Limited effect of reducing pulmonary tuberculosis incidence amid mandatory facial masking for COVID-19.

Although the incidence and mortality rates associated with tuberculosis (TB) have been decreasing in many countries, TB remains a major public health concern. Obligatory facial masking and reduced health-care capacity because of COVID-19 may substantially influence TB transmission and care. The Global Tuberculosis Report 2021 published by the World Health Organization indicated a TB rebound at the end of 2020, which coincided with the COVID-19 pandemic. We explored this rebound phenomenon in Taiwan by investigating whether TB incidence and mortality are affected by COVID-19 because of their common route of transmission. In addition, we investigated whether the incidence of TB varies across regions with different incidences of COVID-19. Data (2010-2021) regarding annual new cases of TB and multidrug-resistant TB were collected from the Taiwan Centers for Disease Control. TB incidence and mortality were assessed in Taiwan's seven administrative regions. Over the last decade, TB incidence decreased continually, even during 2020 and 2021, the years coinciding with the COVID-19 pandemic. Notably, TB incidence remained high in regions with low COVID-19 incidence. However, the overall decreasing trends of TB incidence and mortality remained unchanged during the pandemic. Facial masking and social distancing may prevent COVID-19 transmission but exhibit limited efficacy in reducing TB transmission. Thus, during health-related policymaking, policymakers must consider TB rebound, even in the post-COVID-19 era.

Medications for Chronic Conditions and Mortality in Older Adults.

BACKGROUND: With the population aging, examining the relationship between polypharmacy and mortality based on population data sources is important for clinical management and policy direction. OBJECTIVES: This study aimed to examine the association between the number of chronic medications and the risk of mortality in older adults. METHODS: This population-based retrospective cohort study used data from the National Health Insurance Research Database in Taiwan for information regarding chronic medication use (over 4 years) in older adults aged 65 years and older. The association between medication use and mortality numbers was analyzed using Cox proportional hazards regression models adjusted for demographic variables and comorbidity. RESULTS: The number of medications was significantly associated with high mortality risk. Within polypharmacy, being 65-74 years old, male, living in northern Taiwan, having one type of comorbid disease, and receiving <84 days of refillable chronic prescription were associated with greater mortality risk. Subgroup analyses' results regarding comorbidity showed significant positive associations between the number of medications and mortality in most comorbid diseases except for mental disorders and diseases of the skin and subcutaneous tissue. DISCUSSION: General practitioners should know that chronic polypharmacy is associated with increased mortality risk. Recognizing the possible adverse effects of multiple medication use could help physicians optimize drug regimens in the future.

Exploring the association of metal mixture in blood to the kidney function and tumor necrosis factor alpha using machine learning methods.

This research aimed to approach relationships between metal mixture in blood and kidney function, tumor necrosis factor alpha (TNF-α) by machine learning. Metals levels were measured by Inductively Couple Plasma Mass Spectrometry in blood from 421 participants. We applied K Nearest Neighbor (KNN), Naive Bayes classifier (NB), Support Vector Machines (SVM), random forest (RF), Gradient Boosting Decision Tree (GBDT), Categorical boosting (CatBoost), eXtreme Gradient Boosting (XGBoost), Whale Optimization-based XGBoost (WXGBoost) to identify the effect of plasma metals, TNF-α, and estimated glomerular filtration rate (eGFR by CKD-EPI equation). We conducted not only toxic metals, lead (Pb), arsenic (As), cadmium (Cd) but also included trace essential metals, selenium (Se), copper (Cu), zinc (Zn), cobalt (Co), to predict the interaction of TNF-α, TNF-α/white blood count, and eGFR. The high average TNF-α level group was observed among subjects with higher Pb, As, Cd, Cu, and Zn levels in blood. No associations were shown between the low and high TNF-α level group in blood Se and Co levels. Those with lower eGFR group had high Pb, As, Cd, Co, Cu, and Zn levels. The crucial predictor of TNF-α level in metals was blood Pb, and then Cd, As, Cu, Se, Zn and Co. The machine learning revealed that As was the major role among predictors of eGFR after feature selection. The levels of kidney function and TNF-α were modified by co-exposure metals. We were able to acquire highest accuracy of over 85% in the multi-metals exposure model. The higher Pb and Zn levels had strongest interaction with declined eGFR. In addition, As and Cd had synergistic with prediction model of TNF-α. We explored the potential of machine learning approaches for predicting health outcomes with multi-metal exposure. XGBoost model added SHAP could give an explicit explanation of individualized and precision risk prediction and insight of the interaction of key features in the multi-metal exposure.

The Incident Ocular Diseases Related to Chemotherapy in Cancer Patients are Associated with Increasing Risk of Incident Stroke.

Background: In addition to cardiotoxicity, ocular toxicity induced by chemotherapeutic agents is not uncommon. Objective: This study aimed to explore the association between ocular adverse events and major adverse cardiovascular events (composite endpoint) caused by chemotherapy, and whether specific ocular events could be potential predictors of some specific components of the composite endpoint. Methods: A total of 5378 newly diagnosed patients (age > 18 y/o) with any malignancy or metastatic solid tumors who received chemotherapy from January 1997 to December 2010 were enrolled from the Taiwan National Health Insurance Research Database. Patients who developed new incident ocular diseases were classified as the study group, and those who did not develop incident ocular diseases as the control group. Results: After propensity score matching, there was a significant increase in the incidence of stroke in the ocular diseases group compared to the no ocular diseases group (13.4% vs. 4.5%, p < 0.0001). Tear film insufficiency, keratopathy, glaucoma, and lens disorders were associated with a significantly higher risk of stroke. A longer duration of methotrexate and a longer duration with higher total amount of tamoxifen were associated with both incident ocular diseases and incident stroke. Cox proportional hazards regression showed that the only independent risk factor for stroke was incident ocular diseases [Adjusted relative risk (95% confidence interval): 2.96 (1.66-5.26), p = 0.0002]. In addition, incident ocular disease was the most significant risk factor compared with other traditional cardiovascular risk factors. Conclusions: Incident ocular diseases related to chemotherapy were associated with a significantly higher risk of stroke.

Perineural Invasion is a Powerful Prognostic Factor for Upper Tract Urothelial Carcinoma Following Radical Nephroureterectomy.

BACKGROUND: Taiwan has the highest incidence of upper tract urothelial carcinoma (UTUC) worldwide. Although many pathological factors can predict the prognosis of UTUC, previous studies have rarely discussed perineural invasion (PNI). Therefore, we aimed to investigate the effect of PNI on a well-established cohort of patients with UTUC. METHODS: This retrospective study included 803 patients with non-metastatic UTUC who underwent radical nephroureterectomy between June 2000 and August 2019. Demographic and clinicopathological parameters, including PNI, were collected for analysis. Using the Kaplan-Meier method and Cox proportional hazards model, we evaluated the significance of PNI with respect to progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS). RESULTS: The median follow-up was 30.9 months, and there were 83 cases of PNI (10.3%). PNI-positive patients had unfavorable pathological features, including high pT stage, positive lymph node involvement, high tumor grade, and more lymphovascular invasion (all p < 0.001). Kaplan-Meier analysis showed that PNI was significantly associated with PFS, CSS, and OS (all p < 0.00001), and when combined with lymphovascular invasion, patients could be divided into groups with distinct survival rates (all p < 0.00001). In multivariate analysis, PNI was an independent factor leading to worse PFS (hazard ratio [HR] 1.72, 95% confidence interval [CI] 1.19-2.50; p = 0.004), CSS (HR 2.54, 95% CI 1.58-4.10; p = 0.0001), and OS (HR 1.78, 95% CI 1.19-2.65; p = 0.005). CONCLUSIONS: We demonstrated an association between PNI and the prognosis of UTUC. Routine assessment of PNI in UTUC with standardized protocols may help achieve better risk stratification and subject selection for perioperative treatment.

Associations and Interactions between Heavy Metals with White Blood Cell and Eosinophil Count.

The accumulation of heavy metals in the body has been associated with an elevated immune response. The aim of this study was to investigate the associations among heavy metals and white blood cell (WBC) and eosinophil count in the general population in southern Taiwan. We also explored the interactions and synergetic effects of heavy metals on WBC and eosinophil count. 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 cadmium (Cd), copper (Cu), nickel, arsenic (As), chromium and manganese (Mn). A total of 2,447 participants were enrolled. In multivariable analysis, high concentrations of Pb (log per 1 mg/L; coefficient ß, 0.332; p = 0.005) and Cu (log per 1 µg/dL; coefficient ß, 0.476; p < 0.001) were significantly associated with a high WBC count. In addition, high concentrations of Pb (log per 1 mg/L; coefficient ß, 0.732; p < 0.001), As (log per 1 µg/L; coefficient ß, 0.133; p = 0.015), Cu (log per 1 µg/dL; coefficient ß, 0.181; p = 0.018), and Cd (log per 1 µg/L; coefficient ß, 0.139; p = 0.002) were significantly associated with a high eosinophil count. Further, the effect of interactions between Pb and As (coefficient ß, 0.721; p = 0.029) and Mn and Cu (coefficient ß, 0.482; p = 0.018) on WBC count, and As and Cu (unstandardized coefficient ß, 0.558; p = 0.002) on eosinophil count were statistically significant. In conclusion, the heavy metals Pb, As, Cu, and Cd were associated with WBC and eosinophil count. In addition, synergistic effects of heavy metal poisoning on the association with WBC and eosinophil count were also observed.

The Expression and Prognostic Value of Cancer Stem Cell Markers, NRF2, and Its Target Genes in TAE/TACE-Treated Hepatocellular Carcinoma.

Background and Objectives: Activation of NRF2, a key transcription factor of cytoprotectant against oxidative stress, and its target genes are associated with aggressive tumor progression, metastasis and poor survival. In addition, NRF2 signaling mediates cancer stem cell (CSC)-like properties in hepatocellular carcinoma (HCC) cells. Moreover, CSCs have been associated with HCC onset and unfavorable prognosis. Transcatheter arterial embolization (TAE) and/or transcatheter arterial chemoembolization (TACE), which attempt to restrict blood supply to diminish tumor growth, can create a hypoxic environment. However, its effect on NRF2 signaling and CSC marker CD133 in the context of prognosis of HCCs have not been investigated. Therefore, we studied the possible role of the expressions of NRF2, its target genes and CSC markers CD133 and EpCAM on the survival of HCC patients after TAE/TACE. Materials and Methods: RT-qPCR was performed with 120 tumor (T) and adjacent tumor (N) tissue pairs. Expression of a single marker or combination was assessed for associations with survival of HCC patients after TAE/TACE. Results: The result of multivariate Cox regression showed that vascular invasion (HR, 1.821; p = 0.015), metastasis (HR, 2.033; p = 0.049) and CD133 overexpression (HR, 2.013; p = 0.006) were associated with poor survival. In a Kaplan-Meier survival analysis, patients with high expression of CD133 had shorter overall survival (OS) than those with low expression of CD133 in post-TAE/TACE HCC (p < 0.001). In contrast, neither NRF2 nor components of its signaling pathway correlated with survival. Combination marker analysis showed that co-expression of NQO1 and CD133 was associated with poor outcome. Conclusions: This study suggests that analyzing the expression status of CD133 alone and co-expression of NQO1 and CD133 may have additional value in predicting the outcome of TAE/TACE-treated HCC patients.

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

The Clinical and Laboratory Standards Institute (CLSI) revised the fluoroquinolone MIC breakpoints for Enterobacterales 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 Enterobacterales 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 (n = 63) had a significantly lower survival rate than those infected with low-MIC isolates (n = 245) (P = 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; P = 0.011). We consistently found similar results in a propensity score-matched cohort (OR, 5.38; 95% CI, 1.06 to 27.39; P = 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%; P = 0.065). An estimated area under the concentration-time curve/MIC ratio of ≥87 was significantly associated with better survival (P = 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.

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

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.

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

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 (Ptrend = .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.

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

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.

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

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.

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

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 VO2 < 11.03 mL/kg/ min) and lower physical component score (score < 44.54) had a higher mortality rate than those with a higher peak VO2 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.

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

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.

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

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.

URAT1 inhibition by ALPK1 is associated with uric acid homeostasis.

Objective: The aim of this study was to identify a protein for urate transporter 1 (URAT1) regulation. Methods: The clinical dataset consisted of 492 case-control samples of Han Chinese (104 gout and 388 controls). Three alpha kinase 1 ( ALPK1 ) and SLC22A12 loci associated with high gout risk and uric acid levels were genotyped. The overexpression of ALPK1 on URAT1 protein expression was evaluated in vivo in h ALPK1 transgenic mice. The in vitro protein levels of ALPK1 and URAT1 in ALPK1 small interfering RNA-transfected human kidney-2 cells with MSU crystal stimulation were examined. Results: ALPK1 , which is a single nucleotide polymorphism (SNP) of rs11726117 (M861T; T), reduced the risk of gout via the SLC22A12 gene SNPs rs3825016 and rs475688, as compared with the subject of ALPK1 rs11726117 (C) allele {rs11726117 [CT + TT] vs rs3825016, odds ratio [OR] 0.39 [95% confidence interval (CI) 0.23, 0.67]; rs11726117 [CT + TT] vs rs475688, OR 0.39 [95% CI 0.23, 0.67]}. ALPK1-overexpressed mice demonstrated lower levels of URAT1 protein ( P = 0.0045). Mouse endogenous ALPK1 proteins were detected in renal proximal tubule cells. MSU crystals inhibited URAT1 expressions through an upregulation of ALPK1 in human kidney-2 cells. Conclusion: Elevated ALPK1 expression decreased URAT1 expression. ALPK1 might prevent the impact of urate reuptake via SLC22A12 and appeared to be negatively associated with gout. ALPK1 is a potential repressor of URAT1 protein expression.

Prevalence of Depressive Disorder in Persons With Type 2 Diabetes: A National Population-Based Cohort Study 2000-2010.

BACKGROUND: Diabetes mellitus, a chronic and disabling disease, is epidemic worldwide. Depressive disorder affects the productivity of workers and leads to disability. OBJECTIVE: This study investigated the prevalence of depressive disorder among persons with type 2 diabetes in Taiwan. METHODS: We extracted service claims data for subjects who had at least 2 ambulatory care service claims or 1 inpatient service claim with a principal diagnosis of type 2 diabetes and at least 1 ambulatory or inpatient service claim with a principal diagnosis of depressive disorder from Taiwan's National Health Insurance Database. RESULTS: From 2000-2010, the prevalence of depressive disorder increased from 3.50-4.07% in people with type 2 diabetes, and from 1.05-2.27% in the general population. The higher prevalence of depressive disorder in persons with type 2 diabetes was associated with being female; residence in central, southern, and eastern Taiwan; residence in urban areas; the comorbidities of hemiplegia or paraplegia, cerebrovascular disease, and anxiety disorder; Charlson Comorbidity Index scores ≥1; diabetes duration >9 years; and the use of rapid-acting insulin injection therapy. CONCLUSIONS: The prevalence of depressive disorder is higher among persons with type 2 diabetes than the general population. Consequently, more public health attention should be devoted to the prevention and treatment of this debilitating disease in persons with type 2 diabetes, especially those with the earlier mentioned risk factors.

Prevalence of anxiety disorder in patients with type 2 diabetes: a nationwide population-based study in Taiwan 2000-2010.

This study investigates the prevalence of anxiety disorder (AD) in Taiwanese patients with type 2 diabetes (T2D). Study participants were identified based on at least one service claim for ambulatory or inpatient care with a principal diagnosis of AD and at least 2 service claims for ambulatory care or one service claim for inpatient care with a principal diagnosis of T2D, as listed in the National Health Insurance database of Taiwan. The prevalence of AD decreased from 13.75 to 11.00 % in patients with T2D, whereas it increased from 4.17 to 6.09 % in the general population during the 2000-2010 period. A high prevalence of AD in patients with T2D was associated with age >30 years, the female sex, living in the northern region, comorbidities of congestive heart failure, peripheral vascular disease, cerebrovascular disease, and depression disorder, and a Charlson participant comorbidity index of ≥1. A low prevalence of AD in patients with T2D was associated with residency in urban areas, the comorbidity of hemiplegia or paraplegia, the usage of metformin and sulfonylureas, and rapid-acting insulin injection therapy. The prevalence of AD was higher in patients with T2D than in the general population. Therefore, more public health emphasis is required for preventing and treating AD in patients with T2D, specifically those with the mentioned risk factors.

Additive composite ABCG2, SLC2A9 and SLC22A12 scores of high-risk alleles with alcohol use modulate gout risk.

The aim of the present study was to evaluate the contribution of urate transporter genes and alcohol use to the risk of gout/tophi. Eight variants of ABCG2, SLC2A9, SLC22A12, SLC22A11 and SLC17A3 were genotyped in male individuals in a case-control study with 157 gout (33% tophi), 106 asymptomatic hyperuricaemia and 295 control subjects from Taiwan. The multilocus profiles of the genetic risk scores for urate gene variants were used to evaluate the risk of asymptomatic hyperuricaemia, gout and tophi. ABCG2 Q141K (T), SLC2A9 rs1014290 (A) and SLC22A12 rs475688 (C) under an additive model and alcohol use independently predicted the risk of gout (respective odds ratio for each factor=2.48, 2.03, 1.95 and 2.48). The additive composite Q141K, rs1014290 and rs475688 scores of high-risk alleles were associated with gout risk (P<0.0001). We observed the supramultiplicative interaction effect of genetic urate scores and alcohol use on gout and tophi risk (P for interaction=0.0452, 0.0033). The synergistic effect of genetic urate score 5-6 and alcohol use indicates that these combined factors correlate with gout and tophi occurrence.

The Prognostic Significance of Inflammation-Associated Blood Cell Markers in Patients with Upper Tract Urothelial Carcinoma.

BACKGROUND: Inflammation-related parameters based on blood cells, including white blood cell (WBC) count, neutrophil-lymphocyte ratio, platelet count, and red cell distribution width (RDW), have been shown to be associated with prognosis in many cancers. However, no previous study evaluated these inflammation-associated markers simultaneously in upper tract urothelial carcinoma (UTUC). METHODS: A total of 195 patients with UTUC who received radical nephroureterectomy between 2005 and 2010 were included retrospectively as the derivation cohort to investigate the impact of inflammation markers on overall survival (OS) and cancer-specific survival (CSS). In turn, another independent set of 225 patients were used for validation. Finally, we performed survival analysis in the combined cohort consisting of 420 UTUC patients. RESULTS: The predictive value of RDW and WBC count on outcome was replicable in different cohorts. Multivariate analysis showed high RDW was independently associated with poor OS (P < 0.001), and WBC count was a significant prognosticator for both OS and CSS (both P < 0.001). In subgroup analysis, we found the prognostic significance of RDW for OS was limited in organ-confined disease (≤pT2 without pN+). More importantly, a clear survival difference can be demonstrated by combining RDW and WBC count with other known prognostic factors in the risk stratification model. CONCLUSIONS: RDW and WBC count have the advantage of their common accessibility and are useful markers to predict outcome of UTUC in the preoperative setting. RDW and WBC count could provide additional prognostic value and help physicians identify patients at high risk for mortality and formulate individualized treatment strategy.