Search Results (576)

Purpose: The identification of cardiovascular risk factors in metastatic prostate cancer (PCa) patients prior to the initiation of androgen receptor pathway inhibitors (ARPIs) is important yet challenging. Methods and Results: A nationwide cohort study was conducted utilizing data from the National Health Insurance Research Database containing the Taiwan Cancer Registry. The study population comprised 4739 PCa patients who received abiraterone or enzalutamide between 1 January 2014, and 28 February 2022. The cohort was divided into a training set (n = 3318) and a validation set (n = 1421). Machine learning techniques with random survival forest (RSF) model incorporating 16 variables was developed to predict major adverse cardiovascular events (MACEs). Over a mean follow-up period of 2.1 years, MACEs occurred in 10.9% and 11.3% of the training and validation cohorts, respectively. The RSF model identified five key predictive indicators: age < 65 or ≥75 years, heart failure, stroke, hypertension, and myocardial infarction. The model exhibited robust performance, achieving an area under the curve (AUC) of 85.1% in the training set and demonstrating strong external validity with an AUC of 85.5% in the validation cohort. A positive correlation was observed between the number of risk factors and the incidence of MACEs. Conclusions: This machine learning approach identified five predictors of MACEs in PCa patients receiving ARPIs. These findings highlight the need for comprehensive cardiovascular risk assessment and vigilant monitoring in this patient population. Full article

Background: Obesity is a global health challenge associated with metabolic and cardiovascular diseases. Traditional Chinese Medicine (TCM) body constitution theory offers a unique perspective on individual susceptibility to obesity; however, its integration into public health strategies remains underexplored. Objective: To examine the associations between vegetarian dietary patterns, TCM body constitution types (Phlegm stasis, Yang deficiency, and Yin deficiency), and overweight/obesity in a large-scale national cohort. Methods: Data were obtained from 3597 participants enrolled in the Taiwan Biobank. Socio-demographic variables, lifestyle behaviors (diet, smoking, physical activity), and anthropometric indicators (BMI and waist circumference) were assessed. Participants were categorized by weight status and TCM body constitution. Polytomous logistic regression models were used to evaluate associations between vegetarian dietary patterns, constitution types, and overweight/obesity, adjusting for potential confounders. Results: Among participants (mean age, 50.1 ± 9.4 years), 55.6% had normal BMI, 27.3% were overweight, and 17.1% were obese. Vegetarian dietary patterns were significantly associated with lower odds of Phlegm stasis (OR: 0.96; p < 0.001), Yang deficiency (OR: 0.97; p < 0.001), and Yin deficiency (OR: 0.97; p < 0.001), as well as with lower odds of overweight (OR: 0.72; p < 0.05) and obesity (OR: 0.67; p < 0.05). Physical activity was also associated with lower odds of all three constitution types and obesity. Phlegm stasis constitution was associated with higher odds of obesity (range of ORs: 1.18–1.58; p < 0.001). Conclusions: Vegetarian dietary patterns and regular physical activity were associated with lower odds of obesity and TCM constitution imbalances, particularly Phlegm stasis. These findings suggest a potential role for constitution-informed strategies in obesity-related public health approaches. Longitudinal studies are warranted to clarify temporal relationships and mechanisms. Clinical Trials Registration: ClinicalTrials.gov NCT03938207 (Study Start: 1 October 2022). Full article

Background: Diabetes is rapidly increasing in developing and industrializing nations, primarily due to type 2 diabetes (T2DM). With the global prevalence of diabetes steadily increasing, estimates suggest that by 2045, nearly 548 million people will be living with the disease worldwide. Alzheimer’s disease (AD), recognized as the primary contributor to dementia in aging populations, exhibits an escalating prevalence that parallels the demographic shifts toward older age groups worldwide. This progressive neurodegenerative disorder has emerged as a critical public health challenge, with epidemiological patterns closely tracking the trajectory of population aging across industrialized and developing nations. This study investigates whether metformin may help reduce the risk of dementia. Previous studies from various countries have explored the association between metformin use and dementia risk; however, the findings have been inconsistent. Therefore, we conducted this study to examine whether the observed protective effect of metformin also applies to the Taiwanese (Han Chinese) population, potentially providing valuable insights into ethnic or regional differences in drug response. Methods: We conducted a retrospective cohort study using data from the Longitudinal Health Insurance Database 2000 (LHID2000), including 2 million individuals from 2000 to 2013. Patients with T2DM aged ≥40 years who initiated metformin between 2000 and 2005 formed the exposed group, while those starting other second-line antidiabetic medications formed the non-exposed group. Propensity score matching was used to control for age, sex, index date, and major comorbidities. Incident dementia (2007–2013) was identified using relevant ICD-9-CM codes. Adjusted hazard ratios were estimated using Cox regression with time-dependent covariates. Results: The metformin-exposed cohort demonstrated a risk reduction for dementia incidence relative to the comparator group (adjusted HR 0.472, 95% CI = 0.328–0.679). This protective association remained robust in sex-stratified analyses and age-stratified subgroups. Temporal analysis further revealed a duration-dependent risk attenuation, with extended therapeutic exposure correlating with progressive dementia risk decrement. Conclusions: Our findings suggest that metformin use may be associated with a lower risk of developing dementia in individuals with type 2 diabetes mellitus. Full article

Background/Objectives: The place where a person dies serves as an indicator of end-of-life care quality. This study aims to identify the congruence of place of death (POD) and the reasons behind decision-making among terminally ill cancer patients in East Asia. Methods: We conducted a prospective multicenter cohort study in palliative care units in Japan, Korea, and Taiwan. Data were collected by the responsible physicians during routine clinical practice. Sankey diagrams were applied to present changes in reasons for POD incongruence. Results: A total of 2638 participants from 37 palliative care units in the three countries were enrolled, and most of them died at PCUs (Japan: 95.7%, Korea: 94%, Taiwan: 82%, p < 0.05). The congruence rate of the preferred and actual POD among PCU inpatients ranged from 70% to 80%. Availability of end-of-life care is the most common reason for preferred and eventual PCU death (78.6%, 72.2%, and 52.1%, respectively, p < 0.05). However, 13–22% of patients admitted to PCUs still preferred to die at home, for which traditional culture (20.2%, 40.8%, and 82%, respectively, p < 0.05) or family influence (44.4%, 38.8%, and 51.7%, respectively, p > 0.05) are the main reasons. Cultural and environmental factors, such as influences from family members’ preferences in the three countries or the ownership of housing/housing settings in Japan, are the main challenges in achieving POD congruence. Conclusions: Culturally inclusive strategies in clinical practice and policy implementation for identifying the preferred POD, enhancing communication among stakeholders, and facilitating transitional support may improve the quality of goal-concordant care. Full article

Background/Objectives: While sublobar resection (SLR) is accepted for selected small, early non-small-cell lung cancers (NSCLCs), its efficacy for tumors with visceral pleural invasion (VPI) remains debated. This study aimed to compare lung-cancer-specific survival (LCSS) between SLR and lobectomy in pT2a (tumor ≤ 3 cm with VPI) N0M0 NSCLCs from a nationwide population-based database. Methods: This retrospective study utilized Taiwan Cancer Registry data from 2011 to 2018, selecting patients with pT2a (tumor ≤ 3 cm with VPI) N0M0 NSCLC that underwent SLR or lobectomy, with specific exclusion criteria. Propensity score matching (1:1) was performed using a greedy algorithm with a 0.01 caliper width. LCSS was compared using Kaplan–Meier analysis with log-rank tests and Cox proportional hazards models before and after matching. Results: In the 2460-patient cohort (624 SLR, 1836 lobectomy) before matching, lobectomy was associated with significantly better overall (p = 0.01) and PL1 VPI subgroup (p = 0.009) LCSS. In the matched cohort (523 pairs), no significant difference in LCSS was observed between SLR and lobectomy, either overall (p = 0.21) or when stratified by PL1 (p = 0.11) or PL2 (p = 0.94) status. Multivariate Cox analysis in the matched cohort confirmed no significant association between surgery type and LCSS (adjusted HR 0.75, 95% CI 0.52–1.08, p = 0.124), but older age (>75 years), PL2 VPI, and lymphovascular invasion were independent predictors of worse LCSS (all p < 0.001). Conclusions: This large population-based study, after rigorous adjustment for confounders, found that SLR and lobectomy provided comparable LCSS. SLR may be an alternative for selected patients, but prospective validation is recommended. Full article

Background and Objectives: Acute decompensated heart failure (ADHF) leads to significant impairments in exercise capacity and functional outcomes. This study aimed to evaluate the feasibility and effectiveness of integrating early phase I cardiac rehabilitation with a multidisciplinary heart failure post-acute care (HF-PAC) program to improve functional capacity in patients hospitalized for ADHF, assessed by serial cardiopulmonary exercise testing (CPET). Materials and Methods: We conducted a prospective cohort study at a medical center in Taiwan. Patients hospitalized for ADHF between February 2017 and March 2023 who completed inpatient and six-month follow-up CPET were enrolled. The rehabilitation protocol included supervised aerobic and resistance training during hospitalization, followed by outpatient multidisciplinary care. The primary outcome was the change in peak oxygen uptake (peak VO₂) over six months. Results: A total of 90 patients were included (74.4% male, mean age 58.4 ± 14.7 years). Peak VO₂ significantly improved from 11.57 ± 3.33 to 13.99 ± 4.2 mL/kg/min (p < 0.001). Significant improvements were also observed in 6 min walk distance, anaerobic threshold, heart rate recovery, oxygen uptake efficiency slope, and left ventricular ejection fraction. Conclusions: Early integration of phase I cardiac rehabilitation with multidisciplinary HF-PAC is feasible and enhances exercise capacity in patients with ADHF. Serial CPET provides an objective evaluation of functional recovery and may guide rehabilitation strategies in this high-risk population. Full article

Background and Objectives: The therapeutic effect of para-aortic lymphadenectomy in patients with clinically para-aortic node-negative diseases remains controversial. In this study, we investigated whether combined pelvic and para-aortic lymphadenectomy has a survival benefit compared with pelvic lymphadenectomy alone in patients with clinically FIGO stage IIIC1 high-grade endometrial cancer. Materials and Methods: We retrospectively reviewed patients with clinically FIGO stage IIIC1 high-grade endometrial cancer in the period between January 2000 and December 2020 at two tertiary centers. The patients were stratified according to type of lymphadenectomy and subgroup analyses performed. Kaplan–Meier analysis and a Cox proportional-hazards model were used to evaluate survival outcomes. Results: A total of 56 patients were identified. Of these patients, 18 underwent pelvic lymphadenectomy alone and 38 underwent combined pelvic and para-aortic lymphadenectomy. After staging surgery, 34 (60.7%) patients had pathologically confirmed lymph node metastases. Within a median follow-up of 57.5 months, there were no significant differences in recurrence-free survival (RFS) and overall survival (OS) between the two groups. In subgroup analyses, the node- and lymphovascular space invasion (LVSI)-positive patients characterized by grade 3 endometrioid histologic type (p = 0.010) or negative peritoneal washing cytology (p = 0.035) had an RFS benefit from combined pelvic and para-aortic lymphadenectomy. Conclusions: The addition of para-aortic lymphadenectomy to pelvic lymphadenectomy did not improve survival in patients with clinically FIGO IIIC1 endometrial cancer. However, para-aortic lymphadenectomy may have RFS benefit for patients with grade 3 endometrioid histologic type and positive LVSI. Full article

Background: Population differences in gut microbiota composition and related metabolites may influence their potential causal relationship with chronic kidney disease (CKD); however, this relationship remains poorly understood in the Chinese population. Materials and Methods: We conducted a two-sample Mendelian randomization (MR) study using summary statistics of 500 gut microbial features (9 phyla, 3 classes, 14 orders, 32 families, 95 genera, 248 species, and 99 gut metabolic modules (GMMs)) from the 4D-SZ (from Shenzhen, China) discovery cohort (n = 1539). CKD summary statistics were obtained from the China Kadoorie Biobank (CKB) (489 cases and 75,531 controls). Associations between gut microbiota and CKD were evaluated via inverse variance weighted, MR-Egger, weighted median, and MR-PRESSO. To validate our findings, we replicated the analyses in two independent East Asian CKD GWAS datasets: the Biobank of Japan (BBJ) dataset (2117 cases and 174,345 controls) and the J-Kidney-Biobank (JKB) dataset (382 cases and 3471 controls). We further validated the results via a meta-GWAS of BUN and eGFR in Biobank Japan (BBJ) and the Taiwan Biobank (TWB). Additionally, we analyzed 304 serum proteins from the Guangzhou Nutrition and Health Study (GNHS) and conducted mediation MR analyses to explore potential mediators. Result: At the locus-wide significance threshold, we identified 18 gut microbiome features associated with CKD onset in the China Kadoorie Biobank (CKB). Genus Alistipes (OR 1.02, 95% CI 1.00–1.03, p = 0.03) was associated with incident CKD risk in the JKB cohort. Species Bifidobacterium catenulatum–Bifidobacterium pseudocatenulatum complex (OR 1.0074, 95% CI 1.0070–1.0142, p = 0.01) was associated with incident CKD risk in a meta-GWAS of BUN. Sensitivity analyses, including Cochran’s Q test, MR-Egger intercept analysis, leave-one-out analysis, and funnel plots, yielded consistent results. Mediation analysis revealed that 26.7% (95% CI: 0.006–0.6700, p = 0.04) of the effect of Alistipes on CKD risk was mediated through the serum protein FBLN1. Conclusions: Our study provides Mendelian randomization-based evidence supporting a potential causal relationship between gut microbiota and CKD, highlighting the potential mediating role of FBLN1 in the association between genus Alistipes and CKD. Further studies are needed to explore whether and how genus Alistipes and FBLN1 contribute to CKD development. Full article

Inflammatory bowel disease (IBD), comprising ulcerative colitis (UC) and Crohn’s disease (CD), is a chronic, immune-mediated inflammatory disorder of the gastrointestinal tract. Immunosuppressive therapy administration increases the risk of hepatitis B virus (HBV) and hepatitis C virus (HCV) reactivation. This study aimed to investigate the hepatitis screening rate, serological status, and protective antibody levels among the Taiwanese IBD population. This single-center retrospective study included patients with IBD from January 2016 to December 2024. Hepatitis serological markers were analyzed. Patients were categorized into active HBV infection (HBsAg-positive), resolved HBV infection (HBsAg-negative and anti-HBc-positive), and non-HBV-infected groups, with prevalences of 7.5%, 32.5%, and 0.9%, respectively. This study included 347 patients with IBD (UC: 68.3%; CD: 31.7%), with a mean age of 47.1 ± 16.4 years. Patients born after 1984 demonstrated a significantly reduced HBsAg positivity (0.9% vs. 11.0%; p < 0.05) and resolved HBV infection (52.2% vs. 1.0%; p < 0.05). However, among non-HBV-infected individuals, only 42.0% had protective anti-HBs levels (≥10 mIU/mL), despite vaccination program initiation. In this study, we found an overall HBsAg positivity rate of 7.5% and an anti-HCV seropositivity rate of 0.9% in our IBD population. Taiwan’s HBV vaccination program has effectively reduced the HBV prevalence. However, a significant proportion of vaccinated individuals lack sufficient protective antibody levels, thereby requiring continued HBV screening and booster vaccinations. Full article

In the past, an isolated ventricular septal defect (VSD) was categorized as a simple lesion with assumed negligible long-term risks when treated correctly in childhood; however, evidence has suggested that patients with isolated congenital VSDs carry a substantial burden of cardiovascular morbidity throughout life. This study aimed to investigate the cardiopulmonary function (CPF) in isolated VSD patients of a young age and the relationship of CPF with age, sex and body mass index (BMI). This retrospective cohort study was conducted at a tertiary medical center in southern Taiwan. We recruited children and adolescents (aged 5 to 18 years) with isolated VSDs who underwent the symptom-limited treadmill exercise test. Data from 289 children and adolescents (157 males, 132 females) were included in the analysis. The participants were stratified into three groups according to age. The male patients had a significantly higher oxygen uptake at the anaerobic threshold (AT VO₂) and a higher peak oxygen uptake (peak VO₂) (all p < 0.05). Normalized AT VO₂ (mL/kg/min) and normalized peak VO₂ (mL/kg/min) were significantly negatively associated with BMI. In conclusion, male patients with isolated VSDs had similar or better CPF compared with female patients. BMI had a negative association with CPF in young VSD patients. Full article

Background/Objectives: Evidence has indicated an increased risk of stroke in individuals with influenza infection, and the administration of Oseltamivir revealed a lower stroke risk in these individuals. However, the impacts of Oseltamivir and stroke remain limited. Methods: The data used in this retrospective cohort study were extracted from the Taiwan National Health Insurance Research Database (NHIRD), which included 281,420 Oseltamivir users and 13,394,652 patients between 1 January 2009 and 31 December 2018. The Oseltamivir group was younger (age 40.1 ± 15.3 years) and had a lower prevalence of comorbidities compared to the non-user group (age 46.2 ± 16.0 years). Stroke incidence and mortality were compared using multivariable Cox proportional hazards models. Results: We compared the incidence of ischemic stroke among individuals without a history of ischemic stroke, stratified by Oseltamivir use. After adjusting for age, sex, and comorbidities, Oseltamivir use was not associated with a significantly different risk of stroke (adjusted HR = 1.02, 95% CI: 0.96–1.08; p = 0.511). The mortality among individuals with a history of ischemic stroke, being Oseltamivir users (n = 2502), exhibited a lower cumulative mortality rate compared to non-users (4.08% vs. 6.45%). The association remained significant after multivariable adjustment, with an adjusted hazard ratio for mortality of 0.74 (95% CI: 0.61–0.89; p = 0.002). Conclusions: In this large population-based cohort of patients without a history of ischemic stroke, Oseltamivir use during influenza infection was not associated with stroke incidence after adjusting for age, sex, and comorbidities. Notably, Oseltamivir use in patients with a history of ischemic stroke was associated with reduced all-cause mortality, suggesting a potential survival benefit that warrants further investigation. Full article

Background: Microvascular complications in type 2 diabetes (T2D) and cancer share biological pathways, including chronic inflammation, dysregulated angiogenesis, and endothelial dysfunction, yet their impact on cancer risk and mortality remains unclear. This study evaluated whether T2D patients with microvascular complications face increased cancer incidence or cancer-related mortality. Methods: Using the Taiwan National Health Insurance Research Database, we identified individuals newly diagnosed with T2D (2008–2021) and assessed the outcomes with multivariable Cox proportional hazards models. Results: Our findings indicate that T2D patients with diabetic neuropathy, retinopathy, or chronic kidney disease do not have a significantly increased risk of major cancers, including those of the oral cavity, thyroid, breast, respiratory tract, digestive system, or lymphoid tissues. Similarly, microvascular complications were not associated with higher cancer-related mortality. However, microvascular complications significantly increased all-cause mortality in a dose-dependent manner: adjusted hazard ratio (aHR) 1.16 [95% CI: 1.15–1.17] for one complication, aHR 1.42 [1.38–1.45] for two, and aHR 1.71 [1.60–1.83] for three. Conclusions: In this nationwide cohort study, we demonstrate that while microvascular complications are associated with increased all-cause mortality in T2D, they do not appear to elevate cancer risk or cancer-specific mortality. These findings provide crucial epidemiological insights into the relationship between diabetes complications and cancer. Full article

(1) Background: The role of air pollutants as risk factors for tinnitus remains unclear. To address this gap in research, we conducted a nationwide retrospective cohort study in Taiwan by integrating patients’ clinical data with daily air quality data to evaluate the environmental risk factors associated with tinnitus. (2) Methods: The Taiwan National Health Research Database (NHIRD) includes medical records for nearly all residents of Taiwan. To assess pollution levels, we used daily air quality data from the Taiwan Environmental Protection Agency regarding SO₂, CO, NO, NO_X, and particulate matter (PM_2.5 and PM₁₀). We merged the NHIRD data with air quality information based on the residents’ locations and the positions of air quality monitoring stations. Pollutant levels were then categorized into quartiles (Q1, Q2, Q3, and Q4). (3) Results: This study included 284,318 subjects. After controlling for covariates, the adjusted HR (95 CI%) for tinnitus increased with increasing SO₂, CO, NO, NO_X, PM_2.5, and PM₁₀ exposure levels, specifically from 1.24 (95 CI% = 1.18, 1.30) to 1.35 (95 CI% = 1.28–1.41); from 1.15 (95 CI% = 1.09, 1.21) to 1.90 (95 CI% = 1.81, 2.00); from 0.86 (95 CI% = 0.82, 0.91) to 1.69 (95 CI% = 1.62, 1.77); from 1.62 (95 CI% = 1.54, 1.71) to 1.69 (95 CI% = 1.60, 1.77); from 0.16 (95 CI% = 0.15, 0.18) to 2.70 (95 CI% = 2.57, 2.84); and from 2.53 (95 CI% = 2.38, 2.69) to 3.58 (95 CI% = 3.39, 3.78), respectively, compared to the Q1 concentrations for all air pollutants. (4) Conclusions: During the 15-year follow-up period, we found a significant positive correlation between air pollutant exposure and the risk of tinnitus. Full article

(1) Background: The relationship between air pollution and the risk of developing aphasia is still unclear. We aimed to evaluate air pollution exposure as a risk factor for developing aphasia in Taiwan. (2) Methods: This retrospective population-based cohort study used the Longitudinal Generation Tracking Database (LGTD) and the Taiwan Air Quality Monitoring Database (TAQMD). The incidence rate ratio (IRR) and adjusted hazard ratio (aHR) were calculated to examine the association between aphasia and exposure to six air pollutants: sulfur oxide (SO₂), carbon monoxide (CO), nitric oxide (NO), nitrogen oxide (NOx), and particulate matter (PM_2.5, PM₁₀) from 2003 to 2017. (3) Results: The incidence rate ratio (IRR) of aphasia showed that individuals with high levels of SO₂, CO, and NO were at a higher risk of developing aphasia. Increased exposure to airborne particulate matter (PM_2.5 and PM₁₀) also increased the risk of developing aphasia. The adjusted HRs of the aphasia risk were statistically significant for all the air pollutants at higher concentrations. (4) Conclusions: Individuals exposed to ambient air pollutants have a significantly higher risk of developing aphasia. The greater the exposure to airborne particulate matter and gaseous pollutants, the more likely individuals are to develop aphasia. Full article

Background: Anemia is a common complication of chronic kidney disease (CKD), yet no study has explored differences in anemia risk factors based on disease severity and gender. Therefore, this study investigates potential differences in anemia risk among individuals with varied kidney disease severities and sexes. Methods: This multicenter, longitudinal cohort study was conducted using data (2008–2016) from the Epidemiology and Risk Factors Surveillance of CKD database. This database was associated with Taiwan’s National Health Insurance Research Database (for the 2008–2019 period). To identify predictive risk factors for anemia, we developed a subset multivariate logistic model using stepwise variable selection. Additionally, 10-fold cross-validation was conducted to facilitate model selection and internal validation. Results: Of the 5656 patients with CKD, 519 (9.18%) with anemia and 5137 (90.82%) without. After adjusting for age, sex, and serum creatinine, stepwise logistic regression analysis identified the main independent predictive factors for anemia in CKD patients. Notably, “Receive low sodium diet education” (OR: 0.66, 95% CI: 0.446–0.975), “DBP (mmHg)” (OR: 0.98, 95% CI: 0.965–0.999), “Gout” (OR: 1.86, 95% CI: 1.175–2.937), and “Congestive heart failure” (OR: 1.85, 95% CI: 1.131–3.028) was significantly associated with the presence of anemia among CKD patients. Conclusions: This study identifies gout and cardiovascular disease as important correlates of anemia in patients with CKD. Moreover, it reveals an inverse association between elevated diastolic blood pressure and receiving education on a low-sodium diet with the occurrence of anemia. Full article