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 ),( 대한장연구학회 2014 Intestinal Research Vol.12 No.4

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. (Intest Res 2014;12:287-292)

Outcomes of limited period of adalimumab treatment in moderate to severe Crohn’s disease patients: Taiwan Society of Inflammatory Bowel Disease Study

( Wei-chen Lin ),( Jen-wei Chou ),( Hsu-heng Yen ),( Wen-hung Hsu ),( Hung-hsin Lin ),( Jen-kou Lin ),( Chiao-hsiung Chuang ),( Tien-yu Huang ),( Horng-yuan Wang ),( Shu-chen Wei ),( Jau-min Wong ) 대한장연구학회 2017 Intestinal Research Vol.15 No.4

Background/Aims: In Taiwan, due to budget limitations, the National Health Insurance only allows for a limited period of biologics use in treating moderate to severe Crohn’s disease (CD). We aimed to access the outcomes of CD patients following a limited period use of biologics, specifically focusing on the relapse rate and remission duration; also the response rate to second use when applicable. Methods: This was a multicenter, retrospective, observational study and we enrolled CD patients who had been treated with adalimumab (ADA) according to the insurance guidelines from 2009 to 2015. Results: A total of 54 CD patients, with follow-up of more than 6 months after the withdrawal of ADA, were enrolled. The average period of treatment with ADA was 16.7±9.7 months. After discontinuing ADA, 59.3% patients suffered a clinical relapse. In the univariate analysis, the reason for withdrawal was a risk factor for relapse (P=0.042). In the multivariate analysis, current smoker became an important risk factor for relapse (OR, 3.9; 95% CI, 1.2-14.8; P=0.044) and male sex was another risk factor (OR, 2.9; 95% CI, 1.1-8.6; P=0.049). For those 48 patients who received a second round of biologics, the clinical response was seen in 60.4%, and 1 anaphylaxis occurred. Conclusions: Fifty-nine percent of patients experienced a relapse after discontinuing the limited period of ADA treatment, and most of them occurred within 1 year following cessation. Male sex and current smoker were risk factors for relapse. Though 60.4% of the relapse patients responded to ADA again. (Intest Res 2017;15:487-494)

Acute Hepatitis Due to Agomelatine Use in Elderly Women with Depression: Case Series

Cheng-Chen Chang,Yen-Jen Chen,Yu-An Chen,Yi-Cheng Liao 대한정신약물학회 2021 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.19 No.4

Although agomelatine may be associated with an increased risk of hepatotoxicity, the incidence rate of acute hepatitis seemed divergent between clinical trials and daily practice. Whether aging or gender is a risk factor in developing hepatotoxicity due to agomelatine is not clear. We present 3 older female cases with acute hepatitis occurring due to highly probable idiosyncratic drug-induced liver injury caused by agomelatine. From these cases, regular surveillance on liver function in the older women taking antidepressants would be of benefits.

Risk factor analysis of coexisting endometrial carcinoma in patients with endometrial hyperplasia: a retrospective observational study of Taiwanese Gynecologic Oncology Group

Yu-Li Chen,Kung-Liahng Wang,Min-Yu Chen,Mu-Hsien Yu,Chen-Hsuan Wu,Yu-Min Ke,Yi-Jen Chen,Yin-Yi Chang,Keng-Fu Hsu,Ming-Shyen Yen 대한부인종양학회 2013 Journal of Gynecologic Oncology Vol.24 No.1

Objective: To evaluate the clinical outcome and parameters related to coexisting endometrial carcinoma in women with tissuediagnosed endometrial hyperplasia. Methods: Between January 1991 and December 2009, three hundred and eighty-six patients with the presumptive diagnosis of endometrial hyperplasia were retrieved. Among these, one hundred and twenty-five patients were identified as having coexisting endometrial carcinoma in hysterectomy specimens. The three hundred and eighty-six patients were divided into two groups: the hyperplasia-benign group (261 cases) and the hyperplasia-malignant group (125 cases). Several clinical parameters including age, menopausal status, history of abnormal uterine bleeding, obstetrical history, medical history of diabetes and hypertension, BMI, and preoperative pathologic results were investigated. Results: Age ≥53 (odds ratio [OR], 2.40; 95% confidence interval [CI], 1.26 to 4.57), menopausal status (OR, 2.07; 95% CI, 1.14to 3.76), diabetes history (OR, 7.33; 95% CI, 2.79 to 19.26), abnormal uterine bleeding (OR, 3.99; 95% CI, 1.22 to 13.02), atypical endometrial hyperplasia (OR, 7.38; 95% CI, 4.03 to 13.49), and body mass index ≥27 (OR, 3.24; 95% CI, 1.76 to 5.97) were independent risk factors for prediction of endometrial hyperplasia coexisting with endometrial carcinoma. The diagnostic efficacy of atypical endometrial hyperplasia to predict the endometrial hyperplasia coexisting with endometrial carcinoma was better than or similar to those of other independent factors and combinations of these factors. Conclusion: Coexisting malignancy should be considered when examining endometrial hyperplasia patients with the related risk factors, especially atypical endometrial hyperplasia.

Treatment outcomes of patients with stage II pure endometrioid-type endometrial cancer: a Taiwanese Gynecologic Oncology Group (TGOG-2006) retrospective cohort study

Hung-Chun Fu,Jen-Ruei Chen,Min-Yu Chen,Keng-Fu Hsu,Wen-Fang Cheng,An Jen Chiang,Yu-Min Ke,Yu-Chieh Chen,Yin-Yi Chang,Chia-Yen Huang,Chieh-Yi Kang,Yuan-Yee Kan,Sheng-Mou Hsiao,Ming-Shyen Yen 대한부인종양학회 2018 Journal of Gynecologic Oncology Vol.29 No.5

Objective: Choice of hysterectomy and adjuvant treatment for International Federation of Gynecology and Obstetrics (FIGO) 2009 stage II endometrioid endometrial cancer (EEC) is still controversial. Aims of this study were to evaluate survival benefits and adverse effects of different hysterectomies with or without adjuvant radiotherapy (RT), and to identify prognostic factors. Methods: The patients at 14 member hospitals of the Taiwanese Gynecologic Oncology Group from 1992 to 2013 were retrospectively investigated. Patients were divided into simple hysterectomy (SH) alone, SH with RT, radical hysterectomy (RH) alone, and RH with RT groups. Endpoints were recurrence-free survival (RFS), overall survival (OS), disease-specific survival (DSS), adverse effects and prognostic factors for survival. Results: Total of 246 patients were enrolled. The 5-year RFS, OS, DSS and recurrence rates for the entire cohort were 89.5%, 94.3%, 96.2% and 10.2%, respectively. Patients receiving RH had more adverse effects including blood loss (p<0.001), recurrent urinary tract infections (p=0.013), and leg lymphedema (p=0.038). Age over 50-year (HR=9.2; 95% confidence interval [CI], 1.2–70.9) and grade 3 histology (HR=7.28; 95% CI, 1.45–36.6) were independent predictors of OS. Grade 3 histology was an independent predictor of RFS (HR=5.13; 95% CI, 1.38–19.1) and DSS (HR=5.97; 95% CI, 1.06–58.7). Patients receiving adjuvant RT had lower locoregional recurrence (p=0.046), but no impact on survival. Conclusion: Different treatment modalities yield similar survival outcomes. Patients receiving SH with RT had lower locoregional recurrent with acceptable morbidity. Age and tumor grading remained significant predictors for survival among patients with FIGO 2009 stage II EEC.

Three-Way Data Analysis with lime Lagged Window for On-Line Batch Process Monitoring

Chen, Junghui,Yen, Jen-Hung 한국화학공학회 2003 Korean Journal of Chemical Engineering Vol.20 No.6

In this paper, on-line batch process monitoring is developed on the basis of the three-way data structure and the time-lagged window of process dynamic behavior. Two methods, DPARAFAC (dynamic parallel factor analysis) and DTri-PLS (dynamic trilinear partial least squares), are used here depending on the process variables only or on the process variables and quality indices, respectively. Although multivariate analysis using such PARAFAC (parallel factor analysis) and Tri-PLS (trilinear partial least squares) models has been reported elsewhere, they are not suited for practicing on-line batch monitoring owing to the constraints of their data structures. A simple modification of the data structure provides a framework wherein the moving window based model can be incorporated in the existing three-way data structure to enhance the detectability of the on-line batch monitoring. By a sequence of time window of each batch, the proposed methodology is geared toward giving meaningful results that can be easily connected to the current measurements without the extra computation for the estimation of unmeasured process variables. The proposed method is supported by using two sets of benchmark fault detection problems. Comparisons with the existing two-way and three-war multiway statistical process control methods are also included.

Screening, Purification, and Characterization of an Extracellular Prolyl Oligopeptidase from Coprinopsis clastophylla

Jen-Tao Chen,Mei-Li Chao,Chiou-Yen Wen,Wen-Shen Chu 한국미생물학회 2012 The journal of microbiology Vol.50 No.4

Culture filtrates of 22 mushrooms were screened for extracellular prolyl oligopeptidase activity. Four strains with relatively high enzyme activity were all from inky cap mushrooms. The production of Coprinopsis clastophylla prolyl oligopeptidase was associated with the growth of the fungus and the enzyme was not released by cell lysis. The enzyme was purified 285-fold to a specific activity of 52.05 U/mg. It was purified to a single band on a native polyacrylamide gel. However, the enzyme separated into three bands on a sodium dodecyl sulfate-polyacrylamide gel with mobility corresponding to molecular weights of approximately 84,60, and 26 kDa. The results of tandem mass spectrometric analysis revealed that the 60 kDa protein was likely a degradation product of the 84 kDa protein. The isoelectric point of the purified enzyme was 5.2. The purified enzyme had an optimal pH and temperature of 8.0 and 37°C, respectively. Diisopropyl fluorophosphate (DFP), p-chloromercuribenzoaic acid (PCMB), Hg2+, and Cu2+ strongly inhibited C. clastophylla prolyl oligopeptidase. This enzyme is a serine peptidase and one or more cysteine residues of the enzyme are close to the active site.

Impact of Chronic Hepatitis B and Hepatitis C on Adverse Hepatic Fibrosis in Hepatocellular Carcinoma Related to Betel Quid Chewing

Jeng, Jen-Eing,Tsai, Meng-Feng,Tsai, Hey-Ru,Chuang, Lea-Yea,Lin, Zu-Yau,Hsieh, Min-Yuh,Chen, Shinn-Chern,Chuang, Wan-Lung,Wang, Liang-Yen,Yu, Ming-Lung,Dai, Chia-Yen,Tsai, Jung-Fa Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.2

The pathogenesis of hepatocellular carcinoma (HCC) related to habitual betel quid (BQ) chewing is unclear. Risk of HCCis increased with adverse hepatic fibrosis. This study aimed to assess the impact of chronic viral hepatitis on adverse hepatic fibrosis in HCC related to BQ chewing. This hospital-based case-control study enrolled 200 pairs of age- and gender-matched patients with HCC and unrelated healthy controls. Serologic hepatitis B surface antigen (HBsAg), antibodies to hepatitis C virus (anti-HCV), ${\alpha}$-fetoprotein (AFP), and surrogate markers for significant hepatic fibrosis were measured. Information on substance-use habits was obtained with a questionnaire. By analysis of surrogate markers for hepatic fibrosis, the prevalence of significant hepatic fibrosis in patients chewing BQ was between 45.8% and 91.7%, whereas that for patients without BQ chewing was between 18.4% and 57.9%. The difference was significant (P <0.05 for each surrogate marker). Multivariate analysis indicated that cirrhosis with Child-Pugh C (odds ratio (OR) = 3.28; 95% confidence interval (CI), 1.29-8.37), thrombocytopenia (OR = 3.92, 95% CI, 1.77-8.68), AFP >400 mg/L (OR = 2.21, 95% CI, 1.05-4.66) and male gender (OR = 4.06, 95% CI, 1.29-12.77) were independent factors associated with habitual BQ chewing. In conclusion, adverse hepatic fibrosis and severe liver damage play important roles in the pathogenesis of BQ-related HCC, which could be aggravated by chronic hepatitis B and hepatitis C. BQ-cessation programs and prevention of chronic HBV/HCV infection are needed to prevent HCC related to BQ chewing.

Interventional Procedures in Superficial Lesions: The Value of 2D with Additional Coronal Reformatted 4D Ultrasonography Guidance

Cheng-Yen Chang,Hsin-Kai Wang,Hong-Jen Chiou,Yi-Hong Chou,Tain-Hsiung Chen,See-Ying Chiou 대한영상의학회 2006 Korean Journal of Radiology Vol.7 No.1

Objective: We wanted to assess the usefulness of four-dimensional (4D) ultrasonography (US), i.e., real-time three-dimensional US, as an adjunct for performing various US-guided interventional procedures in superficial lesions. Materials and Methods: Thirty-three patients were referred for US-guided interventional procedures for superficial lesions, including core biopsy in 19, fineneedle aspiration in eight, therapeutic drug injection in four and needle puncture in two. The procedures were performed under 4D US guidance. We reviewed the pathologic/cytologic results of the core biopsies or needle aspirations, and also the outcomes of drug injection or needle puncture. Results: For all the patients who underwent 4D US-guided core biopsy, the specimens were adequate for making the pathological diagnosis, and specimens were successfully obtained for those patients who underwent 4D US-guided aspiration. The patients treated with 4D US-guided therapeutic drug injection or needle puncture had a good response. No major procedure-related complications occurred. The procedural times were similar to those procedural times with using two-dimensional US. Conclusion: Combining the two dimensional and 4D US techniques aids the physician when performing US-guided interventional procedures for the superficial lesions.

Independent and Additive Interaction Between Tumor Necrosis Factor β +252 Polymorphisms and Chronic Hepatitis B and C Virus Infection on Risk and Prognosis of Hepatocellular Carcinoma: a Case-Control Study

Jeng, Jen-Eing,Wu, Hui-Fang,Tsai, Meng-Feng,Tsai, Huey-Ru,Chuang, Lea-Yea,Lin, Zu-Yau,Hsieh, Min-Yuh,Chen, Shinn-Chern,Chuang, Wan-Lung,Wang, Liang-Yen,Yu, Ming-Lung,Dai, Chia-Yen,Tsai, Jung-Fa Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.23

To assess the contribution of tumor necrosis factor $(TNF){\beta}$ +252 polymorphisms to risk and prognosis of hepatocellular carcinoma (HCC), we enrolled 150 pairs of sex- and age-matched patients with HCC, patients with cirrhosis alone, and unrelated healthy controls. $TNF{\beta}$ +252 genotypes were determined by polymerase chain reaction with restriction fragment length polymorphism. Multivariate analysis indicated that $TNF{\beta}$ G/G genotype [odds ratio (OR), 3.64; 95%CI, 1.49-8.91], hepatitis B surface antigen (OR, 16.38; 95%CI, 8.30-32.33), and antibodies to hepatitis C virus (HCV) (OR, 39.11; 95%CI, 14.83-103.14) were independent risk factors for HCC. There was an additive interaction between $TNF{\beta}$ G/G genotype and chronic hepatitis B virus (HBV)/HCV infection (synergy index=1.15). Multivariate analysis indicated that factors associated with $TNF{\beta}$ G/G genotype included cirrhosis with Child-Pugh C (OR, 4.06; 95%CI, 1.34-12.29), thrombocytopenia (OR, 6.55; 95%CI, 1.46-29.43), and higher serum ${\alpha}$-fetoprotein concentration (OR, 2.53; 95%CI, 1.14-5.62). Patients with $TNF{\beta}$ G/G genotype had poor cumulative survival (p=0.005). Cox proportional hazard model indicated that $TNF{\beta}$ G/G genotype was a biomarker for poor HCC survival (hazard ratio, 1.70; 95%CI, 1.07-2.69). In conclusion, there are independent and additive effects between $TNF{\beta}$ G/G genotype and chronic HBV/HCV infection on risk for HCC. It is a biomarker for poor HCC survival. Carriage of this genotype correlates with disease severity and advanced hepatic fibrosis, which may contribute to a higher risk and poor survival of HCC. Chronic HBV/HCV infected subjects with this genotype should receive more intensive surveillance for early detection of HCC.