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.

Risk of Hepatitis B Virus (HBV) Reactivation in HBsAg-Negative, Anti-HBc-Negative Patients Receiving Rituximab for Autoimmune Diseases in HBV Endemic Areas

Lan Ting-Yuan,Lin Yen-Chun,Tseng Tai-Chung,Yang Hung-Chih,Kao Jui-Hung,Cheng Chiao-Feng,Lee Tai-Ju,Huang Shang-Chin,Lu Cheng-Hsun,Li Ko-Jen,Hsieh Song-Chou 거트앤리버 소화기연관학회협의회 2023 Gut and Liver Vol.17 No.2

Background/Aims: Rituximab is known to be associated with high hepatitis B virus (HBV) reactivation rate in patients with resolved HBV infection and hematologic malignancy. However, data regarding HBV reactivation (HBVr) in rheumatic patients receiving rituximab is limited. To assess the HBVr rate in hepatitis B surface antigen (HBsAg)-negative patients receiving rituximab for autoimmune diseases in a large real-world cohort. Methods: From March 2006 to December 2019, 900 patients with negative HBsAg receiving at least one cycle of rituximab for autoimmune diseases in a tertiary medical center in Taiwan were retrospectively reviewed. Clinical outcome and factors associated with HBVr were analyzed. Results: After a median follow-up period of 3.3 years, 21 patients developed HBVr, among whom 17 patients were positive for hepatitis B core antibody (anti-HBc) and four were negative. Thirteen patients had clinical hepatitis flare, while eight patients had HBsAg seroreversion without hepatitis. Old age, anti-HBc positivity, undetectable serum hepatitis B surface antibody level at rituximab initiation and a higher average rituximab dose were associated with a higher HBVr rate. There was no significant difference in the HBVr risk between rheumatoid arthritis and other autoimmune diseases. Among anti-HBc-negative patients, subjects without HBV vaccination at birth had an increased risk of HBVr (4/368, 1.1%) compared with those who received vaccination (0/126, 0%). Conclusions: In HBV endemic areas where occult HBV is prevalent, anti-HBc-negative patients, may still be at risk for HBVr after rituximab exposure. HBVr may still be considered in HBsAgnegative patients developing abnormal liver function after rituximab exposure, even in patients with negative anti-HBc.

Melatonin acts synergistically with pazopanib against renal cell carcinoma cells through p38 mitogen-activated protein kinase-mediated mitochondrial and autophagic apoptosis

( Chien-pin Lai ),( Yong-syuan Chen ),( Tsung-ho Ying ),( Cheng-yen Kao ),( Hui-ling Chiou ),( Shao-hsuan Kao ),( Yi-hsien Hsieh ) 대한신장학회 2023 Kidney Research and Clinical Practice Vol.42 No.4

Background: Mounting evidence indicates that melatonin has possible activity against different tumors. Pazopanib is an anticancer drug used to treat renal cell carcinoma (RCC). This study tested the anticancer activity of melatonin combined with pazopanib on RCC cells and explored the underlying mechanistic pathways of its action. Methods: The 786-O and A-498 human RCC cell lines were used as cell models. Cell viability and tumorigenesis were detected with the MTT and colony formation assays, respectively. Apoptosis and autophagy were assessed using TUNEL, annexin V/propidium iodide, and acridine orange staining with flow cytometry. The expression of cellular signaling proteins was investigated with western blotting. The in vivo growth of tumors derived from RCC cells was evaluated using a xenograft mouse model. Results: Together, melatonin and pazopanib reduced cell viability and colony formation and promoted the apoptosis of RCC cells. Furthermore, the combination of melatonin and pazopanib triggered more mitochondrial, caspase-mediated, and LC3-II-mediated autophagic apoptosis than melatonin or pazopanib alone. The combination also induced higher activation of the p38 mitogen-activated protein kinase (p38MAPK) in the promotion of autophagy and apoptosis by RCC cells than melatonin or pazopanib alone. Finally, tumor xenograft experiments confirmed that melatonin and pazopanib cooperatively inhibited RCC growth in vivo and predicted a possible interaction between melatonin/pazopanib and LC3-II. Conclusion: The combination of melatonin and pazopanib inhibits the growth of RCC cells by inducing p38MAPK-mediated mitochondrial and autophagic apoptosis. Therefore, melatonin might be a potential adjuvant that could act synergistically with pazopanib for RCC treatment.

ONYX-I: Efficacy of Ombitasvir/Paritaprevir/Ritonavir + Dasabuvir in South Korean and Taiwanese Patients with HCV Genotype 1b Infection and without Cirrhosis

( Jeong Heo ),( Wan-Long Chuang ),( Yan Luo ),( Mong Cho ),( Chi-Jen Chu ),( Kwang-Hyub Han ),( Jia-Horng Kao ),( Seung Woon Paik ),( Chun-Yen Lin ),( Jin-Woo Lee ),( Cheng-Yuan Peng ),( Young-Suk Lim 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

Background: Approximately 45-50% of Hepatitis C virus (HCV) infections in South Korea and Taiwan are genotype (GT) 1b. Previous phase 3 studies demonstrated that the direct-acting antiviral (DAA) regimen of ombitasvir (OBV), ritonavir-boosted paritaprevir (PTV/r; identified by Abbvie and Enanta) and dasabuvir (DSV) was well tolerated and achieved sustained virologic response at post-treatment week 12 (SVR12) in 99% of treatment-naive and 100% of treatment- experienced patients with HCV GT1b. ONYX-I (NCT02517515) was designed to evaluate efficacy and safety in Asian patients with HCV GT1b infection without cirrhosis. Methods: Treatment-naive and IFN-based therapy-experienced patients with HCV GT1b infection in South Korea, Taiwan, and China were randomized 1:1 to receive either OBV/PTV/r (25 mg/150 mg/100 mg once daily) and DSV (250 mg twice daily) or placebo for 12 weeks during the double-blind (DB) period. Patients in the placebo arm subsequently received OBV/PTV/r + DSV for 12 weeks during the open-label period. Patients will be followed for 48 weeks after last dose of study drugs. The primary objectives are to compare the SVR12 rates for the treatment-naive and -experienced patients to corresponding historical SVR rates of telaprevir + peg-interferon and ribavirin therapy, and assess the safety of the OBV/PTV/r + DSV regimen. Presented are results from the South Korean and Taiwanese populations. Results: In both South Korea and Taiwan, 120 patients were randomized and treated. Of South Korean patients, 45% were male, 33% were treatment-experienced and 89% had F0-F1 fibrosis. Of Taiwanese patients, 39% were male, 33% were treatment-experienced, and 87% had F0-F1 fibrosis. Safety data and SVR at post-treatment week 4 will be presented. Conclusions: The ONYX-I study is evaluating the safety and efficacy of DAA regimen, OBV/PTV/r + DSV, in Southeast Asian patients without cirrhosis infected with HCV GT1b. Resultant data may help inform treatment guidelines for HCV GT1b in this population.

ALDH2 Gene: Its Effects on the Neuropsychological Functions in Patients with Opioid Use Disorder Undergoing Methadone Maintenance Treatment

Po-Wei Lee,Tzu-Yun Wang,Yun-Hsuan Chang,Sheng-Yu Lee,Shiou-Lan Chen,Ze-Cheng Wang,Po See Chen,Chun-Hsien Chu,San-Yuan Huang,Nian-Sheng Tzeng,I Hui Lee,Kao Chin Chen,Yen Kuang Yang,Jau-Shyong Hong,Ru-B 대한정신약물학회 2020 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.18 No.1

Objective: Patients with opioid use disorder (OUD) have impaired attention, inhibition control, and memory function. The aldehyde dehydrogenase 2 (ALDH2 ) gene has been associated with OUD and ALDH2 gene polymorphisms may affect aldehyde metabolism and cognitive function in other substance use disorder. Therefore, we aimed to investigate whether ALDH2 genotypes have significant effects on neuropsychological functions in OUD patients undergoing methadone maintenance therapy (MMT). Methods: OUD patients undergoing MMT were investigated and followed-up for 12 weeks. ALDH2 gene polymorphisms were genotyped. Connors’ Continuous Performance Test (CPT) and the Wechsler Memory Scale-Revised (WMS-R) were administered at baseline and after 12 weeks of MMT. Multivariate linear regressions and generalized estimating equations (GEEs) were used to examine the correlation between the ALDH2 genotypes and performance on the CPTs and WMS-R. Results: We enrolled 86 patients at baseline; 61 patients completed the end-of-study assessments. The GEE analysis showed that, after the 12 weeks of MMT, OUD patients with the ALDH2 *1/*2+*2/*2 (ALDH2 inactive) genotypes had significantly higher commission error T-scores (p = 0.03), significantly lower hit reaction time T-scores (p = 0.04), and significantly lower WMS-R visual memory index scores (p = 0.03) than did patients with the ALDH2 1 */*1 (ALDH2 active) genotype. Conclusion: OUD patients with the ALDH2 inactive genotypes performed worse in cognitive domains of attention, impulse control, and memory than did those with the ALDH2 active genotype. We conclude that the ALDH2 gene is important in OUD and is associated with neuropsychological performance after MMT.