Background: Hereditary transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive and fatal disease. A97S (p.Ala117Ser) is the most common transthyretin genetic mutation in Taiwan. Tafamidis is ...a transthyretin stabilizer, and it has been shown to improve outcomes. However, its effect on A97S ATTR-CM subtypes remains unknown. Objectives: This study aimed to investigate the efficacy of tafamidis in patients with hereditary A97S ATTR-CM after 6 months of treatment. Methods: We retrospectively analyzed ATTR-CM patients who received tafamidis (61 mg/day) treatment at National Taiwan University Hospital. Functional status, biochemistry and echocardiography were measured at baseline and after 6 months of tafamidis treatment. The outcome measure was to compare the N-terminal pro-brain natriuretic peptide (NT-proBNP) level at baseline and after 6 months of tafamidis treatment. Results: Twenty patients were enrolled in this study. Their mean age was 63.0 ± 5.8 years and 75% were men. The baseline left ventricular (LV) mass index was 200.9 ± 63.9 g/m^2 , and the baseline LV ejection fraction was 58.9 ± 13.5%. After 6 months of treatment, the log NT-proBNP level significantly improved from 2.9 ± 0.6 to 2.7 ± 0.5 (p = 0.036). Subgroup analysis showed that the LV posterior wall thickness and left atrial diameter were significantly higher in the patients with improved NT-proBNP, suggesting the benefits of tafamidis for ATTR-CM patients with severe cardiac involvement. Conclusions: The patients with hereditary A97S ATTR-CM in this study had decreased levels of NT-proBNP after 6 months of tafamidis treatment, and this reduction was especially pronounced in those with more severe cardiac involvement.
Patients with central airway obstruction (CAO) may need endobronchial intervention to relieve their symptoms. This report is on a single-center experience of using interventional bronchoscopy in ...terms of complications and survival. This retrospective study was conducted in a university hospital and involved 614 patients (464 men, 150 women; mean age, 60.2 years) with benign (n = 133) and malignant (n = 481) tracheobronchial disease who received 756 endobronchial intervention procedure during the period 2008 to 2015. Survival was analyzed using the Kaplan-Meier method, while the log-rank test was used for comparisons. A total of 583 patients (95%) achieved endoscopic success after interventional bronchoscopy. Four (0.7%) died within 24 hours of the procedure, while the major morbidities were halitosis (n = 41, 6.7%) and iatrogenic pneumonia (n = 24, 3.9%). Repeat procedures due to recurrent airway obstruction were done on 45 patients with benign conditions and on 60 with malignancies. The median survival after the procedure in patients with lung cancer, other metastatic cancer, and esophageal cancer was 166, 228, and 86 days, respectively. Between patients with inoperable lung cancer and CAO after therapeutic bronchoscopy and patients without CAO, there was no statistically significant difference in survival (P = 0.101). Interventional bronchoscopy is a safe and effective procedure that may be recommended for CAO. Patients with lung metastases have similar lengths of survival as patients with primary lung cancer. Patients with advanced lung cancer and CAO have similar survival as those without CAO.
Atmospheric particulate matters (PMs) were measured in an industry-intensive region in central Taiwan in order to investigate the characteristics and possible sources of PMs. The samplings were ...simultaneously conducted using a 10- and 3-stage Micro Orifice Uniform Deposit Impactor (MOUDI) from 2017 to 2018. In this study, the characteristics of PMs in this region were evaluated by measuring the mass concentration of PMs and analyzing water-soluble ions and metallic elements, as well as dioxins. Additionally, principal component analysis (PCA) was used to identify the potential sources of PMs. The results showed that the mean concentration of coarse (>1.8 μm), fine (0.1–1.8 μm), and ultrafine (<0.1 μm) particles were 13.60, 14.38, and 3.44 μg/m3, respectively. In the industry-intensive region, the size distribution of ambient particles showed a bi-modal distribution with a high concentration of coarse particles in the spring and summer, while fine particles were dominant in the autumn and winter. The most abundant water-soluble ions of PMs were NO3−, Cl−, and SO42−, while the majority of metallic elements were Na, Fe, Ca, Al, and Mg in different particle sizes. The results of Pearson’s correlation analysis for metals indicated that the particles in the collected air samples were related to the iron and steelmaking industries, coal burning, vehicle exhausts, and high-tech industries. The dioxin concentration ranged from 0.0006 to 0.0017 pg I-TEQ/Nm3. Principal component analysis (PCA) revealed that the contribution to PMs was associated with sea salt, secondary pollutants, and industrial process.
The relationship between asthma and ankylosing spondylitis (AS) is controversial. We examined the risk of asthma among AS patients in a nationwide population.
We conducted a retrospective cohort ...study using data from the National Health Insurance (NHI) system of Taiwan. The cohort included 5,974 patients newly diagnosed with AS from 2000 to 2010. The date of diagnosis was defined as the index date. A 4-fold of general population without AS was randomly selected frequency matched by age, gender and the index year. The occurrence and hazard ratio (HR) of asthma were estimated by the end of 2011.
The overall incidence of asthma was 1.74 folds greater in the AS cohort than in the non-AS cohort (8.26 versus 4.74 per 1000 person-years) with a multivariable Cox method measured adjusted HR of 1.54 (95% confidence interval (CI), 1.34-1.76). The adjusted HR of asthma associated with AS was higher in women (1.59; 95% CI, 1.33-1.90), those aged 50-64 years (1.66; 95% CI, 1.31-2.09), or those without comorbidities (1.82; 95% CI, 1.54-2.13).
Patients with AS are at a higher risk of developing asthma than the general population, regardless of gender and age. The pathophysiology needs further investigation.
The development of third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) targeting T790M-mutant non-small cell lung cancer (NSCLC) has raised the importance of ...re-biopsy after EGFR-TKI failure. This study aimed to investigate the feasibility of interventional pulmonology (IP) procedures as re-biopsy methods for identifying the T790M mutation in EGFR-TKI-resistant patients. One hundred and thirty-nine NSCLC patients who underwent IP procedures for re-biopsy as their initial investigation after EGFR-TKI treatment failure were enrolled in this study between January 2020 and August 2022. All patients underwent a first re-biopsy with IP methods, with a diagnostic yield of 81.2% and T790M mutation detection rate of 36%. Thirty patients underwent a second re-biopsy; IP methods were used for 17 (56.6%) patients and non-IP methods for 13 (43.4%) patients; the T790M mutation detection rate was 36.4%. Only six patients underwent a third re-biopsy; no T790M mutation was noted. The T790M mutation detection rate did not differ between IP and non-IP methods (33.6 % vs. 37.5%,
= 0.762). In 11 cases (7.5%), a re-biopsy revealed histologic transformation from lung adenocarcinoma. IP procedures, as first-line re-biopsy methods for NSCLC, are feasible and provide sufficient tissue for identification of the resistance mechanism and target gene T790M mutation.
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•Salinomycin increased TP expression in a p38 MAPK activation manner.•Downregulation of TP expression enhances salinomycin-induced cytotoxicity.•Hsp90 inhibition enhances ...salinomycin-induced cytotoxic effects.
Salinomycin is a polyether ionophore antibiotic having anti-tumorigenic property in various types of cancer. Elevated thymidine phosphorylase (TP) levels, a key enzyme in the pyrimidine nucleoside salvage pathway, are associated with an aggressive disease phenotype and poor prognoses. Heat shock protein 90 (Hsp90) is a ubiquitous molecular chaperone that is responsible for the stabilization and maturation of many oncogenic proteins. In this study, we report whether Hsp90 inhibitor 17-AAG could enhance salinomycin-induced cytotoxicity in NSCLC cells through modulating TP expression in two non-small-cell lung cancer (NSCLC) cell lines, A549 and H1975. We found that salinomycin increased TP expression in a MKK3/6-p38 MAPK activation manner. Knockdown of TP using siRNA or inactivation of p38 MAPK by pharmacological inhibitor SB203580 enhanced the cytotoxic and growth inhibition effects of salinomycin. In contrast, enforced expression of MKK6E (a constitutively active form of MKK6) reduced the cytotoxicity and cell growth inhibition of salinomycin. Moreover, Hsp90 inhibitor 17-AAG enhanced cytotoxicity and cell growth inhibition of salinomycin in NSCLC cells, which were associated with down-regulation of TP expression and inactivation of p38 MAPK. Together, the Hsp90 inhibition induced TP down-regulation involved in enhancing the salinomycin-induced cytotoxicity in A549 and H1975 cells.
This study examines the possible association between urinary tract infection (UTI) and urinary tract cancer (UTC). Data from the National Health Insurance system of Taiwan were used for the analysis. ...The UTI cohort included 70 116 patients who were diagnosed and recruited between 1997 and 2010. Each patient was randomly frequency‐matched with two people without UTI from the general population based on their age, sex, and month of UTI diagnosis. Cox's proportional hazard regression analysis was used to estimate the effects of UTI on UTC risk until the end of follow‐up on December 31, 2010. Patients with UTI had a significantly higher risk of developing UTC than healthy people (adjusted hazard ratio, 4.66; 95% confidence interval, 3.55–6.10). Further analyses indicated that risks are potentially related to the level of the lesion site. This study indicated that patients with UTI had a higher risk of developing UTC.
Various studies have shown that irritable bowel syndrome (IBS) is highly associated with other pathologies, including fibromyalgia (FM). The objective of this study was to analyze the differences ...among risk factors associated with IBS following FM in a nationwide prospective cohort study. We propose that a relationship exists between FM and IBS. This article presents evidence obtained from a cohort study in which we used data from the Taiwan National Health Insurance Research Database to clarify the relationship between FM and IBS. The follow-up period ran from the start of FM diagnosis to the date of the IBS event, censoring, or December 31, 2011. We analyzed the risk of IBS using Cox proportional hazard regression models, including sex, age, and comorbidities. During the follow-up period, from 2000 to 2011, the overall incidence of IBS was higher in FM patients than in non-FM patients (7.47 vs 4.42 per 1000 person-years), with a crude hazard ratio = 1.69 (95% confidence interval CI 1.45-1.63). After adjustment for age, sex, and comorbidities, FM was associated with a 1.54-fold increased risk for IBS. Mutually risk factors may influence the relationship between FM and IBS. We recommend that physiologists conduct annual examinations of FM patients to reduce the incidence of IBS progression.
The effects of the inflammatory mediators involved in systemic lupus erythematous (SLE) on subsequent Parkinson disease have been reported, but no relevant studies have focused on the association ...between the 2 diseases. This nationwide population-based study evaluated the risk of Parkinson disease in patients with SLE.We identified 12,817 patients in the Taiwan National Health Insurance database diagnosed with SLE between 2000 and 2010 and compared the incidence rate of Parkinson disease among these patients with that among 51,268 randomly selected age and sex-matched non-SLE patients. A Cox multivariable proportional-hazards model was used to evaluate the risk factors of Parkinson disease in the SLE cohort.We observed an inverse association between a diagnosis of SLE and the risk of subsequent Parkinson disease, with the crude hazard ratio (HR) being 0.60 (95% confidence interval 0.45-0.79) and adjusted HR being 0.68 (95% confidence interval 0.51-0.90). The cumulative incidence of Parkinson disease was 0.83% lower in the SLE cohort than in the non-SLE cohort. The adjusted HR of Parkinson disease decreased as the follow-up duration increased and was decreased among older lupus patients with comorbidity.We determined that patients with SLE had a decreased risk of subsequent Parkinson disease. Further research is required to elucidate the underlying mechanism.
Previous studies suggest that an association between restless legs syndrome (RLS) and migraine exists. However, population-based data are unavailable in Asian cohorts. Our study thus aims to evaluate ...the association between migraine and RLS in a nationwide, population-based cohort in Taiwan and to examine the effects of age, sex, migraine subtype, and comorbidities on RLS development.Data from the Taiwan National Health Insurance Research Database were used. Patients aged 20 years or older with newly diagnosed migraine from 2000 to 2008 were included; 23,641 patients with newly diagnosed migraine and 94,564 subjects without migraine were randomly selected and followed until RLS development, withdrawal from the National Health Insurance, or until the end of 2011. A multivariate Cox proportional hazards regression model was used to explore the risk of RLS in patients with migraine after adjustment for demographic characteristics and comorbidities.Both cohorts were followed for a mean of 7.38 years. After adjustment for covariates, the risk of RLS was 1.42-fold higher (95% confidence interval = 1.13-1.79) in the migraine cohort than in the nonmigraine cohort (7.19 versus 3.42 years per 10,000 person-years). The increased risk was more prominent in males in the migraine cohort (1.87-fold increased risk, 95% confidence interval 1.22-2.85). Neither comorbidity status nor migraine subtype influenced the RLS risk.This population-based study demonstrated that migraine is associated with an increased risk of RLS compared with those without migraine, particularly in male patients with migraine and regardless of the comorbidity status.
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