Center Hospitalier du Luxembourg

Luxembourg, Luxembourg

Center Hospitalier du Luxembourg

Luxembourg, Luxembourg
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Giuliani M.,Luxembourg Institute of Health | Janji B.,Luxembourg Institute of Health | Berchem G.,Luxembourg Institute of Health | Berchem G.,Center Hospitalier du Luxembourg
Oncotarget | Year: 2017

Natural Killer (NK) cells play a critical role against tumor cells in hematological malignancies. Their activating receptors are essential in tumor cell killing. In Multiple Myeloma (MM) patients, NK cell differentiation, activation and cytotoxic potential are strongly impaired leading to MM escape from immune surveillance in tissues and bone marrow. Mechanisms used by MM to affect NK cell functions are mediated by the release of soluble factors, the expression of activating and inhibitory NK cell ligands, and the expression of immune check-point inhibitors. Lenalidomide represents an efficient clinical approach in MM treatment to improve patients' survival. Lenalidomide does not only promotes tumor apoptosis, but also stimulates T and NK cells, thereby facilitating NK-mediated tumor recognition and killing. This occurs since Lenalidomide acts on several critical points: stimulates T cell proliferation and cytokine secretion; decreases the expression of the immune check-point inhibitor Programmed Death-1 (PD-1) on both T and NK cells in MM patients; decreases the expression of both PD-1 and PD-L1 on MM cells; promotes MM cell death and abrogates MM/stromal microenvironment cross-talk, a process known to promote the MM cell survival and proliferation. This leads to the inhibition of the negative signal induced by PD-1/PDL1 axis on NK cells, restoring NK cell cytotoxic functions. Given the importance of an effective immune response to counteract the MM progression and the promising approaches using anti-PD-1/PD-L1 strategies, we will discuss in this review how Lenalidomide could represent an adequate approach to re-establish the recognition against MM by exhausted NK cell.

Crichton G.E.,University of South Australia | Elias M.F.,University of Maine, United States | Davey A.,Temple University | Delagardelle C.,Center Hospitalier du Luxembourg | Beissel J.,Center Hospitalier du Luxembourg
BMC Public Health | Year: 2014

Background: Cardiovascular disease is the number one cause of death in the United States and in most European countries. Cardiovascular health, as defined by the American Heart Association, is comprised of seven health metrics (smoking, body mass index, physical activity, diet, total cholesterol, blood pressure, and fasting plasma glucose). No studies have compared US data with data collected elsewhere, using this index of cardiovascular health. Methods. We performed comparative analyses of cardiovascular health status in participants from 2 study sites in 2 different countries: the Maine-Syracuse Study, conducted in Central New York, USA in 2001-2006 (n = 673), and the Observation of Cardiovascular Risk Factors in Luxembourg, conducted in 2007-2009 (n = 1145). Results: The Cardiovascular Health Score, the sum of the total number of metrics at ideal levels, was higher in the Luxembourg site than in the Central New York site. Ideal cardiovascular health levels for body mass index, smoking, physical activity, and diet were more prevalent in the Luxembourg site than the Central New York site. Ideal levels for blood pressure were more prevalent in Central New York. Differences between the two sites remained with control for age, gender and socioeconomic indicators. Conclusions: Cardiovascular health, as indexed by seven health metrics, was higher in the European study site than in the US study site. The largest differences were for the four lifestyle/behavior metrics, namely body mass index, smoking, physical activity, and diet. Preventative and intervention strategies will continue to be important for both countries in order to improve cardiovascular health. © 2014 Crichton et al.; licensee BioMed Central Ltd.

Donneau A.-F.,University of Liège | Beissel J.,Center Hospitalier du Luxembourg | Delagardelle C.,Center Hospitalier du Luxembourg | Wagener Y.,Directorate of Health | And 2 more authors.
BMC Public Health | Year: 2010

Background. The ORISCAV-LUX study is the first baseline survey of an on-going cardiovascular health monitoring programme in Grand-Duchy of Luxembourg. The main objectives of the present manuscript were 1) to describe the study design and conduct, and 2) to present the salient outcomes of the study, in particular the prevalence of the potentially modifiable and treatable cardiovascular disease risk factors in the adult population residing in Luxembourg. Method. ORISCAV-LUX is a cross-sectional study based on a random sample of 4496 subjects, stratified by gender, age categories and district, drawn from the national insurance registry of 18-69 years aged Luxembourg residents, assuming a response rate of 30% and a proportion of 5% of institutionalized subjects in each stratum. The cardiovascular health status was assessed by means of a self-administered questionnaire, clinical and anthropometric measures, as well as by blood, urine and hair examinations. The potentially modifiable and treatable risk factors studied included smoking, hypertension, dyslipidemia, diabetes mellitus, and obesity. Both univariate and multivariate statistical analyses used weighted methods to account for the stratified sampling scheme. Results. A total of 1432 subjects took part in the survey, yielding a participation rate of 32.2%. This figure is higher than the minimal sample size of 1285 subjects as estimated by power calculation. The most predominant cardiovascular risk factors were dyslipidemia (69.9%), hypertension (34.5%), smoking (22.3%), and obesity (20.9%), while diabetes amounted 4.4%. All prevalence rates increased with age (except smoking) with marked gender differences (except diabetes). There was a significant difference in the prevalence of hypertension and of lipid disorders by geographic region of birth. The proportion of subjects cumulating two or more cardiovascular risk factors increased remarkably with age and was more predominant in men than in women (P<0.0001). Only 14.7% of men and 23.1% of women were free of any cardiovascular risk factor. High prevalence of non-treated CVRF, notably for hypertension and dyslipidemia, were observed in the study population. Conclusion. The population-based ORISCAV-LUX survey revealed a high prevalence of potentially modifiable and treatable cardiovascular risk factors among apparently healthy subjects; significant gender and age-specific differences were seen not only for single but also for combined risk factors. From a public health perspective, these preliminary findings stress the urgent need for early routine health examinations, preventive interventions and lifestyle behavioural changes, even in young asymptomatic adults, to decrease cardiovascular morbidity and mortality in Luxembourg. © 2010 Alkerwi et al; licensee BioMed Central Ltd.

Corhay J.L.,Center HospitalierUniversitaire du Sart Tilman | Vincken W.,Universitair Ziekenhuis Brussel | Schlesser M.,Center Hospitalier du Luxembourg | Bossuyt P.,Takeda Belgium | Imschoot J.,Takeda Belgium
International Journal of Clinical Practice | Year: 2013

Background: and aims Chronic bronchitis (CB) in chronic obstructive pulmonary disease (COPD) patients is associated with increased mortality, frequent exacerbations and faster disease progression. This study investigates the prevalence of CB in a large population of COPD patients to identify features associated with CB. Methods: Cross-sectional multicentre study in patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 2-4 from Belgium and Luxembourg. Results: The 974 patients included were on average 67.8 ± 9.6 years old; 72% were male, FEV1 was 52.5 ± 15.8% of predicted. The prevalence of CB was 64% (622/974). In patients with CB, the number of pack-years smoked and the prevalence of chronic respiratory failure, cachexia and skeletal muscle wasting were significantly higher, whereas FEV 1 and FEV1/VC were lower. The prevalence of CB increased with GOLD stage and was higher in patients with emphysema and those exposed to occupational risk factors. The CB group had more exacerbations, a higher percentage of patients with frequent exacerbations (37.3% vs. 14.2% of patients; p < 0.0001), increased COPD-related, non-intensive care unit hospitalisations and all-cause hospitalisation rates. In multiple logistic regression analysis, frequent exacerbation was the most important independent variable associated with CB, followed by current smoking, chronic respiratory failure, COPD duration and age. Conclusions: CB prevalence in GOLD stage 2-4 COPD patients is high. CB is related to current tobacco smoking, and prevalence increases with COPD severity and duration, emphysema and age. CB could be the hallmark of a subtype of COPD easy to identify in clinical practice, associated with increased disease severity and increased risk of exacerbation. © 2013 John Wiley & Sons Ltd.

PubMed | ZNA Middelheim Hospital, Jan Medical, Center Du Cancer Of Luniversite Catholique Of Leuven, Grand Hopital de Charleroi and 8 more.
Type: Clinical Trial, Phase II | Journal: PloS one | Year: 2016

Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibition is the preferred first-line treatment of advanced adenocarcinoma of the lung that harbors EGFR activating tyrosine kinase domain mutations. Most data available pertain to Asian populations in which such mutations are more prevalent. We report on the long-term results of first-line treatment with erlotinib in Caucasian patients with advanced adenocarcinoma of the lung that have a somatic EGFR mutation in their tumor.Multicenter academic prospective phase II study with erlotinib in patients with an activating EGFR tyrosine kinase (TK) domain somatic mutation (any exon encoding the kinase domain) in the tumor and no prior treatment for their advanced disease.Phenotypic preselecting of 229 patients led to a high EGFR mutation detection rate of 24% of which 46 patients were included in the phase II study. With a progression free survival (PFS) of 81% at three months the study met its primary endpoint for presumed superiority over chemotherapy. With an overall median PFS of 11 months and a median overall survival (OS) of 23 months, the results compare favorably with results obtained in randomized studies using TKI in first line in EGFR mutation positive adenocarcinoma of the lung.The present study reinforces the use of EGFR tyrosine kinase inhibition (TKI) as a first line treatment of choice for advanced adenocarcinoma of the lung carrying an activating EGFR mutation. The mutation rate in preselected Caucasian patients is higher than previously reported. Issues relevant for clinical practice are NCT00339586.

PubMed | HIS Site Etterbeek Ixelles, Ontario Cancer Institute, IDDI, Clinique Saint Pierre and 9 more.
Type: | Journal: Genomics data | Year: 2015

Validated biomarkers predictive of response/resistance to anthracyclines in breast cancer are currently lacking. The neoadjuvant Trial of Principle (TOP) study, in which patients with estrogen receptor (ER)-negative tumors were treated with anthracycline (epirubicin) monotherapy, was specifically designed to evaluate the predictive value of topoisomerase II-alpha (TOP2A) and develop a gene expression signature to identify those patients who do not benefit from anthracyclines. Here we describe in details the contents and quality controls for the gene expression and clinical data associated with the study published by Desmedt and colleagues in the Journal of Clinical Oncology in 2011 (Desmedt et al., 2011). We also provide R code to easily access the data and perform the quality controls and basic analyses relevant to this dataset.

Alkerwi A.,CRP Sante | Pagny S.,CRP Sante | Lair M.-L.,CRP Sante | Delagardelle C.,Center Hospitalier du Luxembourg | Beissel J.,Center Hospitalier du Luxembourg
PLoS ONE | Year: 2013

Background: In the absence of evidence-based information, assessment of population awareness and management of diabetes, hypertension and dyslipidemia (treatable and preventable cardiovascular risk factors) are important to halt coronary and cerebrovascular diseases and to improve public health. Methods: The analysis was based on a nationally representative sample of 1432 adult subjects, recruited for the ORISCAV-LUX survey (2007-2008). Descriptive and multivariable logistic regression analyses were performed. The 10-year Framingham risk score was calculated for each participant who classified at low, intermediate and high risk. Results: Among the diagnosed cases, 32%, 60%, and 85% were respectively unaware of their diabetes, hypertension and dyslipidemia. Increasing age and BMI were the strongest protective factors against unawareness of hypertension and dyslipidemia. Having a family history decreased the risk of unawareness of hypertension (OR = 0.57; 95% CI 0.36, 0.92; P = 0.021), whereas, not having a family doctor increased double-fold the odd of being unaware of hypertension (P = 0.048). Poor health perception reduced significantly the risk of unawareness of dyslipidemia (OR = 0.27; 95% CI 0.11, 0.68). Concerning the management, diabetes was markedly better treated than hypertension and dyslipidemia. Among diabetic subjects (constituting 4% of the population), 3% were treated vs. 1% not treated. In contrast, 22% of the hypertensive participants (35% of the population) were not treated vs. 13% treated. Concerning dyslipidemia, only 9% of those with lipid disorder (70% of the population) were under medication vs. 61% not treated. For the treated cases of these pathologies, almost only one-third was under control. Framingham risk of developing CHD within 10 years was moderate to high among 62%, 27%, and 17% of the unaware/untreated diabetic, hypertensive, and dyslipidemic participants, respectively. Conclusion: The considerable lack of awareness and insufficient management underscore the urgent need for intensive efforts to reduce the gap in prevention strategies, and control of cases according to explicit clinical guidelines. © 2013 Alkerwi et al.

De Blasi V.,Center Hospitalier du Luxembourg | Facy O.,Center Hospitalier du Luxembourg | Goergen M.,Center Hospitalier du Luxembourg | Poulain V.,Center Hospitalier du Luxembourg | And 2 more authors.
Obesity Surgery | Year: 2013

Background: Laparoscopic Roux-en-Y gastric bypass is one of the main bariatric procedures that require safe and reproducible anastomosis. The objective of this study is to compare the risk of leaks and stenosis of a mechanical gastric pouch jejunal anastomosis between the usual interrupted sutures and a continuous barbed suture for gastrojejunotomy, in order to reduce procedure time and costs. Methods: A comparative trial of 100 consecutive patients undergoing laparoscopic Roux-en-Y gastric bypass was performed between October 2010 and July 2011. The population was divided into two groups of 50 consecutive patients. In the first group, gastrojejunotomy was sutured with resorbable interrupted sutures and the second with continuous barbed suture. Diabetes, body mass index and the American Society of Anaesthesiology score were compared. The time required for suturing and the incidence of anastomotic leaks and stricture were also compared after 6 months. Results: No fistulas or anastomotic stenoses had occurred at post-operative month 6 in either group. Gastrojejunotomy suture time was significantly shorter in the barbed suture group (11 versus 8.22 min; p < 0.01). Total costs of material to complete the reconstruction were significantly lower in the barbed suture group (€26.69 versus €18.33; p < 0.001). Conclusions: The use of barbed suture is as safe as usual sutures and allows easier and faster suture in the closure of gastrojejunotomy. This suture could be incorporated in the standard laparoscopic Roux-en-Y gastric bypass technique. © 2012 Springer Science + Business Media, LLC.

Tarragon A.V.,Center Hospitalier du Luxembourg | Soria J.S.A.,Center Hospitalier du Luxembourg | Lens V.,Center Hospitalier du Luxembourg | Manzoni D.,Center Hospitalier du Luxembourg | And 2 more authors.
Hepato-Gastroenterology | Year: 2013

Background/Aims: The most optimal treatment for acute cholecystitis in high risk patients and severe acute cholecystitis remains still controversial. We review the outcomes of a two step treatment with percutaneous cholecystostomy and delayed laparoscopic cholecystectomy (DLC). Methodology: We collected data prospectively from January 2004 to April 2010 from 26 patients that underwent percutaneous transhepatic CT-guided cholecystostomy and DLC. Results: Percutaneous transhepatic CT-guided cholecystostomy was achieved in all cases with no complications. There was just one catheter dislodgement. Most of patients, 92%, improved after drainage. There was one case of mortality. Laparoscopic cholecystectomy was achieved in 88% of patients with no mortality, and a low rate of morbidity (7.6%) and of conversion to open surgery. Pre-operative percutaneous cholangiogram showed additional and useful information in 55.5% of patients. Conclusions: Two-step minimally invasive treatment combining percutaneous transhepatic CT-guided cholecystostomy and DLC is safe and feasible and report low morbi-mortality rates. © H.G.E. Update Medical Publishing S.A.

Alkerwi A.,Luxembourg Institute of Health LIH | Sauvageot N.,Luxembourg Institute of Health LIH | Gilson G.,Center Hospitalier du Luxembourg | Stranges S.,Luxembourg Institute of Health LIH
Nutrients | Year: 2015

Evidence on vitamin D status and related risk factors in Luxembourg adults is lacking. This study aimed to determine the prevalence of vitamin D deficiency and insufficiency and related risk factors among healthy adults in Luxembourg. Based on clinicians’ observations, it was hypothesized that vitamin D deficiency and insufficiency might be common in our population, constituting a significant public health concern. A nationally representative random sample of 1432 adults was enrolled in the ORISCAV-LUX study, 2007–2008. The participants were divided into four categories according to their serum concentrations of 25-hydroxyvitamin D [25(OH)D]. Descriptive, univariate and multivariate statistical analyses used weighted methods to account for the stratified sampling scheme. Only 17.1% of the population had a “desirable” serum 25(OH)D level ≥75 nmol/L, whereas 27.1% had “inadequate” [serum 25(OH)D level 50–74 nmol/L], 40.4% had “insufficient” [serum 25(OH)D level 25–49 nmol/L], and 15.5% had “deficient” [serum 25(OH)D level <25 nmol/L)]. The prevalence of vitamin D deficiency was greater among current smokers, obese subjects, those having reduced HDL-cholesterol level and fair/poor self-perception of health, compared to their counterparts. The prevalence of vitamin D insufficiency was additionally higher among nondrinkers of alcohol, Portuguese and subjects from non-European countries. The final multivariate logistic regression analyses revealed that smoking status and obesity were independent correlates of vitamin D deficiency and insufficiency, respectively. Inadequate vitamin D status is highly prevalent among adults in Luxembourg and is associated with specific lifestyle factors. Along with the effect of vitamin D deficiency and insufficiency on the risk of several diseases, cancer and mortality, our findings have practical implications for public health dietary recommendations, and of particular importance for healthcare practitioners and policy makers. © 2015 by the authors; licensee MDPI, Basel, Switzerland.

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