Aim The present study aimed to assess the benefits of two-stent techniques for patients with DEFINITION criteria-defined complex coronary bifurcation lesions. Methods and results In total, 653 patients with complex bifurcation lesions at 49 international centres were randomly assigned to undergo the systematic two-stent technique (two-stent group) or provisional stenting (provisional group). The primary endpoint was the composite of target lesion failure (TLF) at the 1-year follow-up, including cardiac death, target vessel myocardial infarction (TVMI), and clinically driven target lesion revascularization (TLR). The safety endpoint was definite or probable stent thrombosis. At the 1-year follow-up, TLF occurred in 37 (11.4%) and 20 (6.1%) patients in the provisional and two-stent groups, respectively [77.8%: double-kissing crush; hazard ratio (HR) 0.52, 95% confidence interval (CI) 0.30–0.90; P = 0.019], largely driven by increased TVMI (7.1%, HR 0.43, 95% CI 0.20–0.90; P = 0.025) and clinically driven TLR (5.5%, HR 0.43, 95% CI 0.19–1.00; P = 0.049) in the provisional group. At the 1 year after indexed procedures, the incidence of cardiac death was 2.5% in the provisional group, non-significant to 2.1% in the two-stent group (HR 0.86, 95% CI 0.31–2.37; P = 0.772). Conclusion For DEFINITION criteria-defined complex coronary bifurcation lesions, the systematic two-stent approach was associated with a significant improvement in clinical outcomes compared with the provisional stenting approach. Further study is urgently warranted to identify the mechanisms contributing to the increased rate of TVMI after provisional stenting. Study registration http://www.clinicaltrials.com; Identifier: NCT02284750.

AimsThe aim of this study was to evaluate the safety and efficacy of transcatheter closure for perimembranous ventricular septal defect (pmVSD) and its long-term results. The most common congenital heart condition is pmVSD. Transcatheter closure of pmVSD is a recently described technique with limited results for mid- to long-term follow-up.Methods and resultsBetween June 2002 and June 2008, 848 patients with pmVSD were enrolled in our study and treated percutaneously with pmVSD occluders. All patients were followed up until December 2008, an average of 37 months. According to colour Doppler transthoracic echocardiography before the intervention and ventriculography, the average end-diastolic pmVSD size was 5.1 and 5.4 mm, respectively. Placement of the device was successful in 832 patients (98.1%) and the median device size was 8.6 mm. During follow-up, 103 adverse events (12.4%) were reported. Most adverse events were categorized as minor and there were nine major adverse events (8.7%), including two complete atrioventricular block requiring pacemaker implantation. Kaplan–Meier estimates showed >85% freedom from major or minor adverse events during a maximal follow-up of 79 months.ConclusionsIn experienced hands, transcatheter pmVSD closure can be performed safely and successfully with low morbidity and mortality. Long-term prognostic results are favourable, and the transcatheter approach provides a less-invasive alternative that may become the first choice in selected pmVSD patients.This trial is registered with ClinicalTrials.gov, number NCT00890799.

Myocardial infarction and stroke are caused by blood clots forming over a ruptured or denuded atherosclerotic plaque (atherothrombosis). Production of prostaglandin E(2) (PGE(2)) by an inflamed plaque exacerbates atherothrombosis and may limit the effectiveness of current therapeutics. Platelets express multiple G-protein coupled receptors, including receptors for ADP and PGE(2). ADP can mobilize Ca(2+) and through the P(2)Y(12) receptor can inhibit cAMP production, causing platelet activation and aggregation. Clopidogrel (Plavix), a selective P(2)Y(12) antagonist, prevents platelets from clotting but thereby increases the risk of severe or fatal bleeding. The platelet EP(3) receptor for PGE(2), like the P(2)Y(12) receptor, also inhibits cAMP synthesis. However, unlike ADP, facilitation of platelet aggregation via the PGE(2)/EP(3) pathway is dependent on co-agonists that can mobilize Ca(2+). We used a ligand-based design strategy to develop peri-substituted bicylic acylsulfonamides as potent and selective EP(3) antagonists. We show that DG-041, a selective EP(3) antagonist, inhibits PGE(2) facilitation of platelet aggregation in vitro and ex vivo. PGE(2) can resensitize platelets to agonist even when the P(2)Y(12) receptor has been blocked by clopidogrel, and this can be inhibited by DG-041. Unlike clopidogrel, DG-041 does not affect bleeding time in rats, nor is bleeding time further increased when DG-041 is co-administered with clopidogrel. This indicates that EP(3) antagonists potentially have a superior safety profile compared to P(2)Y(12) antagonists and represent a novel class of antiplatelet agents.

ObjectivesOur aim was to assess the release level of heparin-binding protein (HBP) in sepsis and septic shock under theThird International Consensus Definitions for Sepsis and Septic Shock(Sepsis-3).DesignProspective cohort study.SettingA general teaching hospital in China.ParticipantsAdult infected patients with suspected sepsis and people who underwent physical examination were included. According to the health status and severity of illness, the research subjects were divided into healthy, local infection, sepsis non-shock and septic shock under Sepsis-3 definitions.Main outcome measuresPlasma levels of HBP, procalcitonin (PCT), C reactive protein (CRP) and complete blood count were detected in all subjects. Single-factor analysis of variance was used to compare the biomarker levels of multiple groups. A receiver operating characteristic (ROC) curve was used to assess the diagnostic capacity of each marker.ResultsHBP levels were significantly higher in patients with sepsis non-shock than in those with local infections (median 49.7ng/mL vs 11.8 ng/mL, p<0.01) at enrolment. Moreover, HBP levels in patients with septic shock were significantly higher than in patients with sepsis without shock (median 153.8ng/mL vs 49.7 ng/mL, p<0.01). The area under the ROC curve (AUC) of HBP (cut-off ≥28.1 ng/mL) was 0.893 for sepsis which was higher than those of PCT (0.856) for a cut-off ≥2.05 ng/mL and of CRP (0.699) for a cut-off ≥151.9 mg/L. Moreover, AUC of HBP (cut-off ≥103.5 ng/mL) was 0.760 for septic shock which was higher than the ROC curve of sequential [sepsis-related] organ failure assessment (SOFA) Score (0.656) for a cut-off ≥5.5. However, there was no significant difference between 28-d survivors (n=56) and 28-d non-survivors (n=37) with sepsis in terms of HBP value (p=0.182).ConclusionsA high level of HBP in plasma is associated with sepsis, which might be a useful diagnostic marker in patients with suspected sepsis.

The ACE gene may be involved in the regulation of skeletal muscle aerobic work efficiency, but is not associated with the ventilatory responses to exercise in COPD patients.

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The relationship between dyslipidemia and type 2 diabetes mellitus (T2D) has been extensively reported, but the global lipid profiles, especially in the East Asia population, associated with the development of T2D remain to be characterized. Liquid chromatography coupled to tandem mass spectrometry was applied to detect the global lipidome in the fasting plasma of 293 Chinese individuals, including 114 T2D patients, 81 prediabetic subjects, and 98 individuals with normal glucose tolerance (NGT). Both qualitative and quantitative analyses revealed a gradual change in plasma lipid features with T2D patients exhibiting characteristics close to those of prediabetic individuals, whereas they differed significantly from individuals with NGT. We constructed and validated a random forest classifier with 28 lipidomic features that effectively discriminated T2D from NGT or prediabetes. Most of the selected features significantly correlated with diabetic clinical indices. Hydroxybutyrylcarnitine was positively correlated with fasting plasma glucose, 2-hour postprandial glucose, glycated hemoglobin, and insulin resistance index (HOMA-IR). Lysophosphatidylcholines such as lysophosphatidylcholine (18:0), lysophosphatidylcholine (18:1), and lysophosphatidylcholine (18:2) were all negatively correlated with HOMA-IR. The altered plasma lipidome in Chinese T2D and prediabetic subjects suggests that lipid features may play a role in the pathogenesis of T2D and that such features may provide a basis for evaluating risk and monitoring disease development.

Prenatal US is the modality of choice for the diagnosis of fetal arachnoid cysts. Serial US examinations are critical to monitor the lesions. Moreover, prenatal MRI is a valuable complementary tool. For live births, the prognosis appears to be good.