Publications of Patrizio Lancellotti
Targeting of C-type lectin-like receptor 2 or P2Y12 for the prevention of platelet activation by immunotherapeutic CpG oligodeoxynucleotides
Delierneux, Céline ; Donis, Nathalie ; et al
in Journal of Thrombosis and Haemostasis (in press)
Background: Synthetic phosphorothioate-modified CpG oligodeoxynucleotides (CpG ODNs) display potent immunostimulatory properties that are widely exploited in clinical trials of anticancer treatment ... [more ▼]
Background: Synthetic phosphorothioate-modified CpG oligodeoxynucleotides (CpG ODNs) display potent immunostimulatory properties that are widely exploited in clinical trials of anticancer treatment. Unexpectedly, a recent study indicates that CpG ODNs activate human platelets via the immunoreceptor tyrosine-based activation motif (ITAM)-coupled receptor glycoprotein VI. Objective: To further analyze the mechanisms of CpG ODN-induced platelet activation and identify potential inhibitory strategies. Methods: In vitro analyses were performed on human and mouse platelets, and on cell lines expressing platelet ITAM receptors. CpG ODN platelet activating effects were evaluated in a mouse model of thrombosis. Results: We demonstrated platelet uptake of CpG ODNs, resulting in platelet activation and aggregation. The C-type lectin-like receptor 2 (CLEC-2) expressed in DT40 cells bound CpG ODNs. CpG ODN uptake did not occur in CLEC-2-deficient mouse platelets. Inhibition of human CLEC-2 with a blocking antibody inhibited CpG ODN-induced platelet aggregation. CpG ODNs caused CLEC-2 dimerization, and provoked its internalization. They induced dense granule release before the onset of aggregation. Accordingly, pretreating platelets with apyrase, or inhibiting P2Y12 with cangrelor or clopidogrel prevented CpG ODN platelet activating effect. In vivo, intravenously injected CpG ODN interacted with platelets adhered to mouse injured endothelium, and promoted thrombus growth, which was inhibited by CLEC-2 deficiency or by clopidogrel. Conclusions: CLEC-2 and P2Y12 are required for CpG ODN-induced platelet activation and thrombosis and might be targeted to prevent adverse events in patients at risk. [less ▲]Detailed reference viewed: 19 (5 ULg)
Coronary microvascular reserve and outcome in aortic stenosis: Pathophysiological significance vs. clinical relevance.
Lancellotti, Patrizio ; Nchimi Longang, Alain
in European Heart Journal (2017)Detailed reference viewed: 27 (1 ULg)
Erratum to: Prospective, long-term study of the effect of cabergoline on valvular status in patients with prolactinoma and idiopathic hyperprolactinemia.
VROONEN, Laurent ; Lancellotti, Patrizio ; et al
in Endocrine (2017), 55(1), 246Detailed reference viewed: 19 (3 ULg)
Three-Dimensional Morphology of the Left Ventricular Outflow Tract: Impact on Grading Aortic Stenosis Severity.
; ; et al
in Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography (2017), 30(1), 28-35
BACKGROUND: Left ventricular outflow tract (LVOT) measurement is a critical step in the quantification of aortic valve area. The assumption of a circular morphology of the LVOT may induce some errors. The ... [more ▼]
BACKGROUND: Left ventricular outflow tract (LVOT) measurement is a critical step in the quantification of aortic valve area. The assumption of a circular morphology of the LVOT may induce some errors. The aim of this study was to assess the three-dimensional (3D) morphology of the LVOT and its impact on grading aortic stenosis severity. METHODS: Fifty-eight patients with aortic stenosis were studied retrospectively. LVOT dimensions were measured using 3D transesophageal echocardiography at three levels: at the hinge points (HP) of the aortic valve and at 4 and 8 mm proximal to the annular plane. Results were compared with standard two-dimensional echocardiographic measurements. RESULTS: Three-dimensional transesophageal echocardiography showed a funnel shape that was more circular at the HP and more elliptical at 4 and 8 mm proximal to the annular plane (circularity index = 0.92 vs 0.83 vs 0.76, P < .001). Cross-sectional area was smaller at the HP and larger at 4 and 8 mm from the annular plane (3.6 vs 3.9 vs 4.1 cm2, P = .001). The best correlation between two-dimensional and 3D transesophageal echocardiographic dimensions was at the HP (intraclass correlation coefficient = 0.75; 95% CI, 0.59-0.86). When the HP approach was selected, there was a reduction in the percentage of patients with low flow (from 41% to 29%). CONCLUSIONS: A large portion of patients with aortic stenosis have funnel-shaped and elliptical LVOTs, a morphology that is more pronounced in the region farther from the annular plane. Two-dimensional LVOT measurement closer to the annular plane has the best correlation with 3D measurements. Measurement of the LVOT closer to the annular plane should be encouraged to reduce measurement errors. [less ▲]Detailed reference viewed: 169 (2 ULg)
Cardiopulmonary exercise testing is a better outcome predictor than exercise echocardiography in asymptomatic aortic stenosis.
; ; et al
in International Journal of Cardiology (2017), 227
BACKGROUND: Objective assessment of maximal aerobic capacity using peak oxygen consumption (peak VO2) can be helpful in the management of patients with asymptomatic aortic stenosis (AS). The relationship ... [more ▼]
BACKGROUND: Objective assessment of maximal aerobic capacity using peak oxygen consumption (peak VO2) can be helpful in the management of patients with asymptomatic aortic stenosis (AS). The relationship between peak VO2 and AS severity criteria derived from rest and supine exercise echocardiography (SEE) has never been explored. OBJECTIVES: We aimed to determine whether low peak VO2 (<85% of predicted value) is associated with severity parameters in SEE, and poor clinical outcome. METHODS: Fifty one asymptomatic patients (mean age of 54+/-21years) with moderate to severe aortic stenosis (Vmax>3m/s) and left ventricle ejection fraction>50% prospectively underwent resting and SEE and cardiopulmonary exercise testing (CPX). RESULTS: Peak VO2 was lower than expected (21.9+/-7.4mL/kg/min), i.e. <85% of predicted value in 57% patients, secondary to cardiac limitation in most of them (69%). In multiple regression analysis, age, BMI and female gender were the only independent determinants of peak VO2. Interestingly no parameter derived from SEE was associated with peak VO2. After 21+/-7month follow-up, no patient died, 20 underwent cardiac surgery. Peak VO2<85% of predicted value was associated with lower event free survival compared to normal peak VO2 (57%+/-11% vs 93+/-6%, p=0.036) whereas no exercise echocardiographic parameter could predict such events. Peak VO2>/=85% had a negative predictive value of 97%. CONCLUSION: CPX detects a high proportion of false asymptomatic AS patients with poorer outcome that cannot be predicted by SEE markers of AS severity. Assessment of aerobic capacity should be part of current approach within a "watchful waiting" strategy. [less ▲]Detailed reference viewed: 19 (2 ULg)
2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines: The Task Force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC).
; Lancellotti, Patrizio ; et al
in European Journal of Heart Failure (2017), 19(1), 9-42Detailed reference viewed: 25 (2 ULg)
The Dual Role of Neutrophils in Inflammatory Bowel Diseases
Wéra, Odile ; Lancellotti, Patrizio ; Oury, Cécile
in Journal of clinical medicine (2016), 5(12),
Inflammatory bowel diseases (IBD), including Crohn's disease and ulcerative colitis, are characterised by aberrant immunological responses leading to chronic inflammation without tissue regeneration ... [more ▼]
Inflammatory bowel diseases (IBD), including Crohn's disease and ulcerative colitis, are characterised by aberrant immunological responses leading to chronic inflammation without tissue regeneration. These two diseases are considered distinct entities, and there is some evidence that neutrophil behaviour, above all other aspects of immunity, clearly separate them. Neutrophils are the first immune cells recruited to the site of inflammation, and their action is crucial to limit invasion by microorganisms. Furthermore, they play an essential role in proper resolution of inflammation. When these processes are not tightly regulated, they can trigger positive feedback amplification loops that promote neutrophil activation, leading to significant tissue damage and evolution toward chronic disease. Defective chemotaxis, as observed in Crohn's disease, can also contribute to the disease through impaired microbe elimination. In addition, through NET production, neutrophils may be involved in thrombo-embolic events frequently observed in IBD patients. While the role of neutrophils has been studied in different animal models of IBD for many years, their contribution to the pathogenesis of IBD remains poorly understood, and no molecules targeting neutrophils are used and validated for the treatment of these pathologies. Therefore, it is crucial to improve our understanding of their mode of action in these particular conditions in order to provide new therapeutic avenues for IBD. [less ▲]Detailed reference viewed: 14 (1 ULg)
Le médicament du mois : Edoxaban (Lixiana (R)): nouvel anticoagulant oral pour le traitement et la prévention secondaire des maladies thromboemboliques
SCHEEN, André ; LANCELLOTTI, Patrizio
in Revue Médicale de Liège (2016)Detailed reference viewed: 28 (8 ULg)
Prospective, long-term study of the effect of cabergoline on valvular status in patients with prolactinoma and idiopathic hyperprolactinemia.
VROONEN, Laurent ; Lancellotti, Patrizio ; et al
in Endocrine (2016)
Since the 1990's cabergoline has been the treatment of choice in prolactinoma, as it permits rapid and effective hormonal and tumor control in most cases. Evidence of cardiac valvulopathy was demonstrated ... [more ▼]
Since the 1990's cabergoline has been the treatment of choice in prolactinoma, as it permits rapid and effective hormonal and tumor control in most cases. Evidence of cardiac valvulopathy was demonstrated in Parkinson's disease patients treated with dopamine agonists. Retrospective studies in prolactinoma patients treated with cabergoline at lower doses did not show such an effect. However, few prospective data with long-term follow-up are available. The aim of this study was to assess the safety of cabergoline regarding cardiac valvular status during prospective follow-up in patients treated for prolactinoma or idiopathic hyperprolactinemia. We report here a series of 100 patients (71F; median age at diagnosis: 41.5 years) treated with cabergoline for endocrine diseases (prolactinoma n = 89, idiopathic hyperprolactinemia n = 11). All patients underwent complete transthoracic echocardiographic studies at baseline and during long-term prospective surveillance using the same equipment and performed by the same technicians. The median interval between baseline and last follow-up echocardiographic studies while on cabergoline was 62.5 months (interquartile range: 34.75-77.0). The median total duration of cabergoline treatment was 124.5 months (interquartile range: 80.75-188.75) and the median cumulative total dose of cabergoline was 277.8 mg (interquartile range : 121.4-437.8 mg) at last follow-up. We found no clinically relevant alterations in cardiac valve function or valvular calcifications with cabergoline treatment. Our data suggest that findings from retrospective analyses are correct and that cabergoline is a safe chronic treatment at the doses used typically in endocrinology. [less ▲]Detailed reference viewed: 18 (4 ULg)
Quantitative Three-Dimensional Color Flow Echocardiography of Chronic Mitral Regurgitation: New Methods, New Perspectives, New Challenges
; ; LANCELLOTTI, Patrizio
in Journal of the American Society of Echocardiography (2016), 29(10), 935-937Detailed reference viewed: 10 (1 ULg)
STRESS (EXERCISE) ECHOCARDIOGRAPHY in asymptomatic AORTIC STENOSIS
LANCELLOTTI, Patrizio ; DULGHERU, Raluca Elena
in ASE's comprehensive echocardiography, second edition (2016)Detailed reference viewed: 32 (3 ULg)
L’étude clinique du mois. PARTNER-2 : TAVI versus chirurgie dans les risques intermédiaires de sténose aortique sévère symptomatique
LANCELLOTTI, Patrizio ; Kulbertus, Henri
in Revue Médicale de Liège (2016), 71(6), 302-307Detailed reference viewed: 11 (0 ULg)
Malignant Mitral Valve Prolapse: Substrates to Ventricular Remodeling and Arrhythmias.
LANCELLOTTI, Patrizio ;
in Circulation: Cardiovascular Imaging (2016), 9(8), 005248Detailed reference viewed: 23 (3 ULg)
STRESS ECHOCARDIOGRAPHY FOR VALVE DISEASE/: AORTIC REGURGITATION AND MITRAL STENOSIS
LANCELLOTTI, Patrizio ;
in ASE's comprehensive echocardiography, second edition (2016)Detailed reference viewed: 18 (0 ULg)
Normal reference values for echocardiography: a call for comparison between ethnicities.
; LANCELLOTTI, Patrizio
in European Heart Journal - Cardiovascular Imaging (2016), 17(5), 523-4Detailed reference viewed: 22 (6 ULg)