Publications of André GOTHOT
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See detailLaboratory divergences in concurrent diagnosis of acute myeloid leukemia relapse and COVID-19: A case report.
NIZET, ADRIEN ULiege; FOGUENNE, Jacques ULiege; Gothot, André ULiege et al

in International journal of laboratory hematology (2021)

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See detailBelgian rare diseases plan in clinical pathology: identification of key biochemical diagnostic tests and establishment of reference laboratories and financing conditions.
Vandevelde, Nathalie M.; Vermeersch, Pieter; Devreese, Katrien M. J. et al

in Orphanet journal of rare diseases (2021), 16(1), 89

BACKGROUND: One objective of the Belgian Rare Diseases plan is to improve patients' management using phenotypic tests and, more specifically, the access to those tests by identifying the biochemical ... [more ▼]

BACKGROUND: One objective of the Belgian Rare Diseases plan is to improve patients' management using phenotypic tests and, more specifically, the access to those tests by identifying the biochemical analyses used for rare diseases, developing new financing conditions and establishing reference laboratories. METHODS: A feasibility study was performed from May 2015 until August 2016 in order to select the financeable biochemical analyses, and, among them, those that should be performed by reference laboratories. This selection was based on an inventory of analyses used for rare diseases and a survey addressed to the Belgian laboratories of clinical pathology (investigating the annual analytical costs, volumes, turnaround times and the tests unavailable in Belgium and outsourced abroad). A proposal of financeable analyses, financing modalities, reference laboratories' scope and budget estimation was developed and submitted to the Belgian healthcare authorities. After its approval in December 2016, the implementation phase took place from January 2017 until December 2019. RESULTS: In 2019, new reimbursement conditions have been published for 46 analyses and eighteen reference laboratories have been recognized. Collaborations have also been developed with 5 foreign laboratories in order to organize the outsourcing and financing of 9 analyses unavailable in Belgium. CONCLUSIONS: In the context of clinical pathology and rare diseases, this initiative enabled to identify unreimbursed analyses and to meet the most crucial financial needs. It also contributed to improve patients' management by establishing Belgian reference laboratories and foreign referral laboratories for highly-specific analyses and a permanent surveillance, quality and financing framework for those tests. [less ▲]

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See detailPyruvate dehydrogenase kinase/lactate axis: a therapeutic target for neovascular age-related macular degeneration identified by metabolomics
LAMBERT, Vincent ULiege; hansen, Sylvain; Schoumacher, Matthieu ULiege et al

in Journal of Molecular Medicine (2020)

Neovascular age-related macular degeneration (nAMD) is the leading cause of blindness in aging populations. Here, we applied metabolomics to human sera of patients with nAMD during an active (exudative ... [more ▼]

Neovascular age-related macular degeneration (nAMD) is the leading cause of blindness in aging populations. Here, we applied metabolomics to human sera of patients with nAMD during an active (exudative) phase of the pathology and found higher lactate levels and a shift in the lipoprotein profile (increased VLDL-LDL/HDL ratio). Similar metabolomics changes were detected in the sera of mice subjected to laser-induced choroidal neovascularization (CNV). In this experimental model, we provide evidence for two sites of lactate production: first, a local one in the injured eye, and second a systemic site associated with the recruitment of bone marrow–derived inflammatory cells. Mechanistically, lactate promotes the angiogenic response and M2-like macrophage accumulation in the eyes. The therapeutic potential of our findings is demonstrated by the pharmacological control of lactate levels through pyruvate dehydrogenase kinase (PDK) inhibition by dichloroacetic acid (DCA). Mice treated with DCA exhibited normalized lactate levels and lipoprotein profiles, and inhibited CNV formation. Collectively, our findings implicate the key role of the PDK/lactate axis in AMD pathogenesis and reveal that the regulation of PDK activity has potential therapeutic value in this ocular disease. The results indicate that the lipoprotein profile is a traceable pattern that is worth considering for patient follow-up. [less ▲]

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See detailPlatelet-rich plasma (PRP) and tendon healing: comparison between fresh and frozen-thawed PRP
KAUX, Jean-François ULiege; Libertiaux, Vincent; Dupont, Laura ULiege et al

in Platelets (2020), 31(2), 221-225

Platelet-rich plasma (PRP) is increasingly used in the treatment of musculoskeletal diseases. Its preservation by freezing it for the realization of multiple injections in clinical use has never been ... [more ▼]

Platelet-rich plasma (PRP) is increasingly used in the treatment of musculoskeletal diseases. Its preservation by freezing it for the realization of multiple injections in clinical use has never been discussed. Calcaneal tendons of rats were surgically sectioned. Platelet concentration of the PRP was 2.5 x 106/μl with autologous plasma of rats. Frozen-thawed PRP was prepared by performing two cycles of freezing and thawing on PRP aliquots. Both platelet preparations were injected in the lesion. Biomechanical and histological evaluations were carried out after 7, 20 or 40 days post surgery. After 7 and 40 days, no significant difference was observed between the PRP and the frozen-thawed PRP group. There is however a difference 20 days after surgery: the ultimate tensile strength (UTS) was greater in the fresh PRP group. No obvious difference with histological aspect was observed between the two groups. In conclusion, fresh PRP and frozen-thawed PRP injections can lead to similar results in the healing process of section calcaneal tendons of rats. Improvements with fresh PRP are slight. PRP could thus be frozen to be preserved if multiple injections are needed (e.g. osteoarthritis). [less ▲]

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See detailHémophilie : une maladie en marche
Peters, Pierre ULiege; Gothot, André ULiege

in Revue Médicale de Liège (2020), 75(5-6), 322-328

Over the last hundred years, the treatment of hemophilia has evolved considerably. To date, its principle is still to prevent the occurrence of hemorrhages by regular intravenous injections of factor VIII ... [more ▼]

Over the last hundred years, the treatment of hemophilia has evolved considerably. To date, its principle is still to prevent the occurrence of hemorrhages by regular intravenous injections of factor VIII or IX concentrate. It allows to reach a life expectancy similar to the general population. The quality of life is constantly improving despite the constraint imposed by the modality and frequency of injections. The main complication remains the development of antibodies that inhibit the administered factors. Concentrates of long-acting factors are now available allowing to limit for example the frequency of injections. A bispecific monoclonal antibody reproducing the action of factor VIII and injectable subcutaneously has recently become available to hemophilia A patients, with the advantage of being effective even in the presence of inhibitors. Other non-substitute products are being studied offering interesting leads. Finally, gene therapy shows promising results, giving hope for access to this therapeutic option in a relatively near future. These advances are, however, a challenge for clinical laboratories, which must adapt their measurement techniques to ensure optimal monitoring. The future is on its way for hemophilia. Treatment remains expensive but it is worth the price. [less ▲]

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See detailDiagnostic différentiel des thrombopénies et thrombopathies constitutionnelles : présentations cliniques et algorithmes décisionnels
HARKATI, Radouan ULiege; Peters, Pierre ULiege; Gothot, André ULiege et al

in Revue medicale de Liege (2019), 74(12), 655-661

The diagnosis of inherited platelet disorders (IPD) is a complex task. Indeed, due to their rarity, their wide clinical spectrum (intensity of hemorrhagic symptoms) and the need for specialized biological ... [more ▼]

The diagnosis of inherited platelet disorders (IPD) is a complex task. Indeed, due to their rarity, their wide clinical spectrum (intensity of hemorrhagic symptoms) and the need for specialized biological assays (only performed in reference centers) IPDs can be diagnosed very late. However, it is important to remember the crucial need for early diagnosis in order to avoid the use of unnecessary and potentially harmful treatments for the patient. A thorough personal and family history, a complete physical examination and a simple biological work up (blood count, blood smear and platelet occlusion time) will lead to the suspicion of an IPD. It will then be up to the physician to refer the patient to a specialist in order to complete the diagnostic work up and therefore establishing a definitive diagnosis. Here is a description of the most well-known IPDs and their diagnostic algorithms. [less ▲]

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See detailComment j’explore… Les thrombopénies et thrombopathies constitutionnelles
Harkati, Radouan ULiege; Peters, Pierre ULiege; Gothot, André ULiege et al

in Revue Médicale de Liège (2019), 74(11), 616-619

Inherited platelet disorders (IPD) include a set of rare diseases whose diagnosis is often difficult because it requires the use of complex biological assays in specialized centers. They are probably ... [more ▼]

Inherited platelet disorders (IPD) include a set of rare diseases whose diagnosis is often difficult because it requires the use of complex biological assays in specialized centers. They are probably under-diagnosed. Clinicians should consider an IPD when facing a chronic thrombocytopenia resistant to intravenous immunoglobulins (IVIG) and steroids together with a family history of thrombocytopenia. A syndromic thrombocytopenia will be suspected by the family survey and specific clinical signs. The confirmation of the diagnosis will then require the use of specialized biological assays such as platelet aggregation, flow cytometry, electron microscopy, platelet secretion assays, karyotype and molecular biology.Les thrombopénies et thrombopathies constitutionnelles constituent un ensemble de pathologies rares dont le diagnostic est souvent difficile car il nécessite le recours à des analyses biologiques souvent réservées à des centres spécialisés. Elles sont probablement sous-diagnostiquées. Le clinicien devra les envisager devant une thrombopénie chronique ne répondant pas aux immunoglobulines intraveineuses et aux corticoïdes et la présence d’antécédents familiaux. Une thrombopénie syndromique sera suspectée en fonction des éléments de l’anamnèse familiale et de signes cliniques spécifiques. La confirmation du diagnostic nécessitera la réalisation d’examens biologiques spécialisés (agrégation plaquettaire, cytométrie en flux, microscopie électronique, tests de sécrétion, caryotype et biologie moléculaire). [less ▲]

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See detailEccentric training for tendon healing after acute lesion: a rat model
Kaux, Jean-François ULiege; Libertiaux, Vincent; Leprince, Pierre ULiege et al

in Towards healthy tendon ageing... (2018, September)

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See detailPlatelet-Rich Plasma (PRP) and tendon healing: comparison between fresh and frozen-thawed PRP
Kaux, Jean-François ULiege; Libertiaux, Vincent; Dupont, Laura ULiege et al

in Towards healthy tendon ageing... (2018, September)

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See detailEffects of Allogeneic Platelet-Rich Plasma (PRP) on the Healing Process of Sectioned Achilles Tendons of Rats: A Methodological Description
Greimers, Laura; Drion, Pierre ULiege; Colige, Alain ULiege et al

in Journal of Visualized Experiments (2018), 133

This article describes the experimental procedures used to observe if PRP can positively affect tendon healing. There are 4 main steps to follow: induce a lesion in the Achilles tendon; prepare PRP and ... [more ▼]

This article describes the experimental procedures used to observe if PRP can positively affect tendon healing. There are 4 main steps to follow: induce a lesion in the Achilles tendon; prepare PRP and inject it (or the saline solution); remove the tendon; and perform biomechanical, molecular, and histological evaluations. At each step, all the procedures and methods are described in detail, so they can be reproduced easily. Achilles tendons have been surgically sectioned (removal of a 5-mm long section). Afterwards, PRP or saline solution was injected to study whether PRP has a positive effect on the healing of the tendon. Three groups of 40 animals (a total of 120 rats were used in this study) were subdivided into 2 subgroups: PRP injection group and a saline injection control group. Rats were sacrificed at increasing time points (Group A: 5 days; Group B: 15 days; Group C: 30 days) and tendons were removed. 90 tendons underwent biomechanical testing before performing transcriptomic analysis and the 30 remaining tendons were submitted to histological analysis. [less ▲]

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See detailExploring the effect of a second closely-timed PRP infiltration for tendinopathy
Kaux, Jean-François ULiege; Croisier, Jean-Louis ULiege; Forthomme, Bénédicte ULiege et al

Conference (2017, December 10)

Introduction: Some clinical series have previously evaluated the effect of PRP in the treatment of proximal patellar tendinopathies. Although it is possible that a single infiltrative administration may ... [more ▼]

Introduction: Some clinical series have previously evaluated the effect of PRP in the treatment of proximal patellar tendinopathies. Although it is possible that a single infiltrative administration may prove to be an effective treatment for this indication, most of the existing studies evaluated the effects of successive infiltrations which is arguably likely to increase the risks of complications. Methods: Our study is a single blinded, randomized controlled clinical trial on 20 leisure sportsmen (2 groups, respectively 1 or 2 infiltrations of pure PRP) with chronic proximal patellar tendinopathies, rebel to classical management. PRP was obtained using an aphaeresis machine. The one-year follow-up evaluation consisted of VAS, IKDC and VISA-P scores, while algometer, isokinetic and ultrasounds evaluations were carried out up to 3 months. Results: The concentration of the PRP used was similar in both groups. The VAS significantly decreased with time over the 3-month follow-up period (p=0.002), with no difference observed between the two groups (p=0.2). Values obtained with the pressure algometer increased with time across both groups over the 3-month follow-up period (p<0.0001), and values were significantly higher for Group 1 (p=0.001). The IKDC score increased with time in both groups over the follow-up period (p=0.034), with values again significantly higher for Group 1 (p=0.0026). The VISA-P score increased with time in both groups over the follow-up period (p=0.0023), with no difference observed between the groups (p=0.41). No improvements in isokinetic physical performance were observed in either group. However, pain during E30 significantly decreased over the 3-month follow-up period (p=0.027) for patients in both groups. No improvement in either jumping performances or in pain was observed in either group during opto-jump evaluation. No improvements in US findings were observed. After one year, 90% patients of group 1 did not report anymore pain during daily activities, in comparison with only 20% in group 2. Conclusions: A second closely-timed infiltration of PRP to treat proximal patellar tendinopathies is not necessary to improve the efficacy of this treatment. [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 detailExploring the effect of a second closely-timed PRP infiltration for tendinopathy
Kaux, Jean-François ULiege; Forthomme, Bénédicte ULiege; Le Goff, Caroline ULiege et al

in European Journal of Sports Medicine (2017, September), 5(Supplement 1), 20-21

INTRODUCTION: Although PRP is very popular in sport, especially since it was removed from the doping list, it remains controversed in literature (3). Up to now, there exists no general agreement on the ... [more ▼]

INTRODUCTION: Although PRP is very popular in sport, especially since it was removed from the doping list, it remains controversed in literature (3). Up to now, there exists no general agreement on the preparation and the use of PRP. Some clinical series have previously evaluated the effect of PRP in the treatment of proximal patellar tendinopathies. Although it is possible that a single infiltrative administration may prove to be an effective treatment for this indication, most of the existing studies evaluated the effects of two or three successive infiltrations. The multiplication of infiltrations is arguably likely to increase the risks of complications, and this treatment can be expensive. PURPOSE: We aimed to evaluate whether two infiltrations of PRP prove more effective than a single treatment. METHODS: Our study is a single blinded, randomized controlled clinical trial on leisure sportsmen with chronic proximal patellar tendinopathies, rebel to classical management, including physiotherapy, shock wave therapy… Twenty patients suffering from proximal patellar tendinopathies for over than 3 months were enrolled into the study. PRP was obtained using an aphaeresis machine (1). The subjects were split into two randomized groups and beneficed of 1 or 2 infiltrations of pure PRP, respectively. The one-year followup evaluation consisted of VAS, IKDC and VISAP scores, while algometer, isokinetic and ultrasounds evaluations were carried out up to 3 months. RESULTS: The concentration of the PRP used for each infiltration was similar in both groups (913.20 ± 65.60 × 103/ L for group 1 and 917.90 ± 63.08for group 2, with virtually no red (<0.001 × 106/ L) nor white cells (<0.001 × 103/ L) in either group). The VAS significantly decreased with time over the 3 month followup period (p = 0002), with no difference observed between the two groups (p = 0.2). Values obtained with the pressure algometer increased with time across both groups over the 3 month followup period (p < 0.0001), and values were significantly higher for Group 1 (p = 0.001). The IKDC score increased with time in both groups over the followup period (p = 0.034), with values again significantly higher for Group 1 (p = 0.0026). The VISAP score increased with time in both groups over the followup period (p = 0.0023), with no difference observed between the groups (p = 0.41). No improvements in isokinetic physical performance were observed in either group. However, pain during E30 significantly decreased over the 3 month followup period (p = 0.027) for patients in both groups. No improvement in either jumping performances or in pain was observed in either group during optojump evaluation. No improvements in US findings were observed. However, an increase of the sagittal hypoechoic area was observed in Group1 (p = 0.0038). After one year, 90% patients of group 1 did not report anymore pain during daily activities, in comparison with only 20% in group 2. In group 1, 20% of subjects still described pain during work activities and 40% during practicing sports versus 40% and 70%, respectively, in group 2. One patient in each group did not return to sport; both subjects still experienced pain through daily and occupational work activities. Six subjects among the group 1 (67%) and 7 among the group 2 (78%) returned to their former sport, and 55% of both groups to the former level than before the tendinopathy. However, 44% of the group 1 and 78% of the group 2 still experienced pain during sports activities. The practiced sports were football, handball, cycling, running, fitness.On the other hand, patients with only few months of symptoms did not evolved more favorably than those with symptoms for longer. CONCLUSIONS: The comparison between 1 or 2 infiltrations of PRP did not reveal any difference between the 2 groups after a followup period of 3 months. A second closely timed infiltration of PRP to treat proximal patellar tendinopathies is not necessary to improve the efficacy of this treatment in the short term (2). However, there remains a need to evaluate the longer term results. REFERENCES: Kaux JF, Croisier JL, Bruyere O, Rodriguez De La Cruz C, Forthomme B, Brabant G, Lapraille S, Lonneux V, Noel D, Le Goff C, Gothot A, Collette J, Crielaard JM. One injection of plateletrich plasma associated to a submaximal eccentric protocol to treat chronic jumper's knee. J Sports Med Phys Fitness. 2015 Sep;55(9):95361 Kaux JF, Croisier JL, Forthomme B, Le Goff C, Buhler F, Savanier B, Delcour S, Gothot A, Crielaard JM. Using plateletrich plasma to treat jumper's knees: Exploring the effect of a second closelytimed infiltration. J Sci Med Sport. 2016 Mar;19(3):2004. Kaux JF, Drion P, Croisier JL, Crielaard JM. Tendinopathies and plateletrich plasma (PRP): from preclinical experiments to therapeutic use. J Stem Cells Regen Med. 2015 May 30;11(1):717. A10 [less ▲]

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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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