Search

Objectives Isoniazid-monoresistant tuberculosis (HR-TB) is the most prevalent form of drug-resistant TB worldwide and in France and is associated with poorer treatment outcomes compared with drug-susceptible TB (DS-TB). The objective of this study was to determine the characteristics of HR-TB patients in France and to compare outcomes and safety of treatment for HR-TB and DS-TB. Methods We performed a case-control multicenter study to identify risk factors associated with HR-TB and compare treatment outcomes and safety between HR-TB patients and DS-TB patients. Results Characteristics of 99 HR-TB patients diagnosed and treated in the university hospitals of Paris, Lille, Caen and Strasbourg were compared with 99 DS-TB patients. Female sex (OR = 2.2; 1.0–4.7), birth in the West-Pacific World Health Organization region (OR = 4.6; 1.1–18.7) and resistance to streptomycin (OR = 77.5; 10.1–594.4) were found to be independently associated with HR-TB. Rates of treatment success did not differ significantly between HR-TB and DS-TB. Conclusions Factors associated with HR-TB are not significant enough to efficiently screen TB patients at risk of HR-TB. The systematic implementation of rapid molecular testing on clinical samples remains the only effective way to make the early diagnosis of HR-TB and adapt treatment.

Resume Introduction L’infection urinaire (IU) constitue la deuxieme cause d’infection bacterienne communautaire chez le sujet âge. Ce diagnostic est difficile car les symptomes sont souvent atypiques. Nous presentons les caracteristiques des patients ayant une IU parmi une population geriatrique (signes fonctionnels urinaires et/ou syndrome infectieux). Nous avons egalement evalue la sensibilite et la specificite de la bandelette urinaire (BU) pour le diagnostic d’IU dans cette population. Patients et methode Nous avons realise une etude observationnelle, prospective, monocentrique, d’avril 2017 a janvier 2018, incluant tous les patients hospitalises en geriatrie, presentant des signes fonctionnels urinaires et/ou un syndrome infectieux sans point d’appel, pour lesquels un examen cytobacteriologique des urines (ECBU) a ete demande. Une BU etait systematiquement realisee pour tous ces patients. Les caracteristiques cliniques et biologiques des patients ont ete etudiees selon le diagnostic definitif. En outre, les resultats des BU ont ete compares a ceux des ECBU en cas de diagnostic final d’IU. Resultats Au total, 165 patients ont ete inclus. Parmi eux, 67 (40,6 %) avaient une IU et 98 (59,4 %) avaient un autre diagnostic. Il y avait significativement plus de femmes ( p p La BU presentait une sensibilite elevee (92 %) et une VPN elevee (91 %) interessantes dans notre population. Conclusion En cas d’IU chez le sujet âge, peu de criteres sont discriminants avec une autre origine. Par ailleurs, une BU negative suggere l’absence d’IU en raison de sa bonne valeur predictive negative.

Although the COVID-19 pandemic has left no country untouched there has been limited research to understand clinical and immunological responses in African populations. Here we characterise patients hospitalised with suspected (PCR-negative/IgG-positive) or confirmed (PCR-positive) COVID-19, and healthy community controls (PCR-negative/IgG-negative). PCR-positive COVID-19 participants were more likely to receive dexamethasone and a beta-lactam antibiotic, and survive to hospital discharge than PCR-negative/IgG-positive and PCR-negative/IgG-negative participants. PCR-negative/IgG-positive participants exhibited a nasal and systemic cytokine signature analogous to PCR-positive COVID-19 participants, predominated by chemokines and neutrophils and distinct from PCR-negative/IgG-negative participants. PCR-negative/IgG-positive participants had increased propensity for Staphylococcus aureus and Streptococcus pneumoniae colonisation. PCR-negative/IgG-positive individuals with high COVID-19 clinical suspicion had inflammatory profiles analogous to PCR-confirmed disease and potentially represent a target population for COVID-19 treatment strategies., Clinical management of COVID-19 in resource-poor settings has distinct challenges and detailed patient characterisation is needed. Here, the authors describe the clinical and immunological profiles of patients at a hospital in Malawi with confirmed and suspected COVID-19.

Summary Introduction The Coronavirus disease-2019 outbreak (COVID-19) has been declared a pandemic by the World Health Organization. Studies report both a severe inflammatory syndrome and a procoagulant state in severe COVID-19 cases, with an increase of venous thromboembolism, including pulmonary embolism (PE) and deep vein thrombosis (DVT). In this context, we discuss the use of doppler ultrasonography (DUS) in the screening and diagnosis of DVT in ambulatory and hospitalized patients with, or suspected of having, COVID-19, outside the intensive care unit (ICU). Material and methods Non-systematic review of the literature. Results In patients hospitalized for or suspected of COVID-19 infection with the presence of either (a) DVT clinical symptoms, (b) a strong DVT clinical probability (Wells score > 2) or (c) elevated D-dimer levels without DVT clinical symptoms and without PE on lung CT angio-scan, DVT should be investigated with DUS. In the presence of PE diagnosed clinically and/or radiologically, additional systematic DVT screening using DUS is not recommended during the COVID-19 pandemic. The use of 4-points compression DUS for DVT screen and diagnosis is the most appropriate method in this context. Discussion Systematic DUS for DVT screening in asymptomatic COVID patients is not recommended unless the patient is in the ICU. This would increase the risk of unnecessarily exposing medical staff to SARS-CoV-2 and monopolizing limited resources during this period.

Real-time MR-imaging has been clinically adapted for monitoring thermal therapies since it can provide on-the-fly temperature maps simultaneously with anatomical information. However, proton resonance frequency based thermometry of moving targets remains challenging since temperature artifacts are induced by the respiratory as well as physiological motion. If left uncorrected, these artifacts lead to severe errors in temperature estimates and impair therapy guidance. In this study, we evaluated deep learning for on-line correction of motion related errors in abdominal MR-thermometry. For this, a convolutional neural network (CNN) was designed to learn the apparent temperature perturbation from images acquired during a preparative learning stage prior to hyperthermia. The input of the designed CNN is the most recent magnitude image and no surrogate of motion is needed. During the subsequent hyperthermia procedure, the recent magnitude image is used as an input for the CNN-model in order to generate an on-line correction for the current temperature map. The method's artifact suppression performance was evaluated on 12 free breathing volunteers and was found robust and artifact-free in all examined cases. Furthermore, thermometric precision and accuracy was assessed for in vivo ablation using high intensity focused ultrasound. All calculations involved at the different stages of the proposed workflow were designed to be compatible with the clinical time constraints of a therapeutic procedure., 21 pages, 9 figures, 1 table

Objectives Environmental contamination by patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through respiratory droplets suggests that surfaces and equipment could be a medium of transmission. We aimed to assess the surface and equipment contamination by SARS-COV-2 of an emergency department (ED) during the coronavirus infectious disease-2019 (COVID-19) outbreak. Methods We performed multiple samples from different sites in ED patients care and non-patient care areas with sterile premoistened swabs and used real-time reverse transcriptase polymerase chain reaction (RT-PCR) to detect the presence of SARS-CoV-2 ribonucleic acid (RNA). We also sampled the personal protective equipment (PPE) from health care workers (HCWs). Results Among the 192 total samples, 10 (5.2%) were positive. In patient care areas, 5/46 (10.9%) of the surfaces directly in contact with COVID-19 patients revealed the presence of SARS-CoV-2 RNA, and 4/56 (7.1%) of the surfaces that were not directly in contact with COVID-19 patients were positive. SARS-CoV-2 RNA was present only in the patients’ examination and monitoring rooms. Before decontamination SARS-CoV-2 RNA was present on the saturation clip, the scuff for blood pressure measurement, the stretcher, the plastic screens between patients and the floor. After decontamination, SARS-CoV-2 RNA remained on the scuff, the stretcher and the trolleys. All samples from non-patient care areas or staff working rooms were negative. Only one sample from the PPE of the HCWs was positive. Conclusions Our findings suggest that surfaces and equipment contamination by SARS-CoV-2 RNA in an ED during the COVID-19 outbreak is low and concerns exclusively patients’ examination and monitoring rooms, preserving non-patient care areas.

Résumé: But: évaluer les résultats de la prise en charge du cancer localisé de la prostate classé à haut risque de récidive selon les groupes pronostiques de D’Amico. Patients et méthode: Il s’agissait d’une étude rétrospective allant du 1er Mars 2002 au 31 octobre 2016.Cette étude intéressait patients opérés pour un cancer de la prostate localisé classé dans les hauts risques de récidive après une prostatectomie radicale selon les groupes pronostiques de D’Amico. Les paramètres étudiés étaient: les facteurs de risques préopératoires, les paramètres histopathologiques postopératoires, la cinétique du PSA après la prostatectomie, les paramètres fonctionnels (continence et function érectile). Résultats: Il s’agissait de 35 patients. La tumeur intéressait les deux lobes de la prostate chez 51,4% des patients, 51,4 % des patients avaient un taux de PSAT préopératoire supérieur à 20 ng/ml.La quasi-totalité (97,1%) des patients avaient un cancer qui occupait les deux lobes de la prostate à l’histologie. Le PSAT était indétectable chez 18 patients. La survie sans récidive à 5 ans était de 70% et la survie spécifique à 6 ans est de 90 %. Dix-neuf patients avaient une continence satisfaisante. Vingt patients avaient une dysfonction érectile. Conclusion: Ces résultats confirment la place de la prostatectomie dans le traitement du cancer localisé de la prostate à haut risque de récidive. Abstract: Objective: To determine the histo-clinical, pathological, therapeutic and prognostic characteristics of renal chromophobe carcinomas.Subjects and methods This is a retrospective study including 16 cases of chromophobe carcinoma among 86 of renal cancers diagnosed in the Urology Department B of Rabat University Hospital between January 2011 and August 2017. Results: This is 12 women and 4 men. The average age of discovery is 57.5 years. They are distributed in 62.5% predominantly eosinophilic, 37.5% of mixed tumors. The nuclei are irregular and incisured. Tumor T1 (31.5%) and T2 (56.25%) are the most common. The majority of patients had a low grade of Furhman, 43.8% grade 2 and 31.2% grade 3. Only one patient had a local recurrence. The overall 5-year survival rate is 92%. A death related to the disease has been reported. Nephrectomy is the gold standard for 100% of patients. The average overall survival rate is 34.4 months. Conclusion: Chromophobic kidney cancer is a particular anatomo-clinical entity, characterized by a favorable prognosis due to a low Furhman grade and its limitation to the kidney

MR-guided high-dose-rate (HDR) brachytherapy has gained increasing interest as a treatment for patients with localized prostate cancer because of the superior value of MRI for tumor and surrounding tissues localization. To enable needle insertion into the prostate with the patient in the MR bore, a single needle MR-compatible robotic system involving needle-by-needle dose delivery has been developed at our institution. Throughout the intervention, dose delivery may be impaired by: (1) sub-optimal needle positioning caused by e.g. needle bending, (2) intra-operative internal organ motion such as prostate rotations or swelling, or intra-procedural rectum or bladder filling. This may result in failure to reach clinical constraints. To assess the first aforementioned challenge, a recent study from our research group demonstrated that the deposited dose may be greatly improved by real-time adaptive planning with feedback on the actual needle positioning. However, the needle insertion sequence is left to the doctor and therefore, this may result in sub-optimal dose delivery. In this manuscript, a new method is proposed to determine and update automatically the needle insertion sequence. This strategy is based on the determination of the most sensitive needle track. The sensitivity of a needle track is defined as its impact on the dose distribution in case of sub-optimal positioning. A stochastic criterion is thus presented to determine each needle track sensitivity based on needle insertion simulations. To assess the proposed sequencing strategy, HDR prostate brachytherapy was simulated on 11 patients with varying number of needle insertions. Sub-optimal needle positioning was simulated at each insertion (modeled by typical random angulation errors). In 91% of the scenarios, the dose distribution improved when the needle was inserted into the most compared to the least sensitive needle track. The computation time for sequencing was less than 6 s per needle track. The proposed needle insertion sequencing can therefore assist in delivering an optimal dose in HDR prostate brachytherapy.

International audience; For the successful completion of medical interventional procedures, several concepts, such as daily positioning compensation, dose accumulation or delineation propagation, rely on establishing a spatial coherence between planning images and images acquired at different time instants over the course of the therapy. To meet this need, image-based motion estimation and compensation relies on fast, automatic, accurate and precise registration algorithms. However, image registration quickly becomes a challenging and computationally intensive task, especially when multiple imaging modalities are involved. In the current study, a novel framework is introduced to reduce the computational overhead of variational registration methods. The proposed framework selects representative voxels of the registration process, based on a supervoxel algorithm. Costly calculations are hereby restrained to a subset of voxels, leading to a less expensive spatial regularized interpolation process. The novel framework is tested in conjunction with the recently proposed EVolution multi-modal registration method. This results in an algorithm requiring a low number of input parameters, is easily parallelizable and provides an elastic voxel-wise deformation with a subvoxel accuracy. The performance of the proposed accelerated registration method is evaluated on cross-contrast abdominal T1/T2 MR-scans undergoing a known deformation and annotated CT-images of the lung. We also analyze the ability of the method to capture slow physiological drifts during MR-guided high intensity focused ultrasound therapies and to perform multi-modal CT/MR registration in the abdomen. Results have shown that computation time can be reduced by 75% on the same hardware with no negative impact on the accuracy.

Medical imaging is currently employed in the diagnosis, planning, delivery and response monitoring of cancer treatments. Due to physiological motion and/or treatment response, the shape and location of the pathology and organs-at-risk may change over time. Establishing their location within the acquired images is therefore paramount for an accurate treatment delivery and monitoring. A feasible solution for tracking anatomical changes during an image-guided cancer treatment is provided by image registration algorithms. Such methods are, however, often built upon elements originating from the computer vision/graphics domain. Since the original design of such elements did not take into consideration the material properties of particular biological tissues, the anatomical plausibility of the estimated deformations may not be guaranteed. In the current work we adapt two existing variational registration algorithms, namely Horn-Schunck and EVolution, to online soft tissue tracking. This is achieved by enforcing an incompressibility constraint on the estimated deformations during the registration process. The existing and the modified registration methods were comparatively tested against several quality assurance criteria on abdominal in-vivo MR and CT data. These criteria included: the Dice Similarity Coefficient (DSC), the Jaccard index, the target registration error (TRE) and three additional criteria evaluating the anatomical plausibility of the estimated deformations. Results demonstrated that both the original and the modified registration methods have similar registration capabilities in high-contrast areas, with DSC and Jaccard index values predominantly in the 0.8 - 0.9 range and an average TRE of 1.6 - 2.0 mm. In contrast-devoid regions of the liver and kidneys, however, the three additional quality assurance criteria have indicated a considerable improvement of the anatomical plausibility of the deformations estimated by the incompressibility-constrained methods. Moreover, the proposed registration models maintain the potential of the original methods for online image-based guidance of cancer treatments.

Background Impact of comedications and comorbidities upon OS isn’t well described in cancer patients (pts). We aimed to evaluate their impacts on DFS and OS on pts resected from a stage III colon cancer and treated by adjuvant FOLFOX-4 +/- cetuximab in the PETACC8 study. Methods Treatments (trts) categories were defined according to the WHO ATC classification system. We focused on 4 medication classes: anticoagulant, cardiovascular, antidiarrheal and antidiabetic trts. We classified the 2559 pts in each category if they took trt at baseline or during study whatever the duration was. Kaplan-Meier method and Cox model were used to compare survival curves. Multivariate analyses were performed on the overall population and according to trt arm. Results Only 1% of pts had no comedications. Comedications with anticoagulant, cardiovascular, antidiarrheal and antidiabetic trts were observed respectively in 18%, 40%, 30% and 9% of the cases. Patients with antidiabetic or cardiovascular trts had more comorbidities. For each other comedication categories, baseline characteristics were balanced between pts treated or not. All comedication categories, except antidiarrheals, were associated with a significant decrease of DFS and OS (Table). Dose-intensity was balanced and may not explain survival differences. For pts treated with at least one cardiac, diabetic or anticoagulant trts, severe events were more frequently reported, including 9 early deaths. The use of antidiarrheals is maybe associated to a better exposure to chemotherapy as reflected by a higher rate of grade ≥3 adverse events but also a potential better efficacy. Table. Comedications impact on DFS and OS. Table . 549P Overall analysis DFS OS HR [95%CI] p HR [95%CI] p Anticoagulants Intake vs no 1.33 [1.10–1.62] .003 1.34 [1.07–1.67] .01 Antidiarrheals Intake vs no 0.87 [0.73–1.04] .12 0.78 [0.63–0.96] .02 Cardiovascular trts Intake vs no 1.20 [1.03–1.41] .02 1.28 [1.07–1.54] .01 Antidiabetics Intake vs no 1.37 [1.07–1.76] .01 1.45 [1.09–1.92] .01 Conclusions Comorbidities related to analyzed ATC classes negatively impact OS and DFS in PETACC8 pts, except antidiarrheal agents which positively impact OS and DFS. Clinical trial identification PETACC8; 2005-003463-23. Legal entity responsible for the study Federation Francophone de Cancerologie Digestive, Dijon. Funding Merck and Sanofi. Disclosure J. Taieb: Advisory / Consultancy: Merck; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Roche Genentech; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Amgen. All other authors have declared no conflicts of interest.

It is difficult to thoroughly explain what leads private enterprises in Burkina Faso into the practice of corruption. The argument most often offered is that corruption provides some gains. In this article, we have attempted to determine if the practice of corruption helps small and medium-sized enterprises (SME) improve their productivity. The data were collected from 351 private SMEs in the two largest cities in Burkina Faso. The survey only covers enterprises dealing in the supply of materials and office supplies. After checking the endogeneity of corruption under the methods of Two-stage Probit least squares (TSPLS) and Heckman two stages, the results indicate that corruption negatively affects the SMEs that practice it at the scale of the entire sector studied. Nevertheless, when considering only the SMEs that take part in the government’s tender invitations, we notice that the SMEs that give bribes are more productive than those that do not. Original Research Article Akouwerabou and Bako; BJEMT, 6(2): 129-144, 2015; Article no.BJEMT.2015.048 130

IF 11.855; International audience; BackgroundOutcome of intermediate risk rectal cancer may be improved by the addition of oxaliplatin during 5-fluoruracil concomitant neoadjuvant chemoradiotherapy. The purpose of this study is to analyze the main clinical results of the ACCORD12 trial (NCT00227747) in rectal cancer after 5 years of follow-up.Patients and methodsInclusion criteria were as follows: rectal adenocarcinoma accessible to digital examination staged T3-T4 Nx M0 (or T2 Nx distal anterior rectum). Two neoadjuvant chemoradiotherapy regimens were randomized: CAP45 (RT 45 Gy + capecitabine) and CAPOX50 (RT 50 Gy + capecitabine and oxaliplatin). Main end point was sterilization of the operative specimen. Acute and late toxicities were prospectively analyzed with dedicated questionnaires.ResultsBetween November 2005 and July 2008, 598 patients were included in the trial. After a median follow-up of 60.2 months, there was no difference between treatment arms in multivariate analysis either for disease-free survival or overall survival (OS) [P = 0.9, hazard ratio (HR)=1.02; 95% confidence interval (CI), 0.76–1.36 and P = 0.3, HR = 0.87; 95% CI, 0.66–1.15, respectively]. There was also no difference of local control in univariate analysis (P = 0.7, HR = 0.92; 95% CI, 0.51–1.66). Late toxicities were acceptable with 1.6% G3 anal incontinence, and

International audience; 4D-MRI is a promising tool for organ exploration, target delineation and treatment planning. Intra-scan motion artifacts may be greatly reduced by increasing the imaging frame rate. However, poor signal-to-noise ratios (SNR) are observed when increasing spatial and/or frame number per physiological cycle, in particular in the abdomen. In the current work, the proposed 4D-MRI method favored spatial resolution, frame number, isotropic voxels and large field-of-view (FOV) during MR-acquisition. The consequential SNR penalty in the reconstructed data is addressed retrospectively using an iterative back-projection (IBP) algorithm. Practically, after computing individual spatial 3D deformations present in the images using a deformable image registration (DIR) algorithm, each 3D image is individually enhanced by fusing several successive frames in its local temporal neighborood, these latter being likely to cover common independent informations. A tuning parameter allows one to freely readjust the balance between temporal resolution and precision of the 4D-MRI. The benefit of the method was quantitatively evaluated on the thorax of 6 mice under free breathing using a clinically acceptable duration. Improved 4D cardiac imaging was also shown in the heart of 1 mice. Obtained results are compared to theoretical expectations and discussed. The proposed implementation is easily parallelizable and optimized 4D-MRI could thereby be obtained with a clinically acceptable duration.

Resume Les infections fongiques sont les infections opportunistes (IO) les plus frequentes au cours de l’infection par le VIH, meme si leur incidence a diminue depuis l’instauration des multitherapies antiretrovirales (cART). Elles sont un bon marqueur de la severite du deficit immunitaire et s’observent generalement chez des patients naifs de traitement, en echec therapeutique ou non observant. La pneumocystose est la seconde IO la plus frequente en France et la cryptococcose reste un probleme majeur dans l’hemisphere sud. Avec le developpement des voyages, les mycoses d’importation sont importantes a connaitre car elles peuvent mimer d’autres infections, notamment une tuberculose. Ces infections ont, pour la grande majorite un tropisme pulmonaire, mais le bilan initial doit toujours tenir compte de la dissemination eventuelle chez les patients VIH+. Les delais d’initiation du traitement cART par rapport aux traitements antifongiques sont etablis en fonction du risque de progression sida en l’absence de cART et du risque de toxicite cumulee et de syndrome de reconstitution immunitaire (IRIS) en cas d’instauration trop precoce. Les infections fongiques chez les patients VIH+ restent donc un probleme d’actualite a l’ere des cART et les IRIS peuvent compliquer la prise en charge et necessitent une gestion therapeutique optimisee.

In France, only a third of demented patients have an established diagnostic of dementia. Hospitalization is often an opportunity to perform a diagnostic of dementia. Real benefits for patients of such a diagnostic process are unknown. The objective of the study was to observe prognosis of elderly patients hospitalized in geriatric courses in terms of mortality, hospitalization rate and entry into an institution. This was a monocentric prospective study with a one-year follow-up of 90 patients hospitalized in an acute geriatric ward with either dementia known by general practitioner, either diagnosed during the hospitalization according to DSM IV criteria. A one year follow-up by phone has been conducted. From a consecutive set of 159 inpatients for 18 weeks, we included in this study 49 patients with a known dementia (group 1, mean age 85.7±4.6 years, mean Mini-mental state examination (MMSE) score 12.4±6.2) and 41 patients with dementia diagnosed during hospitalization (group 2, mean age 88.4±6.4 years, mean MMSE score 16.1±6.5). Differences between the two groups were significant for age (p0.03) and MMSE score (p0.02). One-year mortality rate was near 30% in the 2 groups. Rate of institutionalization was 33% in group 1 and 49% in group 2 (not statistically significant). There was a significant difference in number of days spent at home between group 1 and group 2, respectively 190.9±159.9 days vs 111.1±148.1 days (p0.03). Demented patients previously diagnosed lived longer at home at one year than patients newly diagnosed. These results tend to support the diagnosis of dementia in very elderly patients with multiple comorbidities. Conditions of living at home, in particular the quality of life, should be the object of further studies.

Image registration is part of a large variety of medical applications including diagnosis, monitoring disease progression and/or treatment effectiveness and, more recently, therapy guidance. Such applications usually involve several imaging modalities such as ultrasound, computed tomography, positron emission tomography, x-ray or magnetic resonance imaging, either separately or combined. In the current work, we propose a non-rigid multi-modal registration method (namely EVolution: an edge-based variational method for non-rigid multi-modal image registration) that aims at maximizing edge alignment between the images being registered. The proposed algorithm requires only contrasts between physiological tissues, preferably present in both image modalities, and assumes deformable/elastic tissues. Given both is shown to be well suitable for non-rigid co-registration across different image types/contrasts (T1/T2) as well as different modalities (CT/MRI). This is achieved using a variational scheme that provides a fast algorithm with a low number of control parameters. Results obtained on an annotated CT data set were comparable to the ones provided by state-of-the-art multi-modal image registration algorithms, for all tested experimental conditions (image pre-filtering, image intensity variation, noise perturbation). Moreover, we demonstrate that, compared to existing approaches, our method possesses increased robustness to transient structures (i.e. that are only present in some of the images).

Objective Thermal therapies are rapidly gaining importance in oncology as an alternative to radiotherapy and surgery. The possibility to locally deposit thermal energy in a non-invasive way opens a path towards new therapeutic strategies with improved reliability and reduced associated trauma leading to improved efficacy, reduced hospitalisation and costs. Liver and kidney tumors represent a major health problem because not all patients are suitable for curative treatment with surgery. Currently, radiofrequency is the most used method for percutaneous ablation and the development of a completely non-invasive method based on MR-guided high intensity focused ultrasound (HIFU) treatments is of particular interest, since the energy source is located outside the body. This project addressed technological challenges for the treatment of liver and kidney, related to their motion and their location within the thoracic cage. Material and methods This project proposed safe and non-invasive methods for MR-guided thermal ablation of malignant tumors of liver and kidney with HIFU. Real-time MRI was used to precisely control heat deposition with HIFU within the targeted pathological area despite the motion of these organs, in order to provide an effective treatment with a reduced duration and an increased level of safety for the patient. New technologies were studied for the development of matrix transducers able to generate high acoustic power. Discussion 3D Real-Time MRI guidance of a HIFU intervention as well as intercostal firing were realized in vivo in pig liver during breathing under real-time MR-thermometry over sustained periods of several minutes. The ability to generate acoustic power as high as up to five time the usual level was demonstrated in vitro thanks to the development of the new transducer technology proposed in this project. Conclusion A fully MR-integrated HIFU treatment platform dedicated to the treatment of cancer in mobile abdominal organs was developed.

The aging of our population and the frequent occurrence of cancer warrants the adaptation of our management strategies in medical and surgical geriatric oncology. Geriatric assessment, including knowledge of the autonomy of patients and their comorbidities is needed to consider the best treatment, including when it comes to surgery. Delirium is the most common complication observed in the postoperative period. Knowledge of risk factors for the occurrence of this syndrome should be a part of good practice. Proximity between surgeons, anesthesists and geriatricians should improve the quality of care given to elderly patients with cancer.

International audience; This study investigated the long-term outcome of patients with tuberculosis (TB) as a complication of tumour necrosis factor (TNF)-alpha blocker therapy. All TB cases (n = 21) complicating TNF-alpha blocker therapy from French university hospitals were collated between January 2000 and September 2002. Outcome was assessed via a postal questionnaire during September 2005. The mortality rate after 4 years was 4.8%, and one patient had relapsed and six (29%) patients had recommenced TNF-alpha antagonist treatment, after appropriate anti-TB therapy, without reactivation. These data support the concept that TNF-alpha antagonists can be restarted in TB patients provided that adequate anti-TB treatment has been completed.

International audience; BACKGROUND:Metastatic colorectal cancer (mCRC) frequently occurs in elderly patients. However, data from a geriatric tailored randomized trial about tolerance to and the efficacy of doublet chemotherapy (CT) with irinotecan in the elderly are lacking. The benefit of first-line CT intensification remains an issue in elderly patients.PATIENTS AND METHODS:Elderly patients (75+) with previously untreated mCRC were randomly assigned in a 2 × 2 factorial design (four arms) to receive 5-FU (5-fluorouracil)-based CT, either alone (FU: LV5FU2 or simplified LV5FU2) or in combination with irinotecan [IRI: LV5FU2-irinotecan or simplified LV5FU2-irinotecan (FOLFIRI)]. The CLASSIC arm was defined as LV5FU2 or LV5FU2-irinotecan and the SIMPLIFIED arm as simplified LV5FU2 or FOLFIRI. The primary end point was progression-free survival (PFS). Secondary end points were overall survival (OS), safety and objective response rate (ORR).RESULTS:From June 2003 to May 2010, 71 patients were randomly assigned to LV5FU2, 71 to simplified LV5FU2, 70 to LV5FU2-irinotecan and 70 to FOLFIRI. The median age was 80 years (range 75-92 years). No significant difference was observed for the median PFS: FU 5.2 months versus IRI 7.3 months, hazard ratio (HR) = 0.84 (0.66-1.07), P = 0.15 and CLASSIC 6.5 months versus SIMPLIFIED 6.0 months, HR = 0.85 (0.67-1.09), P = 0.19. The ORR was superior in IRI (P = 0.0003): FU 21.1% versus IRI 41.7% and in CLASSIC (P = 0.04): CLASSIC 37.1% versus SIMPLIFIED 25.6%. Median OS was 14.2 months in FU versus 13.3 months in IRI, HR = 0.96 (0.75-1.24) and 15.2 months in CLASSIC versus 11.4 months in SIMPLIFIED, HR = 0.71 (0.55-0.92). More patients presented grade 3-4 toxicities in IRI (52.2% versus 76.3%).CONCLUSION:In this elderly population, adding irinotecan to an infusional 5-FU-based CT did not significantly increase either PFS or OS. Classic LV5FU2 was associated with an improved OS compared with simplified LV5FU2.CLINICALTRIALSGOV:NCT00303771.

Many techniques of thermotherapy have emerged over the last several years in the field of oncology using different types of physical agents, including ultrasound. Only ultrasound can target deep seated lesions non-invasively without need for percutaneous probe insertion. Depending on their utilization, it is possible to select either thermal effects, in a continuous mode, at low temperature (allowing thermo-induced biological effects) or at high temperature (allowing thermoablation), or mechanical effects, in a pulsed mode, at low energy level (allowing biological effects) or at high energy levels (histotripsy). Thermoablation by focused ultrasound is now developing fast for applications in many organs. It gained a well defined role for the treatment of prostatic cancer and uterine leiomyoma but needs to be better evaluated in other organs such as the breast. Treatment of abdominal tumors must still be considered as experimental as long as problems related to acoustic interfaces (produced by ribs and gas) and movement correction are not resolved. Biological applications of focused ultrasound are currently being explored and have a great long term potential.

Objectives To compare the coverage for the third dose and the compliance to two hepatitis B vaccination schedules: 0,1,4 versus 0,1,6 months, in commercial sex workers (CSW) in Belgium; to compare the immunogenicity of the actually administered schedules. Methods In seven health centres in Belgium, hepatitis B vaccination was offered free of charge to CSW. In a randomised, prospective study a commercialised hepatitis B vaccine (Engerix-B™ 20 mcgr) was offered according to one of both schedules. After complete vaccination, bleeding was performed to assess immunogenicity. Results Between June 2003 and September 2004, 615 non-immune CSW were enrolled, of whom 52% in the 0,1,4 month schedule (n = 322). Coverage of the third dose was 57% overall, 59% (0,1,4) and 54% (0,1,6), respectively. Age, the health centre and drug use significantly influenced the compliance and the coverage of dose 3, whereas the planned vaccination did not. When comparing the immunogenicity results as a function of the actually administered vaccination schedule, immune responses did not significantly differ between CSW receiving the third dose 4–6 months and those receiving it at least 6 months after the first dose. In total, 19 persons (8%) were not protected after a full vaccination course (anti-HBs Conclusions In this highly mobile at-risk population, a 0,1,4 month schedule is more easy to offer and confers equal protection within a shorter period of time. We therefore propose this 0,1,4 month schedule to vaccinate CSW in the future.

International audience; Focal High-Dose-Rate (HDR) for prostate cancer has gained an increasing interest as an alternative to whole gland therapy as it may contribute to reduction of treatment related toxicity. For focal treatment, optimal needle guidance and placement is warranted. This can be achieved under MRI guidance. However, MRI-guided needle placement is currently not possible due to space restrictions in the closed MR bore. To overcome this problem, a MR-compatible, single-divergent needle-implant robotic device is under development at the University Medical Centre, Utrecht (UMCU): placed between the legs of the patient inside the MR bore, this robot will tap the needle in a divergent pattern from a single rotation point into the tissue. This rotation point is just beneath the perineal skin to have access to the focal prostate tumor lesion. Currently, there is no treatment planning system commercially available which allows optimization of the dose distribution with such needle arrangement. The aim of this work is to develop an automatic inverse dose planning optimization tool for focal HDR prostate brachytherapy with needle insertions in a divergent configuration. A complete optimizer workflow is proposed which includes the determination of (1) the position of the center of rotation, (2) the needle angulations and (3) the dwell times. Unlike most currently used optimizers, no prior selection or adjustment of input parameters such as minimum or maximum dose or weight coefficients for treatment region and organs at risk is required. To test this optimizer, a planning study was performed on 10 patients (treatment volumes ranged from 8.5cm 3 to 23.3cm 3 ) by using 2 to 14 needle insertions. The total computation time of the optimizer workflow was below 20 minutes and a clinically acceptable plan was reached on average using only four needle insertions.

Image processing such as deformable image registration finds its way into radiotherapy as a means to track non-rigid anatomy. With the advent of magnetic resonance imaging (MRI) guided radiotherapy, intrafraction anatomy snapshots become technically feasible. MRI provides the needed tissue signal for high-fidelity image registration. However, acquisitions, especially in 3D, take a considerable amount of time. Pushing towards real-time adaptive radiotherapy, MRI needs to be accelerated without degrading the quality of information. In this paper, we investigate the impact of image resolution on the quality of motion estimations. Potentially, spatially undersampled images yield comparable motion estimations. At the same time, their acquisition times would reduce greatly due to the sparser sampling. In order to substantiate this hypothesis, exemplary 4D datasets of the abdomen were downsampled gradually. Subsequently, spatiotemporal deformations are extracted consistently using the same motion estimation for each downsampled dataset. Errors between the original and the respectively downsampled version of the dataset are then evaluated. Compared to ground-truth, results show high similarity of deformations estimated from downsampled image data. Using a dataset with (2.5 mm)3 voxel size, deformation fields could be recovered well up to a downsampling factor of 2, i.e. (5 mm)3. In a therapy guidance scenario MRI, imaging speed could accordingly increase approximately fourfold, with acceptable loss of estimated motion quality.

Despite increasing reports of human infection, data about the optimal care of Phaeoacremonium infections are missing. We report a case of an infection due to Phaeoacremonium parasiticum and Paraconiothyrium cyclothyrioides , initially localized to skin and soft tissue, in a kidney transplant patient. Despite surgical drainage and excision of the lesion and combination antifungal therapy with voriconazole and liposomal amphotericin B, a disseminated infection involving the lungs and brain developed and led to death. We performed a systematic literature review to assess the general features and outcome of human infections due to Phaeoacremonium species. Thirty-six articles were selected, and 42 patients, including ours, were reviewed. Thirty-one patients (74%) were immunocompromised because of organ or bone marrow transplantation ( n = 17), diabetes or glucose intolerance ( n = 10), rheumatoid arthritis or Still's disease ( n = 4), chronic hematological diseases ( n = 3), or chronic granulomatous disease ( n = 3). Ten patients (24%) reported initial cutaneous trauma. Skin and soft tissue infections represented 57% of infections ( n = 24), and disseminated infections, all occurring in immunocompromised patients, represented 14% of infections ( n = 6). The main antifungal drugs used were azoles ( n = 41) and amphotericin B ( n = 16). Surgical excision or drainage was performed in 64% of cases ( n = 27). The cure rate was 67% ( n = 28). There were 10% cases of treatment failure or partial response ( n = 4), 19% relapses ( n = 8), and 7% losses to follow-up ( n = 3). The death rate was 19% ( n = 8). Management of Phaeoacremonium infections is complex because of slow laboratory identification and limited clinical data, and treatment relies on a combination of surgery and systemic antifungal therapy.

International audience; no abstract

MR-guided HIFU ablation is a promising technique for the non-invasive treatment of breast cancer. A phase I study was performed to assess the safety and treatment accuracy and precision of MR-HIFU ablation in breast cancer patients (n=10) using a newly developed MR-HIFU platform dedicated to applications in the breast. In this paper a technical analysis of the performance of the dedicated breast MR-HIFU system during breast tumors ablation is described. The main points of investigation were the spatial targeting accuracy and precision of the system and the performance of real-time respiration-corrected MR thermometry.The mean targeting accuracy was in the range of 2.4-2.6 mm, whereas the mean targeting precision was in the range of 1.5-1.8 mm. To correct for respiration-induced magnetic field fluctuations during MR temperature mapping a look-up-table (LUT)-based correction method was used. An optimized procedural sedation protocol in combination with the LUT-based correction method allowed for precise MR thermometry during the ablation procedure (temperature standard deviation3 °C). No unwanted heating in the near field (i.e. skin) nor in the far field (pectoral muscle) was detected.The newly developed dedicated breast MR-HIFU system allows for safe, accurate and precise ablation of breast tumors.

Summary. In industrialized countries, transmission of hepatitis C occurs primarily through injecting drug use. Transmission of hepatitis C in injecting drug users is mainly associated with the sharing of contaminated syringes/needles, although evidence for risk of hepatitis C infection through sharing of other injecting paraphernalia is increasing. In this paper, the independent effects of sharing paraphernalia other than syringes/needles have been estimated. The prevalence and force of infection were modelled using three serological data sets from drug users in three centres in Belgium as a function of the sharing behaviour. It was found that sharing of materials other than syringes/needles indeed seemed to contribute substantially to the spread of hepatitis C among injecting drug users.

A 10-year-old, neutered male Cairn terrier was examined after experiencing intermittent vomiting of several months' duration and sudden onset of acute depression. Abdominal ultrasound examination revealed an adrenal mass invading the suprarenal part of the caudal vena cava. The vascular invasion could not be corrected so en bloc ligation/excision of the adrenal neoplasm and the suprarenal part of the vena cava was performed. Microscopic examination identified an adrenal phaeochromocytoma. The dog recovered well and had no significant vascular or renal dysfunction at follow-up 20 months after surgery. To the authors' knowledge, this is the first report of a dog surviving long term after resection of the suprarenal caudal vena cava.

International audience; Purpose. We have previously demonstrated the feasibility of monitoring ultrasound-mediated uptake of a hydrophilic model drug in real time with dynamic confocal fluorescence microscopy. In this study, we evaluate and correct the impact of photobleaching to improve the accuracy of pharmacokinetic parameter estimates.Procedures. To model photobleaching of the fluorescent model drug SYTOX Green, a photobleaching process was added to the current two-compartment model describing cell uptake. After collection of the uptake profile, a second acquisition was performed when SYTOX Green was equilibrated, to evaluate the photobleaching rate experimentally.Results. Photobleaching rates up to 5.0 10-3 s-1 were measured when applying power densities up to 0.2 W.cm-2. By applying the three-compartment model, the model drug uptake rate of 6.0 10-3 s-1 was measured independent of the applied laser power.Conclusions. The impact of photobleaching on uptake rate estimates measured by dynamic fluorescence microscopy was evaluated. Subsequent compensation improved the accuracy of pharmacokinetic parameter estimates in the cell population subjected to sonopermeabilization.

En hepato-gastroenterologie, les condamnations pour faute technique sont relativement rares. Par contre, les condamnations pour defaut d’information sont de plus en plus frequentes, conduisant a des indemnisations parfois aussi elevees qu’en cas de faute technique. Les processus d’information et de CE du patient sont des outils efficaces de prevention des complications et de leurs suites judiciaires. Ces processus ne sont pas seulement une obligation legale, ils constituent une reelle opportunite d’amelioration de la qualite des soins. Bien que l’entretien individuel entre le patient et le medecin en soit le pivot, le recours a l’ecrit est une aide significative pour ameliorer la qualite des processus d’information et de CE en pratique courante. Encore faut-il que les documents utilises soient valides et irreprochables. Les fiches d’information de la SFED et de la SNFGE peuvent et doivent encore etre ameliorees en tenant compte des recommandations de l’ANAES [9]. En particulier, elles devraient etre revisees en partenariat avec des associations de patients. Pour la fiche coloscopie, le risque d’une colostomie provisoire devrait probablement etre signale. De meme, le patient devrait etre informe des limites de l’examen et que, bien que faite dans les regles de l’art, la coloscopie peut manquer des polypes, voire des cancers. Les schemas des differentes fiches pourraient etre ameliores de facon a etre utilisables pour eclairer le patient sur son propre cas. Enfin, un formulaire standardise de CE devrait etre elabore qui pourrait s’inspirer du formulaire que nous avons redige avec un groupe de patients.

International audience; We report 3 consecutive episodes of invasive aspergillosis in a single hematopoietic stem cell transplant patient successively attributed to TR(34) /L98H azole-resistant Aspergillus fumigatus and to a first occurrence of invasive Emericella sublata infection. This case illustrates potential selection of resistant molds during antifungal therapy in hematological patient.

MR spectroscopy of the posterior fossa is pitted with numerous technical difficulties. It is, however, of great clinical interest in the study of the degenerative diseases and tumors of this area. We have developed a method to perform 2D CSI of this area, by using a sagittal slice and a careful positioning of outer volume saturation. We performed this acquisition in 30 healthy volunteers to determine the normal metabolic ratios in five voxels of this area (mesencephalon, pons, medulla oblongata, vermis, cerebellar white matter). The main technical difficulty was magnetic field inhomogeneity in the lower brainstem generated by dental alloys. However, 88% of the voxels were of sufficient quality to be analyzed. The statistically significant regional variations were a higher NAA/Cr ratio in the pons than in the medulla oblongata, higher Cho/Cr in the pons than in the mesencephalon and higher Cho/Cr in the cerebellar white matter than in the vermis. We conclude that 2D CSI of the brainstem, although technically delicate can be performed in most patients.

L'auteur rappelle la legislation et les recommandations en vigueur en France en matiere d'information des patients. Il precise les modalites d'application des textes en pratique quotidienne en tenant compte de la jurisprudence. Les rares etudes evaluant les fiches francaises d'informations medicales en endoscopie digestive sont rapportees. La question de l'information du patient a l'heure de l'endoscopie «openaccess» est abordee de meme que le probleme du consentement eclaire signe. Enfin, l'auteur propose quelques pistes d'amelioration dans les domaines de l'information du patient et du consentement eclaire.

To design safety automated systems, the designer must study safety according to various points of view. This paper deals with safety analysis at the stage of control architecture design. The benefits of our work is the taking into account of both software and hardware aspects of the control to analyze the system safety. We illustrate our matter with an example: a cable car system. Several control architectures are considered. First, the reliability of a critical function is analyzed. This analysis will support the choice of an architecture rather than an other one. Second, the performances of suggested architectures are evaluated. This evaluation obtained with a Petri nets simulation will allow us to qualify the critical functions.

We report a case of a 71-year-old woman with carcinoid heart disease admitted in ICU after tricuspid valve replacement. She quickly developed a acute heart right failure. Optimal medical treatment failed and we implanted ventricular assistance. After 10 days of support, patient improved and the right ventricle recovered. Temporary devices can provide a successful bridge to cardiac recovery. However, the risk of infection that is a major prognosis factor should be carefully considered particularly when temporary assistance implanted on immunosuppressed patients.

Purpose: To develop adaptive planning with feedback for MRI-guided focal HDR prostate brachytherapy with a single divergent needle robotic implant device. After each needle insertion, the dwell positions for that needle are calculated and the positioning of remaining needles and dosimetry are both updated based on MR imaging. Methods: Errors in needle positioning may occur due to inaccurate needle insertion (caused by e.g. the needle’s bending) and unpredictable changes in patient anatomy. Consequently, the dose plan quality might dramatically decrease compared to the preplan. In this study, a procedure was developed to re-optimize, after each needle insertion, the remaining needle angulations, source positions and dwell times in order to obtain an optimal coverage (D95% PTV>19 Gy) without exceeding the constraints of the organs at risk (OAR) (D10% urethra

Recent developments made MRI-guided radiotherapy feasible. Simultaneously performed imaging during dose delivery reveals the influence of changes in anatomy not yet known at the planning stage. When targeting highly motile abdominal organs, respiratory gating is commonly employed in MRI and investigated in external beam radiotherapy to mitigate malicious motion effects. The purpose of the presented work is to investigate anatomy-adaptive dose reconstruction in the treatment of abdominalorgans using concurrent (duplex) gating of an integrated MRlinac modality.Using navigators, 3D-MR images were sampled during exhale phase, requiring 3s per axial volume (360×260×100mm{sup 3}, waterselective T1w-FFE). Deformation vector fields (DVF) were calculated for all imaging dynamics with respect to initial anatomy, yielding an estimation of anatomy changes over the time of a fraction. A pseudo-CT was generated from the outline of a reference MR image, assuming a water-filled body. Consecutively, a treatment was planned on a fictional kidney lesion and optimized simulating a 6MV linac in a 1.5T magnetic field. After delivery, using the DVF, the pseudo-CT was deformed and dose accumulated for every individual gating interval yielding the true accumulated dose on the dynamic anatomy during beam-on.Dose-volume parameters on the PTV show only moderate changes when incorporating motion, i.e. ΔD{sub 99} (GTV)=0.3Gymore » with D{sub 99} (GTV)=20Gy constraints. However, local differences in the PTV region showed underdosages as high as 2.7Gy and overdosages up to 1.4Gy as compared to the optimized dose on static anatomy.A dose reconstruction toolchain was successfully implemented and proved its potential in the duplex gated treatment of abdominal organs by means of an MR-linac modality. While primary dose constraints were not violated on the fictional test data, large deviations could be found locally, which are left unaccounted for in conventional treatments. Dose-tracking of both target structures and organs at risk using 3D MRI during treatment enables truly adaptive hypofractionated radiotherapy. This work was funded by the SoRTS consortium, which includes the industry partners Elekta, Philips and Technolution.« less