Cliniques universitaires Saint Luc

Brussels, Belgium

Cliniques universitaires Saint Luc

Brussels, Belgium
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The 2003 discovery of a new protein called PCSK9 (proprotein convertase subtilisin/kexin type 9), involved in LDL particle metabolism, resulted in the development of a new class of highly potent cholesterol-lowering agents. Given this context, several monthly or bimonthly subcutaneously administered monoclonal antibodies that inhibit PCSK9 (evolocumab, Amgen; alirocu-mab, Sanofi/Regeneron; bococizumab, Pfizer) were shown to reduce LDL cholesterol by 45-75%, with a very good tolerance and safety profile. This paved the way for a new therapeutic strategy aimed at helping patients achieve their LDL-cholesterol targets while compensating the statins' limitations of use.


AT OZET R contains two active agents, atorvastatin and ezetimibe, which inhibit the pathways pertaining to hepatic synthesis and intestinal absorption of cholesterol, thereby reducing the LDL levels by 50 to 65%. Each active ingredient has proven its effectiveness to significantly reduce the incidence of cardiovascular disease. From a practical point of view, the reimbursement conditions (INAMI/RIZIV) for this combination pack have been rightly adjusted to the latest European and Belgian recommendations, allowing patients at very high risk to be optimally treated. The combination 'two in one' is also likely to facilitate therapeutic adherence. AT OZET R is particularly indicated in secondary prevention, in primary prevention, and in patients with a very high SCORE (≥10%), patients with diabetes, or those with familial hypercholesterolemia whose LDL cholesterol levels remain inadequately controlled by statin monotherapy alone.


Donnez J.,Societe de Recherche Pour lInfertilite | Dolmans M.-M.,Cliniques Universitaires Saint Luc
Nature Reviews Endocrinology | Year: 2013

In women, ∼10% of cancers occur in those <45 years old. Chemotherapy, radiotherapy and bone marrow transplantation can cure >90% of girls and young women with diseases that require such treatments. However, these treatments can result in premature ovarian failure, depending on the follicular reserve, the age of the patient and the type and dose of drugs used. This article discusses the different fertility preservation strategies: medical therapy before chemotherapy; ovarian transposition; embryo cryopreservation; oocyte vitrification; and ovarian tissue cryopreservation. The indications, results and risks of these options are discussed. Whether medical therapy should be used to protect the gonads during chemotherapy remains a source of debate. Fertility preservation needs to be completed before chemotherapy and/or irradiation is started and might take 2-3 weeks with established techniques such as embryo or oocyte cryopreservation. Further studies are needed in patients with cancer to confirm the excellent outcomes obtained in patients without cancer or in egg donation programmes. For prepubertal girls or cases where immediate therapy is required, cryopreservation of ovarian tissue is the only available option. Finally, possible future approaches are reviewed, including in vitro maturation of nonantral follicles, the artificial ovary, oogonial stem cells and drugs to prevent follicle loss. © 2013 Macmillan Publishers Limited.


Sepsis is defined as a systemic inflammatory response to infection, while severe sepsis (SS) is a sepsis complicated by acute organ dysfunction. Lung infections, in particular community-acquire pneumonia (CAP), are the leading cause of SS. The pathophysiologic mechanism of CAP-mediated SS is the complete dysregulation of the patients immune system. In an initial phase, the systemic hyperactivation of the host immune response against infection leads to high levels of inflammatory mediators, systemic vasodilatation, micro-vascular thrombosis and organ failure. In a second phase, the exaggerated activation of the immune response leads to a state of immunoparalysis, which is characterized by the occurrence of secondary, opportunistic infections. This makes CAP-mediated SS a life-threatening condition with mortality rates as high as 28-50%. The current standard of care (infection removal and control, functional support) does not improve the high mortality and, thus, CAP-mediated SS represents a major unmet medical need with a huge social burden. Therefore, treatments with the potential to modulate both the initial exacerbated immunoactivation and the subsequent immunosuppression are needed. Mesenchymal stem cells (MSCs), including adipose mesenchymal stem cells (ASCs), are known for their broad range of immunomodulatory properties, targeting multiple pro- and anti-inflammatory pathways, and possess antimicrobial capacities (releasing bactericidal peptides and promoting the phagocytosis by immune cells). Indeed, therapeutic benefit of MSC treatment in in vivo experimental models of sepsis has been extensively reported. The SEPCELL consortium believes that cell therapy with allogeneic ASCs may be an innovative therapeutic approach in order to re-establish the normal immune homeostasis of CAP-mediated SS patients, reducing organ injury and restoring organ functionality. A phase Ia/IIb clinical trial will be performed to test this possibility.


IMMUNOSABR is geared towards opening up a new paradigm in treating metastatic cancer by obtaining clinical proof of concept for a novel bi-modal curative treatment strategy. High precision stereotactic ablative radiotherapy (SABR) is combined with immunotherapy to form a powerful synergistic anti-tumour strategy. The approach relies on the direct cytotoxic effect of SABR, the abscopal effect of radiation observed at distance from the irradiated metastatic site(s), and the effect of the tumour-specific immunocytokine L19-IL2 (watch our animation explaining the concept at https://youtu.be/6wDE6RkrikA). Palliative treatment is the current standard of care for patients with metastatic non small cell lung cancer (NSCLC), unless there is an actionable mutation. By using the concept of limited metastatic disease (10 sites, WHO 0-1: oligo\) we aim to develop a therapy with curative intent. IMMUNOSABR will gather evidence for the clinical efficacy of our bi-modal treatment strategy in a multicentre randomised phase II study (clinicaltrials.gov no. NCT02735850) in patients with limited metastatic NSCLC. IMMUNOSABR is complemented by two strong biomarker work packages which focus on developing an ambitious personalised biomarker strategy, to identify patients who can benefit from the novel treatment strategy. This includes promising non-invasive imaging techniques and state-of-the-art immunological monitoring approaches on tumour tissue and blood. IMMUNOSABR will spur further development of L19-IL2 as a commercial drug and translate the bi-modal treatment strategy towards clinical implementation.


Grant
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-11-2015 | Award Amount: 6.44M | Year: 2016

The objective of the SPCCT project is to develop and validate a widely accessible, new quantitative and analytical in vivo imaging technology combining Spectral Photon Counting CT and contrast agents, to accurately and early detect, characterize and monitor neurovascular and cardiovascular disease. Spectral Photon Counting Computed Tomography (SPCCT) is a new imaging modality, currently in development, with a totally new type of detection chain designed to provide high count-rate capabilities while offering energy discrimination with high spatial resolution of 200m. Based on this discrimination, SPCCT can detect and quantify accurately a large variety of atoms (including Gadolinium, Gold, Bismuth) by using the K-edge technique. SPCCT, by a more accurate, less invasive (in comparison with IVUS and coronary angiography) and reliable evaluation of vascular inflammation will allow earlier disease diagnosis such as plaque inflammation before rupture, leading to improved clinical decisions and outcomes. This will be achievable with a high spatial resolution combined to the newly developed vascular inflammation specific contrast agent detected with high quality K-edge technique that can only be provided by a multi-spectral X-ray system. The project will therefore provide a complete tool (acquisition system and specific probes) dedicated to CV imaging. It will finally contribute to: Improved early diagnosis of atherosclerosis, prevention of acute event (MI, stroke) and personalized preventive treatment; Improved management of patient presenting with an acute CV event and clinical validation of treatment efficiency; Sustainability and harmonization of healthcare systems, as costly disorders of heart failure and stroke-related disability would be better prevented and efficiently treated; Economic growth in the EU diagnostics sector, through the development of new targeted contrast materials for SPCCT by SMEs.


Grant
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-18-2015 | Award Amount: 8.19M | Year: 2016

Liver cancer in the paediatric population is rare with an incidence approximately 1-1.5 per million population. The commonest tumour seen in the childhood population is hepatoblastoma (HB), usually seen in young children and infants. Much rarer (about 10% of paediatric liver cancers) is hepatocellular carcinoma (HCC), usually seen in the teenage population and sometimes associated with underlying cirrhotic liver diseases. The ChiLTERN project relates to topic PHC 18 establishing effectiveness of health care interventions in the paediatric population. The ChiLTERN project builds on a unique opportunity to undertake a comprehensive research programme linked to an ambitious global partnership which will see the single largest clinical trial (the Paediatric Hepatic International Tumour Trial - PHITT) ever undertaken in this population of patients, with several randomised questions in six subgroups of patients. ChiLTERN will allow us to move towards an era of personalised therapy in which each patient will receive the correct amount of chemotherapy and will undergo has the best surgical operation (surgical resection or liver transplant). By using both clinical and biological information, we can assign patients more accurately to risk groups based on their survival. Using genetic tests and biomarkers, we will determine those children who may be at risk of developing long term side effects (deafness, heart failure, kidney damage). In addition, biomarkers will allow us to monitor during therapy and detect toxicities early before serious damage is done so that we can adapt treatment and prevent these problems. Finally, we will be using imaging technology tools which will help our surgeons plan liver operations more safely and effectively. Ultimately ChiLTERN will allow us to cure more children with liver cancer, expose fewer children to toxic chemotherapy and ensure their surgery is both effective and safe.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2007-3.1-5 | Award Amount: 3.88M | Year: 2009

Recombinant growth hormone (GH) has been used since 1985. Current indications for GH use in children include GH deficiency and an increasing number of conditions where childhood short stature is not primarily due to deficient GH secretion. Approximately 40 000 children in the EU are treated with daily injections of GH. The efficacy of GH to increase adult height is undisputed in children with severe GH deficiency but is more limited in other indications where current estimates suggest a gain of about 1 cm of adult height per year of treatment. The clinical significance of height gains has been poorly evaluated. The possibility has been raised that GH use in childhood might increase the risk of cancer later in life. However, little data is available to further explore this concern. SAGhE is an integrated consortium of paediatric endocrinologist, epidemiologists and biostatisticians that will collect and analyse data to address the questions of appropriateness and safety of childhood GH treatments. The impact on both height and psychosocial components will be evaluated on a large unbiased metacohort of patients followed to adult height. Safety will be evaluated by analysing long term mortality and long term cancer incidence. The data obtained will then be integrated and disseminated to several levels of users. SAGhE will contribute to the aims of the FP7 Health work programme and to the new Community Action programme of public Health in the field of better use of medicines. It will realize the application of evidence-based medicine in Europe, by the size and design of the study, the independence and scientific quality of data analysis and its translation into evidence-based guidelines. It will be comprehensive at the EU level and will test for national differences. It will address patient safety, one of the key points of the work programme. SAGhE is unique worldwide in its design, size and potential to answer important questions raised on childhood GH treatments.


Donnez J.,SRI | Dolmans M.-M.,Cliniques Universitaires Saint Luc
Best Practice and Research: Clinical Obstetrics and Gynaecology | Year: 2014

Since the first live birth after orthotopic transplantation of frozen-thawed ovarian tissue, >40 babies have been born. It is time to consider fertility preservation in women as one of the foremost challenges of the next decade and to offer women facing the risk of induced or iatrogenic premature menopause the best chances of becoming mothers. Heterotopic transplantation has also been attempted, with consistent restoration of endocrine function; nonetheless, its clinical value remains questionable as it may not provide an optimal environment for follicular development, possibly because of differences in temperature, pressure, paracrine factors and blood supply. Finally, orthotopic allo-transplantation of fresh human ovarian tissue has been successfully attempted between monozygotic twins and also between genetically different sisters. The next step in this field will be the development of an artificial ovary, using, as a support, a biodegradable scaffold made of an alginate matrigel matrix onto which isolated preantral follicles and ovarian cells can be grafted. © 2014 Elsevier Ltd. All rights reserved.


Thienpont E.,Cliniques Universitaires Saint Luc
Clinical Orthopaedics and Related Research | Year: 2014

Background: Cryotherapy has been used to enhance recovery after orthopaedic surgery. Several cooling devices are available but few can guarantee a fixed temperature during a prolonged time and therefore have been criticized. The arrival of new advanced cryotherapy devices made it possible to test the effect of prolonged cooling on rehabilitation after joint replacement.Questions/purposes: The hypotheses of this randomized controlled trial (RCT) were that advanced cryotherapy devices compared with cold packs result in (1) better postoperative pain control resulting in a lower consumption of narcotics; (2) better early ROM; and (3) less postoperative bleeding and swelling.Methods: A priori sample size calculation had determined that to detect a difference of 2 points on the VAS, a sample size of 50 subjects per group at followup would be required, given a study power of 80%. One hundred sixteen patients were included and randomly allocated to receive advanced cryotherapy (n = 58) or use of cold packs (n = 58). The primary outcomes for the study were to evaluate pain with the VAS and analgesics consumption. Secondary outcomes were postoperative ROM, swelling, and blood loss. One hundred (50 in each group) patients had complete data available for analysis.Results: No statistically significant differences in VAS, need for analgesics, nor in secondary outcomes were observed, except for substantially reduced flexion at 6 weeks in the advanced cryotherapy group (114° versus 120°).Conclusions: Advanced cryotherapy with a continuous temperature for a prolonged period does not deliver expected results of superior early recovery after knee arthroplasty. Greater sample sizes are required to fully determine significant differences between the two techniques for these study parameters. Immobilization of the knee in extension during the prolonged cryotherapy session resulted in lower active flexion at 6 weeks after surgery for the advanced cryotherapy group. Advanced cryotherapy should not be used in fast track knee arthroplasty if the economic cost is higher than the price of cold packs or offers no other concomitant advantages.Level of Evidence: Level II, therapeutic study. See the Instructions for Authors for a complete description of levels of evidence. © 2014, The Association of Bone and Joint Surgeons®.

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