Publications by authors named "Hung-Pin Tu"

81 Publications

The association between hepatitis C virus infection and renal function.

J Chin Med Assoc 2021 Jun 1. Epub 2021 Jun 1.

Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC Department of Medical Research and Development, PubMend Medical Research Center, Ulaanbaatar, Mongolia Department of Internal Medicine, Institute of Medical Sciences, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia Hepatobiliary Section, Department of Internal Medicine & Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC Department of Public Health and Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC Department of Chemistry, National Sun Yat-Sen University, Kaohsiung, Taiwan, ROC Department of Biological Science and Technology, College of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsin-Chu, Taiwan, ROC.

Background: It is controversial that the association of hepatitis C virus (HCV) infection and chronic kidney disease (CKD). We wanted to investigate whether HCV really affect to renal function, also to analyze the association between clinical effects of CHC and decreased kidney function assessed by estimated glomerular filtration rate (eGFR) level.

Methods: The 3360 patients with hepatitis C virus infection and 3360 age and sex matched community based control individuals without HCV were enrolled (1:1, case and control ratio) in this study between 2004 and 2016. We used the Modification of Diet in Renal Diseases (MRDR) for calculate eGFR. Demographic and laboratory parameters were assessed and appropriate statistical methods were performed for the analysis.

Results: Multivariate logistic regression analysis revealed that serum alanine aminotransferase (ALT) (OR-0.998; 95% CI - 0.997-0.999; p=0.001) level, platelet (OR-0.997; 95% CI - 0.995-0.999; p=0.002) count and hypertension (OR-1.31; 95% CI - 1.03-1.66; p=0.027) were significantly associated with HCV infection and serum triglycerides (OR-1.001; 95% CI -1.00-1.002; p=0.005) level, platelet (OR-0.996; 95% CI - 0.995-0.997; p<0.001) count, BMI>25 (OR-1.43; 95% CI- 1.23-1.67; p<0.001), hypertension (OR-1.69; 95% CI - 1.42-1.99; p<0.001), hyperlipidemia (OR- 1.32; 95% CI - 1.02-1.71; p=0.035) and diabetes (OR-1.33; 95% CI-1.03-1.71; p=0.032) were significantly associated with low eGFR (<90ml/min/m3) in control subjects. The BMI >25kg/m2, hypertension, and diabetes were associated with low eGFR interaction with the HCV infection by multivariate analysis.

Conclusion: Our study indicated that the patients with HCV infection are associated with low eGFR compared with non HCV infected patients. This association is consistent in obese, diabetic and hypertensive patients.
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http://dx.doi.org/10.1097/JCMA.0000000000000561DOI Listing
June 2021

Risk of cancer development in patients with keloids.

Sci Rep 2021 Apr 30;11(1):9390. Epub 2021 Apr 30.

Department of Dermatology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, No. 123, Ta Pei Rd., Niaosong Dist., Kaohsiung, 833, Taiwan.

Keloid is a skin disease characterized by exaggerated scar formation, excessive fibroblast proliferation, and excessive collagen deposition. Cancers commonly arise from a fibrotic microenvironment; e.g., hepatoma arises from liver cirrhosis, and oral cancers arise from submucosal fibrosis. As keloids are a prototypic fibroproliferative disease, this study investigated whether patients with keloids have an increased cancer risk. In a matched, population-based study, first 17,401 patients treated for keloids during 1998-2010 with 69,604 controls without keloids at a ratio of 1:4 were evaluated. The association between keloids and risk of cancer was estimated by logistic regression or Cox proportional hazard regression models after adjustment of covariates. In total, 893 first-time cases of cancer were identified in the 17,401 patients with keloids. The overall cancer risk was 1.49-fold higher in the keloids group compared to controls. Regarding specific cancers, the keloids group, had a significantly higher risk of skin cancer compared to controls (Relative risk = 1.73). The relative risk for skin cancer was even higher for males with keloids (Relative risk = 2.16). Further stratified analyses also revealed a significantly higher risk of developing pancreatic cancer in female patients with keloids compared to controls (Relative risk = 2.19) after adjustment for known pancreatic cancer risk factors. This study indicates that patients with keloids have a higher than normal risk for several cancer types, especially skin cancers (both genders) and pancreatic cancer (females). Therefore, patients with keloids should undergo regular skin examinations, and females with keloids should regularly undergo abdominal ultrasonography.
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http://dx.doi.org/10.1038/s41598-021-88789-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087779PMC
April 2021

Different Curve Shapes of Fasting Glucose and Various Obesity-Related Indices by Diabetes and Sex.

Int J Environ Res Public Health 2021 03 17;18(6). Epub 2021 Mar 17.

Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung 812, Taiwan.

Fasting plasma glucose (FPG) and obesity-related indices are prognostic factors for adverse outcomes in both subjects with and without diabetes. A few studies have investigated sex differences in obesity indices related to the risk of diabetes, however no studies have compared the relationship between FPG and obesity-related indices by diabetes and sex. Therefore, in this study, we compared the curve shapes of FPG and various obesity-related indices by diabetes, and further explored sex differences in these associations. Data were derived from the Taiwan Biobank database, which included 5000 registered individuals. We used an adjusted generalized linear regression model and calculated the difference of least square means (Lsmean; standard error, SE) for males and females with and without diabetes. Associations between obesity-related indices and fasting glucose level by diabetes and sex groups were estimated, and the ORTHOREG procedure was used to construct B-splines. The post-fitting for linear models procedure was used to determine the range at which the trends separated significantly. The diabetes/sex/FPG interaction term was significant for all obesity-related indices, including body mass index, waist circumference, hip circumference, waist-to-hip ratio, waist-to-height ratio, lipid accumulation product, body roundness index, conicity index, body adiposity index and abdominal volume index. B-spline comparisons between males and females did not reach significance. However, FPG affected the trend towards obesity-related indices. As the fasting glucose level increased, the values of obesity-related indices varied more obviously in the participants without diabetes than in those with diabetes mellitus. The current study revealed that there was a different relationship between FPG and obesity-related indices by diabetes and sex. FPG affected the trend towards obesity-related indices more obviously in participants without diabetes than in those with diabetes. Further studies with a longitudinal design would provide a better understanding of the underlying mechanisms for the relationships.
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http://dx.doi.org/10.3390/ijerph18063096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002721PMC
March 2021

Clinical Impact of the Revised 2019 CLSI Levofloxacin Breakpoints in Patients with Bacteremia.

Antimicrob Agents Chemother 2021 05 18;65(6). Epub 2021 May 18.

Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

The Clinical and Laboratory Standards Institute (CLSI) revised the fluoroquinolone MIC breakpoints for in 2019, based on pharmacokinetic/pharmacodynamic analyses. However, clinical evidence supporting these breakpoint revisions is limited. A retrospective study was conducted at 3 hospitals in Taiwan between January 2017 and March 2019. Patients treated with levofloxacin for bacteremia caused by members of the with high MICs (1 or 2 μg/ml; levofloxacin susceptible by pre-2019 CLSI breakpoints) were compared with those with low-MIC bacteremia (≤0.5 μg/ml; levofloxacin susceptible by 2019 CLSI breakpoints) to assess therapeutic effectiveness by multivariable logistic regression. The primary outcome was 30-day mortality, and the secondary outcome was the emergence of levofloxacin-resistant isolates within 90 days after levofloxacin initiation. A total of 308 patients were eligible for the study. Kaplan-Meier analysis showed that patients infected with high-MIC isolates ( = 63) had a significantly lower survival rate than those infected with low-MIC isolates ( = 245) ( = 0.001). Multivariable logistic regression revealed that high levofloxacin MIC was a predictor of 30-day mortality (odds ratio [OR], 6.05; 95% confidence interval [CI], 1.51 to 24.18; = 0.011). We consistently found similar results in a propensity score-matched cohort (OR, 5.38; 95% CI, 1.06 to 27.39; = 0.043). The emergence of levofloxacin-resistant isolates was more common in the high-MIC group than the low-MIC group (25.0% versus 7.5%;  = 0.065). An estimated area under the concentration-time curve/MIC ratio of ≥87 was significantly associated with better survival ( = 0.002). In conclusion, patients infected with isolates with levofloxacin MICs within the pre-2019 CLSI susceptible range of 1 or 2 μg/ml exhibited higher mortality than those infected with isolates with MICs of ≤0.5 μg/ml.
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http://dx.doi.org/10.1128/AAC.00074-21DOI Listing
May 2021

Associations among Heavy Metals and Proteinuria and Chronic Kidney Disease.

Diagnostics (Basel) 2021 Feb 11;11(2). Epub 2021 Feb 11.

Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung 812, Taiwan.

Background: The prevalence of chronic kidney disease (CKD) is increasing annually in Taiwan. In addition to traditional risk factors, heavy metals contribute to the development of CKD. The aim of this study was to investigate associations among heavy metals and proteinuria and CKD in the general population in Southern Taiwan. We also explored the interaction and synergetic effects among heavy metals on proteinuria.

Methods: We conducted a health survey in the general population living in Southern Taiwan between June 2016 and September 2018. Seven heavy metals were measured: blood lead (Pb) and urine nickel (Ni), chromium (Cr), manganese (Mn), arsenic (As), copper (Cu), and cadmium (Cd). Proteinuria was measured using reagent strips. CKD was defined as an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m.

Results: The mean age of the 2447 participants was 55.1 ± 13.2 years and included 977 males and 1470 females. Participants with high blood Pb and high urine Ni, Mn, Cu, and Cd were significantly associated with proteinuria. Interactions between blood Pb and urine Cr, and between urine Cd and Cu, had significant effects on proteinuria. The participants with high blood Pb and high urine Cu were significantly associated with an eGFR of <60 mL/min/1.73 m.

Conclusion: High blood Pb and high urine Cu may be associated with proteinuria and an eGFR of <60 mL/min/1.73 m. High urine Ni, Mn, and Cd were significantly associated with proteinuria. Co-exposure to Cd and Cu, and Pb and Cr, may have synergistic effects on proteinuria.
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http://dx.doi.org/10.3390/diagnostics11020282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918558PMC
February 2021

Air Pollutants Interaction and Gender Difference on Bone Mineral Density T-Score in Taiwanese Adults.

Int J Environ Res Public Health 2020 12 8;17(24). Epub 2020 Dec 8.

Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan.

Osteoporosis is defined as a systemic skeletal disease characterized by a reduction in bone mass and microarchitectural deterioration of bone tissue. Previous studies have reported associations between air pollution and lower bone mineral density; however, few studies have investigated the association between air pollution and osteoporosis. In this study, we combined two databases, the first including 5000 individuals registered in the Taiwan Biobank, and the second containing detailed daily data on air pollution. After multivariable adjustments, ozone (O) (unstandardized coefficient β, 0.015; = 0.008) was significantly positively associated with T-score, whereas carbon monoxide (CO) (unstandardized coefficient β, -0.809; < 0.001), sulfur dioxide (SO) (unstandardized coefficient β, -0.050; = 0.005), nitric oxide (NO) (unstandardized coefficient β, -0.040; < 0.001), nitrogen dioxide (NO) (unstandardized coefficient β, -0.023; < 0.001), and nitrogen oxide (NO) (unstandardized coefficient β, -0.017; < 0.001) were significantly negatively associated with T-score. The interactions between CO and NO ( = 0.001) and SO and NO ( = 0.004) on T-score were statistically significant. An increase in exposure to CO, NO and NO was associated with a faster decline in T-score in the female participants compared to the male participants. In addition, an increase in O was associated with a faster increase in T-score in the female participants compared to the male participants. In conclusion, the air pollutants CO, SO, NO, NO, and NO were associated with osteoporosis. In addition, there were interaction and synergetic effects between CO and NO and SO and NO on T-score. We also observed differences in the associations between air pollutants and T-score between the female and male participants.
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http://dx.doi.org/10.3390/ijerph17249165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764089PMC
December 2020

Statin use and the risk of chronic kidney disease in patients with psoriasis: A nationwide cohort study in Taiwan.

PLoS One 2020 25;15(8):e0237816. Epub 2020 Aug 25.

Department of Dermatology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.

Background: Psoriasis is associated with hyperlipidemia. Few studies have examined the association among psoriasis, hyperlipidemia, and chronic kidney disease (CKD). It remains a topic of debate whether statin treatment for hyperlipidemia prevents the development of CKD in patients with psoriasis.

Objective: We investigated whether there is an association among psoriasis, hyperlipidemia and CKD. If so, we asked whether statin treatment for hyperlipidemia reduces the risk of CKD in patients with psoriasis.

Methods: A Taiwan nationwide population-based cohort study between 1997 and 2010 included 2,912 patients with psoriasis and 8,736 matched patients without psoriasis (1:3 propensity score matched according to age, sex, and region); 104,609 patients without psoriasis but with hyperlipidemia and 104,609 matched patients without psoriasis or hyperlipidemia (1:1). The hazard ratios, relative risks, and 95% confidence intervals were calculated using Cox proportional hazards model.

Results: Psoriasis significantly increased the risk of CKD (adjusted hazard ratio 2.48, 95% confidence interval 1.81-3.40), and so did hyperlipidemia (adjusted hazard ratio 2.93, 95% confidence interval 2.79-3.08). Compared to treatment without statins, statin treatment for hyperlipidemia reduced the risk of CKD in patients with psoriasis (adjusted relative risk 0.58, 95% confidence interval 0.55-0.62).

Conclusion: As well as hyperlipidemia, psoriasis significantly increased the risk of CKD. Statin treatment for hyperlipidemia reduced the risk of CKD in patients with psoriasis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0237816PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447019PMC
October 2020

There is a U shaped association between non high density lipoprotein cholesterol with overall and cardiovascular mortality in chronic kidney disease stage 3-5.

Sci Rep 2020 07 29;10(1):12749. Epub 2020 Jul 29.

Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.

Dyslipidemia is common in patients with chronic kidney disease (CKD), however the relationship between dyslipidemia and mortality in patients with moderate to severe CKD remains controversial. Non-high-density lipoprotein (HDL) cholesterol has been reported to be a more accurate predictor of clinical outcomes than conventional lipid measurements. Hence, the aim of this study was to investigate associations between non-HDL cholesterol and the risk of overall and cardiovascular mortality in patients with CKD stage 3-5. We enrolled 429 pre-dialysis patients with stage 3 to 5 CKD from May 2006 to January 2010. The patients were divided into four groups according to quartiles of non-HDL cholesterol. The patients were followed until death or until January 2020. During a median 11.6 years of follow-up, there were 78 (18.2%) deaths overall and 32 (7.5%) cardiovascular deaths. In adjusted models, the patients in quartile 1 (hazard ratio [HR] 3.368; 95% confidence interval [CI] 1.388-8.176; p = 0.007), quartile 3 (HR 3.666; 95% CI 1.486-9.044; p = 0.005), and quartile 4 (HR 2.868; 95% CI 1.136-7.240; p = 0.026) of non-HDL cholesterol had a higher risk of overall mortality (vs. quartile 2). In addition, the patients in quartile 1 (HR 19.503; 95% CI 2.185-174.0925 p = 0.008), quartile 3 (HR 28.702; 95% CI 2.990-275.559; p = 0.004), and quartile 4 (HR 11.136; 95% CI 1.126-110.108; p = 0.039) had a higher risk of cardiovascular mortality (vs. quartile 2). Our study showed a U-shaped relationship between non-HDL cholesterol and the risk of overall and cardiovascular mortality in patients with CKD stage 3-5. Assessing non-HDL cholesterol may help to identify subjects at high-risk of adverse outcomes.
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http://dx.doi.org/10.1038/s41598-020-69794-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392750PMC
July 2020

Effect modification of hyperlipidemia and hypertension on the association between type 2 diabetes and gout.

Prim Care Diabetes 2020 12 24;14(6):654-662. Epub 2020 Jun 24.

Department of Public Health and Environmental Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. Electronic address:

Aims: We evaluated the association between type 2 diabetes and gout by a retrospective cohort study.

Methods: Data of 17,259 male and 18,318 female patients with type 2 diabetes were retrieved for the 1998-2010 period. These patients were matched to a comparison group (n=34,518 and n=36,636, respectively) in a 1:2 ratio by age and region.

Results: We found that patients with type 2 diabetes after adjustment for hyperlipidemia and hypertension had a lower risk of incident gout than the matched population (incidence rate ratio, men: 0.39 [95% CI: 0.36-0.42]; women: 0.78 [0.72-0.84]). Specifically, type 2 diabetes alone without hyperlipidemia and hypertension was associated with a reduced risk of incident gout in men (adjusted relative risk [RR]: 0.29, 95% CI: 0.22-0.39), but not in women (0.86, 95% CI: 0.55-1.36). We found that insulin users with hyperlipidemia and hypertension associated with risk of incident gout and no sex-specific differences were noted (adjusted RR, men: 1.28 [95% CI: 1.11-1.48]; women: 1.32 [95% CI: 1.14-1.53]). Specifically, insulin users alone without hyperlipidemia and hypertension were not statistically significantly associated with gout risk (P≥.0954).

Conclusions: The results of this study indicated that hyperlipidemia and hypertension modified the association between type 2 diabetes and gout.
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http://dx.doi.org/10.1016/j.pcd.2020.06.002DOI Listing
December 2020

Increased Vascular Adhesion Protein 1 (VAP-1) Levels are Associated with Alternative M2 Macrophage Activation and Poor Prognosis for Human Gliomas.

Diagnostics (Basel) 2020 Apr 27;10(5). Epub 2020 Apr 27.

Department of Neurosurgery, Kaohsiung Medical University Chung Ho Memorial Hospital, Kaohsiung 80756, Taiwan.

Glioma is characterized by a high heterogeneity in the brain tumor. Abundant tumor-associated macrophages (TAMs) exist as neoplastic tissues, implicating tumor plasticity and thus leading to therapeutic challenges. Vascular adhesion protein (VAP-1) potentially serves as a mediator for TAM immunity in tumor milieu. We previously demonstrated that VAP-1 could contribute to tumor malignancy, but its characteristics in TAM immunity of glioma progression are still unclear. This study explored the association of VAP-1 expression with TAM distribution as well as the resulting clinical significance and prognostic value in human gliomas. An in-depth analysis of (VAP-1) gene expression was performed using 695 glioma samples derived from the cancer genome atlas (TCGA)-lower grade glioma and glioblastoma (GBMLGG) cohort. Bioinformatic analysis confirmed that VAP-1 expression is associated with poor prognosis of glioma patients ( = 0.0283). VAP-1 and TAM biomarkers (CD68, iNOS, and CD163) were evaluated by immunohistochemistry in 108 gliomas from Kaohsiung Medical University Hospital. VAP-1+ was expressed in 56 (51.85%) cases and this phenotype revealed a significant association with overall survival in Kaplan-Meier analysis ( < 0.0001). Immunohistochemical double staining showed that VAP-1 immunoreactivity was present around CD163+ M2 infiltration location, including aggressive lesions and neighboring neovasculature. We demonstrated that high VAP-1 expression levels positively correlated with CD163+ M2 activation and coexpression of these two proteins was associated with worse survival in gliomas ( < 0.0001). Multivariate analysis indicated that VAP-1 alone and co-expressed with CD163 were the significantly independent indicators (both < 0.0001). Furthermore, VAP-1/CD163 coexpression exhibited excellent diagnostic accuracy in gliomas (AUC = 0.8008). In conclusion, VAP-1 and TAM CD163 M2 coexpression was found in glioma tissues belonging to a highly malignant subgroup that was associated with poor prognosis. These results implied VAP-1 abundance is closely linked to alternative M2 activation during glioma progression. From the aforementioned data, a reasonable inference is that VAP-1 combined with targeting M2 immunity might be an effective therapeutic target for human gliomas.
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http://dx.doi.org/10.3390/diagnostics10050256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278017PMC
April 2020

Validation of Hyponatremia as a Prognostic Predictor in Multiregional Upper Tract Urothelial Carcinoma.

J Clin Med 2020 Apr 23;9(4). Epub 2020 Apr 23.

Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.

Hyponatremia has been shown to be associated with prognosis in various cancers, but its role in upper tract urothelial carcinoma (UTUC) is largely unidentified. We created an international multiregional cohort of UTUC, consisting of 524 and 213 patients from Taiwan and the U.S., to validate the significance of hyponatremia. Clinicopathologic characteristics were compared according to the presence of hyponatremia. Univariate and multivariate Cox regression models were used to investigate the association of hyponatremia with disease progression and survival. The impact of hyponatremia in patients from distinct regions was also analyzed. Hyponatremia was found in 143 (19.4%) patients. Hyponatremic patients had significantly worse Eastern Cooperative Oncology Group (ECOG) performance status ( = 0.00001) and higher pT stage ( = 0.002). In multivariate analysis, hyponatremia was an independent prognostic factor for progression (HR 1.585, 95% CI 1.115-2.253, = 0.010), cancer-specific death (HR 2.225, 95% CI 1.457-3.397, = 0.0002), and overall mortality (HR 1.819, 95% CI 1.299-2.545, = 0.0005). Kaplan-Meier analysis showed the consistent adverse effect of hyponatremia on all outcomes in patients from Taiwan and the U.S. (all < 0.05). Hyponatremia is commonly accessible and can serve as a negative marker for both the general health condition and disease severity of UTUC patients. A similar implication of hyponatremia in progression and survival despite patients' region of presentation suggests its general applicability across different ethnicities.
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http://dx.doi.org/10.3390/jcm9041218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231247PMC
April 2020

Generalized anxiety disorder in type 2 diabetes mellitus: prevalence and clinical characteristics.

Braz J Psychiatry 2020 Nov-Dec;42(6):621-629

Department of Psychiatry, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

Objective: This study investigated the prevalence of generalized anxiety disorder (GAD) in Taiwanese patients with type 2 diabetes mellitus (T2DM).

Methods: This retrospective observational study was conducted with a random sample of patients from the entire population of National Health Insurance enrollees during 2000-2010 and used ICD-9-CM diagnostic codes to identify T2DM patients and GAD. The prevalence of GAD was compared between T2DM patients and the general population.

Results: Between 2000 and 2010, the prevalence of GAD was significantly greater in the T2DM patients than the general population, while the increase of GAD was higher in the general population (from 0.25 to 0.63%) than among T2DM patients (from 0.81 to 1.03%). In T2DM patients, GAD was associated with female gender, a Charlson Comorbidity Index ≥ 1, diabetes mellitus duration > 9 years, and the following comorbidities: congestive heart failure, peripheral vascular disease, and depressive disorder. The prevalence of GAD among T2DM patients was negatively associated with rapid-acting insulin injection therapy and with the use of metformin and sulfonylureas.

Conclusion: Since the prevalence of GAD was greater among T2DM patients than the general population, public health initiatives are needed to prevent and treat GAD in T2DM patients, specifically those with the above mentioned risk factors.
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http://dx.doi.org/10.1590/1516-4446-2019-0605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678902PMC
November 2020

Interethnic differences in the impact of body mass index on upper tract urothelial carcinoma following radical nephroureterectomy.

World J Urol 2021 Feb 21;39(2):491-500. Epub 2020 Apr 21.

Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.

Purpose: Inconsistent prognostic implications of body mass index (BMI) in upper tract urothelial carcinoma (UTUC) have been reported across different ethnicities. In this study, we aimed to analyze the oncologic role of BMI in Asian and Caucasian patients with UTUC.

Methods: We retrospectively collected data from 648 Asian Taiwanese and 213 Caucasian American patients who underwent radical nephroureterectomy for UTUC. We compared clinicopathologic features among groups categorized by different BMI. Kaplan-Meier method and Cox regression model were used to examine the impact of BMI on recurrence and survival by ethnicity.

Results: According to ethnicity-specific criteria, overweight and obesity were found in 151 (23.2%) and 215 (33.2%) Asians, and 79 (37.1%) and 78 (36.6%) Caucasians, respectively. No significant association between BMI and disease characteristics was detected in both ethnicities. On multivariate analysis, overweight and obese Asians had significantly lower recurrence than those with normal weight (HR 0.631, 95% CI 0.413-0.966; HR 0.695, 95% CI 0.493-0.981, respectively), and obesity was an independent prognostic factor for favorable cancer-specific and overall survival (HR 0.521, 95% CI 0.342-0.794; HR 0.545, 95% CI 0.386-0.769, respectively). There was no significant difference in outcomes among normal, overweight and obese Caucasians, but obese patients had a relatively poorer 5-year RFS, CSS, and OS rates of 52.8%, 60.5%, and 47.2%, compared to 54.9%, 69.1%, and 54.9% for normal weight patients.

Conclusion: Higher BMI was associated with improved outcomes in Asian patients with UTUC. Interethnic differences could influence preoperative counseling or prediction modeling in patients with UTUC.
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http://dx.doi.org/10.1007/s00345-020-03204-0DOI Listing
February 2021

Higher risk of herpes zoster in stroke patients.

PLoS One 2020 4;15(2):e0228409. Epub 2020 Feb 4.

Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

Background: Stroke is a leading cause of death, morbidity and disability worldwide. Infection is a common complication in the acute phase after stroke. Herpes zoster is a common viral disease, in which the most debilitating complication is post-herpetic neuralgia, which can have a very large negative impact on quality of life. The aim of this study was to investigate whether stroke increases the risk of herpes zoster.

Methods: This cohort study compared patients who had herpes zoster with and without a first incident of stroke. The Taiwan National Health Insurance Research Database was utilized to identify 20,551 stroke patients and 20,551 controls matched for age, gender, age categories and Charlson Comorbidity Index (CCI) score categories at a one-to-one ratio. Cox proportional-hazards regression models were employed to estimate herpes zoster risk in the stroke group relative to general population.

Results: Compared to the control group, the stroke group had a greater risk for herpes zoster, especially within 1 year after stroke (adjust HR = 25.27). Both hemorrhagic stroke and ischemic stroke were significantly associated with herpes zoster (hemorrhagic type (IRR = 2.31, 95% CI, 1.67-3.20); ischemic type (IRR = 2.51, 95% CI 2.09-3.02)). However, the hemorrhagic stroke patients had a higher risk of herpes zoster ophthalmicus (IRR = 12.46, 95% CI 4.00-38.76) whereas the ischemic stroke patients had a higher risk of post-herpetic neuralgia (IRR = 2.24, 95% CI 1.56-3.20).

Conclusion: Physicians should know about that adults with stroke have a higher than normal risk of herpes zoster. Thus, physicians must be acquainted with proper antiviral therapy and pain control to bring down the morbidity that ensues from herpes zoster. Use of herpes zoster vaccine may be considered in stroke patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0228409PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6999860PMC
April 2020

A haplotype-specific linkage disequilibrium pattern of monoamine oxidase A gene associated with regular smoking in women.

J Gene Med 2019 12 17;21(12):e3142. Epub 2019 Dec 17.

Environment-Omics-Disease Research Center, China Medical University Hospital, Taichung, Taiwan.

Background: Cigarette smoking in women is raising a public health problem. The X-linked monoamine oxidase A (MAOA) was considered as a susceptibility gene to substance abuse of tobacco, but the evolutionary effect of MAOA may lead to a positive or negative association between genetic variations and smoking development among study regions.

Methods: Based on linkage disequilibrium (LD), we performed a haplotype-based association to explore the effect of MAOA gene on women's smoking risk in a case-control study.

Results: Genotyped single nucleotide polymorphisms (SNPs) of MAOA gene, rs5953210G>A, rs2283725A>G and rs1137070T>C, were significantly associated with current smoking risk in women, and the increased level of plasma MAO-A activity was raised with per copy increment of risk allele in current smokers (P < .01). The haplotype patterns with minor haplotype frequency >.05 were constructed using the Expectation-Maximization algorithm, and the haplotype-specific A-G-C pattern raised the 2-fold risk to develop regular smoking (P = .0005). In the diplotype analysis based on X-inactivation mechanism relative to no and full dosage compensation, we showed that A-G-C haplotype not only increased regular smoking risk in a dose-dependent manner (P = .0011) but also contributed to smoking risk in the dosage compensation mechanism. Compared to non-smokers, the effect of A-G-C haplotype on random X-activation was associated with the raised MAO-A activity in women smokers (P < .05) although the lifetime cigarette consumption showed a difference that was not statistically significant.

Conclusion: This study provides information on MAOA LD-based haplotype and diplotype patterns in women smoking.
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http://dx.doi.org/10.1002/jgm.3142DOI Listing
December 2019

Early Post-Operative Intervention of Whole-Body Vibration in Patients After Total Knee Arthroplasty: A Pilot Study.

J Clin Med 2019 Nov 7;8(11). Epub 2019 Nov 7.

Department of Physical Medicine and Rehabilitation, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.

(1) Background: Knee osteoarthritis causes pain, weakness, muscle atrophy, and disability. The application of whole-body vibration in patients with knee osteoarthritis can improve strength, balance, and functional activities. The purpose of the study is to evaluate the effects of early whole-body vibration intervention in patients after total knee arthroplasty. (2) Method: A single-blinded randomized control trial. Fifty-two patients with knee osteoarthritis post total knee replacement from a medical center in southern Taiwan were randomly assigned to either a whole-body vibration group or control group. Main outcome measures included pain severity, leg circumference, knee range of motion, knee extensor strength, a five-times sit to stand test, and a timed up and go test. (3) Results: Immediately post treatment, the patients in the vibration group showed a significant increase in knee extensor strength and improvement in calf swelling compared to the control group. A trend toward decrease in pain severity and improvement in functional performance were observed in both groups without a significant difference between the groups. There was no significant difference in knee range of motion (ROM) and functional performance between the groups. (4) Conclusions: The whole-body vibration intervention in patients early post total knee arthroplasty showed significant immediate effect in increasing knee extensor strength and decreasing calf swelling.
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http://dx.doi.org/10.3390/jcm8111902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912668PMC
November 2019

The incidence of anxiety may not be correlated with severity of psoriasis: A prospective pilot study.

Med Hypotheses 2019 Sep 1;130:109254. Epub 2019 Jun 1.

Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Dermatology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Dermatology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address:

Psoriasis is associated with certain psychiatric disorders such as anxiety and depression. Although a growing body of literature has indicated high prevalence of anxiety in patients with psoriasis, it is unclear if the incidence of anxiety is correlated with severity of psoriasis. In this article, we hypothesize that anxiety is not correlated with severity of psoriasis, and therefore the issue of anxiety should not be neglected in patients with mild psoriasis. To testify this hypothesis, we performed a pilot study to investigate the correlation between anxiety questionnaires and severity of psoriasis. Thirty-two patients with psoriasis were recruited. The patients were further classified into mild or moderate to severe psoriasis according to their body surface area or Psoriasis Area Severity Index (PASI). Zung's self-rating anxiety scale (SAS) and SF-36 were adopted to evaluate anxiety and quality of life, respectively. Spearman's rank correlation coefficients were calculated between SAS and each scale of SF-36 among these 32 patients. SAS is negatively correlated with role limitation due to emotional problems, vitality, emotional well-being of SF-36. Although SAS is not significantly different between mild and moderate to severe psoriasis, the detected levels of anxiety were higher than normative standards. Physicians should not neglect potential anxiety in patients who have mild psoriasis. Inter-discipline collaboration between psychiatry and dermatology is required to provide comprehensive patient care.
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http://dx.doi.org/10.1016/j.mehy.2019.109254DOI Listing
September 2019

Is asthma a protective factor for dengue fever? In vitro experiment and nationwide population-based cohort analysis.

Allergol Int 2019 Oct 24;68(4):486-493. Epub 2019 Jun 24.

Department of Pediatrics, Chang Gung Memorial Hospital - Kaohsiung Medical Centre, Kaohsiung, Taiwan.

Background: Dengue fever (DF) is the most rapidly spreading mosquito-borne viral disease. Practical vaccines or specific therapeutics are still expected. Environmental factors and genetic factors affect the susceptibility of Dengue virus (DV) infection. Asthma is a common allergic disease, with house dust mites (HDMs) being the most important allergens. Asthmatic patients are susceptible to several microorganism infections.

Methods: A nationwide population-based cohort analysis was designed to assess whether to determine whether asthma can be a risk factor for DF.

Results: Unexpectedly, our data from a nationwide population-based cohort revealed asthmatic patients are at a decreased risk of DF. Compared to patients without asthma, the hazard ratio (HR) for DF in patients with asthma was 0.166 (95% CI: 0.118-0.233) after adjustment for possible confounding factors. In the age stratification, the adjusted HR for DF in young adult patients with asthma was 0.063. Dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) of dendritic cells (DCs) is an important entry for DV. Through another in vitro experiment, we found that HDM can diminish surface expression of DC-SIGN in monocyte-derived DCs and further decrease the cellular entry of DV.

Conclusions: Decreased DC-SIGN expression in DCs of allergic asthmatic patient may be one of many factors for them to be protected against DF. This could implicate the potential for DC-SIGN modulation as a candidate target for designing therapeutic strategies for DF.
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http://dx.doi.org/10.1016/j.alit.2019.06.001DOI Listing
October 2019

Bavachin attenuates LPS-induced inflammatory response and inhibits the activation of NLRP3 inflammasome in macrophages.

Phytomedicine 2019 Jun 10;59:152785. Epub 2018 Dec 10.

Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan; Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. Electronic address:

Background: Bavachin is a natural product isolated from Psoralea corylifolia L. that has been applied as a traditional medicine in Asian countries. However, the anti-inflammatory effects of bavachin on LPS-induced inflammation and NLRP3 inflammasome activation by macrophages remain unclear.

Purpose: We investigated the anti-inflammatory effects of bavachin on LPS-activated murine macrophage cell line J774A.1 cells and murine peritoneal macrophages.

Methods: J774A.1 cells and murine peritoneal macrophages were pre-treated with bavachin following LPS treatment. The concentrations of NO, PGE, IL-6 and IL-12p40 in cell culture supernatant were analyzed. The expressions of iNOS, COX-2, mPGES-1 and MAPKs were analyzed using Western blotting, while NF-κB activity was detected using promoter reporter assay. To examine the activation of NLRP3 inflammasome, J774A.1 cells were incubated with LPS, and then treated with bavachin following treatment with ATP. The concentration of IL-1β in the cell culture supernatant was measured. The expressions of NLRP3, ASC, caspase-1 and IL-1β were analyzed using Western blotting. The formation of inflammasome complex was observed by immunofluorescence microscopy.

Results: Bavachin suppressed LPS-induced NO and PGE production, and decreased iNOS and mPGES-1 expression. Bavachin also reduced LPS-induced IL-6 and IL-12p40 production and decreased the activation of MAPKs and NF-κB. Additionally, bavachin suppressed NLRP3 inflammasome-derived IL-1β secretion, decreased caspase-1 activation, repressed mature IL-1β expression, and inhibited inflammasome complex formation. Furthermore, bavachin also suppressed the production of NO, IL-6 and IL-12p40 by LPS-stimulated murine peritoneal macrophages.

Conclusion: Our experimental results indicated anti-inflammatory effects of bavachin exhibit attenuation of LPS-induced inflammation and inhibit activation of NLRP3 inflammasome in macrophages. These results suggest that bavachin might have potential in treating inflammatory and autoimmune diseases.
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http://dx.doi.org/10.1016/j.phymed.2018.12.008DOI Listing
June 2019

Epidemiology of Depression in Patients with Psoriasis: A Nationwide Population-based Cross-sectional Study.

Acta Derm Venereol 2019 May;99(6):530-538

Department of Dermatology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.

The epidemiology of depression in patients with psoriasis has not been well defined in the Asian population. This study evaluated the epidemiological features of, and risk factors for, depression among patients with psoriasis in Taiwan. A nationwide population-based cross-sectional study was undertaken using the National Health Insurance Research Database. This study included 17,086 patients with psoriasis and 1,607,242 patients from the general population. The prevalence of depression in patients with psoriasis was 11.52%, while the prevalence of depression in the general population was 7.73% (prevalence ratio 1.49, 95% confidence interval 1.43-1.55). Multivariable analysis showed that, in patients with psoriasis, risk factors associated with depression were: age 20-50 years, female sex, low income, and major comorbid diseases, including liver cirrhosis, renal disease, cardiovascular disease and cerebrovascular disease. Therefore, the prevalence of depression is higher in patients with psoriasis, particularly in young and middle-aged women with low income and major comorbidities.
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http://dx.doi.org/10.2340/00015555-3145DOI Listing
May 2019

Comprehensive Exercise Capacity and Quality of Life Assessments Predict Mortality in Patients with Pulmonary Arterial Hypertension.

Acta Cardiol Sin 2019 Jan;35(1):55-64

Department of Physical Medicine and Rehabilitation, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.

Background: The 6-minute walk test (6MWT) and cardiopulmonary exercise test (CPET) are exercise tests associated with physical function, quality of life and hemodynamic data in patients with pulmonary arterial hypertension (PAH). This study was conducted to assess correlations between exercise capacity, quality of life and disease functional classification, and to analyze the value of comprehensive assessments in predicting mortality in patients with PAH.

Methods: Fifty-four patients with PAH were enrolled. Comprehensive assessments including exercise capacity evaluated using the 6MWT and CPET, and health-related quality of life evaluated using the Short Form 36 (SF-36) questionnaire were performed in all participants. The patients were followed for 2 years with the end point of mortality.

Results: The survivors had a longer 6-minute walking distance, higher peak oxygen uptake and higher physical component score of the SF-36 than the non-survivors. In addition, exercise capacity combined with SF-36 predicted 2-year mortality in the patients with PAH. The patients with lower peak oxygen uptake (peak VO < 11.03 mL/kg/ min) and lower physical component score (score < 44.54) had a higher mortality rate than those with a higher peak VO and higher physical component score (adjusted hazard ratio = 19.95, p = 0.011).

Conclusions: Comprehensive assessments of exercise capacity and quality of life can be used to predict 2-year mortality in patients with PAH.
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http://dx.doi.org/10.6515/ACS.201901_35(1).20180608ADOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6342835PMC
January 2019

Risk of incident gout in kidney transplant recipients: A retrospective cohort study.

Int J Rheum Dis 2018 Nov 18;21(11):1993-2001. Epub 2018 Oct 18.

Department of Public Health and Environmental Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

Aim: Gout is a common complication in kidney transplant recipients. This study evaluated the association between kidney transplant recipients and the long-term risk of incident gout.

Method: For this age-matched and sex-matched retrospective cohort study, the Catastrophic Illness Certificate Database and the National Health Insurance Research Database were combined between 1997 and 2010. The study included 5917 patients with kidney transplants and 23 668 matched kidney transplant-free subjects. Hazard ratio (HR) for risk of incident gout was calculated using the Cox proportional hazards regression.

Results: In this study, of the 5917 kidney transplant recipients, 521 (8.8%) had gout. The kidney transplant group had a higher risk of incident gout than those in the matched kidney transplant-free group (adjusted HR = 1.55, 95% confidence intervals [CI] = 1.36-1.77), particularly within 3 years following kidney transplant recipients (adjusted HR = 2.61, 95% CI = 2.13-3.20). We observed that at the >3 to 6 years and the >6 to 9 years follow-up, patients with kidney transplant did not have a significant association with risk of incident gout (adjusted HR = 0.92, P = 0.4806 and adjusted HR = 1.26, P = 0.1901, respectively).

Conclusion: These findings revealed that risk of incident gout increased within 3 years following kidney transplant recipients and the individual's long-term risk of incident gout between kidney transplant recipients and the general population remained similar.
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http://dx.doi.org/10.1111/1756-185X.13393DOI Listing
November 2018

Schizophrenia in type 2 diabetes mellitus: Prevalence and clinical characteristics.

Eur Psychiatry 2018 10 4;54:102-108. Epub 2018 Sep 4.

Department of Psychiatry, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Adult Psychiatry, Kai-Suan Psychiatric Hospital, Kaohsiung, Taiwan. Electronic address:

Background: This study investigated the prevalence and characteristics of schizophrenia in patients with type 2 diabetes mellitus (T2DM) in Taiwan.

Methods: National Health Insurance claims data for patients with principal diagnoses of schizophrenia and T2DM were analysed.

Results: Compared with patients with schizophrenia in the general population (GP), those with schizophrenia and T2DM were more likely to have higher Charlson comorbidity index (CCI) scores and multiple comorbidities, and were older. The prevalence of schizophrenia was significantly higher in patients with T2DM than in the GP from 2000 to 2010. In addition, during this period, the prevalence of schizophrenia in patients with T2DM increased from 0.64% to 0.85%; such an increase in the GP was also observed. A high prevalence of schizophrenia was observed in patients with T2DM aged less than 60 years old; those residing in eastern Taiwan; those with incomes of ≤NT$17,280, NT$17,281-NT$22,880, NT$22,881-NT$28,800, and NT$36,301-NT$45,800; and those with CCI > 2.

Conclusions: Our study found the prevalence of schizophrenia is higher in patients with T2DM than in the GP, particularly those with earlier ages less than 60 years old. Public health initiatives are necessary to prevent and treat schizophrenia in patients with T2DM, specifically for those with the aforementioned and premature death risk.
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http://dx.doi.org/10.1016/j.eurpsy.2018.08.002DOI Listing
October 2018

Metformin is associated with a lower risk of active tuberculosis in patients with type 2 diabetes.

Respirology 2018 11 25;23(11):1063-1073. Epub 2018 Jun 25.

Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.

Background And Objective: Metformin is an oral anti-diabetic therapy (ADT) to manage type 2 diabetes mellitus (T2DM), and has been reported to have potential anti-tuberculosis (TB) effects. This study investigates the risk of active TB among persons with T2DM who were treated with various ADT and insulin therapies.

Methods: We conducted a nationwide population-based cohort study using the Taiwan Longitudinal Health Insurance Database, including 49 028 T2DM patients who were metformin users (n = 44 002) or non-users (n = 5026). A total of 5026 propensity score-matched pairs of metformin users and non-users with T2DM were evaluated from 1998 to 2010. The data were analysed using Cox proportional hazard models.

Results: Patients with T2DM had a significantly higher rate of incident TB than did the control subjects (adjusted hazard ratio: 2.01; 95% confidence interval (95% CI): 1.80-2.25). After adjusting for comorbidities, diabetes complications, ADT type and statin use, metformin use was an independent factor for predicting a reduced risk of active TB (adjusted relative risk (aRR): 0.24; 95% CI: 0.18-0.32). The association between metformin use and active TB risk was also consistent in most subgroup analyses, except for patients with metabolic disorders (aRR: 0.46; 95% CI: 0.11-1.87). This protective effect of metformin was dose-dependent but diminished gradually in the elderly population.

Conclusion: Among all types of ADT and insulin therapies, metformin is the only agent with a decreased risk of active TB in the T2DM population. However, this effect was diminished in the elderly population and was not observed in patients with metabolic disorders.
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http://dx.doi.org/10.1111/resp.13338DOI Listing
November 2018

Preeclampsia-eclampsia and future cardiovascular risk among women in Taiwan.

Taiwan J Obstet Gynecol 2018 Jun;57(3):364-369

Department of Public Health and Environmental Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address:

Objective: This study aims to examine the long-term cardiovascular and cerebrovascular risks in a large cohort of women with past history of preeclampsia and/or eclampsia.

Materials And Methods: This is a retrospective longitudinal study using National Health Insurance Research Database from 1996 to 2010. We identified 1295 women with preeclampsia and eclampsia. The control group was 5180 pregnant women without preeclampsia/eclampsia, who were matched for age and date of delivery. The incidences of diabetes, dyslipidemia, hypertension and cardiovascular events after pregnancy were identified from medical records after the date of delivery to the date of an event or the end of the study.

Results: The median follow-up duration was 9.8 years (interquartile 5.1-12.7 years). The incidences of diabetes, dyslipidemia, hypertension, congestive heart failure and cerebrovascular disease events were significantly greater in women with eclampsia or preeclampsia than those in controls. Eclampsia or preeclampsia increased the risk of diabetes, dyslipidemia, hypertension, congestive heart failure and cerebrovascular disease events (hazard ratio [HR] 3.84 and 5.42, P < 0.0001; HR 2.75 and 3.40, P < 0.0001; HR 6.52 and 7.31, P < 0.0001; HR 9.07, P = 0.0060 and 7.39, P < 0.0001; HR 10.71, P < 0.0001 and 3.47, P = 0.0048, respectively). The survival curves for the development of congestive heart failure and cerebrovascular disease in women with eclampsia/preeclampsia and in control differed significantly (Log-rank test P < 0.0001). From the curve, we can find dramatic increases of congestive heart failure and cerebrovascular disease incidences at roughly 3 years and 10 years since the diagnosis of eclampsia/preeclampsia.

Conclusions: Our study revealed that women with a history of preeclampsia/eclampsia were at increased risks for subsequent diagnoses of diabetes, dyslipidemia, hypertension, congestive heart failure and cerebrovascular disease. Preventive counseling, more vigilant screening and management for the modifiable risks should be provided to the affected women. Clinicians should closely monitor these patients in the first three years postpartum and continuously for up to at least a decade.
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http://dx.doi.org/10.1016/j.tjog.2018.04.035DOI Listing
June 2018

Association of bacterial genotypes and epidemiological features with treatment failure in hemodialysis patients with methicillin-resistant Staphylococcus aureus bacteremia.

PLoS One 2018 4;13(6):e0198486. Epub 2018 Jun 4.

Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.

Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) infections in the hemodialysis (HD) population are epidemiologically classified as healthcare-associated infections. The data about the clinical impact and bacterial characteristics of hospital-onset (HO)- and community-onset (CO)-MRSA in HD patients are scarce. The current study analyzed the difference in the clinical and molecular characteristics of HO-MRSA and CO-MRSA.

Methods: We performed a retrospective review and molecular analysis of clinical isolates from 106 HD patients with MRSA bacteremia from 2009 to 2014. CA genotypes were defined as isolates carrying the SCCmec type IV or V, and HA genotypes were defined as isolates harboring SCCmec type I, II, or III.

Results: CO-MRSA infections occurred in 76 patients, and 30 patients had HO-MRSA infections. There was no significant difference in the treatment failure rates between patients with CO-MRSA infections and those with HO-MRSA infections. CA genotypes were associated with less treatment failure (odds ratio [OR]: 0.18; 95% confidence interval [95% CI], 0.07-0.49; p = 0.001). For isolates with a vancomycin minimum inhibitory concentration (MIC) < 1.5 mg/L, the multivariate analysis revealed that HA genotypes and cuffed tunneled catheter use were associated with treatment failure. For isolates with a vancomycin MIC ≥1.5 mg/L, the only risk factor for treatment failure was a higher Pitt score (OR: 1.76; 95% CI, 1.02-3.05; p = 0.043).

Conclusion: CA genotypes, but not the epidemiological classification of CO-MRSA, impacted the clinical outcome of MRSA bacteremia in the HD population.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0198486PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5986133PMC
December 2018

Risk of incident benign prostatic hyperplasia in patients with gout: a retrospective cohort study.

Prostate Cancer Prostatic Dis 2018 06 1;21(2):277-286. Epub 2018 Jun 1.

Department of Public Health and Environmental Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

Background: This retrospective cohort study evaluated the association between gout and the risk of benign prostatic hyperplasia among men by using data from Taiwan's National Health Insurance Research Database.

Methods: Population-based representative insurance (outpatient and inpatient) claims data of 29,269 patients with gout and 29,269 matched patients without gout (1:1 ratio) for the period of 1997-2010 in Taiwan were identified. The association between gout and benign prostatic hyperplasia was evaluated using the Cox proportional hazards model. The associations of age by gout and gout phenotypes with benign prostatic hyperplasia risk were estimated.

Results: Patients with gout had a higher incidence rate of benign prostatic hyperplasia than those in the matched gout-free group (19.62 vs. 10.11 events per 1000 person-years). Compared with the gout-free group, the adjusted hazard ratios (HRs) (95% confidence intervals (CIs)) for benign prostatic hyperplasia were 1.30 (1.24-1.36). The gout-to-benign prostatic hyperplasia association was modified by age (P < 0.0001) in gout patients the age groups of 20-40 years (adjusted HR 2.74, P < 0.0001) and 41-60 years (adjusted HR 1.39, P < 0.0001) but not in the age group of >60 years (adjusted HR 1.07, P = 0.063). Compared with gouty tophi, a higher risk of benign prostatic hyperplasia was noted in gouty nephropathy (adjusted HR 1.30, 95% CI 1.12-1.50).

Conclusions: Our results suggest that male gout is positively related to benign prostatic hyperplasia, particularly in young gout patients and those with gouty nephropathy.
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http://dx.doi.org/10.1038/s41391-018-0047-8DOI Listing
June 2018

RNA-seq transcriptome analysis of breast cancer cell lines under shikonin treatment.

Sci Rep 2018 02 8;8(1):2672. Epub 2018 Feb 8.

Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan.

Shikonin is a naphthoquinone isolated from the dried root of Lithospermum erythrorhizon, an herb used in Chinese medicine. Although several studies have indicated that shikonin exhibits antitumor activity in breast cancer, the mechanism of action remains unclear. In the present study, we performed transcriptome analysis using RNA-seq and explored the mechanism of action of shikonin in regulating the growth of different types of breast cancer cells. The IC of shikonin on MCF-7, SKBR-3 and MDA-MB-231 cells were 10.3 μΜ, 15.0 μΜ, 15.0 μΜ respectively. Our results also demonstrated that shikonin arrests the progression of cell cycle and induces apoptosis in MDA-MB-231 cells. Using RNA-seq transcriptome analysis, we found 38 common genes that significantly express in different types of breast cancer cells under shikonin treatment. In particular, our results indicated that shikonin induces the expression of dual specificity phosphatase (DUSP)-1 and DUSP2 in both RNA and protein levels. In addition, shikonin also inhibits the phosphorylation of JNK and p38, the downstream signaling molecules of DUSP1 and DUSP2. Therefore, our results suggest that shikonin induces the expression of DUSP1 and DUSP2 which consequently switches off JNK and p38 MAPK pathways and causes cell cycle arrest and apoptosis in breast cancer cells.
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http://dx.doi.org/10.1038/s41598-018-21065-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5805692PMC
February 2018

Association between bipolar disorder and subsequent traumatic brain injury in patients who received inpatient treatment.

Psychiatry Res 2018 03 10;261:517-521. Epub 2018 Jan 10.

Department of Psychiatry, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Psychiatry, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address:

Mental disorders may confer a high risk of traumatic brain injury, but only rare studies have investigated mood disorders. This nationwide cohort study compared the risk of traumatic brain injury in patients with and without bipolar disorder. We compared 1017 patients with bipolar disorder who received inpatient treatment and 9080 compared patients. The annual incidence rate of traumatic brain injury was calculated as the number of new cases divided by the total number of person-years in the available records. The incidence of subsequent traumatic brain injury was significantly higher in the bipolar group than in control group. The adjusted hazard ratio for those with multiple hospitalizations was higher than the counterpart. Except for patients in the 50-59-year age group, those in all other age groups had higher risks of traumatic brain injury. Our findings reveal a higher risk of traumatic brain injury in patients with bipolar disorder. Patients with recurrent hospitalization and multiple psychotropic use had an increased risk of traumatic brain injury. Age may modify the risk of traumatic brain injury, with a higher risk in middle-aged patients.
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http://dx.doi.org/10.1016/j.psychres.2017.12.061DOI Listing
March 2018

Variants of ALPK1 with ABCG2, SLC2A9, and SLC22A12 increased the positive predictive value for gout.

J Hum Genet 2018 Jan 8;63(1):63-70. Epub 2017 Nov 8.

Environment-Omics-Disease Research Center, China Medical University Hospital, China Medical University, Taichung, 40402, Taiwan.

We investigated the interactions of ALPK1 variants and the loci of ABCG2, SLC2A9, and SLC22A12 on gout risk. We conducted two case-control studies. Participants were recruited from hospitals (n = 410; 104 gout cases and 306 controls) and communities (n = 678; 373 gout cases and 305 controls) in Taiwan. The genotypes of ALPK1 (rs11726117 M861T, rs231247 R1084R, and rs231253 3' UTR), ABCG2 (rs2231142 Q141K and rs2231137 V12M), SLC2A9 (rs3733591 R265H and rs1014290), and SLC22A12 (rs3825016 H86H, rs11231825 H142H, and rs475688) were genotyped. Under a recessive model, the joint effects of ALPK1 variants and the SNPs rs2231142 of ABCG2, rs1014290 of SLC2A9, or rs475688 and rs3825016 of SLC22A12 were associated with gout. The rs11726117 [CC] of ALPK1 and rs2231142 [TT] of ABCG2 with the sequential addition of the rs1014290 [AA] of SLC2A9 and rs3825016 [CC] of SLC22A12 were associated with gout risk (odds ratio (OR): 13.01, 15.11, and 55.00 and positive predictive value (PPV): 56%, 69%, and 99% in the Han group, respectively; OR: 3.76, 5.78, and 12.30 and PPV: 74%, 80%, and 81% in the aboriginal group, respectively). Combined exposure to the four high-risk genotypes of ALPK1 and the uric-acid-related loci of ABCG2, SLC2A9, and SLC22A12 was associated with an increased gout risk and a high PPV for gout.
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http://dx.doi.org/10.1038/s10038-017-0368-9DOI Listing
January 2018