Publications of Patrizio Lancellotti
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See detailPlatelets contribute to the initiation of colitis-associated cancer by promoting immunosuppression
Servais, Laurence ULiege; Wéra, Odile ULiege; Dibato Epoh, John et al

in Journal of Thrombosis and Haemostasis (in press)

Background: Clinical and experimental evidence support a role for inflammation in the development of colorectal cancer, though the mechanisms are not fully understood. Beyond thrombosis and hemostasis ... [more ▼]

Background: Clinical and experimental evidence support a role for inflammation in the development of colorectal cancer, though the mechanisms are not fully understood. Beyond thrombosis and hemostasis, platelets are key actors of inflammation; they also have been involved in cancer. However, whether platelets participate in the link between inflammation and cancer is unknown. Objective: To investigate the contribution of platelets and platelet-derived proteins to inflammation-elicited colorectal tumor development. Methods: We used a clinically relevant mouse model of colitis-associated cancer. Platelet secretion and their reactivity to thrombin were assessed at each stage of carcinogenesis. We conducted an unbiased proteomic analysis of releasates of platelets isolated at pre-tumoral stage to identify soluble factors that might act on tumor development. Plasma levels of the identified proteins were measured during the course of carcinogenesis. We then treated the mice with clopidogrel to efficiently inhibit platelet release reaction. Results: At pre-tumoral stage, hyperactive platelets were a major source of circulating pro-tumoral serum amyloid A (SAA) proteins. Clopidogrel prevented the early elevation of plasma SAA, decreased colitis severity, and delayed the formation of dysplastic lesions and adenocarcinoma. Platelet inhibition hindered the expansion and function of immunosuppressive myeloid cells as well as their infiltration in tumors, while tissue CD8 T cells were augmented. Platelets or releasates of platelets from cancer mice both were able to polarize myeloid cells toward an immunosuppressive phenotype. Conclusions: Thus, platelets promote initiation of colitis-associated cancer by enhancing myeloid cell dependent immunosuppression. Antiplatelet agents may help prevent inflammation-elicited carcinogenesis by restoring antitumor immunity. [less ▲]

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See detailSepsis prediction in critically ill patients by platelet activation markers on ICU admission: a prospective pilot study
LAYIOS, Nathalie ULiege; Delierneux, Céline ULiege; Hego, Alexandre ULiege et al

in Intensive Care Medicine Experimental (2017), 5(1), 32

Background: Platelets have been involved in both surveillance and host defense against severe infection. To date, whether platelet phenotype or other hemostasis components could be associated with ... [more ▼]

Background: Platelets have been involved in both surveillance and host defense against severe infection. To date, whether platelet phenotype or other hemostasis components could be associated with predisposition to sepsis in critical illness remains unknown. The aim of this work was to identify platelet markers that could predict sepsis occurrence in critically ill injured patients. Results: This single-center, prospective, observational, 7-month study was based on a cohort of 99 non-infected adult patients admitted to ICUs for elective cardiac surgery, trauma, acute brain injury and post-operative prolonged ventilation and followed up during ICU stay. Clinical characteristics and severity score (SOFA) were recorded on admission. Platelet activation markers, including fibrinogen binding to platelets, platelet membrane P-selectin expression, plasma soluble CD40L, and platelet-leukocytes aggregates were assayed by flow cytometry at admission and 48h later, and also at the time of sepsis diagnosis (Sepsis-3 criteria) and 7 days later for sepsis patients. Hospitalization data and outcomes were also recorded. Of the 99 patients, 19 developed sepsis after a median time of 5 days. SOFA at admission was higher; their levels of fibrinogen binding to platelets (platelet-Fg) and of D-dimers were significantly increased compared to the other patients. Levels 48h after ICU admission were no longer significant. Platelet-Fg % was an independent predictor of sepsis (P = 0.030). By ROC curve analysis cutoff points for SOFA (AUC=0.85) and Platelet-Fg (AUC=0.75) were 8 and 50%, respectively. The prior risk of sepsis (19%) increased to 50% when SOFA was above 8, to 46% when Platelet-Fg was above 50%, and to 87% when both SOFA and Platelet-Fg were above their cutoff values. By contrast, when the two parameters were below their cutoffs, the risk of sepsis was negligible (3.8%). Patients with sepsis had longer ICU and hospital stays and higher death rate. Conclusion: In addition to SOFA, platelet-bound fibrinogen levels assayed by flow cytometry within 24h of ICU admission help identifying critically ill patients at risk of developing sepsis. [less ▲]

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See detailRADIONUCLIDE IMAGING OF INFECTIVE ENDOCARDITIS: state of art and future perspective
MARCHETTA, Stella ULiege; WITHOFS, Nadia ULiege; ERBA, Paola Anna et al

in Current Cardiovascular Imaging Reports (2017), 10(27),

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See detailPlatelets promote immunosuppression and colorectal tumor formation: inhibition by clopidogrel
Servais, Laurence ULiege; Delierneux, Céline; Wéra, Odile ULiege et al

Poster (2017, July)

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See detailMaladie coronaire et pratique sportive
ANCION, Arnaud ULiege; KAUX, Jean-François ULiege; PIERARD, Luc ULiege et al

in Revue Médicale de Liège (2017), 72(6), 281-287

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See detailLe cas clinique du mois. Embolie pulmonaire compliquée d’un œdème laryngé angioneurotique.
LOPEZ IGLESIAS, Raphaelle ULiege; CUPPENS, Benoit ULiege; ROBINET, Sébastien ULiege et al

in Revue Médicale de Liège (2017), 72(6), 275-280

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See detailA Highly Durable RNAi Therapeutic Inhibitor of PCSK9
LANCELLOTTI, Patrizio ULiege; Oury, Cécile ULiege

in New England Journal of Medicine (2017), 376

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See detailTargeting of C-type lectin-like receptor 2 or P2Y12 for the prevention of platelet activation by immunotherapeutic CpG oligodeoxynucleotides
Delierneux, Céline ULiege; Donis, Nathalie ULiege; servais, laurence et al

in Journal of Thrombosis and Haemostasis (2017), 15(5), 983-997

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 ▲]

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See detailROLE OF IMAGING IN LEFT ATRIAL APPENDAGE OCCLUSION
LEMPEREUR, Mathieu ULiege; AMINIAN, Adel; DULGHERU, Raluca Elena ULiege et al

in international journal of cardiovascular practice (2017), 2(2), 33-43

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See detailPlace du traitement médical bradycardisant dans l’insuffisance cardiaque
tridetti, j; KRZESINSKI, François ULiege; D'ORIO, Virginie ULiege et al

in Revue Médicale de Liège (2017), 72

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See detailInvited Commentary
Lancellotti, Patrizio ULiege; Nchimi Longang, Alain ULiege

in Annals of Thoracic Surgery (2017), 103(1), 81-82

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See detailChronic ischemic mitral regurgitation
DULGHERU, Raluca Elena ULiege; LANCELLOTTI, Patrizio ULiege

in Applied echocardiography in coronary artery disease (2017)

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See detailSyndrome de platypnee-orthodeoxie: Une observation clinique perspicace.
CANIVET, Antoine ULiege; Lancellotti, Patrizio ULiege

in Revue Médicale de Liège (2017), 72(11), 494-498

We report the case of a patient admitted to the Intensive Care Unit with dyspnea and refractory hypoxemia after surgical resection of a benign bronchogenic cyst. Etiological research approach excluded ... [more ▼]

We report the case of a patient admitted to the Intensive Care Unit with dyspnea and refractory hypoxemia after surgical resection of a benign bronchogenic cyst. Etiological research approach excluded conventional postoperative hypoxemia causes. Thereafter a platypnea-orthodeoxia syndrome has been diagnosed. Additional tests will demonstrate the existence of a patent foramen ovale. This diagnosis was suitable with the patient's syndrome and was eligible for percutaneous closure procedure allowing immediate resolution of symptoms and confirming the diagnosis. [less ▲]

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See detailCardiac Imaging: Multimodality Advances and Surveillance Strategies in Detection of Cardiotoxicity.
MOONEN, Marie ULiege; Oury, Cécile ULiege; Lancellotti, Patrizio ULiege

in Current Oncology Reports (2017), 19(10), 63

Contemporary cancer management has increased the overall number of cancer survivors, but cardiotoxicity remains a subject of concern, which is a major cause of noncancer mortality among survivors. Among ... [more ▼]

Contemporary cancer management has increased the overall number of cancer survivors, but cardiotoxicity remains a subject of concern, which is a major cause of noncancer mortality among survivors. Among the potential cardiovascular complications, left ventricular (LV) systolic dysfunction is a poor prognostic factor. The importance of its early detection is based on the principle that the likelihood of response to heart failure (HF) treatment is temporally related to the initiation of HF treatment. For these reasons, cardiac monitoring is commonly applied in general practice, based on serial measurements of LV ejection fraction (LVEF); transthoracic echocardiography (TTE) is generally used. However, the LVEF, as a diagnostic and predictive parameter, has significant limitations, which calls for more effective multimodality imaging strategies. This approach requires further study, but there is increasing available data in the literature, encouraging the combination of multimodality imaging parameters and techniques for early cancer therapeutic-related cardiac dysfunction (CTRCD) detection. [less ▲]

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See detailExercise Testing and Stress Imaging in Mitral Valve Disease.
Voilliot, Damien; Lancellotti, Patrizio ULiege

in Current Treatment Options in Cardiovascular Medicine (2017), 19(3), 17

OPINION STATEMENT: Mitral valve disease represented by mitral stenosis and mitral regurgitation is the second most frequent valvulopathy. Mitral stenosis leads to an increased left atrial pressure whereas ... [more ▼]

OPINION STATEMENT: Mitral valve disease represented by mitral stenosis and mitral regurgitation is the second most frequent valvulopathy. Mitral stenosis leads to an increased left atrial pressure whereas mitral regurgitation leads to an increased left atrial pressure associated with a volume overload. Secondary to an upstream transmission of this overpressure, both mitral stenosis and regurgitation lead to pulmonary hypertension and right heart failure. In addition, mitral regurgitation also leads to left ventricular dilatation and dysfunction with left heart failure. Depending on the anatomy of the valvular and subvalvular apparatus, valve repair (percutaneous mitral commissurotomy for mitral stenosis and valvuloplasty for mitral regurgitation) might be possible. If the anatomy is not favorable, valve replacement by mechanical or biological prosthesis is indicated. Most of the intervention indications are based on clinical symptoms and resting transthoracic echocardiography. Outcomes of patients operated based upon resting echo abnormalities might however not be optimal. Therefore early intervention might be beneficial based upon abnormal exercise testing, which has been demonstrated to more sensitive to identify high-risk patients. In this last decade, especially exercise echocardiography has been found to be a crucial tool in the management of patients with mitral valve disease. [less ▲]

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See detailThe need for appropriate use criteria: the proof of the pudding.
Lancellotti, Patrizio ULiege; Garbi, Madalina

in European Heart Journal - Cardiovascular Imaging (2017)

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See detailCHADS2 risk score and rate of stroke or systemic embolism and major bleeding in patients with non-valvular atrial fibrillation receiving non-vitamin K antagonist oral anticoagulants.
Van Mieghem, Walter; Lancellotti, Patrizio ULiege

in Acta Cardiologica (2017), 72(4), 390-396

Randomized trials showed non-inferior or superior results of the non-vitamin K antagonist oral anticoagulants (NOACs) compared with warfarin in patients with non-valvular atrial fibrillation (AF). Despite ... [more ▼]

Randomized trials showed non-inferior or superior results of the non-vitamin K antagonist oral anticoagulants (NOACs) compared with warfarin in patients with non-valvular atrial fibrillation (AF). Despite the absence of direct head-to-head comparisons between the different NOACs, certain molecules have been proposed for subgroups of patients based mainly on the perception of different bleeding risks. The CHADS2 score has been uniformly used in the inclusion criteria of these studies and shared similar risk factors as the haemorrhagic risk score HAS-BLED. The aim of the present report was to highlight the relationships between CHADS2 score and the rate of stroke or systemic embolism, and the rate of major bleeding in patients with AF on treatment with NOACs. Overall, in all the available randomized studies, a fairly good continuous relationship was observed between the CHADS2 risk score and the rate of stroke or systemic embolism, and the rate of major bleeding in the different studies. Larger registries are needed to confirm this hypothesis. [less ▲]

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