Atypical location of intracranial germinoma: a case report.

peer reviewe

Pain complaints in a patient with schizophrenia

peer reviewedSchizophrenia is a complex pathology. Its prevalence reaches almost 1 %. Its semiology can be diversified. Sensorial perception can be altered included pain perception. Most of the studies conclude that psychotic patients have a hypoalgesia. It's important to consider this fact to avoid missing potentially grave somatic disease

L'ERETHISME CARDIAQUE

editorial reviewe

Mode of administration of glucocorticoids and osteonecrosis in children treated for acute lymphoblastic leukemia: An update

peer reviewedEn tant que tumeur pédiatrique la plus fréquente, de surcroît grevée d’un excellent pronostic global, la leucémie lymphoblastique aiguë (LAL) représente la plus grande pourvoyeuse de survivants exposés à la toxicité des traitements chimiothérapeutiques. L’ostéonécrose est une complication bien décrite du traitement de la leucémie touchant jusqu’à un enfant sur dix, avec un tropisme particulier pour les adolescents atteints de leucémie à haut risque. Cette complication est liée à l’emploi des corticoïdes, dont la toxicité osseuse est potentialisée par l’emploi d’autres molécules, telles l’asparaginase et le méthotrexate. L’incidence de cette complication est plus élevée chez les patients recevant la dexaméthasone à titre de corticoïde principal. De récents protocoles thérapeutiques ont adopté, dans le but de réduire l’incidence de l’ostéonécrose, l’usage du schéma thérapeutique baptisé « split dexamethasone », une initiative du Children's Oncology Group (COG) consistant à marquer une pause de quelques jours dans l’administration de la dexaméthasone lors de la phase de réintensification. À ce jour, seuls un modèle animal et deux essais randomisés contrôlés du COG ont évalué l’intérêt de cette pratique. Ces derniers mettent en évidence un bénéfice de la méthode, avec une réduction de l’incidence d’ostéonécrose à 5 ans de l’ordre de 50 % pour le CCG 1961 et de 33 % chez les patients entre 10 et 12 ans pour le AALL0232, sans modification de la survie sans événement à 5 ans (EFS-5), qui reste de l’ordre de 75 % chez ces patients à haut risque. En conclusion, la prévention de l’apparition des lésions d’ostéonécrose via des amendements thérapeutiques, tel le « split dexamethasone » est non seulement réalisable et efficace, mais semble également sans danger sur le plan pronostic

Study protocol for THINK : a multinational open-label phase I study to assess the safety and clinical activity of multiple administrations of NKR-2 in patients with different metastatic tumour types

Introduction: NKR-2 are autologous T cells genetically modified to express a chimeric antigen receptor (CAR) comprising a fusion of the natural killer group 2D (NKG2D) receptor with the CD3 zeta signalling domain, which associates with the adaptor molecule DNAX-activating protein of 10 kDa (DAP10) to provide co-stimulatory signal upon ligand binding. NKG2D binds eight different ligands expressed on the cell surface of many tumour cells and which are normally absent on non-neoplastic cells. In preclinical studies, NKR-2 demonstrated long-term antitumour activity towards a breadth of tumour indications, with maximum efficacy observed after multiple NKR-2 administrations. Importantly, NKR-2 targeted tumour cells and tumour neovasculature and the local tumour immunosuppressive microenvironment and this mechanism of action of NKR-2 was established in the absence of preconditioning. Methods and analysis: This open-label phase I study will assess the safety and clinical activity of NKR-2 treatment administered three times, with a 2-week interval between each administration in different tumour types. The study will contain two consecutive segments: a dose escalation phase followed by an expansion phase. The dose escalation study involves two arms, one in solid tumours (five specific indications) and one in haematological tumours (two specific indications) and will include three dose levels in each arm: 3x10(8), 1x10(9) and 3x10(9) NKR-2 per injection. On the identification of the recommended dose in the first segment, based on dose-limiting toxicity occurrences, the study will expand to seven different cohorts examining the seven different tumour types separately. Clinical responses will be determined according to standard Response Evaluation Criteria In Solid Tumors (RECIST) criteria for solid tumours or international working group response criteria in haematological tumours. Ethics approval and dissemination: Ethical approval has been obtained at all sites. Written informed consent will be taken from all participants. The results of this study will be disseminated through presentation at international scientific conferences and reported in peer-reviewed scientific journals

Glioma Stem Cells in Pediatric High-Grade Gliomas: From Current Knowledge to Future Perspectives.

In children, high-grade gliomas (HGG) and diffuse midline gliomas (DMG) account for a high proportion of death due to cancer. Glioma stem cells (GSCs) are tumor cells in a specific state defined by a tumor-initiating capacity following serial transplantation, self-renewal, and an ability to recapitulate tumor heterogeneity. Their presence was demonstrated several decades ago in adult glioblastoma (GBM), and more recently in pediatric HGG and DMG. In adults, we and others have previously suggested that GSCs nest into the subventricular zone (SVZ), a neurogenic niche, where, among others, they find shelter from therapy. Both bench and bedside evidence strongly indicate a role for the GSCs and the SVZ in GBM progression, fostering the development of innovative targeting treatments. Such new therapeutic approaches are of particular interest in infants, in whom standard therapies are often limited due to the risk of late effects. The aim of this review is to describe current knowledge about GSCs in pediatric HGG and DMG, i.e., their characterization, the models that apply to their development and maintenance, the specific signaling pathways that may underlie their activity, and their specific interactions with neurogenic niches. Finally, we will discuss the clinical relevance of these observations and the therapeutic advantages of targeting the SVZ and/or the GSCs in infants

A randomized trial comparing structured and lifestyle goals in an internet-mediated walking program for people with type 2 diabetes

Abstract Background The majority of individuals with type 2 diabetes do not exercise regularly. Pedometer-based walking interventions can help; however, pedometer-based interventions targeting only total daily accumulated steps might not yield the same health benefits as physical activity programs specifying a minimum duration and intensity of physical activity bouts. Methods This pilot randomized trial compared two goal-setting strategies: 1) lifestyle goals targeting total daily accumulated step counts and 2) structured goals targeting bout steps defined as walking that lasts for 10 minutes or longer at a pace of at least 60 steps per minute. We sought to determine which goal-setting strategy was more effective at increasing bout steps. Participants were sedentary adults with type 2 diabetes. All participants: wore enhanced pedometers with embedded USB ports; uploaded detailed, time-stamped step-count data to a website called Stepping Up to Health; and received automated step-count feedback, automatically calculated goals, and tailored motivational messages throughout the six-week intervention. Only the automated goal calculations and step-count feedback differed between the two groups. The primary outcome of interest was increase in steps taken during the previously defined bouts of walking (lasting at least 10 minutes or longer at a pace of at least 60 steps per minute) between baseline and end of the intervention. Results Thirty-five participants were randomized and 30 (86%) completed the pilot study. Both groups significantly increased bout steps, but there was no statistically significant difference between groups. Among study completers, bout steps increased by 1921 ± 2729 steps a day. Those who received lifestyle goals were more satisfied with the intervention (p = 0.006) and wore the pedometer more often (p < 0.001) than those who received structured goals. Conclusion In this six-week intervention, Lifestyle Goals group participants achieved increases in bout steps comparable to the increases seen in the Structured Goals group, representing almost a mile a day of additional moderate intensity bout activity. Pedometer-based walking programs that emphasize total accumulated step counts are more acceptable to participants and are as effective at increasing moderate intensity bouts of physical activity as programs that use structured goals. Trial registration NCT00151021http://deepblue.lib.umich.edu/bitstream/2027.42/112366/1/12966_2007_Article_136.pd

A randomized trial comparing structured and lifestyle goals in an internet-mediated walking program for people with type 2 diabetes

BACKGROUND: The majority of individuals with type 2 diabetes do not exercise regularly. Pedometer-based walking interventions can help; however, pedometer-based interventions targeting only total daily accumulated steps might not yield the same health benefits as physical activity programs specifying a minimum duration and intensity of physical activity bouts. METHODS: This pilot randomized trial compared two goal-setting strategies: 1) lifestyle goals targeting total daily accumulated step counts and 2) structured goals targeting bout steps defined as walking that lasts for 10 minutes or longer at a pace of at least 60 steps per minute. We sought to determine which goal-setting strategy was more effective at increasing bout steps. Participants were sedentary adults with type 2 diabetes. All participants: wore enhanced pedometers with embedded USB ports; uploaded detailed, time-stamped step-count data to a website called Stepping Up to Health; and received automated step-count feedback, automatically calculated goals, and tailored motivational messages throughout the six-week intervention. Only the automated goal calculations and step-count feedback differed between the two groups. The primary outcome of interest was increase in steps taken during the previously defined bouts of walking (lasting at least 10 minutes or longer at a pace of at least 60 steps per minute) between baseline and end of the intervention. RESULTS: Thirty-five participants were randomized and 30 (86%) completed the pilot study. Both groups significantly increased bout steps, but there was no statistically significant difference between groups. Among study completers, bout steps increased by 1921 ± 2729 steps a day. Those who received lifestyle goals were more satisfied with the intervention (p = 0.006) and wore the pedometer more often (p < 0.001) than those who received structured goals. CONCLUSION: In this six-week intervention, Lifestyle Goals group participants achieved increases in bout steps comparable to the increases seen in the Structured Goals group, representing almost a mile a day of additional moderate intensity bout activity. Pedometer-based walking programs that emphasize total accumulated step counts are more acceptable to participants and are as effective at increasing moderate intensity bouts of physical activity as programs that use structured goals. TRIAL REGISTRATION: NCT0015102

Consensus definitions of 14 severe acute toxic effects for childhood lymphoblastic leukaemia treatment: a Delphi consensus

Although there are high survival rates for children with acute lymphoblastic leukaemia, their outcome is often counterbalanced by the burden of toxic effects. This is because reported frequencies vary widely across studies, partly because of diverse definitions of toxic effects. Using the Delphi method, 15 international childhood acute lymphoblastic leukaemia study groups assessed acute lymphoblastic leukaemia protocols to address toxic effects that were to be considered by the Ponte di Legno working group. 14 acute toxic effects (hypersensitivity to asparaginase, hyperlipidaemia, osteonecrosis, asparaginase-associated pancreatitis, arterial hypertension, posterior reversible encephalopathy syndrome, seizures, depressed level of consciousness, methotrexate-related stroke-like syndrome, peripheral neuropathy, high-dose methotrexate-related nephrotoxicity, sinusoidal obstructive syndrome, thromboembolism, and Pneumocystis jirovecii pneumonia) that are serious but too rare to be addressed comprehensively within any single group, or are deemed to need consensus definitions for reliable incidence comparisons, were selected for assessment. Our results showed that none of the protocols addressed all 14 toxic effects, that no two protocols shared identical definitions of all toxic effects, and that no toxic effect definition was shared by all protocols. Using the Delphi method over three face-to-face plenary meetings, consensus definitions were obtained for all 14 toxic effects. In the overall assessment of outcome of acute lymphoblastic leukaemia treatment, these expert opinion-based definitions will allow reliable comparisons of frequencies and severities of acute toxic effects across treatment protocols, and facilitate international research on cause, guidelines for treatment adaptation, preventive strategies, and development of consensus algorithms for reporting on acute lymphoblastic leukaemia treatment