Validation of Pharyngeal Acid Reflux Episodes Using Hypopharyngeal Multichannel Intraluminal Impedance-pH

Yen-Yang Chen,Chen-Chi Wang,Ying-Cheng Lin,John Y Kao,Chun-Yi Chuang,Yung-An Tsou,Ja-Chih Fu,Sheng-Shun Yang,Chi-Sen Chang,Han-Chung Lien 대한소화기 기능성질환∙운동학회 2023 Journal of Neurogastroenterology and Motility (JNM Vol.29 No.1

Background/AimsHypopharyngeal multichannel intraluminal impedance-pH (HMII-pH) technology incorporating 2 trans-upper esophageal sphincter impedance channels has been developed to detect pharyngeal reflux. We used the HMII-pH technique to validate the candidate pharyngeal acid reflux (PAR) episodes based on the dual-pH tracings and determined the interobserver reproducibility. MethodsWe conducted a cross-sectional study in tertiary centers in Taiwan. Ninety patients with suspected laryngopharyngeal reflux and 28 healthy volunteers underwent HMII-pH test when off acid suppressants. Candidate PAR episodes were characterized by pharyngeal pH drops of at least 2 units and reaching a nadir pH of 5 within 30 seconds during esophageal acidification. Two experts manually independently identified candidate PAR episodes based on the dual-pH tracings. By reviewing the HMII-pH tracings, HMII-pH-proven PAR episodes were subsequently confirmed. The consensus reviews of HMII-pH-proven PAR episodes were considered to be the reference standard diagnosis. The interobserver reproducibility was assessed. ResultsA total of 105 candidate PAR episodes were identified. Among them 84 (80.0%; 95% CI, 71.0-87.0%) were HMII-pH-proven PAR episodes (82 in 16 patients and 2 in 1 healthy subject). Patients tended to have more HMII-pH-proven PAR episodes than healthy controls (median and percentile values [25th, 75th, and 95th percentiles]: 0 [0, 0, 3] vs 0 [0, 0, 0], P = 0.067). The concordance rate in diagnosing HMII-pH-proven PAR episodes between 2 independent observers was 92.2%. ConclusionOur preliminary data showed that 80.0% (71.0-87.0%) of the proposed candidate PAR episodes were HMII-pH-proven PAR episodes, among which the interobserver reproducibility was good.

The Clinical Outcomes of Different First-Line EGFR-TKIs Plus Bevacizumab in Advanced EGFR-Mutant Lung Adenocarcinoma

Yen-Hsiang Huang,Kuo-Hsuan Hsu,Chun-Shih Chin,Jeng-Sen Tseng,Tsung-Ying Yang,Kun-Chieh Chen,Kang-Yi Su,Sung-Liang Yu,Jeremy J.W. Chen,Gee-Chen Chang 대한암학회 2022 Cancer Research and Treatment Vol.54 No.2

Purpose The aim of this study was to investigate the efficacy of various epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitors (TKIs) plus bevacizumab in advanced EGFR-mutant lung adenocarcinoma patients. Materials and Methods From August 2016 to October 2020, we enrolled advanced lung adenocarcinoma patients harboring exon 19 deletion or L858R receiving gefitinib, erlotinib and afatinib plus bevacizumab as the first-line treatment for the purposes of analysis. Results A total of 36 patients were included in the final analysis. Three patients received gefitinib, 17 received erlotinib, and 16 received afatinib combined with bevacizumab as the first-line treatment. The objective response rate was 77.8%, and disease control rate was 94.4%. The overall median progression-free survival (PFS) was 16.4 months, while the median PFS was 17.1 months in patients with exon 19 deletion, and 16.2 months in patients with L858R mutation (p=0.311). Regarding the use of different EGFR-TKIs, the median PFS was 17.1 months in the erlotinib group and 21.6 months in the afatinib group (p=0.617). In patients with brain metastasis at baseline, the median PFS was 18.9 months in the erlotinib group and 16.4 months in the afatinib group (p=0.747). Amongst patients harboring exon 19 deletion, the median PFS was 16.2 months in the erlotinib group and not-reached in the afatinib group (p=0.141). In patients with L858R mutation, the median PFS was 18.9 months in the erlotinib group and 16.2 months in the afatinib group (p=0.481). Conclusion Our research demonstrates that not only erlotinib combined with bevacizumab, but also afatinib plus bevacizumab as first-line treatment, provides solid clinical efficacy in advanced EGFR-mutant lung adenocarcinoma patients. PurposeThe aim of this study was to investigate the efficacy of various epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitors (TKIs) plus bevacizumab in advanced <i>EGFR</i>-mutant lung adenocarcinoma patients.Materials and MethodsFrom August 2016 to October 2020, we enrolled advanced lung adenocarcinoma patients harboring exon 19 deletion or L858R receiving gefitinib, erlotinib and afatinib plus bevacizumab as the first-line treatment for the purposes of analysis.ResultsA total of 36 patients were included in the final analysis. Three patients received gefitinib, 17 received erlotinib, and 16 received afatinib combined with bevacizumab as the first-line treatment. The objective response rate was 77.8%, and disease control rate was 94.4%. The overall median progression-free survival (PFS) was 16.4 months, while the median PFS was 17.1 months in patients with exon 19 deletion, and 16.2 months in patients with L858R mutation (p=0.311). Regarding the use of different EGFR-TKIs, the median PFS was 17.1 months in the erlotinib group and 21.6 months in the afatinib group (p=0.617). In patients with brain metastasis at baseline, the median PFS was 18.9 months in the erlotinib group and 16.4 months in the afatinib group (p=0.747). Amongst patients harboring exon 19 deletion, the median PFS was 16.2 months in the erlotinib group and not-reached in the afatinib group (p=0.141). In patients with L858R mutation, the median PFS was 18.9 months in the erlotinib group and 16.2 months in the afatinib group (p=0.481).ConclusionOur research demonstrates that not only erlotinib combined with bevacizumab, but also afatinib plus bevacizumab as first-line treatment, provides solid clinical efficacy in advanced <i>EGFR</i>-mutant lung adenocarcinoma patients.

The Association of Acquired T790M Mutation with Clinical Characteristics after Resistance to First-Line Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor in Lung Adenocarcinoma

Yen-Hsiang Huang,Kuo-Hsuan Hsu,Jeng-Sen Tseng,Kun-Chieh Chen,Chia-Hung Hsu,Kang-Yi Su,Jeremy J. W. Chen,Huei-Wen Chen,Sung-Liang Yu,Tsung-Ying Yang,Gee-Chen Chang 대한암학회 2018 Cancer Research and Treatment Vol.50 No.4

Purpose The main objective of this study was to investigate the relationship among the clinical characteristics and the frequency of T790M mutation in advanced epidermal growth factor receptor (EGFR)mutant lung adenocarcinoma patients with acquired resistance after firstline EGFRtyrosine kinase inhibitor (TKI) treatment. Materials and Methods We enrolled EGFR-mutant stage IIIB-IV lung adenocarcinoma patients, who had progressed to prior EGFR-TKI therapy, and evaluated their rebiopsy EGFRmutation status. Results A total of 205 patients were enrolled for analysis. The overall T790M mutation rate of rebiopsy was 46.3%. The T790M mutation rates among patients with exon 19 deletion mutation, exon 21 L858R point mutation, and other mutations were 55.0%, 37.3%, and 27.3%, respectively. Baseline exon 19 deletion was associated with a significantly higher frequency of T790M mutation (adjusted odds ratio, 2.14; 95% confidence interval [CI], 1.20 to 3.83; p=0.010). In the exon 19 deletion subgroup, there was a greater prevalence of T790M mutation than other exon 19 deletion subtypes in patients with the Del E746-A750 mutation (61.6% vs. 40.6%; odds ratio, 2.35; 95% CI, 1.01 to 5.49; p=0.049). The progression- free survival (PFS) of first-line TKI treatment > 11 months was also associated with a higher T790M mutation rate (54.1% vs. 39.3%; adjusted odds ratio, 1.82; 95% CI, 1.02 to 3.25; p=0.044). Patients who underwent rebiopsy at metastatic sites had more chance to harbor T790M mutation (52.6% vs. 33.8%; adjusted odds ratio, 1.97; 95% CI, 1.06 to 3.67; p=0.032). Conclusion PFS of first-line EGFR-TKI, rebiopsy site, EGFR exon 19 deletion and its subtype Del E746- A750 mutation are associated with the frequency of T790M mutation.

Equal Z standard-setting method to estimate the minimum number of panelists for a medical school’s objective structured clinical examination in Taiwan: a simulation study

Ying-Ying Yang,Pin-Hsiang Huang,Ling-Yu Yang,Chia-Chang Huang,Chih-Wei Liu,Shiau-Shian Huang,Chen-Huan Chen,Fa-Yauh Lee,Shou-Yen Kao,Boaz Shulruf 한국보건의료인국가시험원 2022 보건의료교육평가 Vol.19 No.-

Purpose Undertaking a standard-setting exercise is a common method for setting pass/fail cut scores for high-stakes examinations. The recently introduced equal Z standard-setting method (EZ method) has been found to be a valid and effective alternative for the commonly used Angoff and Hofstee methods and their variants. The current study aims to estimate the minimum number of panelists required for obtaining acceptable and reliable cut scores using the EZ method. Methods The primary data were extracted from 31 panelists who used the EZ method for setting cut scores for a 12-station of medical school’s final objective structured clinical examination (OSCE) in Taiwan. For this study, a new data set composed of 1,000 random samples of different panel sizes, ranging from 5 to 25 panelists, was established and analyzed. Analysis of variance was performed to measure the differences in the cut scores set by the sampled groups, across all sizes within each station. Results On average, a panel of 10 experts or more yielded cut scores with confidence more than or equal to 90% and 15 experts yielded cut scores with confidence more than or equal to 95%. No significant differences in cut scores associated with panel size were identified for panels of 5 or more experts. Conclusion The EZ method was found to be valid and feasible. Less than an hour was required for 12 panelists to assess 12 OSCE stations. Calculating the cut scores required only basic statistical skills.

Striatal Dopamine Transporter Availability is Associated with Sleep Disturbance among Patients with Bipolar I Disorder: A Single-photon Emission Computed Tomography Study Using [99mTc] TRODAT-1

Tsung-Hua Lu(Tsung-Hua Lu),Shih-Hsien Lin(Shih-Hsien Lin),Huai-Hsuan Tseng(Huai-Hsuan Tseng),Yen Kuang Yang(Yen Kuang Yang),Nan Tsing Chiu(Nan Tsing Chiu),Po See Chen(Po See Chen) 대한정신약물학회 2022 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.20 No.4

Objective: Bipolar disorder (BD) is characterized by the poor sleep quality. Whether the striatal dopamine transporter (DAT) availability is related to sleep quality among patients with BD is unclear. Methods: Fifty-three euthymic patients with BD (24 BD-I and 29 BD-II) and sixty-eight healthy controls were enrolled. The Chinese Version of the Pittsburgh Sleep Quality Index (PSQI) was used, and the availability of DAT was assessed by single-photon emission computed tomography (SPECT) using [99mTc] TRODAT-1. Results: The sleep disturbance component of the PSQI was significantly associated with the level of DAT availability among patients with BD. Conclusion: The striatal dopaminergic activity that contributes to resilience to adversity was associated with sleep pattern among patients with BD.

Disturbance Suppression and Contour Following Accuracy Improvement: An Adaptive PI-Type Sliding Mode Nonlinear Extended State Observer Approach

Yen-Chun Chen,Yan-Rou Cai,Ming-Yang Cheng,Ke-Han Su 한국정밀공학회 2023 International Journal of Precision Engineering and Vol.24 No.3

The main idea behind the conventional extended state observer is that the total disturbance including nonlinearity, modeling error, and external disturbance, etc., is regarded as an augmented state variable which can be estimated using system input/output, system parameters and a nonlinear function. In order to further improve estimation accuracy, this paper proposes an adaptive PI-type sliding mode nonlinear extended state observer (APISMESO). In particular, a nonlinear function that contains an integral term is used in the proposed observer structure to reduce estimation error, especially when dealing with static friction and high-frequency noise often existing in servomechanisms. Moreover, an adaptive law is designed to provide on-line estimation of system parameters. In addition, the stability of the complementary sliding mode control scheme with the proposed APISMESO is investigated using the Lyapunov stability theory. Several contour following experiments are performed to compare the performance of the proposed APISMESO with that of several existing variants of extended state observers. Experimental results reveal that the proposed APISMESO outperforms the other variants of extended state observers also tested in the experiment.

Pharmacokinetics of (-)-Epicatechin in Rabbits

Yen-An Chen,Kuang-Yang Hsu 대한약학회 2009 Archives of Pharmacal Research Vol.32 No.1

The aim of this study was to investigate the pharmacokinetics of (-)-epicatechin (EC) in rabbits after intravenous, intraperitoneal, and oral administration. A two-compartment model was used to describe the pharmacokinetics of EC after intravenous administration. EC showed dose-independent pharmacokinetics after intravenous administration. In addition, the area under the concentration-time curve was proportional to the dose over the range 5-25 mg/kg. After intraperitoneal administration of 25 mg/kg, a high percentage of EC escaped from first-pass hepatic elimination. After oral administration of 50 mg/ kg, there was a great variation in the pharmacokinetics, and the mean oral bioavailability of EC was 4%. There was no significant difference in the elimination rate constants in all treatments (p>0.05). In conclusion, after intravenous, intraperitoneal, and oral administration of EC, the EC exhibits dose-independent pharmacokinetics in rabbits. The first-pass effect did not participate in the low oral bioavailability. Base on the results of the present study, the other factors may contribute the low oral bioavailability.

The Novel Membrane-Type Micro-system to Assess the Bonus Effect of Physiological and Physical Stimuli on Bone Regeneration

Yen-Ching Yang,Qian-Hui Hong,Kin Fong Lei,Alvin Chao-Yu Chen 한국바이오칩학회 2021 BioChip Journal Vol.15 No.3

The periosteal progenitor cell is suitable for bone tissue regeneration duo to its multipotent differentiation in osteogenesis and chondrogenesis. It was found that both physical and physiological stimuli can induce the differentiation of periosteal progenitor cells. However, the combined-effect of these two stimuli is not clear. The imitation of the nature movement—the cyclic tensile strain stimulation and the multiple growth factors producing cells—adipose-derived stem cells (ADSCs) were used as physical and physiological stimuli to investigate the differentiation of rabbit periosteal cells in this study. For this, a new membrane-type micro-system was invented to provide a simple examination platform for both factors in one single system. The specific rectangular culture chamber not only provided two different types of cells to grow separately but also delivered the single axial tensile strain generated in the micro-system to the cells. It was found that application of either physical or physiological stimuli alone was sufficient to induce the differentiation of periosteal cells. The low tensile strain (4, 5, 6 kPa) led to osteogenesis whereas high tensile strain (7 kPa) induced chondrogenesis. Even though the co-culture of ADSCs only induced osteogenic differentiation of periosteal cells, the co-culture of ADSCs to tensile strain treated periosteal cells further strengthened the osteogenic and chondrogenic differentiation potent in low and high tensile strain, respectively. This study provided the pre-clinical evidence of the stem cell therapy and continuous exercise in cell level bone tissue regeneration.

Simulation of axisymmetric scramjet inlet flow fields using anti-diffusive WENO Navier-Stokes solver

Juan-Chen Huang,Jaw-Yen Yang,Yu-Hsuan Lai,Jeng-Shan Guo 대한기계학회 2015 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.29 No.5

This study is based on the theory of gas dynamics and uses the Navier-Stokes equations as the governing equations to solve the hypersonicflow problems of the scramjet. For the turbulent flow, we use the Spalart-Allmaras one equation turbulence model, which producesbetter results for near wall and boundary layer flow field problems. The lower-upper symmetric Gauss-Seidel implicit scheme, whichenables results to converge efficiently under steady state conditions, is combined with the anti-diffusive weighted essentially nonoscillatory(WENO) scheme to yield an accurate and efficient simulation tool for an axisymmetric scramjet flow field analysis. Using theWENO scheme’s high-order accuracy and its non-oscillatory solution at discontinuous regions, we can solve the hypersonic flow problemsinvolving complex shock-shock/shock-boundary layer interactions inside the flow path. This simulation procedure is first verifiedagainst two existing partial examples to ensure its accuracy, and is then applied to a complete scramjet model with different initial conditionsfor a full flow field analysis. The aerodynamic data of Mach number, density, static temperature and pressure are obtained and theresults discussed. The anti-diffusive WENO scheme produces more accurate resolution of shock and slip lines and their complex multipleinteractions than other numerical approaches. This is of crucial importance for the scramjet complete flow field analysis as multipleshock-boundary layer and discontinuities interactions often occur within the long flow path.

Efficacy of Epigallocatechin-3-Gallate and Amla (Emblica officinalis) Extract for the Treatment of Diabetic-Uremic Patients

Tung-Sheng Chen,Show-Yih Liou,Hsi-Chin Wu,Fuu-Jen Tsai,Chang-Hai Tsai,Chih-Yang Huang,Yen-Lin Chang 한국식품영양과학회 2011 Journal of medicinal food Vol.14 No.7

Uremic patients with diabetes suffer from high levels of oxidative stress due to regular hemodialysis therapy (neutrophil activation induced by hemo-incompatibility between the hemodialyser and blood) and complications associated with diabetes. Several plasma biomarkers were screened in 13 uremic diabetic patients after receiving the mixture of (–)-epigallocatechin gallate (EGCG), a major component of green tea extract, and Amla extract (AE), from Emblica officinalis, the Indian gooseberry, for 3 months. We found that oral administration of a 1:1 mixture of EGCG and AE for 3 months significantly improved antioxidant defense as well as diabetic and atherogenic indices in uremic patients with diabetes. Furthermore, no significant changes in hepatic function, renal function, or inflammatory responses were observed. These results suggest that a 1:1 combination of EGCG and AE is a safe and effective treatment for uremic patients with diabetes.