Publications of André GOTHOT
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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 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 detailUnconventional richter syndrome with plasmablastic transformation
LADANG, Aurélie ULiege; SIMUL, Mickael ULiege; SOMJA, Joan ULiege et al

Poster (2017, February)

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See detailRichter syndrome with plasmablastic lymphoma
LADANG, Aurélie ULiege; SIMUL, Mickael ULiege; SOMJA, Joan ULiege et al

Conference (2017, February)

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See detailHuman bone marrow harbors cells with neural crest-associated characteristics like human adipose and dermis tissues.
Coste, Cécile ULiege; Neirinckx, Virginie ULiege; Sharma, Anil et al

in PLoS ONE (2017), 12(7), 0177962

Adult neural crest stem-derived cells (NCSC) are of extraordinary high plasticity and promising candidates for use in regenerative medicine. Several locations such as skin, adipose tissue, dental pulp or ... [more ▼]

Adult neural crest stem-derived cells (NCSC) are of extraordinary high plasticity and promising candidates for use in regenerative medicine. Several locations such as skin, adipose tissue, dental pulp or bone marrow have been described in rodent, as sources of NCSC. However, very little information is available concerning their correspondence in human tissues, and more precisely for human bone marrow. The main objective of this study was therefore to characterize NCSC from adult human bone marrow. In this purpose, we compared human bone marrow stromal cells to human adipose tissue and dermis, already described for containing NCSC. We performed comparative analyses in terms of gene and protein expression as well as functional characterizations. It appeared that human bone marrow, similarly to adipose tissue and dermis, contains NESTIN+ / SOX9+ / TWIST+ / SLUG+ / P75NTR+ / BRN3A+/ MSI1+/ SNAIL1+ cells and were able to differentiate into melanocytes, Schwann cells and neurons. Moreover, when injected into chicken embryos, all those cells were able to migrate and follow endogenous neural crest migration pathways. Altogether, the phenotypic characterization and migration abilities strongly suggest the presence of neural crest-derived cells in human adult bone marrow. [less ▲]

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See detailExome copy number variation detection: Use of a pool of unrelated healthy tissue as reference sample
Wenric, Stéphane ULiege; Sticca, Tiberio ULiege; CABERG, Jean-Hubert ULiege et al

in Genetic Epidemiology (2017), 41

An increasing number of bioinformatic tools designed to detect CNVs (copy number variants) in tumor samples based on paired exome data where a matched healthy tissue constitutes the reference have been ... [more ▼]

An increasing number of bioinformatic tools designed to detect CNVs (copy number variants) in tumor samples based on paired exome data where a matched healthy tissue constitutes the reference have been published in the recent years. The idea of using a pool of unrelated healthy DNA as reference has previously been formulated but not thoroughly validated. As of today, the gold standard for CNV calling is still aCGH but there is an increasing interest in detecting CNVs by exome sequencing. We propose to design a metric allowing the comparison of two CNV profiles, independently of the technique used and assessed the validity of using a pool of unrelated healthy DNA instead of a matched healthy tissue as reference in exome-based CNV detection. We compared the CNV profiles obtained with three different approaches (aCGH, exome sequencing with a matched healthy tissue as reference, exome sequencing with a pool of eight unrelated healthy tissue as reference) on three multiple myeloma samples. We show that the usual analyses performed to compare CNV profiles (deletion/amplification ratios and CNV size distribution) lack in precision when confronted with low LRR values, as they only consider the binary status of each CNV. We show that the metric-based distance constitutes a more accurate comparison of two CNV profiles. Based on these analyses, we conclude that a reliable picture of CNV alterations in multiple myeloma samples can be obtained from whole-exome sequencing in the absence of a matched healthy sample. [less ▲]

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See detailGenomic Studies of Multiple Myeloma Reveal an Association between X Chromosome Alterations and Genomic Profile Complexity.
Sticca, Tiberio ULiege; CABERG, Jean-Hubert ULiege; Wenric, Stéphane ULiege et al

in Genes, Chromosomes and Cancer (2017), 56

The genomic profile of multiple myeloma (MM) has prognostic value by dividing patients into a good prognosis hyperdiploid group and a bad prognosis non-hyperdiploid group with a higher incidence of IgH ... [more ▼]

The genomic profile of multiple myeloma (MM) has prognostic value by dividing patients into a good prognosis hyperdiploid group and a bad prognosis non-hyperdiploid group with a higher incidence of IgH translocations. This classification, however, is inadequate and many other parameters like mutations, epigenetic modifications and genomic heterogeneity may influence the prognosis. We performed a genomic study by array-based comparative genomic hybridization (aCGH) on a cohort of 162 patients to evaluate the frequency of genomic gains and losses. We identified a high frequency of X chromosome alterations leading to partial Xq duplication, often associated with Xi deletion in female patients. This partial X duplication could be a cytogenetic marker of aneuploidy as it is correlated with a high number of chromosomal breakages. Patient with high level of chromosomal breakage had reduced survival regardless the region implicated. A higher transcriptional level was shown for genes with potential implication in cancer and located in this altered region. Among these genes, IKBKG and IRAK1 are members of the NFKB pathway which plays an important role in MM and is a target for specific treatments. [less ▲]

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See detailHuman Adult Bone Marrow and Adipose Tissue Harbor Stem Cells with Neural Crest Characteristics.
Coste, Cécile ULiege; Neirinckx, Virginie; Rogister, Bernard ULiege et al

Poster (2015, December 03)

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