Purpose: Active surveillance (AS) is one of the management options for patients with low-risk and select intermediate-risk prostate cancer (PC). However, factors predicting disease reclassification and conversion to active treatment from a large population of pure Asian cohorts regarding AS are less evaluated. This study investigated the intermediate-term outcomes of patients with localized PC undergoing AS. Materials and Methods: This cohort study enrolled consecutive men with localized non-high-risk PC diagnosed in Taiwan between June 2012 and Jan 2023. The study endpoints were disease reclassification (either pathological or radiographic progression) and conversion to active treatment. The factors predicting endpoints were evaluated using the Cox proportional hazards model. Results: A total of 405 patients (median age: 67.2 years) were consecutively enrolled and followed up with a median of 64.6 months. Based on the National Comprehensive Cancer Network (NCCN) risk grouping, 70 (17.3%), 164 (40.5%), 140 (34.6%), and 31 (7.7%) patients were classified as very low-risk, low-risk, favorable-intermediate risk, and unfavorable intermediate-risk PC, respectively. The 5-year reclassification rates were 24.8%, 27.0%, 18.6%, and 25.3%, respectively. The 5-year conversion rates were 20.4%, 28.8%, 43.6%, and 37.8%, respectively. A prostate-specific antigen density (PSAD) of ≥0.15 ng/mL2 predicted reclassification (hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.17–2.88) and conversion (HR 1.56, 95% CI 1.05–2.31). A maximal percentage of cancer in positive cores (MPCPC) of ≥15% predicted conversion (15% to <50%: HR 1.41, 95% CI 0.91–2.18; ≥50%: HR 1.97, 95% CI 1.1453–3.40) compared with that of <15%. A Gleason grade group (GGG) of 3 tumor also predicted conversion (HR 2.69, 95% CI 1.06–6.79; GGG 3 vs 1). One patient developed metastasis, but none died of PC during the study period (2,141 person-years). Conclusions AS is a viable option for Taiwanese men with non-high-risk PC, in terms of reclassification and conversion. High PSAD predicted reclassification, whereas high PSAD, MPCPC, and GGG predicted conversion.

Background: To compare risk of diabetic retinopathy (DR) between patients taking sodium-glucose cotransporter-2 inhibitors (SGLT2is) and those taking glucagon-like peptide-1 receptor agonists (GLP1-RAs) in routine care. Methods: This retrospective cohort study emulating a target trial included patient data from the multi-institutional Chang Gung Research Database in Taiwan. Totally, 33,021 patients with type 2 diabetes mellitus using SGLT2is and GLP1-RAs between 2016 and 2019 were identified. 3,249 patients were excluded due to missing demographics, age <40 years, prior use of any study drug, a diagnosis of retinal disorders, a history of receiving vitreoretinal procedure, no baseline glycosylated hemoglobin, or no follow-up data. Baseline characteristics were balanced using inverse probability of treatment weighting with propensity scores. DR diagnoses and vitreoretinal interventions served as the primary outcomes. Occurrence of proliferative DR and DR receiving vitreoretinal interventions were regarded as vision-threatening DR. Results: There were 21,491 SGLT2i and 1,887 GLP1-RA users included for the analysis. Patients receiving SGLT2is and GLP-1 RAs exhibited comparable rate of any DR (subdistribution hazard ratio [SHR], 0.90; 95% confidence interval [CI], 0.79 to 1.03), whereas the rate of proliferative DR (SHR, 0.53; 95% CI, 0.42 to 0.68) was significantly lower in the SGLT2i group. Also, SGLT2i users showed significantly reduced risk of composite surgical outcome (SHR, 0.58; 95% CI, 0.48 to 0.70). Conclusion Compared to those taking GLP1-RAs, patients receiving SGLT2is had a lower risk of proliferative DR and vitreoretinal interventions, although the rate of any DR was comparable between the SGLT2i and GLP1-RA groups. Thus, SGLT2is may be associated with a lower risk of vision-threatening DR but not DR development.

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.

Objective: Schizophrenia has been associated with dysfunction of the hypothalamic-pituitary-adrenal axis. Furthermore, alterations in neurotrophic factors might contribute to the pathogenesis of schizophrenia. We aimed to evaluate the effects of a simulated laughter intervention on the levels of cortisol and BDNF and to determine whether the effects associated with simulated laughter could be sustained after discontinuation of the intervention. Methods: In this randomized controlled study, patients with schizophrenia according to DSM-IV clinical criteria were randomly assigned to receive either 8-week-long simulated laughter intervention (n=32) or treatment-as-usual group (control group, n=27). The serum levels of BDNF and cortisol were measured at baseline, week 8, and four weeks after discontinuation (week 12) of the intervention program. Results: After an 8-week simulated laughter intervention, the laughter group had significantly higher levels of BDNF; however, four weeks after discontinuation of the intervention, the levels of BDNF significantly dropped. Interestingly, the levels of cortisol did not change significantly at week 8, but they were significantly elevated at week 12. The levels of BDNF and cortisol in the control group did not change significantly between week 0 and week 8. Conclusion These findings suggest that the simulated laughter intervention has an early effect on neurogenesis with a significant delayed effect on stress regulation in subjects with schizophrenia.

OBJECTIVE: To investigate the efficacy of frankincense and myrrha in the treatment of acute interstitial cystitis/painful bladder syndrome (IC/PBS). METHODS: The effects of frankincense and myrrha on the proliferation and migration of primary human urothelial cells (HUCs) were assessed in vitro. In the animal study, 48 virgin female rats were randomized into 4 groups (12 in each group): (1) control group (saline-injected control); (2) cyclophosphamide (CYP) group (intraperitoneal injected 150 mg/kg CYP); (3) CYP + pentosan polysulfate sodium group (orally received 50 mg/kg pentosan polysulfate sodium); and (4) CYP + frankincense and myrrha group [orally received frankincense (200 mg/kg) and myrrha (200 mg/kg)]. Rats orally received pentosan polysulfate sodium or frankincense and myrrha on day 1, 2, and 3. The experiments were performed on day 4. Pain and cystometry assessment behavior test were performed. Voiding interval values were assessed in rats under anesthesia. Finally, immunohistochemistry and Western blot were used to confirm the location and level, respectively, of cell junction-associated protein zonula occludens-2 (ZO-2) expression. RESULTS: Low dose frankincense and myrrha increased cell proliferation and migration in HUCs compared with control (P<0.05). Rats with acute IC/PBS rats exhibited lower voiding interval values, pain tolerance, and ZO-2 expression (P<0.05). Voiding interval values and pain tolerance were higher in the frankincense and myrrha group than CYP group (P<0.05). ZO-2 expression in the bladder was increased in the CYP + pentosan polysulfate and frankincense + myrrha groups compared with the CYP-induced acute IC/PBS group (P<0.05). CONCLUSION frankincense and myrrha modulate urothelial wound healing, which ameliorates typical features of acute IC/PBS in rats.

Objective: Schizophrenia has been associated with dysfunction of the hypothalamic-pituitary-adrenal axis. Furthermore, alterations in neurotrophic factors might contribute to the pathogenesis of schizophrenia. We aimed to evaluate the effects of a simulated laughter intervention on the levels of cortisol and BDNF and to determine whether the effects associated with simulated laughter could be sustained after discontinuation of the intervention. Methods: In this randomized controlled study, patients with schizophrenia according to DSM-IV clinical criteria were randomly assigned to receive either 8-week-long simulated laughter intervention (n=32) or treatment-as-usual group (control group, n=27). The serum levels of BDNF and cortisol were measured at baseline, week 8, and four weeks after discontinuation (week 12) of the intervention program. Results: After an 8-week simulated laughter intervention, the laughter group had significantly higher levels of BDNF; however, four weeks after discontinuation of the intervention, the levels of BDNF significantly dropped. Interestingly, the levels of cortisol did not change significantly at week 8, but they were significantly elevated at week 12. The levels of BDNF and cortisol in the control group did not change significantly between week 0 and week 8. Conclusion These findings suggest that the simulated laughter intervention has an early effect on neurogenesis with a significant delayed effect on stress regulation in subjects with schizophrenia.

Hepatocellular carcinoma(HCC)is a malignant tumor with a fairly poor prognosis(5-year survival of less than 50％).Using sorafenib,the only food and drug administration(FDA)-approved drug,HCC cannot be effectively treated;it can only be controlled at most for a couple of months.There is a great need to develop efficacious treatment against this debilitating disease.Glypican-3(GPC3),a member of the glypican family that attaches to the cell surface by a glycosylphosphatidylinositol anchor,is overex-pressed in HCC cases and is elevated in the serum of a large proportion of patients with HCC.GPC3 expression contributes to HCC growth and metastasis.Furthermore,several different types of antibodies targeting GPC3 have been developed.The aim of this review is to summarize the current literatures on the GPC3 expression in human HCC,molecular mechanisms of GPC3 regulation and antibodies targeting GPC3.

OBJECTIVE: The therapeutic effect of methylphenidate (MPH) in treating attention-deficit/hyperactivity disorder (ADHD) has been related to the alpha-2A adrenergic receptor (ADRA2A) gene -1291C/G single nucleotide polymorphism (SNP). We investigated the effect of MPH in treating Taiwanese children and adolescent with ADHD and its relation to the ADRA2A gene -1291C/G SNP. METHODS: The subjects with DSM-IV ADHD diagnosis underwent a titration period to find out the dose of MPH for maintenance treatment. After 4 weeks maintenance treatment, the effect of MPH was evaluated by the Swanson, Nolan and Pelham version IV total scores. The subjects with more than 25% score reduction were referred to responders and those with ≥50% improvement were considered as better responders. The -1291C/G variant of the ADRA2A gene was identified by DNA sequencing and what relevance it has to the MPH response was examined by binary logistic regression analysis. RESULTS: Of the 59 subjects, 44 (74.6%) were responsive to MPH treatment and the responsiveness was not shown to be associated with the ADRA2A gene -1291C/G SNP. As the responsive subjects were categorized as moderate responders and better responders and subjected to statistical analysis, the GG homozygotes showed a greater chance to have a better response to MPH treatment than CC homozygotes (p=0.02), with an odds ratio of 32.14 (95% CI=1.64–627.80). CONCLUSION: The ADRA2A gene -1291C/G SNP is associated with the efficacy of MPH for the treatment of ADHD in Taiwanese children and adolescents. The responsive subjects bearing homozygous -1291G allele are more likely to have a better response to MPH treatment.
Adolescent* ; Alleles ; Child* ; Diagnosis ; Diagnostic and Statistical Manual of Mental Disorders ; Homozygote ; Humans ; Logistic Models ; Methylphenidate* ; Odds Ratio ; Pharmacogenetics ; Polymorphism, Single Nucleotide* ; Receptors, Adrenergic, alpha-2* ; Sequence Analysis, DNA

Osteoporosis and its associated fragility fractures are becoming a severe burden in the healthcare system globally. In the Asian-Pacific (AP) region, the rapidly increasing in aging population is the main reason accounting for the burden. Moreover, the paucity of quality care for osteoporosis continues to be an ongoing challenge. The Fracture Liaison Service (FLS) is a program promoted by International Osteoporosis Foundation (IOF) with a goal to improve quality of postfracture care and prevention of secondary fractures. In this review article, we would like to introduce the Taiwan FLS network. The first 2 programs were initiated in 2014 at the National Taiwan University Hospital and its affiliated Bei-Hu branch. Since then, the Taiwan FLS program has continued to grow exponentially. Through FLS workshops promoted by the Taiwanese Osteoporosis Association (TOA), program mentors have been able to share their valuable knowledge and clinical experience in order to promote establishments of additional programs. With 22 FLS sites including 11 successfully accredited on the best practice map, Taiwan remains as one of the highest FLS coverage countries in the AP region, and was also granted the IOF Best Secondary Fracture Prevention Promotion award in 2017. Despite challenges faced by the TOA, we strive to promote more FLS sites in Taiwan with a main goal of ameliorating further health burden in managing osteoporotic patients.
Aging ; Awards and Prizes ; Delivery of Health Care ; Education ; Financing, Organized ; Humans ; Mentors ; Osteoporosis ; Practice Guidelines as Topic ; Taiwan