Age-related changes in peripheral T-cell subpopulations in elderly individuals: An observational study.

The age-related decline in T-cell function among elderly individuals remains unclear. We thus investigated the interrelationship between T-cell subsets and age to identify the changes in T-cell phenotypes and develop an age prediction model for the elderly population. A total of 127 individuals aged >60 years were divided into three groups (youngest-old group, 61-70 years, n = 34; middle-old group, 71-80 years, n = 53; and oldest-old group, ≥ 81 years, n = 40). The percentage of CD8+CD28- cells (P = 0.001) was highest in the oldest-old group and then followed by the middle-old group, while the youngest-old group was the lowest. Both females and males demonstrated significant decreases in the absolute counts of CD4+CD45RA+ cells (P = 0.020; P = 0.002) and CD8+CD28+ cells (P = 0.015; P = 0.005) with age. Multivariate linear regression showed that the percentage of CD8+CD28- cells (P < 0.001) was an independent predictor of aging after adjusting for sex, body mass index, hospitalization duration, smoking, drinking, chronic medical illness, and medications at admission. In conclusion, our results suggest that aging in elderly individuals is accompanied by a decrease in the counts of T-cell subpopulations. CD8+CD28- cells may be potential targets for elderly individuals in antiaging-related immunosenescence.

Drug hypersensitivity syndrome induced by sulfasalazine: A case report.

INTRODUCTION: Drug hypersensitivity syndrome (DHS) induced by sulfasalazine is a serious systemic delayed adverse drug reaction, which is associated with significant morbidity and mortality. PATIENT CONCERNS: A 52-year-old man was hospitalized for developing a rash after 3 weeks of sulfasalazine treatment for ulcerative colitis (UC). DIAGNOSIS: The patient was diagnosed with DHS based on his drug history, clinical manifestations, and laboratory test results. INTERVENTIONS: The patient was administered intravenous glucocorticoids. The patient's condition improved after treatment with human immunoglobulin and antihistamines. OUTCOMES: Combination therapy of glucocorticoid and gamma globulin, the whole-body pruritus disappeared, and no new rash appeared. The whole-body rash subsided or turned dark red. CONCLUSION: This article describes the diagnosis and treatment process of a case of sulfasalazine-induced DHS and reviews the relevant literature to improve clinician understanding and avoid misdiagnosis and missed diagnosis.

Comparative Efficacy of Five SGLT2i on Cardiorenal Events: A Network Meta-analysis Based on Ten CVOTs.

BACKGROUND: The relative efficacy of different sodium-glucose transporter 2 inhibitors (SGLT2i) on cardiorenal outcomes is unclear. METHODS: We included cardiovascular outcome trials (CVOTs) of SGLT2i. The eight endpoints of interest were major adverse cardiovascular events (MACE), myocardial infarction (MI), stroke, cardiovascular death (CVD), CVD or hospitalization for heart failure (HHF), HHF, kidney function progression (KFP), and all-cause death (ACD). We conducted a Bayesian network meta-analysis and calculated the surface under the cumulative ranking curve (SUCRA) probability to rank treatments. RESULTS: We included ten CVOTs involving five SGLT2i. Canagliflozin (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.53-0.77), dapagliflozin (HR 0.70; 95% CI 0.62-0.79), empagliflozin (HR 0.68; 95% CI 0.59-0.78), ertugliflozin (HR 0.70; 95% CI 0.54-0.90), and sotagliflozin (HR 0.66; 95% CI 0.56-0.77) versus placebo reduced HHF, whereas none reduced MI and stroke. Empagliflozin reduced CVD or HHF (HR 0.81; 95% CI 0.67-0.99) and KFP (HR 0.65; 95% CI 0.45-0.93), and dapagliflozin reduced KFP (HR 0.69; 95% CI 0.52-0.92), versus ertugliflozin. Canagliflozin had the greatest SUCRA values for the reduction of MACE, stroke, and HHF, whereas empagliflozin had the greatest SUCRA values for the reduction of MI, CVD, CVD or HHF, KFP, and ACD. CONCLUSIONS: Canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, and sotagliflozin versus placebo reduce HHF but none reduces MI and stroke. Canagliflozin is most effective in reducing MACE and HHF, and empagliflozin is most effective in reducing CVD, CVD or HHF, KFP, and ACD. These findings will guide the use of specific SGLT2i in the prevention of different cardiorenal events.

Factors affecting the efficacy of SGLT2is on heart failure events: a meta-analysis based on cardiovascular outcome trials.

BACKGROUND: The efficacy of sodium-glucose transporter 2 inhibitors (SGLT2is) on heart failure outcomes is unestablished in various subgroups defined by clinically important factors. We intended to evaluate the effects of six important factors on the efficacy of SGLT2is on heart failure outcomes. METHODS: We included cardiovascular outcome trials (CVOTs) concerning SGLT2is. We assessed the heart failure composite outcome of cardiovascular death (CVD) or hospitalization for heart failure (HHF). Meta-analysis was conducted stratified by the following 6 factors: type of underlying diseases, type of SGLT2is, left ventricular ejection fraction (LVEF) level, New York Heart Association (NYHA) class, region, and race. RESULTS: Ten CVOTs were included. Compared with placebo, SGLT2is reduced heart failure composite outcome by 25% [hazard ratio (HR) 0.75, 95% confidence interval (CI), 0.72-0.78] independent of type of underlying diseases, type of SGLT2is, LVEF level, and region (Psubgroup: 0.673, 0.244, 0.429, and 0.127, respectively). SGLT2is led to greater reduction in the composite outcome in patients with NYHA class II (HR 0.66, 95% CI, 0.59-0.74) than in patients with NYHA class III or IV (HR 0.86, 95% CI, 0.75-0.99; Psubgroup=0.004), and in Black (HR 0.63, 95% CI, 0.49-0.82) and Asian (HR 0.64, 95% CI, 0.53-0.77) patients than in White patients (HR 0.81, 95% CI, 0.76-0.86; Psubgroup=0.016). CONCLUSIONS: SGLT2is reduce heart failure composite outcome by 25% independent of type of underlying diseases, type of SGLT2is, LVEF level, and region. SGLT2is lead to greater reduction in the composite outcome in patients with NYHA class II than in patients with NYHA class III or IV, and in Black and Asian patients than in White patients. KEYWORDS: Sodium-glucose transporter 2 inhibitors (SGLT2is); heart failure; chronic kidney disease (CKD); type 2 diabetes.

Effects of patient characteristics on the efficacy of complete revascularization for treatment of ST-segment elevation myocardial infarction with multivessel disease: A meta-analysis.

BACKGROUND: Several randomized controlled trials (RCTs) have evaluated the efficacy of complete vs culprit-only revascularization for treatment of ST-segment elevation myocardial infarction (STEMI) with multivessel disease. However, the efficacy of complete revascularization vs culprit-only revascularization in some STEMI patient subgroups remains unclear. METHODS: We searched PubMed and Embase for related RCTs from the start date of databases to January 3, 2020. The endpoint assessed in this meta-analysis was major adverse cardiac events (MACE). Random-effects meta-analysis was conducted stratified by each of the 5 factors of interest (i.e., sex, age, history of diabetes, ECG infarct location, and the number of arteries with stenosis) to estimate pooled hazard ratio and 95% confidence interval. Random-effects meta-regression was conducted to assess subgroup differences. We examined publication bias by drawing funnel plots and performing Egger test. This meta-analysis is reported according to the PRISMA statement. RESULTS: Six RCTs were included for pooled analysis. Compared with culprit-only revascularization, complete revascularization significantly reduced the risk of MACE (hazard ratio 0.48, 95% confidence interval 0.42-0.55; I2 = 0%; P for relative effect < .001). This significant reduction in the risk of MACE exhibited by complete revascularization was observed in most of the subgroups of interest. All of the subgroup effects based on the 5 factors of interest were not statistically significant (Psubgroup ranged from 0.198 to 0.556). Publication bias was not suggested by funnel plots and Egger test. CONCLUSIONS: Compared with culprit-only revascularization, complete revascularization significantly reduces the MACE risk in patients with STEMI and multivessel disease, which is independent of sex, age, history of diabetes, ECG infarct location, and the number of arteries with stenosis.

Worldwide prevalence of early repolarization pattern in general population and physically active individuals: A meta-analysis.

BACKGROUND: The early repolarization pattern (ERP) has recently been associated with cardiac events such as ventricular arrhythmias and sudden cardiac death. However, estimates of the prevalence of ERP vary widely, especially between the general population and physically active individuals. We performed this systematic review and meta-analysis to quantitatively evaluate the worldwide prevalence of ERP in the general population and physically active individuals. METHODS: We thoroughly searched the PubMed, EMBASE, Web of science, the Cochrane Library, and Scopus databases for relevant studies published until December 20, 2020. Studies in which prevalence was presented or could be estimated from eligible data were included. The pooled prevalence was analyzed using a random-effect model. RESULTS: Finally, we included 29 studies (182,135 subjects) in the general population and 14 studies (8087 subjects) in the physically active individuals. The worldwide pooled prevalence of ERP in the general population was 11.6% (95% confidence interval [CI]: 10.0%-13.3%). The incidence of ERP was 17.0% and 6.2% in men and women, respectively. The prevalence was 20.9% in blacks, 13.4% in Asians, and 10.1% in Caucasians. Additionally, the prevalence of ERP in physically active individuals was 33.9% (95% CI: 25.3%-42.6%). CONCLUSION: A significant difference in the worldwide prevalence of ERP is revealed in this study. The ERP is highly prevalent in men, blacks, and physically active individuals.

Comprehensive analysis of the safety of semaglutide in type 2 diabetes: a meta-analysis of the SUSTAIN and PIONEER trials.

The PIONEER and SUSTAIN serial trials are designed to assess the efficacy outcomes with semaglutide in patients with type 2 diabetes, but are not powered to assess various safety outcomes. We sought to assess the risk of semaglutide in leading to various serious adverse events (SAEs) in patients with type 2 diabetes. Studies eligible for inclusion were the PIONEER and SUSTAIN trials of semaglutide. We conducted meta-analysis to generate pooled risk ratios (RRs) and 95% confidence intervals (CIs). Meta-analysis was performed using both random-effects and fixed-effects model to evaluate the robustness of pooled results. We implemented subgroup analysis according to drug dosages and routes of administration and type of comparators. Twenty-one trials were included. Semaglutide versus control significantly reduced total SAEs (RR 0.92, 95% CI 0.87-0.97; I2 = 0) and atrial fibrillation (RR 0.69, 95% CI 0.50-0.95; I2 = 0), but significantly increased deep vein thrombosis (RR 3.66, 95% CI 1.09-12.25; I2 = 0) and diarrhoea (RR 2.66, 95% CI 1.19-5.95; I2 = 0). Semaglutide had no significant effects on 248 other kinds of SAEs. No statistically significant subgroup effects were observed. Semaglutide has a good safety profile in general and reduces atrial fibrillation by 31%, but increases diarrhoea by 166% and deep vein thrombosis by 266%. These findings may guide that semaglutide should be preferred or avoided in T2D patients with specific susceptibility factors.

Safety of four SGLT2 inhibitors in three chronic diseases: A meta-analysis of large randomized trials of SGLT2 inhibitors.

There are no relevant meta-analyses that have assessed the safety of the sodium-glucose transporter 2 (SGLT2) inhibitors in different chronic diseases. We aimed at evaluating the safety of four SGLT2 inhibitors in three chronic diseases by meta-analysis of the large randomized trials of SGLT2 inhibitors. We performed random-effects meta-analysis and carried out subgroup analysis according to type of underlying diseases and type of SGLT2 inhibitors. SGLT2 inhibitors versus placebo significantly reduced the risk of acute kidney injury (RR 0.75, 95% CI 0.66-0.85), and showed the reduced trend in the risk of severe hypoglycemia (RR 0.86, 95% CI 0.71-1.03). SGLT2 inhibitors significantly increased the risks of diabetic ketoacidosis (RR 2.57), genital infection (RR 3.75), and volume depletion (RR 1.14); and showed the increased trends in the risks of fracture (RR 1.07), amputation (RR 1.21), and urinary tract infection (RR 1.07). These effects exhibited by SGLT2 inhibitors were consistent across three chronic diseases (i.e. type 2 diabetes, chronic heart failure, and chronic kidney disease) and four SGLT2 inhibitors (i.e. dapagliflozin, empagliflozin, ertugliflozin, and canagliflozin) (all Psubgroup > 0.05). These findings will guide that specific adverse events are monitored when SGLT2 inhibitors are used in clinical practice.

Double antithrombotic therapy for prevention of bleeding and ischemic events after percutaneous coronary intervention in patients with atrial fibrillation: A meta-analysis.

BACKGROUND: The efficacy of double antithrombotic therapy (DAT) vs. triple antithrombotic therapy (TAT) for prevention of bleeding and ischemic events in patients with atrial fibrillation following percutaneous coronary intervention (PCI) is unclear in those subgroups defined by the 5 factors (i.e., sex, age, race, history of diabetes, and type of P2Y12 inhibitor). We aimed to assess the efficacy of DAT vs TAT in these patient subgroups. METHODS: We searched PubMed and relevant websites to include related randomized controlled trials (RCTs). Two endpoints of interest were clinically significant bleeding and major adverse cardiac events (MACE). Meta-analysis was performed stratified by 5 factors of interest (i.e., sex, age, race, history of diabetes, and type of P2Y12 inhibitor) to obtain pooled hazard ratio (HR) and 95% confidence interval (CI). Meta-regression analysis was conducted to evaluate subgroup effects. We detected publication bias by Egger test and funnel plots. RESULTS: We included 4 RCTs for meta-analysis. DAT vs TAT significantly reduced the risk of clinically significant bleeding (HR 0.56, 95% CI 0.50-0.63). This effect of DAT was observed in most subgroups of interest (HR ranged from 0.54 to 0.69), and was consistent across various subgroups defined by each of the 5 factors of interest (Psubgroup ranged from 0.290 to 0.794). DAT vs TAT led to the similar risk of MACE (HR 0.98, 95% CI 0.89-1.08). This effect of DAT was observed in all subgroups of interest (all 95% CIs of HRs were across 1.0), and was consistent across various subgroups defined by each of the 5 factors of interest (Psubgroup ranged from 0.308 to 0.828). Publication bias was found only in one subgroup. CONCLUSIONS: Compared with TAT, DAT significantly reduces the risk of clinically significant bleeding and leads to the similar risk of MACE in patients with atrial fibrillation following PCI, irrespective of sex, age, race, history of diabetes, and type of P2Y12 inhibitor used at baseline.

Comparative Efficacy of Glucagon-like Peptide 1 Receptor Agonists and Sodium Glucose Cotransporter 2 Inhibitors for Prevention of Major Adverse Cardiovascular Events in Type 2 Diabetes: A Network Meta-analysis.

ABSTRACT: The comparative efficacy of different glucagon-like peptide 1 receptor agonists and sodium glucose cotransporter 2 inhibitors for prevention of major adverse cardiovascular events (MACE) in type 2 diabetes with or without cardiorenal disease is undefined. PubMed and Embase were searched for relevant randomized trials. We conducted network meta-analysis within the Bayesian framework. Effect sizes were measured using hazard ratio (HR) and 95% confidence interval (CI). We calculated surface under the cumulative ranking curve (SUCRA) values to rank drug interventions for different type 2 diabetic subgroups. Albiglutide (HR 0.76, 95% CI 0.63-0.93) and subcutaneous semaglutide (HR 0.71, 95% CI 0.52-0.95), with the maximum SUCRA values, significantly reduced MACE versus lixisenatide in people with diabetes with cardiovascular disease; albiglutide (HRs: 0.69 and 0.72), with the maximum SUCRA value, significantly reduced MACE versus dapagliflozin and exenatide in people with diabetes with heart failure; and canagliflozin (HRs: 0.72 and 0.72) and liraglutide (HRs: 0.68 and 0.68), with the maximum SUCRA values, significantly reduced MACE versus exenatide and lixisenatide in people with diabetes with chronic kidney disease. In preventing MACE in type 2 diabetes, subcutaneous semaglutide and albiglutide are most effective for diabetes with cardiovascular disease, albiglutide is most effective for diabetes with heart failure, and canagliflozin and liraglutide are most effective for diabetes with chronic kidney disease.

Comparison of the risk of SGLT2is and NonSGLT2is in leading to amputation: A network meta-analysis.

OBJECTIVE: Whether sodium-glucose cotransporter 2 inhibitors (SGLT2is) increase the risk of amputation or not remains controversial. We aimed to evaluate the relative risk of different SGLT2is and Non-SGLT2i antihyperglycemic drugs (NonSGLT2is) in leading to amputation by network meta-analysis of large sample studies. METHODS: We searched Embase and PubMed for relevant large sample studies. We conducted Bayesian network meta-analysis using random-effects model. Effect size was presented as hazard ratio (HR) and 95% confidence interval (CI). RESULTS: Seventeen large studies involving 1 million SGLT2i users and 3 million NonSGLT2i users were included in network meta-analysis. SGLT2is [HR (95% CI): 1.38 (1.02, 1.91)] versus NonSGLT2is significantly increased the amputation risk, whereas SGLT2is [HR (95% CI): 1.45 (0.94, 2.17)] versus placebo did not. Compared with glucagon-like peptide 1 receptor agonists (GLP1RAs), canagliflozin [HR (95% CI): 1.5 (1.01, 2.33)] along with incorporative SGLT2is [HR (95% CI): 1.64 (1.07, 2.53)] significantly increased the amputation risk, whereas empagliflozin [HR (95% CI): 1.46 (0.83, 2.67)] and dapagliflozin [HR (95% CI): 1.22 (0.7, 2.23)] did not due to the wide 95% CIs of HRs. CONCLUSION: Although SGLT2is versus placebo do not significantly increase the amputation risk, SGLT2is (especially, canagliflozin) versus NonSGLT2is (especially, GLP1RAs) significantly increase that risk.

The expression and the role of PIWI like RNA-mediated gene silencing 3 (PIWIL3) in lung cell line.

BACKGROUND: To determine the expression and role of PIWI-like RNA-mediated gene silencing 3 (PIWIL3) in human lung cancer. METHODS: Immunohistochemistry was performed to measure the expression of PIWIL3 in 30 of pairs lung cancer and corresponding paracancer tissues. Quantitative PCR (qPCR) was conducted to analyze the expression of PIWIL3 in four breast cancer cell lines. siRNA was used to silence PIWIL3 in the lung cancer cells (A549). Methylthiazoletetrazolium (MTT) proliferation assay and colony formation assay were conducted to detect the growth of A549 cells. Fluorescence-activated cell sorting (FACS) was performed to measure the apoptosis of A549 cells. Transwell migration assay and wound scratch healing assay were used to analyze the migration and invasion ability of A549 cells. SPSS 20.0 was used to analyze the data. RESULTS: The expression of PIWIL3 protein was higher in tumor tissues than that in paracancer tissues. In addition, PIWIL3 mRNA was highly expressed in all four lung cancer cell lines. Furthermore, RPS15A knockdown significantly suppressed cell proliferation (P<0.01), induced apoptosis (P<0.01) and inhibited metastasis (P<0.01) of A549 cells. CONCLUSIONS: PIWIL3 was highly expressed in lung cancer tissues and could promote the progression of lung cancer.

[Calcium ionophore induces the differentiation of chronic myeloid leukemia cells into dendritic cells].

The aim of this study was to investigate the ability of calcium ionophore (CI ) to induce the differentiation of CML cells into dendritic cells (DC), to analyze the P210 expression in DCs and to evaluate the stimulatory effect of CML-DC on production of cytotoxic activity against CML cells via activating the autologous T cells. The mononuclear cells were isolated from bone marrow of CML patients whose WBC counts were more than 30x10(9)/L when samples were collected, then the lymphocytes and monocytes were discarded by pouring out supernatant twice at different culture time point. Slightly adherent cells were cultured in RPMI 1640 containing 10% FCS, with or without CI (375 ng/ml) and GM-CSF (200 ng/ml) at 37 degrees C, 5% CO2, fully humidified atmosphere for 96 hours. The cell morphology was observed under the inverted microscope and electron microscope; the expression of CD antigens was analyzed with flow cytometry; the P210 expression was measured with Western blot. LDH assay was used to evaluate the effect of cultured CML cells (CML-DC) generating cytotoxic T lymphocyte (CTL) activity against CML cells. The results indicated that after treatment with calcium ionophore and GM-CSF for 96 hours, CML cells showed DC morphological characteristics under inverted microscope and electron microscope. The expression of CD83, CD86, CD40, CD80 and HLA-DR increased remarkably. P210 was expressed in the CML-DC, but the expression level was lower than that in CML cells without CI and GM-CSF treatment. LDH assay showed that the CTL activity against CML was found greater in autologous T cells activated by CML-DC than that by CML cells. It is concluded that the CML cells can be induced to quickly differentiate into DC when cultured with CI and GM-CSF. CML-DC expresses P210, but the expression level is lower than that in CML cells. CML-DC can stimulate autologous T cells to produce CTL against CML.