Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

Background/Aims: Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. Methods: We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Results: Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. Conclusions Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

Objective: Hypoactivity in the reward system among patients with attention deficit hyperactivity disorder (ADHD) is a well-known phenomenon. Whether the activity in the reward pathway is related to harm avoidance, such as in sensitivity to punishment, is unclear. Evidence regarding the potential difference between ADHD patients and controls in terms of this association is scarce. Methods: Event-related functional magnetic resonance imaging was conducted on subjects performing the Iowa gambling test. Fourteen adults with ADHD and 14 controls were enrolled in the study. Results: Harm avoidance was found to be positively correlated with the activities of the bilateral orbitofrontal cortex and right insula in individuals with ADHD. A group difference was also confirmed. Conclusion Understanding the roles of harm avoidance and brain activation during risk tasks is important.

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.

Objective: Limited evidence exists regarding real-world 3-monthly paliperidone palmitate (PP3M) treatment retention and associated factors. Methods: We conducted a retrospective, nationwide cohort study using the Taiwan National Health Insurance Research Database between October 2017 and December 2019. Adult patients with schizophrenia initiated on PP3M were enrolled. The primary outcomes were time to PP3M discontinuation, time to psychiatric hospitalization, and the proportions of patients receiving the next PP3M dose within 120 days among first-, second-, and third-dose completers. Key covariates included prior PP1M duration and adequate PP3M initiation. Results: The PP3M treatment retention rates were 79.7%, 66.3%, and 52.5% after 6, 12, and 24 months, respectively, with 86.4%, 90.6%, and 90.0% of respective first-, second-, and third-dose completers receiving the next PP3M dose. Adequate PP3M initiation and prior PP1M treatment duration ＞ 180 days were associated with favorable PP3M treatment retention. In multivariate analyses, PP1M durations of 180−360 days (adjusted relative risk [aRR], 1.76) or ＜ 180 days (aRR, 2.79) were associated with PP3M discontinuation at the second dose. Inadequate PP3M initiation was associated with discontinuation at the third dose (aRR, 2.18). Patients fully adherent to PP3M treatment in the first year had a higher probability of being free from psychiatric hospitalization (86.7% at 2 years), compared with those partially adherent or non-adherent to PP3M in the first year. Conclusion Prior PP1M duration and adequate PP3M initiation are major factors affecting PP3M treatment retention. Higher PP3M treatment retention is associated with a lower risk of psychiatric hospitalization.

Repetitive transcranial magnetic stimulation (rTMS) and intermittent theta-burst stimulation (iTBS) are evidenced-based treatments for patients with major depressive disorder (MDD) who fail to respond to standard first-line therapies. However, although various TMS protocols have been proven to be clinically effective, the response rate varies across clinical applications due to the heterogeneity of real-world psychiatric comorbidities, such as generalized anxiety disorder, posttraumatic stress disorder, panic disorder, or substance use disorder, which are often observed in patients with MDD. Therefore, individualized treatment approaches are important to increase treatment response by assigning a given patient to the most optimal TMS treatment protocol based on his or her individual profile. This literature review summarizes different rTMS or TBS protocols that have been applied in researches investigating MDD patients with certain psychiatric comorbidities and discusses biomarkers that may be used to predict rTMS treatment response. Furthermore, we highlight the need for the validation of neuroimaging and electrophysiological biomarkers associated with rTMS treatment responses. Finally, we discuss on which directions future efforts should focus for developing the personalization of the treatment of depression with rTMS or iTBS.

Repetitive transcranial magnetic stimulation (rTMS) and intermittent theta-burst stimulation (iTBS) are evidenced-based treatments for patients with major depressive disorder (MDD) who fail to respond to standard first-line therapies. However, although various TMS protocols have been proven to be clinically effective, the response rate varies across clinical applications due to the heterogeneity of real-world psychiatric comorbidities, such as generalized anxiety disorder, posttraumatic stress disorder, panic disorder, or substance use disorder, which are often observed in patients with MDD. Therefore, individualized treatment approaches are important to increase treatment response by assigning a given patient to the most optimal TMS treatment protocol based on his or her individual profile. This literature review summarizes different rTMS or TBS protocols that have been applied in researches investigating MDD patients with certain psychiatric comorbidities and discusses biomarkers that may be used to predict rTMS treatment response. Furthermore, we highlight the need for the validation of neuroimaging and electrophysiological biomarkers associated with rTMS treatment responses. Finally, we discuss on which directions future efforts should focus for developing the personalization of the treatment of depression with rTMS or iTBS.

Background: Dacryocystorhinostomy (DCR) is a surgical treatment for site of obstruction in the nasolacrimal duct system [1]. This surgery is performed in cases of congenital nasolacrimal obstruction, partial and complete occlusion of the nasolacrimal duct in adults, chronic tearing disorders, ineffective probing treatment and placement of a silicone tube in the nasolacrimal system [2,3]. the present findings indicate that preservation of lacrimal sac flaps with end-to-end anastomosis to the nasal mucosa using histoacryl has a positive impact on surgical outcome in patients undergoing endonasal endoscopic dacryocystorhinostomy [4]. Histoacryl glue is one of the most commonly surgical materials used recently. The basis of our study is the lack of research on the use of this glue in the practice of oculoplastic and reconstructive surgery. Purpose: The purpose of this study to comparing outcomes of surgical methods of histoacryl glue and silicone tube during endoscopic endonasal dacryocystorhinostomy. Methods: Retrospective, case series study. The study included 83 patients who underwent endonasal endoscopic dacryocystorhinostomy between January 2017 to June 2020. Whole case was divided into two groups. In group 1, an anastomosis was made during surgery by using histoacryl glue to the posterior wall of the lacrimal sac and the wall formed by the nasal mucosa [5]. In group 2, a silicone tube was placed in the nasolacrimal duct during endonasal dacryocystorhinostomy and the results were evaluated in the 1st, 3rd, 6th, and 12th months after surgery. Statistical calculations were performed using SPSS software. Results: The age of the whole cases was between 17 and 82 years. There were no significant difference among the age groups. In terms of gender, n=48 (78.7%) were female and n=13 (21.3%) were male, indicating that dacryocystitis was predominant in women. Study reports no significant difference in intraoperative and postoperative complication. The surgical success rate was significantly higher in histoacryl group 94.9%, than silicone tube group 79.5%. Recurrent cases n=2 (5.1%) in group 1 and n=9 (20.4%) in group 2 respectively. Conclusion Histoacryl glue is highly effective, commodity, inexpensive and easy to apply during endonasal endoscopic dacryocystorhinostomy surgery.

Introduction: Dacryocystorhinostomy (DCR) is a surgical treatment for site of obstruction in the nasolacrimal duct system. This surgery is performed in cases of congenital nasolacrimal obstruction, partial and complete occlusion of the nasolacrimal duct in adults, chronic tearing disorders, ineffective probing treatment and placement of a silicone tube in the nasolacrimal system. the present findings indicate that preservation of lacrimal sac flaps with end-to-end anastomosis to the nasal mucosa using histoacryl has a positive impact on surgical outcome in patients undergoing endonasal endoscopic dacryocystorhinostomy. Histoacryl glue is one of the most commonly surgical materials used recently. The basis of our study is the lack of research on the use of this glue in the practice of oculoplastic and reconstructive surgery. Purpose: To report the use of fibrin glue as an adjunctive procedure in endoscopic dacryocystorhinostomy (En-DCR) surgery and compare it to silicone tubing Material and Method: Patients with primary nasolacrimal duct obstruction were retrospectively reviewed for endo-DCR between January 2017 and December 2019. Group I patients applied fibrin glue and Group II used silicone tube insertion. The fibrin glue group received end-to-end anastomosis of the nasal mucosa and lacrimal sac using fibrin glue at the end of surgery. The demographics, recurrence, causes of failure, formation of scars, final ostium size and the success rate were compared. This study was approved by the Institutional Review Board of the Chang Gung Memorial Hospital Clinical Research Ethnics Committee and followed the Declaration of Helsinki. All statistical analysis was performed with SPSS version 24.0 software (SPSS Inc., Chicago, IL, USA), and a P value < .05 was considered statistically significant. Continuous variables were presented as mean ± standard deviation, while categorical data was represented as numbers and percentages. Independent t-tests were used to compare the differences in parametric variables. The Mann-Whitney U test was performed to compare the follow-up period. Pearson’s chi-squared and Fisher’s exact tests were used to compare categorical variables. Multivariate logistic regression was used to identify the risk factors associated with recurrence. Result: The age of the whole cases was between 17 and 82 years. There was no significant difference among the age groups. In terms of gender, n=48 (78.7%) were female and n=13 (21.3%) were male, indicating that dacryocystitis was predominant in women. Study reports no significant difference in intraoperative and postoperative complication. The surgical success rate was significantly higher in histoacryl group 94.9%, than silicone tube group 79.5%. Recurrent cases n=2 (5.1%) in group 1 and n=9 (20.4%) in group 2 respectively. Conclusion Fibrin glue improves the surgical outcome in patients undergoing Endo-DCR compared to commonly used silicone stenting by securing flaps apposition and maintaining the ostium opening.

BACKGROUND/OBJECTIVES: Heavy alcohol consumption causes the development of alcoholic liver disease (ALD), a neglected but important public health problem. Many studies have pointed out that probiotics could improve gut health, which is also considered to be a cause of ALD. Therefore, this study screened the probiotics, Lactobacillus casei GKC1 (GKC1), L. fermentum GKF3 (GKF3), Bifidobacterium lactis GKK2 (GKK2), L. rhamnosus GKLC1 (GKLC1), L. paracasei GKS6 (GKS6), and L. plantarum GKM3 (GKM3), for their potential benefits in alleviating ALD for applications to disease prevention. SUBJECTS/METHODS: C57BL/6N mice were divided into 8 groups (n = 6 in each): normal control, positive control (alcohol-diet fed), and treatments of feeding probiotics GKC1, GKF3, GKK2, GKLC1, GKS6, and GKM3 under an oral dose 0.82 g/kg B.W. per day by oral gavage. The experiment was conducted for 8 weeks, and the concentrations of alanine aminotransferase (ALT), aspartate aminotransferase, triglyceride (TG), and total cholesterol (TC) in mice were measured. The glutathione (GSH), catalase (CAT), and histology were analyzed after sacrifice. RESULTS: The results showed a decrease in the serum ALT, liver TG, and liver TC levels in the GKS6, GKM3, and GKLC1 groups compared to the positive control. In addition, the decreasing GSH and CAT levels were inhibited in the GKS6 and GKM3 groups. The histopathological results showed that all probiotics could reduce the accumulation of liver fat. Furthermore, there was a significant difference in GKLC1 with lower stomach damage compared to the alcohol-fed mice without any addition of probiotics. CONCLUSIONS GKLC1, GKS6, and GKM3 can be used as supplements for alleviating the development of ALD.