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Although antimony (Sb) contamination has been observed to increase in urban areas, knowledge gaps remain concerning the contributions of the different sources to the Sb urban biogeochemical cycle, including non-exhaust road traffic emissions, urban materials leaching/erosion and waste incineration. Additionally, details are lacking about Sb chemical forms involved in urban soils, sediments and water bodies. Here, trace element contamination was studied with a focus on Sb geochemistry in three highway stormwater pond systems, standing as a model of surface environments receiving road-water runoff. In all systems differentiated on the basis of lead isotopic signatures, Sb shows the higher enrichment factor with respect to the geochemical background, up to 130, compared to other traffic-related inorganic contaminants (Co, Cr, Ni, Cu, Zn, Cd, Pb). Measurements of Sb isotopic composition (δ

The present aim of the GERODIAB study was to examine the evolution of geriatric syndromes and their relationship with survival in 987 older type 2 diabetic patients over 5 years. Institutional living, impaired activity and difficulties in instrumental daily activity, cognitive disorders, orthostatic hypotension and hypoglycaemia strongly increased during the follow-up. Institutional living, impaired activities, cognitive disorders and hypoglycaemia were strongly associated with reduced survival but not falls. Our results confirm the prognostic interest of using yearly geriatric markers in older diabetic patient management. Although one in three patients with diabetes in Western countries is over 70 years-old, geriatric syndromes and their relationship with survival remain seldom studied. The present aim of the GERODIAB study was to examine the evolution of geriatric disorders and their relationship with survival in older type 2 patients with diabetes with initial sufficient autonomy. We performed a prospective, observational study over 5 years in patients with diabetes aged 70 years or above. A total of 987 consecutive type 2 patients with diabetes (mean age 77 years, range 70–94 years, 65.2% were 75 years and above, 52.1% women) were included from 56 French diabetic centres. Individual characteristics, diabetes parameters and geriatric parameters (autonomy, nutrition, cognitive alteration, depression, orthostatic hypotension, falls) were annually recorded. Survival was analysed using the Kaplan–Meier method and proportional hazards regression models. Institutional living, impaired activity and difficulties in instrumental daily activity, cognitive disorders, malnutrition, depression, orthostatic hypotension and hypoglycaemia strongly increased during the follow-up. Institutional living, impaired activity and difficulties in instrumental daily activity, cognitive disorders and hypoglycaemia were strongly associated with reduced survival, but not falls. In hazard ratio models, living in an institution (HR = 2.39; CI = 1.77–3.24; p

In this chapter, CFD computations for a steady turn manoeuvre are compared to experiments performed in the QinetiQ rotating arm basin. The validation data provided to the group consists of forces and moments measured on the appended hull during the turn. As for the other chapters, a huge amount of data is collected given the number of institutions, computational codes and turbulence models or grid methodologies. The comparison between the CFD and the experiments is then the largest collaborative validation database known to date and provides the state of the art for CFD methodologies on submarines in complex manoeuvres. The validation exercise concludes that the dominant forces and moments Y , K and M are predicted consistently with the experiments but that more accurate information on the uncertainties in the measurements is needed to strengthen the conclusions. It is also concluded that the discrepancies observed in the comparisons are originating from the presence (or absence) of stall on the aft control surfaces. These differences in the local flows around the control surfaces are mostly attributed to the turbulence models and, as concluded in the previous chapters, the complete knowledge of the implementation of the models is found necessary to understand the results. Further validation studies on this turning manoeuvre would require aft control surfaces dedicated measurements of forces and wall shear stress to fully validate the computational methodologies. The analysis of the flow variables in the vortices confirms previous conclusions in the variability of the results due to the differences in the local grid refinements, and experimental data is necessary to achieve validation of the numerical prediction of these flow features.

Helicopters landing operations on ship are challenging for the pilots due to the aerodynamic interaction of the helicopter wake with the flow perturbations caused by the superstructures of the ship [1]. The flow on the helideck is highly turbulent and pilots must go through strong airwake for landing operations. The addition of helidecks movements, rotor wake, visibility and pilot experience to this unsteady flow conditions is often characterized by an increased workload for the pilots [2]. In addition to these constraints during the landing procedure, there is the difficulty of establishing - and even more so of predetermining - the operational limits. To date, only the Ship Helicopter Operating Limits (SHOL) allows to answer this question. It defines the boundaries of safe operation for a particular ship-helicopter combination in terms of maximum allowable wind speed and direction relative to the ship. The development of SHOL requires to perform numerous trials at-sea that are extremely expensive, time-consuming and associated with high risk. To alleviate these constraints, researches have shown promising results with active flow control applied on the helideck [3]. This paper presents an experimental framework to identify the effect of active flow control on the helideck with and without an hovering helicopter rotor. To this aim, two main steps are proposed: identification of flow characteristics according to the control strategies implemented followed by the strong coupling between ship airwake with and without control and the rotor wake while helicopter is in an hover position above the flight deck. To study the flow topology, static pressure and Stereo PIV (SPIV) are used in the test campaign presented in this paper. The experimental setup consists of a simplified but representative frigate geometry and a 4-bladed rotor model. The ship model is a 1:50 scaled-model. The active flow control is realized by continuous blowing through eight slots of 2 mm width located along the sides of the hangar. The blowing jets exit tangentially to the geometry side toward the flight deck platform or with an angle of 30 deg toward the center flight deck platform. The incoming mass flow comes from underneath the wind tunnel and separates into four branches that independently feed four pair of slots. This power supply allows independent adjustment by pair of the eight slots. The experiments were conducted in the L2 low-speed wind tunnel at ONERA Lille. The test section of the wind tunnel is closed and rectangular (6 m width by 2.4 m height by 13 m long). A turntable setup of 5.96 m in diameter allows the azimuthal adjustment. In these experiments, the drift angle varies from -40 to 40 deg by 10 degrees steps. The upstream velocity U0 is measured by pitot probes located at the test section inlet and is set to 15 m/s, equivalent to about 30 kn. Here three velocity ratios (Uj/U0 equal to 2, 3 and 4) are used in the wind tunnel experiments, where Uj is the mean jet velocity at the slot exit. The helideck platform is equipped with 88 static pressure taps, 32 additional static pressure taps are on the superstructure and the hangar door. A specific setup is used for the SPIV measurements. The laser source and the mirror are directly integrated into the model and an optical glass replaces a part of the hangar door. Two configurations are used, one parallel to the platform with the plane at mid-height of the hangar and a perpendicular one with the plane oriented along the deck centreline. The two cameras used for the PIV measurements are located either on the wind tunnel roof or on the floor for, respectively, the parallel or perpendicular configuration. By such embedded setup, the recording of the flowfield at different drift angles is made easier. First results show a reduction of the recirculation area with continuous steady blowing around the hangar, observed at different drift angles. The jets direction towards the center of the deck looks to be more efficient in terms of flows modification and requires a lower velocity ratio.

Type 1 diabetes mellitus (T1DM) is associated with a high risk of cardiovascular (CV) complications, even after controlling for traditional CV risk factors. Therefore, determinants of the residual increased CV morbidity and mortality remain to be discovered. This prospective cohort of people living with T1DM in France (SFDT1) will include adults and children aged over six years living with T1DM, recruited throughout metropolitan France and overseas French departments and territories. The primary objective is to better understand the parameters associated with CV complications in T1DM. Clinical data and biobank samples will be collected during routine visits every three years. Data from connected tools, including continuous glucose monitoring, will be available during the 10-year active follow-up. Patient-reported outcomes, psychological and socioeconomic information will also be collected either at visits or through web questionnaires accessible via the internet. Additionally, access to the national health data system (Health Data Hub) will provide information on healthcare and a passive 20-year medico-administrative follow-up. Using Health Data Hub, SFDT1 participants will be compared to non-diabetic individuals matched on age, gender, and residency area. The cohort is sponsored by the French-speaking Foundation for Diabetes Research (FFRD) and aims to include 15,000 participants.

Objective Male sex is one of the determinants of severe coronavirus diseas-e-2019 (COVID-19). We aimed to characterize sex differences in severe outcomes in adults with diabetes hospitalized for COVID-19. Methods We performed a sex-stratified analysis of clinical and biological features and outcomes (i.e. invasive mechanical ventilation (IMV), death, intensive care unit (ICU) admission and home discharge at day 7 (D7) or day 28 (D28)) in 2380 patients with diabetes hospitalized for COVID-19 and included in the nationwide CORONADO observational study (NCT04324736). Results The study population was predominantly male (63.5%). After multiple adjustments, female sex was negatively associated with the primary outcome (IMV and/or death, OR: 0.66 (0.49–0.88)), death (OR: 0.49 (0.30–0.79)) and ICU admission (OR: 0.57 (0.43–0.77)) at D7 but only with ICU admission (OR: 0.58 (0.43–0.77)) at D28. Older age and a history of microvascular complications were predictors of death at D28 in both sexes, while chronic obstructive pulmonary disease (COPD) was predictive of death in women only. At admission, C-reactive protein (CRP), aspartate amino transferase (AST) and estimated glomerular filtration rate (eGFR), according to the CKD-EPI formula predicted death in both sexes. Lymphocytopenia was an independent predictor of death in women only, while thrombocytopenia and elevated plasma glucose concentration were predictors of death in men only. Conclusions In patients with diabetes admitted for COVID-19, female sex was associated with lower incidence of early severe outcomes, but did not influence the overall in-hospital mortality, suggesting that diabetes mitigates the female protection from COVID-19 severity. Sex-associated biological determinants may be useful to optimize COVID-19 prevention and management in women and men.

Aims/hypothesis This is an update of the results from the previous report of the CORONADO (Coronavirus SARS-CoV-2 and Diabetes Outcomes) study, which aims to describe the outcomes and prognostic factors in patients with diabetes hospitalised for coronavirus disease-2019 (COVID-19). Methods The CORONADO initiative is a French nationwide multicentre study of patients with diabetes hospitalised for COVID-19 with a 28-day follow-up. The patients were screened after hospital admission from 10 March to 10 April 2020. We mainly focused on hospital discharge and death within 28 days. Results We included 2796 participants: 63.7% men, mean age 69.7 ± 13.2 years, median BMI (25th–75th percentile) 28.4 (25.0–32.4) kg/m2. Microvascular and macrovascular diabetic complications were found in 44.2% and 38.6% of participants, respectively. Within 28 days, 1404 (50.2%; 95% CI 48.3%, 52.1%) were discharged from hospital with a median duration of hospital stay of 9 (5–14) days, while 577 participants died (20.6%; 95% CI 19.2%, 22.2%). In multivariable models, younger age, routine metformin therapy and longer symptom duration on admission were positively associated with discharge. History of microvascular complications, anticoagulant routine therapy, dyspnoea on admission, and higher aspartate aminotransferase, white cell count and C-reactive protein levels were associated with a reduced chance of discharge. Factors associated with death within 28 days mirrored those associated with discharge, and also included routine treatment by insulin and statin as deleterious factors. Conclusions/interpretation In patients with diabetes hospitalised for COVID-19, we established prognostic factors for hospital discharge and death that could help clinicians in this pandemic period. Trial registration Clinicaltrials.gov identifier: NCT04324736 Graphical abstract

Although one in three patients with diabetes in Western countries is over 70 years-old, geriatric syndromes and their relationship with survival remain seldom studied. The present aim of the GERODIAB study was to examine the evolution of geriatric disorders and their relationship with survival in older type 2 patients with diabetes with initial sufficient autonomy.We performed a prospective, observational study over 5 years in patients with diabetes aged 70 years or above. A total of 987 consecutive type 2 patients with diabetes (mean age 77 years, range 70-94 years, 65.2% were 75 years and above, 52.1% women) were included from 56 French diabetic centres. Individual characteristics, diabetes parameters and geriatric parameters (autonomy, nutrition, cognitive alteration, depression, orthostatic hypotension, falls) were annually recorded. Survival was analysed using the Kaplan-Meier method and proportional hazards regression models.Institutional living, impaired activity and difficulties in instrumental daily activity, cognitive disorders, malnutrition, depression, orthostatic hypotension and hypoglycaemia strongly increased during the follow-up. Institutional living, impaired activity and difficulties in instrumental daily activity, cognitive disorders and hypoglycaemia were strongly associated with reduced survival, but not falls. In hazard ratio models, living in an institution (HR = 2.39; CI = 1.77-3.24; p 0.0001) and impaired Activity of Daily Living scale score were the most significant and independent predictors of death (HR = 1.59; CI = 1.19-2.13; p = 0.0016), associated with HbA1c ≥ 70 mmol/mol (HR = 1.62; CI = 1.12-2.36; p = 0.011).Our findings show the considerable alteration of geriatric parameters and their relationship with decreased survival after a 5-year follow-up in type 2 patients with diabetes, independent of HbA1c and age. They, therefore, confirm the prognostic interest of using yearly geriatric markers in older diabetic patient management, especially the ADL, IADL and MMSE scales. Taking into account these prognostic parameters should contribute to target appropriate HbA1c goals.Registered at clinicaltrials.gov (21/01/2011): NCT01282060.

IntroductionThe offloading is crucial to heal neuropathic diabetic foot ulcer (DFU). Removable offloading are the most used devices. Orthèse diabète is a new customized removable knee-high offloading device immobilizing foot and ankle joints, with some specific and innovative features that may improve offloading. We aimed to evaluate the efficiency of this device in DFU healing.Research, design and methodsThe evaluation of Offloading using a new removable ORTHOsis in DIABetic foot study is a French multicenter (13 centers) randomized controlled trial with blinded end points evaluation. Adults with neuropathic DFU were randomly assigned to either Orthèse Diabète (experimental device), or any type of conventional (usually used in France) removable offloading devices (control group). The primary outcome was the 3-month proportion of patients with fully healed DFU.ResultsAmong 112 randomized patients (men 78%, age 62±10 years), the primary outcome occurred in 19 (33%) participants using conventional device vs 19 (35%) Orthèse Diabète users (p=0.79). Study groups were also comparable in terms of prespecified secondary end points including occurrence of new DFU (25% vs 27% in conventional and experimental groups), ipsilateral lower-limb amputation (4% vs 10%) or infectious complications (14% vs 13%) (p>0.05 for all). Adverse events were comparable between groups, including 4 deaths unrelated to study allocation (1 sudden death, 2 ventricular arrhythmias and 1 pancreatic cancer). Adverse events believed to be related to the device were higher in the Orthèse Diabète group than in the control group (15% vs 4%). Orthèse Diabète was less frequently worn than conventional devices (46% vs 66%, p=0.04).ConclusionsOrthèse Diabète, a new removable offloading orthosis immobilizing foot and ankle joints did not show superiority compared with conventional removable devices in neuropathic DFU healing and cannot be recommended to heal DFU.Trial registration numberNCT01956162.

El tratamiento de la diabetes del paciente anciano representa un reto de salud publica, y el medico general es el que se encuentra en el centro del sistema de salud para este paciente particular. Tiene que individualizar el tratamiento, pero teniendo en cuenta la dimension geriatrica del paciente y, en particular, el exito de su envejecimiento. Debe centrar la atencion en la deteccion de la fragilidad, la desnutricion, los trastornos cognitivos y la hipoglucemia. Todas estas complicaciones a menudo se pasan por alto o se subestiman, aunque tienen consecuencias graves sobre el pronostico del paciente.

Resume Pendant des decennies, le traitement du diabete de type 2 (DT2) etait simple. En cas d’insuffisance de la metformine, le choix etait limite aux sulfamides hypoglycemiants ou a l’insuline. La mise sur le marche de nouvelles classes therapeutiques et de nouvelles insulines permet aujourd’hui de mieux individualiser les prescriptions medicamenteuses a chaque malade. Ce progres est particulierement bienvenu dans les pays du Maghreb, et notamment au Maroc, ou l’epidemie de DT2 devient une priorite de sante publique. Malheureusement, les difficultes liees au mode de vie et les contingences economiques font que beaucoup des patients diabetiques sont encore mal equilibres.

Introduction Nous rapportons l’observation d’une patiente avec hyperparathyroidie primitive ancienne non traitee, admise aux urgences pour hypercalcemie majeure. Observation Une patiente de 72 ans presentant une hyperparathyroidie primitive depuis 8 ans etait admise aux urgences pour hypercalcemie majeure et asthenie au long cours. Le bilan biologique aux urgences notait : calcium serique > 7,5 mmol/L (2,2–2,5), albumine = 44,8 g/L, calcium ionise = 2,48 mmol/L (1,15–1,29), phosphates 1,01 mmol/L (0,81–1,45), PTH = 2805 ng/L (15–65), vitamine D (25OHD3) = 6 μg/L. L’echographie cervicale notait un volumineux adenome parathyroidien P3 gauche iso- et hypoechogene richement vascularise avec une portion kystique. La cytoponction montrait des atypies de signification indeterminee, voire suspectes de malignite. La PTH in situ etait significative, dosee a 2198 ng/L. Apres un traitement par hydratation et diphosphonates, la patiente etait operee, permettant de retirer un nodule parathyroidien gauche unique benin de 3 cm, restaurant rapidement une calcemie normale, sans hungry bone syndrome. Le scanner thoraco-abdomino-pelvien notait des lesions osteolytiques iliaques, dont les 2 plus notables etaient mesurees a 2,3 cm et 2,8 cm. Ces lesions correspondaient a des tumeurs brunes qui n’ont pas ete biopsiees compte tenu du contexte clinique tres evocateur. Discussion L’hyperparathyroidie primitive entraine une hypercalcemie chronique qui peut etre longtemps bien toleree, malgre un calcium tres eleve. Les tumeurs brunes sont des lesions benignes correspondant a des osteites fibro-kystiques, resultant d’une anomalie du metabolisme osseux dans le cadre d’une hyperparathyroidie primaire, secondaire ou tertiaire. Elles surviendraient dans 2 a 5 % des hyperparathyroidies primitives et 1,5 a 1,7 % des hyperparathyroidie secondaire.

Introduction Nous decrivons le cas d’une cause rare d’insuffisance surrenalienne chez un homme de 31 ans. Observation Un patient est adresse pour prescription de testosterone apres orchidectomie bilaterale (retrait de masses testiculaires suspectes de leydigomes). L’anatomopathologie conclut a une hyperplasie benigne des cellules de Leydig. Le patient presente outre l’hypogonadisme, une fatigue importante. Le bilan hormonal note l’hypogonadisme peripherique et une insuffisance surrenalienne : cortisol = 44 μg/L, ACTH > 1250 pg/ml, Ac anti-21hydroxylase A p.Glu314Lys et c.1393C > T p.Arg465Trp), chacune transmise par l’un des parents. Discussion Le patient presente un syndrome adrenogenital, situation exceptionnelle, en rapport avec 2 mutations du gene CYP11A1. Goursaud et al. [1] ont rapporte que les consequences fonctionnelles de ces mutations peuvent expliquer un phenotype incomplet : insuffisance surrenalienne tardive et/ou troubles du developpement des organes genitaux chez les sujets 46,XY. Si la mutation Arg465Trp abolit toute activite de l’enzyme, les effets de l’autre mutation n’entrainent qu’une perte seulement partielle, par degradation de la proteine. La sœur du patient doit poursuivre un traitement oestro-progestatif pour preserver sa fonction ovarienne.

The burden of hypoglycaemia is important, particularly in elderly type 2 diabetes (T2D) patients. Unfortunately, however, few studies are available concerning this population. GERODIAB is a prospective, multicentre, observational study that aims to describe the 5-year morbidity and mortality of 987 T2D patients aged 70 years and older. After analyzing the frequency of and factors associated with hypoglycaemia in the 6 months prior to study inclusion, it was found that hypoglycaemia was associated with retinopathy, lower levels of LDL cholesterol and altered mini-Geriatric Depression Scale (GDS) scores.

Resume Le diabete de la personne âgee se complique frequemment de troubles cognitifs, eventuellement severes. Le but de cet article est de revoir la litterature recente etablissant ce constat, et d’analyser les differents mecanismes physiopathologiques qui conduisent a cette dysfonction cognitive. Dans ce cadre, le role deletere potentiel de l’hyperglycemie et de l’hypoglycemie dans la genese des troubles de la cognition de la personne âgee, sont discutes.

Resume SUDOSCAN et EZSCAN utilisent la meme technique de mesure de la conductance electrochimique de la sueur (CES). Cette methode est simple, non invasive, totalement indolore, et dure au total moins de 3 minutes. Elle est, par consequent, tres bien acceptee par les malades et peut facilement etre repetee. Les anomalies de la CES temoignent d’une atteinte de l’innervation sympathique des glandes sudorales, qui est precoce au cours du diabete et qui reflete l’atteinte vegetative des autres organes et, en particulier, du coeur. Les resultats bruts des CES obtenus avec SUDOSCAN au niveau des paumes et des plantes sont exprimes en micro-Siemens (μS). La valeur normale est superieure a 60 μS, une valeur de conductance situee entre 40 et 60 μS temoigne d’une atteinte vegetative moderee, et d’une forme severe lorsque ce resultat est inferieur a 40 μS. Cette technique s’applique donc a l’evaluation precise du degre d’atteinte vegetative sudorale, qui est un bon indicateur des autres atteintes vegetatives. Dans l’application EZSCAN, un certain nombre de parametres du malade comme le sexe, l’âge, l’indice de masse corporelle et la pression arterielle systolique doivent etre fournis et entres dans un algorithme. Les scores sont exprimes en pourcentage de risque, allant de 0 a 100 %. Cette application concerne le depistage des sujets diabetiques ou a risque de le devenir. Ainsi, SUDOSCAN et EZSCAN offrent de nouvelles perspectives pour l’exploration de la neuropathie vegetative des diabetiques, ainsi que pour le depistage du diabete dans les pays emergents ou les moyens medicaux sont limites.

Le diabète n’épargne pas la communauté militaire. Devant cette pathologie, le médecin militaire a un rôle difficile dans la prévention, la prise en charge mais aussi dans l’expertise. En effet, la découverte d’un diabète implique des restrictions d’aptitude du patient militaire qui sont justifiées par la gravité de cette maladie et de ses complications aiguës et chroniques et ont pour but de préserver la santé du patient et la capacité opérationnelle de nos troupes.

La grande fréquence des nodules thyroïdiens, estimée entre 2 et 8 % de la population générale, amène le médecin d’unité à découvrir régulièrement ces nodules à la palpation en visite périodique, ou lors d’une imagerie cervicale prescrite pour une tout autre raison. La démarche diagnostique, centrée sur la préoccupation de ne pas méconnaître un cancer de la thyroïde, est basée sur l’interrogatoire, l’examen clinique, l’échographie cervicale, et le plus souvent, la prescription d’une cytoponction à l’aiguille fine écho-guidée, dont l’interprétation, basée sur la conférence de Bethesda de 2007 doit être précise et pertinente. Le but de ce travail est de rapporter des données récentes dans ce domaine, de préciser la conduite à tenir devant un nodule thyroïdien au vu du texte de recommandation publié par la société française d’endocrinologie en 2011, et enfin de présenter notre point de vue dans le domaine de l’aptitude, y compris pour les nodules cancéreux.

Les polyendocrinopathies auto-immunes de type 2 correspondent à une association d’au moins deux affections endocriniennes liées à une perturbation de la tolérance du système immunitaire. Nous rapportons l’observation d’une patiente, âgée de 38 ans, chez qui est découverte une maladie d’Addison, deux mois après l’introduction de lévothyroxine dans le traitement d’une thyroïdite à anticorps anti-thyroperoxydase, cette association étant auparavant connue sous l’appellation de syndrome de Schmidt. Ce cas clinique illustre les difficultés diagnostiques des polyendocrinopathies auto-immunes et permet de rappeler les principales associations rencontrées dans les polyendocrinopathie auto-immune de type 2. Enfin les modalités pratiques du dépistage systématique des endocrinopathies associées, non consensuelles, sont discutées.

Les complications cardiovasculaires du diabete representent la premiere cause de mortalite des diabetiques et la maladie coronaire y occupe une place preponderante. Cependant, la cardiomyopathie diabetique merite d’etre mieux connue en raison de sa frequence et de sa gravite. Elle se presente, cliniquement, par une insuffisance cardiaque en rapport avec une dysfonction diastolique precedant une alteration de la fonction systolique. Le pronostic de l’insuffisance cardiaque des diabetiques est mauvais. Un depistage plus precoce s’avere donc necessaire afin d’ameliorer la prise en charge par une equipe reunissant cardiologues et diabetologues.

Resume L’HbA1c, bien qu’elle souffre de quelques limites, constitue aujourd’hui l’outil essentiel pour la surveillance de l’equilibre glycemique des diabetiques. Les grandes etudes ont montre qu’un traitement intensif, fonde sur des objectifs ambitieux d’HbA1c, reduisait a court terme les complications microvasculaires et a long terme les complications micro- et macrovasculaires du diabete. La normalisation precoce de la glycemie est indispensable, tandis que la survenue d’hypoglycemies severes doit absolument etre evitee. La necessite de controler l’ensemble des facteurs de risque cardiovasculaires, notamment de la pression arterielle et des lipides, est un fait aujourd’hui bien etabli a la lecture des resultats de l’etude Steno 2. La definition des objectifs d’HbA1c doit tenir compte de l’âge, de l’anciennete du diabete et des facteurs de risque cardiovasculaire. Ainsi, le traitement intensif du diabete de type 2 necessite d’etre precoce, pas trop rapide, d’eviter les hypoglycemies et de s’associer a un controle rigoureux des autres facteurs de risque cardiovasculaires. L’HbA1c est donc un objectif essentiel dans la prise en charge des diabetiques de type 2, mais il ne doit pas etre le seul.

Objectif Analyser les modalites d’instauration de l’association fixe Degludec-Liraglutide (IdegLira), chez des sujets diabetiques de type 2 (DT2) en situation de « vie reelle ». Patients et methodes Cette etude multicentrique a analyse retrospectivement les conditions de prescription et les facteurs influencant le choix de la dose initiale chez 479 patients DT2 ayant debute IdegLira entre septembre 2016 et juin 2017. Resultats Caracteristiques initiales des sujets : âge 60,1 ± 10,3 ans, femmes 49,8 %, duree diabete 15,3 ± 9,0 ans, IMC 33,2 ± 6,0 kg/m2, HbA1c 9,1 ± 1,8 %, retinopathie 36,4 %, nephropathie 38,6 %, coronaropathie 18,9 %. IDegLira a ete prescrit dans un objectif de simplification (46,6 %) ou intensification (46,9 %) therapeutique, en ambulatoire dans 47,3 % des cas. Le traitement prealable comprenait : antidiabetiques oraux (ADO) seuls (6,9 %), GLP-1RA ± ADO (9,6 %), insuline basale ± ADO (16,7 %), multi-injections d’insuline (MI) ± ADO (12,7 %), insuline basale + GLP-1RA ± ADO (43,8 %) ou MI + GLP-1RA ± ADO (10,2 %). Lors de cette prescription initiale, la metformine etait maintenue (99 %), les sulfonylurees le plus souvent maintenus a dose identique (61,1 %) et l’insuline rapide interrompue dans 36,4 % des cas. La dose initiale d’IdegLira etait de 28,3 ± 11,0 U/jour. Chez les sujets prealablement sous insuline basale et liraglutide, le choix de la dose initiale d’IDegLira etait uniquement correle a la posologie anterieure d’insuline basale. Discussion En France, les prescriptions d’IDegLira concernent majoritairement des patients ayant un diabete ancien et un schema therapeutique complexe. En depit des restrictions initiales du perimetre de remboursement, l’initiation s’inscrit equitablement dans des objectifs de simplification ou d’intensification therapeutique.

Introduction Les adenomes geants representent entre 0,4 et 4 % des adenomes hypophysaires. Les prolactinomes font exception dans la prise en charge de ces adenomes geants puisqu’ils peuvent beneficier le plus souvent d’un traitement medical en premiere intention malgre la taille et la localisation de la lesion. Nous rapportons le cas d’un patient presentant un macroprolactinome geant, chez qui le traitement par cabergoline a permis une reduction rapide du taux de prolactine et du volume tumoral. Patient et methode Un patient de 25 ans etait admis pour majoration de cephalees chroniques evoluant depuis 5 ans. L’IRM retrouvait une masse intra- et suprasellaire de 5,1 × 3,4 × 4 cm, le dosage de la prolactine etait > 100 000 UI confirmant le diagnostic de prolactinome, il s’y associait un deficit gonadotrope, mais pas d’atteinte campimetrique. Un traitement par cabergoline 1 mg/semaine etait introduit. Resultats A 48 h de l’introduction du traitement, la prolactine etait recontrolee a 19 207 mUI/, soit une baisse de 80,8 % avec amelioration nette des cephalees. A un mois, on observait une baisse de 90 % avec parallelement une diminution du plus grand diametre tumoral de 30 et de 50 % a 3 mois. Discussion Le traitement par agoniste dopaminergique en premiere intention dans la prise en charge des macroprolactinomes geant est maintenant bien etabli. Pour notre patient, les effets de la cabergoline ont ete spectaculaires en termes de baisse du taux de prolactine et du volume tumoral a dose usuelle. En cas de resistance au traitement medical, un traitement multimodal est parfois necessaire pour aboutir a une reponse therapeutique.

UNLABELLED Multicentric registers such as The French Acromegaly Register provide data on rare disorders that are otherwise difficult to obtain, so avoiding extrapolation from limited data sets. This study focuses on clinical, hormonal and therapy characteristics of acromegaly in people over 70 years old. The objective was to compare this population with the youngest to disclose if the medical management was similar. PATIENTS AND METHODS The data were obtained from the 30 centres that have registered patients in the Acromegaly Register since 1999. RESULTS The register listed 644 acromegaly patients on 1st January 2005, of whom 68 (22 men and 46 women) were over 70 years old, independently of the diagnosis date of their disease. Their average age was 76.8 + or - 5 years (range: 70-95) and they had suffered from acromegaly for 11 + or - 6 years (compared to 7 years in those aged less than 70). Their BMI were similar. Diabetes and hypertension were more frequent than in younger acromegalic patients and in the general French population matched for age. Circulating GH and IGF-1 concentrations were lower than in the younger acromegalic patients on inclusion and 1 year after treatment. There was no significant difference in the tumor size. Only 44% of the patients over 70 underwent surgery, against 90% of patients under 70 years. However, the fractions of young and elderly patients with a controlled disease 1 year after inclusion were the same (51%). CONCLUSION In the limits of the use of register, these data reveal a high prevalence of diabetes and hypertension in the eldest acromegalic patients. Despite much less frequent surgical intervention, patients' disease under control is equivalent to the younger population 1 year after the initial interview, confirming the effectiveness of the choices of treatment.

Resume Toutes les estimations montrent qu’en France, le vieillissement de la population s’accompagne d’une majoration de la prevalence du diabete qui depasse 10 % chez les seniors de plus de 65 ans. L’influence du diabete sur les fonctions cerebrales est soulignee par tous, mais peu d’etudes controlees permettent de l’affirmer de maniere indiscutable. Les consequences du diabete sur les fonctions cerebrales sont representees par le declin cognitif et les demences, les etats depressifs et les accidents vasculaires cerebraux (AVC). Ces complications s’associent frequemment pour alterer la qualite de vie de ces malades et generer des consequences socioeconomiques considerables. Si les resultats des etudes sont parfois contradictoires, il est globalement possible de conclure a la responsabilite du diabete souvent associe a l’hypertension arterielle, dans le declin cognitif de ces malades ainsi que dans la frequence et la gravite des AVC. Ces considerations invitent a une meilleure prise en charge de ces patients et a la mise en place de travaux cooperatifs pour preciser la responsabilite de la maladie diabetique et des differents facteurs de risque cardiovasculaires dans la survenue des demences, des AVC et enfin des syndromes depressifs dont les consequences sont probablement sous-estimees.

All diabetes specialists are aware of the frequency and severity of coronary disease in diabetics. Non-invasive diagnostic tests perform well, but they could be better. Aim To assess the role of computed tomographic coronary angiography in diabetics. New cardiac imaging techniques such as CT coronary angiography are promising tools for the selection of patients for conventional X-ray coronary angiography, which remains the key for diagnosis and angioplasty. The limitations of CT coronary angiography, even using the most advanced machines with a 64-slice capacity, are its resolution, the need for an iodine contrast agent and the cumulative radiation from repeated examinations. Conclusion CT coronary angiography appears to have great potential for patients at risk where non-invasive tests cannot absolutely exclude coronary disease and for the follow-up of coronary bypass surgery.

Introduction Hypercalcemia is a rare complication of non-Hodgkin lymphoma. Usually, hypercalcemia occurs late in the disease course, except for high-grade lymphoma. Most often hypercalcemia is related to excessive level of circulating PTH-rP or sometimes, 1,25(OH)2D3. Concomitant high plasmatic concentration of PTH-rP and 1,25(OH)2D3 is uncommon. Exegesis We report the case of a 82-year-old man who presented with abdominal pain and weight loss, leading to the diagnosis of diffuse large-B-cell lymphoma (high-grade lymphoma) associated with symptomatic hypercalcemia (3.21 mmol/l). PTH-rP and 1,25(OH)2D3 plasmatic levels were high. Calcium concentration was normalized with glucocorticoids and sequential chemotherapy. Conclusion This case report confirms that hypercalcemia, as consequence of excessive plasmatic level of PTH-rP secreted by tumoral cells, can occur early in the course of high-grade lymphoma. Glucocorticoids and chemotherapy are the best treatment options.

Resume Propos Le syndrome de Nelson est une complication grave de la surrenalectomie bilaterale realisee dans le traitement de certaines maladies de Cushing et sa prise en charge reste difficile. A travers l'observation d'une patiente atteinte d'une forme severe de ce syndrome depuis plus de dix ans, les auteurs se proposent de realiser une revue de la litterature ou sont exposes les principaux modes de traitement actuels. Actualite et points forts De nombreuses molecules ont ete utilisees avec des resultats tres divers. Dans notre observation, en accord avec quelques publications recentes, la cabergoline a la dose de 2 mg/semaine semble etre efficace avec un recul de trois ans et demi. Cet agoniste dopaminergique, bien plus que la bromocriptine, donne en effet des perspectives tres interessantes pour la prise en charge de la maladie. En outre, si les traitements classiques comme l'acide valproique ou la cyproheptadine sont peu efficaces, les analogues de la somatostatine semblent avoir un certain interet therapeutique. Perspectives et projets De nouvelles molecules sont en cours d'evaluation, mais les etudes sont difficiles en raison de la faible prevalence de la maladie. L'analyse des recepteurs des cellules tumorales constitue sans doute une voie d'avenir pour la mise en evidence de nouvelles cibles therapeutiques.

The disorder now known as metabolic syndrome has been recognized for 50 years, but its multiple definitions have led to some confusion and even doubt about its very nature. Metabolic syndrome is directly linked to the presence of android obesity, which indicates insulin resistance and lies at the root of all risk factors and early indications of type 2 diabetes. It is diagnosed by systematic measurements of waist size and its direct interpretation taking ethnic origin into account. This pragmatic approach avoids the uncertainties generated by differing definitions and is subtler than the presence or absence of metabolic syndrome in a given patient. Drug-free treatment of an android obese patient is inexpensive and effective, but this apparently simple approach masks difficulties of application. However, these are sociological problems.

Les complications du diabete et notamment le pied diabetique sont devenues un veritable enjeu de sante publique en raison de leur cout humain et financier. Le diabete reste ainsi aujourd’hui en France la premiere cause d’amputation non traumatique des membres inferieurs. La physiopathologie expliquant la frequence et la gravite des complications trophiques des membres inferieurs chez les diabetiques est multifactorielle et dominee par la neuropathie sensitive. Celle-ci peut etre depistee par l’utilisation d’un monofilament de type Semmes-Weinstein. L’etat vasculaire doit egalement etre parfaitement evalue. Les lesions vasculaires chez le diabetique sont souvent diffuses et distales, rendant difficiles les gestes de revascularisation. Toutes les plaies sont volontiers infectees et compliquees d’osteite. La determination du germe responsable est indispensable a l’efficacite de l’antibiotherapie qui doit etre prolongee en cas d’atteinte osseuse. Le traitement doit toujours debuter par la mise en decharge du pied. Cette decharge est souvent difficile a obtenir, mais est indispensable pour esperer une cicatrisation. Les soins locaux sont essentiels et reposent sur la competence et la motivation des acteurs paramedicaux; dans ce cadre, la participation d’un pedicure-podologue bien forme a ce type de pathologie constitute un apport irremplacable, permettant de depister les anomalies statiques et d’ameliorer les chances de guerison. L’hospitalisation est parfois necessaire, notamment si la situation sociale ou l’etat septique sont mal maitrises. Une antibiotherapie ne sera debutee qu’en cas de signe clinique d’infection, et sa duree dependra de l’importance des lesions, notamment de l’existence d’une atteinte osseuse sous-jacente. Tous les efforts doivent tendre vers le developpement des mesures preventives et de l’education therapeutique des patients, mais aussi des acteurs de sante. L’implication harmonieuse d’equipe multidisciplinaire constitute l’element essentiel de l’amelioration de la qualite des soins.

Resume Introduction. – Le syndrome metabolique est une association de facteurs de risque cardiovasculaire et l'hyperhomocysteinemie represente un facteur de risque reconnu. Objectif. – Rechercher si l'hyperhomocysteinemie est associee au syndrome metabolique. Methodes. – « EPIMIL » est une enquete prospective qui a debute par l'evaluation transversale des facteurs de risque d'une population qui sera suivie pendant dix ans. Les donnees initiales ont ete recueillies, un ECG, une mesure de la pression arterielle et des prelevements (biologie, ADN) effectues. Les criteres du syndrome metabolique utilises sont ceux du NCEP ATP III. Resultats. – Sur 2045 hommes âges de 20 a 58 ans (37,7 ± 8,7 ans), 185 (9 %) ont un syndrome metabolique (au moins trois criteres), 587 (29 %) une homocysteinemie egale ou superieure a 12 μmol/L et 202 (10 %) egale ou superieure a 15 μmol/L. L'homocysteinemie moyenne de l'ensemble de la population est de 10,97 ± 5,01 μmol/L. Elle ne differe pas selon la presence (11,4 ± 6 μmol/L) ou l'absence (10,9 ± 5 μmol/L) du syndrome metabolique, tout comme la distribution de ses valeurs. Elle n'est pas correlee avec l'indice de masse corporelle, les tours de taille et de hanches, ni avec la glycemie, l'HbA1c et l'insulinoresistance, ni non plus avec les marqueurs de risque cardiovasculaire (CRP ultrasensible, microalbuminurie). Elle est faiblement correlee a la pression arterielle systolique et diastolique, a la clairance de la creatinine, au tabagisme, a la cholesterolemie, a la triglyceridemie et aux acides gras libres mais non aux fractions HDL et LDL, ni a la lipoproteine (a). Elle contribue faiblement au risque cardiovasculaire a dix ans, selon les equations de Framingham ou Score. Conclusions. – Dans cette population, la prevalence de l'hyperhomocysteinemie n'est pas affectee par la presence d'un syndrome metabolique et, non correlee a ses principales composantes, en est independante.

The Metabolic syndrome is considered to be an important public health problem, but few epidemiological studies have defined the present situation in France. EPIMIL is a prospective epidemiological study that began on February 1, 2003.This study was designed to identify the clinical and laboratory parameters of metabolic syndrome and cardiovascular risk factors in a population of 2045 male military personnel based in the Paris region. The initial 1-year cross-sectional study will be followed by a 10-year follow-up and patient care.The 2045 subjects included 185 (9%) presented at least 3 of the 5 NCEP ATP III criteria defining metabolic syndrome. They were significantly older (42.2 +/- 8.5 yrs) than the other subjects (37.3 +/- 8.7 yrs, P0.001), had a higher BMI (29.5 +/- 3.4 vs 24.8 +/- 2.9 kg/m2, P0.001) and a greater body weight at age 20 (75.4 +/- 11 vs 70.4 +/- 8.5 kg, P0.01). Smoking, little physical activity and family histories of diabetes and arterial hypertension were more frequent in these men. While levels of the cholesterol and CRP us were higher, Lp(a) and homocysteine concentrations were normal. Plasma insulin and BMI (r = 0.456 P0.0001) and plasma insulin and waist circumference (r = 0.446 P0.0001) were well correlated. Lastly, plasma insulin, free fatty acids and cardiovascular risk increased steadily with the increase in the number of metabolic syndrome criteria.These results in a large and particularly uniform population of men show the prevalence of metabolic syndrome in adult men, and demonstrate its link with insulin resistance. Men with several risk factors require specific care, particularly for hypertension and dyslipidemia; the effectiveness of this care will be evaluated during the follow-up period.

The relationship between diabetes mellitus and cancer of the pancreas is complex and incompletely understood. Nevertheless, it is generally agreed that new-onset diabetes in a patient over 50 Years old is a classical indication of pancreatic cancer. But there is no official directive in France that a scan should routinely be performed in such cases. We have studied 115 patients aged over 50 who were hospitalized for new-onset diabetes (fewer than 30 days) whose instability required insulin treatment. Routine imaging revealed abdominal disorders in 14 patients, 6 (5.2%) of whom were suffering from pancreatic adenocarcinomas. No clinical indication or laboratory test, apart from an unusually severe anorexia, suggested the discovered disorders. We therefore routinely carry out a pancreas scan, preferably by MRI, on all patients over 50 Years old presenting with new-onset diabetes, even if there are not clinical or laboratory indications of cancer. This is the only way in which small pancreatic cancers can be detected, thus providing the best hopes for successful treatment. Unfortunately, too often, this approach also detects only tumors that are already well developed. However, nowadays, it is not conceivable for a clinical team to discharge a patient from hospital with such a serious disease undiagnosed.

Resume Definition L’hypo-uricemie (uricemie inferieure a 120 μmol/l) est une anomalie biologique souvent de decouverte fortuite, avec une faible prevalence variant, selon son caractere permanent ou transitoire, de 0,15 a 3,38 %. Nouveaux concepts physiologiques du bilan de l’acide urique Ces dernieres annees, la comprehension des mecanismes physiopathologiques des hypo-uricemies a ete marquee par l’identification de 3 systemes de transports renaux et extra-renaux de l’acide urique : un echangeur Cl/urate (URAT1), une famille d’echangeurs d’anions organiques (OAT) et un canal a urate. Etiologies et complications des hypo-uricemies Par l’interrogatoire, une cause medicamenteuse ou toxique (allopurinol…), qui explique environ la moitie des hypo-uricemies, est generalement vite reconnue. L’hypo-uricemie peut etre rattachee a une maladie connue : insuffisance hepato-cellulaire, neoplasie, diabete, syndrome d’immunodeficience acquise, syndrome de secretion inappropriee d’hormone antidiuretique. Sinon, l’hypo-uricemie peut apparaitre isolee, justifiant la mesure de la clairance de l’acide urique dont la normalite ou la baisse oriente vers un defaut de l’activite de la xanthine-oxydase et l’elevation vers une anomalie du transport tubulaire proximal d’acide urique (syndrome de Fanconi, hypo-uricemie idiopathique familiale). L’hypo-uricemie ne semble exposer directement a aucun danger mais la survenue d’une lithiase urinaire ou d’une insuffisance renale aigue, secondaire a la conjonction d’une hypo-uricemie profonde et d’un stress oxydatif, est toujours possible.

Resume La regression de la pathologie infectieuse a permis aux consequences de l’atherosclerose d’occuper le devant de la scene et de constituer la premiere cause de mortalite dans les pays occidentalises. Sous l’effet de facteurs de risque dont beaucoup sont accessibles a la therapeutique, les plaques d’atherome se developpent sur l’ensemble du reseau arteriel en privilegiant les gros vaisseaux et leurs zones de division. La symptomatologie presentee est alors fonction de l’importance et de la nature des plaques dont les plus dangereuses sont les plus instables car elles peuvent se rompre et entrainer la thrombose du vaisseau. Les progres des techniques d’exploration non invasives et de la pharmacopee apportent une amelioration indiscutable de la prise en charge de ces si nombreux malades. Malheureusement, toutes ces avancees ne peuvent pallier l’explosion epidemique de cette pathologie dont la genese provient pour l’essentiel des modifications du mode de vie conduisant au surpoids puis au diabete et a l’hypertension. Seule la poursuite des mesures de sante publique et l’information de la population permettront d’endiguer ce fleau.

Resumen Hoy en dia, la aterosclerosis y sus consecuencias son la primera causa de muerte en los paises occidentales debido a la regresion de las enfermedades infecciosas.Bajo la influencia de factores de riesgo, muchos de ellos modificables mediante tratamiento, las placas de ateroma se desarrollan en toda la red arterial, especialmente en los grandes vasos y en las bifurcaciones. La sintomatologia dependera del tamano y naturaleza de las placas; las inestables son las mas peligrosas, porque se pueden romper y desprenderse y producir trombos. Los avances en las tecnicas de exploracion no agresivas y en la farmacologia han permitido mejorar el tratamiento de los numerosos pacientes. Desafortunadamente, estos progresos no han conseguido paliar el caracter epidemico que ha desarrollado esta patologia, debido esencialmente al cambio en los habitos de vida que conducen al sobrepeso, a la diabetes y a la hipertension. Solo la aplicacion de medidas de sanidad publica y la correcta informacion a la poblacion detendran la expansion de las enfermedades vasculares.

Introduction Certaines formes graves d’orbitopathie basedowienne peuvent necessiter une chirurgie urgente. Nous decrivons ici l’observation d’une patiente pour laquelle une exceptionnelle decompression orbitaire par voie posterieure s’est averee necessaire. Observation Mme M., 51 ans, presente une maladie de Basedow depuis 2013 (T4L = 60 pmol/L, TRAK = 10,2 UI/L) avec orbitopathie severe : œdeme des paupieres, exophtalmie de stade III. Nous retrouvons dans ses antecedents un cancer du sein droit et une arteriopathie obliterante des membres inferieurs. Elle poursuit cependant un tabagisme toujours actif et important : un paquet/jour depuis l’âge de 12 ans. Un traitement par thiamazole est propose, mais devant d’importantes fluctuations de la TSH, la persistance de TRAK eleves (> 40 UI/L) et l’absence de controle de la maladie, une thyroidectomie totale est proposee en mai 2015, encadree par une corticotherapie par voie intraveineuse. Il est cependant observe une aggravation de l’orbitopathie avec acuite visuelle a 5/10e a droite, diplopie, et a l’IRM orbitaire une hypertrophie des muscles extraoculaires plus evidents sur les muscles mediaux, avec comblement des apex orbitaux et atteinte des deux nerfs optiques. Une corticotherapie IV (methylprednisolone 1 g/24 heures sur 3 jours) est inefficace. L’atteinte etant trop severe pour une utilisation de rituximab, il est decide la realisation d’une decompression du nerf optique droit par voie posterieure, d’abord nasal endoscopique en milieu neurochirurgical, permettant la recuperation d’une acuite visuelle a 8/10e. Discussion La decompression neurochirurgicale d’un nerf optique par voie posterieure en urgence dans une maladie de Basedow est d’indication exceptionnelle. Le suivi doit etre specialise et l’arret du tabac, imperatif.

Resume Introduction. – Le syndrome de Willi-Prader fait partie des obesites genetiques et une observation caricaturale est rapportee. Exegese. – Le tableau debute initialement par une hypotonie neonatale severe avec difficultes alimentaires, a laquelle succede une boulimie intense responsable d’une obesite morbide, associee a un retard statural, un syndrome dysmorphique avec acromicrie et des troubles du comportement. Le diagnostic est avant tout clinique et sera confirme par la mise en evidence de l’anomalie genetique, sur le chromosome 15, qui caracterise le syndrome de Willi-Prader, premiere affection pour laquelle a ete mise en evidence chez l’homme le mecanisme d’empreinte genomique. Conclusion. – Tout l’interet de la connaissance de ce syndrome repose aujourd’hui sur la necessite d’une prise en charge precoce et avec alors des possibilites therapeutiques par hormone de croissance.

Summary Home blood pressure monitoring in diabetic population Normalization of blood pressure is today as necessary as an optimal blood glucose control. These targets aim at reducing the negative consequences of hypertension which is particulary frequent and of poor prognosis for these patients. Nevertheless, the definition of the real blood pressure of these patients is uneasy because of the lack of precision of clinical blood pressure measurement. New methods have been developed to address this insufficiency. Home blood pressure monitoring is characterised by good compliance and accuracy, but patient education needs a special training and validated automated devices. This method has to be proposed to the diabetic population as soon as hypertension may be a problem. These patients will contribute to monitor their own blood pressure as they do it with blood glucose control.

Oesophagus perforation, despite an often-loud symptomatology, is lately diagnosed. A similar course is illustrated by the observation of a patient who presented a Candida albicans-induced empyema. The oesophagus rupture was diagnosed by thoracoscopy made because of extensive hydropneumothorax on the thoracic CT 3 days after ablation of the thoracic drain. Temporary oesophagus exclusion and pleural drainage in close proximity of the perforation were performed. A nosocomial pneumonia complicated the development but the patient could endly issue from ICU. This mode of revelation was unusual and the authors recommend thinking of the diagnosis of oesophagus rupture when a patient is admitted for a candidosis empyema.