Febuxostat provides renoprotection in patients with hyperuricemia or gout: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: It is unknown whether febuxostat can delay the progression of kidney dysfunction and reduce kidney endpoint events. The aim was to evaluate the renoprotective effect of febuxostat in patients with hyperuricemia or gout by performing a meta-analysis of randomized controlled trials (RCTs). METHODS: MEDLINE, Web of science, EMBASE, ClinicalTrials.gov, and the Cochrane Central Register for Randomized Controlled Trials were searched. The main outcomes included kidney events (serum creatinine doubling or progression to end-stage kidney disease or dialysis). The secondary outcomes were the rate of change in the estimated glomerular filtration rate (eGFR) and changes in the urine protein or urine albumin to creatinine ratio from baseline to the end of follow-up. We used random-effects models to calculate the pooled risk estimates and 95% CIs. RESULTS: A total of 16 RCTs were included in the meta-analysis. In comparison with the control group, the patients who received febuxostat showed a reduced risk of kidney events (RR = 0.56, 95% CI 0.37-0.84, p = 0.006) and a slower decline in eGFR (WMD = 0.90 mL/min/1.73 m2, 95% CI 0.31-1.48, p = 0.003). The pooled results also revealed that febuxostat use reduced the urine albumin to creatinine ratio (SMD = -0.21, 95% CI -0.41 to -0.01, p = 0.042). CONCLUSION: Febuxostat use is associated with a reduced risk of kidney events and a slow decline in eGFR. In addition, the urine albumin to creatinine ratio decreased in febuxostat users. Accordingly, it is an effective drug for delaying the progression of kidney function deterioration in patients with gout.Systematic review registration: PROSPERO CRD42021272591.

The Efficacy of SARS-CoV-2 Vaccination in the Elderly: A Systemic Review and Meta-analysis.

BACKGROUND: Given the reduced immune response to vaccines in older populations, this study aimed to evaluate the efficacy of COVID-19 vaccinations and its impact on breakthrough infection, hospital admission, and mortality in the elderly. METHODS: We carried out a systemic review and meta-analysis where MEDLINE, Web of Science, EMBASE, ClinicalTrials.gov, and Cochrane Central Register for Controlled Trials were queried to identify relevant literature. We included randomized controlled trials (RCTs), non-randomized trials, prospective, observational cohort, and case-control studies assessing breakthrough infection, hospital admission, and mortality after coronavirus 2 (SARS-CoV-2) vaccination in the elderly (≥ 60 years old). RESULTS: Overall, 26 studies were included in this meta-analysis. Compared with the unvaccinated group, the vaccinated group showed a decreased risk of SARS-CoV-2 infection after 28-34 (relative risk [RR] = 0.42, 95% confidence interval [CI] 0.37-0.49) and 35-60 days (RR = 0.49, 95% CI 0.37-0.62). There was a step-wise increase in efficacy with additional doses with the two-dose group experiencing decreased risk of breakthrough infection (RR = 0.37, 95% CI 0.32-0.42), hospital admissions (RR = 0.25, 95% CI 0.14-0.45), disease severity (RR = 0.38, 95% CI 0.20-0.70), and mortality (RR = 0.21, 95% CI 0.14-0.32) compared with those receiving one or no doses. Similarly three-dose and four-dose vaccine groups also showed a decreased risk of breakthrough infection (3-dose: RR = 0.14, 95% CI 0.10-0.20; 4-dose RR = 0.46, 95% CI 0.4-0.53), hospital admissions (3-dose: RR = 0.11, 95% CI 0.07-0.17; 4-dose: RR = 0.42, 95% CI 0.32-0.55), and all-cause mortality (3-dose: RR = 0.10, 95% CI 0.02-0.48; 4-dose: RR = 0.48, 95% CI 0.28-0.84) Subgroup analysis found that protection against mortality for vaccinated vs. unvaccinated groups was similar by age (60-79 years: RR = 0.59; 95% CI, 0.47-0.74; ≥ 80 years: RR = 0.76; 95% CI, 0.59-0.98) and gender (female: RR = 0.66; 95% CI, 0.50-0.87, male: (RR = 0.58; 95% CI, 0.44-0.76), and comorbid cardiovascular disease (CVD) (RR = 0.69; 95% CI, 0.52-0.92) or diabetes (DM) (RR = 0.59; 95% CI, 0.39-0.89. CONCLUSIONS: Our pooled results showed that SARS-CoV-2 vaccines administered to the elderly is effective in preventing prevent breakthrough infection, hospitalization, severity, and death. What's more, increasing number of vaccine doses is becoming increasingly effective.

Association of remnant cholesterol with risk of cardiovascular disease events, stroke, and mortality: A systemic review and meta-analysis.

BACKGROUND AND AIMS: Lipid disorders are associated with the risk of cardiovascular diseases (CVDs). Remnant cholesterol (RC), a non-traditional previously neglected risk factor for CVD, has received much attention in recent years. The aim of this study is to evaluate the association of RC with the risks of CVD, stroke, and mortality. METHODS: MEDLINE, Web of Science, EMBASE, ClinicalTrials.gov, and Cochrane Central Register for Controlled Trials were searched. We included randomized controlled trials (RCTs), non-RCTs, and observational cohort studies assessing the association of RC with the risks of cardiovascular (CV) events, coronary heart disease (CHD), stroke, and mortality. RESULTS: Overall, 31 studies were included in this meta-analysis. Compared with low RC, elevated RC was associated with an increased risk of CVD, CHD, stroke, CVD mortality, and all-cause mortality (RR = 1.53, 95% CI 1.41-1.66; RR = 1.41, 95% CI 1.19-1.67; RR = 1.43, 95% CI 1.24-1.66; RR = 1.83, 95% CI 1.53-2.19; and RR = 1.39, 95% CI 1.27-1.50; respectively). A subgroup analysis demonstrated that each 1.0 mmol/L increase in RC was associated with an increased risk of CVD events and CHD. The association of RC with an increased CVD risk was not dependent on the presence or absence of diabetes, a fasted or non-fasted state, total cholesterol, or triglyceride or ApoB stratification. CONCLUSIONS: Elevated RC is associated with an increased risk of CVD, stroke, and mortality. In addition to the traditional cardiovascular risk factors, such as total cholesterol and LDL-C, clinicians should also pay attention to RC in clinics.

Experience of double plasma purification in 603 patients from a single center in Shanghai, China.

INTRODUCTION: To summarize the clinical experiences with double plasma purification (DPP). METHOD: Using Plasauto iQ automatic blood purification system, model KM-9000 for DPP. RESULTS: A total of 603 patients with different entity undergoing 811 purification procedures were included in this study. The most common purification modes were dual filtration plasma plasmapheresis (DFPP). Hyperlipidemia was the lead entity, 423 patients with hyperlipidemia performed DFPP, and two cases of severe acute pancreatitis caused by extremely high triglyceride levels completely recovered after two consecutive DFPP treatments. DFPP combined with immunosuppressants tended to decrease independent HD and reduced HD frequency in 53 patients with antineutrophil cytoplasmic antibody-associated vasculitis. Two patients developed hypotensive or hypoglycemia episodes, respectively, during purification procedures. CONCLUSION: DPP is rapid for the treatment of patients with severe hyperlipidemia and acute pancreatitis caused by severely high triglyceride levels. For those who are intolerant to statins，DPP provides another treatment choice. DPP process is safe.

Clinical characteristics and short-term mortality of 102 hospitalized hemodialysis patients infected with SARS-CoV-2 omicron BA.2.2.1 variant in Shanghai, China.

Background: The aim of this study was to analyze clinical features and short-term mortality in hemodialysis (HD) patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) omicron BA.2.2.1 variant. Methods: In a retrospective single-center case series, 102 consecutive hospitalized HD patients infected with the coronavirus omicron variant were assessed at Pudong Hospital in Shanghai, China, from April 6 to April 18, 2022; the final date of follow-up was May 16, 2022. Clinical, laboratory, chest CT, and treatment data were collected and analyzed. The association between these factors and all-cause mortality was studied using univariate and multivariate analyses. The relationship between lymphocyte count and short-term mortality was based on receiver operating characteristic (ROC) curve analysis. Kaplan-Meier analysis was used to assess overall survival. Results: In total, 102 patients were included in this study. The patients were divided into two groups: HD patients with pneumonia (N = 46) and without pneumonia (N = 56). Of the 102 patients, 12 (11.8%) died. Multivariate regression analysis revealed that all-cause mortality was correlated with lymphocyte counts and type B natriuretic peptide (BNP), C-reactive protein (CRP), and D-dimer levels (P < 0.05). The cut-off value of lymphocyte counts was 0.61 × 109/L for all-cause mortality. The overall survival rate was significantly different between HD patients with and without pneumonia (P < 0.05). Conclusions: Lymphocyte counts are important for the prediction of short-term mortality in HD patients with SARS-CoV-2 infection. HD patients with lung involvement have poorer survival rates than those without lung involvement.

Statin use and the risk of CVD events, stroke, and all-cause mortality in patients with diabetes: A systematic review and meta-analysis.

AIMS: Considering the lack of evidence on statin use and the risk of cardiovascular disease (CVD) in patients with diabetes in primary and secondary prevention, this study aimed to evaluate the effect of statin use in individuals with diabetes for primary and secondary prevention. DATA SYNTHESIS: The MEDLINE, Web of Science, Embase, ClinicalTrials.gov, and Cochrane Central Register for Controlled Trials databases were searched. We included studies that assessed the effect of statin use in individuals with diabetes for at least 1 year. The outcomes included CVD, all-cause mortality, and stroke. A total of 24 studies including 2,152,137 patients with diabetes were included in the meta-analysis. Compared with statin non-users, patients who received statins showed a lower risk of CVD events (primary prevention: risk ratio [RR] = 0.80, 95% confidence interval [CI] 0.69-0.94, P = 0.006; secondary prevention: RR = 0.75, 95% CI 0.65-0.87, P < 0.0001). No association was observed between statin and non-statin users and the risk of all-cause mortality. The pooled results also revealed that statin use reduced the risk of ischemic stroke in patients with diabetes (primary prevention: RR = 0.83, 95% CI 0.70-0.97, P = 0.020; secondary prevention: RR = 0.74, 95% CI 0.63-0.85, P < 0.0001). CONCLUSIONS: Statin use significantly reduced the risk of CVD events and stroke, but not all-cause mortality, in individuals with diabetes undergoing both primary and secondary prevention. More data are required to verify the effects of statins in patients with diabetes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021281132.

Association of the Coexistence of Somnipathy and Diabetes With the Risks of Cardiovascular Disease Events, Stroke, and All-Cause Mortality: A Systematic Review and Meta-analysis.

Background Somnipathy and diabetes are independently associated with an increased risk of cardiovascular disease (CVD). However, whether a combination of both conditions is associated with a higher risk of CVD events remains uncertain. Therefore, the aim of this meta-analysis was to clarify this association. Methods and Results We searched MEDLINE, Web of Science, EMBASE, ClinicalTrials.gov, and the Cochrane Central Register for Controlled Trials. We included randomized controlled trials, nonrandomized trials, and prospective observational cohort studies that assessed the combined effect of diabetes and comorbid somnipathy on CVD risk and mortality for at least 1 year. Outcomes included CVD, coronary heart disease, stroke, and all-cause mortality. Twelve studies involving 582 267 participants were included in the meta-analysis. Patients with somnipathy and comorbid diabetes exhibited increased risks of CVD, coronary heart disease, stroke, and all-cause mortality (risk ratio [RR], 1.27 [95% CI, 1.12-1.45], P<0.0001; RR, 1.40 [95% CI, 1.21-1.62], P<0.0001; RR, 1.28 [95% CI, 1.08-1.52], P=0.004, and RR, 1.56 [95% CI, 1.26-1.94], P<0.0001, respectively). Conclusions The coexistence of somnipathy and diabetes is associated with higher risks of CVD, coronary heart disease, stroke, and mortality than somnipathy or diabetes alone. Resolving sleep problems in patients with diabetes may reduce the risks of CVD, stroke, and mortality. Registration Information https://www.crd.york.ac.uk/prospero/. Identifier: PROSPERO CRD42021274566.

Association of oral endothelin receptor antagonists with risks of cardiovascular events and mortality: meta-analysis of randomized controlled trials.

BACKGROUND: Endothelin receptor antagonists (ERAs) are widely used in a variety of disorders, including pulmonary artery hypertension, systemic sclerosis, diabetic and kidney diseases, and several tumors. However, reported adverse events, especially increased risks of cardiovascular disease (CVD) morbidity and mortality, have cast doubt on their potential clinical application. Therefore, we conducted this meta-analysis to confirm whether ERAs increased CVD risk and mortality. METHODS: We systematically searched PubMed (1966-2015), EMBASE (1974-2015), ClinicalTrials.gov, and the Cochrane Controlled Clinical Trials Register Database for randomized controlled trials published between Jan 1, 1990 and Mar 18, 2015. Inclusion criteria included a study duration of more than 3 weeks, the use of a randomized control group receiving an oral ERA or placebo, and the availability of outcome data for cardiovascular events and all-cause death. RESULTS: A total of 33 trials met the inclusion criteria. There were 8098 cases in the ERA group and 5074 cases in the placebo group. Compared with the control group, the risk ratio (RR) for all-cause death in the ERA group was 0.983 [95% confidence interval (CI), 0.883 to 1.094, P = 0.754]. The summary RR for cardiovascular events was 1.651 in the ERA group (95% CI, 1.164 to 2.34, P = 0.005). The pooled results showed that ERAs treatment could lead to more edema, anemia, and abnormal transaminase levels. Also, there was an increased proportion of discontinued therapy in the ERA treatment because of side effects (RR = 1.322, 95% CI, 1.036 to 1.686, P = 0.025). There were no significant differences in the experienced episodes of headache and dyspnea between the active therapy and control groups. CONCLUSIONS: ERAs therapy is not significantly associated with increased all-cause death, but there are more cardiovascular events and edema or fluid retention, anemia, and liver enzymes disorder. Large clinical randomized controlled studies are needed to further confirm the safety of the clinical application of ERAs.

Low-dose aspirin for prevention of cardiovascular disease in patients on hemodialysis: A 5-y prospective cohort study.

Introduction Aspirin is an effective antiplatelet drug for preventing cardiovascular events in high-risk subjects. However, for patients with chronic kidney disease and undergoing hemodialysis (HD), its preventive efficacy remains controversial. The present study aimed to determine whether aspirin therapy reduces the risk of cardiovascular disease (CVD) and all-cause mortality in patients on HD. Methods We conducted a 5-y prospective cohort study involving patients on HD. Major exposure variables included prescription of aspirin (100 mg/d) and no aspirin (nonaspirin). The primary outcomes included all-cause death, cardiovascular events, hemorrhage, and ischemic stroke. The secondary outcome included bleeding events defined by the requirement of hospitalization. Findings In this study, 406 patients on regular HD were involved during a 5-y follow-up. Among these, 152 and 254 propensity-matched patients were enrolled in the aspirin and nonaspirin cohort, respectively. The cumulative survival rate was not significantly higher in the aspirin than in the nonaspirin users (log rank χ2 = 1.080, P = 0.299). Aspirin use was not significantly associated with reduced all-cause mortality, fatal and nonfatal congestive heart failure, as well as acute myocardial infarction and ischemic stroke. The risk of fatal cerebral hemorrhage was not significantly increased in the aspirin users (HR = 1.795, 95% CI 0.666-4.841, P = 0.174). After adjustment for other confounders, aspirin use was also not associated with decreased risk of all-cause mortality and CVD. Discussion The present prospective cohort study suggests that low-dose aspirin use is not associated with a significant decrease in the risks of all-cause mortality, CVD, and stroke in population undergoing HD (ClinicalTrials.gov number, NCT02261025).

Antioxidant N-acetylcysteine protects pancreatic ß-cells against aldosterone-induced oxidative stress and apoptosis in female db/db mice and insulin-producing MIN6 cells.

Previous studies have shown that primary aldosteronism is associated with glucose-related metabolic disorders. However, the mechanisms by which aldosterone (ALDO) triggers ß-cell dysfunction remains unclear. This study aimed to investigate whether oxidative stress is involved in and whether the antioxidant N-acetylcysteine (NAC) or the mineralocorticoid receptor antagonist spironolactone (SPL) could prevent or delay ß-cell damage in vivo and in vitro. As expected, 8 weeks after ALDO treatment, 12-week-old female diabetic db/db mice exhibited impaired oral glucose tolerance, decreased ß-cell mass, and heightened levels of oxidative stress marker (urinary 8-hydroxy-2'-deoxyguanosine). NAC reversed these symptoms completely, whereas SPL treatment did so only partially. After exposure to ALDO, the mouse pancreatic ß-cell line MIN6 exhibited decreased viability and increased caspase-3 activity, as well as reduced expression of Bcl-2/Bax and p-AKT, even if mineralocorticoid receptor was completely suppressed with small interfering RNA. NAC, but not SPL, suppressed oxidative stress in MIN6 cells, as revealed by the decrease in inducible NOS levels and expression of the proteins p22-phox and p67-phox. These findings suggest that oxidative stress may be involved in ALDO-induced ß-cell dysfunction and that NAC, but not SPL, may protect pancreatic ß-cells of mice from ALDO-induced oxidative stress and apoptosis in a manner independent of its receptor.

Erythropoietin improves insulin resistance via the regulation of its receptor-mediated signaling pathways in 3T3L1 adipocytes.

Recombinant human erythropoietin (rHuEPO) reduces serum insulin levels, increases insulin sensitivity, and reduces insulin resistance (IR). However, the mechanisms behind these effects are unclear. This study aimed to investigate the mechanism by which rHuEPO effects IR in 3T3L1 adipocytes. After treatment with different concentrations of rHuEPO, glucose consumption, and tumor necrosis factor (TNF-α), adiponectin, and leptin levels were assayed with a commercial enzyme-linked immunosorbent assays. Endogenous erythropoietin receptor (EPOR) expression was inhibited using small interfering RNA (siRNA). EPOR protein and mRNA expression was detected via immunofluorescence and real-time PCR analyses, respectively. The expression of pAKT/AKT and p-STAT5/STAT5 was determined via Western blot analysis. rHuEPO treatment improved glucose uptake, increased adiponectin levels, and reduced TNF-α and leptin levels in 3T3L1 adipocytes with dexamethasone-induced IR. Whereas EPOR protein and gene expression was absent in preadipocytes, it was observed in mature 3T3L1 adipocytes. However, the expression of EPOR in insulin resistant 3T3L1 adipocytes was significantly decreased (p<0.05). rHuEPO increased the expression of EPOR, and upregulated the expression of pAKT/AKT and pSTAT5/STAT5 in 3T3L1 adipocytes (p<0.05), which was blocked by siEPOR, the phosphatidylinositol-3-kinase (PI3K) inhibitor, LY294002, and a STAT5 inhibitor, respectively. In summary, rHuEPO reduced IR in adipocytes by increasing glucose uptake and improving the adipokine profile. rHuEPO-induced EPOR protein expression and subsequent induction of pAKT and pSTAT5 suggest that the EPO-EPOR system may play a role in glucose metabolism within adipocytes.