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La thrombose veineuse profonde est une pathologie fréquente et potentiellement grave, avec un risque de complication aiguë (embolie pulmonaire) et de complications chroniques (récidive et syndrome post-thrombotique [SPT]). Son traitement associe l’anticoagulation et la compression veineuse (CV). L’adhésion des patients au port régulier et prolongé de la CV est primordiale pour obtenir la résolution de l’épisode initial et pour limiter le risque de séquelles et de complications à moyen et long termes.

Labrasol®and Gelucire®44/14 are lipid-based excipients used for the oral drug delivery of poorly water-soluble drugs. These macrogolglycerides are composed of acylglycerols and PEG esters, potential substrates of digestive lipases. We developed an in vitro method to simulate the gastrointestinal lipolysis of these excipients and to evaluate the impact of lipolysis in vivo. At the end of the gastric phase, the composition of both excipients was significantly modified underlining the importance of gastric lipolysis in vivo. We also studied the influence of excipients’ lipolysis on the solubilization of a poorly water-soluble drug, cinnarizine, in aqueous phase. Gastrointestinal lipolysis of Labrasol®was a prerequisite to maintain cinnarizine in aqueous solution, whereas the lipolysis of Gelucire®44/14 did not affect the cinnarizine solubilization.

Gelucire®44/14, a lauroyl polyoxylglycerides obtained by polyglycolysis of hydrogenated coconut oil with PEG-32, is used to increase the oral bioavailability of poorly-water soluble drugs. It is a solid dispersion composed of a PEG ester fraction under a lamellar phase of 120 Å with a helical conformation and an acylglycerol fraction under a hexagonal packing. This excipient spontaneously evolves to its most stable phase of 120 Å after storage at 25 °C for 21 hours leading to physically stable formulations. Gelucire®44/14 is a hydrophilic system that hydrates and swells in contact with water and forms cubic mesophases before complete erosion/emulsification. It is also lipolyzed by various enzymes such as gastric lipase or carboxyl ester hydrolase. After an in vitro gastrointestinal lipolysis simulation, the main components remaining are mono and diesters of PEG-32. These amphiphilic metabolites can explain the beneficial role of Gelucire®44/14 on the solubility of poorly-water soluble drugs such as cinnarizine even after partial lipolysis of the lipid-based system. Finally that excipient can also increase the bioavailability of active substances by interacting with enterocyte-based proteins like P-glycoprotein or cytochromes P450.

Le but de cette étude est d’étudier les pratiques des médecins généralistes (MG) face à un goitre rapidement progressif (GRP) pour améliorer le délai d’adressage du cancer anaplasique de la thyroïde (CAT).

The rise of intraoperative information threatens to outpace our abilities to process it. Context-aware systems, filtering information to automatically adapt to the current needs of the surgeon, are necessary to fully profit from computerized surgery. To attain context awareness, representation of medical knowledge is crucial. However, most existing systems do not represent knowledge in a reusable way, hindering also reuse of data. Our purpose is therefore to make our computational models of medical knowledge sharable, extensible and interoperational with established knowledge representations in the form of the LapOntoSPM ontology. To show its usefulness, we apply it to situation interpretation, i.e., the recognition of surgical phases based on surgical activities. Considering best practices in ontology engineering and building on our ontology for laparoscopy, we formalized the workflow of laparoscopic adrenalectomies, cholecystectomies and pancreatic resections in the framework of OntoSPM, a new standard for surgical process models. Furthermore, we provide a rule-based situation interpretation algorithm based on SQWRL to recognize surgical phases using the ontology. The system was evaluated on ground-truth data from 19 manually annotated surgeries. The aim was to show that the phase recognition capabilities are equal to a specialized solution. The recognition rates of the new system were equal to the specialized one. However, the time needed to interpret a situation rose from 0.5 to 1.8 s on average which is still viable for practical application. We successfully integrated medical knowledge for laparoscopic surgeries into OntoSPM, facilitating knowledge and data sharing. This is especially important for reproducibility of results and unbiased comparison of recognition algorithms. The associated recognition algorithm was adapted to the new representation without any loss of classification power. The work is an important step to standardized knowledge and data representation in the field on context awareness and thus toward unified benchmark data sets.

Évaluer la prévalence et l’évolution des comorbidités cardiovasculaires, métaboliques et osseuses dans les HBMS.

The objective of this study was to evaluate the use of glyceryl behenate as a plasticizer and release modifier in solid dispersion systems containing itraconazole and carbamazepine. Amorphous solid dispersions of high molecular weight polyvinylpyrrolidone were prepared by hot-melt extrusion, the processing of which was improved by the inclusion of glyceryl behenate. Dispersions were milled and subsequently compressed into tablets. Solid dispersions were also prepared by KinetiSol Dispersing, which allowed for the manufacture of monolithic tablets of the same composition and shape as compressed tablets. Tablets without glyceryl behenate and all compressed tablets were observed to have an incomplete release profile likely due to drug crystallization within the tablet as this occurred at conditions in which dissolution concentrations were below saturation. Monolithic tablets formulated to be more hydrophobic, by including glyceryl behenate, allowed for sustained release below and above saturation conditions.

Immune checkpoint inhibitors (ICI) are used to treat cancers including metastatic melanomas and can induce endocrine side effects. The thyroid is frequently affected with classically transient thyrotoxicosis followed by hypothyroidism. The evolution of thyroid nodules and goiters under ICI therapy is poorly described.A 72-year-old male presenting with hyperthyroidism due to a toxic nodule in a multinodular goiter (MNG) started ICI therapy combining ipilimumab and nivolumab to treat metastatic melanoma. After an initial worsening of thyrotoxicosis, treated with carbimazole, he developed profound hypothyroidism, persisting after carbimazole discontinuation, needing a long-term levothyroxine supplementation. Ultrasound control performed 6 months after ICIs treatment initiation revealed diffuse thyroid atrophy with involution of all nodules. 123I-scintigraphy confirmed a destructive mechanism.The evolution of MNG and toxic nodules is poorly described in patients treated with ICI since systematic US evaluations are lacking. We describe for the first time a toxic nodule cured by ICI therapy inducing destructive thyroiditis.Pre-existing nodules and MNG, even if toxic, are not a contraindication for ICI treatment provided the patients are carefully monitored.

In order to explore pituitary adenoma (PA), magnetic resonance imaging (MRI) remains the cornerstone. However, there are some limitations and MRI can be non-conclusive. The development of additional imaging modalities like nuclear medicine explorations may help to confirm PA diagnosis, guide management and follow up. Nuclear medicine uses radiopharmaceuticals for imaging with single photon emission computed tomography (SPECT), or positron emission tomography (PET), coupled to CT scan. Radiopharmaceuticals products target specific cellular elements which allow to explore several biological pathways. Nuclear medicine may also be used for therapeutic purposes and recent developments of approach based on Peptide Receptor Radionuclide Therapy (PRRT) for treatment of aggressive PA and pituitary carcinoma will be reviewed. Several radiotracers have been studied in the context of PA, and the aim of this paper is to discuss their respective performances and clinical interest.

•A backgroundless 1H-13C radiofrequency coil is presented.•1H background signals are removed and spurious 13C peaks are minimized.•An optimization protocol to perform efficient cross-polarization is given.•A 13C polarization of ∼60% is observed for [1-13C]sodium acetate.

The LFCS Consortium was established to develop standardized in vitrotests for lipid-based formulations (LBFs) and to examine the utility of these tests to probe the fundamental mechanisms that underlie LBF performance. In this publication, the impact of bile salt (sodium taurodeoxycholate, NaTDC) concentration and drug loading on the ability of a range of representative LBFs to generate and sustain drug solubilization and supersaturation during in vitrodigestion testing has been explored and a common driver of the potential for drug precipitation identified. Danazol was used as a model poorly water-soluble drug throughout. In general, increasing NaTDC concentrations increased the digestion of the most lipophilic LBFs and promoted lipid (and drug) trafficking from poorly dispersed oil phases to the aqueous colloidal phase (APDIGEST). High NaTDC concentrations showed some capacity to reduce drug precipitation, although, at NaTDC concentrations ≥3 mM, NaTDC effects on either digestion or drug solubilization were modest. In contrast, increasing drug load had a marked impact on drug solubilization. For LBFs containing long-chain lipids, drug precipitation was limited even at drug loads approaching saturation in the formulation and concentrations of solubilized drug in APDIGESTincreased with increased drug load. For LBFs containing medium-chain lipids, however, significant precipitation was evident, especially at higher drug loads. Across all formulations a remarkably consistent trend emerged such that the likelihood of precipitation was almost entirely dependent on the maximum supersaturation ratio (SRM) attained on initiation of digestion. SRMdefines the supersaturation “pressure” in the system and is calculated from the maximum attainable concentration in the APDIGEST(assuming zero precipitation), divided by the solubility of the drug in the colloidal phases formed post digestion. For LBFs where phase separation of oil phases did not occur, a threshold value for SRMwas evident, regardless of formulation composition and drug solubilization reduced markedly above SRM> 2.5. The threshold SRMmay prove to be an effective tool in discriminating between LBFs based on performance.

Validation is now considered as a mandatory step in any development of new medical image processing methods, systems, or components. It allows studying performances and adequacy with clinical applications, and comparison with similar solutions. Being able to correctly answer these three issues requires proper design, performance, and report of validation studies and results. This could be made easier by 1) the use of standardized solutions and 2) the explicit formalization and description of validation study components when designing and reporting such studies. In this paper, we will identify the major components involved in a validation study of a medical image processing (MIP) method, embedded or not in a wider clinical system. Emphasis will be given on the study conditions, and especially on the validation data sets. Main freely available validation data sets usable for MIP validation will be listed and shortly described. Finally, we will outline the need for validating the validation study itself and explain the two main aspects it includes.

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ABSTRACTChagas' disease is a global public health problem due to the recent exchange of population between Latin America and other regions, including Europe. The recent development of rapid diagnostic tests (RDTs) for Trypanosoma cruziinfection may improve patient access to diagnosis and care worldwide. We evaluated the diagnostic accuracy of the Chagas Stat-Pak RDT in a cohort of undocumented Latin-American migrants living in Geneva, Switzerland. Study participants were enrolled in a primary health care center. The Chagas Stat-Pak test was performed independently on blood and serum samples. A combination of two commercialized enzyme-linked immunosorbent assay (ELISA)-based serological tests was used for comparison (reference standard). A total of 999 adults (median age, 36 years) were included in the study; the majority were women (83%) and originally from Bolivia (47%) or Brazil (25%). A total of 125 participants (12.5%) were diagnosed with T. cruziinfection; with the exception of three individuals, all individuals diagnosed with T. cruziwere originally from Bolivia. The sensitivity and specificity of the Chagas Stat-Pak test on blood samples were 95.2% (95% confidence interval [95% CI], 89.2% to 97.9%) and 99.9% (95% CI, 99.3% to 100%), respectively. When the test was performed on serum samples, the sensitivity was 96% (95% CI, 91% to 98.3%), and the specificity was 99.8% (95% CI, 99.2% to 99.9%). The concordance of test results for blood and serum samples was 99.7%. Both negative and positive predictive values were above 98%. The Chagas Stat-Pak is an accurate diagnostic test for T. cruziinfection among Latin-American migrants living in Europe. The mild deficit in sensitivity should be interpreted in light of its ease of use and capacity to provide immediate results, which allow more people at risk to have access to diagnosis and care both in countries where Chagas' disease is endemic and in countries where this disease is not endemic.