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Memon A.A.,University of Nottingham | Memon A.A.,Health Science University | Hussein N.R.,University of Nottingham | Hussein N.R.,University of Dohuk | And 3 more authors.
Journal of Clinical Microbiology | Year: 2014

The Helicobacter pylori virulence gene, cagA, and active forms of the vacuolating cytotoxin gene, vacA, are major determinants of pathogenesis. However, previous studies linking these factors to disease risk have often included patients using aspirin/nonsteroidal anti-inflammatory agents (NSAIDs) or acid-suppressing drugs, both of which may confound results. Also, particularly for gastric cancer (GC), controls have often been of quite different ages. Here, we performed a careful study in a "clean" Belgian population with gastric cancer cases age and sex matched to 4 controls and with a parallel duodenal ulcer (DU) group. As in other populations, there was a close association between the presence of cagA and the vacA s1 genotype. For GC, associations were found for vacA s1-positive (P=0.01, odds ratio [OR], 9.37; 95% confidence interval [CI], 1.16 to 201.89), i1-positive (P=0.003; OR, 12.08; 95% CI, 1.50 to 259.64), and cagA-positive status (P<0.05; OR, infinity; 95% CI, 0.76 to infinity). For DU, associations were found with vacA s1 (P=0.002; OR, 6.04; 95% CI, 1.52 to 27.87) and i1 (P=0.004; OR, 4.35; 95% CI, 1.36 to 14.78) status but not with cagA status. Neither condition showed independent associations with the vacA m1 allele or with more biologically active forms of cagA with longer 3′ variable regions. In this Belgian population, the best markers of gastric cancer- and duodenal ulcer-associated strains are the vacA s1 and i1 genotypes. This fits with experimental data showing that the s and i regions are the key determinants of vacuolating cytotoxin activity. Copyright © 2014, American Society for Microbiology. All Rights Reserved.


Noubouossie D.C.F.,Center Hospitalier University Brugmann | Le P.-Q.,Hopital University des Enfants Reine Fabiola | Rozen L.,Center Hospitalier University Brugmann | Debaugnies F.,Center Hospitalier University Brugmann | And 2 more authors.
Thrombosis Research | Year: 2012

Background: The mechanisms of hypercoagulability in sickle cell disease (SCD) are poorly understood. Objective: We aimed to explore the procoagulant activity of endogenous phospholipids (ePL) in the platelet-free plasma of SCD children. Methods: A factor Xa clotting time (XACT), thrombin generation (TG) and a capture-based assay for the detection of procoagulant microparticles (PMP) were used. Forty three SCD children (35 SS, 6 SC and 2 Sβ +) were evaluated at steady-state and compared to 20 controls. Fourteen patients were also evaluated during vaso-occlusive crisis. TG was performed using 10pM tissue factor without addition of exogenous phospholipids. A control condition was also performed using 10pM tissue factor and 4 μM phospholipids. Percentages of the test/control conditions were calculated for the peak height (% peak), endogenous thrombin potential (% ETP) and velocity index (% VI). Results: XACT times were shorter, PMP levels, peak height and velocity index of thrombin generation were higher in SCD patients than controls. Lag time and ETP were not different between the two groups. % peak, % ETP and % VI were higher in patients than controls. Significant correlations were found between PMP levels and XACT, also between PMP levels and peak height, velocity index, ETP and their respective percentages to the control condition, but not with lag time. Double heterozygous patients showed intermediate values for XACT and TG parameters. No significant difference was observed when comparing patients at steady-state versus vaso-occlusive crisis. Conclusion: High procoagulant activity of ePL was observed in the platelet-free plasma of SCD children, probably borne by procoagulant microparticles. This may contribute to a high hemostatic potential and predisposition to thrombotic complications in these patients. © 2011 Elsevier Ltd. All rights reserved.


Faraoni D.,Center Hospitalier University Brugmann | Willems A.,HUDERF | Melot C.,Erasme University Hospital | De Hert S.,Ghent University | Van der Linden P.,Center Hospitalier University Brugmann
European Journal of Cardio-thoracic Surgery | Year: 2012

The benefit-to-risk ratio of using tranexamic acid (TXA) in paediatric cardiac surgery has not yet been determined. This systematic review evaluated studies that compared TXA to placebo in children undergoing cardiac surgery. A systematic search was conducted in all relevant randomized controlled trials. The following information was extracted from the studies and analysed if relevant: demographic data, TXA dose and regimen of administration, cardiopulmonary bypass time, blood loss and blood product transfusion at 24 h. From the studies screened, only 8 (848 patients) were included in the analysis. Most data were heterogeneously distributed and could not be analysed. Further, transfusion policies were not well defined for each study. TXA reduced the need for red blood cell transfusion by 6.4 ml kg-1 day-1 (I2 = 0%, P = 0.45), platelet transfusion by 3.7 ml kg-1 day-1 (I2 = 0%, P = 0.46) and fresh frozen plasma transfusion by 5.4 ml kg-1 day-1 (I2 = 0%, P = 0.53). The number of children who avoided all blood product transfusions was not reported in most of the studies. Evaluation of the side effects associated with TXA use and the effects of the agent on postoperative morbidity and mortality was not possible from the data. There was marked variability in the dosage and infusion schemes used in different studies. This systematic review showed that in paediatric cardiac surgery, the benefit-to-risk ratio associated with the use of TXA cannot be adequately defined. Evidence supporting the routine use of TXA in paediatric cardiac surgery remains weak. © The Author 2012. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.


Plessier A.,University Paris Diderot | Darwish-Murad S.,Erasmus University Rotterdam | Consigny Y.,University Paris Diderot | Fabris F.,IRCCS Maggiore Hospital | And 12 more authors.
Hepatology | Year: 2010

Current recommendations for early anticoagulation in acute portal vein thrombosis unrelated to cirrhosis or malignancy are based on limited evidence. The aim of this study was to prospectively assess the risk factors, outcome, and prognosis in patients managed according to these recommendations. We enrolled 102 patients with acute thrombosis of the portal vein, or its left or right branch. Laboratory investigations for prothrombotic factors were centralized. Thrombus extension and recanalization were assessed by expert radiologists. A local risk factor was identified in 21% of patients, and one or several general prothrombotic conditions in 52%. Anticoagulation was given to 95 patients. After a median of 234 days, the portal vein and its left or right branch were patent in 39% of anticoagulated patients (versus 13% initially), the splenic vein in 80% (versus 57% initially), and the superior mesenteric vein in 73% (versus 42% initially). Failure to recanalize the portal vein was independently related to the presence of ascites (hazard ratio 3.8, 95% confidence interval 1.3-11.1) and an occluded splenic vein (hazard ratio 3.5, 95% confidence interval 1.4-8.9). Gastrointestinal bleeding and intestinal infarction occurred in nine and two patients, respectively. Two patients died from causes unrelated to thrombosis or anticoagulation therapy. Conclusion: Recanalization occurs in one-third of patients receiving early anticoagulation for acute portal vein thrombosis, whereas thrombus extension, intestinal infarction, severe bleeding, and death are rare. Alternative therapy should be considered when ascites and splenic vein obstruction are present. Copyright © 2009 by the American Association for the Study of Liver Diseases.


Plessier A.,University Paris Diderot | Hoekstra J.,Erasmus University Rotterdam | Dell'Era A.,University of Milan | Mandair D.,Queen Elizabeth Hospital Birmingham | And 11 more authors.
Hepatology | Year: 2013

Budd-Chiari syndrome (BCS) is a rare, life-threatening disease caused by obstruction of hepatic venous outflow. The aim of the study was to assess long-term outcome and identify prognostic factors in BCS patients managed by a step-wise approach using anticoagulation, angioplasty/thrombolysis, transjugular intrahepatic portosystemic shunting (TIPS), and orthotopic liver transplantation (OLT). We reviewed long-term data on 157 patients previously included by the European Network for Vascular Disorders of the Liver, a multicenter prospective study of newly diagnosed BCS patients in nine European countries. Patients were followed for a median of 50 months (range, 0.1-74.0). During the study, 88 patients (56%) received at least one invasive intervention (22 patients angioplasty/thrombolysis, 62 TIPS, and 20 OLT) and 36 (22.9%) died. Most interventions and/or deaths occurred in the first 2 years after diagnosis. The Rotterdam score was excellent in predicting intervention-free survival, and no other variable could significantly improve its prognostic ability. Moreover, BCS-TIPS prognostic index (PI) score (based on international normalized ratio, bilirubin, and age) was strongly associated with survival and had a discriminative capacity, which was superior to the Rotterdam score. Conclusions: The current study confirms, in a large cohort of patients with BCS recruited over a short period, that a step-wise treatment approach provides good long-term survival. In addition, the study validates the Rotterdam score for predicting intervention-free survival and the BCS-TIPS PI score for predicting survival. (HEPATOLOGY 2013;) Copyright © 2013 American Association for the Study of Liver Diseases.


Badot V.,Catholic University of Louvain | Badot V.,Center Hospitalier University Brugmann | Luijten R.K.M.A.C.,UMC Utrecht | Van Roon J.A.,UMC Utrecht | And 5 more authors.
Annals of the Rheumatic Diseases | Year: 2013

Background: The soluble form of the interleukin 7 receptor (sIL-7R) is produced by fibroblasts after stimulation with proinflammatory cytokines. Increased sIL-7R serum and synovial fluid levels were recently demonstrated in patients with rheumatoid arthritis. Objectives: To investigate whether sIL-7R production is dysregulated in systemic lupus erythematosus (SLE), and whether this correlates with disease activity. Methods: Serum and urine sIL-7R concentrations were measured by ELISA, and sIL-7R quantitative PCR (qPCR) studies were performed in peripheral blood mononuclear cells (PBMCs). IL-7R, tumour necrosis factor α (TNFα), IL-1β and IL-17 immunostainings were performed on kidney sections. Results: sIL-7R concentrations were significantly higher in SLE sera than in controls, and correlated with SLE Disease Activity Index (SLEDAI) scores. Accordingly, serum sIL-7R levels were strongly raised in patients with nephritis. Moreover in patients with lupus nephritis, serum sIL-7R decreased upon treatment. sIL-7R gene expression in PBMCs was similar in patients with lupus nephritis and controls. By contrast, abundant perivascular IL-7R expression was seen in SLE kidney biopsy specimens, which was associated with expression of TNFα in the surrounding tissue. Conclusions: Our data indicate that sIL-7R is a marker of SLE disease activity, especially nephritis. In contrast to conventional disease activity markers, sIL-7R is not produced by immune cells, but might instead reflect activation of tissue cells in the target organ.


Wissing K.M.,Vrije Universiteit Brussel | Wissing K.M.,Center Hospitalier University Brugmann | Pipeleers L.,Vrije Universiteit Brussel
Transplantation Reviews | Year: 2014

The prevalence of the metabolic syndrome in dialysis patients is high and further increases after transplantation due to weight gain and the detrimental metabolic effects of immunosuppressive drugs. Corticosteroids cause insulin resistance, hyperlipidemia, abnormal glucose metabolism and arterial hypertension. The calcineurin inhibitor tacrolimus is diabetogenic by inhibiting insulin secretion, whereas cyclosporine causes hypertension and increases cholesterol levels. Mtor antagonists are responsible for hyperlipidemia and abnormal glucose metabolism by mechanisms that also implicate insulin resistance. The metabolic syndrome in transplant recipients has numerous detrimental effects such as increasing the risk of new onset diabetes, cardiovascular disease events and patient death. In addition, it has also been linked with accelerated loss of graft function, proteinuria and ultimately graft loss. Prevention and management of the metabolic syndrome are based on increasing physical activity, promotion of weight loss and control of cardiovascular risk factors. Bariatric surgery before or after renal transplantation in patients with body mass index >35kg/m2 is an option but its long term effects on graft and patient survival have not been investigated. Steroid withdrawal and replacement of tacrolimus with cyclosporine facilitate control of diabetes, whereas replacement of cyclosporine and mtor antagonists can improve hyperlipidemia. The new costimulation inhibitor belatacept has potent immunosuppressive properties without metabolic adverse effects and will be an important component of immunosuppressive regimens with better metabolic risk profile. Medical treatment of cardiovascular risk factors has to take potential drug interactions with immunosuppressive medication and drug accumulation due to renal insufficiency into account. © 2014 Elsevier Inc.


Spapen P.,Center Hospitalier University Brugmann
Psychotropes (Belgium) | Year: 2014

The impact of the consumption of cannabis is considered from a reflexion on the cultural context and the developmental stakes during adolescence. Then, some intervention tracks will be suggested for adolescents who have a problematic consumption. © 2014 De Boeck Supérieur. Tous droits réservés pour tous pays.


Vanderhulst J.,Center Hospitalier University Brugmann
Acta Clinica Belgica: International Journal of Clinical and Laboratory Medicine | Year: 2015

Gastrointestinal sarcoidosis is a rare form of extrapulmonary sarcoidosis. Most of the cases are represented by gastric involvement. We describe a patient with previous systemic sarcoidosis who presented with non-specific abdominal complaints. The workup showed the unusual combination of isolated active gastric sarcoidosis and quiescent activity of the disease elsewhere. We briefly review the clinical, diagnostic and therapeutic aspects of gastric sarcoidosis. We hope to increase awareness about this rare disease. © Acta Clinica Belgica 2015.


Faraoni D.,Center Hospitalier University Brugmann | Van Linden P.D.,Center Hospitalier University Brugmann
Minerva Anestesiologica | Year: 2014

Every year, more than a million people die as a result of trauma. This huge mortality could be partially explained by the development of an acute traumatic coagulopathy, present in a large part of all major trauma patients, soon after injury, which contributes to ongoing hemorrhage. The coagulopathy induced by trauma is independently associated with mortality, increased transfusion requirements, multiple organ dysfunction, infections, increased intensive care unit (ICU) length of stay, and costs. The pathophysiological mechanisms implicated in this acute traumatic coagulopathy are complexes and lead to generate a vicious circle leading to the activation of different pathways: thrombin generation, plasmin generation, inflammation activation. All of these processes will impair the balance between clot formation and clot lysis, with an increased tendency of hyperfibrinolysis. In 2010, the CRASH-2 trial demonstrated that tranexamic acid (TXA) administration was associated with a reduction in all cause mortality (14.5% vs. 16%, P=0.0035), including the risk of death due to bleeding (4.9% vs. 5.8%, P=0.0077), without an increase in fatal or non-fatal vascular occlusive events. Finally, the CRASH-3 trial is now recruiting patients with traumatic brain injury without extracranial bleeding. This study aims at determining the safety and efficacy of TXA administration in this particular setting. Our experience from the cardiac surgery setting highlighted a dose-dependent increased seizure incidence associated with the administration of TXA. For this reason, further studies are needed to better define the "optimal" dose scheme based on pharmacokinetic and pharmacodynamic studies. Copyright © 2014 Edizioni Minerva Medica.

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