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High uric acid (UA) can act as a pro-oxidant in normal physiological conditions; however, emerging evidence is still debatablewith regard to the association between highUAand poor outcomes among chronic hemodialysis (HD) patients. In the present study, 27,229 stable prevalent HD patients were enrolled and divided into four groups according to the quartiles of baseline UA concentration, and 5737 died during a median follow-up of 38 months. Multivariate Cox regression analysis showed that a UA level of <6.1 mg/dL was associated with a higher risk of all-cause mortality compared with a UA level of >8.1 mg/dL [HR, 1.20, 95% CI (1.10-1.31)] adjusting for baseline demographic and biochemical parameters. Moreover, a UA level of <6.1 mg/dL was associated with greater risks of cardiovascular mortality [HR, 1.26, 95% CI (1.13-1.41)] and stroke-related mortality [HR, 1.59, 95% CI (1.12-2.25)], respectively. In vitro experiments further showed an increase in oxidative stress and an inhibition nitric oxide synthesis by indoxyl sulfate (IS) in human aortic endothelial cells, which were significantly attenuated by UA in a dose-dependent manner. We concluded that higher UA in serum was associated with lower risk of all-cause and cardiovascular mortality among HD patients probably through its antioxidant property in ameliorating the IS-related vascular toxicity. [ABSTRACT FROM AUTHOR]

An increasing amount of evidence suggests that metabolic alterations play a key role in chronic kidney disease (CKD) pathogenesis. In this issue of the JCI, Long et al. report that the long noncoding RNA (lncRNA) taurine-upregulated 1 (Tug1) contributes to CKD development. The authors show that Tug1 regulates mitochondrial function in podocytes by epigenetic targeting of expression of the transcription factor PPARγ coactivator 1α (PGC-1α, encoded by Ppargc1a). Transgenic overexpression of Tug1 specifically in podocytes ameliorated diabetes-induced CKD in mice. Together, these results highlight an important connection between lncRNA-mediated metabolic alterations in podocytes and kidney disease development. [ABSTRACT FROM AUTHOR]

A case study of a 74 year old man developing adynamic ileus post insertion of peritonial dialysis catheter for the management of his end-stage renal disease, is presented. Reportedly, after undergoing catheterization his postoperative progress was normal. However, on the second day he complained of nausea, abdominal distention with dull pain. Abdomen computed tomography (CT) revealed bladder perforation due to catheter. Patient recovered fully from the complication after removal of catheter.

A response from Ho-Han Wu and colleagues to a letter to the editor on their article related to the perforation of urinary bladder after implantation of a peritoneal dialysis (PD) catheter, is presented.

Background. Although modest seasonal variations in blood biochemical composition have been reported in end-stage renal disease patients treated with haemodialysis, there have been no adequate explanations. The current study aimed to explore whether these phenomena are present in peritoneal dialysis patients and to discuss these variations. Methods. This was a retrospective study with an enrollment of 44 anuric PD patients. Serum biochemical parameters, peritoneal function, dialysis adequacy, peritoneal ultrafiltration volume and body weight were analysed in relation to climate variables for a study period of 2 years. Results. PD patients exhibited cyclic variations in blood biochemical concentrations. Monthly mean outdoor temperature was inversely correlated with serum concentrations of sodium (r = −0.712, P r = −0.697, P r = −0.642, P r = −0.654, P r = −0.496, P = 0.012), peritoneal ultrafiltration volume (r = −0.723, P = 0.001) and body weight (r = −0.623, P Conclusions. PD patients showed seasonal variations in serum electrolyte concentration and peritoneal ultrafiltration volume. Monthly outdoor mean temperature was inversely correlated with serum electrolytes and ultrafiltration volume. A likely explanation is loss of these electrolytes through perspiration. Neglect of this annual cycle in PD patients may lead to biases in interpretation of clinical study and individual laboratory data. [ABSTRACT FROM AUTHOR]

Background: To control tuberculosis (TB), it is critical to identify at risk populations. Schizophrenia is recognized as an important risk factor for TB. However, previous studies have been confounded by comorbidities, and reports of TB infection outcomes are rare. Therefore, the current nation-wide study aimed to compare the adjusted incidence and outcome of TB diseases in schizophrenics and the general population. Method: Using the National Health Insurance Research Database from 1998 to 2009, this retrospective longitudinal study included 60,409 schizophrenics and general population matched for age, Charlson's score, and comorbidities. Diagnosis of TB was based on the international classification of disease, ninth revision and use of anti-TB drugs. Unfavorable outcome for TB was defined as death, loss to follow-up, or use of anti-TB treatment for more than 9 months. Results: The adjusted incidence of TB in schizophrenics was significantly higher than in the general population [hazard ratio, 1.52; 95% confidence interval (CI), 1.29-1.79; p < 0.001; Kaplan-Meier log-rank test, p < 0.001]. Cox regression revealed age and male gender as risk factors for newly-diagnosed TB. The outcome of TB was comparable in schizophrenics and the general population [odds ratio (OR), 0.78; 95% CI, 0.55-1.09; p =0.144]. Logistic regression revealed a statistical trend for diabetes mellitus to predict poor outcome in schizophrenics with TB (OR, 2.30; 95% CI, 0.96-5.74; p = 0.062). Conclusions: Schizophrenics are at increased risk for TB, and screening may be warranted for those living in areas with high prevalence of TB. [ABSTRACT FROM AUTHOR]

The article reports on the case of an elderly male patient who underwent surgery to remove a vesicle stone that blocked his urinary bladder in order to restore normal renal function. It discusses the history of neurogenic bladder, prostate hyperplasia and persistent urinary tract infection from prolonged use of a catheter. It focuses on the results of the laboratory examination and computed tomography that required the vesicolithotomy.

Background: Pleiotropic effects on cardiovascular protection have been suggested in several oral antidiabetic drugs (OAD). The impacts of OADs on aortic aneurysm (AA) growth have been found in animal studies, but the evidence of their beneficial effects for AA protection in human are lacking. We investigated the relationship between OAD therapy and the risk of developing AA. Methods: We conducted a nested case-control analysis using the database extracted from Taiwan's National Health Insurance Research Database. The database consists of 1.2 million diabetic patients representing the majority of the type 2 diabetes population in Taiwan from 2000 to 2013. Cases were identified as those with either inpatient or outpatient diagnosis code of AA. One control was selected for each case matching on duration of follow-up, age, sex, urbanization, monthly income, severity of diabetes, and risk factor for AA. We identified variable classes of OADs, including metformin, sulfonylureas, thiazolidinedione (TZD), alpha-glucosidase inhibitors, meglitinide, dipeptidyl peptidase-4 (DPP-4) inhibitors prior to the development of AA. Results: A total of 4468 cases diagnosed with AA and 4468 matched controls were identified. Metformin use, sulfonylurea use, and TZD were associated with lower risk of developing AA, odds ratio [OR] 0.72 (95 % confidence interval [CI] 0.64-0.80), 0.82 (95 % CI 0.74-0.92), and 0.82 (95 % CI 0.69-0.98), respectively. The effects of metformin and sulfonylurea on AA were dose responsive. Neither alpha-glucosidase inhibitors (OR 0.95; 95 % CI 0.81-1.11) nor DPP-4 inhibitors (OR 0.85; 95 % CI 0.68-1.07) was significantly associated with AA events. Conclusions: Metformin, sulfonylurea, and TZD treated patients were associated with lower risks of AA development, but not DPP-4 inhibitors or alpha-glucosidase inhibitor. The protective effects of hypoglycemic agents are further confirmed by the dose responsive relations in metformin and sulfonylurea groups. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the long-term survival rate of critically ill sepsis survivors following cardiopulmonary resuscitation on a national scale.Design: Retrospective and observational cohort study.Setting: Data were extracted from Taiwan's National Health Insurance Research Database.Patients: A total of 272,897 ICU patients with sepsis were identified during 2000-2010. Patients who survived to hospital discharge were enrolled. Post-discharge survival outcomes of ICU sepsis survivors who received cardiopulmonary resuscitation were compared with those of patients who did not experience cardiopulmonary arrest using propensity score matching with a 1:1 ratio.Intervention: None.Measurements and Main Results: Only 7% (n = 3,207) of sepsis patients who received cardiopulmonary resuscitation survived to discharge. The overall 1-, 2-, and 5-year postdischarge survival rates following cardiopulmonary resuscitation were 28%, 23%, and 14%, respectively. Compared with sepsis survivors without cardiopulmonary arrest, sepsis survivors who received cardiopulmonary resuscitation had a greater risk of all-cause mortality after discharge (hazard ratio, 1.38; 95% CI, 1.34-1.46). This difference in mortality risk diminished after 2 years (hazard ratio, 1.11; 95% CI, 0.96-1.28). Multivariable analysis showed that independent risk factors for long-term mortality following cardiopulmonary resuscitation were male sex, older age, receipt of care in a nonmedical center, higher Charlson Comorbidity Index score, chronic kidney disease, cancer, respiratory infection, vasoactive agent use, and receipt of renal replacement therapy during ICU stay.Conclusion: The long-term outcome was worse in ICU survivors of sepsis who received in-hospital cardiopulmonary resuscitation than in those who did not, but this increased risk of mortality diminished at 2 years after discharge. [ABSTRACT FROM AUTHOR]

Catheter-related blood stream infection (CRBSI) is a major complication in hemodialysis patients. We assessed the efficacy of systemic daptomycin (DPT) plus DPT antibiotic lock therapy (DPT-ALT) for catheter salvage in patients with Gram-positive CRBSIs. This is a retrospective study of hemodialysis patients with tunneled and cuffed hemodialysis catheters. All patients were from a single institution in Taipei and received systemic DPT plus DPT-ALT for the treatment of Gram-positive CRBSI. Successful resolution of CRBSI was implemented. Resolution of fever within 48 hours, negative result of repeated blood cultures after resolution of fever, no clinical evidence of CRBSI relapse and no need for catheter removal were measured. Fifteen hemodialysis patients received DPT-ALT for CRBSI, nine with coagulase-negative Staphylococcus (CONS), two with methicillin-resistant Staphylococcus aureus (MRSA), three with methicillin-sensitive Staphylococcus aureus (MSSA) and one with polymicrobial infections. Systemic DPT plus DPT-ALT cured 11 patients (73.3%). Treatment failed in all three MRSA cases (two with MRSA and one with MRSA + Enterococcus faecalis). Retrospective design and small sample size were the limitations of this study. Systemic DPT plus DPT-ALT appears to be a promising treatment for CRBSI from CONS and MSSA, but not for MRSA CRBSI. Systemic DPT plus DPT-ALT should be considered for patients with CRBSIs caused by certain species. [ABSTRACT FROM AUTHOR]

Background: Whether oral anticoagulant use should be considered in patients undergoing hemodialysis with atrial fibrillation (AF) remains controversial because of the uncertainty regarding risk-benefit assessments. The purpose of this study was to investigate the risk of ischemic stroke in patients undergoing hemodialysis with new-onset AF, in comparison with those without arrhythmia.Methods and Results: This nationwide, population-based, propensity score-matched cohort study used data from Taiwan's National Health Insurance Research Database during 1998 to 2011 for patients on hemodialysis with new-onset nonvalvular AF and matched subjects without arrhythmia. The clinical end points were ischemic stroke (fatal or nonfatal), all-cause death, and other serious adverse cardiovascular events. In comparison with the matched cohort, patients with AF (n=6772) had higher risks of ischemic stroke (adjusted hazard ratio [aHR], 1.27; 95% confidence interval [CI], 1.13-1.43), all-cause death (aHR, 1.59; 95% CI, 1.52-1.67), in-hospital cardiovascular death (aHR, 1.83; 95% CI, 1.71-1.94), myocardial infarction (aHR, 1.33; 95% CI, 1.17-1.51), and hospitalization for heart failure (aHR, 1.90; 95% CI, 1.76-2.05). After considering in-hospital death as a competing risk, AF significantly increased the risk of heart failure (HR, 1.56; 95% CI, 1.45-1.68), but not those of ischemic stroke and myocardial infarction. Additionally, the predictive value of the CHA2DS2-VASc score for ischemic stroke was diminished in the competing-risk model.Conclusions: The risk of stroke was only modestly higher in patients undergoing hemodialysis with new-onset AF than in those without AF, and it became insignificant when accounting for the competing risk of in-hospital death. [ABSTRACT FROM AUTHOR]

Background: Recent studies concluded that dipeptidyl peptidase-4 (DPP-4) inhibitors provide glycemic control but also raised concerns about the risk for heart failure in patients with type 2 diabetes mellitus (T2DM). However, large-scale studies of the effects on cardiovascular outcomes of adding DPP-4 inhibitors versus sulfonylureas to metformin therapy remain scarce.Objective: To compare clinical outcomes of adding DPP-4 inhibitors versus sulfonylureas to metformin therapy in patients with T2DM.Design: Nationwide study using Taiwan's National Health Insurance Research Database.Setting: Taiwan.Patients: All patients with T2DM aged 20 years or older between 2009 and 2012. A total of 10,089 propensity score-matched pairs of DPP-4 inhibitor users and sulfonylurea users were examined.Measurements: Cox models with exposure to sulfonylureas and DPP-4 inhibitors included as time-varying covariates were used to compare outcomes. The following outcomes were considered: all-cause mortality, major adverse cardiovascular events (MACEs) (including ischemic stroke and myocardial infarction), hospitalization for heart failure, and hypoglycemia. Patients were followed until death or 31 December 2013.Results: DPP-4 inhibitors were associated with lower risks for all-cause death (hazard ratio [HR], 0.63 [95% CI, 0.55 to 0.72]), MACEs (HR, 0.68 [CI, 0.55 to 0.83]), ischemic stroke (HR, 0.64 [CI, 0.51 to 0.81]), and hypoglycemia (HR, 0.43 [CI, 0.33 to 0.56]) compared with sulfonylureas as add-on therapy to metformin but had no effect on risks for myocardial infarction and hospitalization for heart failure.Limitation: Observational study design.Conclusion: Compared with sulfonylureas, DPP-4 inhibitors were associated with lower risks for all-cause death, MACEs, ischemic stroke, and hypoglycemia when used as add-ons to metformin therapy.Primary Funding Source: None. [ABSTRACT FROM AUTHOR]

Background There is substantial debate regarding the development of acute coronary syndrome in patients using proton pump inhibitors (PPIs) combined with clopidogrel. However, data remain limited to address the effect of PPIs alone on the subsequent risk of myocardial infarction (MI). We aimed to explore the subsequent risk of MI in PPI users who had no previous history of MI. Methods The records of inpatients and outpatients with PPI prescriptions were retrieved from the Taiwan National Health Insurance Research Database between 2000 and 2009. We conducted two different study designs, the first using propensity score (PS)-matching analyses and the second using case-crossover analyses. The risk of developing MI for PPI users was analyzed in the PS-matched study. The association between risk of MI and prior PPI exposure was further validated in the case-crossover study. Results In the PS-matched study, we included 126,367 PPI users and 126,367 PS-matched PPI non-users. After 120 days of follow-up, PPI use was associated with a 1.58-fold greater risk of MI (adjusted hazard ratio [HR] = 1.58, 95% confidence interval [CI] = 1.11 to 2.25). In the case-crossover study, adjusted odds ratios of PPI for MI risk were 4.61 (95% CI = 1.76 to 12.07) for the 7-day window and 3.47 (95% CI = 1.76 to 6.83) for the 14-day window. Conclusions Use of PPIs may be independently associated with an increased risk of MI. However, the benefits of PPIs may greatly outweigh the risks of adverse cardiovascular effects, with number needed to harm of 4357. [ABSTRACT FROM AUTHOR]

Background--Substantial infective endocarditis (IE)-related morbidity and mortality may occur even after successful treatment. However, no previous study has explored long-term hard end points (ie, stroke, myocardial infarction, heart failure, cardiovascular death) in addition to all-cause mortality in IE survivors. Methods and Results--A nationwide population-based cohort study was conducted among IE survivors identified with the use of the Taiwan National Health Insurance Research Database during 2000 to 2009. IE survivors were defined as those who survived after discharge from first hospitalization with a diagnosis of IE. A total of 10 116 IE survivors were identified. IE survivors were matched to control subjects without IE at a 1:1 ratio through the use of propensity scores. The primary outcomes were stroke, myocardial infarction, readmission for heart failure, and sudden cardiac death or ventricular arrhythmia. The secondary outcomes were repeat IE and all-cause mortality. Compared with the matched cohort, IE survivors had higher risks of ischemic stroke (adjusted hazard ratio [aHR], 1.59; 95% confidence interval [CI], 1.40-1.80), hemorrhagic stroke (aHR, 2.37; 95% CI, 1.90-2.96), myocardial infarction (aHR, 1.44; 95% CI, 1.17-1.79), readmission for heart failure (aHR, 2.24; 95% CI, 2.05-2.43), sudden death or ventricular arrhythmia (aHR, 1.69; 95% CI, 1.44-1.98), and all-cause death (aHR, 2.27; 95% CI, 2.14-2.40). Risk factors for repeat IE were older age, male sex, drug abuse, and valvular replacement after an initial episode of IE. Conclusion--Despite treatment, the risk of long-term major adverse cardiac events was substantially increased in IE survivors. [ABSTRACT FROM AUTHOR]

The aim of our study was to determine whether pre-emptive statin therapy was associated with improved outcome of infective endocarditis (IE). We conducted a nationwide, population-based, propensity score-matched cohort study with the Taiwan's National Health Insurance Research Database. All patients with IE between January 2000 and December 2010 were enrolled. The primary outcome was in-hospital mortality. The secondary outcome included all-cause mortality within the first 3 months, 6 months, and one year after the diagnosis of IE. Among 13,584 patients with IE, we applied propensity score-matching on a 1:4 ratio, in which 370 statin users were matched to 1,480 statin non-users. Compared with statin non-users, statin users had a significantly lower risk of in-hospital mortality (adjusted hazard ratio [aHR] 0.65, 95% confidence interval [CI], 0.49-0.86). The reduction in mortality from IE remained significant for follow-up 3 months (aHR 0.68, 95% CI, 0.53e0.88), 6 months (aHR 0.73, 95% CI, 0.58e0.91), and 12 months (aHR 0.68, 95% CI, 0.55e0.84). Statin therapy was associated with a reduced risk of ICU admission rates, shock events, the need for mechanical ventilation, but not significantly with the need for heart valvular replacement surgery. In conclusion, our study found that statin therapy is associated with a reduced risk of in-hospital and subsequent mortality of IE. [ABSTRACT FROM AUTHOR]

Objective: The association between selective serotonin receptor inhibitors (SSRIs) and risk of upper gastrointestinal bleeding remains controversial. Previous studies have generally evaluated the issue for approximately 3 months, even though the SSRl-mediated inhibition of platelet serotonin concentrations occurs within 7-14 days. The authors explored the risk of upper gastrointestinal bleeding after short-term SSRI exposure by a case-crossover design. Method: The records of psychiatric inpatients with upper gastrointestinal bleeding were retrieved from the Taiwan National Health Insurance Database (1998-2009). Rates of antidepressant use were compared for case and control periods with time windows of 7, 14, and 28 days. The adjusted self-matched odds ratios from a conditional logistic regression model were used to determine the association between SSRI use and upper gastrointestinal bleeding. Results: A total of 5,377 patients with upper gastrointestinal bleeding were enrolled. The adjusted odds ratio for the risk of upper gastrointestinal bleeding after SSRI exposure was 1.67 (95% 0=1.23-2.26) for the 7-day window, 1.84 (95% CI=1.42-2.40) for the 14-day window, and 1.67 (95% CI=1.34-2.08) for the 28-day window. SSRIs with high and intermediate, but not low, affinity for serotonin transporter were associated with upper gastrointestinal bleeding. An elevated risk of upper gastrointestinal bleeding after SSRI exposure was seen in male but not female patients. Conclusions: Short-term SSRI use (7-28 days) is significantly associated with upper gastrointestinal bleeding. Gender differences may exist in the relationship between SSRI use and upper gastrointestinal bleeding. Physicians should carefully monitor signs of upper gastrointestinal bleeding even after short-term exposure to SSRIs, as is done with nonsteroidal anti-inflammatory drugs and aspirin. [ABSTRACT FROM AUTHOR]