Search

International audience; Aortic stenosis is a frequent disease in the elderly. Its prevalence is 0.4% with a sharp increase after the age of 65, and its outcome is very poor when the patient becomes symptomatic. The interventional procedure known as TAVI (trans-catheter aortic valve implantation), which was developed in France and carried out for the first time in Rouen by Prof. Alain Cribier and his team in 2002, has proven to be a valid alternative to surgical aortic valve replacement. At first, this technique was shown to be efficient in patients with contra-indications to surgical treatment or deemed to be at high surgical risk. Given the very promising outcomes achieved as a result of close heart team collaboration, appropriate patient selection, simplified procedures and reduced complication rates, transfemoral (TF) TAVI is now preferred in symptomatic intermediate risk patients>75 years old according to the latest ESC guidelines. In 2017, in France, TAVI is currently performed in 50 centers with on-site cardiac surgery. The 2016 TAVI outcomes recorded in the French national TAVI registry (France TAVI) are very encouraging and show that for 7133 patients treated (age 83.4±7 years, logistic Euroscore 14%), 87% of whom via the TF approach, cross-over to surgery was very low (0.5%) with a 3.0% in-hospital mortality rate. The substantial increase in TAVI indications and the improvement of its outcomes may in the near future call for a reconsideration of the number of high volume centers authorized to carry out this technique.

International audience; Magnetic resonance imaging (MRI) has become the reference imaging technique for the management of a large number of diseases. The number of MRI examinations increases every year, simultaneously with the number of patients receiving a cardiac electronic implantable device (CEID). The presence of a CEID was considered an absolute contraindication for MRI for many years. The progressive replacement of conventional pacemakers and defibrillators by "magnetic resonance (MR)-conditional" CEIDs and recent data on the safety of MRI in patients with "MR-non-conditional" CEIDs have gradually increased the demand for MRI in patients with a CEID. However, some risks are associated with MRI in CEID carriers, even with MR-conditional devices, because these devices are not "MR safe". Specific programming of the device in "MR mode" and monitoring patients during MRI remain mandatory for all patients with a CEID. A standardized patient workflow based on an institutional protocol should be established in each institution performing such examinations. This joint position paper of the Working Group of Pacing and Electrophysiology of the French Society of Cardiology and the French Society of Diagnostic and Interventional Cardiac and Vascular Imaging describes the effect of and risks associated with MRI in CEID carriers. We propose recommendations for patient workflow and monitoring and CEID programming in MR-conditional, "MR-conditional non-guaranteed" and MR-non-conditional devices.; L’imagerie par résonance magnétique (IRM) est devenue l’imagerie de référence pour le diagnostic d’un grand nombre de pathologies. Le nombre d’examens IRM est en augmentation constante, parallèlement au nombre de patients implantés avec un dispositif électronique cardiaque implantable (DECI). L’IRM était considérée comme une contre-indication absolue à l’IRM jusqu’à il y a quelques années. Le remplacement progressif des stimulateurs et des défibrillateurs conventionnels par des dispositifs « IRM compatibles sous conditions » ainsi que les données récentes sur la sécurité des examens IRM chez les patients porteurs de dispositifs « non-IRM compatible » ont considérablement accru la demande d’examens IRM chez les patients porteurs de DECI. Cependant, les IRM peuvent être associés à certains risques chez les porteurs de DECI, y compris ceux « IRM compatibles sous conditions ». La programmation spécifique de l’appareil en mode « IRM » et la surveillance des patients pendant l’examen restent obligatoires pour tous les patients porteurs de DECI. Une prise en charge standardisée s’appuyant sur un protocole institutionnel est recommandée dans chaque établissement effectuant de tels examens. Ce document conjoint du Groupe Rythmologie et Stimulation Cardiaque de la Société Française de Cardiologie et de la Société Française d’Imagerie Cardiaque et Vasculaire Diagnostique et Interventionnelle décrit les effets et les risques associés à l’IRM chez des porteurs de DECI. Nous proposons des recommandations pour la prise en charge de ces patients, leur surveillance, ainsi que la programmation des dispositifs qu’ils soient « IRM compatibles sous conditions », « IRM compatibles sous conditions hors garantie constructeur » ou « non-IRM compatibles ».

Introduction: Olfactory and taste disorders (OTDs) have been reported in COVID-19 caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the mechanisms of which remain unclear. We conducted a detailed analysis of OTDs as part of 2 seroepidemiological investigations of COVID-19 outbreaks. Methods: Two retrospective cohort studies were conducted in a high school and primary schools of Northern France following a COVID-19 epidemic in February-March 2020. Students, their relatives, and school staff were included. Anti-SARS-CoV-2 antibodies were identified using a flow-cytometry-based assay detecting anti-S IgG. Results: Among 2,004 participants (median [IQR] age: 31 [11–43] years), 303 (15.2%) tested positive for SARS-CoV-2 antibodies. OTDs were present in 91 (30.0%) and 92 (30.3%) of them, respectively, and had 85.1 and 78.0% positive predictive values for SARS-CoV-2 infection, respectively. In seropositive participants, OTDs were independently associated with an age above 18 years, female gender, fatigue, and headache. Conclusion: This study confirms the higher frequency of OTDs in females than males and adults than children. Their high predictive value for the diagnosis of COVID-19 suggests that they should be systematically searched for in patients with respiratory symptoms, fever, or headache. The association of OTDs with headache, not previously reported, suggests that they share a common mechanism, which deserves further investigation.

Background Smart scales are increasingly used at home by patients to monitor their body weight and body composition, but scale accuracy has not often been documented. Objective The goal of the research was to determine the accuracy of 3 commercially available smart scales for weight and body composition compared with dual x-ray absorptiometry (DEXA) as the gold standard. Methods We designed a cross-sectional study in consecutive patients evaluated for DEXA in a physiology unit in a tertiary hospital in France. There were no exclusion criteria except patient declining to participate. Patients were weighed with one smart scale immediately after DEXA. Three scales were compared (scale 1: Body Partner [Téfal], scale 2: DietPack [Terraillon], and scale 3: Body Cardio [Nokia Withings]). We determined absolute error between the gold standard values obtained from DEXA and the smart scales for body mass, fat mass, and lean mass. Results The sample for analysis included 53, 52, and 48 patients for each of the 3 tested smart scales, respectively. The median absolute error for body weight was 0.3 kg (interquartile range [IQR] –0.1, 0.7), 0 kg (IQR –0.4, 0.3), and 0.25 kg (IQR –0.10, 0.52), respectively. For fat mass, absolute errors were –2.2 kg (IQR –5.8, 1.3), –4.4 kg (IQR –6.6, 0), and –3.7 kg (IQR –8.0, 0.28), respectively. For muscular mass, absolute errors were –2.2 kg (IQR –5.8, 1.3), –4.4 kg (IQR –6.6, 0), and –3.65 kg (IQR –8.03, 0.28), respectively. Factors associated with fat mass measurement error were weight for scales 1 and 2 (P=.03 and P Conclusions Smart scales are not accurate for body composition and should not replace DEXA in patient care. Trial Registration ClinicalTrials.gov NCT03803098; https://clinicaltrials.gov/ct2/show/NCT03803098

Background: The coronavirus disease 2019 (COVID-19) pandemic raises the concern that other non-COVID conditions will be affected by a decline in care. Therefore, we aimed to investigate the decline in ambulatory presentations for vascular events (stroke, transient ischemic attack [TIA], and myocardial infarction [MI]) during the COVID-19 pandemic. Methods: Patients with a diagnosis of ischemic stroke, TIA, or MI documented anonymously in 1,262 general practices in Germany were included. We studied the differences between 2019 and 2020 (between April and June) in terms of rates and baseline characteristics by comparing monthly absolute frequencies. Results: A total of 3,496 patients with stroke (mean age: 72.2 years), 1,608 patients with TIA (mean age: 71.5 years), and 2,385 patients with MI (mean age: 66.8 years) were identified between April and June 2020, indicating a decrease of 10% (stroke), 16% (TIA), and 9% (MI) compared to 2019. For patients with stroke, the decrease in men was 13% (women: −6%) but reached 17% in the age category 51–60 years. For MI, the decrease was only obvious in males (14%). The largest decrease in stroke (−17%) and MI (−19%) was noted in April, while that for TIA occurred in May (−22%). In June for all 3 conditions, the previous year’s level was achieved. Only in TIA, the age differs between 2019 and 2020 (mean age: 69.9 vs. 71.5 years; p < 0.05). In patients with stroke and MI, the proportions of men were lower in 2019 than in 2020 (stroke: 54.8–50.5%, p < 0.05 and MI: 64–60.2%, p < 0.05). Conclusion: Although the decline in the number of patients presenting with stroke, TIA, and MI was not as noticeable in the ambulatory sector as it was in the area of emergency hospital-based care, our data indicate that the COVID-19 pandemic affected all sectors within the medical care system.

Although influenza vaccination of hospital healthcare workers (HCWs) has been associated with a reduction in patient mortality and morbidity, HCW vaccine coverage is low in France. Previous studies identified the role of perceptions of vaccine efficacy and safety as well as practical issues (e.g., limited time). We aimed to determine whether HCW behavior toward influenza vaccine was associated with occupation-related psycho-social issues and perceptions of management. Between February and August 2018, an anonymous online questionnaire explored the perceptions and behavior of nurses and nurse aides regarding the influenza vaccine, as well as the perceived quality of professional management, perceived psychological contract breach, perceived workload, and compassion fatigue using previously validated scales. Among the 791 respondents (mean age 36.9 ± 10 years, female 85.0%; nurses 76.4%), 28.6% had been vaccinated during the current year (i.e., the study year) and 13.0% during the previous year. Among those not vaccinated during the study year, their vaccination intention for the coming year on a 1–5 scale was 1/5 for 68.5% and 5/5 for 15.4%. Positive behavior/intention regarding the influenza vaccine (recent vaccination and/or high future intention) was positively correlated with perceptions of management and negatively correlated with feelings of a psychological contract breach and compassion fatigue. In multivariate analysis, this positive behavior/intention was correlated with management perception independently of the perceptions of vaccination itself. Among nurses and nurse aides, the propensity to be vaccinated appears to depend closely on the perceived working conditions. These factors should be addressed when promoting vaccination among these populations.

International audience; Influenza vaccine adherence remains low. Communication of virological diagnosis to adults hospitalized with influenza-like illness (ILI) could improve their willingness to be subsequently vaccinated. We prospectively assessed, in adults hospitalized with ILI in six French university hospitals, their willingness to be vaccinated against influenza in the subsequent season, both before and after the communication of RT-PCR Influenza laboratory result; we identified then the determinants associated with the willingness to be vaccinated. A total of 309 patients were included during the 2012-2013 and 2013-2014 influenza seasons; 43.8% reported being vaccinated against influenza for the current season; before communication of influenza laboratory results, 65.1% reported willingness to be vaccinated during the subsequent season. Influenza was virologically confirmed in 103 patients (33.3%). The rate of vaccine willingness increased to 70.4% (p=0.02) after communication of influenza laboratory results. Factors independently associated with the willingness to be vaccinated were the perception of influenza vaccine benefits (adjusted relative risk (aRR) 1.06, 95%CI 1.02-1.10), cues to action (aRR 1.08, 95%CI 1.03-1.12), current season influenza vaccination (aRR 1.38, 95%CI 1.20-1.59) and communication of a positive influenza laboratory result (aRR 1.18, 95%CI 1.03-1.34). This last was associated with the willingness to be vaccinated only in the subpopulation of patients not vaccinated (aRR 1.53, 95%CI 1.19-1.96). In patients hospitalized with ILI, communication of a positive influenza diagnostic led to a better appreciation of the disease's severity and increased the willingness to be vaccinated. This approach might be particularly beneficial in patients who do not have a history of influenza vaccination.

The translation of cardioprotection from robust experimental evidence to beneficial clinical outcome for patients suffering acute myocardial infarction or undergoing cardiovascular surgery has been largely disappointing. The present review attempts to critically analyse the evidence for confounders of cardioprotection in patients with acute myocardial infarction and in patients undergoing cardiovascular surgery. One reason that has been proposed to be responsible for such lack of translation is the confounding of cardioprotection by co-morbidities and co-medications. Whereas there is solid experimental evidence for such confounding of cardioprotection by single co-morbidities and co-medications, the clinical evidence from retrospective analyses of the limited number of clinical data is less robust. The best evidence for interference of co-medications is that for platelet inhibitors to recruit cardioprotection per se and thus limit the potential for further protection from myocardial infarction and for propofol anaesthesia to negate the protection from remote ischaemic conditioning in cardiovascular surgery. LINKED ARTICLES: This article is part of a themed issue on Risk factors, comorbidities, and comedications in cardioprotection. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.23/issuetoc.

// Vincent Fleury 1 , Ludovic Ferrer 2, 4 , Mathilde Colombie 1 , Daniela Rusu 1 , Maelle Le Thiec 1 , Francoise Kraeber-Bodere 1, 2 , Loic Campion 2, 3 and Caroline Rousseau 1, 2 1 Nuclear Medicine Unit, ICO Cancer Center, Saint Herblain, France 2 Nantes-Angers Cancer Research Center, INSERM U892, CNRS UMR 6299, University of Nantes, Nantes, France 3 Biometrics Unit, ICO Gauducheau Cancer Center, Saint Herblain, France 4 Medical Physics Unit, ICO Cancer Center, Saint Herblain, France Correspondence to: Vincent Fleury, email: vfleury245@gmail.com Keywords: SPECT/CT; bone scan; bone metastases; bone index; prostate cancer Received: March 29, 2018 Accepted: July 18, 2018 Published: August 03, 2018 ABSTRACT Propose: The aim of our study was to evaluate the potential benefit of a systematic trunk SPECT/CT associated with a Planar Bone Scan (PBS) in breast cancer (BC) and prostate cancer (PCa) patients at initial staging or recurrence. Results: In 328 patients, sensitivities and specificities were between 74.4–93% and 78.8–97.5% for PBS and 97.7–100% and 96.8–98.6% for SPECT/CT respectively. PBS was considered equivocal for 67 compared to only 6 patients for trunk SPECT/CT. Regardless of “optimistic” or “pessimistic” analysis of equivocal trunk SPECT/CT lesions, the trunk SPECT/CT was almost perfect, allowing to rely on this result for excluding metastatic disease which was corroborated by ROC curve analysis. The trunk SPECT/CT allowed downstaging for 62 patients (19%) and upstaging for 11 patients. Materials and Methods: PBS and a trunk SPECT/CT were systematically performed in all patients. Independent review of PBS and trunk SPECT/CT was performed for each patient and an abnormality interpretative score (Sc) with 3 levels was built: Sc 1: metastatic or probably metastatic pattern, Sc 2: equivocal pattern, Sc 3: benign or probably benign pattern or no abnormality. The bone pattern status was defined by at least 1 year follow-up. The clinical impact was evaluated in terms of down and upstaging in patient analysis. Conclusions: Trunk SPECT/CT improves the performance of PBS in BC and PCa assessments and results in improvements in both the detection performance of bone metastases as well as a better characterization of equivocal lesions.

International audience; To determine whether spa therapy has a beneficial effect on pain and disability in patients with chronic shoulder pain, this single-blind randomised controlled clinical trial included patients with chronic shoulder pain due to miscellaneous conditions attending one of four spa centres as outpatients. Patients were randomised into two groups: spa therapy (18 days of standardised treatment combining thermal therapy together with supervised mobilisation in a thermal pool) and controls (spa therapy delayed for 6 months: 'immediate versus delayed treatment' paradigm). All patients continued usual treatments during the 6-month follow-up period. The main endpoint was the mean change in the French-Quick DASH (F-QD) score at 6 months. The effect size of spa therapy was calculated, and the proportion of patients reaching minimal clinically important improvement (MCII) was compared. Secondary endpoints were the mean change in SF-36, treatment use and tolerance. One hundred eighty-six patients were included (94 patients as controls, 92 in the spa group) and analysed by intention to treat. At 6 months, the mean change in the F-QD score was statistically significantly greater among spa therapy patients than controls (- 32.6 versus - 8.15%; p

// Elodie Jobard 1, 2 , Olivier Tredan 2 , Thomas Bachelot 2 , Arnaud M. Vigneron 3 , Celine Mahier Ait-Oukhatar 4 , Monica Arnedos 5 , Maria Rios 6 , Jacques Bonneterre 7 , Veronique Dieras 8 , Marta Jimenez 4 , Jean-Louis Merlin 9, 10 , Mario Campone 11 and Benedicte Elena-Herrmann 1 1 Universite de Lyon, Institut des Sciences Analytiques, UMR 5280, CNRS, Universite Lyon 1, ENS de Lyon, Villeurbanne, France 2 Universite de Lyon, Centre Leon Berard, Departement d’oncologie medicale, Lyon, France 3 Universite de Lyon, Centre de Cancerologie de Lyon, UMR Inserm 1052 CNRS 5286, Centre Leon Berard, Lyon, France 4 R&D Unicancer, UNICANCER, Paris, France 5 Department of Medicine, Gustave Roussy, Villejuif, France 6 Department of Medical Oncology, Centre Alexis Vautrin, Vandoeuvre-les-Nancy, France 7 Department of Medical Oncology, Centre Oscar Lambret, Lille, France 8 Department of Medical Oncology, Institut Curie, Paris, France 9 CNRS UMR7039 CRAN, Universite de Lorraine, Vandoeuvre-les-Nancy, France 10 Department of Biopathology Unit, Institut de Cancerologie de Lorraine, Vandoeuvre-Les-Nancy, France 11 Institut de Cancerologie de l’Ouest, Centre Rene Gauducheau, Saint-Herblain, France Correspondence to: Benedicte Elena-Herrmann, email: benedicte.elena@ens-lyon.fr Olivier Tredan, email: olivier.tredan@lyon.unicancer.fr Keywords: HER-2 positive breast cancer, metabolomics, nuclear magnetic resonance, targeted therapies, mTOR inhibitor Received: April 04, 2017 Accepted: May 23, 2017 Published: June 28, 2017 ABSTRACT The mammalian target of rapamycin complex 1 (mTORC1) is an attractive target for HER-2 positive breast cancer therapy because of its key role in protein translation regulation, cell growth and metabolism. We present here a metabolomic investigation exploring the impact of mTOR inhibition on serum metabolic profiles from patients with non-metastatic breast cancer overexpressing HER-2. Baseline, treatment-related and post-treatment serum samples were analyzed for 79 patients participating in the French clinical trial RADHER, in which randomized patients with HER-2 positive breast cancer received either trastuzumab alone (arm T) or a trastuzumab and everolimus combination (arm T+E). Longitudinal series of NMR serum metabolic profiles were exploited to investigate treatment effects on the patients metabolism over time, in both group. Trastuzumab and everolimus combination induces faster changes in patients metabolism than trastuzumab alone, visible after only one week of treatment as well as a residual effect detectable up to three weeks after ending the treatment. These metabolic fingerprints highlight the involvement of several metabolic pathways reflecting a systemic effect, particularly on the liver and visceral fat. Comparison of serum metabolic profiles between the two arms shows that everolimus, an mTORC1 inhibitor, is responsible for host metabolism modifications observed in arm T+E. In HER-2 positive breast cancer, our metabolomic approach confirms a fast and persistent host metabolism modification caused by mTOR inhibition.

// Cedric Rossi 1, 2 , Morgane Mounier 3 , Pauline Brice 4 , Violaine Safar 5 , Emmanuelle Nicolas-Virelizier 6 , Philippe Rey 6 , Aspasia Stamatoullas-Bastard 7 , Marion Alcantara 7 , Adrien Chauchet 8 , Emilie Reboursiere 9 , Lauriane Filliatre 10 , Aurore Perrot 10 , Sylvain Garciaz 11 , Gilles Salles 6 , Bertrand Coiffier 6 , Herve Ghesquieres 5, 6 and Rene-Olivier Casasnovas 1, 12 1 Hematologie Clinique, CHU Le Bocage, Dijon, France 2 INSERM UMR 1037 - Cancer Research Center of Toulouse, Toulouse, France 3 Registre des Hemopathies Malignes de Cote d’Or, EA4184, Universite de Bourgogne, Dijon, France 4 Hematologie Clinique, CHU Paris-GH St-Louis Lariboisiere F-Widal - Hopital Saint-Louis, Paris, France 5 Hematologie Clinique, Centre Hospitalier Lyon Sud, Pierre-Benite, France 6 Hematologie Clinique, Centre Regional de Lutte Contre le Cancer Leon Berard, Lyon, France 7 Hematologie Clinique, Centre Henri Becquerel, Rouen, France 8 Hematologie Clinique, CHU Besancon, Besancon, France 9 Hematologie Clinique, CHU Caen, Caen, France 10 Hematologie Clinique, CHRU Nancy, Nancy, France 11 Hematologie Clinique, Institut Paoli-Calmettes, Marseille, France 12 INSERM UMR 1231, Universite Bourgogne Franche-Comte, Dijon, France Correspondence to: Cedric Rossi, email: cedric.rossi66@gmail.com Keywords: Hodgkin lymphoma, infradiaphragmatic, radiotherapy Received: March 21, 2017 Accepted: June 19, 2017 Published: July 19, 2017 ABSTRACT Introduction: Infradiaphragmatic Hodgkin Lymphoma (IDHL) accounts for 3-11% of adult cases of stage I-II Hodgkin Lymphoma and the treatment strategy in IDHL is still heterogeneous. All previous published studies were conducted before the PET-CT era. PET may provide a more accurate evaluation of IDHL stage. The aim of this study was to analyze the clinical and biological characteristics of IDHL patients staged by CT scan or PET-CT in eight French hematology departments and their impact on outcomes in these patients. Methods: Baseline clinical and biological data and outcomes in patients with a first diagnosis of stage I-II IDHL treated with ABVD +/- radiotherapy were retrospectively collected. Results: Among the 99 patients included, 65 (66%) were staged with PET-CT. These patients were older (53 years vs 46 years, p=0.043), had lower ESR (27 vs 58mm, p=0.022), higher hemoglobin level (13.6 vs 12.8g/dL, p=0.015), less frequent Ann Arbor stage II (74% vs 91%) and less central adenopathy involvement (60% vs 82%, p=0.024). Treatment was chemotherapy alone in 55% of patients and the remaining patients received chemo-radiotherapy (CRT). Five-year PFS and OS rates in PET-CT-staged patients were 78% (95% CI 64-87) and 88% (95% CI 73-95), respectively, compared with 65% (p=0.225) and 82% (p=0.352) in CT-staged patients. The CRT strategy was associated with fewer relapses (p=0.027). Conclusion: This study showed that the characteristics of CT-staged IDHL patients were less favorable than those of PET-CT-staged patients and indicated that CRT provided better PFS than did chemotherapy alone.

// Asma Beldi-Ferchiou 1, 2, 11 , Marion Lambert 1, 2 , Stephanie Dogniaux 3 , Frederic Vely 4, 5 , Eric Vivier 4, 5 , Daniel Olive 6 , Stephanie Dupuy 1 , Frank Levasseur 1 , David Zucman 7 , Celeste Lebbe 8 , Damien Sene 1, 2, 9 , Claire Hivroz 4 , Sophie Caillat-Zucman 1, 2, 10 1 Institut National de Recherche Medicale (INSERM) UMR1149, Centre de Recherche Sur l’Inflammation, Equipe Immunite Innee Chez l’enfant, Hopital Robert Debre, Paris, France 2 Universite Paris Diderot, Sorbonne Paris Cite, Paris, France 3 Institut Curie, Centre de Recherche, PSL Research University, INSERM U932 Immunite et Cancer, Paris, France 4 Centre d’Immunologie de Marseille-Luminy, Aix-Marseille Universite UM2, INSERM U1104, CNRS UMR7280, Marseille, France 5 Immunologie, Hopital de la Conception, Assistance Publique- Hopitaux de Marseille, Marseille, France 6 Centre de Cancerologie de Marseille, INSERM U1068, Equipe Immunite et Cancer, Institut Paoli-Calmettes, Aix-Marseille Universite, CNRS, UMR7258, Marseille, France 7 Hopital Foch, Service de Medecine Interne, Suresnes, France 8 Assistance Publique-Hopitaux de Paris (AP-HP), Hopital Saint-Louis, Departement de Dermatologie, INSERM U976, Universite Paris Diderot, Paris, France 9 Assistance Publique-Hopitaux de Paris (AP-HP), Hopital Lariboisiere, Departement de Medecine Interne, Paris, France 10 Assistance Publique-Hopitaux de Paris (AP-HP), Hopital Saint-Louis, Laboratoire d’Immunologie, Paris, France 11 Present address: Assistance Publique-Hopitaux de Paris (AP-HP), Hopital Henri Mondor, Laboratoire d’Immunologie, Creteil, France Correspondence to: Sophie Caillat-Zucman, email: sophie.caillat@inserm.fr Keywords: NK cells, Kaposi sarcoma, PD-1, immune checkpoint, tumor escape Received: March 31, 2016 Accepted: September 13, 2016 Published: September 20, 2016 ABSTRACT Programmed Death-1 (PD-1), an inhibitory receptor expressed by activated lymphocytes, is involved in regulating T- and B-cell responses. PD-1 and its ligands are exploited by a variety of cancers to facilitate tumor escape through PD-1-mediated functional exhaustion of effector T cells. Here, we report that PD-1 is upregulated on Natural Killer (NK) cells from patients with Kaposi sarcoma (KS). PD-1 was expressed in a sub-population of activated, mature CD56 dim CD16 pos NK cells with otherwise normal expression of NK surface receptors. PD-1 pos NK cells from KS patients were hyporesponsive ex vivo following direct triggering of NKp30, NKp46 or CD16 activating receptors, or short stimulation with NK cell targets. PD-1 pos NK cells failed to degranulate and release IFNγ, but exogenous IL-2 or IL-15 restored this defect. That PD-1 contributed to NK cell functional impairment and was not simply a marker of dysfunctional NK cells was confirmed in PD-1-transduced NKL cells. In vitro , PD-1 was induced at the surface of healthy control NK cells upon prolonged contact with cells expressing activating ligands, i.e. a condition mimicking persistent stimulation by tumor cells. Thus, PD-1 appears to plays a critical role in mediating NK cell exhaustion. The existence of this negative checkpoint fine-tuning NK activation highlights the possibility that manipulation of the PD-1 pathway may be a strategy for circumventing tumor escape not only from the T cell-, but also the NK-cell mediated immune surveillance.

// Lucille Lopez-Delisle 1,2 , Cecile Pierre-Eugene 1,2 , Evelyne Bloch-Gallego 3,4 , Marie-Christine Birling 5 , Jean-Loup Duband 6,7 , Estelle Durand 8 , Thomas Bourgeois 8 , Boris Matrot 8,9 , Tania Sorg 5 , Michel Huerre 10 , Hamid Meziane 5 , Michel J. Roux 5 , Marie-France Champy 5 , Jorge Gallego 9 , Olivier Delattre 1,2 , Isabelle Janoueix-Lerosey 1,2 1 Inserm U830, Paris, France; 2 Institut Curie, Centre de Recherche, Paris, France; 3 Institut Cochin, Universite Paris Descartes, CNRS (UMR 8104), Paris, France; 4 Inserm, U1016, Paris, France; 5 Institut Clinique de la Souris, Illkirch-Graffenstaden, France; 6 Sorbonne Universites, Universite Pierre et Marie Curie-Paris 6, Paris, France; 7 CNRS, Laboratoire de Biologie du Developpement, Paris, France; 8 PhenoPups SAS, Evry, France; 9 Inserm U1141, Hopital Robert Debre, Paris, France; 10 Institut Curie, Departement de Pathologie, Paris, France. Correspondence: Isabelle Janoueix-Lerosey, email: // Keywords : ALK, brainstem, neonatal lethality, plethysmography, feeding difficulties Received : March 24, 2014 Accepted : April 01, 2014 Published : April 02, 2014 Abstract The ALK (Anaplastic Lymphoma Kinase) gene encodes a tyrosine kinase receptor preferentially expressed in the central and peripheral nervous systems. A syndromic presentation associating congenital neuroblastoma with severe encephalopathy and an abnormal shape of the brainstem has been described in patients harbouring de novo germline F1174V and F1245V ALK mutations. Here, we investigated the phenotype of knock-in (KI) mice bearing the Alk F1178L mutation (F1174L in human). Although heterozygous KI mice did not reproduce the severe breathing and feeding difficulties observed in human patients, behavioral tests documented a reduced activity during dark phases and an increased anxiety of mutated mice. Matings of heterozygotes yielded the expected proportions of wild-type, heterozygotes and homozygotes at birth but a high neonatal lethality was noticed for homozygotes. We documented Alk expression in several motor nuclei of the brainstem involved in the control of sucking and swallowing. Evaluation of basic physiological functions 12 hours after birth revealed slightly more apneas but a dramatic reduced milk intake for homozygotes compared to control littermates. Overall, our data demonstrate that Alk activation above a critical threshold is not compatible with survival in mice, in agreement with the extremely severe phenotype of patients carrying aggressive de novo ALK germline mutations.

PURPOSE: The purpose of this study was to analyse the results of total knee arthroplasty (TKA) in stiff knees (flexion ?90° and/or flexion contracture ?20°). Our hypothesis was that despite having poorer results than those obtained in a "standard" population and a high rate of complications, TKA was a satisfactory treatment in patients with osteoarthritis of the knee associated with significant stiffness. METHODS: Three hundred and four consecutive primary HLS TKAs (Tornier), whose data were prospectively collected between October 1987 and October 2012, were retrospectively analysed at a mean of 60 months (range, 12-239) postoperatively. Two groups, those with a "flexion contracture" and those with a "flexion deficit", were assessed for postoperative range of motion (as integrated to the Knee Society score [KSS]), physical activity level and patient satisfaction. RESULTS: At the latest follow-up, range of motion was significantly improved, as was the KSS. Ninety-four percent of patients were satisfied or very satisfied, and activity levels were increased after surgery. The complication rate, however, was high in patients with a preoperative flexion deficit (17%). Pain and residual stiffness were the most common complications. CONCLUSION: TKA provides satisfactory results in patients with knee osteoarthritis associated with significant pre-operative stiffness. The surgical plan should be adapted to anticipate complications, which are particularly frequent in the presence of a flexion deficit.

International audience; This study prospectively assessed the outcome of 134 cemented titanium stems and serum ion levels. The stems were polished (0.1 microm Ra) with circular cross section. At the end point, only one stem revision was performed for aseptic loosening, and two were planned due to subsidence greater than 5 mm. Non-progressive radiolucencies in zones 1 and 7 were observed in 16 hips at the cement-bone interface without osteolysis. Median serum titanium concentrations were below the detection limit (30 nmol/l) except in patients with failed stems. The overall stem survival rate was 97.7% at nine years, which is comparable to other series of cemented stems. The protective layer of titanium oxide coating the stem and a thick cement mantle may help resist aseptic loosening. In addition, satisfactory monitoring of the stem was reached using titanium serum level determination.

Background: In intra-arterial (IA) thrombolysis trials, higher rates of symptomatic intracerebral haemorrhage (sICH) were found than in trials with intravenous (IV) recombinant tissue plasminogen activator (tPA); this observation could have been due to the inclusion of more severely affected patients in IA thrombolysis trials. In the present study, we investigated the rate of sICH in IA and combined IV + IA thrombolysis versus IV thrombolysis after adjusting for differences in clinical and MRI parameters. Methods: In this multicenter study, we systematically analyzed data from 645 patients with anterior-circulation strokes treated with either IV or IA thrombolysis within 6 h following symptom onset. Thrombolytic regimens included (1) IV tPA treatment (n = 536) and (2) IA treatment with either tPA or urokinase (n = 74) or (3) combined IV + IA treatment with either tPA or urokinase (n = 35). Results: 44 (6.8%) patients developed sICH. sICH patients had significantly higher scores on the National Institutes of Health Stroke Scale (NIHSS) at admission and pretreatment DWI lesions. The sICH risk was 5.2% (n = 28) in IV thrombolysis, which is significantly lower than in IA (12.5%, n = 9) or IV + IA thrombolysis (20%, n = 7). In a binary logistic regression analysis including age, NIHSS score, time to thrombolysis, initial diffusion weighted imaging lesion size, mode of thrombolytic treatment and thrombolytic agent, the mode of thrombolytic treatment remained an independent predictor for sICH. The odds ratio for IA or IV + IA versus IV treatment was 3.466 (1.19–10.01, 95% CI, p < 0.05). Conclusion: In this series, IA and IV + IA thrombolysis is associated with an increased sICH risk as compared to IV thrombolysis, and this risk is independent of differences in baseline parameters such as age, initial NIHSS score or pretreatment lesion size.

International audience; Featured Application: This paper focuses on improvement in patient care and it also helps practitioners optimize their dermatology services by means of computer-assisted diagnostic software using data from reflectance confocal microscopy devices. Abstract: Reflectance confocal microscopy is an appropriate tool for the diagnosis of lentigo maligna. Compared with dermoscopy, this device can provide abundant information as a mosaic and/or a stack of images. In this particular context, the number of images per patient varied between 2 and 833 images and the objective, ultimately, is to be able to discern between benign and malignant classes. First, this paper evaluated classification at the image level, with the help of handcrafted methods derived from the literature and transfer learning methods. The transfer learning feature extraction methods outperformed the handcrafted feature extraction methods from literature, with a F 1 score value of 0.82. Secondly, this work proposed patient-level supervised methods based on image decisions and a comparison of these with multi-instance learning methods. This study achieved comparable results to those of the dermatologists, with an AUC score of 0.87 for supervised patient diagnosis and an AUC score of 0.88 for multi-instance learning patient diagnosis. According to these results, computer-aided diagnosis methods presented in this paper could be easily used in a clinical context to save time or confirm a diagnosis and can be oriented to detect images of interest. Also, this methodology can be used to serve future works based on multimodality.

Part 2: Long and Short Papers; International audience; Handoffs are moments of critical transition in which clinicians engage to maintain continuous coverage of patient care. This paper reports on an observational study of continuous coverage in an Emergency Department (ED), where three types of handoffs that occur during the same shift were identified: lunch breaks, ad hoc breaks and high workloads. The findings show these “in-shift handoffs” are managed not only through temporal linear coordination, but also through the local coordination among nurses working nearby. In-shift handoffs are crucial to maintaining continuous coverage in hospital settings.However,insufficient understanding of in-shift handoffs in Electronic Medical System (EMR) design may lead to a separation of information and responsibility, and an illusion of communicationin patient care.The findings of this study call for attention to in-shift handoffs in future system design and for improving the traditional handoff process through the coordination of local awareness during ED work.

In this paper, we evaluate computationally the influence of blood flow eccentricity and valve phenotype (bicuspid (BAV) and tricuspid (TAV) aortic valve) on hemodynamics in ascending thoracic aortic aneurysm (ATAA) patients. 5 TAV ATAA, 5 BAV ATAA (ascending aorta diameter > 35 mm) and 2 healthy subjects underwent 4D flow MRI. The 3D velocity profiles obtained from 4D flow MRI were given as input boundary conditions to a computational fluid dynamics analysis (CFD) model. After performing the CFD analyses, we verified that the obtained time-averaged velocity profiles and flow eccentricity were in good agreement with 4D flow MRI. Then we used the CFD analyses to evaluate the time-averaged wall shear stress (TAWSS) and the local normalized helicity (LNH). We found that the flow eccentricities at the aortic root were not significantly different (p > 0.05) between TAV and BAV phenotypes. TAWSS (R2 = 0.697, p = 0.025) and absolute LNH (R2 = 0.964, p 0.001) are in good correlation with flow eccentricity. We conclude that eccentricity at the aortic root is a major determinant of hemodynamics patterns in ATAA patients regardless of the aortic valve phenotype.

Intermittent Claudication due to Peripheral Arterial Disease (PAD-IC) induces ischemic pain in exercising muscles, and therefore impaired gait. In a pathological context, the analysis of the Vertical component of Ground Reaction Force (VGRF) is frequently used to describe gait pattern. This paper aims to define gait profiles according to the relative difference between peaks of VGRF; a Rearfoot and a Forefoot profile revealing a more loading or push-off strategy. We evaluated 70 participants (24 with unilateral disease (Unilat-IC), 22 with bilateral disease (Bilat-IC) and 24 Controls) during a walk test on an instrumented treadmill. Results indicate that Unilat-IC patients present a Rearfoot-profile in both legs during the pain-free gait period, likely to stabilize their gait. With the onset and increase of pain, the asymptomatic leg changes for a Forefoot-profile. This asymmetrical pattern suggests that a compensatory mechanism occurred to unload the symptomatic (painful) leg, possibly creating an imbalance. In Bilat-IC and Controls subjects, a Forefoot-profile is found, with a symmetrical pattern. However, there is a trend for lower propulsive capacity in case of Bilat-IC due to ischemic pain, but patients did not have the ability to compensate as in Unilat-IC. Therefore, Bilat-IC should not be considered as a "double" Unilat-IC. This study highlights the existence of gait profiles based on VGRF in PAD-IC patients. These profiles are dependent on the type of disease. Analysis of these gait profiles can 1) provide a simple way to identify gait alterations and 2) participate in improving physical rehabilitation strategies in PAD-IC patients.

International audience; Aim: The objective of this review was to evaluate the role of diabetes as a risk factor for herpes zoster (HZ) and to discuss implications of prevention by vaccination with available HZ vaccines.Methods: We reviewed studies that investigated the incidence rates of HZ in patients with diabetes. Papers in English or French published between January 2000 and December 2018 have been selected from PubMed and Google Scholarship by using appropriate key words.Results: The risk of HZ was significantly higher in patients with diabetes as compared to controls in 11 studies out of 16, although the magnitude of risk associated to diabetes varied across studies from 1.06 to 2.38 (p < 0.05). The incidence of HZ in patients with diabetes increased with age and was higher in women than in men. The incidence of the most common complication of HZ, i.e. post-herpetic neuralgia was also higher in patients with diabetes.Conclusions: The presence of HZ adds supplementary complications to the pre-existing comorbidity in patients with diabetes. Investigating the impact of preventive measure by HZ vaccination is therefore of paramount importance in patients with diabetes.

International audience; Background and purpose: Little is known about the long-term association between transient ischaemic attack (TIA) and stroke. Therefore, the goal of this study was to analyze the long-term risk of stroke and associated predictors in a large cohort of TIA patients followed in general practices in Germany. Methods: This study included patients with an initial TIA diagnosis and subsequently followed up in one of 1262 general practices in Germany between January 2007 and December 2016 (N = 19 824 patients). The primary outcome of the study was the risk of ischaemic stroke within 10 years of the initial diagnosis of TIA. The secondary outcome was the identification of demographic, clinical and pharmaceutical variables significantly associated with stroke in TIA patients. Results: Within 10 years of the initial TIA diagnosis, 18.3% of individuals were diagnosed with stroke. Age was positively associated with stroke, with hazard ratios ranging from 1.88 in patients aged 51–60 years to 4.00 in those aged >80 years (reference group: patients aged ≤50 years). Furthermore, male sex, hypertension, diabetes mellitus, atrial fibrillation and ischaemic heart diseases had an additional impact on the risk of stroke. Finally, new oral anticoagulants, heparins, diuretics, angiotensin II receptor blockers and platelet aggregation inhibitors were identified as protective factors. Conclusions: In a cohort of almost 20 000 TIA patients, 18.3% were diagnosed with stroke within 10 years after the TIA index event. Several demographic, clinical and pharmaceutical variables significantly predicted the long-term risk of stroke in TIA patients.

The paper by Ferdowsi et al , reported a 23-item composite damage index to quantify organ damage in systemic sclerosis (SSc).1 In this index, sicca symptoms (item 3) play an important role (weight score=3). Actually, sicca symptoms are frequently reported by patients with SSc (7.5%–68%) and could be due to a fibrosis process of the salivary glands (SGs).2–4 In recent years, ultrasonography (US) of the parotid and submandibular glands has been widely used for identifying SG modifications in patients with primary Sjogren’s syndrome (pSS). In order to assess modifications in the SG echostructure in patients with SSc and compare them with those of patients with pSS or controls with sicca symptoms, we prospectively enrolled patients with SSc fulfilling the American College of Rheumatology/European League against Rheumatism (ACR/EULAR) 2013 classification criteria, patients with pSS according …

International audience; Mineralogical analyses of clinical samples have been proven useful to identify a causal relationship between exposure to airborne particles and pulmonary diseases. However, this type of analysis only considers the micron-sized fraction of the particles, neglecting the specific impact of submicron/nano-sized particles which have been otherwise shown to be reactive and able to induce biological effects. To fill this gap, we previously developed an innovative protocol to isolate micron-sized particles from submicron/nano-sized particles contained in 100 bronchoalveolar lavage (BAL) and bronchial washing (BW) samples from patients who suffered from interstitial lung diseases (ILDs) (NanoPI, ClinicalTrials.gov Identifier: NCT02549248). We then determined qualitatively and quantitatively the metal load in each of these fractions. The aim of the present paper is to investigate correlations between these mineralogical analyses and clinical data. The mean concentration of submicron silica particles was found to be significantly higher in the BAL and BW samples from patients suffering from sarcoidosis than those from patients suffering from other ILDs (501 vs. 246 ng mL−1 for BAL and 564 vs. 292 ng mL−1 for BW, respectively). This finding suggests a potential role of submicron silica particles in the etiology of sarcoidosis and highlights the usefulness of comprehensive mineralogical analyses to obtain new insights into the role of inhaled biopersistent particles in lung diseases.

International audience; This is a review paper, essentially a commentary with summary of literature that actualizes the problem of epilepsy in patients with multiple sclerosis. There is a bidirectional relation between multiple sclerosis and epilepsy. A possible associate pathophysiological pathway is considered. In multiple sclerosis, a combination of gray matter involvement and inflammation could influence epileptogenesis. Patients with multiple sclerosis have individual profiles and an inter-individual variability of epileptogenicity. No treatment guidelines have been specified for these patients. We postulate that an epileptic manifestation means a relapse or an aggravation of the inflammatory process. In this condition, over time, this symptom could integrate into the Expanded Disability Status Scale. Epileptogenesis is an active process and an interesting question is if disease-modifying therapy in multiple sclerosis can prevent, or mitigate, epilepsy. In light of the latest knowledge of the inflammatory process in epilepsy, the possibility of preventing epileptogenesis with actual treatment of MS is emphasized. We would argue that it is a strong argument for starting treatment quicker for both diseases. Over the last few years, the concepts of epilepsy have completely changed. The model of epilepsy in multiple sclerosis can currently be regarded as a network disease and this new concept can have a highly significant clinical impact.

Objective: To determine the impact of endobronchial coils on health-related quality-of-life (HRQoL). This paper utilizes trial data to identify the predictors of HRQoL in patients with severe emphysema, and subsequently estimates the impact of a new treatment on HRQoL (measured by utilities). These utility estimates are used to generate indicative long-term QALY estimates for a range of clinically plausible scenarios as a precursor to cost-effectiveness analyses.Methods: Patient level HRQoL data from RENEW and the National Emphysema Treatment Trial (NETT) were combined and mapped to generic EuroQol 5-dimension health utility questionnaire (EQ-5D) values using a published algorithm. Multilevel statistical models were developed using treatment, time, response, and baseline characteristics (EQ-5D, age, gender, FEV1, lung RV) to predict EQ-5D over time. Lifetime QALY estimates were generated using published survival data from NETT (assuming no impact of treatment on mortality) and four clinically plausible response profiles. Each response profile was combined with assumptions around treatment impact (constant or time varying).Results: After controlling for baseline characteristics, both treatment and response had a statistically significant impact (p Conclusions: Coils and SoC resulted in statistically significant improvements in HRQoL compared to SoC alone in patients with severe emphysema.

International audience; Many medical devices are created and rejected because of their lack of adequacy to the clinician needs and situation. The implication of a clinician in the design process may prevents the creation of solution than seems pushed to the users but in contrary create a solution calibrated to their usages. In this paper a UCD cycle was applied to the development of an information system for patients’ motor evaluation using the motion analysis sensor Kinect. The system should support the therapist in its evaluations and provide a way to improve the evaluation. The context exploration, requirements definition, so-lution proposition and adequacy evaluation was applied. The model allowed to emphasis the aspects that are important and were rightfully answered but also on the revision needs for a second cycle to generate an acceptable device.

International audience; Destination memory refers to the ability to remember to whom a piece of information was previously transmitted. Our paper assessed this ability in schizophrenia. Twenty-five patients with schizophrenia and 25 control participants told proverbs (e.g., "send a thief to catch a thief") to pictures of celebrities (e.g., Elvis Presley). Afterward, participants had to indicate to which celebrity they had previously said the proverbs. Participants also completed a binding task in which they were required to associate letters with their corresponding context (i.e., location). Analysis revealed worse destination memory and binding in patients with schizophrenia than in controls. In both populations, destination memory was significantly correlated with performances on the binding task. Our findings suggest difficulty in the ability to attribute information to its appropriate destination in schizophrenia. This difficulty may be related to compromise in binding separate cues together to form a coherent representation of an event in memory.

A central issue in olfaction concerns the characterization of loss of olfactory function: partial (hyposmia) or total (anosmia). This paper reports the application in a clinical setting of the European Test of Olfactory Capabilities (ETOC), combining odor detection and identification. The study included three phases. In phase 1, anosmics, hyposmics and controls were tested with the 16-items version of the ETOC. In phase 2, a short version of the ETOC was developed: patients with and controls without olfactory impairment were tested on a 6-items ETOC. In phase 3, to predict olfactory impairments in new individuals, the 16-items ETOC was administered on samples of young and older adults, and the 6-items version was applied in samples of young, elderly participants and Alzheimer patients. In phase 1, linear discriminant analysis (LDA) of ETOC scores classified patients and controls with 87.5 % accuracy. In phase 2, LDA provided 84 % correct classification. Results of phase 3 revealed: (1) 16-items ETOC: whereas in young adults, 10 % were classified as hyposmic and 90 % as normosmic, in elderly, 1 % were classified as anosmic, 39 % hyposmic and 60 % normosmic; (2) 6-items ETOC: 15 % of the young adults were classified as having olfactory impairment, compared to 28 % in the older group and 83 % in Alzheimer patients. In conclusion, the ETOC enables characterizing the prevalence of olfactory impairment in young subjects and in normal and pathological aging. Whereas the 16-items ETOC is more discriminant, the short ETOC may provide a fast (5-10 min) tool to assess olfaction in clinical settings.

There are hypotheses that traumatic brain injury (TBI) and schizophrenia might exhibit similar patterns of cognitive disorders in attention, executive function and memory. Yet, empirical studies comparing directly the two populations are extremely rare. The aim of this exploratory study was to compare performance of patients with TBI and schizophrenia in a task of selective attention. A group of TBI patients ( n = 18), a group of patients with schizophrenia ( n = 21), and a control group with no history of neurologic or psychiatric illness ( n = 31) participated in this study. A paced paper-and-pencil cancellation task was completed by each participant, allowing for discrimination between intact and impaired attention subcomponents. Compared to the controls, both patient groups had (a) slower processing speed, (b) reduced target processing efficiency, (c) instant attentional overload, and (d) difficulties in discriminating targets from distractors. However, these deficits were of different degrees between the groups. Furthermore, (e) a marked selective impairment of processing of distractors was observed in patients with schizophrenia only, as well as (f) a failure to regulate attentional resources over time. Finally, (g) none of the groups showed any shifts in response strategies. These results suggest that there are large similarities in disturbances in selective attention between these two pathologies. Yet, whenever similar, these disturbances are of different degrees. Furthermore, there are some qualitative differences between the two pathologies.

We read with great interest the paper by Yotti et al. [(1)][1] regarding vascular load and transcatheter aortic valve replacement (TAVR). This study underlines the interaction between valvular and vascular functions in patients with aortic stenosis (AS). The authors highlighted the increase of

International audience; Cardiac resynchronization therapy (CRT) is a recommended treatment in patients with electrical dyssynchrony such as left bundle branch block (LBBB). The determination of the optimal leads position, and the quantification of the changes in electrical activation are two current major challenges. In this paper, we investigate these aspects through electroanatomical data from a controlled experimental protocol, which studied pigs with no structural disease under LBBB and CRT conditions. We propose to use a quasi-conformal mapping technique to standardize electroanatomical maps of endo- and epi-cardial walls of both ventricles to a common reference geometry, in which simple quantitative indices can be computed. Then, we investigate the relation between leads and simple surrogates of the recovery of the electrical activation based either on total activation times or on the spatial distribution of the patterns. Our methodology allows a better understanding of the complex electrical activation patterns in LBBB and CRT, and confirms hypotheses about the optimal leads position from previous studies.

International audience; Besides the crucial role of genetic susceptibility in the development of early-onset obesity, it has been shown that feeding behavior could contribute to increased body weight. A significant association between obesity/overweight and ADHD has been reported, suggesting that these two conditions, despite their heterogeneity, might share common molecular pathways. Although the co-occurrence of obesity and ADHD is increasingly supported by empirical evidence, the complex pathogenetic link between these two conditions is still unclear. Here, we focus on the relationship between MC4R gene mutations and ADHD in children with early-onset obesity. Mutations in the gene MC4R lead to the most common form of monogenic obesity. We hypothesize that dysregulated eating behavior in a subset of patients with MC4R mutation might be due to comorbid ADHD symptoms, underpinned by abnormal reward mechanisms. Therefore, we speculate that it is possible to prevent obesity in a subset of patients with MC4R mutation, even if these patients are genetically programmed to "be fat", via an appropriate treatment of ADHD symptoms. We hope that our paper will stimulate further studies testing if the early screening for ADHD symptoms and their appropriate treatment may be an effective way to prevent obesity in a subset of children with MC4R mutation.

People with severe motor disabilities present reduction or absence of motor control. However, in different stages of these conditions, some people can perform voluntary movements of low amplitude. This paper presents the development of an Human Computer Interface - HCI - for controlling an augmented and alternative communication system. The device consists of an accelerometer to capture voluntary movements performed by users who have restricted movement such as patients with amyotrophic lateral sclerosis. The sensitivity of the device is calibrated according to the amplitude of the dynamic action executed by the user, allowing the placement of the sensor in different body regions, for which the use has some level of motor control. The system was tested successfully in healthy subjects suggesting that the accelerometer can be used in patients with motor disabilities.

International audience; Intravenous (IV) catheterization is the most important phase in medical practices of daily life. It is hard to localize veins in patients who have deep veins, minor age or dark skin; hence multiple attempts become indispensable for proper catheterization in such cases. Near Infrared (NIR) Imaging allow to visualize the veins underneath the skin of persons having non-visibility of veins problem. This paper reports the pre-selection of illuminants that ensure best veins/tissues contrast for patients having different skin tone. The sample subjects have been divided in four different classes based on the Luminance value of their skin tone in order to extract the best illuminant wavelengths range for each class. A multispectral approach has been used which provides the flexibility of wavelength range from visible to NIR (380 to 1040nm). The veins/tissue reflectance contrast obtained helps in determining the best wavelengths range where the contrast is maximum for each of the four classes. Using these results, we are planning to build a prototype system which can automatically select the illuminants based on different physiological characteristics of a subject.

A (home) care plan defines the health cares or supportive cares delivered by health care professionals in patients’ homes. Such a care plan is usually constructed through a complex process involving a comprehensive assessment of patient’s needs as well as its social and physical environment. Managing home care plans is challenging because care plans are inherently non-structured processes which require complex interdisciplinary cooperation. This paper addresses the problems underlying the design and management of home care plans. First, we present a DSL (Domain Specific Language) based approach tailored to express home care plans using high level and user-oriented abstractions. Then, we describe and discuss preliminary results regarding formalization of the proposed DSL abstractions using timed automata in order to provide basic services to support analysis, verification, enactment and management of home care plans.

International audience; While the physical disability aspect of multiple sclerosis (MS) is of great importance, quality of life (QoL) measurements are being considered increasingly important with regard to evaluating disease progression, treatment, and the management of care provided to MS patients. Despite the acknowledged need to consider QoL issues, QoL assessment remains underutilized in clinical practice. These issues should be explored and understood to promote the use of measuring QoL in MS clinical practice. We explore the difficulties for clinicians: choosing and determining the most appropriate QoL measure and how to best integrate QoL measurements into clinical practice. This paper discusses several avenues to provide to clinicians arguments of the clinical relevance and accuracy of QoL instruments and ultimately to enhance the use of QoL measures in clinical practice for MS patients.

International audience; Purpose : To develop a reproducible definition for each mediastinal lymph node station based on the new TNM classification for lung cancer. Methods and Materials : This paper proposes an atlas using the new international lymph node map used in the seventh edition of the TNM classification for lung cancer. Four radiation oncologists and 1 diagnostic radiologist were involved in the project to put forward a reproducible radiologic description for the lung lymph node stations.Results : The International Association for the Study of Lung Cancer lymph node definitions for stations 1 to 11 have been described and illustrated on axial computed tomographic scan images using a certified radiotherapy planning system. Conclusions : This atlas will assist both diagnostic radiologists and radiation oncologists in accurately defining the lymph node stations on computed tomographic scan in patients diagnosed with lung cancer.

International audience; Treating cancer patients with metastatic disease remains an ultimate challenge in clinical oncology. Because invasive cancer precludes or limits the use of surgery, metastatic setting is often associated with (poor) survival, rather than sustained remission, in patients with common cancers like lung, digestive or breast carcinomas. Mathematical modeling may help us better identify non detectable metastatic status to in turn optimize treatment for patients with metastatic disease. In this paper we present a family of models for the metastatic growth. They are based on four principles : to be as simple as possible, involving the least possible number of parameters, the main informations are obtained from the primary tumor and being able to recover the variety of phenomena observed by the clinicians. Several simulations of therapeutic strategies are presented illustrating possible applications of modeling to the clinic.

International audience; Sjögren's syndrome is an autoimmune disease characterized by an autoimmune exocrinopathy involving mainly salivary and lacrimal glands. The histopathological hallmark is periductal lymphocytic infiltration of the exocrine glands, resulting in loss of their secretory function. Several systemic manifestations may be found in patients with Sjögren's syndrome including neurological disorders. Neurological involvement ranges from 0 to 70% among various series and may present with central nervous system and/or peripheral nervous system involvement. This paper endeavors to review the main clinical neurological manifestations in Sjögren syndrome, the physiopathology, and their therapeutic response.

International audience; Movement disorders in patients with Parkinson's disease may require functional surgery, when medical therapy isn't effective. In Deep Brain Stimulation (DBS), electrodes are implanted within the brain to stimulate deep structures such as SubThalamic Nucleus (STN). This paper describes successive steps for constructing digital atlases gathering patient's location of electrode contacts and clinical scores. Three motor and three neuro- psychological scores were integrated in the study. Correlations between active contacts localization and clinical data were carried out using an adapted Hierarchical Ascendant Classification and have enabled the extraction of clusters aiming to suggest optimum sites for therapeutic STN DBS. The postero-superior region has been found to be effective for motor score improvement whereas the antero-inferior region revealed noticeable neuro- psychological scores deterioration. Comparison with existing results has shown that such atlases are very promising for understanding phenomena better.

Surgery is currently the best approach for treating either primary or metastatic hepatic malignancies. Because only 20% of hepatic cancers are operable in patients, several types of regional therapy (RT) are emerging as alternate treatment modalities. However, RTs can have their own limitations at controlling tumor growth or may lack the ability to detect such metastases. Additional strategies can be implemented to enhance their efficacy. An animal model of hepatic metastases coupled with a gastroduodenal artery (GDA) cannulation technique may provide a site to apply such therapies. In our study, splenic injections were performed with CC531 adenocarcinoma cells, which generated metastatic hepatic tumors in WAG/RijHsd rats. Cannulation of GDA was achieved via a polyethylene catheter. Infusion of generation 3 polyamidoamine 4-amino-1,8-naphthalimide dendrimer containing 8 europium ions (Eu-G3P4A18N) via the GDA resulted in luminescence of the hepatic metastatic nodules. Imaging of the metastatic hepatic nodules was obtained with the help of a cooled charge coupled device (CCD) camera.Hepatic malignancies represent a major therapeutic challenge, despite the available surgical and oncologic treatment modalities. In this paper, an animal model of hepatic adenocarcinoma is used in demonstrating successful targeting of spleen metastases with generation 3 polyamidoamine 4-amino-1,8-naphthalimide dendrimer containing 8 europium ions (Eu-G3P4A18N) for luminescence imaging.

International audience; A Random Walk (RW) algorithm was designed to quantify the level of diffuse heterogeneous perfusion in brain SPECT images in patients suffering from systemic brain disease or from drug-induced therapy. The goal of the present paper is to understand the behavior of the RW method on different kinds of images (extrinsic parameters) and also to understand how to choose the right parameters of the RW (intrinsic parameters) depending on the image characteristics (i.e. SPECT images). "Extrinsic parameters" are related to the image characteristics (level/size of defect and diffuse heterogeneity) and "intrinsic" parameters are related to the parameters of the method (number (N(rw)) and length of walk (L(rw)), temperature (T) and slowing parameter (S)). Two successive studies were conducted to test the influence of these parameters on the RW result. In the first study, calibrated checkerboard images are used to test the influence of "extrinsic parameters" (i.e. image characteristics) on the RW result (R-value). The R-value was tested as a function of (i) the size of black & white (B&W) squares simulating the size of a cortical defect, (ii) the intensity level gaps between the B&W squares simulating the intensity of the cortical defect and (iii) intensity (=variance) of noise, simulating the diffuse heterogeneity. The second study was constructed with simulated representative brain SPECT images, to test the "intrinsic" parameters. The R-value was tested regarding the influence of four parameters: S, T, N(rw) and L(rw). The third study is constructed so as to see if the classification by diffuse heterogeneity of real brain SPECT images is the same if it's made by senior clinicians or by RW algorithm. RESULTS: Study 1: the RW was strongly influenced by all the characteristics of the images. Moreover, these characteristics interact with each other. The RW is influenced most by diffuse heterogeneity, then by intensity and finally by the size of a defect. Study 2: N(rw) and L(rw) values of 1000 give an optimal reproducibility of the measurement (mean standard deviation

To evaluate the differences in meibomian fatty acid composition in healthy subjects and in patients suffering from meibomian gland dysfunction or aqueous-deficient dry eye.We collected meibomian oil using a sterile Schirmer paper in healthy individuals (n = 20), dry eye patients (aqueous-deficient) (n = 32) and meibomian gland dysfunction (MGD) patients (n = 25) after gentle massage of the lid margin. Meibomian fatty acids were directly transmethylated and analysed using gas chromatography (GC) and GC mass spectrometry.Meibomian fatty acids were similar in healthy individuals and in dry eye patients but were different in MGD patients, who showed significantly higher levels of branched-chain fatty acids (29.8% vs 20.2%) (p0.0001) and lower levels of saturated fatty acids (9.3 vs 24.6%) (p0.0001), in particular lower levels of palmitic (C16) and stearic (C18) acids.The increase in branched-chain fatty acids may reflect greater quantities of wax and cholesterol esters and triglycerides in meibomian gland excreta. Since wax and cholesterol esters are the main lipids of meibum, these differences may have physical consequences for tear-film lipid-layer fluidity and stability. Meibomian fatty acid composition and particularly the increase in branched chains could be a marker for meibomian gland dysfunction.

Focal cortical dysplasia (FCD) is the most frequent malformation of cortical development in patients with medically intractable epilepsy. On MRI, FCD lesions are not easily differentiable from the normal cortex and defining their spatial extent is challenging. In this paper, we introduce a method to segment FCD lesions on T1-weighted MRI. It relies on two successive three-dimensional deformable models, whose evolutions are based on the level set framework. The first deformable model is driven by probability maps obtained from three MRI features: cortical thickness, relative intensity and gradient. These features correspond to the visual characteristics of FCD and allow discriminating lesions and normal tissues. In a second stage, the previous result is expanded towards the underlying and overlying cortical boundaries, throughout the whole cortical section. The method was quantitatively evaluated by comparison with manually traced labels in 18 patients with FCD. The automated segmentations achieved a strong agreement with the manuals labels, demonstrating the applicability of the method to assist the delineation of FCD lesions on MRI. This new approach may become a useful tool for the presurgical evaluation of patients with intractable epilepsy related to cortical dysplasia.