Search

Aims/Introduction The convergence of tuberculosis (TB) and diabetes mellitus (DM) is a new challenge in Asia as a result of the rising prevalence of diabetes mellitus with higher TB infection rates, and also because diabetes mellitus itself enhances TB disease activity and consequently the spread of TB. We aimed to address the risk presented by diabetes mellitus for TB infection. Materials and Methods Patients with diabetes mellitus were retrospectively recruited. The baseline assessments included age, sex, body mass index, fasting blood glucose, glycated hemoglobin, urine albumin‐to‐creatinine ratio and estimated glomerular filtration rate. TB was determined by meeting the international classification of disease, for TB diagnosis and receiving anti‐TB treatment for at least 2 months. Results In total, 9,750 individuals with diabetes mellitus were recruited. The event rate of TB was 47 (0.48%). Younger age, lower proportion of men, higher fasting blood glucose and glycated hemoglobin values, and better renal function (estimated glomerular filtration rate and urine albumin‐to‐creatinine ratio) were observed in the metformin‐exposed groups. Old age and male sex were associated with higher TB infection risk on multivariate analysis. Metformin users had a significantly lower risk for TB infection, whereas insulin users had a higher risk for TB infection. However, glycemic status had no effect on TB infection risk. Conclusions This study provides clinical evidence from a survey of TB in individuals with diabetes mellitus. Old age, male sex and insulin use were risk factors for TB infection. Metformin remains the first choice of treatment for diabetes mellitus and has a potential protective effect against TB infection.

Chronic Kidney Disease (CKD) and neurodegenerative diseases are aging-related diseases. CKD with declined renal function is associated with an elevation of circulating indoxyl sulfate, a metabolite synthesized by gut microbes. We explored the roles of gut microbial metabolites in linking with Central Nervous System (CNS) diseases by administrating indoxyl sulfate intraperitoneally to male C57BL/6 mice with unilateral nephrectomy. Upon exposure, the accumulation of indoxyl sulfate was noted in the blood, prefrontal cortical tissues, and cerebrospinal fluid. Mice showed behavioral signs of mood disorders and neurodegeneration such as anxiety, depression, and cognitive impairment. Those behavioral changes were accompanied by disturbed neuronal survival, neural stem cell activity, expression of Brain-Derived Neurotrophic Factor, serotonin, corticosterone, and Repressor Element-1 Silencing Transcription Factor, and post-receptor intracellular signaling, as well as upregulated oxidative stress and neuroinflammation. Uremic toxin adsorbent AST-120 improved the above mentioned changes. Intriguingly, intracerebroventricular indoxyl sulfate administration only caused limited alterations in the normal mice and the alterations were reversed by aryl hydrocarbon receptor antagonism. The findings suggest pathogenic roles of indoxyl sulfate in the development of CNS diseases, and highlight gut microbiota as alternative targets for intervention with the aim of slowing down the progression of CKD and decreasing CNS complications.

Background Angiotensin receptor blockers (ARBs) have been reported to ameliorate anxiety and mood disorders in animal models. Cohort links between ARB use and suicide risk in humans require clarification. Methods Data were obtained from the National Health Insurance Research Database. Patients diagnosed as having hypertension according to the criteria of the International Classification of Diseases, Ninth Revision, Clinical Modification (401-405) from January 1, 2000 to December 31, 2012 were enrolled as the target population. We defined enrollees who had received ARB prescriptions for at least 28 days as ARB users. Those who had never taken ARB prior or during the study period were defined as ARB nonusers and were propensity score–matched with ARB users. The end outcome was confirmation of a suicide attempt. Results After propensity score matching was conducted, 40,976 ARB users and 40,976 nonusers were selected as the matched cohorts. The overall incidence rate of suicide attempt was significantly lower in ARB users than in nonusers (0.51 vs. 1.07 per 10,000 person-years; adjusted hazard ratio = 0.48, 95% confidence interval = 0.26–0.87). A Kaplan–Meier survival analysis with a log-rank test revealed a lower cumulative incidence of suicide attempt in ARB users than in nonusers (p Conclusions ARB use was not associated with an increased risk for suicide compared with non-ARB use.

The cellular and molecular mechanisms underlying leptin-mediated brain protection against cerebral ischemia were investigated at the blood-brain barrier (BBB) and neutrophil level. Through the ischemia/reperfusion (I/R) animal model, we found that leptin expression level was significantly decreased in ischemic hemisphere. Brain injection with leptin (15 μg/kg, intracisternally) could block the I/R-increased BBB permeability, activation of matrix metallopeptidase 9 (MMP-9) and brain infiltration of blood-borne neutrophils to reduce the infarct volume of ischemic brain. The brain expression level of tight junction protein ZO-1 as well as number and motility of neutrophils in blood was all increased by the same injection, indicating BBB stability (rather than reduction in neutrophils) played a major role in the leptin-inhibited brain infiltration of neutrophils. Leptin-mediated protection of BBB was further confirmed in vitro, through a BBB cellular model under the in vitro ischemic condition (G/R: glucose-oxygen-serum deprivation followed by GOS restoration). The results showed that leptin again could block the G/R-increased neutrophil adherence to EC layer as well as BBB permeability, likely by stimulating the endothelial expression of ZO-1 and VE-Cadherin. The study has demonstrated that leptin could protect ischemic brain via multiple ways (other than neuronal protection), by inhibiting the BBB permeability, brain infiltration of the blood-borne neutrophils and neutrophil adherence to vascular ECs. The role of leptin in vascular biology of stroke could further support its therapeutic potential in other neurodegenerative diseases, associated with BBB disorder.

Background We hypothesized that renin–angiotensin system (RAS) blockers have systemic protective effects beyond the respiratory tract and could reduce the risk of viral infections. Methods We used the National Health Insurance Research Database and identified 2 study cohorts: the angiotensin receptor blocker (ARB) cohort and angiotensin-converting enzyme inhibitor (ACEI) cohort. Propensity score matching was applied at a 1:1 ratio by all associated variables to select 2 independent control cohorts for the ARB and ACEI cohorts. A Cox proportional hazards model was applied to assess the end outcome of viral infection. Results The number of ARB and ACEI users was 20 207 and 18 029, respectively. The median age of ARB users and nonusers was 53.7 and 53.8 years, respectively. The median follow-up duration of ARB users and nonusers was 7.96 and 7.08 years; the median follow-up duration of ACEI users and nonusers was 8.70 and 8.98 years, respectively. The incidence rates of viral infections in ARB users and nonusers were 4.95 and 8.59 per 1000 person-years, respectively, and ARB users had a lower risk of viral infection than nonusers (adjusted hazard ratio [aHR], 0.53 [95% confidence interval {CI}, .48–.58]). The incidence rates of viral infections in ACEI users and nonusers were 6.10 per 1000 person-years and 7.72 per 1000 person-years, respectively, and ACEI users had a lower risk of viral infection than nonusers (aHR, 0.81 [95% CI, .74–.88]). Conclusions Hypertensive patients using either ARBs or ACEIs exhibit a lower risk of viral infection than nonusers.

Objective: Better glycemic control for hospitalized diabetic patients significantly reduces health expenditures and improves disease outcomes. We developed a dynamic dashboard with a remote management system and evaluated its impact on inpatient glycemic control. Methods: This was an observational institution-wide study; study participants were enrolled from a 1,500-bed public medical center from 2016 to 2018. We evaluated the impact of a dynamic dashboard system, which analyzed and monitored all glucose data with virtual glycemic management recommendation by a team of endocrinologists, over 3 × 1-year periods: 2016 (pre-implementation), 2017 (development), and 2018 (implementation). Results: A total of 51,641 discharges with 878,159 blood glucose measurements were obtained during the 3-year period. After implementation of the dashboard system, the proportion of patients with poor glycemic control (hyperglycemia or hypoglycemia) was reduced by 31% (from 10.2 to 7.0 per day per 100 patients with glucose monitoring; P Conclusion: We successfully installed a dynamic, electronic medical records-based dashboard monitoring system to improve inpatient glycemic control. The system, supported by a team of endocrinologists via remote recommendations, could efficiently fill an important need for improved glycemic management among hospitalized adults. Abbreviations: CDE = certified diabetes educator; DM = diabetes mellitus; EMR = electronic medical record; POC = point-of-care; TCVGH = Taichung Veterans General Hospital; UCSF = University of California, San Francisco; U.S. = United States; vGMS = virtual glucose management service

Purpose To assess the relationship between changes in abdominal adipose tissue and metabolic syndrome (MetS) in men with obesity after a weight reduction program (WRP). Patients and Methods Adult men with obesity and MetS were recruited for this prospective single-arm intervention study. Participants consumed an energy-restricted diet of 1200 kcal/day and performed 50-mins aerobic exercise daily for 12 weeks. Changes in the components of MetS were recorded. Changes in subcutaneous abdominal fat area (SAFA) and intra-abdominal fat area (IAFA) at the umbilicus level were determined using magnetic resonance imaging. Results A total of 30 men (mean age, 42.3 ± 10.0 years; body mass index, 33.7 ± 4.1 kg/m2) were included in this study. A moderate (8.0%) weight reduction occurred. Reversion of MetS was observed in 15 (50%) participants after the WRP. There was significant reduction in SAFA (68.3 ± 20.2 vs. 51.5 ± 18.6 cm2; P < 0.001) and IAFA (96.3 ± 15.6 vs. 86.0 ± 16.5 cm2; P < 0.001); the magnitude of reduction was greater for SAFA than for IAFA (-16.8 ± 7.7 vs. -10.3 ± 8.3 cm2; P < 0.001). Multivariate logistic regression analysis showed a reduction in IAFA to be an independent factor to decrease the risk of persistent MetS after WRP by adjustment for age, baseline IAFA, and change in SAFA (odds ratio = 0.25, 95% confidence interval: 0.07-0.95, P = 0.041). Reduction in SAFA was not significantly associated with the reversion of MetS (P = 0.411). Conclusion Reduction in IAFA via a 12-week WRP may help reverse MetS in men with obesity and MetS.

Background We aimed to identify associations between the risk of acute respiratory failure (ARF) and types of antihypertensive agents in patients with viral pneumonia. Methods In this case-control study, data extracted from the Taiwan National Health Insurance Research Database were analysed. The base population comprised patients with viral pneumonia treated from 2000 to 2013. The case group comprised patients with ARF and the control group comprised participants without ARF. Adjusted odds ratios (ORs) were calculated using a multivariable logistic regression model. Results In total, 4427 viral pneumonia patients with ARF and 4427 matched control participants without ARF were recruited. Patients with diabetes, alcohol-related disease, asthma, chronic kidney disease or end-stage renal disease, chronic obstructive pulmonary disease, cancer, congestive heart failure, stroke, acute pulmonary oedema and shock had increased odds of developing ARF, especially shock (adjusted OR = 49.3; 95% CI = 27.4, 88.7), cancer (12.6; 8.67, 18.2) and stroke (7.51; 5.32, 10.6). Increasing odds of developing ARF were noted in patients using potassium-sparing diuretics (2.95; 1.54, 5.64), loop diuretics (68.2; 48.1, 96.6), calcium channel blockers (1.64; 1.26, 2.13) and angiotensin-converting enzyme inhibitors (1.70; 1.15, 2.53). Patients with prescriptions of α-blockers (0.44; 0.26, 0.74), β-blockers (0.37; 0.26, 0.52), thiazides (0.38; 0.25, 0.59) and angiotensin receptor blockers (0.65; 0.51, 0.83) had lower odds of having ARF. Conclusion Patients with viral pneumonia who received α-blockers, β-blockers, thiazides or angiotensin receptor blockers during hospitalisation had a lower risk of developing ARF.

Background: Air pollution is speculated to affect the reproductive health of women. However, a longitudinal association between exposure to air pollution and dysmenorrhea has not been identified, which this study aimed to examine this point.Methods: Two nationwide databases, namely the Taiwan Air Quality Monitoring database and the Taiwan National Health Research Institutes database were linked. Women with a history of dysmenorrhea (International Classification of Disease, Ninth Revision, Clinical Modification code 625.3) before 2000 were excluded. All participants were followed from January 1, 2000 until the diagnosis of dysmenorrhea, withdrawal from National Health Insurance, or December 31, 2013. Furthermore, air pollutants were categorized into quartiles with three cut-off points (25th, 50th, and 75th percentiles). The Cox regression model was used to calculate the hazard ratios of dysmenorrhea.Results: This study enrolled 296,078 women. The mean concentrations of yearly air pollutants were 28.2 (±12.6) ppb for nitric oxides (NOx), 8.91 (±7.93) ppb for nitric oxide (NO), 19.3 (±5.49) ppb for nitrogen dioxide (NO2), 0.54 (±0.18) ppm for carbon monoxide (CO), and 31.8 (±6.80) μg/m3 for PM2.5. In total, 12,514 individuals developed dysmenorrhea during the 12-year follow-up. Relative to women exposed to Q1 concentrations of NOx, women exposed to Q4 concentrations exhibited a significantly higher dysmenorrhea risk [adjusted hazard ratio (aHR)= 27.9, 95% confidence interval (CI) = 21.6–31.3]; similarly higher risk was found for exposure to NO (aHR = 16.7, 95% CI = 15.4–18.4) and NO2 (aHR = 33.1, 95% CI = 30.9–37.4). For CO, the relative dysmenorrhea risk in women with Q4 level exposure was 28.7 (95% CI = 25.4–33.6). For PM2.5, women at the Q4 exposure level were 27.6 times (95% CI = 23.1–29.1) more likely to develop dysmenorrhea than those at the Q1 exposure level.Conclusion: Our results showed that women would have higher dysmenorrhea incidences while exposure to high concentrations of NO, NO2, NOx, CO, and PM2.5.

Background Day care service (DCS) provides various activities in a professional environment to meet the old people with functional limitations. However, relatively little is known about the effects of DCS on physical and mental functions. Methods This was a retrospective study that we used a comprehensive geriatric assessment to evaluate the changes before and after DCS among participants in a hospital-affiliated geriatric day care center in Taiwan. The burden of the participants’ families was also assessed. Results The 18 participants with a median age of 80.9 (interquartile range (IQR) 75.2–86.6 y/o) were enrolled and followed up for 6 months. Based on the clinical dementia rating (CDR), disease stage was very mild in 3 participants, mild in 10, moderate in 3, and severe in 2. The activities of daily living (ADL) scores of the participants improved significantly from 75 (IQR 60.0–80.0) at baseline to 77.5 (IQR 65.0–90.0) at the 6 month (p p = 0.026). There was a positive correlation of baseline mini-nutritional assessment-short form score and the 3-level version of the European Quality of Life-5 dimensions utility index with both ADL and MMSE scores at the 6-month follow-up. In addition, the family burden scale was reduced from 22 to 15 (p = 0.002). Conclusions The physical and cognitive functions in old people with dementia who received DCS were maintained or partially improved, and their families’ stress burden was alleviated.

Background: In patients with chronic kidney disease (CKD), physical functional limitations and heart failure (HF) are common, and each is associated with adverse outcomes. However, their joint effects on mortality are not clear.Design and Methods: Using administration data from the geriatric department in a tertiary hospital, retrospective longitudinal analyses of patients aged ≥65 years with CKD were consecutively enrolled from February 2010 to November 2015. Baseline CKD stages, HF with reduced and preserved ejection fraction (HFrEF and HFpEF), Rockwood frailty index, handgrip strength (HGS), 6-m walking speed, and timed up-and-go test were used to predict the prevalence of frailty, physical disability, and all-cause mortality.Results: Among 331 old patients with CKD, their mean age was 81.3 ± 6.6 years. CKD stages showed the following distributions: stage 3, 74.9%; stage 4, 15.7%; stage 5, 9.4%. The prevalence of HF was 23.3%, and Rockwood frailty was 74.3%. Rockwood frailty and HF were both significantly associated with CKD stages. After a mean follow-up period of 3.1 ± 2.1 years, 44 patients died, and a crude analysis showed that stage 4, stage 5 CKD, low HGS, and Rockwood frailty index were associated with mortality. Regarding the survival of these patients, the adjusted mortality hazard ratio for CKD stage 5 was 3.84 against stage 3A [95% confidence interval (CI) 1.51–9.75], 1.04 (95% CI 1.01–1.07) for higher Rockwood frailty score, 4.78 (95% CI 1.26–18.11) for HFrEF, and 3.47 (95% CI 1.15–10.42) for low HGS. Survival analysis using Kaplan–Meier survival plots showed that patients with both HF and poor HGS had the poorest survival.Conclusions: Our study shows that both low physical performance and HF were common in old CKD patients and were associated with CKD stages. HF, frailty, and HGS all independently predicted the mortality of these CKD patients. The mortality is especially high amongst individuals with both HF and decreased HGS.

Visits by older people to the Emergency Department (ED) have increased in recent decades with higher revisiting and admission rates after discharge, particularly for those with frailties. This study used a before–after design aimed at evaluating Comprehensive Geriatric Assessment (CGA) screening in older ED patients (aged ≥ 75 years) during the 12-month preintervention period. Additionally, a CGA-based structured follow-up program after ED discharge was executed during the next 12-month intervention period. Amongst the 358 participants (median age 82 years), involving 122 in the preintervention period and 236 in the intervention period, 77 participants (21.5%) were identified as pre-frailty, while 274 (76.5%) were identified as frail using the Fried frailty phenotype. One-hundred ten (110) (30.7%) patients revisited the ED with 73 (20.4%) being admitted and 20 (5.6%) dying within three months after ED discharge. Compared with preintervention and intervention period, it was shown that the rates of admission at the index ED visit (50.8% vs. 23.1%), and mortality (10.7% vs. 3.0%), were both were significantly reduced. Using multivariate regression analysis, it was shown frailty was significantly associated with three-month mortality after adjusting for potential confounders. On the contrary, the program significantly decreased admission and death rate. It is suggested that frailty was prevalent amongst the older ED patients, and should be screened for in order to decrease revisits/admissions after ED discharge.

Background The risk of venous thromboembolism (VTE) in generally ill patients, both under outpatient and inpatient care, following blood transfusion has not been determined. Methods This retrospective population-based cohort study was conducted using the National Health Insurance Research Database. We studied patients who received blood transfusion, defined as red blood cell transfusion of any type, from January 1, 2000 to December 31, 2011. The index date was defined as the date of blood transfusion. The primary outcome was VTE. Propensity score matching and Cox proportional hazard models were used. Results A total of 41,866 patients who underwent blood transfusion and 41,866 matched controls were studied. Generally, the blood transfusion cohort has 2.98 times higher risk of VTE than the control cohort (95% confidence interval [CI] = 1.23–7.22). The blood transfusion cohort had respectively 1.99 and 1.64 times higher risk of deep vein thrombosis (DVT) and pulmonary embolism (PE) compared with the control cohort (DVT, 95% CI = 1.65–2.41; PE, 95% CI = 1.19–2.26). Patients in the blood transfusion cohort who did not use warfarin were 1.95 times more likely to develop VTE than those in the control cohort (adjusted hazard ratio [HR]: 1.95, 95% CI = 1.65–2.31). Patients in the blood transfusion cohort were 1.74 times more likely to die than those in the control cohort (adjusted HR: 1.74, 95% CI = 1.48–2.05). Conclusion Blood transfusion is associated with an increased risk of VTE. The risk of VTE decreased in those who took warfarin.

Hyperglycemia and inflammation, with their augmented interplay, are involved in cases of stroke with poor outcomes. Interrupting this vicious cycle thus has the potential to prevent stroke disease progression. Tumor necrosis factor-α (TNF-α) is an emerging molecule, which has inflammatory and metabolic roles. Studies have shown that TNF-α receptor inhibitor R-7050 possesses neuroprotective, antihyperglycemic, and anti-inflammatory effects. Using a rat model of permanent cerebral ischemia, pretreatment with R-7050 offered protection against poststroke neurological deficits, brain infarction, edema, oxidative stress, and caspase 3 activation. In the injured cortical tissues, R-7050 reversed the activation of TNF receptor-I (TNFRI), NF-κB, and interleukin-6 (IL-6), as well as the reduction of zonula occludens-1 (ZO-1). In the in vitro study on bEnd.3 endothelial cells, R-7050 reduced the decline of ZO-1 levels after TNF-α-exposure. R-7050 also reduced the metabolic alterations occurring after ischemic stroke, such as hyperglycemia and increased plasma corticosterone, free fatty acids, C reactive protein, and fibroblast growth factor-15 concentrations. In the gastrocnemius muscles of rats with stroke, R-7050 improved activated TNFRI/NF-κB, oxidative stress, and IL-6 pathways, as well as impaired insulin signaling. Overall, our findings highlight a feasible way to combat stroke disease based on an anti-TNF therapy that involves anti-inflammatory and metabolic mechanisms.

Background: We investigated the association between glucose excursions and the dawn phenomenon, and the effects of oral-glucose lowering drugs on the dawn phenomenon in patients with type 2 diabetes (T2D). Methods: We conducted a post hoc analysis using data from a previous randomized trial. Patients with T2D on metformin monotherapy were randomized to receive add-on acarbose or glibenclamide for 16 weeks. Ambulatory continuous glucose monitoring (CGM) was conducted before randomization and at the end of the study. Using the CGM data, we assessed glucose excursions as indicated by mean amplitude of glycemic excursions (MAGE). The magnitude of the dawn phenomenon was calculated as the difference between the nocturnal nadir (0:00 to 6:00 a.m.) and prebreakfast glucose level. Results: A total of 50 patients with T2D [mean age 53.5 ± 8.2 years, mean glycated hemoglobin (HbA1c) 8.4 ± 1.2%] were analyzed. There was an independent association between MAGE and the dawn phenomenon [β coefficient 0.199, 95% confidence interval (CI) 0.074–0.325, p = 0.003]. HbA1c improved significantly after treatment with acarbose or glibenclamide. However, only treatment with acarbose significantly improved glucose excursions. The dawn phenomenon decreased significantly only in patients treated with acarbose (from 35.9 ± 15.7–28.3 ± 16.5 mg/dl, p = 0.037), but not in those treated with glibenclamide (from 35.9 ± 20.6–34.6 ± 17.0 mg/dl, p = 0.776). Conclusion: Glucose excursions were independently associated with the dawn phenomenon in patients with T2D on metformin monotherapy. Both glucose excursions and the dawn phenomenon improved after treatment with acarbose, but not after treatment with glibenclamide.

The evidence indicates that the optimal observation period following renal biopsy ranges between 6 and 8 h. This systematic review and meta-analysis explored whether differences exist in the complication rates of renal biopsies performed in outpatient and inpatient settings. Methods: We searched the MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews from 1985 to February 2020. Two reviewers independently selected studies evaluating the bleeding risk from renal biopsies performed in outpatient and inpatient settings and reviewed their full texts. The primary and secondary outcomes were risks of bleeding and major events (including mortality) following the procedure, respectively. Subgroup analysis was conducted according to the original study design (i.e., prospective or retrospective). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random effect meta-analysis. Heterogeneity was assessed using the I2 test. Results:Data from all 10 eligible studies, which included a total of 1801 patients and 203 bleeding events, were included for analysis. Renal biopsies in outpatient settings were not associated with a higher bleeding risk than those in inpatient settings (OR = 0.81, 95% CI, 0.59–1.11, I2 = 0%). The risk of major events was also comparable across both groups (OR = 0.45, 95% CI, 0.16–1.29, I2 = 4 %). Conclusions:Similar rates of bleeding and major events following renal biopsy in outpatient and inpatient settings were observed.

Background Few large-scale cohort studies have investigated the association between community acquired pneumonia and the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs). We aimed to study whether using ACEIs or ARBs had protective effects for community acquired pneumonia. Methods This database cohort study was conducted retrospectively in Taiwan. The hypertensive patients were the target population of this study. Patients with ARB use were defined as our first study cohort. The second study cohort comprised patients who used ACEI. Propensity-score matching at 1:1 was used between ARB users and non-ARB users. We recruited 67 944 participants for the ARB study and 58 062 participants for the ACEI study. The same matching was also performed between ACEI users and non-ACEI users. Cox proportional hazard regression was used to analyze the risk of the outcome of viral pneumonia. Results The hazard ratio of community acquired pneumonia for ARB users relative to non-ARB users was 0.33. The hazard ratio of community acquired pneumonia was 0.71 times in ACEI users compared with ACEI nonusers. In stratification analysis, both ARB and ACEI both exhibited a protective effect for community acquired pneumonia in each age and sex group. In the analysis of the effects of therapy duration, patients using ARB for fewer than 100 days exhibited a greater reduction in the risk of community acquired pneumonia (adjusted HR = 0.58) compared with the non-ARB cohort. For the ACEI study, patients who used ACEI for 121 to 450 days were more likely to exhibit reduced risks of community acquired pneumonia (adjusted HR = 0.5). Conclusion Both ACEI and ARB uses were associated with decreased risk of community acquired pneumonia infection.

Background Whether a sex difference exists in long-term cardiovascular (CV) outcomes after acute myocardial infarction (AMI) is worth exploration. This study is sought to investigate the relationships among sex, age and the long-term prognosis after AMI. Methods This population-based retrospective cohort study used Taiwan's National Health Insurance Research Database (NHIRD) to investigate the sex differences in in-hospital and long-term CV outcomes in patients with AMI. We enrolled patients who were first diagnosed with AMI from January 1, 2000 to December 31, 2013. The outcomes of interest included all-cause mortality, CV death, nonfatal stroke, nonfatal heart failure, and AMI recurrence during hospitalization and 5-year follow up. The CV outcomes were also analyzed by age stratification. Results Overall, 201,921 patients with AMI were analyzed; 68.72% were men and 31.28% were women, with mean ages of 65.34 ± 14.12 and 73.05 ± 12.22 years, respectively. Major adverse cardiac events (MACE) during hospitalization and up to 5 years were consistently greater in women than in men. Multivariable regression analysis revealed no sex difference existed in long-term all-cause and CV mortality. Men of all age groups consistently showed higher risk of both short- and long-term recurrence of AMI. Nonetheless, the female sex still independently predicted increased risk of nonfatal stroke and heart failure from hospitalization until 3-year follow up. Conclusion Women with AMI had poorer short-term and long-term outcomes. The sex differences in long-term all-cause and CV death disappear after multivariate analysis. Nonetheless, female AMI patients independently predicted higher risk of stroke and heart failure from hospitalization until a 3-year follow-up. To better understand the pathophysiology of female patients with AMI and develop more effective management, more studies in this field are necessary in the future.

Background: Fine air pollutant particles have been reported to be associated with risk of preeclampsia. The association between air pollutant exposure and preeclampsia risk in heavily air polluted Taiwan warrants investigation.Methods: We combined data from Taiwan National Health Insurance (NHI) Research Database (NHIRD) and Taiwan Air Quality Monitoring Database. Women aged 16–55 years were followed from January 1, 2000, until appearance of ICD-9 coding of preeclampsia withdrawal from the NHI program, or December 31, 2013. Daily concentration of NOx, NO, NO2, and CO was calculated by Kriging method. The Cox proportional hazard regression model was used for risk assessment.Results: For NOx, Relative to Quartile [Q] 1 concentrations, the Q2 (adjusted hazard ratio adjusted = 2.20, 95% CI = 1.50–3.22), Q3 (aHR = 7.28, 95% CI = 4.78–11.0), and Q4 (aHR = 23.7, 95% CI = 13.7–41.1) concentrations were associated with a significantly higher preeclampsia or eclampsia risk. Similarly, for NO, relative to Q1 concentrations, the Q2 (aHR = 1.82, 95% CI = 1.26–2.63), Q3 (aHR = 7.53, 95% CI = 5.12–11.0), and Q4 (aHR = 11.1, 95% CI = 6.72–18.3) concentrations were correlated with significantly higher preeclampsia or eclampsia risk. Furthermore, for NO2, relative to Q1 concentration, the Q2 (aHR = 1.99, 95% CI = 1.37–2.90), Q3 (aHR = 6.15, 95% CI = 3.95–9.57), and Q4 (aHR = 32.7, 95% CI = 19.7–54.3) concentrations also associated with a significantly higher preeclampsia or eclampsia risk.Conclusion: Women exposed to higher NOX, NO, NO2, and CO concentrations demonstrated higher preeclampsia incidence.

Idiopathic pulmonary fibrosis (IPF) is a rare lung disease with high mortality. Finding an effective predictor of survival is therefore important for both clinicians and patients. In this prospective observational study, we evaluated the prognostic value of the parameters of cardiopulmonary exercise test (CPET), pulmonary function test (PFT), 6-min walk test (6MWT), and certain questionnaires on mortality in Asian patients with IPF. A total of 34 patients diagnosed with IPF were enrolled and followed up for 12 months, during which 6 patients died. The non-survivors had significantly higher minute ventilation to carbon dioxide output (VE/VCO2) slope, more oxygen desaturation during CPET and 6MWT, less heart rate recovery one minute after CPET, higher dead space, higher Gender-Age-Physiology (GAP) index and Modified Medical Research Council (mMRC) score. GAP index, mMRC score, VE/VCO2 slope, and end-tidal partial pressure of carbon dioxide (PETCO2) at maximal exercise demonstrated an area under curve (AUC) of >0.7, and the corresponding cutoff values were 4, 2, 35.1 and 3.6 kPa. Therefore, GAP index, mMRC scores, VE/VCO2 slope, and PETCO2 at maximal exercise could be important predictors for mortality in Asian patients with IPF.

Background Frailty, a syndrome characterized by a decline in function reserve, is common in older patients with heart failure (HF) and is associated with prognosis. This study aimed to evaluate the impact of frailty on outcomes in older patients with preserved and reduced cardiac function. Methods In total, 811 adults aged ≥65 years were consecutively enrolled from 2009 to 2018. HF was diagnosed according to the ICD9 code and a 2D echocardiogram was categorized by reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). The index date was registered at the time of HF. All patients received a comprehensive geriatric assessment, and clinical outcomes were examined with adjustment of the other prognostic variables. Results Mean age was 80.5 ± 7.1 years. The prevalence of HF, HFpEF, HFrEF, Fried, and Rockwood frailty indicators was 28.5, 10.4, 9.7, 52.5, and 74.9%, respectively. At baseline, scores in the Timed Up and Go test was closely associated with the severity of HF, either with HFpEF or HFrEF. After a mean follow-up of 3.2 ± 2.0 years, we found that HF patients with low handgrip strength (HGS) had the poorest survival, followed by non-HF patients with decreased HGS, and HF with fair HGS in comparison with non-HF with fair HGS (p = 0.008) if participants were arbitrarily divided into two HGS groups. In all patients, a high Rockwood frailty index was independently associated with increased mortality (adjusted hazard ratio [aHR] = 1.05; 95% confidence interval [CI]: 1.0004 to 1.10). In addition, the adjusted mortality HR was 3.42 with decreased HGS (95% CI: 1.03 to 11.40), 7.65 with use of mineralocorticoid receptor antagonist (95% CI: 2.22 to 26.32), and 1.26 with associated multi-comorbidities assessed by Charlson comorbidity index (95% CI: 1.05 to 1.51). Conclusions Our study results indicate that frailty and decreased physical functions were associated with HF. Besides, frailty and HGS predicted prognosis in the patients, and there was a combined effect of HF and low HGS on survival.

We investigated the association between postchallenge glucose increment and hemoglobin glycation index (HGI), the difference between observed and predicted glycated hemoglobin (HbA1c), in subjects with no history of diabetes. We enrolled 1381 subjects who attended our outpatient clinic for an oral glucose tolerance test (OGTT) to screen for diabetes. HGI was defined as observed HbA1c minus predicted HbA1c. The predicted HbA1c was calculated by entering fasting plasma glucose (FPG) level into an equation [HbA1c(%)=FPG(mg/dL)*0.029+2.9686] determined from an HbA1c versus FPG regression analysis using data from an independent cohort of 2734 subjects with no history of diabetes. The association between 2-hour glucose increment and HGI was analyzed using linear regression analyses with adjustment of relevant parameters. Overall, the proportions of subjects with normal glucose tolerance, pre-diabetes, and newly diagnosed diabetes were 42.3%, 41.3%, and 16.4%, respectively. Compared with subjects who had an HGI≤0, subjects with an HGI>0 had a lower FPG (95.0±13.3 vs 98.5±15.3 mg/dL, p

Objectives We aimed to investigate whether the risk of diabetes mellitus (DM) is heightened in patients with prostate cancer receiving injection therapy. Methods Men diagnosed with prostate cancer between 2000 and 2012 were included in the case cohort, and men without prostate cancer were included as controls. Each patient with prostate cancer was matched with a control patient with the same index year, demographic variables and comorbidities, and comparisons were made using propensity score matching. The hazard ratio of DM was estimated using the Cox proportional hazards model. Results This cohort study consisted of 1213 patients with prostate cancer and 1213 control patients. The risk of DM in patients with prostate cancer was 1.60 times (95% CI = 1.12, 2.27) that of patients without prostate cancer. Compared with the controls, the hazard ratios of DM for patients with prostate cancer not receiving oral hormone therapy, patients with prostate cancer receiving oral hormone therapy, and patients with prostate cancer not receiving injection hormone therapy were 1.65 (95% CI = 1.01, 2.70), 1.57 (95% CI = 1.07, 2.70), and 1.94 (95% CI = 1.34, 2.81), respectively. The risk of DM in patients who received injection hormone therapy was 0.45 times (95% CI = 0.25, 0.82) that of patients who did not receive injection hormone therapy. Conclusion Patients with prostate cancer had an increased risk of DM compared with patients without prostate cancer. Patients with prostate cancer who received injection therapy had a lower risk of DM compared with those who did not.

Background Chronic kidney disease (CKD), low serum albumin, and anemia are known risk factors for cognitive decline in older people. We investigated the association between kidney function and cognitive impairment severity in oldest-old people with a diagnosis of Alzheimer’s disease (AD). Methods A cross-sectional study of patients aged 80 years and older was conducted at a veterans’ home in Taiwan between 2012 and 2016. Their estimated glomerular filtration rate (eGFR) was determined using the Modification of Diet in Renal Diseases (MDRD) equation. Cognitive function was evaluated with the Mini-Mental State Examination (MMSE) and Clinical Dementia Rating (CDR). Results A total of 84 patients (age mean ± SD, 86.6 ± 3.9 years) had MMSE scores of 10.1 ± 6.7, and CDR scores of 1.6 ± 0.7. The average eGFR was 61.7 ± 21.5 mL/min/1.73m2. The mean hemoglobin concentration was 12.7 ± 1.7 g/dl, and the mean albumin concentration was 4.5 ± 4.8 g/dl. Multivariate regression analyses showed that scores of CDR were significantly correlated with eGFR after adjustment for potential confounders. The scores of MMSE were significantly correlated with serum albumin and hemoglobin after adjustment for potential confounders. Conclusions We found dementia severity was significantly associated with kidney function, serum albumin, and hemoglobin in the oldest-old with AD. We recommend that oldest-old people with a diagnosis of AD be evaluated to determine kidney function, as well as nutritional and hematological status. Further study is needed to establish whether prevention of CKD deterioration, and correction of malnutrition and anemia may help to slow cognitive decline in oldest-old people with dementia.

Background: This retrospective cohort study compared patient survival and technique survival between patients on continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD) using recent data at a single tertiary medical center in Taiwan. Methods: From medical records, we identified incident 459 CAPD patients and 266 APD patients on dialysis for at least 90 days and aged more than 18 years to estimate mortality and technique failure rates, and related hazard ratio (HR) and 95% confidence interval (CI) from 2007 to 2018. Results: There were more women (52.3%) in the CAPD group, whereas patients in the APD group were younger. Compared to CAPD patients, APD patients had a lower mortality rate (2.83 vs. 5.79 per 100 person-years) with an adjusted HR of 0.69 (95% CI = 0.47–1.02), and a lower technique failure rate (9.70 vs. 17.52 per 100 person-years) with an adjusted HR of 0.65 (95% CI = 0.51–0.83). Further subgroup analyses revealed that, compared to CAPD, APD was associated with a significant lower risk of technique failure in male patients, patients aged 50–65 years, diabetic patients, patients without cardiovascular disease (CVD), patients with higher peritoneal permeability, or patients initiating PD in an earlier era. Conclusions: The mortality risk was not significant between CAPD and APD patients. APD is associated with a lower risk of technique failure than CAPD, particularly for male patients, and patients aged 50–65 years, with diabetes, without CVD, with high or high average peritoneal permeability, or initiating PD in an earlier era.

Glycaemic traits are used to diagnose and monitor type 2 diabetes, and cardiometabolic health. To date, most genetic studies of glycaemic traits have focused on individuals of European ancestry. Here, we aggregated genome-wide association studies in up to 281,416 individuals without diabetes (30% non-European ancestry) with fasting glucose, 2h-glucose post-challenge, glycated haemoglobin, and fasting insulin data. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P-8), 80% with no significant evidence of between-ancestry heterogeneity. Analyses restricted to European ancestry individuals with equivalent sample size would have led to 24 fewer new loci. Compared to single-ancestry, equivalent sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase understanding of diabetes pathophysiology by use of trans-ancestry studies for improved power and resolution.

Anesthetics, particularly volatile anesthetics, have been shown to impair glucose metabolism and cause hyperglycemia, closely linking them with mortality and morbidity as related to surgery. Beyond being an anesthetic used for general anesthesia and sedation, intravenous hypnotic propofol displays an effect on glucose metabolism. To extend the scope of propofol studies, its effects on glucose metabolism were evaluated in male Sprague-Dawley rats of various ages. Unlike chloral hydrate and isoflurane, propofol had little effect on basal glucose levels in rats at 2 months of age, although it did reduce chloral hydrate- and isoflurane-induced hyperglycemia. Propofol reduced postload glucose levels after either intraperitoneal or oral administration of glucose in both 7- and 12-month-old rats, but not those at 2 months of age. These improved effects regarding propofol on glucose metabolism were accompanied by an increase in insulin, fibroblast growth factor-21 (FGF-21), and glucagon-like peptide-1 (GLP-1) secretion. Additionally, an increase in hepatic FGF-21 expression, GLP-1 signaling, and FGF-21 signaling, along with a decrease in endoplasmic reticulum (ER) stress, were noted in propofol-treated rats at 7 months of age. Current findings imply that propofol may turn into insulin-sensitizing molecules during situations of existing insulin resistance, which involve FGF-21, GLP-1, and ER stress.

Background and Objective: Idiopathic pulmonary fibrosis (IPF) is a lung disease with a high mortality rate. Finding an effective predictor of survival is therefore important for clinicians and patients. Several parameters have been established to predict mortality, but none of these have been validated in the Asian population. In this study, we evaluated the prognostic value of the parameters of cardiopulmonary exercise test (CPET), pulmonary function test (PFT), 6-min walk test (6MWT), and certain questionnaires on mortality in Asian patients with IPF. Methods: This prospective observational study analysed patient data, including age, gender, height, and body weight; scores of Saint George’s Respiratory Questionnaire (SGRQ), Modified Medical Research Council (mMRC) for dyspnoea, and Short Form-36 (SF-36); and parameters of PFT, 6MWT, and CPET. Results: In total, 24 patients diagnosed as having IPF were followed up for 14 months, during which 3 patients died. The nonsurvivors had significantly lower body weight; lower forced vital capacity (FVC); higher ratio of forced expiratory volume in 1 s to forced vital capacity (FEV1/FVC); higher gender, age, and pulmonary physiology (GAP) index; shorter walk distance in 6MWT; lower end-tidal pressure of carbon dioxide (DLCO); higher functional aerobic impairment (FAI) during exercise; and higher mMRC score. FEV1/FVC, FAI, GAP index, and mMRC dyspnoea score demonstrated an area under curve (AUC) of >0.7, and the corresponding cut-off values were 89%, 54%, 7, and 3. Conclusions: The predictive abilities of PFT, CPET, and mMRC scores were validated successfully in the study cohort of Asian patients with IPF.

Background Whether patients with end-stage renal disease (ESRD) have a higher risk of idiopathic polyneuropathy (IPN) than those without ESRD remains unclear. We hypothesised that carpal tunnel syndrome (CTS) is a prodrome of IPN in patients with ESRD. Methods Data were collected from the Taiwan National Health Insurance research database (NHIRD) for the 2000-2011 period. Two matching strategies, age- and sex-matching and propensity matching, were used, which yielded 2596 age- and sex-matched patients with ESRD and 2210 propensity-matched patients with ESRD. The comparison cohort was chosen in a 1:4 ratio for the age- and sex-matched method and in a 1:1 ratio for the propensity-matching method. The primary outcome was the incidence of IPN. Cox proportional hazards modelling was used. Results In the age- and sex-matched cohort, the IPN incidence was 7.64 and 2.88 per 1000 person-years for the ESRD and controls cohorts, respectively. After we adjusted for age, sex, comorbidities and medications relative to controls, having ESRD was significantly associated with increased risk of IPN (hazard ratio [HR] = 2.45, 95% confidence interval [CI] = 1.76-3.41). Competing risk of death as sensitivity analysis revealed that having ESRD with CTS was still associated with higher risk of IPN than having CTS without ESRD (HR = 2.85, 95% CI = 1.87-4.34). Conclusion Patients with ESRD with CTS had higher incidences of idiopathic peripheral neuropathy than those without ESRD with CTS.

Ischemic stroke provokes an inflammatory response concurrent with both sympathetic nervous system activation and hyperglycemia. Currently, their crosstalk and consequences in stroke outcomes are of clinical attraction. We have provided experimental evidence showing the suppressive effects of the nonselective &beta, adrenoreceptor antagonist propranolol on hyperglycemia, inflammation, and brain injury in a rat model experiencing cerebral ischemia. Pretreatment with propranolol protected against postischemic brain infarction, edema, and apoptosis. The neuroprotection caused by propranolol was accompanied by a reduction in fasting glucose, fasting insulin, glucose tolerance impairment, plasma C-reactive protein, plasma free fatty acids, plasma corticosterone, brain oxidative stress, and brain inflammation. Pretreatment with insulin alleviated&mdash, while glucose augmented&mdash, postischemic brain injury and inflammation. Additionally, the impairment of insulin signaling in the gastrocnemius muscles was noted in rats with cerebral ischemia, with propranolol improving the impairment by reducing oxidative stress and tumor necrosis factor-&alpha, signaling. The anti-inflammatory effects of propranolol were further demonstrated in isoproterenol-stimulated BV2 and RAW264.7 cells through its ability to decrease cytokine production. Despite their potential benefits, stroke-associated hyperglycemia and inflammation are commonly linked with harmful consequences. Our findings provide new insight into the anti-inflammatory, neuroprotective, and hypoglycemic mechanisms of propranolol in combating neurodegenerative diseases, such as stroke.

Background: Direct evidence of lung cancer risk in Asian users of angiotensin-converting enzyme inhibitors (ACEIs) is lacking. Methods: The ACEI cohort comprised 22,384 patients aged &ge, 18 years with a first prescription of ACEI. The comparison angiotensin receptor blocker (ARB) cohort consisted of age-, sex- and comorbidity-matched patients at a ratio of 1:1. The primary outcome was the incidence of lung cancer, which was evaluated using a proportional hazard model. Results: The overall incidence rates of lung cancer in the ACEI and ARB cohorts were 16.6 and 12.2 per 10,000 person-years, respectively. The ACEI cohort had a significantly higher risk of lung cancer than the ARB cohort (adjusted hazard ratio [aHR]. = 1.36, 95% confidence interval [CI]. = 1.11&ndash, 1.67). Duration&ndash, response and dose&ndash, response analyses revealed that compared with patients who did not receive ACEIs, patients who received ACEIs for more than 45 days per year (aHR = 1.87, 95% CI = 1.48&ndash, 2.36) and patients who received more than 540 defined daily doses of ACEIs per year (aHR =1.80, 95% CI = 1.43&ndash, 2.27) had a significantly higher risk of lung cancer. The cumulative incidence of lung cancer was also significantly higher in the ACEI cohort than in the ARB cohort (log-rank test, p = 0.002). Conclusions: ACEI use is associated with an increased risk of lung cancer compared with ARB use. Patients using ARBs have a significantly lower risk of lung cancer than non-ARB users.

Obesity is associated with a wide range of chronic diseases, including cancer. It has been noted that the integration of metabolic mechanisms in obese patients may predispose them to suffer from cancer incidence and its progression. Thus, a better understanding of metabolic alterations in obesity, along with the development of feasible therapeutic approaches for intervention, are theoretically relevant to the prevention and treatment of cancer malignancy. Using a syngeneic tumor model involving Lewis Lung Carcinoma (LLC) cells and C57BL/6 mice fed with a high fat diet, obesity was found to be associated with dysregulated glucose and glutamine metabolism, inflammation, along with platelet activation and the promotion of tumor growth. Tumor-bearing lowered glucose levels while moderately increasing inflammation, platelet activation, and glutamine levels. The antiplatelet drug aspirin, mitigated tumor growth in obese mice, paralleled by a decrease in systemic glucose, insulin, inflammation, platelet activation, glutamine and tumor expression of cell proliferation, aerobic glycolysis, glutaminolysis, platelets, and leukocyte molecules. The anti- and pro-cell proliferation, aerobic glycolysis, and glutaminolysis effects of aspirin and glutamine were further demonstrated in a LLC cell study. Although there remains limitations to our experiments, glucose and glutamine metabolism are proposed targets for the anticancer effects of aspirin.

Background: The objective of this study was aimed to investigate whether sleep apnea patients had a higher risk of traumatic brain injury. Methods: Data were collected from the Taiwan Longitudinal Health Insurance Database during the period of 2000–2012. The study cohort comprised 6,456 patients aged ≥20 years with a first diagnosis of sleep apnea. The primary outcome was the incidence of traumatic brain injury. Kaplan-Meier survival analysis and Cox proportional-hazards modeling were used. Results: After adjustments for associated comorbidities and hypnotic medications, sleep apnea patients were associated with a 1.19-fold higher risk of traumatic brain injury (95% CI, 1.07–1.33) compared with patients without sleep apnea. Sleep apnea patients who took benzodiazepine (BZD) had a 1.30-fold increased risk of traumatic brain injury compared with patients without sleep apnea (95% CI, 1.14–1.49). However, this risk was not statistically significant, with a 1.03-fold risk of traumatic brain injury in sleep apnea patients without BZD use (95% CI, 0.84–1.25) compared with patients without sleep apnea. Compared with patients without sleep apnea, the risk of traumatic brain injury in sleep apnea patients aged 65–79 years old was higher (adjusted hazard ratio, 1.36; 95% CI, 1.06–1.74). Conclusion: Sleep apnea patients, regardless of hypnotic use, had a higher risk of traumatic brain injury compared with patients without sleep apnea.

Background: Association between hydroxychloroquine (HCQ) and bacterial infections required to be determined. Whether hydroxychloroquinehad use could reduce lesser risk of bacterial infections are unknown. We aimed to conduct a retrospective cohort propensity-matching study to investigate the association between HCQ use and the incidence of bacterial pneumonia in rheumatic patients. Methods: The Longitudinal Health Insurance Database (LHID), a one million extract from Taiwan National Health Insurance Research Database (NHIRD) of 23 million Taiwanese populations was used. We included patients who newly diagnosed rheumatic and immune disease (ICD-9-CM codes 696.0, 710, 714) within 2000-2012.HCQ users and nonusers were then matched according to age, sex, urbanization level, monthly income, comorbidities and medications in the ratio of 1:1 by the propensity score matching. Cox proportional hazard model was used to evaluate the risk of bacterial pneumonia in rheumatic patients who used HCQ and who did not use HCQ. Results: There were total 3285 patients with rheumatic and immune disease enrolled. The cumulative incidence curve of patients with the use of HCQ sulfate had no difference to that of patient without the use of HCQ sulfate in propensity score matched cohort, (Log-rank test: p-value=0.5). However, patients used HCQ sulfate for more than 1400 average use days had a lesser risk of bacterial pneumonia (adjusted HR=0.55, 95% CI=0.35, 0.89) in the cohort matched, with regarding HCQ nonusers as a reference. Conclusion: Rheumatic patients taking HCQ had no overall significant differences of bacterial pneumonia incidences compared with rheumatic patients not taking HCQ. HCQ used more than >1400 days was associated with lower risk of bacteria pneumonia. Funding Statement: This study is supported in part by Taiwan Ministry of Health and Welfare Clinical Trial Center (MOHW109-TDU-B-212-114004), China Medical University Hospital (CMU107-ASIA-19, DMR-109-231); MOST Clinical Trial Consortium for Stroke (MOST 108-2321-B-039-003-), Tseng-Lien Lin Foundation, Taichung, Taiwan. No additional external funding was received for this study. Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: This study was approved by the Institutional Review Board of the China Medical University Hospital (CMUH104-REC2-115(AR-4)).

Renal ischemia/reperfusion (I/R) is an alternation of renal hemodynamics, which results in diverse postischemic responses and eventually acute kidney injury. Although renal ischemic preconditioning (IPC) is known to protect the kidney from I/R injury, the precise renoprotective mechanisms are not completely understood. The multiple renoprotective effects of IPC underscore the importance in understanding molecular mechanisms and the targets of action involved. This study aimed to identify the biochemical changes in renal I/R injury and investigate the renoprotective mechanisms of IPC. Herein, renal I/R was produced in adult male Sprague-Dawley rats through the bilateral ligation of renal pedicles for 45 min, followed by reperfusion for 24 h. For the IPC group, rats were subjected to three cycles of 2-min ischemia, followed by a 5-min reperfusion, 15 min prior to renal I/R. Our data confirmed the beneficial effects that IPC has on renal I/R injury. IPC-mediated renoprotection was associated with the resolution of oxidative stress, inflammation, apoptosis, and hyperglycemia. Among the numerous signaling molecules involved in the renoprotective mechanisms of IPC, an elevated protein expression of Nrf2, HO-1, LC3 II conversion, along with Atg12 and protein phosphorylation of AMPK, as well as a decreased protein phosphorylation of ERK, p38 MAPK, and Akt and NF-κB DNA binding activity were identified. Importantly, the post renal I/R overproduction of counter-regulatory hormones, impaired hepatic insulin action, and augmented hepatic gluconeogenesis were improved through IPC. As counter-regulatory hormones have been implicated in the induction of oxidative stress, inflammation, apoptosis, impaired insulin action, hyperglycemia, and tissue destruction, our findings suggest that counter-regulatory hormones may well be valuable targets of IPC for combatting renal I/R injury. © 2018 IUBMB Life, 71(3):321-329, 2019.

Background The aim of the present study was to investigate the association between serum aryl hydrocarbon receptor (AhR) levels and insulin resistance and β-cell function in patients undergoing coronary angiography with no history of diabetes. Methods Patients with no history of diabetes who had undergone coronary angiography underwent an oral glucose tolerance test (OGTT) 2-4 weeks after discharge from hospital; blood samples were collected for measurements of glucose, insulin, and AhR. Patients' glucose regulation status was determined on the basis of the OGTT. Insulin resistance was assessed using the homeostasis model assessment of insulin resistance (HOMA-IR). β-Cell function was assessed using the insulinogenic index (IGI). Results The study included 473 patients (mean (±SD) age 61 ±12 years, 81.8% male, mean body mass index 26.1 ±3.6 kg/m2 ). Overall, mean serum AhR concentrations were 25.1 ±12.2 pg/mL. Patients with normal glucose tolerance had a lower serum AhR concentrations than patients with prediabetes or newly diagnosed diabetes (23.4 ±10.8 vs 26.2 ±13.2 and 26.9 ±12.3 pg/mL, respectively; P = 0.029). Linear regression analysis revealed that serum AhR concentrations were not associated with HOMA-IR, but were negatively associated with IGI after adjustment for several confounders, including HOMA-IR (β = -0.162; 95% confidence interval - 0.302, -0.022; P = 0.023). Conclusions In patients with no history of diabetes, serum AhR concentrations were negatively associated with β-cell function, independent of several confounders, including insulin resistance.

Aim To investigate the effect of changes in fasting plasma glucose (FPG) variability, as assessed by 2-year trajectories of FPG variability, on mortality risk in patients with type 2 diabetes (T2D). Methods From 2009 to 2012, outpatients with T2D, aged>18 years, were enrolled from a medical centre. FPG was measured every 3 months for 2 years in 3569 people. For each of the eight 3-month intervals, FPG variability and means were calculated, with variability defined as the coefficient of variation of FPG. Also, trajectories of FPG variability and means were determined separately, using group-based trajectory analysis with latent class growth models. These models were fitted using the SAS Proc Traj procedure. The primary outcome was all-cause mortality, which was followed-up to the end of 2014. Results Five distinct trajectories of FPG variability (low, increasing, fluctuating, decreasing and high) and means (well controlled, stable control, worsening control, improving control and poor control) were established. The five trajectories of mean FPG were all associated with the same mortality risk. In contrast, in comparison to the low FPG variability trajectory, the fluctuating, decreasing and high variability trajectories all had significantly higher risks of mortality, with respective hazards ratios of 2.63 (95% CI: 1.40–4.93; P = 0.003), 2.78 (95% CI: 1.33–5.80; P = 0.007) and 4.44 (95% CI: 1.78–11.06; P = 0.001) after multivariable adjustment. Conclusion Changes in FPG variability were independently associated with increased mortality risk in patients with T2D.

AIM We used insurance claims data of Taiwan to compare the risk of non-traumatic lower extremity amputation between haemodialysis (HD) and peritoneal dialysis (PD) patients. METHODS We identified 77 669 HD patients and 10 035 PD patients without prior amputation from 2000 to 2010. Incidence rates and hazard ratios (HRs) of lower extremity amputation, and subsequent 30-day mortality after amputation were evaluated up to 31 December 2011. RESULTS There were 2427 and 216 patients undergoing lower extremity amputation during follow-up in the HD and PD groups with incidence rates of 8.35 and 5.79 per 1000 person-years, respectively. Compared with the HD group, the overall adjusted HR of lower extremity amputation for the PD group was 1.27 (95% CI = 1.10-1.46). The impact of diabetes status on the risk of lower extremity amputation interacted with dialysis modality significantly (P

Mounting evidence suggests that physical exercise shows health benefits in a range of diseases, including psychiatric disorders. Perinatal opioid exposure produces neurobehavioral abnormality, which includes depression symptoms, in patients and their offspring following chronic use of buprenorphine, a mixed agonist/antagonist with a high affinity to opioid receptors, for pain control. Previously, we demonstrated that prenatal buprenorphine exposure in pregnant Sprague-Dawley rats starting from gestation day 7 and lasting for 14 days caused the development of depression-like phenotypes in pups at postnatal day 21. Using the same prenatal buprenorphine exposure model, we further demonstrated that a 4-week course of moderate treadmill exercise conducted on pups starting from postnatal day 22 improved depression-like neurobehaviors. Prenatal buprenorphine exposure-induced neurobehavioral changes were accompanied by reductions of neuronal survival, neural stem cell-associated genes, plasma level of brain-derived neurotrophic factor (BDNF) and serotonin, phosphorylated tropomyosin-related kinase receptor type B (TrkB), phosphorylated extracellular signal-regulated kinase (ERK), PKA activity, phosphorylated cAMP response element-binding protein (CREB), and CREB DNA binding activity, as well as elevation of repressor element-1 silencing transcription factor (REST), oxidative stress, and inflammatory responses. Those changes in parameters of plasma and brain were improved by treadmill exercise. In conclusion, the findings of the current study suggest that a non-pharmacological option, i.e., moderate treadmill exercise, alleviated the development of depression-like neurobehaviors by resolving the oxidative and inflammatory burden as well as by enhancing neurochemical and neuroendocrine signaling.

Background Prostate cancer (PC) can be related to increased systemic oxidative stress and dihydrotestosterone level, which are also reported to be involved in the pathogenesis of age-related macular degeneration (AMD). We conducted a cohort study to determine whether patients with PC have an increased risk of AMD. Patients and methods Data were collected from the Taiwan Longitudinal Health Insurance Database for the 1999–2010 period. The study PC cohort comprised 22 084 patients aged ≥18 years with a first diagnosis of PC. The comparison cohort consisted of age-, occupation-, and urbanization level-matched patients at a ratio of 1 : 1. The primary outcome was the incidence of AMD, which was evaluated using Kaplan–Meier survival analysis and proportional hazards modeling. Results The mean follow-up periods (standard deviation) for the patients with AMD in the age-, occupation-, and urbanization level-matched PC cohort and non-PC cohorts were 4.69 (2.90) and 5.51 (2.82) years. The mean age of the PC cohort was 73.9 years and that of the non-PC cohort was 73.2 years, with approximately 85.9% of the patients aged >65 years. The PC cohort had a higher risk of AMD than did the propensity score-matched non-PC cohort with an adjusted hazard ratio of 1.25 (95% confidence interval, 1.12–1.39). Compared with PC cohort receiving no injection hormone therapy, the PC cohort receiving injection hormone therapy had a lower risk of AMD (adjusted hazard ratio, 0.56; 95% confidence interval, 0.41–0.76). Conclusion PC is associated with an increased risk of AMD. Patients with PC receiving injected form of androgen deprivation therapy had a lower risk of AMD than patients with PC not receiving injected form of androgen-deprivation therapy.

We investigated the associations of fibroblast growth factor 21 (FGF-21) with cardiovascular risk and β-cell function in patients who had no history of diabetes.We enrolled 269 outpatients who had been referred for an oral glucose tolerance test (OGTT). Plasma glucose, insulin, and FGF-21 were measured before and at 2h after the OGTT. β-cell function was assessed using the insulinogenic index, corrected for insulin resistance. Patients' 10-year coronary heart disease (CHD) risk was assessed using the Chinese Multi-provincial Cohort Study functions.Overall, there was a 10% decrease in FGF-21 after OGTT (p0.001). The decrease of FGF-21 after OGTT in patients with normal glucose tolerance, prediabetes, and diabetes was 8%, 10%, and 21%, respectively (all p0.05). Patients with a history of admission for coronary angiography had a higher 10-year CHD risk and fasting FGF-21 (both p0.001). In multivariate regression analysis, fasting FGF-21 was positively associated with 10-year CHD risk, while FGF-21 relative change 2h after OGTT was positively associated with β-cell function.In patients who had no history of diabetes, fasting FGF-21 was positively associated with 10-year CHD risk, while FGF-21 relative change 2h after OGTT was positively associated with β-cell function.

Background This study compared the risk of developing new-onset diabetes between hemodialysis (HD) and peritoneal dialysis (PD) patients. We further investigated the effectiveness of icodextrin in reducing the risk of new-onset diabetes in PD patients. Methods From the Taiwan health insurance database, 36 879 incident HD patients and 6382 incident PD patients from 2000 to 2010 were identified as study cohorts. We further selected an additional HD cohort matched by propensity scores (PSs) of PD patients. Incidence rates and hazard ratios (HRs) of new-onset diabetes were assessed among cohorts and between icodextrin users and nonusers by the end of 2011. Results For the unmatched cohorts, the incidence of new-onset diabetes was higher in PD patients than in HD patients (9.16 versus 8.18 per 1000 person-years), with an adjusted HR of 1.51 (95% CI 1.30-1.75) for PD patients. For the PS-matched cohorts, the corresponding incidence rates were 9.43 and 5.90 per 1000 person-years, respectively, with an adjusted HR of 1.61 (95% CI 1.32-1.97). Among PD patients, the incidence was lower in icodextrin users than in nonusers (6.22 versus 12.1 per 1000 person-years), with an adjusted HR of 0.66 (95% CI 0.50-0.88) for users. Conclusions Our study suggests that PD patients are at a higher risk of developing new-onset diabetes than HD patients. Icodextrin is recommended for PD patients to reduce the risk of new-onset diabetes.

// Shih-Yi Lin 1, 2, 3 , Cheng-Li Lin 4, 5 , Chao-Hsiang Chang 6 , His-Chin Wu 6 , I-Kuan Wang 1, 2, 3 , Che-Yi Chou 1, 2, 3 and Ji-An Liang 1, 7 1 Graduate Institute of Clinical Medical Science, College of Medicine, China Medical University, Taichung, Taiwan 2 Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan 3 Division of Nephrology and Kidney Institute, China Medical University Hospital, Taichung, Taiwan 4 Managment Office for Health Data, China Medical University Hospital, Taichung, Taiwan 5 College of Medicine, China Medical University, Taichung, Taiwan 6 Department of Urology, China Medical University Hospital, Taichung, Taiwan 7 Department of Radiation Oncology, China Medical University Hospital, Taichung, Taiwan Correspondence to: Ji-An Liang, email: d4615@mail.cmuh.org.tw Keywords: upper tract urothelial carcinoma, acute myocardial infarction, mortality, radical nephroureterectomy, multivariable Cox proportional hazard regression analysis Received: April 07, 2017 Accepted: May 29, 2017 Published: June 15, 2017 ABSTRACT Background: The outcomes of upper tract urothelial carcinoma (UTUC) receiving radical nephroureterectomy were usually limited to small sample size, case-control studies, and often focused on cancer progression. Risk of acute myocardial infarction (AMI) in these patients was never investigated. Results: The overall incidences of AMI were 3.39, 1.44, and 1.70 per 10,000 person-years in the radical nephroureterectomy, nonnephroureterectomy, and non-UTUC cohorts, respectively. Multivariable Cox proportional hazard regression analysis revealed a significantly higher AMI risk in the radical nephroureterectomy cohort [adjusted HR (aHR) = 1.83, 95% confidence interval (CI) = 1.08–3.11], compared with non-UTUC cohorts. The risk of mortality were the highest in patients with UTUC who had undergone radical nephroureterectomy [adjusted HR (aHR) = 5.37, 95% confidence interval (CI) = 4.80–6.02]. Materials and Methods: From the Taiwan National Health Insurance claims data, 1,359 patients with UTUC who had undergone radical nephroureterectomy and 3,154 patients with UTUC who had undergone nephron sparing surgery and were newly diagnosed between 2000 and 2010 were identified. For each patient, 4 individuals without UTUC were randomly selected and frequency matched by age, sex, and diagnosis year. Conclusions: Patients with UTUC who have undergone radical nephroureterectomy are at a higher risk of developing AMI, compared with those receiving nephron sparing surgery.

Aim It has been reported that many people with dementia require hospitalizations. The objective of the present study was to determine predictive factors for hospitalizations in people with dementia. Methods A total of 70 individuals with dementia living in a veterans’ home in southern Taiwan were consecutively enrolled. During prospective follow up, all hospitalization events were recorded. Results The mean age of residents with dementia was 86.1 ± 4.0 years, and the mean follow-up time for this population was 2.2 ± 1.1 years. Among individuals, 62.9% suffered from malnutrition or were at risk of malnutrition (minimal nutritional assessment-short form score ≤11), and 8.6% of individuals had a body mass index of

Aim To develop experimental multi-domain interventions for older people with mild-to-moderate dementia, and to evaluate the effect of delaying cognitive and physical decline, and improvement or prevention of geriatric syndromes during 1-year follow up. Methods Participants aged 65 years and older with mild-to-moderate dementia (clinical dementia rating [CDR] 1 or 2) were grouped as intervention in Jia-Li Veterans Home and usual care model in the community (Memory clinic). All residents in Jia-Li Veterans Home received comprehensive intervention, including Multi-disciplinary team consultation and intervention, Multi-component non-pharmacological management, geriatric syndromes survey and intervention by CGA, and a dementia friendly medical Green channel Approach (2MCGA). The decline of cognitive and physical function are determined by the change of Mini-Mental State Examination score, CDR and the sum of CDR box, as well as activities of daily living based on the Barthel Index. We also screened geriatric syndromes at baseline and 1 year later. Results Participants in the intervention group were older and had a lower educational level, lower body mass index, poor baseline activities of daily living function, lower visual impairment, and higher rates of hearing impairment, polypharmacy and risk of malnutrition. The residents receiving 2MCGA had lower baseline Mini-Mental State Examination scores, and higher CDR. For residents in Jia-Li Veterans Home, all cognitive measurements except Mini-Mental State Examination were significantly associated with delaying the decline of cognition after analyzing by multiple linear regression, and multivariate logistic regression also showed that patients living in the community was independently associated with a higher odds ratio for activities of daily living decline (3.180, 95% CI 1.384–7.308, P = 0.006). There are also more improvement in their baseline geriatric syndromes and suffered less from new geriatric syndromes, including falls, urinary incontinence, and risk of malnutrition. Conclusions The 2MCGA intervention shows strong delays in the decline of cognition and physical function for older residents with mild-to-moderate dementia. Furthermore, this strategy can also improve or prevent the onset of new geriatric syndromes, especially fall episodes, urinary incontinence and risk of malnutrition. Geriatr Gerontol Int 2017; 17 (Suppl. 1): 36–43.

Backgrounds Worldwide, the incidence of acute kidney injury (AKI) has been increasing. However, information on the long-term incidence of Parkinson disease (PD) in patients with AKI has not been reported. Methods A total of 9380 patients with AKI and 37,484 age- and sex-matched patients who did not have AKI were identified during 2003–2011. All patients were tracked until a diagnosis of PD, death, or the end of 2011. Cumulative incidences and hazard ratios (HRs) were calculated. Results The mean follow-up time for PD was 6.89 (SD = 3.30) years in the AKI cohort and 6.78 (SD = 3.29) years in the non-AKI cohort. The overall incidence densities of PD were significantly higher in the AKI cohort than in the non-AKI cohort (6.04 vs. 3.99/1000 person-years), with an adjusted HR of 1.47 (95% confidence interval [CI] = 1.18–1.83). Compared with the patients in the non-AKI cohort aged ≤ 64 years, the relative risk (95% CI) of PD was 2.17 (1.12–4.18), 14.1 (9.16–21.8), and 14.1 (8.43–23.6) for the patients in the AKI cohort aged ≤ 64, 65–79, and ≥ 80 years, respectively. Conclusion Patients with AKI were associated with a higher long-term risk of PD.

Background: Air pollutants cause endocrine disorders and hormone disruption. The relationship between air pollutants and polycystic ovary syndrome (PCOS) must be carefully investigated using a nationwide cohort. Methods: Data were extracted from two nationwide databases, namely Longitudinal Health Insurance Database and Taiwan Air Quality Monitoring Database, and analyzed. The study considered a range of data that began on 1 January 2000 and ended on 31 December 2013. Women diagnosed with PCOS were excluded. From the residential data, the study assessed the daily concentrations of sulfur dioxide (SO2), nitrogen oxides (NOx), nitrogen monoxide (NO), nitrogen dioxide (NO2), and PM2.5 the women were exposed to. A Cox proportional hazard regression model was applied to assess PCOS risk. Results: In total, 91,803 women were enrolled in this study, of those women, 2072 developed PCOS after 12 years of follow-up. The mean daily concentrations of SO2, NOx, NO, NO2, and PM2.5 women were exposed to were 4.25 (&plusmn, 1.44) ppb, 20.41 (&plusmn, 6.65) ppb, 9.25 (&plusmn, 4.36) ppb, 20.99 (&plusmn, 3.33) ppb, and 30.85 (&plusmn, 6.16) &mu, g/m3, respectively. Compared with the first-quartile levels of exposure, the fourth-quartile levels of exposure to SO2, NOx, NO, NO2, and PM2.5 increased PCOS risk by 10.31 times (95% CI = 8.35&ndash, 12.7), 3.37 times (95% CI = 2.86&ndash, 3.96), 4.18 times (95% CI = 3.57&ndash, 4.89), 7.46 times (95% CI = 6.38&ndash, 8.71), and 3.56 times (95% CI = 3.05&ndash, 4.15), respectively. Conclusion: Women exposed to a high concentrations of air pollutants, namely SO2, NO, NO2, NOx, and PM2.5, had a high PCOS risk.

Air pollutants have been reported to be a possible risk factor of chronic kidney disease (CKD). However, epidemiologic results regarding acidic gases and CKD have yet to be elucidated. We linked the Taiwan Air Quality Monitoring Database (TAQMD) to the Longitudinal Health Insurance Database. An observational cohort of 161,970 Taiwan citizens who had not been diagnosed with CKD was formed. The concentrations of air pollutant were classified into four levels based on quartile. Multivariable and univariable Cox proportional hazard regression models were used to assess the risk of developing CKD and end-stage renal disease (ESRD). Compared with Q1-level SO2, exposure to the Q4 level was at a 1.46-fold risk of developing CKD (95% confidence interval [CI] = 1.28-1.65) and 1.32-fold risk of ESRD (95% CI = 1.03-1.70). Compared with Q1-level NOx, exposure to the Q4 level was at a 1.39-fold higher risk of developing CKD (95% CI = 1.22-1.58) and 1.70-fold risk of ESRD (95% CI = 1.33-2.18). Compared with Q1-level NO, exposure to the Q4 level was at a 1.48-fold risk of CKD (95% CI = 1.30-1.68) and 1.54-fold risk of ESRD (95% CI = 1.20-1.98). Compared with Q1-level particles2.5 μm (PM2.5), exposure to the Q4 level were at a 1.74-fold risk of CKD (95% CI = 1.53-1.98) and 1.69-fold risk of ESRD (95% CI = 1.32-2.16). Exposure to particulate and acidic gas air pollution was observed to be associated with an increased risk of CKD and ESRD.

Objective To investigate whether strength or aerobic training can offer significantly more benefits with regarding the activities of daily living of elderly patients with dementia as well as to determine the effects of exercise on cognition, depression, and biochemical markers. Design Single-blind randomized controlled trial. Setting A nursing home for veterans. Participants A volunteer sample of participants (N=80) whose scores on the Mini-Mental State Examination were between 15 and 26 were included. Because of cardiopulmonary or orthopedic conditions that prohibit exercise training, along with any cognitive problems that may impede answering the contents of our questionnaires, 11 participants were excluded. During the exercise training period, 8 participants voluntarily dropped out of the study. Interventions The participants were randomly assigned to perform either strength or aerobic training for a total of 4 weeks. Main Outcome Measures The main outcome measure was the Barthel Index. Other outcome measures included the Mini-Mental State Examination, Montreal Cognitive Assessment, Geriatric Depression Scale, plasma monocyte chemotactic protein-1 levels, insulin-like growth factor-1 levels, and serum brain-derived neurotrophic factor levels. Results After completion of the program, we discovered a significant improvement in the patients’ Barthel Index, Mini-Mental State Examination, Montreal Cognitive Assessment, and plasma monocyte chemotactic protein-1 levels in the strength-training group. For the patients who had received aerobic training, their serum brain-derived neurotrophic factor also improved significantly. However, the degree of improvement regarding these outcome measures did not achieve significant statistical difference between the 2 groups. Conclusions Through our study, an intensive 4-week exercise program, whether it be strength or aerobic training, is evidenced to bring significant benefits to elderly patients with dementia, while the serum brain-derived neurotrophic factor was additionally improved through aerobic training.