Cross validation of experts versus registration methods for target localization in deep brain stimulation.

In the last five years, Deep Brain Stimulation (DBS) has become the most popular and effective surgical technique for the treatent of Parkinson's disease (PD). The Subthalamic Nucleus (STN) is the usual target involved when applying DBS. Unfortunately, the STN is in general not visible in common medical imaging modalities. Therefore, atlas-based segmentation is commonly considered to locate it in the images. In this paper, we propose a scheme that allows both, to perform a comparison between different registration algorithms and to evaluate their ability to locate the STN automatically. Using this scheme we can evaluate the expert variability against the error of the algorithms and we demonstrate that automatic STN location is possible and as accurate as the methods currently used.

Cancer du sein: radiothérapie et signalisation oestrogénique [Breast cancer: radiotherapy and estrogen signaling].

Hormone receptors are expressed in more than 75% of breast cancer. Therefore, two prescription modalities of endocrine therapy could be proposed: either sequential or concomitant to breast cancer irradiation. If combined to radiotherapy, is endocrine therapy a radiosensitizer? Does endocrine therapy enhance the risk factor of radio-induced toxicity? Here, we will distinguish the interaction of ionizing radiation combined with therapies targeting oestrogen receptor (REα) from the interaction of ionizing radiation with oestrogen. This review aims at making clear all these items.

Fractures du calcanéum: du traumatisme aux séquelles [Fractures of the calcaneus: the injury and its sequelae]

The calcaneus gives shape to the heel. Its special position places it in direct contact with the floor, upon which rests the weight of the body. It assures the transition between the vertical skeleton and horizontal surface of the foot, thus permitting ambulation. The calcaneus is subjected to high physical stress, yet at the same time its complex articulating surfaces permit fine adaptation to the ground. Fractures of the calcaneus result from a high energy injury, usually a fall from a height. The treatment of such fractures poses difficult problems. The functional sequelae of the injury may be severe, prolonged, and frequently results in a permanent disability. This is due not only to the type of fracture, but the orthopaedic management as well. Careful evaluation of the patient, fracture pattern, soft tissue condition, and treatment modalities is obligatory to achieve the optimal result.

Drug utilisation in a neonatal intensive care unit of a swiss university hospital

Introduction Medication errors in hospitalsmay occur at any step of the medication process including prescription, transcription, preparation and administration, and may originate with any of the actors involved. Neonatal intensive care units (NICU) take care of extremely frail patients in whom errors could have dramatic consequences. Our objective was to assess the frequency and nature of medication errors in the NICU of a university hospital in order to propose measures for improvement.Materials & Methods The design was that of an observational prospective study over 4 consecutivemonths. All patients receiving C 3drugs were included. For each patient, observations during the different stages were compiled in a computer formulary and compared with the litterature. Setting: The 11-bed NICU of our university hospital.Main outcome measures:(a) Frequency and nature of medication errors in prescription,transcription, preparation and administration.(b) Drugs affected by errors.Results 83 patients were included. 505 prescriptions and transcriptions, 447 preparations and 464 administrations were analyzed. 220 medications errors were observed: 102 (46.4%) at prescription, 25 (11.4%) at transcription, 19 (8.6%) at preparation and 73 (33.2%) at administration. Uncomplete/ambiguous orders (24; 23.5%) were the most common errors observed at prescription, followed by wrong name (21; 20.6%), wrong dose (17; 16.7%) and omission (15; 14.7%). Wrong time (33; 45.2%) and wrong administration technique (31; 42.5%) were the most important medication errors during administration. According to the ATC classification, systemic antibacterials (53; 24.1%) were the most implicated, followed by perfusion solutions (40; 18.2%), respiratory system products (30; 13.6%), and mineral supplements and antithrombotic agents (20; 9.1%).Discussions, Conclusion Proposed recommendations: ? Better teaching of neonatal prescription to medical interns;? Improved prescription form to avoid omissions and ambiguities;? Development of a neonatal drug formulary, including prescription,preparation and administration modalities to reduce errors at different stages;? Presence of a clinical pharmacist in the NICU.Disclosure of Interest None Declared

New insights into the mechanisms of organ-specific breast cancer metastasis.

Despite the substantial advances obtained in the treatment of localized malignancies, metastatic disease still lacks effective treatment and remains the primary cause of cancer mortality, including in breast cancer. Thus, in order to improve the survival of cancer patients it is necessary to effectively improve prevention or treatment of metastasis. To achieve this goal, complementary strategies can be envisaged: the first one is the eradication of established metastases by adding novel modalities to current treatments, such as immunotherapy or targeted therapies. A second one is to prevent tumor cell dissemination to secondary organs by targeting specific steps governing the metastatic cascade and organ-specific tropism. A third one is to block the colonization of secondary organs and subsequent cancer cell growth by impinging on the ability of disseminated cancer cells to adapt to the novel microenvironment. To obtain optimal results it might be necessary to combine these strategies. The development of therapeutic approaches aimed at preventing dissemination and organ colonization requires a deeper understanding of the specific genetic events occurring in cancer cells and of the host responses that co-operate to promote metastasis formation. Recent developments in the field disclosed novel mechanisms of metastasis. In particular the crosstalk between disseminated cancer cells and the host microenvironment is emerging as a critical determinant of metastasis. The identification of tissue-specific signals involved in metastatic progression will open the way to new therapeutic strategies. Here, we will review recent progress in the field, with particular emphasis on the mechanisms of organ specific dissemination and colonization of breast cancer.

A Playful Glance at Hierarchical Questions for Two-Way Alternating Automata

Two-way alternating automata were introduced by Vardi in order to study the satisfiability problem for the modal μ-calculus extended with backwards modalities. In this paper, we present a very simple proof by way of Wadge games of the strictness of the hierarchy of Motowski indices of two-way alternating automata over trees.

Effect of repetitive arm cycling following botulinum toxin injection for poststroke spasticity: evidence from FMRI.

BACKGROUND AND OBJECTIVE: Investigations were performed to establish if repetitive arm cycling training enhances the antispastic effect of intramuscular botulinum toxin (BTX) injections in postischemic spastic hemiparesis. Effects on cerebral activation were evaluated by functional magnetic resonance imaging (fMRI). METHODS: Eight chronic spastic hemisyndrome patients (49 ± 10 years) after middle cerebral artery infarction (5.5 ± 2.7 years) were investigated. BTX was injected into the affected arm twice, 6 months apart. Spasticity was assessed using the Ashworth Scale and range of motion before and 3 months after BTX injections. Images were analyzed using Brain Voyager QX 1.8, and fMRI signal changes were corrected for multiple comparisons. RESULTS: During passive movements of affected and nonaffected hands, fMRI activity was increased bilaterally in the sensorimotor cortex (MISI), secondary somatosensory areas (SII), and supplementary motor area predominantly in the contralesional hemisphere, compared with the rest. Following repetitive arm cycling, fMRI activity increased further in MISI of the lesioned hemisphere and SII of the contralesional hemisphere. For patients with residual motor activity, treatment-related fMRI activity increases were associated with reduced spasticity; in completely plegic patients, there was no fMRI activity change in SII but increased spasticity after training. CONCLUSION: Increased activity in SII of the contralesional hemisphere and in MISI of the lesioned hemisphere reflect a treatment-induced effect in the paretic arm. It is hypothesized that the increased BOLD activity results from increased afferent information related to the antispastic BTX effect reinforced by training.

Generative FDG-PET and MRI model of aging and disease progression in Alzheimer's disease.

The failure of current strategies to provide an explanation for controversial findings on the pattern of pathophysiological changes in Alzheimer's Disease (AD) motivates the necessity to develop new integrative approaches based on multi-modal neuroimaging data that captures various aspects of disease pathology. Previous studies using [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) and structural magnetic resonance imaging (sMRI) report controversial results about time-line, spatial extent and magnitude of glucose hypometabolism and atrophy in AD that depend on clinical and demographic characteristics of the studied populations. Here, we provide and validate at a group level a generative anatomical model of glucose hypo-metabolism and atrophy progression in AD based on FDG-PET and sMRI data of 80 patients and 79 healthy controls to describe expected age and symptom severity related changes in AD relative to a baseline provided by healthy aging. We demonstrate a high level of anatomical accuracy for both modalities yielding strongly age- and symptom-severity- dependant glucose hypometabolism in temporal, parietal and precuneal regions and a more extensive network of atrophy in hippocampal, temporal, parietal, occipital and posterior caudate regions. The model suggests greater and more consistent changes in FDG-PET compared to sMRI at earlier and the inversion of this pattern at more advanced AD stages. Our model describes, integrates and predicts characteristic patterns of AD related pathology, uncontaminated by normal age effects, derived from multi-modal data. It further provides an integrative explanation for findings suggesting a dissociation between early- and late-onset AD. The generative model offers a basis for further development of individualized biomarkers allowing accurate early diagnosis and treatment evaluation.

Photodynamic therapy as an adjunct to surgery for malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM) is increasingly observed in industrial countries. Despite concerted efforts and combined treatments including surgery, chemotherapy and irradiation patients eventually succumb from relentless local progression of the disease. Recent publications have demonstrated an improved response rate with the cytostatic agent pemetrexed which will be tested in a neoadjuvant setting followed by surgery. However, effective tumor control requires new loco-regional treatment modalities, eventually in combination with neoadjuvant chemotherapy. Intraoperative photodynamic therapy (PDT) of the chest cavity has been proposed as an attractive treatment concept for MPM since a selective treatment of the tumor bed following resection has the potential to improve local tumor control. It has been shown to afford tumor destruction in patients with mesothelioma but efficiency and selectivity is not yet sufficient for routine clinical application. Experimental work on MPM has shown that tumor selectivity of PDT depend on treatment conditions and can be improved by structural modification and improved targeting of the sensitizers. Refinements of PDT for mesothelioma will depend on a more detailed understanding of the pathways for preferential sensitizer accumulation within the tumor as well as on synergistic effects between PDT and chemotherapeutic agents.

Traitement des plagiocéphalies postérieures d'origine positionnelle [Treatment of posterior positional plagiocephaly]

In 1992, the American academy of paediatrics has recommended that infants be placed on their backs to sleep, because prone sleeping has been correlated with sudden infant death syndrome. Following this article, medical paediatric community has documented an exponential increase in the diagnosis of posterior cranial deformities, which were considered as the consequence of unrelieved pressure onto the occiput during infant sleep. These last 15 years, management of posterior positional plagiocephaly has evolved but is still not standardized; it varies according to local specificities, and medical or parental preferences. Treatment of deformational plagiocephaly includes preventive counseling, repositioning adjustments and exercises, physiotherapy, osteopathy, treatment by dynamic cranial orthosis. On extremely rare occasions, corrective surgery is proposed. This article aims at reviewing the epidemiologic, diagnostic, and various therapeutic options of posterior positional plagiocephaly.

Simultaneous measurement of regional cerebral blood flow by perfusion CT and stable xenon CT: a validation study.

BACKGROUND AND PURPOSE: Knowledge of cerebral blood flow (CBF) alterations in cases of acute stroke could be valuable in the early management of these cases. Among imaging techniques affording evaluation of cerebral perfusion, perfusion CT studies involve sequential acquisition of cerebral CT sections obtained in an axial mode during the IV administration of iodinated contrast material. They are thus very easy to perform in emergency settings. Perfusion CT values of CBF have proved to be accurate in animals, and perfusion CT affords plausible values in humans. The purpose of this study was to validate perfusion CT studies of CBF by comparison with the results provided by stable xenon CT, which have been reported to be accurate, and to evaluate acquisition and processing modalities of CT data, notably the possible deconvolution methods and the selection of the reference artery. METHODS: Twelve stable xenon CT and perfusion CT cerebral examinations were performed within an interval of a few minutes in patients with various cerebrovascular diseases. CBF maps were obtained from perfusion CT data by deconvolution using singular value decomposition and least mean square methods. The CBF were compared with the stable xenon CT results in multiple regions of interest through linear regression analysis and bilateral t tests for matched variables. RESULTS: Linear regression analysis showed good correlation between perfusion CT and stable xenon CT CBF values (singular value decomposition method: R(2) = 0.79, slope = 0.87; least mean square method: R(2) = 0.67, slope = 0.83). Bilateral t tests for matched variables did not identify a significant difference between the two imaging methods (P >.1). Both deconvolution methods were equivalent (P >.1). The choice of the reference artery is a major concern and has a strong influence on the final perfusion CT CBF map. CONCLUSION: Perfusion CT studies of CBF achieved with adequate acquisition parameters and processing lead to accurate and reliable results.

Cross-sectional analysis of testosterone therapies in hypopituitary men on stable pituitary hormone replacement.

OBJECTIVE: The last decade has seen a proliferation in options for testosterone replacement. However, little is known as to the benefits of different treatment modalities. Our objective was to determine the testosterone prescription pattern and to examine the impact on various outcome measures. SUBJECTS AND METHODS: A total of 816 adult-onset hypopituitary males on stable pituitary replacement for at least 1 year were identified from the KIMS database. Patients were classified as either eugonadal (n = 106), or hypogonadal (n = 710) on intramuscular (IM, n = 558), oral (n = 74), transdermal (n = 61), and depot (n = 17) testosterone. RESULTS: After 1 year of stable pituitary replacement therapy, body composition, cardiovascular parameters, GH replacement and quality of life were not significantly different in androgen-replaced hypogonadal patients compared to eugonadal patients. There were no differences in outcome variables within the hypogonadal group according to the testosterone replacement regimen used and no difference in response to GH therapy. CONCLUSIONS: The majority of hypopituitary patients in the last decade have received IM testosterone. Body composition, cardiovascular parameters, GH replacement and quality of life were not different between eugonadal and hypogonadal patients and were not differentially affected by the mode of testosterone replacement. These findings are reassuring that there is no major difference in response to different testosterone replacement regimens.

Auditory-somatosensory multisensory interactions in humans: dissociating detection and spatial discrimination.

Simple reaction times (RTs) to auditory-somatosensory (AS) multisensory stimuli are facilitated over their unisensory counterparts both when stimuli are delivered to the same location and when separated. In two experiments we addressed the possibility that top-down and/or task-related influences can dynamically impact the spatial representations mediating these effects and the extent to which multisensory facilitation will be observed. Participants performed a simple detection task in response to auditory, somatosensory, or simultaneous AS stimuli that in turn were either spatially aligned or misaligned by lateralizing the stimuli. Additionally, we also informed the participants that they would be retrogradely queried (one-third of trials) regarding the side where a given stimulus in a given sensory modality was presented. In this way, we sought to have participants attending to all possible spatial locations and sensory modalities, while nonetheless having them perform a simple detection task. Experiment 1 provided no cues prior to stimulus delivery. Experiment 2 included spatially uninformative cues (50% of trials). In both experiments, multisensory conditions significantly facilitated detection RTs with no evidence for differences according to spatial alignment (though general benefits of cuing were observed in Experiment 2). Facilitated detection occurs even when attending to spatial information. Performance with probes, quantified using sensitivity (d'), was impaired following multisensory trials in general and significantly more so following misaligned multisensory trials. This indicates that spatial information is not available, despite being task-relevant. The collective results support a model wherein early AS interactions may result in a loss of spatial acuity for unisensory information.

Therapeutic concepts in adult and paediatric eosinophilic oesophagitis.

Eosinophilic oesophagitis (EoE) was first described in the early 1990s. Although initially reported to be a rare entity, EoE has rapidly become a regularly diagnosed disease with a prevalence of approximately 1 in 2,000 individuals in the USA and Europe. The disease is characterized by a combination of oesophageal dysfunction and predominant eosinophilic infiltration of the oesophageal tissue. At diagnosis, other diseases that can be associated with oesophageal eosinophilic infiltration must be ruled out. Children with EoE present with a wide variety of symptoms, whereas adults mostly present with dysphagia for solid food and chest pain. Histologic features of EoE resemble those of T-helper type 2 inflammation. Endoscopy should be carried out to establish the diagnosis, but endoscopic abnormalities are not pathognomonic for EoE and the examination might not show histologic abnormality. Treatment modalities for EoE include drugs (corticosteroids, PPIs, antiallergic and biologic agents), hypoallergenic diets and oesophageal dilatation for strictures that are unresponsive to medical therapy. Unresolved eosinophilic inflammation leads to the formation of oesophageal strictures, which probably increase the risk of food bolus impactions. To date, long-term strategies for the therapeutic management of this chronic inflammatory disease remain poorly defined.

Glucose metabolism, gray matter structure, and memory decline in subjective memory impairment.

OBJECTIVE: To identify biological evidence for Alzheimer disease (AD) in individuals with subjective memory impairment (SMI) and unimpaired cognitive performance and to investigate the longitudinal cognitive course in these subjects. METHOD: [¹⁸F]fluoro-2-deoxyglucose PET (FDG-PET) and structural MRI were acquired in 31 subjects with SMI and 56 controls. Cognitive follow-up testing was performed (average follow-up time: 35 months). Differences in baseline brain imaging data and in memory decline were assessed between both groups. Associations of memory decline with brain imaging data were tested. RESULTS: The SMI group showed hypometabolism in the right precuneus and hypermetabolism in the right medial temporal lobe. Gray matter volume was reduced in the right hippocampus in the SMI group. At follow-up, subjects with SMI showed a poorer performance than controls on measures of episodic memory. Longitudinal memory decline in the SMI group was associated with reduced glucose metabolism in the right precuneus at baseline. CONCLUSION: The cross-sectional difference in 2 independent neuroimaging modalities indicates early AD pathology in SMI. The poorer memory performance at follow-up and the association of reduced longitudinal memory performance with hypometabolism in the precuneus at baseline support the concept of SMI as the earliest manifestation of AD.