appeared to be protective (HR: 0.32, 95% CI: 0.11-0.97, p = 0.043). Risk management plan (RMP) for TB before initiation of biologics commenced in 2012. The 2-year TB risks after RMP was compared with that before 2012 (HR:0.67, 95% CI: 0.30-1.49, p = 0.323). Elderly RA patients with a history of previous TB infection and concomitant moderate dose glucocorticoid were at higher risk of TB disease. Concurrent sulfasalazine treatment appeared to be a protective factor against TB disease.
  12. Chen M, Wong WW, Law MG, Kiertiburanakul S, Yunihastuti E, Merati TP, et al.
    PLoS ONE, 2016;11(3):e0150512.
    PMID: 26933963 DOI: 10.1371/journal.pone.0150512
    BACKGROUND: We assessed the effects of hepatitis B (HBV) or hepatitis C (HCV) co-infection on outcomes of antiretroviral therapy (ART) in HIV-infected patients enrolled in the TREAT Asia HIV Observational Database (TAHOD), a multi-center cohort of HIV-infected patients in the Asia-Pacific region.

    METHODS: Patients testing HBs antigen (Ag) or HCV antibody (Ab) positive within enrollment into TAHOD were considered HBV or HCV co-infected. Factors associated with HBV and/or HCV co-infection were assessed by logistic regression models. Factors associated with post-ART HIV immunological response (CD4 change after six months) and virological response (HIV RNA <400 copies/ml after 12 months) were also determined. Survival was assessed by the Kaplan-Meier method and log rank test.

    RESULTS: A total of 7,455 subjects were recruited by December 2012. Of patients tested, 591/5656 (10.4%) were HBsAg positive, 794/5215 (15.2%) were HCVAb positive, and 88/4966 (1.8%) were positive for both markers. In multivariate analysis, HCV co-infection, age, route of HIV infection, baseline CD4 count, baseline HIV RNA, and HIV-1 subtype were associated with immunological recovery. Age, route of HIV infection, baseline CD4 count, baseline HIV RNA, ART regimen, prior ART and HIV-1 subtype, but not HBV or HCV co-infection, affected HIV RNA suppression. Risk factors affecting mortality included HCV co-infection, age, CDC stage, baseline CD4 count, baseline HIV RNA and prior mono/dual ART. Shortest survival was seen in subjects who were both HBV- and HCV-positive.

    CONCLUSION: In this Asian cohort of HIV-infected patients, HCV co-infection, but not HBV co-infection, was associated with lower CD4 cell recovery after ART and increased mortality.

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