Julien Mancini

High on-treatment platelet reactivity after prasugrel loading dose and cardiovascular events after percutaneous coronary intervention in acute coronary syndromes.

OBJECTIVES The aim of this study was to investigate the relationship between platelet reactivity (PR) after a loading dose (LD) of prasugrel and thrombotic events. BACKGROUND Post-treatment PR has been shown to be strongly associated with the occurrence of major adverse cardiac events (MACE) after percutaneous coronary intervention (PCI) in the clopidogrel era. Prasugrel is a new P2Y(12)-adenosine diphosphate receptor with a higher potency on PR. METHODS A prospective multicenter study included patients who underwent successful PCI for acute coronary syndromes and received prasugrel therapy. Vasodilator-stimulated phosphoprotein (VASP) index was measured after the prasugrel LD. High on-treatment PR was defined as a VASP index ≥50%. MACE included cardiovascular death, myocardial infarction, and definite stent thrombosis at 1 month. RESULTS Three hundred one patients were enrolled. The mean VASP index after 60 mg of prasugrel was 34.3 ± 23.1%. High on-treatment PR was observed in 76 patients (25.2%). Patients experiencing thrombotic events after PCI had significantly higher VASP indexes compared with those free of events (64.4 ± 14.4% vs. 33.4 ± 22.7%; range: 51% to 64% and 5% to 47.6%, respectively; p = 0.001). Kaplan-Meier analysis comparing good responders and patients with high on-treatment PR demonstrated a significantly higher rate of MACE in patients with suboptimal PR inhibition (log-rank p < 0.001). Receiver-operating characteristic curve analysis found a cutoff value of 53.5% of the VASP index to predict thrombotic events at 1 month (r = 0.86, p < 0.001). Patients with minor or major Thrombolysis In Myocardial Infarction unrelated to coronary artery bypass grafting bleeding and those without had similar VASP indexes (30 ± 17.8% vs. 34.3 ± 23%, p = 0.70). CONCLUSIONS Despite the use of prasugrel, a significant number of patients undergoing PCI in the setting of acute coronary syndromes do not achieve optimal PR inhibition. Such patients have a higher risk for MACE after PCI.

The timing of surgery influences mortality and morbidity in adults with severe complicated infective endocarditis: a propensity analysis

AIMS To determine whether the timing of surgery could influence mortality and morbidity in adults with complicated infective endocarditis (IE). METHODS AND RESULTS In 291 consecutive adults with definite IE who underwent surgery during the active phase, we compared those operated on within the first week of antimicrobial therapy (n=95) to those operated on later (n=191). The impact of the timing of surgery on 6-month mortality, relapses, and postoperative valvular dysfunctions (PVD) was analysed using propensity score (PS) analyses. After stratification of the cohort into quintiles based on the PS, ≤1st week surgery was associated with a trend of decrease in 6-month mortality in the quintile of patients with the most likelihood of undergoing this early surgical management [quintile 5: 11% vs. 33%, odds ratio (OR)=0.18, 95% CI (confidence interval) 0.04-0.83, P=0.03]. Patients of this subgroup were younger, were more likely to have Staphylococcus aureus infections, congestive heart failure, and larger vegetations. Besides, ≤1st week surgery was associated with an increased number of relapses or PVD (16% vs. 4%, adjusted OR=2.9, 95% CI 0.99-8.40, P=0.05). CONCLUSION Surgery performed very early may improve survival in patients with the most severe complicated IE. However, a greater risk of relapses and PVD should be expected when surgery is performed very early.

Clopidogrel Loading Dose Adjustment According to Platelet Reactivity Monitoring in Patients Carrying the 2C19*2Loss of Function Polymorphism

OBJECTIVES We aimed to investigate the biological impact of a tailored clopidogrel loading dose (LD) according to platelet reactivity monitoring in carriers of the cytochrome (CYP) 2C19*2 loss-of-function polymorphism undergoing percutaneous coronary intervention for an acute coronary syndromes. BACKGROUND CYP2C19*2 polymorphism is associated with reduced clopidogrel metabolism and a worse prognosis after percutaneous coronary intervention. METHOD A prospective multicenter study enrolling 411 patients with non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention was performed. Platelet reactivity was measured using the vasodilator-stimulated phosphoprotein (VASP) index, and a cutoff value of ≥ 50% was used to define high on-treatment platelet reactivity (HTPR). The genetic polymorphism of CYP2C19 was determined by allele-specific polymerase chain reaction. In patients carrying CYP2C19*2 and exhibiting HTPR after a first 600-mg LD of clopidogrel, dose adjustment was performed by using up to 3 additional 600 mg LDs to obtain a VASP index <50%. RESULTS One hundred thirty-four patients (35.3%) carried at least one 2C19*2 allele (11 homozygotes [2.7%] and 123 heterozygotes [32.6%]). The VASP index in these patients was significantly higher than in homozygotic patients for the wild-type alleles (61.7 ± 18.4% vs. 49.2 ± 24.2%; p < 0.001). Of the 134 carriers of the loss-of-function polymorphism, 103 were considered to have HTPR. After a second clopidogrel LD, the VASP index was significantly decreased in these patients (69.7 ± 10.1% vs. 50.6 ± 17.6%; p < 0.0001). Finally, dose adjustment according to platelet reactivity monitoring, enabled 88% of 2C19*2 carriers exhibiting HTPR to reach a VASP index <50%. CONCLUSIONS Increased and tailored clopidogrel loading dose according to platelet reactivity monitoring overcome HTPR in carriers of the loss-of-function CYP2C19*2 polymorphism.

Relationship between post-treatment platelet reactivity and ischemic and bleeding events at 1-year follow-up in patients receiving prasugrel

Summary.  Background:  Post‐treatment platelet reactivity (PR) is associated with ischemic and bleeding events in patients receiving P2Y12 receptor antagonists.

Long-term outcomes following infection of cardiac implantable electronic devices: a prospective matched cohort study

Objective To assess long-term outcomes and predictors of mortality in patients treated according to current recommendations for cardiac implantable electronic device (CIED) infection. Design Two-group matched cohort study. Setting Tertiary-care institution. Patients Consecutive patients admitted for CIED infection between 2004 and 2008 were prospectively enrolled. Study subjects were matched to a cohort of uninfected CIED patients by age, sex and type of device. Interventions In all infected patients, the therapeutic approach consisted of complete hardware removal whenever possible, antimicrobial therapy, and implantation of a new device, if indicated. Patients were systematically followed, with standardised outcomes assessment. Main outcome measures All-cause mortality and predictors of long-term mortality. Results 197 patients were included and matched 1:1 to controls. Pocket infections were present in 41.1% and definite or suspected infective endocarditis in 58.9%. Total or subtotal hardware removal was achieved in 98.5% of cases. Median follow up was 25 months (12–70). Mortality rates in the study group and controls were 14.3% vs 11.0% (NS) at 1 year and 35.4% vs 27.0% (p=NS) at 5 years. Independent predictors of long-term mortality were older age (HR=1.09, p<0.001), cardiac resynchronisation therapy (HR=3.70, p=0.001), thrombocytopenia (HR=5.10, p=0.003) and renal insufficiency (HR=2.66, p=0.006). In patients with reimplanted devices, epicardial right ventricular pacemakers were associated with higher mortality (HR=2.85, p=0.034). Conclusion In patients with CIED infection managed by recommended therapy, long-term mortality rates are similar to comparable controls. Independent predictors include patient and disease-related factors, in addition to implantation of right ventricular epicardial pacemakers.

Mortality associated with systemic lupus erythematosus in France assessed by multiple-cause-of-death analysis.

To assess the mortality profile of systemic lupus erythematosus (SLE) patients in France using multiple‐cause‐of‐death analysis.

Disrupting the right prefrontal cortex alters moral judgement

Humans daily face social situations involving conflicts between competing moral decision. Despite a substantial amount of studies published over the past 10 years, the respective role of emotions and reason, their possible interaction, and their behavioural expression during moral evaluation remains an unresolved issue. A dualistic approach to moral evaluation proposes that the right dorsolateral prefrontal cortex (rDLPFc) controls emotional impulses. However, recent findings raise the possibility that the right DLPFc processes emotional information during moral decision making. We used repetitive transcranial magnetic stimulation (rTMS) to transiently disrupt rDLPFc activity before measuring decision making in the context of moral dilemmas. Results reveal an increase of the probability of utilitarian responses during objective evaluation of moral dilemmas in the rTMS group (compared to a SHAM one). This suggests that the right DLPFc function not only participates to a rational cognitive control process, but also integrates emotions generated by contextual information appraisal, which are decisive for response selection in moral judgements.

Impact of laparoscopy simulator training on the technical skills of future surgeons in the operating room: a prospective study

BACKGROUND The efficacy of laparoscopy simulators remains controversial. METHODS This was a comparative prospective study that evaluated the impact of simulator training on technical competence during a real surgical procedure. Residents were divided into 3 groups: the Mcgill Inanimate System for Training and Evaluation of Laparoscopic Skills (MISTELS) group, training on a simple simulator; LAP Mentor group, training on a virtual simulator; and control group. An initial evaluation was made by a validated score during a laparoscopic cholecystectomy. Each resident was then trained for 1 month. A second evaluation was then performed. RESULTS Before/after scores were significantly improved in the MISTELS (P = .042) and LAP Mentor (P = .026) groups. It was not the case in the control group. There was a better progression in the MISTELS (P = .026) and LAP Mentor (P = .007) groups than in the control group. There was no significant difference between the MISTELS and LAP Mentor groups. CONCLUSIONS Simulator training provides a more rapid acquisition of competence in surgical technique.

Plasmatic Level of Leukocyte-Derived Microparticles Is Associated With Unstable Plaque in Asymptomatic Patients With High-Grade Carotid Stenosis

OBJECTIVES This study sought to analyze whether the plasmatic level of leukocyte-derived microparticles (LMP) is associated with unstable plaques in patients with high-grade carotid stenosis. BACKGROUND Preventive carotid surgery in asymptomatic patients is currently debated given the improvement of medical therapy. Therefore, noninvasive biomarkers that can predict plaque instability are needed. The LMPs, originating from activated or apoptotic leukocytes, are the major microparticle (MP) subset in human carotid plaque extracts. METHODS Forty-two patients with >70% carotid stenosis were enrolled. Using a new standardized high-sensitivity flow cytometry assay, LMPs were measured before thromboendarterectomy. The removed plaques were characterized as stable or unstable using histological analysis according to the American Heart Association criteria. The LMP levels were analyzed according to the plaque morphology. RESULTS The median LMP levels were significantly higher in patients with unstable plaque (n = 28; CD11bCD66b+ MP/μl 240 [25th to 75th percentile: 147 to 394], and CD15+ MP/μl 147 [60 to 335]) compared to patients with stable plaque (16 [0 to 234] and 55 [36 to 157]; p < 0.001 and p < 0.01, respectively). The increase in LMP levels was also significant when considering only the group of asymptomatic patients with unstable plaque (n = 10; CD11bCD66b+ MP/μl 199 [153 to 410] and CD15+ MP/μl 78 [56 to 258] compared with patients with stable plaque (n = 14; 20 [0 to 251] and 55 [34 to 102]; p < 0.05 and p < 0.05, respectively). After logistic regression, the neurologic symptoms (odds ratio: 48.7, 95% confidence interval: 3.0 to 788, p < 0.01) and the level of CD11bCD66b+ MPs (odds ratio: 24.4, 95% confidence interval: 2.4 to 245, p < 0.01) independently predicted plaque instability. CONCLUSIONS LMP constitute a promising biomarker associated with plaque vulnerability in patients with high-grade carotid stenosis. These data provide clues for identifying asymptomatic subjects that are most at risk of neurologic events.

FDG-PET predicts survival in recurrent high-grade gliomas treated with bevacizumab and irinotecan

Prognosis of recurrent high-grade glioma (HGG) is poor, although bevacizumab has been documented in that context. This study aimed to determine the independent prognostic value of fluorodeoxyglucose (FDG)-PET on progression-free survival (PFS) and overall survival (OS) of recurrent HGG after combined treatment with bevacizumab and irinotecan, compared with other documented prognostic variables. Twenty-five adult patients with histologically proven HGG were included at recurrence. Brain FDG-PET imaging was performed within 6 weeks of starting chemotherapy with bevacizumab and irinotecan. Response based on MRI was assessed every 2 months according to revised assessment in Neuro-Oncology (RANO) criteria. Median PFS and OS were 4 months (range, 0.9-10.4 months) and 7.2 months (range, 1.2-41.7 months), respectively. At 6 months, PFS and OS rate were 16.0% and 72.0%. FDG uptake was the most powerful predictor of both PFS and OS, using either univariate or multivariate analysis, among all variables tested: histological grade, Karnofsky performance status, steroid intake, and number of previous treatments. Moreover, FDG uptake was also prognostic of response to bevacizumab-based therapy. This study provides the first evidence that pretreatment FDG-PET can serve as an imaging biomarker in recurrent HGG for predicting survival following anti-angiogenic therapy with bevacizumab.