Clinical and Echocardiographic Features of Patients With Infective Endocarditis and Bicuspid Aortic Valve According to Echocardiographic Definition of Valve Morphology.

BACKGROUND: The influence of different bicuspid aortic valve (BAV) morphology in the clinical course of infective endocarditis (IE) has not yet been investigated. This study aimed to describe the clinical and echocardiographic features of IE in patients with BAV (BAVIE) according to valve morphology. METHODS: Patients with definite BAVIE prospectively enrolled in 4 high-volume referral centers from 2000 to 2019 were evaluated and divided into 2 groups according to the echocardiographic definition of fused BAV morphology: right-left coronary (RL type) and right noncoronary or left noncoronary (non-RL type) cusp fusion. All patients were followed up for 1 year. RESULTS: One hundred thirty-eight patients with BAVIE were included (77.7% male; median age, 52 [36.83-61.00] years): 112 patients with RL type (81%) and 26 patients with non-RL type BAV (19%), with no significant differences in age, sex, and comorbidities between groups. Although 43% of the cohort had known BAV, the referral was late after symptom onset, particularly for the RL phenotype; time from symptom onset to hospitalization >30 days (31.3% vs 11.5%; P = .032) and New York Heart Association class ≥ II (64.3% vs 42.3%; P = .039) were more frequent in patients with RL type BAV than in patients with non-RL type BAV. Conversely, patients with non-RL type BAV had a higher incidence of hemorrhagic stroke (19.2% vs 5.4%; P = .034) and high-grade atrioventricular block (11.5% vs 0.9%; P = .021). Streptococcus viridans was more frequently isolated in patients with non-RL type BAV than in patients with RL type BAV (44% vs 24.1%; P = .045). No difference in short- and intermediate-term mortality was observed between groups. CONCLUSIONS: Clinical profile and echocardiographic features in BAVIE patients may differ according to valve morphology, and patients with BAVIE appear to be referred late, even when BAV disease is previously known.

Influence of the healthcare pathway on the outcome of patients with infective endocarditis.

AIMS: To determine the prognosis of patients treated for infective endocarditis (IE) according to their healthcare pathway. To assess how the ESC guidelines are implemented concerning the performance of transoesophageal echocardiography, the use of antibiotic therapy, and the performance of valve surgery; and to compare the epidemiological profile of IE according to the type of centres in which the patients are hospitalized. METHODS AND RESULTS: In a prospective multicentric study including 22 hospitals in the South-East of France, 342 patients were classified into three groups according to their healthcare pathway: 119 patients diagnosed and taken care entirely in a reference centre or hospital with cardiac surgery [Referral Center (RC) group], 111 patients diagnosed and initially taken care in a non-RC (NRC), then referred in a centre including cardiac surgery [transferred to the Referral Center (TRC) group] and 112 patients totally taken care in the NRC (NRC group). One-year mortality was 26% (88 deaths) and was not significantly different between Groups 1 and 2 (20 vs. 21%, P = 0.83). Patients in the NRC group had a higher mortality (37%) compared with patients in the RC and TRC groups (P < 0.001). ESC guidelines were not implemented similarly depending on the healthcare pathway (P = 0.04). Patients in the NRC group were significantly older (P < 0.001) and had more comorbidities (P < 0.001) than patients treated in referral centres. CONCLUSION: Prognosis of patients with IE is influenced by their healthcare pathway. Patients treated exclusively in NRC have a worse prognosis than patients treated in referral or surgical centres.

18F-fluorodeoxyglucose positron emission tomography/computed tomography for the diagnosis of native valve infective endocarditis: A prospective study.

BACKGROUND: 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG PET/CT) has recently been added as a major criterion in the European Society of Cardiology (ESC) 2015 infective endocarditis guidelines. PET/CT is currently used in patients with suspected prosthetic valve and cardiac device-related endocarditis. However, the value of the ESC classification and the clinical impact of PET findings are unknown in patients with native valve endocarditis (NVE). AIMS: Our aims were: to assess the value of the ESC criteria (including PET/CT) in NVE; to determine the usefulness of PET/CT concerning embolic detection; and to describe a new PET/CT feature (diffuse splenic uptake). METHODS: Between 2012 and 2017, 75 patients with suspected NVE were included prospectively, after exclusion of patients with uninterpretable or unfeasible PET/CT. Using gold standard expert consensus, 63 cases of infective endocarditis were confirmed and 12 were rejected. RESULTS: Significant valvular uptake was observed in 11 of 63 patients with definite NVE and in no patients who had the diagnosis of infective endocarditis rejected (sensitivity 17.5%, specificity 100%). Among the 63 patients with NVE, a peripheral embolism or mycotic aneurysm was observed in 20 (31.7%) cases. Application of the ESC criteria increased Duke criteria sensitivity from 63.5% to 69.8% (P<0.001), without a change in specificity. Diffuse splenic uptake was observed in 39 (52.0%) patients, including 37 (58.7%) with a final diagnosis of NVE (specificity 83.3%). CONCLUSIONS: 18F-FDG PET/CT has poor sensitivity but high specificity in the diagnosis of NVE. The usefulness of 18F-FDG PET/CT is high for embolic detection. Diffuse splenic uptake represents a possible new diagnostic criterion for NVE.

Comparison Between ESC and Duke Criteria for the Diagnosis of Prosthetic Valve Infective Endocarditis.

OBJECTIVES: The primary objective was to assess the value of the European Society of Cardiology (ESC) criteria, including 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in prosthetic valve infective endocarditis (PVE). Secondary objectives were: 1) to assess the reproducibility of 18F-FDG-PET/CT; 2) to compare its diagnostic value with that of echocardiography; and 3) to assess the diagnostic value of the presence of a diffuse splenic uptake BACKGROUND: 18F-FDG PET/CT has been added as a major criterion in the ESC 2015 infective endocarditis (IE) guidelines, but the benefit of the ESC criteria has not been prospectively compared with the conventional Duke criteria. METHODS: Between 2014 and 2017, 175 patients with suspected PVE were prospectively included in 3 French centers. After exclusion of patients with uninterpretable 18F-FDG PET/CT, 115 patients were evaluated, including 91 definite and 24 rejected IE, as defined by an expert consensus. RESULTS: Cardiac uptake by 18F-FDG PET/CT was observed in 67 of 91 patients with definite PVE and 6 with rejected IE (sensitivity 73.6% [95% confidence interval (CI): 63.3% to 82.3%], specificity 75% [95% CI: 53.3% to 90.2%]). The ESC 2015 classification increased the sensitivity of Duke criteria from 57.1% (95% CI: 46.3% to 67.5%) to 83.5% (95% CI: 74.3% to 90.5%) (p < 0.001), but decreased its specificity from 95.8% (95% CI: 78.9% to 99.9%) to 70.8% (95% CI: 48.9% to 87.4%). Intraobserver reproducibility of 18F-FDG PET/CT was good (kappa = 0.84) but interobserver reproducibility was less satisfactory (kappa = 0.63). A diffuse splenic uptake was observed in 24 (20.3%) patients, including 23 (25.3%) of definite PVE, and only 1 (4.2%) rejected PVE (p = 0.024). CONCLUSIONS: 18F-FDG PET/CT is a useful diagnostic tool in suspected PVE, and explains the greater sensitivity of ESC criteria than Duke criteria. However, 18F-FDG PET/CT also presents with important limitations concerning its feasibility, specificity, and reproducibility. Our study describes for the first time a new endocarditis criterion, that is, the presence of a diffuse splenic uptake on 18F-FDG PET/CT.

Use of Direct Oral Anticoagulants in Patients with Sickle Cell Disease and Venous Thromboembolism: A Prospective Cohort Study of 12 Patients.

Patients with sickle cell disease have an increased risk of venous thromboembolism (VTE) and with a mortality 2-fold higher. The anticoagulation of VTE in a young population is an important question. Indeed, hemorrhagic complications of anticoagulation may occur more frequently than in the general population. The use of a direct oral anticoagulant (DOAC) is not recommended for VTE in patients with sickle cell disease because those patients were not included in the clinical studies. We aimed to study the safety of using DOACs in a prospective cohort of patients with sickle cell disease and VTE. We prospectively followed the cohort of all sickle cell disease patients undergoing recent DOAC treatment for VTE at a sickle cell disease reference center. Twelve patients received rivaroxaban for VTE (eight women and four men). The median age was 27 years (20-45). The sickle cell disease variants included homozygous Hb SS (HBB: c.20A>T) in eight patients, Hb S-ß+-thalassemia (Hb S-ß+-thal) in two, Hb S-ß0-thal in one and Hb S-Hb C (HBB: c.19G>A) in one. The cumulative duration of follow-up was 3134 days under rivaroxaban treatment. There were two thrombotic events, including a patient with a double positivity of antiphospholipid antibodies. No major bleeding was observed, and 6/12 patients presented minor bleeding (epistaxis: n = 4; anal fissure bleeding: n = 1; menorrhagia n = 4). Of these, 3/6 required their treatment to be switched to apixaban, which stopped the bleeding. Direct oral anticoagulants may be an alternative treatment for VTE in patients with sickle cell disease, except for an associated antiphospholipid syndrome.

Prognostic Value of 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Infective Endocarditis.

BACKGROUND: 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is commonly used for the diagnosis of infective endocarditis (IE), but its prognostic value remains unknown. OBJECTIVES: This study sought to assess the prognostic value of 18F-FDG PET/CT in prosthetic valve endocarditis (PVE) and native valve endocarditis (NVE). METHODS: This study prospectively included 173 consecutive patients (109 PVE and 64 NVE) with definite left-sided IE who had an 18F-FDG PET/CT and were followed-up for 1 year. The primary endpoint was a composite of major cardiac events: death, recurrence of IE, acute cardiac failure, nonscheduled hospitalization for cardiovascular indication, and new embolic event. RESULTS: 18F-FDG PET/CT was positive in 100 (58%) patients, 83% (n = 90 of 109) in the PVE, and 16% (n = 10 of 64) in the NVE group. At a mean follow-up of 225 days (interquartile range: 199 to 251 days), the primary endpoint occurred in 94 (54%) patients: 63 (58%) in the PVE group and 31 (48%) in the NVE group. In the PVE group, positive 18F-FDG PET/CT was significantly associated with a higher rate of primary endpoint (hazard ratio [HR]: 2.7; 95% confidence interval [CI]: 1.1 to 6.7; p = 0.04). Moderate to intense 18F-FDG valvular uptake was also associated with worse outcome (HR: 2.3; 95% CI: 1.3 to 4.5; p = 0.03) and to new embolic events in PVE (HR: 7.5; 95% CI: 1.24 to 45.2; p = 0.03) and in NVE (HR: 8.8; 95% CI: 1.1 to 69.5; p = 0.02). In the NVE group, 18F-FDG PET/CT was not associated with occurrence of the primary endpoint CONCLUSIONS: In addition to its good diagnostic performance, 18F-FDG PET/CT is predictive of major cardiac events in PVE and new embolic events within the first year following IE.

Flow Cytometry Sorting to Separate Viable Giant Viruses from Amoeba Co-culture Supernatants.

Flow cytometry has contributed to virology but has faced many drawbacks concerning detection limits, due to the small size of viral particles. Nonetheless, giant viruses changed many concepts in the world of viruses, as a result of their size and hence opened up the possibility of using flow cytometry to study them. Recently, we developed a high throughput isolation of viruses using flow cytometry and protozoa co-culture. Consequently, isolating a viral mixture in the same sample became more common. Nevertheless, when one virus multiplies faster than others in the mixture, it is impossible to obtain a pure culture of the minority population. Here, we describe a robust sorting system, which can separate viable giant virus mixtures from supernatants. We tested three flow cytometry sorters by sorting artificial mixtures. Purity control was assessed by electron microscopy and molecular biology. As proof of concept, we applied the sorting system to a co-culture supernatant taken from a sample containing a viral mixture that we couldn't separate using end point dilution. In addition to isolating the quick-growing Mimivirus, we sorted and re-cultured a new, slow-growing virus, which we named "Cedratvirus." The sorting assay presented in this paper is a powerful and versatile tool for separating viral populations from amoeba co-cultures and adding value to the new field of flow virometry.

Clinical implications of very low on-treatment platelet reactivity in patients treated with thienopyridine: the POBA study (predictor of bleedings with antiplatelet drugs).

OBJECTIVES: This study was designed to define the hyperresponse to thienopyridine (very low on-treatment platelet reactivity [VLTPR]) as the most predictive threshold value of platelet reactivity index vasodilator-stimulated phosphoprotein (PRI VASP) for the prediction of non-access site-related bleeding events. We also aimed to identify predictors of bleeding and VLTPR in patients treated with thienopyridines. BACKGROUND: New P2Y12 blockers and platelet monitoring has been proposed to optimize platelet inhibition after acute coronary syndromes and improve ischemic outcomes. However, bleeding complications remain the Achilles' heel of antiplatelet therapy, and platelet monitoring could be useful to evaluate this risk. METHODS: A total of 1,542 consecutive patients undergoing coronary stenting for ACS were included in the present study (287 taking clopidogrel 75 mg, 868 taking clopidogrel 150 mg, and 387 taking prasugrel 10 mg). RESULTS: During 6-month follow-up, 9% of patients (n = 139) experienced nonaccess site-related Bleeding Academic Research Consortium bleeding complications. These patients were more often women and nondiabetic and had lower PRI VASP values than others (p < 0.001). Receiver-operating characteristic curve analysis (0.71, p < 0.01) identified a threshold value for VLTPR of PRI VASP ≤10% to predict bleeding events with a sensitivity of 17% and a specificity of 97%. Although prasugrel was the main predictor of VLTPR in the whole population (odds ratio: 10.2, 95% confidence interval: 3.0 to -34.2; p < 0.001), VLTPR was the strongest and independent predictor of bleeding (odds ratio: 4.7, 95% confidence interval: 2.7 to 8.3; p < 0.001). CONCLUSIONS: The present study identified VLTPR (PRI VASP ≤10%) as the strongest predictor of bleeding complications in patients treated with thienopyridines. This marker could be useful for tailored therapy and bleeding prevention.

Immunoglobulin G anticardiolipin antibodies and progression to Q fever endocarditis.

BACKGROUND: Immunoglobulin G (IgG) anticardiolipin (aCL) antibodies are associated with valvulopathy and endocarditis in patients with lupus and other diseases. During acute Q fever, high IgG aCL prevalence has been reported, but the clinical significance remains unknown. METHODS: To test if increased IgG aCL at acute Q fever diagnosis is associated with an increased risk of progression to endocarditis, all patients diagnosed in the French National Referral Center for Q fever from January 2007 to December 2011 were included and followed regularly until January 2013 in a 5-year prospective cohort study. Q fever endocarditis was defined according to recently updated criteria. RESULTS: Seventy-two patients were followed for a median time of 31 months (interquartile range, 18-47 months). Of these, 13 patients with valvulopathy without antibiotic prophylaxis progressed to endocarditis. IgG aCL levels were highly prevalent (57%) and significantly higher in the presence of a valvulopathy (P = .005). Using Cox regression analysis, highly increased levels of IgG aCL (adjusted hazard ratio [AHR], 12.95; 95% confidence interval, 2.85-58.95; P = .001) and high levels of phase II immunoglobulin M (IgM; AHR, 6.59; 95% CI, 1.37-31.62; P = .018) were the only independent predictors of progression to endocarditis. CONCLUSIONS: Rapid progression from acute Q fever to endocarditis is associated with high levels of IgG aCL and high levels of phase II IgM, findings that should be critical in the prevention of endocarditis.

Effect of CYP2C19*2 and *17 genetic variants on platelet response to clopidogrel and prasugrel maintenance dose and relation to bleeding complications.

The present study was performed to compare the influence of cytochrome P459 2C19 (CYP2C19) *2 and *17 genetic variants on the platelet response to clopidogrel and prasugrel maintenance therapy and to assess the relation between platelet reactivity and bleeding complications. A total of 730 patients were included (517 patients treated with clopidogrel 150 mg/day and 213 discharged with prasugrel 10 mg). Platelet reactivity was assessed at 1 month with the platelet reactivity index vasodilator-stimulated phosphoprotein (PRI VASP). High on-treatment platelet reactivity was defined as PRI VASP >50% and low on-treatment platelet reactivity (LTPR) as PRI VASP <20%. The patients were classified according to their genotypes as poor metabolizers (*2/non *17), intermediate metabolizers (*2/*17 or non *2/non *17) and ultrametabolizers (non *2/*17). At 1 month, the prasugrel response was significantly better than the clopidogrel response in all groups of patients, with a lower incidence of high on-treatment platelet reactivity but a greater incidence of LTPR, regardless of the genetic variants. The genetic distribution had a significant effect on the mean PRI VASP values, the incidence of high on-treatment platelet reactivity, and LTPR with both clopidogrel and prasugrel (p <0.05 for all). LTPR identified a group of patients at a greater risk of bleeding (odds ratio 4.8, 95% confidence interval 2.7 to 8.3; p <0.0001). In conclusion, the present study showed that both clopidogrel and prasugrel have genetic modulation by CYP2C19 *2 and *17 alleles and that prasugrel provides greater platelet inhibition, regardless of the genotypes. In addition, LTPR was associated with a greater risk of bleeding.

Relationship between aspirin and clopidogrel responses in acute coronary syndrome and clinical predictors of non response.

OBJECTIVES: We have prospectively investigated the association between aspirin and clopidogrel responses and the clinical predictors of non response. METHODS: 635 Non ST Elevation Acute Coronary Syndrome (NSTE ACS) patients were included and received loading doses of 250 mg aspirin and 600 mg clopidogrel. We analyzed post-treatment maximal intensity of arachidonic acid and ADP-induced platelet aggregation (AA-Ag and ADP-Ag) and Platelet Reactivity Index of VAsodilator-Stimulated Phosphoprotein (PRI VASP). Aspirin and clopidogrel non responses were defined respectively by AA-Ag>30% and ADP-Ag>70%. RESULTS: Aspirin non responders patients had significantly higher ADP-Ag and PRI VASP than aspirin responders: 63.7+/-15.9% vs 55+/-19% (p=0.0001) and 73.6+/-13.3% vs 53+/-23% (p=0.0001) respectively and the rate of clopidogrel non responders was higher among aspirin non responders than aspirin responders: 36.7% vs 22.7% (p=0.003). In addition, clopidogrel non responders had significantly higher AA-Ag and rate of aspirin non responders than clopidogrel responders: 21.6+/-24% vs 10.3+/-19% (p=0.0001) and 22.8% vs 12.9% (p=0.003) respectively. Age and Body Mass Index (BMI) were significantly associated with non response to Clopidogrel (p=0.035 and 0.02 respectively) and diabetes mellitus by trend (p=0.07). CONCLUSION: We observed a relationship between aspirin and clopidogrel non responses and an association between age, BMI and diabetes mellitus and clopidogrel response.

Metronomic etoposide/cyclophosphamide/celecoxib regimen given to children and adolescents with refractory cancer: a preliminary monocentric study.

BACKGROUND: Metronomic chemotherapy (MC) is the administration of chemotherapy at doses below the maximal tolerated dose on a frequent schedule of administration, with no prolonged drug-free breaks. OBJECTIVE: The aim of this research was to assess the effectiveness and tolerance of a metronomic etoposide/ cyclophosphamide/celecoxib regimen in children and adolescents with refractory cancer. METHODS: This retrospective, single-center study evaluated the use of MC with etoposide 25 mg/m(2).d(-1) (days 1-14), cyclophosphamide 25 mg/m(2) d(-1) (days 15-28), and celecoxib 100 to 400 mg/d (days 1-28), in children with refractory, or high-risk relapsing, cancer. Adverse events were determined through laboratory analyses and investigator observations. RESULTS: From January 2005 to December 2007, 17 children and adolescents were treated. The best responses observed were stabilizations of the disease that lasted over 20 weeks in 7 patients (41%). Most importantly, in 4 patients (24%) antalgic treatment could be transiently diminished or stopped, and in 1 patient (6%) oxygen support could be stopped for several weeks. Four grade IV platelet toxicities were noted in 3 patients; 2 grade IV anemia occurred in 2 patients (who had platelet and red blood cell transfusions before initiation of treatment); and 1 patient had grade III neutropenia. No other grade III or IV toxicities were noted. Grade II alopecia and stomatitis were observed in 1 patient and grade II vomiting was observed in 2 patients. One patient with meningeal carcinomatosis developed bilateral subdural hematoma for which the role of MC could not be ruled out. Circulating endothelial cells were elevated in 3 out of 3 patients in whom they were quantified and who were progressing while under MC. CONCLUSION: The MC regimen we report here was associated with disease stabilization without major toxicities. This assessment of MC in children and adolescents warrants further studies.

ADP-induced platelet aggregation and platelet reactivity index VASP are good predictive markers for clinical outcomes in non-ST elevation acute coronary syndrome.

Clopidogrel responsiveness has been proposed to be involved in recurrent ischemic events after stenting for non-ST elevation acute coronary syndromes (NSTE ACS). However, its biological definition is not consensual. We assess the value of ADP-induced platelet aggregation (ADP-Ag) and platelet reactivity index VASP (PRI VASP) in predicting recurrent ischemic events in patients with NSTE ACS undergoing percutaneous coronary intervention (PCI). We studied 195 consecutive NSTE ACS patients undergoing PCI after a 600 mg loading dose of clopidogrel. ADP-Ag and PRI VASP were analysed. The primary end-point was recurrent ischemic events within 30 days of PCI. It occurred in 14 patients (7%). Construction of ROC curves to examine the value of predictive models showed that sensitivity and specificity for primary endpoint were 79% and 76%, respectively, for a maximal intensity of ADP-Ag >or=70%, 93% and 50% for PRIVASP > 53%. The positive and negative predictive values were 21% and 98%, respectively, for ADP-Ag >or=70%, 12% and 99% for PRIVASP > 53%. In patients with NSTE ACS undergoing PCI, ADP-Ag and PRI VASP identify low responders to clopidogrel with an increased risk of recurrent ischemic events with respective cut-off values of 70% and 53%.

Role of the T744C polymorphism of the P2Y12 gene on platelet response to a 600-mg loading dose of clopidogrel in 597 patients with non-ST-segment elevation acute coronary syndrome.

BACKGROUND: Variability in platelet response to clopidogrel and its clinical relevance have been well described. However, the underlying mechanisms remain unclear. Recently, the T744C polymorphism of the P2Y12 receptor gene has been associated with enhanced platelet aggregation in healthy volunteers, suggesting a possible mechanism for modulation of clopidogrel response. AIM OF THIS STUDY: To assess whether the clopidogrel response may be influenced by the T744C P2Y12 gene polymorphism in patients with non ST elevation acute coronary syndrome (NSTE ACS). METHODS: 597 NSTE ACS patients were included in our study and were divided into 3 groups: CC homozygotes, CT heterozygotes ad TT homozygotes. All patients received loading doses of 600 mg clopidogrel and 250 mg aspirin at least 12 hours before blood samples. Clopidogrel response was assessed by post-treatment ADP 10 micromol/L-induced platelet aggregation (ADP-Ag), VASP phosphorylation (PRI VASP) and P-selectin expression (PS). Clopidogrel resistance was defined by persistence of High Post-treatment Platelet Reactivity (HPPR=ADP-Ag>70%). RESULTS: Significant variability in the distribution of platelet parameters was observed in the overall study population. No significant difference in platelet parameter profiles was observed within patients having the same genotype, for ADP-Ag (p=0.39), PRI VASP (p=0.97) and PS (p=0.62). The genotype frequencies of the T744C polymorphism of the P2Y12 gene were similar in responders and non responders defining by HPPR (p=0.75). CONCLUSION: Our study did not show any influence of the T744C polymorphism of the P2Y12 receptor gene on clopidogrel response assessed by ADP-Ag, PRI VASP or P-selectin expression in NSTE ACS patients.

Lack of association between the 807 C/T polymorphism of glycoprotein Ia gene and post-treatment platelet reactivity after aspirin and clopidogrel in patients with acute coronary syndrome.

Variability in platelet response to antiplatelet therapy and its clinical relevance have been well described. However, the underlying mechanisms remain unclear. It was the aim of the present study to assess whether the response to aspirin and clopidogrel may be influenced by the 807 C/T polymorphism of the glycoprotein Ia (GpIa) gene in patients with non-ST elevation acute coronary syndrome (NSTE ACS). Six hundred one NSTE ACS patients were included in our study and were divided into three groups: CC homozygotes, CT heterozygotes ad TT homozygotes. All patients received loading doses of 600 mg clopidogrel and 250 mg aspirin at least 12 hours before blood samples were drawn. Post-treatment platelet reactivity was assessed by post treatment ADP 10 microM-induced platelet aggregation (ADP-Ag), VASP phosphorylation (PRI VASP) and P-selectin expression. Non-response to dual antiplatelet therapy was defined by high post-treatment platelet reactivity (HPPR=ADP-Ag > 70%). Significant variability in the distribution of platelet parameters was observed in the overall study population. No significant difference in platelet parameters profiles was observed within patients having the same genotype, for ADP-Ag (p=0.33), PRIVASP (p=0.72) and P-selectin expression (p=0.37). The genotype frequencies of the 807 C/T polymorphism of the GpIa gene were similar in responders and non-responders defined by persistent HPPR (p=0.104). In conclusion, our study did not show any influence of 807 C/T polymorphism of GpIa gene on post-treatment platelet reactivity assessed by ADP-Ag, PRI VASP or P-selectin expression in 601 NSTE ACS patients.

Platelet-endothelial cell adhesion molecule-1 and CD146: soluble levels and in situ expression of cellular adhesion molecules implicated in the cohesion of endothelial cells in idiopathic inflammatory myopathies.

OBJECTIVE: Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of diseases characterized by chronic inflammation of muscles. We investigated the role of cellular adhesion molecules implicated in the cohesion of endothelial cells in IIM. METHODS: In 22 patients with IIM we investigated plasma concentrations of soluble junctional adhesion molecules [platelet-endothelial cell adhesion molecule (sPECAM-1) and sCD146] and cellular adhesion molecules [sP-selectin, sE-selectin, intercellular adhesion molecule (sICAM-1), and vascular cell adhesion molecule (sVCAM-1)] implicated in leukocyte/endothelial cell interactions. Results were compared to a control group. Muscle biopsy samples from 8 out of 22 IIM patients were studied by immunohistochemistry for tissue expression of these molecules and compared to normal muscle samples. PECAM-1 and CD146 expression was also studied using immunoblots from muscle biopsies from 5 patients and 2 controls. RESULTS: We observed distinct patterns of soluble levels and in situ expression between dermatomyositis (DM), polymyositis (PM), and sporadic inclusion body myositis (s-IBM). PM samples showed significantly increased levels of sCD146, sPECAM-1, and s-ICAM1 and increased expression of CD146, CD31, and ICAM-1 in endothelial cells, whereas CD146 and ICAM-1 were also recorded in some muscle fibers. In DM, sE-selectin, sP-selectin, and sPECAM-1 were significantly increased, with abnormal expression of ICAM-1 in endothelial cells and perifascicular muscle fibers. In the small group of s-IBM samples, results were similar to PM, but the only significant increase was the level of sPECAM-1. Immunoblots confirmed increased expression of PECAM-1 and CD146 in all IIM muscles in comparison to controls, with the highest expression in PM and IBM samples. CONCLUSION: We observed abnormal increases of soluble levels of adhesion molecules implicated in endothelial cell junctions in PM (sCD146, sPECAM-1) and to a lesser extent in DM and s-IBM (sPECAM-1). We conclude that the distinctly different profiles between PM/s-IBM and DM reflect differences in the pathophysiological background of these diseases.