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Association between predialysis creatinine and mortality in acute kidney injury patients requiring dialysis.
Chang, HH, Wu, CL, Tsai, CC, Chiu, PF
PloS one. 2022;(9):e0274883
Abstract
BACKGROUND Creatinine is widely used to estimate renal function, but this is not practical in critical illness. Low creatinine has been associated with mortality in many clinical settings. However, the associations between predialysis creatinine level, Sepsis-related Organ Failure Assessment (SOFA) score, fluid overload, and mortality in acute kidney injury patients receiving dialysis therapy (AKI-D) has not been fully addressed. METHODS We extracted data for AKI-D patients in the eICU and MIMIC databases. We conducted a retrospective observational cohort study using the eICU dataset. The study cohort was divided into the high-creatine group and the low-creatinine group by the median value (4 mg/dL). The baseline patient information included demographic data, laboratory tests, medications, and comorbid conditions. The independent association of creatinine level with 30-day mortality was examined using multivariate logistic regression analysis. In sensitivity analyses, the associations between creatinine, SOFA score, and mortality were analyzed in patients with or without fluid overload. We also carried out an external validity using the MIMIC dataset. RESULTS In all 1,600 eICU participants, the 30-day mortality rate was 34.2%. The crude overall mortality rate in the low-creatinine group (44.9%) was significantly higher than that in the high-creatinine group (21.9%; P < 0.001). In the fully adjusted models, the low-creatinine group was associated with a higher risk of 30-day mortality (odds ratio, 1.77; 95% confidence interval, 1.29-2.42; P < 0.001) compared with the high-creatinine group. The low-creatinine group had higher SOFA and nonrenal SOFA scores. In sensitivity analyses, the low-creatinine group had a higher 30-day mortality rate with regard to the BMI or albumin level. Fluid overloaded patients were associated with a significantly worse survival in the low-creatinine group. The results were consistent when assessing the external validity using the MIMIC dataset. CONCLUSIONS In patients with AKI-D, lower predialysis creatinine was associated with increased mortality risk. Moreover, the mortality rate was substantially higher in patients with lower predialysis creatinine with concomitant elevation of fluid overload status.
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Prevention of Early Alzheimer's Disease by Erinacine A-Enriched Hericium erinaceus Mycelia Pilot Double-Blind Placebo-Controlled Study.
Li, IC, Chang, HH, Lin, CH, Chen, WP, Lu, TH, Lee, LY, Chen, YW, Chen, YP, Chen, CC, Lin, DP
Frontiers in aging neuroscience. 2020;:155
Abstract
OBJECTIVE To investigate the efficacy and safety of three H. erinaceus mycelia (EAHE) capsules (350 mg/capsule; containing 5 mg/g erinacine A active ingredient) per day for the treatment of patients with mild Alzheimer's Disease (AD). METHODS This study comprised a 3-week no-drug screening period, followed by a 49-week double-blind treatment period with 2-parallel groups in which eligible patients were randomized to either three 5 mg/g EAHE mycelia capsules per day or identical appearing placebo capsules. Cognitive assessments, ophthalmic examinations, biomarker collection, and neuroimaging were followed throughout the study period. RESULTS After 49 weeks of EAHE intervention, a significant decrease in Cognitive Abilities Screening Instrument score was noted in the placebo group, a significant improvement in Mini-Mental State Examination score was observed in the EAHE group and a significant Instrumental Activities of Daily Living score difference were found between the two groups. In addition, EAHE group achieved a significantly better contrast sensitivity when compared to the placebo group. Moreover, only the placebo group observed significantly lowered biomarkers such as calcium, albumin, apolipoprotein E4, hemoglobin, and brain-derived neurotrophic factor and significantly elevated alpha1-antichymotrypsin and amyloid-beta peptide 1-40 over the study period. Using diffusion tensor imaging, the mean apparent diffusion coefficient (ADC) values from the arcuate fasciculus region in the dominant hemisphere significantly increased in the placebo group while no significant difference was found in the EAHE group in comparison to their baselines. Moreover, ADC values from the parahippocampal cingulum region in the dominant hemisphere significantly decreased in the EAHE group whereas no significant difference was found in the placebo group when compared to their baselines. Lastly, except for four subjects who dropped out of the study due to abdominal discomfort, nausea, and skin rash, no other adverse events were reported. CONCLUSION Three 350 mg/g EAHE capsules intervention for 49 weeks demonstrated higher CASI, MMSE, and IADL scores and achieved a better contrast sensitivity in patients with mild AD when compared to the placebo group, suggesting that EAHE is safe, well-tolerated, and may be important in achieving neurocognitive benefits. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, identifier NCT04065061.
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Gender Differences with Dose⁻Response Relationship between Serum Selenium Levels and Metabolic Syndrome-A Case-Control Study.
Lu, CW, Chang, HH, Yang, KC, Chiang, CH, Yao, CA, Huang, KC
Nutrients. 2019;11(2)
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Selenium (Se) is an antioxidative micronutrient that activates Se-containing proteins known as selenoproteins. The aim of this study was to examine the relationship between serum Se level and metabolic syndrome including each metabolic factor. A secondary aim was to find a correlation between obesity, insulin resistance, and gender. The study is a case control study based on the comparison of Se levels between patients with and without metabolic syndrome. The study enrolled a total of 1165 ambulatory males or females, aged more than 40 years. Results showed a positive association between serum Se level and the risk of metabolic syndrome. Also, the serum Se concentration was positively associated with a number of metabolic factors following a dose–response relationship. Authors conclude that gender stratification analyses clearly highlighted the gender differences in insulin resistance, adiposity, and lipid metabolism.
Abstract
Few studies have investigated the association between selenium and metabolic syndrome. This study aimed to explore the associations between the serum selenium level and metabolic syndrome as well as examining each metabolic factor. In this case-control study, the participants were 1165 adults aged ≥40 (65.8 ± 10.0) years. Serum selenium was measured by inductively coupled plasma-mass spectrometry. The associations between serum selenium and metabolic syndrome were examined by multivariate logistic regression analyses. The least square means were computed by general linear models to compare the serum selenium levels in relation to the number of metabolic factors. The mean serum selenium concentration was 96.34 ± 25.90 μg/L, and it was positively correlated with waist circumference, systolic blood pressure, triglycerides, fasting glucose, and homeostatic model assessment insulin resistance (HOMA-IR) in women, but it was only correlated with fasting glucose and HOMA-IR in men. After adjustment, the odds ratios (ORs) of having metabolic syndrome increased with the selenium quartile groups (p for trend: <0.05), especially in women. The study demonstrated that the serum selenium levels were positively associated with metabolic syndrome following a non-linear dose⁻response trend. Selenium concentration was positively associated with insulin resistance in men and women, but it was associated with adiposity and lipid metabolism in women. The mechanism behind this warrants further confirmation.
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Effect of memantine on C-reactive protein and lipid profiles in bipolar disorder.
Chang, HH, Chen, PS, Wang, TY, Lee, SY, Chen, SL, Huang, SY, Hong, JS, Yang, YK, Lu, RB
Journal of affective disorders. 2017;:151-157
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Abstract
BACKGROUND Balance in the immune system plays roles in bipolar disorder (BD) and its metabolic co-morbidities. Memantine is an NMDA receptor antagonist with anti-inflammatory effects. However, the effects of memantine adjunct treatment on metabolic status of BD are unclear. METHODS During the 12 weeks period, a total of 191 BD patients were enrolled and split into valproate (VPA) + placebo and VPA + memantine (5mg/day) arms. The fasting plasma levels of high-sensitivity C-reactive protein (CRP) and metabolic indices were assessed. BD patients were stratified according to their initial CRP level. RESULTS A cut-off value of initial CRP level of 2322ng/mL discriminated the waist circumference in these BD patients after 12-week VPA treatment. In the high CRP (> 2322ng/mL) group, patients in the VPA + memantine arm had a significantly decreased in their CRP (p= 0.009), total cholesterol (p= 0.002), LDL (p= 0.002) levels, BMI (p= 0.001), and waist circumference (p< 0.001), compared to those in the VPA + placebo arm. However, analysis of the low CRP group did not showed the effect. LIMITATIONS We recruited BD patients in depressed states and the sample size was relative small. The effects of the fixed dose of memantine on metabolic indices were 12-week follow up in BD patients treated with VPA. CONCLUSIONS BD patients with high initial CRP levels receiving memantine adjunct treatment have a reduced risk of inflammation and metabolic imbalance. Prospective studies are needed to confirm the long-term outcome for memantine adjunct therapy in BD patients.
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Modulation of Endothelial Injury Biomarkers by Traditional Chinese Medicine LC in Systemic Lupus Erythematosus Patients Receiving Standard Treatments.
Chang, HH, Luo, SF, Hsue, YT, Chang, CM, Lee, TY, Huang, YC, Hsu, ML, Chen, YJ
Scientific reports. 2016;:19622
Abstract
LC is an herbal remedy effectively reduced therapeutic dosage of glucocorticoid for systemic lupus erythematosus (SLE) patients in clinical trial (ISRCTN81818883). This translational research examined the impact of LC on biomarkers of endothelial injury in the enrolled subjects. Fifty seven patients with SLE were randomized to receive standard treatment without or with LC supplements. Blood samples were taken serially for quantification of endothelial progenitor cells (EPCs), circulating endothelial cells (CECs) and serological factors. The proportion of EPCs in the placebo group continued to increase during trial and was further elevated after withdrawal of standard treatment. The EPC ratio of LC group remained stationary during the entire observation period. The CEC ratio in placebo group exhibited an increasing trend whereas that in LC group declined. The ratio of apoptotic CECs had an increasing trend in both groups, to a lesser extent in LC group. After treatment, the levels of VEGF and IL-18 have a trend declined to a level lower in the LC group than the placebo group. No significant alteration was noted in serum levels of IFN-α, IL-1β and IL-6. The reduction of the steroid dosage by adding LC might be correlated with less extensive endothelial injury in SLE patients.
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High serum selenium levels are associated with increased risk for diabetes mellitus independent of central obesity and insulin resistance.
Lu, CW, Chang, HH, Yang, KC, Kuo, CS, Lee, LT, Huang, KC
BMJ open diabetes research & care. 2016;(1):e000253
Abstract
OBJECTIVE Selenium is an essential micronutrient for human health. Although many observational and interventional studies have examined the associations between selenium and diabetes mellitus, the findings were inconclusive. This study aimed to investigate the relationship between serum selenium levels and prevalence of diabetes, and correlated the relationship to insulin resistance and central obesity. RESEARCH DESIGN AND METHODS This was a hospital-based case-control study of 847 adults aged more than 40 years (diabetes: non-diabetes =1:2) in Northern Taiwan. Serum selenium was measured by an inductively coupled plasma-mass spectrometer. The association between serum selenium and diabetes was examined using multivariate logistic regression analyses. RESULTS After adjusting for age, gender, current smoking, current drinking, and physical activity, the ORs (95% CI, p value) of having diabetes in the second (Q2), third (Q3), and fourth (Q4) selenium quartile groups were 1.24 (95% CI 0.78 to 1.98, p>0.05), 1.90 (95% CI 1.22 to 2.97, p<0.05), and 5.11 (95% CI 3.27 to 8.00, p<0.001), respectively, compared with the first (Q1) quartile group. Further adjustments for waist circumference and homeostatic model assessment-insulin resistance (HOMA-IR) largely removed the association of serum selenium levels with diabetes but not in the highest quartile (compared with Q1, Q3: 1.57, 95% CI 0.91 to 2.70, Q4: 3.79, 95% CI 2.17 to 6.32). CONCLUSIONS We found that serum selenium levels were positively associated with prevalence of diabetes. This is the first human study to link insulin resistance and central obesity to the association between selenium and diabetes. Furthermore, the association between selenium and diabetes was independent of insulin resistance and central obesity at high serum selenium levels. The mechanism behind warrants further confirmation.
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Quantifying midbrain serotonin transporter in depression: a preliminary study of diagnosis and naturalistic treatment outcome.
Tsai, HC, Lin, SH, Chen, PS, Chang, HH, Lee, IH, Yeh, TL, Chen, KC, Chiu, NT, Yao, WJ, Liao, MH, et al
Pharmacopsychiatry. 2015;(2):58-64
Abstract
INTRODUCTION Serotonin may play an important role in the pathology of major depressive disorder (MDD). However, the relationship between serotonin transporter (SERT) availability and the medical outcome of antidepressant treatment is uncertain. METHODS In this naturalistic study, SERT availability (expressed as the specific uptake ratio, SUR) in the midbrain of 17 drug-free patients with MDD and 17 controls matched for age and gender was measured using SPECT with [(123)I]ADAM. The severity of MDD was measured by the Hamilton Depression Rating Scale before, and after 6 weeks of non-standardized antidepressant treatment. RESULTS A total of 12 patients completed the study. The SUR of the patients with MDD was significantly lower than that of the healthy controls. The SUR of SERT was not found to have a linear relationship with the treatment outcome; however, supplemental analysis found a curvilinear relationship between treatment outcome and the SUR of SERT. DISCUSSION The findings indicate that the SUR of SERT is lower in patients with MDD; however it did not predict treatment outcome in a linear fashion. Studies with larger sample sizes are required.
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Low serum selenium level is associated with low muscle mass in the community-dwelling elderly.
Chen, YL, Yang, KC, Chang, HH, Lee, LT, Lu, CW, Huang, KC
Journal of the American Medical Directors Association. 2014;(11):807-11
Abstract
OBJECTIVES Elderly persons with low muscle mass (LMM) or sarcopenia are prone to frailty and functional decline. This study aimed to investigate the relationship between serum selenium level and skeletal muscle mass in community-dwelling elderly. DESIGN Cross-sectional observational study. SETTING AND PARTICIPANTS A total of 327 elderly Taipei citizens (mean age 71.5 ± 4.7 years) were recruited from the community. MEASUREMENTS Skeletal muscle mass was measured by bioelectrical impedance analysis. LMM was defined by low skeletal muscle index (SMI: muscle mass (kg)/[height (m)](2)). All participants were further divided into quartiles by serum selenium level and the risk for LMM among these quartiles was examined using multivariate logistic regression analyses. Estimated serum selenium levels for the LMM group vs the normal group and estimated SMI in the quartiles of serum selenium were computed by least square method in linear regression models. RESULTS The estimated mean (±standard deviation) of serum selenium level was significantly lower in the LMM group compared with the normal group after adjusting for confounders (1.01 ± 0.03 μmol/L vs 1.14 ± 0.02 μmol/L, P < .001). After adjusting for age, sex, lifestyle, and physical and metabolic factors, the odds ratios (95% confidence interval, P value) of LMM in the bottom, second, and third selenium quartile groups were 4.62 (95% CI 2.11-10.10, P < .001), 2.30 (95% CI 1.05-5.03, P < .05) and 1.51 (95% CI 0.66-3.46, P = .327), respectively, compared with the top quartile group of serum selenium level. The least square mean of SMI increased with the quartiles of serum selenium (P < .001). CONCLUSIONS This is the first study to demonstrate that low serum selenium is independently associated with low muscle mass in the elderly. The causality and underlying mechanism between selenium and low muscle mass or sarcopenia warrant further research.
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The diagnosis and classification of autoimmune coagulopathy: an updated review.
Chang, HH, Chiang, BL
Autoimmunity reviews. 2014;(4-5):587-90
Abstract
Autoantibodies against coagulation factors can develop in patients associated with autoimmune disorders, malignancies, pregnancy, and drug-induced or dermatological diseases. These antibodies can bind to functional epitopes of individual coagulation factors, neutralize their activity or promote their clearance, and clinically leading to bleeding conditions. Among them, the most common one is that directed against factor VIII (FVIII). Patients with autoantibodies against FVIII often have severe hemorrhage and delayed diagnosis can contribute to high mortality in these patients. Further, autoantibodies against other coagulation factors, such as Factors V, XI, XII, XIII, and the vitamin-K dependent proteins, occur more rarely. The pathogenesis for developing autoantibodies against these coagulation factors is still unclear. A mechanism of breakdown in immune tolerance, which may be derived from a combination of genetic and environmental factors as well as the aging of the immune system in elderly individuals, may be responsible for the development of autoantibodies against FVIII. In this article, we reviewed and updated the classification and diagnostic algorithms for identifications of autoantibodies against the coagulation factors in clotting cascade.
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Clinical features, risk factors, and treatment experience: a review of 74 patients with ST-segment elevation myocardial infarction complicated by ventricular fibrillation.
Wang, W, Chen, QF, Yin, RX, Zhu, JJ, Li, QB, Chang, HH, Wu, YB, Michelson, E
The Journal of emergency medicine. 2014;(6):729-35
Abstract
BACKGROUND Ventricular fibrillation (VF) is one of the most serious complications of acute myocardial infarction, with a high mortality rate. There is a lack of value of rescue thrombolysis in ST-segment elevation myocardial infarction (STEMI) complicated by VF. OBJECTIVE To examine the relationship between risk factors and mortality, and assess the value of rescue thrombolysis in STEMI complicated by VF. METHODS A total 74 cases of STEMI complicated by VF were enrolled. The experimental group consisted of 26 patients who underwent rescue thrombolysis, and the control group included 48 cases without rescue thrombolysis. The two groups were compared in terms of demographic and clinical features including gender, age, onset time, blood pressure, patient's history, creatine kinase-MB, infarct area, complications, therapy, and outcomes, including mortality. RESULTS The mortality rate of the experimental group was 15.38%, lower than 37.50% of the control group (p < 0.05). The bleeding rate was 34.62% (n = 9) in the experimental group. The risk factors of smoking, shock, and rescue thrombolysis were correlated with mortality of STEMI complicated by VF (p < 0.05 for all): Smoking and shock both were positively correlated with mortality, their regression coefficients/odds ratios (OR) were, respectively, 4606/100,041 and 5552/247,711; the rescue thrombolysis was negatively correlated with mortality, its regression coefficient/OR was -1942/0.143. CONCLUSIONS Rescue thrombolysis combined with cardiopulmonary resuscitation and defibrillation is beneficial to patients with STEMI complicated by VF. Smoking, shock upon admission, and lack of rescue thrombolysis were risk factors for mortality in STEMI complicated by VF.