Correction: Long-term efficacy and safety of carotid artery stenting versus endarterectomy: A meta-analysis of randomized controlled trials.

[This corrects the article DOI: 10.1371/journal.pone.0180804.].

Long-term efficacy and safety of carotid artery stenting versus endarterectomy: A meta-analysis of randomized controlled trials.

BACKGROUND: Many recent trials have investigated the long-term efficacy and safety of endarterectomy versus stenting in treating patients with carotid artery stenosis. We aimed to determine the long-term comparative efficacy and safety of both procedures by pooling this evidence in a meta-analysis. METHODS: We searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials for studies published until May 6, 2016. Randomized controlled trials, which reported outcomes of interest with a median follow-up of at least 4-year, were included. RESULTS: Eight trials involving 7005 patients and 41824 patient-years of follow-up were included. In terms of the periprocedural outcomes, stenting was associated with a lower risk of myocardial infarction (OR: 0.51; 95% CI: 0.33 to 0.80; P = 0.003) but a higher risk of death or stroke (the composite endpoint, OR: 1.76; 95% CI: 1.38 to 2.25; P < 0.0001), a result that was primarily driven by minor stroke (OR: 2.19; 95% CI: 1.59 to 3.01; P < 0.0001), less so by periprocedural death (OR: 1.68; 95% CI: 0.82 to 3.44; P = 0.16) and major stroke (OR: 1.41; 95% CI: 0.95 to 2.09; P = 0.09). In terms of the long-term outcomes, stenting was associated with a higher risk of stroke (OR 1.45; 95% CI: 1.22 to 1.73; P < 0.0001) and the composite outcome of death or stroke (OR 1.25; 95% CI: 1.05 to 1.48; P = 0.01). No difference was found in long-term all-cause mortality between stenting and endarterectomy (OR: 1.09; 95% CI: 0.95 to 1.26; P = 0.21) and restenosis (OR: 1.48 (95% CI: 0.93 to 2.35; P = 0.10). No evidence of significant heterogeneity was found in any of the analyses. CONCLUSIONS: Carotid endarterectomy was found to be superior to stenting for short- and long-term outcomes, although endarterectomy was associated with a higher risk of periprocedural myocardial infarction. Carotid endarterectomy should be offered as the first choice for carotid stenosis at present, however, more evidence is needed because rapid progress in concurrent devices and medical treatments is being made.

Next-generation sequencing identifies pathogenic and modifier mutations in a consanguineous Chinese family with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a highly heterogeneous disease displaying considerable interfamilial and intrafamilial phenotypic variation, including disease severity, age of onset, and disease progression. This poorly understood variance raises the possibility of genetic modifier effects, particularly in MYBPC3-associated HCM.In a large consanguineous Chinese HCM family, we identified 8 members harboring the MYBPC3 c.3624delC (p.Lys1209Serfs) disease-causing mutation, but with very disparate phenotypes. Genotyping ruled out the modifying effect of previously described variants in renin-angiotensin-aldosterone system. Afterwards, we screened for modifying variants in all known causing genes and closely related genes for cardiomyopathy and channelopathy by performing targeted next-generation sequencing. For first time, we showed that a c.1598C>T (p.Ser533Leu) mutation in voltage-dependent l-type calcium channel subunit beta-2 (CACNB2) was present in all severely affected HCM patients, but not in those moderately affected or genotype-positive phenotype-negative patients. This CACNB2 p.Ser533Leu mutation is extremely conserved in evolution, and was not found in 550 healthy controls.Our results suggest that CACNB2 is a possible candidate genetic modifier of MYBPC3-associated familial HCM, but more genetic evidence and functional experiments are needed to confirm.

Oncostatin M was associated with thrombosis in patients with atrial fibrillation.

The mechanism underlying thrombosis in atrial fibrillation (AF) is not yet clearly understood. Oncostatin M (OSM), as a member of IL-6 family, is involved in atherosclerosis-mediated thrombosis. The present study hypothesizes that OSM and its downstream factors play a role in thrombogenesis in AF.The specimens of left atrial appendages collected from patients with rheumatic mitral stenosis who underwent valve replacement were divided into 3 groups: sinus rhythm, AF(+)/thrombus(-), and AF(+)/thrombus(+) group. The macrophage infiltration in atrial tissue was assessed by immunohistochemistry, and the amount of OSM, tissue factor (TF), and tissue factor pathway inhibitors (TFPIs) was detected by Western blot.The infiltration of the M1 macrophages was significantly increased in the AF with thrombus group compared with the sinus rhythm group (P = .03). Moreover, the expression of OSM and TF was much higher in the AF with thrombus group compared with the sinus rhythm group (P = .02, .009, respectively) while the TFPI was decreased in the AF with thrombus group (P = .04).OSM might be correlated with thrombosis in patients with AF mediated by TF and TFPI.

Percutaneous intervention versus coronary artery bypass graft surgery in left main coronary artery stenosis: a systematic review and meta-analysis.

BACKGROUND: The optimal revascularization technique in patients with left main coronary artery disease (CAD) remains controversial. We aimed to compare the long-term performance of percutaneous coronary intervention (PCI) versus coronary artery bypass graft (CABG) surgery in treatment of left main CAD. METHODS: PubMed, EMBASE, and the Cochrane Library were searched until November 16, 2016. RESULTS: Six randomized controlled trials and 22 matched observational studies including 22,487 patients and 90,167 patient-years of follow-up were included. PCI was associated with an overall higher risk for the major adverse cardiac and cerebrovascular events (hazard ratio (HR), 1.42; 95% confidence interval (CI), 1.14-1.77), mainly driven by higher rates of myocardial infarction (HR, 1.69; 95% CI, 1.22-2.34) and revascularization (HR, 2.80; 95% CI, 1.86-4.22). The overall risks for all-cause death (HR, 1.05; 95% CI, 0.93-1.20), cardiac death (HR, 1.05; 95% CI, 0.69-1.59), stroke (HR, 0.64; 95% CI, 0.33-1.24), and the composite safety endpoint of death, myocardial infarction, or stroke (HR, 1.06; 95% CI, 0.97-1.16) were similar between PCI and CABG. Stratified analysis based on stent types showed that the increased risk for myocardial infarction associated with PCI was only evident in patients with bare-metal stents or early-generation drug-eluting stents (DES), but not newer-generation DES. Stratified analyses based on study designs showed largely similar findings with the overall analyses, except for a significantly higher incidence of myocardial infarction in adjusted studies (HR, 2.01; 95% CI, 1.64-2.45) but a trend toward higher incidence in randomized trials (HR, 1.39; 95% CI, 0.85-2.27) associated with PCI. CONCLUSIONS: Compared with CABG, PCI with newer-generation DES might be a safe alternative revascularization strategy for treatment of left main CAD, but is associated with more repeat revascularization.

Increased M1 Macrophages Infiltration Is Associated with Thrombogenesis in Rheumatic Mitral Stenosis Patients with Atrial Fibrillation.

Atrial fibrillation (AF) is the most common arrhythmia. In patients with AF, the role of macrophage subsets in thrombogenesis is unclear. In the present study, we analyzed the role of M1 and M2 macrophages and related cytokines in thrombogenesis of AF. Immunohistochemistry, Western blot, and TUNEL assay were used to detect M1/M2 macrophage infiltration, the expression pattern of IL-1ß and inflammasome components, and apoptosis of cardiomyocytes in 71 specimens obtained from the left atrial appendage of patients with rheumatic mitral stenosis (MS) with or without thrombosis. We demonstrated that proinflammatory M1 macrophages were predominant in the atrium of MS patients with AF and thrombus. NLRP3 inflammasomes and IL-1ß, which are primarily functional in macrophages, were activated in those patients. We also showed that increased cell death was associated with thrombogenesis in MS patients. These data indicate that infiltration of M1 macrophages and over-activation of NLRP3 inflammasomes may play a role in progressive atrial inflammation and thrombogenesis in rheumatic mitral stenosis patients with AF.

[HPLC determination of metformin hydrochloride-related substances].

OBJECTIVE: To develop a HPLC assay for the determination of metformin hydrochloride-related substances. METHODS: The separation was performed on SHIMADZU VP-ODS (250 4.6 mm, 5 microm) column. The mobile phase of dicyandiamide was composed of methyl alcohol-1 mmol x L(-1) sodium dodecylsulfate in 10 mmol x L(-1) phosphate salt solution (60:40) (pH=5.5). The mobile phase of other related substances was composed of methyl alcohol-1 mmol x L(-1) sodium dodecysulfate in 10 mmol x L(-1) phosphate salt solution (55:45)(pH=5.5). The detection wavelength was 232 nm, and the running speed was 0.8 ml min(-1) at room temperature. RESULT: Good resolution of dicyandiamide and main peak was obtained. The test results were reproducible. CONCLUSION: The method is simple, rapid and suitable for the determination of dicyandiamide and other metformin hydrochloride-related substances.