Alain Duhamel

CHRU de Strasbourg, Strasburg, Alsace, France

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Publications (329)1243.46 Total impact

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    ABSTRACT: After more than 50 years of treating Parkinson's disease with l-DOPA, there are still no guidelines on setting the optimal dose for a given patient. The dopamine transporter type 1, now known as solute carrier family 6 (neurotransmitter transporter), member 3 (SLC6A3) is the most powerful determinant of dopamine neurotransmission and might therefore influence the treatment response. We recently demonstrated that methylphenidate (a dopamine transporter inhibitor) is effective in patients with Parkinson's disease with motor and gait disorders. The objective of the present study was to determine whether genetic variants of the dopamine transporter type 1-encoding gene (SLC6A3) are associated with differences in the response to treatment of motor symptoms and gait disorders with l-DOPA and methylphenidate (with respect to the demographic, the disease and the treatment parameters and the other genes involved in the dopaminergic neurotransmission). This analysis was part of a multicentre, parallel-group, double-blind, placebo-controlled, randomized clinical trial of methylphenidate in Parkinson's disease (Protocol ID:2008-005801-20; ClinicalTrials.gov:NCT00914095). We scored the motor Unified Parkinson's Disease Rating Scale and the Stand-Walk-Sit Test before and after a standardized acute l-DOPA challenge before randomization and then after 3 months of methylphenidate treatment. Patients were screened for variants of genes involved in dopamine metabolism: rs28363170 and rs3836790 polymorphisms in the SLC6A3 gene, rs921451 and rs3837091 in the DDC gene (encoding the aromatic L-amino acid decarboxylase involved in the synthesis of dopamine from l-DOPA), rs1799836 in the MAOB gene (coding for monoamine oxidase B) and rs4680 in the COMT gene (coding for catechol-O-methyltransferase). Investigators and patients were blinded to the genotyping data throughout the study. Eighty-one subjects were genotyped and 61 were analysed for their acute motor response to l-DOPA. The SLC6A3 variants were significantly associated with greater efficacy of l-DOPA for motor symptoms. The SLC6A3 variants were also associated with greater efficacy of methylphenidate for motor symptoms and gait disorders in the ON l-DOPA condition. The difference between motor Unified Parkinson's Disease Rating Scale scores for patients with different SLC6A3 genotypes was statistically significant in a multivariate analysis that took account of other disease-related, treatment-related and pharmacogenetic parameters. Our preliminary results suggest that variants of SLC6A3 are genetic modifiers of the treatment response to l-DOPA and methylphenidate in Parkinson's disease. Further studies are required to assess the possible value of these genotypes for (i) guiding l-DOPA dose adaptations over the long term; and (ii) establishing the risk/benefit balance associated with methylphenidate treatment for gait disorders. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
    Brain 03/2015; DOI:10.1093/brain/awv063 · 10.23 Impact Factor
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    ABSTRACT: The objectives of the present study were to (i) better characterize visual emotional experience in patients with temporal lobe epilepsy (TLE), (ii) identify clinical risk factors that might be predictive of a change in emotional experience, and (iii) study the relationships between emotional experience and psychobehavioral/quality-of-life factors. Fifty patients with TLE and fifty matched controls evaluated the emotional content of unpleasant, pleasant, and neutral pictures with respect to their valence (unpleasant-to-pleasant) and arousal (low-to-high) levels. Demographic, cognitive, and psychobehavioral data were recorded for all participants, and clinical data and factors related to quality of life were also collected for patients with TLE. There were no significant differences between the group with TLE and the control group in terms of valence evaluations. However, arousal scores for neutral pictures were significantly higher in patients with TLE than in controls. There was also a nonsignificant trend towards lower arousal scores for pleasant pictures in patients with TLE than in controls. Although none of the recorded clinical factors were found to be related to emotional experience, the level of apathy was predictive of greater arousal experience for neutral pictures in patients with TLE. In conclusion, emotional experience appears to be modified in TLE and might be related to apathy. Changes in emotional experience should be taken into account in studies in which neutral stimuli are used to establish a baseline level when assessing emotional and cognitive processing. Copyright © 2015 Elsevier Inc. All rights reserved.
    Epilepsy & Behavior 03/2015; 45:15-20. DOI:10.1016/j.yebeh.2015.02.005 · 2.06 Impact Factor
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    ABSTRACT: The prognosis of myelodysplastic syndromes (MDS) after allogeneic stem cell transplantation is critically determined by cytogenetic abnormalities, as previously defined by International Prognostic Scoring System (IPSS) cytogenetics. It has been shown that a new cytogenetic classification, included in the IPSS-R (cytogenetic-IPSS-R [C-IPSS-R]), can better predict the outcome of untreated MDS patients. In this study, we assessed the impact of the IPSS-R cytogenetic score (C-IPSS-R) on the outcome of 367 MDS patients transplanted from HLA-identical siblings or HLA allele-matched unrelated donors. According to the C-IPSS-R, 178 patients (48%) fell in the good risk, 102 (28%) in the intermediate risk, 77 (21%) in the poor risk, and 10 (3%) in the very poor risk group. In multivariate analysis, after a median follow-up of 4 years, the poor and very poor-risk categories correlated with shorter overall survival (OS) (4-year OS, 32%; hazard ratio [HR], 1.59; P = 0.009 and OS, 10%; HR, 3.18; P = 0.002, respectively) and higher cumulative incidence of relapse (CIR) (CIR, 52%; HR, 1.82; P = 0.004 and CIR, 60%; HR, 2.44; P = 0.060, respectively). Overall, the C-IPSS-R changed the IPSS cytogenetic risk only in 8% of cases but identified a new risk group, the very poor C-IPSS-R category, with dismal outcome after allogeneic stem cell transplantation (10% 4-year OS, 60% 4-year CIR). Posttransplantation maintenance therapy should be investigated in prospective trials for patients with high-risk C-IPSS-R karyotypes.
    Transplantation 03/2015; DOI:10.1097/TP.0000000000000649 · 3.78 Impact Factor
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    ABSTRACT: Performances of 99mTc-mebrofenin hepatobiliary scintigraphy (HBS) are currently evaluated before major hepatic resection for early detection of liver failure in high risk patients. Published studies included small numbers of patients with planar scintigraphy, and more recently SPECT data. Our aim was to evaluate intra- and interobserver reproducibility of HBS in planar and SPECT modalities for functional assessment of the future remnant liver (FRL) before major hepatic resection. We also evaluated the impact of potential variability factors such as biliary excretion and isocontour threshold choice.
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    ABSTRACT: Objective: Although an inhibin B assay may be useful in the assessment of testicular function in a number of genital conditions, reliable reference ranges are still lacking. This study sought to establish the reference range for serum inhibin B by applying the updated Gen II assay. Design: This prospective study included 818 men referred for semen analysis: 377 were normozoospermic (reference group) and 441 presented at least one abnormal semen parameter (case group). Methods: Semen parameters were interpreted according to the 2010 WHO manual and David's modified classification for normal morphology. The inhibin B concentration was determined with the currently enzyme-linked immunosorbent assay. Results: In the reference group, the 2.5th percentile for inhibin B was 92 pg/mL and the 97.5th percentile for FSH was 7.8 IU/L. In the overall population, an inhibin B level <92 pg/ml was associated with increased odds ratio [95% Confidence Interval] for oligozoospermia (16.93 [9.82-29.18], p<0.0001), asthenozoospermia (4.87 [2.88-8.10], p<0.0001) and teratozoospermia (2.20 [1.31-3.68]. The combination of a FSH >7.8 IU/L and an inhibin B <92 pg/ml was associated with greater odds ratio for oligozoospermia (98.74 [23.99-406.35], p<0.0001) than for each hormone considered separately. Conclusion(s): A new reference range for serum inhibin B was established by the use of updated immunoassay. The correlations between hormone levels and semen parameters highlighted the importance of establishing these values with respect to the spermogram. When combined with FSH assay, the inhibin B range may be of value in the evaluation of spermatogenesis in a number of male genital conditions.
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    ABSTRACT: The purpose of the study was to evaluate the prevalence of compressive lymphadenopathy on pulmonary veins (PV) and left atrium (LA) in patients with sarcoidosis. A total of 101 consecutive patients underwent a chest computed tomography angiographic examination with specific analysis of: (a) 3 nodal stations (ie, 7, 8, and 9 stations) for detection of LA compression; (b) 2 nodal stations (ie, 10 and 11 right and left stations) for detection of PV compression. Lymphadenopathy was present in 64 patients (64/101; 63.4%) with computed tomography features of venoatrial compression in 17 patients (17/101; 16.8%). This subgroup included 10 patients with LA compression alone (10/64; 15.6%), 6 patients with PV compression alone (6/64; 9.4%), and 1 patient with both (1/64; 1.5%). The mean diameter of enlarged lymph nodes compressing the LA and PVs was 3.18±0.73 cm (range: 2.1 to 4.4 cm) and 1.9±0.45 cm (range: 1 to 2.9 cm), respectively. PV compression was depicted in a total of 7 patients (7/101; 6.9%), observed as a unilateral (n=5) or bilateral (n=2) finding, with a mean number of 3.0 PVs compressed per patient (range: 1 to 7). A total of 10 venous sections showed features of compression, at the level of a lobar confluence (n=6) or individual segmental veins (V6; n=4), with a mean reduction in the venous cross-sectional area of 51.09%±12.85% (median: 50.06%). Nonfibrotic lung infiltration associated with sarcoidosis was observed in 88.2% of patients with compressive lymphadenopathy (15/17). The prevalence of venoatrial compression in sarcoidosis is 16.8% in the studied population.
    Journal of Thoracic Imaging 02/2015; DOI:10.1097/RTI.0000000000000134 · 1.49 Impact Factor
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    ABSTRACT: To compare the quality of low-dose CT images with sinogram affirmed iterative reconstruction (SAFIRE), and full-dose CT with filtered back projection reconstructions (FBP). Fifty pulmonary CT performed by a dual-source technique (120kVp; 110mAs) with (a) the same energy in both tubes, and (b) the distribution of reference mAs with 40% in tube A (44mAs) and 60% in tube B (66mAs). Each acquisition allowed reconstruction of: (a) full-dose images (with both tubes) with FBP reconstructions (group 1); and (b) low-dose images (from tube A) reconstructed with SAFIRE (group 2). Group 2 images presented: (a) a significant objective reduction in noise measured in the trachea on mediastinal (16.04±5.66 vs 17.66±5.84) (P=0.0284) and pulmonary (29.77±6.79 vs 37.96±9.03) (P<0.0001) images; (b) a similar subjective perception of noise and overall image quality (P=1), which was considered to be excellent in 66% (33/50) of the cases, with no influence on the detection of elementary pulmonary lesions of infiltration (98.4%; 95% CI=[96.9%-99.9%]). Despite a 60% reduction in radiation dose, the image quality with iterative reconstruction is objectively better and subjectively similar to full-dose FBP images. Copyright © 2015 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.
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    ABSTRACT: Access to the renal transplantation (RT) waiting list depends on factors related to lower mortality rates and often occurs after dialysis initiation. The aim of the study was to use a flexible regression model to determine if registration on the RT waiting list is associated with mortality on dialysis, independent of the comorbidities associated with such registration. Data from the French REIN registry on 7138 incident hemodialysis (HD) patients were analyzed. A multi-state model including four states ('HD, not wait-listed', 'HD, wait-listed', 'death', and 'RT') was used to estimate the effect of being wait-listed on the probability of death. During the study, 1392 (19.5%) patients were wait-listed. Of the 2954 deaths observed in the entire cohort during follow-up, 2921 (98.9%) were observed in the not wait-listed group compared with only 33 (1.1%) in the wait-listed group. In the multivariable analysis, the adjusted hazard ratio for death associated with non-registration on the waiting list was 3.52 (95% CI, 1.70-7.30). The risk factors for death identified for not wait-listed patients were not found to be significant risk factors for wait-listed patients, with the exception of age. The use of a multi-state model allowed a flexible analysis of mortality on dialysis. Patients who were not wait-listed had a much higher risk of death, regardless of co-morbidities associated with being wait-listed, and did not share the same risk factors of death as wait-listed patients. Registration on the waiting list should therefore be taken into account in survival analysis of patients on dialysis.
    Journal of Epidemiology 02/2015; 25(2):133-141. DOI:10.2188/jea.JE20130193 · 2.86 Impact Factor
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    ABSTRACT: To evaluate the impact of iterative reconstruction on the detectability of clots. Fifty-three patients were enrolled in a study comparing reduced-dose and full-dose images, available from the same dual-source data set. From each acquisition, three series of images were generated: (1) full-dose images (from both tubes), reconstructed with filtered back projection (FBP) (group 1; standard of reference), (2) reduced-dose images (from tube A only; 60 % dose reduction) reconstructed with FBP (group 2) and iterative reconstruction (SAFIRE) (group 3). In group 1 (mean DLP: 264.6 mGy.cm), (1) PE was diagnosed in 8 patients (15 %) with 82 clots in the central (n = 5), segmental (n = 39) and subsegmental (n = 38) arteries and (2) mean level of noise was 30.56 ± 5.07. In group 2 (mean DLP: 105.8 mGy.cm), a significant increase in noise (44.56 ± 6.24; p < 0.0001) (1) hampered detection of PE in one patient and (2) altered detection of peripheral clots (12 false-negative and 2 false-positive results). In group 3, image noise was not significantly different from that in group 1 (p = 0.1525; effect size: 0.2683), with a similar detection of PE compared to group 1 (p = 1). Reconstruction of reduced-dose images (60 % dose reduction) with SAFIRE provided image quality and diagnostic value comparable to those of full-dose FBP images. • Iterative reconstruction does not alter the detection of endoluminal clots. • Iterative reconstruction allows dose reduction in the context of acute PE. • Iterative reconstruction allows radiologists to approach the prospects of submilliSievert CT.
    European Radiology 01/2015; 25(4). DOI:10.1007/s00330-014-3393-5 · 4.34 Impact Factor
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    ABSTRACT: High center procedural volume has been shown to reduce postoperative mortality (POM); however, the cause of POM has been poorly studied previously. The aim of this study was to define the pattern of POM and major morbidity in relation to center procedural volume. Data from 2,944 consecutive adult patients undergoing esophagectomy for esophageal cancer in 30 centers between 2000 and 2010 were retrospectively collected. Data between patients who suffered 30-day POM were compared with those who did not. Factors associated with POM were identified using binary logistic regression, with propensity matching to compare low- (LV) and high-volume (HV) centers. The 30-day and in-hospital POM rates were 5.0 and 7.3 %, respectively. Pulmonary complications were the most common, affecting 38.1 % of patients, followed by surgical site infection (15.5 %), cardiovascular complications (11.2 %), and anastomotic leak (10.2 %). Factors that were independently associated with 30-day POM included American Society of Anesthesiologists grade IV, LV center, anastomotic leak, pulmonary, cardiovascular and neurological complications, and R2 resection margin status. Surgical complications preceded POM in approximately 30 % of patients compared to medically-related causes in 68 %. Propensity-matched analysis demonstrated LV centers were significantly associated with increased 30-day POM, and POM secondary to anastomotic leak, and pulmonary- and cardiac-related causes. The results of this large, multicenter study provide further evidence to support the centralization of esophagectomy to HV centers, with a lower rate of morbidity and better infrastructure to deal with complications following major surgery preventing further mortality.
    Annals of Surgical Oncology 01/2015; DOI:10.1245/s10434-014-4310-5 · 3.94 Impact Factor
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    ABSTRACT: Our aim was to analyse the potential role of chemokines receptors CXCR2 and CXCR4 signalling pathways in liver metastatic colorectal cancer (CRC) relapse. CXCR2, CXCR4 and their chemokine ligands were evaluated in liver metastases of colorectal cancer in order to study their correlation with overall and disease-free survivals of patients having received or not a neoadjuvant chemotherapy regimen.qRT-PCR, and CXCR2 immunohistochemical staining were performed using CRC liver metastasis samples. Expression levels of CXCR2, CXCR4 and their ligands were statistically analysed according to the administration of neoadjuvant chemotherapy and patients’ outcome.CXCR2 and CXCL7 overexpression are correlated to shorter overall and disease-free survival By multivariate analysis, CXCR2 and CXCL7 expressions are independent factors of overall and disease-free survivals. Neoadjuvant chemotherapy increases significantly the expression of CXCR2: treated group 1.89(0.02-50.92) versus 0.55(0.07-3.22), p=0.016. CXCL7 is overexpressed close to significance, 0.40 (0.00- 7.85) vs. 0.15 (0.01-7.88), p=0.12.We show the involvement of CXCL7/CXCR2 signalling pathways as predictive factor of poor outcome in metastatic CRC. 5FU-based chemotherapy regimens increase the expression of these genes in liver metastasis, providing one explanation for aggressiveness of relapsed drug-resistant tumours. Selective blockage of CXCR2/CXCL7 signalling pathways could provide new potential therapeutic opportunities.This article is protected by copyright. All rights reserved.
    Cancer Science 01/2015; DOI:10.1111/cas.12603 · 3.53 Impact Factor
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    ABSTRACT: Pseudomonas aeruginosa is an opportunistic Gram-negative bacterium that causes pneumonia in immunocompromised humans and severe pulmonary damage in patients with cystic fibrosis. Imbalanced fatty acid incorporation in membranes, including increased arachidonic acid and decreased DHA concentrations, is known to play a critical role in chronic inflammation associated with bacterial infection. Other lipids, such as EPA and alkylglycerols, are also known to play a role in inflammation, particularly by stimulating the immune system, decreasing inflammation and inhibiting bacterial growth. In this context, the goal of the present study was to assess the effect of dietary DHA/EPA, in a 2:1 ratio, and alkylglycerols, as natural compounds extracted from oils of rays and chimeras, respectively, on the inflammatory reaction induced by P. aeruginosa pulmonary infection in mice. To this end, mice were fed with a control diet or isolipidic, isoenergetic diets prepared with oils enriched in DHA/EPA (2:1) or alkylglycerols for 5 weeks before the induction of acute P. aeruginosa lung infection by endotracheal instillation. In our model, DHA/EPA (2:1) significantly improved the survival of mice after infection, which was associated with the acceleration of bacterial clearance and the resolution of inflammation leading to the improvement of pulmonary injuries. By contrast, alkylglycerols did not affect the outcomes of P. aeruginosa infection. Our findings suggest that supplementation with ray oil enriched in DHA/EPA (2:1) can be considered as a preventive treatment for patients at risk for P. aeruginosa infection.
    British Journal Of Nutrition 01/2015; DOI:10.1017/S0007114514003705 · 3.34 Impact Factor
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    ABSTRACT: Background Standardised measurement of remnant liver volume (RLV), where total liver volume (TLV) is calculated from patients’ body surface area (RLV-sTLV), has been advocated. Extrapolating the model of living donor liver transplantation, we showed in a pilot study that the simplified RLV/body weight ratio (RLVBWR) was accurate in assessing the functional limit of hepatectomy. The aim of the study was to compare in a prospective series of extended right hepatectomy the predictive value of the RLVBWR and the RLV-sTLV at a cut-off of 0.5% (RLVBWR0.5%) and 20% (RLV-sTLV20%), respectively. Methods We studied the impact of RLVBWR0.5% and of RLV-sTLV20% on three months morbidity and mortality in 74 non-cirrhotic patients operated on for malignant tumours. Of these, 47 patients who were not included in the initial pilot study were enrolled in a prospective validation cohort to reappraise the predictive value of each method. Results RLVBWR and RLV-sTLV were highly correlated (Pearson correlation coefficient, 0.966). Three months overall and severe morbidity (grade 3b–5) and mortality were significantly increased in groups RLVBWR ≤ 0.5% and RLV-sTLVs ≤ 20% compared to groups >0.5% and >20%, respectively. The sensitivity and specificity in predicting death from liver failure were 100 and 84.1% for RLVBWR0.5% and 60 and 94.2% for RLV-sTLV20%, respectively. Similar results were observed in the validation cohort for the RLVBWR0.5% (lack of statistical power for RLV-sTLV as only 2 patients showed a RLV-sTLV ≤ 20%). Conclusions The RLVBWR0.5% is a method of assessing the remnant liver that is simple and as reliable as the standardised RLV-sTLV20%.
    World Journal of Surgery 01/2015; DOI:10.1007/s00268-014-2929-9 · 2.35 Impact Factor
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    ABSTRACT: Objective: The aim of this study was to the determine impact of severe esophageal anastomotic leak (SEAL) upon long-term survival and locoregional cancer recurrence. Background: The impact of SEAL upon long-term survival after esophageal resection remains inconclusive with a number of studies demonstrating conflicting results. Methods: A multicenter database for the surgical treatment of esophageal cancer collected data from 30 university hospitals (2000-2010). SEAL was defined as a Clavien-Dindo III or IV leak. Patients with SEAL were compared with those without in terms of demographics, tumor characteristics, surgical technique, morbidity, survival, and recurrence. Results: From a database of 2944 operated on for esophageal cancer between 2000 and 2010, 209 patients who died within 90 days of surgery and 296 patients with a R1/R2 resection were excluded, leaving 2439 included in the final analysis; 208 (8.5%) developed a SEAL and significant independent association was observed with low hospital procedural volume, cervical anastomosis, tumoral stage III/IV, and pulmonary and cardiovascular complications. SEAL was associated with a significant reduction in median overall (35.8 vs 54.8 months; P = 0.002) and disease-free (34 vs 47.9 months; P = 0.005) survivals. After adjustment of confounding factors, SEAL was associated with a 28% greater likelihood of death [hazard ratio = 1.28; 95% confidence interval (CI): 1.04-1.59; P = 0.022], as well as greater overall (OR = 1.35; 95% CI: 1.15-1.73; P = 0.011), locoregional (OR = 1.56; 95% CI: 1.05-2.24; P = 0.030), and mixed (OR = 1.81; 95% CI: 1.20-2.71; P = 0.014) recurrences. Conclusions: This large multicenter study provides strong evidence that SEAL adversely impacts cancer prognosis. The mechanism through which SEAL increases local recurrence is an important area for future research.
    Annals of Surgery 01/2015; DOI:10.1097/SLA.0000000000001011 · 7.19 Impact Factor
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    ABSTRACT: Self-expanding metallic stents (SEMSs) have been used as a bridge to surgery, relieving dysphagia and maintaining nutrition, in patients with operable but obstructive esophageal cancer (EC). However, the impact of SEMSs on oncologic outcomes is unknown. The aim of this study was to evaluate the impact of SEMS insertion before EC surgery on oncologic outcomes. From 2000 to 2010, two thousand nine hundred and forty-four patients who underwent an operation for EC with a curative intent were included in a multicenter European cohort. Through propensity score analysis, patients who underwent SEMS insertion (SEMS group, n = 38) were matched 1:4 to control patients who did not undergo SEMS insertion (control group, n = 152). The SEMS and control groups were comparable according to age, sex, tumor location, clinical stage, American Society of Anesthesiologists score, dysphagia, malnutrition, neoadjuvant treatment administration, histology, and surgical procedure. Self-expanding metallic stent insertion was complicated by tumoral perforation in 2 patients. The in-hospital postoperative mortality and morbidity rates for the SEMS vs control groups were 13.2% vs 8.6% (p = 0.370) and 63.2% vs 59.2% (p = 0.658), respectively. The R0 resection rate (71.0% vs 85.5%; p = 0.041), median time to recurrence (6.5 vs 9.0 months; p = 0.040), and 3-year overall survival (25% vs 44%; p = 0.023) were significantly reduced in the SEMS group, and the 3-year locoregional recurrence rate was increased (62% vs 34%; p = 0.049). The results remained significant after excluding SEMS-related esophageal perforations. After adjusting for confounding factors, SEMS insertion was a predictor of poor prognosis (hazard ratio = 1.6; p = 0.038). Self-expanding metallic stent insertion, as a bridge to surgery, has a negative impact on oncologic outcomes in EC. Clinicaltrials.gov ID: NCT 01927016. Copyright © 2015 American College of Surgeons. Published by Elsevier Inc. All rights reserved.
    Journal of the American College of Surgeons 12/2014; 220(3). DOI:10.1016/j.jamcollsurg.2014.11.028 · 4.45 Impact Factor
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    ABSTRACT: Background and purposeSelective agonists of sigma-1 (σ1) protein are generally reported to protect against neuronal damage and modulate oligodendrocyte differentiation. Human and rodent lymphocytes possess saturable, high-affinity binding sites for σ ligands and potential immunomodulatory properties have been described for σ1 compounds. Experimental auto-immune encephalomyelitis (EAE) has unequivocal value as a model of the inflammatory aspects of multiple sclerosis (MS). Here, we have assessed the role of σ1 agonist containing the tetrahydroisoquinoleine-hydantoin structure in EAE.Experimental approachEAE was induced in SJL/J female mice by active immunization with myelin proteolipid protein (PLP)139-151 peptide. The σ1 agonist was injected i.p. at immunization time (D0). Disease severity was assessed clinically and by histopathological evaluation of the central nervous system (CNS). Phenotyping of B-cell subsets and Tregs were performed by flow cytometry in spleen and cervical lymph nodes.Key resultsProphylactic treatment of EAE mice with σ1 agonist prevented mononuclear cell accumulation and demyelination in brain and spinal cord and increased T2 B cells and Tregs, resulting in an overall reduction in the clinical progression of EAE.Conclusions and implicationsσ1 agonist containing the tetrahydroisoquinoleine-hydantoin structure dampened the magnitude of inflammation in EAE. This was associated with the increase in the proportion of B-cell subsets and Tregs with potential immunoregulatory functions. Targeting σ1 might thus provide new therapeutic opportunities for MS.
    British Journal of Pharmacology 12/2014; 172(7). DOI:10.1111/bph.13037 · 5.07 Impact Factor
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    ABSTRACT: Apathy is a frequent and disabling behavioral disorder in patients with Parkinson's disease (PD). Its prevalence in treatment-naive patients with early-stage PD has not been extensively investigated. Moreover, whether apathy is related to other non-motor symptoms in early-stage PD is unknown. Our objective was to determine the prevalence and features of apathy and associated factors in a group of treatment-naive patients with early-stage PD. Ninety-five treatment-naive patients with early-stage PD participated in the study. Apathy, depression, motor symptoms, and overall cognitive efficiency were assessed. The presence of the main non-motor symptoms was checked during a detailed clinical interview. Group comparisons were carried out to investigate the association with apathy. Eighteen patients (18.95%) were diagnosed as apathetic, and five of the latter had concomitant depression. Apathetic patients had significantly more severe motor symptoms (P < 0.001) and a lower cognitive status (P = 0.032) than non-apathetic patients. When considering non-motor symptoms, apathy was significantly associated only with fatigue (P = 0.007) and anhedonia (P = 0.010), both of which were more prevalent in apathetic patients than in non-apathetic patients. In treatment-naive patients with early-stage PD, apathy was significantly associated with more severe motor symptoms and a lower cognitive status. After adjustment for these factors, apathy appeared to be a relatively isolated, independent symptom because the only other associated non-motor symptoms were fatigue and anhedonia. © 2014 International Parkinson and Movement Disorder Society
    Movement Disorders 12/2014; 29(14). DOI:10.1002/mds.26058 · 5.63 Impact Factor
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    ABSTRACT: Objectives: To assess the impact of neoadjuvant chemoradiotherapy (NCRT) on anastomotic leakage (AL) and other postoperative outcomes after esophageal cancer (EC) resection. Background: Conflicting data have emerged from randomized studies regarding the impact of NCRT on AL. Methods: Among 2944 consecutive patients operated on for EC between 2000 and 2010 in 30 European centers, patients treated by NCRT after surgery (n = 593) were compared with those treated by primary surgery (n = 1487). Multivariable analyses and propensity score matching were used to compensate for the differences in some baseline characteristics. Results: Patients in the NCRT group were younger, with a higher prevalence of male sex, malnutrition, advanced tumor stage, squamous cell carcinoma, and surgery after 2005 when compared with the primary surgery group. Postoperative AL rates were 8.8% versus 10.6% (P = 0.220), and 90-day postoperative mortality and morbidity rates were 9.3% versus 7.2% (P = 0.110) and 33.4% versus 32.1% (P = 0.564), respectively. Pulmonary complication rates did not differ between groups (24.6% vs 22.5%; P = 0.291), whereas chylothorax (2.5% vs 1.2%; P = 0.020), cardiovascular complications (8.6% vs 0.1%; P = 0.037), and thromboembolic events (8.6% vs 6.0%; P = 0.037) were higher in the NCRT group. After propensity score matching, AL rates were 8.8% versus 11.3% (P = 0.228), with more chylothorax (2.5% vs 0.7%; P = 0.030) and trend toward more cardiovascular and thromboembolic events in the NCRT group (P = 0.069). Predictors of AL were high American Society of Anesthesiologists scores, supracarinal tumoral location, and cervical anastomosis, but not NCRT. Conclusions: Neoadjuvant chemoradiotherapy does not have an impact on the AL rate after EC resection (NCT 01927016).
    Annals of Surgery 11/2014; 260(5):764-771. DOI:10.1097/SLA.0000000000000955 · 7.19 Impact Factor
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    ABSTRACT: Objective: The question of whether breastfeeding has a protective effect against the development of overweight or obesity later in life remains controversial, especially during adolescence. The objective was to assess the relationship between breastfeeding and adolescents' body composition. Methods: The HELENA study is a cross-sectional study involving 3,528 adolescents from 10 European cities. The outcome measures were body weight and height, subscapular skinfolds as well as waist circumferences. Breastfeeding, smoking status, and parental socioeconomic status were assessed by self-administered questionnaires. Dietary intake was recorded using two 24-hour recall surveys. Two adjustment approaches were used: i) covariance analysis adjusted for confounding factors (propensity score adjustment) and ii) multivariate quantile regression. Results: After adjustment, no significant associations were observed between breastfeeding and body composition parameters (BMI Z-score; sum of skinfolds; waist-to-height ratio). An adjusted quantile regression analysis showed a non-significant trend for a protective effect of breastfeeding toward the highest percentiles of adiposity in boys but not in girls. This is of particular interest with respect to the superiority of the waist-to-height ratio over waist circumference and BMI for detecting cardiometabolic risk factors. Conclusion: This first European study, including a large set of factors influencing adolescents' body composition, showed a non-significant trend toward a protective effect of breastfeeding on highest percentiles of adolescent's abdominal adiposity. © 2014 S. Karger GmbH, Freiburg.
    Obesity Facts 10/2014; 7(5):289-301. DOI:10.1159/000368583 · 1.58 Impact Factor
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    ABSTRACT: Background Uncontrolled use of tanning beds is a major public health problem. The role of UV in skin carcinogenesis has in fact been clearly demonstrated. Aims The main purpose of the study was to assess the motivations and beliefs of the population concerning the use of indoor tanning. The secondary objectives were to compare the knowledge of users and non-users and to screen for addiction criteria among users. Patients and methods This was a transversal descriptive study conducted between April and June 2013 in Lille town center. The motivations of the participants were determined using a multiple-choice questionnaire. A Likert scale was used to assess beliefs and an m-CAGE questionnaire was used to screen for addiction. Results Of the 200 respondents, 30% (n = 60) had used tanning beds in a non-medical setting. The median age of first use was 23 years (15–59). 11.7% of respondents had started before the authorised age of 18 years. “To prepare the skin for exposure to the sun” was the main reason given (68.3%) for use of tanning beds. The population was aware that use of such apparatus favours onset of skin cancer and ageing of the skin. Users were more convinced than non-users that UV cabins “prepare the skin for exposure to the sun” (75% vs. 49.6%, P = 0.0009) and that they “favour skin cancer” (56.9% against 36.2%, P = 0.0444). Addictive behaviour was detected in 3.3% (2/60) of users. Conclusion Users are aware of the carcinogenic risk of UV cabins but expose themselves to such risk, as they believe it prepares their skin for sun exposure.
    Annales de Dermatologie et de Vénéréologie 10/2014; DOI:10.1016/j.annder.2014.09.006 · 0.67 Impact Factor

Publication Stats

5k Citations
1,243.46 Total Impact Points

Institutions

  • 2001–2015
    • CHRU de Strasbourg
      Strasburg, Alsace, France
  • 1997–2015
    • University of Lille Nord de France
      Lille, Nord-Pas-de-Calais, France
  • 1999–2014
    • Centre Hospitalier Régional Universitaire de Lille
      • Division of Neurology
      Lille, Nord-Pas-de-Calais, France
  • 2001–2013
    • Université du Droit et de la Santé Lille 2
      • Faculty of Medicine
      Lille, Nord-Pas-de-Calais, France
  • 2000–2011
    • Lille Catholic University
      Lille, Nord-Pas-de-Calais, France