Endothelial Dysfunction in Primary Aldosteronism Chen, Zheng-Wei; Tsai, Cheng-Hsuan; Pan, Chien-Ting ...
International journal of molecular sciences,
10/2019, Letnik:
20, Številka:
20
Journal Article
Recenzirano
Odprti dostop
Primary aldosteronism (PA) is characterized by excess production of aldosterone from the adrenal glands and is the most common and treatable cause of secondary hypertension. Aldosterone is a ...mineralocorticoid hormone that participates in the regulation of electrolyte balance, blood pressure, and tissue remodeling. The excess of aldosterone caused by PA results in an increase in cardiovascular and cerebrovascular complications, including coronary artery disease, myocardial infarction, stroke, transient ischemic attack, and even arrhythmia and heart failure. Endothelial dysfunction is a well-established fundamental cause of cardiovascular diseases and also a predictor of worse clinical outcomes. Accumulating evidence indicates that aldosterone plays an important role in the initiation and progression of endothelial dysfunction. Several mechanisms have been shown to contribute to aldosterone-induced endothelial dysfunction, including aldosterone-mediated vascular tone dysfunction, aldosterone- and endothelium-mediated vascular inflammation, aldosterone-related atherosclerosis, and vascular remodeling. These mechanisms are activated by aldosterone through genomic and nongenomic pathways in mineralocorticoid receptor-dependent and independent manners. In addition, other cells have also been shown to participate in these mechanisms. The complex interactions among endothelium, inflammatory cells, vascular smooth muscle cells and fibroblasts are crucial for aldosterone-mediated endothelial dysregulation. In this review, we discuss the association between aldosterone and endothelial function and the complex mechanisms from a molecular aspect. Furthermore, we also review current clinical research of endothelial dysfunction in patients with PA.
This study aimed to investigate the association of add-on dipeptidyl peptidase-4 inhibitor (DPP4i) therapy and the progression of diabetic retinopathy (DR). In this retrospective population-based ...cohort study, we examined Taiwanese patients with type 2 diabetes, preexisting DR, and aged ≥40 years from 2009 to 2013. Prescription of DPP4i was defined as a medication possession ratio of ≥80% during the first 6 months. The outcomes included vitreous hemorrhage (VH), tractional retinal detachment, macular edema, and interventions including retinal laser therapy, intravitreal injection (IVI), and vitrectomy. Of 1,767,640 patients, 62,824 were eligible for analysis. After matching, the DPP4i and non-DPP4i groups each contained 20,444 patients. The risks of VH (p = 0.013) and macular edema (p = 0.035) were higher in the DPP4i group. The DPP4i group also had higher risks of receiving surgical interventions (retinal laser therapy (p < 0.001), IVI (p = 0.049), vitrectomy (p < 0.001), and any surgical intervention (p < 0.001)). More patients in the DPP4i group received retinal laser therapy (p < 0.001) and IVI (p = 0.001) than in the non-DPP4i group. No between-group differences in cardiovascular outcomes were noted. In the real-world database study, add-on DPP4i therapy may be associated with the progression of DR in patients with type 2 diabetes. No additional cardiovascular risks were found. The early progression of DR in rapid glycemic control was inconclusive in our study. The possible effect of add-on DPP4i therapy in the progression of DR in patients with type 2 diabetes requires further research.
Midurethral sling surgery is the current gold standard worldwide for stress urinary incontinence (SUI) surgery, with over 90% of surgeons worldwide using the midurethral sling for SUI between 2008 ...and 2018. However, concerns surround mesh-related adverse events associated with the midurethral sling. The decision to use the midurethral sling for surgical treatment has become a challenging one for clinicians, surgeons and patients. We sought to determine the factors for 5-year complications after midurethral sling surgery, to improve the clinical decision-making process. Records were reviewed from a total of 1961 female patients who underwent their first midurethral sling surgery for SUI between 2003 and 2018 at a single teaching hospital in Taiwan. A multivariable Cox proportional hazard model calculated the hazard ratios of risk factors for surgical complications, after adjusting for confounders. Surgical complications (i.e., secondary surgery and urinary retention) occurred in 93 (4.7%) patients within 5 years following the index operations. These patients were more likely to be older, to have a history of menopausal syndrome within 1 year prior to the index operation, a medication history of oral antidiabetic drug use, hormone replacement therapy (HRT), slower average flow rate, and longer voiding time compared with patients without surgical complications. In the multivariate analysis, HRT (adjusted hazard ratio, 1.787; 95% confidence interval, 1.011-3.158, p = 0.04) was significantly associated with surgical complications at 5 years, after adjusting for age, gender, diabetes, menopause syndrome, average flow rate, and sling type. Our findings suggest that a medication history of HRT may be a risk factor associated with surgical complications, especially urinary retention, at 5 years in women undergoing midurethral sling surgery for SUI.
: Adult-onset Still's disease (AOSD) is a rheumatic disease characterized by systemic inflammatory symptoms, including intermittent spiking fever, polyarthritis and a distinctive salmon-colored rash. ...Corticosteroids are the first-line treatment for AOSD. However, corticosteroids are potentially hepatotoxic in certain cases and may complicate the course of the disease.
: A 29-year-old female suffering from fever of unknown origin for two weeks was diagnosed with AOSD according to Yamaguchi's criteria. She received corticosteroids as the first-line treatment for AOSD and developed acute severe hepatitis. A diagnostic protocol has been performed.
: Corticosteroid-induced liver injury was confirmed by clinical observation and rechallenge of the drug in this case. The result of liver biopsy also supported the diagnosis. Mycophenolic acid, a disease-modifying antirheumatic drug (DMARD) was chosen as an alternative treatment. AOSD remission was achieved under this treatment after three months.
: Severe acute hepatitis induced by corticosteroids, although very rare, may be observed in patients with AOSD. Drug-induced liver injury needs to be kept in mind when unexpected acute hepatitis is found. Mycophenolic acid could be a proper substitute medication in these cases.
Advanced non-small cell lung cancer (NSCLC) patients treated with chemotherapy experience functional decline and decreased quality of life. The purpose of this study was to evaluate the effects of a ...web-based health education program on global quality of life, quality of life-related functional dimensions, and symptom distress of initially diagnosed advanced non-small cell lung cancer patients. This study used a randomized, pre- and post-repeated measures design. A total of 55 participants were randomly assigned to an experimental group (
n
= 27) and a control group (
n
= 28). The experimental group participated in a web-based health education program, and the control group received usual care. Patients were assessed at 4 time points: baseline assessment (T0), and then 1, 2, and 3 months (T1, T2, and T3) after participating in the web-based health education program or receiving usual care. Patients in the experimental group had significantly greater global quality of life and emotional function, and significantly less top ten significant symptom distresses compared to those in the control group. There were no differences between the groups and within groups with respect to physical function, role function, cognitive function, and social function. The web-based health education can improve global quality of life, emotional function, and top ten significant symptom distresses in patients receiving chemotherapy during the first 3 months after initial diagnosis of advanced NSCLC. Web-based health education can improve quality of life and lessen distress of initially diagnosed NSCLC patients treated with chemotherapy.
Estimating the magnitude of earthquake-induced groundwater level (GWL) based on poroelastic theory is a challenge for researchers. To address this challenge, the present study explores this topic in ...the context of volumetric strain induced by ground shaking. Specifically, GWL records on the Chi-Chi earthquake in Taiwan, along with other selected events from 2004 to 2020, are analyzed to identify the persistent and instantaneous changes of GWL under distinct geological conditions. The magnitude of the persistent GWL change is highly correlated with peak ground acceleration, and thickness and density of sandy layers. This finding is explained by the magnitude of volumetric strains caused by soil particle rearrangement associated with ground motion intensities and site-specific conditions. Meanwhile, the instantaneous GWL change caused by seismic wave propagation exhibits a highly negative correlation with the vertical ground motion velocity time history because the compression wave induces instantaneous contraction or dilation of the soil. Moreover, the peak instantaneous GWL change correlates well with the peak ground velocity (PGV) in the vertical direction because the compressional (volumetric) strain is theoretically proportional to the PGV of vertical motion.
•Earthquake-induced groundwater level (GWL) changes and strong motion records in Taiwan are analyzed.•Persistent and instantaneous changes of GWL are discussed in relation to ground shaking-induced volumetric strain in soil.•Rearrangement of soil particles due to ground shaking well explains the magnitude of earthquake-induced GWL changes.•A high correlation between the time history of the instantaneous GWT change and that of vertical ground velocity.
Staphylococcus lugdunensis endophthalmitis is an uncommon intraocular infection with potentially visually devastating consequences. S. lugdunensis endophthalmitis have been reported following ...cataract surgery, trauma, intravitreal injections of anti-vascular endothelial growth factor agents and dexamethasone implant. We report four cases of postoperative S. lugdunensis endophthalmitis after cataract extraction (three patients) and combined pars plana vitrectomy and cataract extraction (one patient). The onset of presentation of endophthalmitis was acute (within 2 weeks) in two patients, subacute (2 to 6 weeks) in one patient, and chronic (more than 6 weeks) in one patient. All patients had presenting visual acuity (VA) of hand motions or worse and were treated with pars plana vitrectomy with intravitreal antibiotics. The final VA was 20/50 in two patients, 4/200 in one patient with pre-existing myopic maculopathy, and no light perception in one patient with retinal detachment. In antibiotic susceptibility testing, S. lugdunensis isolates were resistant to penicillin (3/4, 75%), but all were susceptible to vancomycin, oxacillin, teicoplanin, tigecycline, and sulfamethoxazole-trimethoprim. S. lugdunensis may be associated with acute or chronic endophthalmitis. Favorable visual outcomes can be achieved with prompt diagnosis and management.
Background:
Costs of medical care have been found to be highest at the end of life.
Aim:
To evaluate the effect of provider reimbursement for hospice care on end-of-life costs.
Design:
The policy ...expanded access to hospice care for end-stage renal disease patients, a policy previously limited to cancer patients only. This study employed a difference-in-differences analysis using a generalized linear model. The main outcome is inpatient expenditures in the last 30 days of life.
Setting/participants:
A cohort of 151,509 patients with chronic kidney disease or cancer, aged 65 years or older, who died between 2005 and 2012 in the National Health Insurance Research Database, which contains all enrollment and inpatient claims data for Taiwan.
Results:
Even as end-of-life costs for cancer are declining over time, expanding hospice care benefits to end-stage renal disease patients is associated with an additional reduction of 7.3% in end-of-life costs per decedent, holding constant patient and provider characteristics. On average, end-of-life costs are also high for end-stage renal disease (1.88 times higher than those for cancer). The cost savings were larger among older patients—among those who died at 80 years of age or higher, the cost reduction was 9.8%.
Conclusion:
By expanding hospice care benefits through a provider reimbursement policy, significant costs at the end of life were saved.
The link among perfluoroalkyl and polyfluoroalkyl substances (PFASs), abnormal glucose homeostasis and the risk of diabetes has been intensively debated with conflicting evidence.
We evaluated the ...associations among PFASs, oral glucose tolerance testing (OGTT) curves and diabetes prevalence in 571 working-aged Taiwanese participants.
Exposure measures included serum perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluoroundecanoic acid (PFUA). Outcomes were OGTT curves and prevalent diabetes defined by fasting blood glucose (FBG) ≥126mg/dL, 2-h glucose ≥200mg/dL, or glycated hemoglobin ≥6.5%. Analyses were performed with multiple logistic regression and functional data analysis.
A total of 39 participants (6.8%) had diabetes in this study. After full adjustment, the increase in the geometric means of FBG, 2-h glucose concentrations, and area under the OGTT curve (AUC120) with a doubling increase in PFOS was 3% (95% CI 1–4), 8% (5–12), and 6% (4–9), respectively. Compared to the lowest-quartile of PFOS concentrations (<2.4ng/ml), the OGTT trajectories were significantly steeper in participants of the highest-quartile PFOS exposure (>4.8ng/ml) and the vertical shifting of the mean curve for each PFOS quartile showed a dose–response pattern. The adjusted odds ratio for diabetes comparing the highest to lowest quartile was 3.37 (95% CI 1.18–9.65). For PFOA, PFNA, and PFUA, the opposite pattern of OGTT trajectory and the opposite risk profile for diabetes were observed.
Chronic PFOS exposure was associated with impaired glucose homeostasis and the increased prevalence of diabetes. However, PFOA, PFNA, and PFUA showed a potential protective effect against glucose intolerance and the risk of diabetes. Future research focusing on clarifying possible differential effects of different species of PFASs on glucose homeostasis and establishing the prospective associations between PFASs and diabetes is needed.
•Chronic PFOS exposure may associate with impaired glucose homeostasis and the increased prevalence of diabetes.•PFOA, PFNA, and PFUA may have a potential protective effect against glucose intolerance and the risk of diabetes.•The underlying mechanisms responsible for the differential diabetogenic effects of different PFASs require further research.•Well-designed prospective studies are warranted to confirm these findings and to inform prevention and policy strategies.
Purpose
Breast cancer is a molecularly heterogeneous disease, and multiple genetic variants contribute to its development and prognosis. Most of previous genome-wide association studies (GWASs) and ...polygenic risk scores (PRSs) analyses focused on studying breast cancers of Caucasian populations, which may not be applicable to other population. Therefore, we conducted the largest breast cancer cohort of Taiwanese population to fill in the knowledge gap.
Methods
A total of 152,534 Participants recruited by China Medical University Hospital between 2003 and 2019 were filtered by several patient selection criteria and GWAS quality control steps, resulting in the inclusion of 2496 cases and 9984 controls for this study. We then conducted GWAS for all breast cancers and PRS analyses for all breast cancers and the four breast cancer subtypes, including luminal A, luminal B, basal-like, and HER2-enriched.
Results
The GWAS analyses identified 113 SNPs, 50 of which were novel. The PRS models for all breast cancers and the luminal A subtype showed positively correlated trends between the PRS and the risk of developing breast cancer. The odds ratios (95% confidence intervals) for the groups with the highest PRS in all breast cancers and the luminal A subtype were 5.33 (3.79–7.66) and 3.55 (2.13–6.14), respectively.
Conclusion
In summary, we explored the association of genetic variants with breast cancer in the largest Taiwanese cohort and developed two PRS models that can predict the risk of developing any breast cancer and the luminal A subtype in Taiwanese women.
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