Les répercussions de la maladie au coronavirus 2019 (COVID-19) sur la morbidité et la mortalité chez les enfants se sont révélées relativement faibles. Si un enfant se présente à ma clinique avec une ...fièvre persistante et une hyperinflammation systémique sans aucune exposition connue à la COVID-19, quelle est la probabilité qu'il soit atteint du syndrome inflammatoire multisystémique de l'enfant (MIS-C)? Que sait-on actuellement du MIS-C et quel est le pronostic pour les enfants qui en souffrent? RÉPONSE: En plein cœur de la pandémie de la COVID-19, l'émergence d'un nouveau problème présente encore une fois un défi additionnel aux cliniciens, aux professionnels de la santé publique et à la population pédiatrique. Le syndrome inflammatoire multisystémique chez les enfants est rare, mais potentiellement grave, et il a été observé chez des enfants dont la maladie à la COVID-19 a été confirmée environ 2 à 6 semaines avant l'apparition des symptômes. Au nombre des signes et des symptômes courants figurent une fièvre persistante, une hyperinflammation systémique, des malaises gastro-intestinaux (p. ex. douleurs abdominales, vomissements, diarrhée), des changements mucocutanés (p. ex. éruptions cutanées, conjonctivite), une céphalée ou une dysfonction cardiaque. Étant donné que de nombreux enfants sont asymptomatiques ou ne présentent que des symptômes légers de la COVID-19, le développement du MIS-C peut sembler soudain et surprenant aux familles et aux médecins. Même si les enfants atteints du MIS-C nécessitent habituellement une hospitalisation, les issues sont largement favorables grâce à une reconnaissance rapide du syndrome et à une thérapie intense.
Poor central nervous system penetration of cytotoxic drugs due to the blood brain barrier (BBB) is a major limiting factor in the treatment of brain tumors. Most recurrent glioblastomas (GBM) occur ...within the peritumoral region. In this study, we describe a hyperthemic method to induce temporary disruption of the peritumoral BBB that can potentially be used to enhance drug delivery.
Twenty patients with probable recurrent GBM were enrolled in this study. Fourteen patients were evaluable. MRI-guided laser interstitial thermal therapy was applied to achieve both tumor cytoreduction and disruption of the peritumoral BBB. To determine the degree and timing of peritumoral BBB disruption, dynamic contrast-enhancement brain MRI was used to calculate the vascular transfer constant (Ktrans) in the peritumoral region as direct measures of BBB permeability before and after laser ablation. Serum levels of brain-specific enolase, also known as neuron-specific enolase, were also measured and used as an independent quantification of BBB disruption.
In all 14 evaluable patients, Ktrans levels peaked immediately post laser ablation, followed by a gradual decline over the following 4 weeks. Serum BSE concentrations increased shortly after laser ablation and peaked in 1-3 weeks before decreasing to baseline by 6 weeks.
The data from our pilot research support that disruption of the peritumoral BBB was induced by hyperthemia with the peak of high permeability occurring within 1-2 weeks after laser ablation and resolving by 4-6 weeks. This provides a therapeutic window of opportunity during which delivery of BBB-impermeant therapeutic agents may be enhanced.
ClinicalTrials.gov NCT01851733.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Glioblastoma (GBM) is the most common and lethal intracranial malignancy, with few advances in treatment over the last several decades. Much excitement surrounded the initial approval for bevacizumab ...for recurrent GBM, given the marked radiographic responses and improvement in progression-free survival observed in early studies. However, phase III studies have failed to demonstrate an overall survival advantage with the use of this agent. An overview of the mechanism of action and activity of bevacizumab in adult gliomas, a timeline of pivotal clinical trials, data on its impact on quality of life and imaging, and its role in managing the sequelae of treatment provide evidence for its current use. Investigations into combinatorial approaches utilizing bevacizumab with reirradiation and immunotherapy and ongoing work to identify biomarkers to select patient subsets who may benefit from treatment elucidate important unanswered questions that will further define the role of bevacizumab in the management of patients with GBM.
This guideline provides recommendations for the use of PET imaging in gliomas. The review examines established clinical benefit in glioma patients of PET using glucose ((18)F-FDG) and amino acid ...tracers ((11)C-MET, (18)F-FET, and (18)F-FDOPA). An increasing number of studies have been published on PET imaging in the setting of diagnosis, biopsy, and resection as well radiotherapy planning, treatment monitoring, and response assessment. Recommendations are based on evidence generated from studies which validated PET findings by histology or clinical course. This guideline emphasizes the clinical value of PET imaging with superiority of amino acid PET over glucose PET and provides a framework for the use of PET to assist in the management of patients with gliomas.
Dysbiosis of the gut microbiota has been linked to disease pathogenesis in type 1 diabetes, yet the functional consequences to the host of this dysbiosis are unknown. We investigated the functional ...interactions between the microbiota and the host associated with type 1 diabetes disease risk.
We performed a cross-sectional analysis of stool samples from subjects with recent-onset type 1 diabetes (
= 33), islet autoantibody-positive subjects (
= 17), low-risk autoantibody-negative subjects (
= 29), and healthy subjects (
= 22). Metaproteomic analysis was used to identify gut- and pancreas-derived host and microbial proteins, and these data were integrated with sequencing-based microbiota profiling.
Both human (host-derived) proteins and microbial-derived proteins could be used to differentiate new-onset and islet autoantibody-positive subjects from low-risk subjects. Significant alterations were identified in the prevalence of host proteins associated with exocrine pancreas output, inflammation, and mucosal function. Integrative analysis showed that microbial taxa associated with host proteins involved in maintaining function of the mucous barrier, microvilli adhesion, and exocrine pancreas were depleted in patients with new-onset type 1 diabetes.
These data support that patients with type 1 diabetes have increased intestinal inflammation and decreased barrier function. They also confirmed that pancreatic exocrine dysfunction occurs in new-onset type 1 diabetes and show for the first time that this dysfunction is present in high-risk individuals before disease onset. The data identify a unique type 1 diabetes-associated signature in stool that may be useful as a means to monitor disease progression or response to therapies aimed at restoring a healthy microbiota.
To assess clinical characteristics and outcomes of severe acute respiratory syndrome coronavirus 2-associated multisystem inflammatory syndrome in children (MIS-C).
Children with MIS-C admitted to ...pediatric intensive care units in New York City between April 23 and May 23, 2020, were included. Demographic and clinical data were collected.
Of 33 children with MIS-C, the median age was 10 years; 61% were male; 45% were Hispanic/Latino; and 39% were black. Comorbidities were present in 45%. Fever (93%) and vomiting (69%) were the most common presenting symptoms. Depressed left ventricular ejection fraction was found in 63% of patients with median ejection fraction of 46.6% (IQR, 39.5-52.8). C-reactive protein, procalcitonin, d-dimer, and pro-B-type natriuretic peptide levels were elevated in all patients. For treatment, intravenous immunoglobulin was used in 18 (54%), corticosteroids in 17 (51%), tocilizumab in 12 (36%), remdesivir in 7 (21%), vasopressors in 17 (51%), mechanical ventilation in 5 (15%), extracorporeal membrane oxygenation in 1 (3%), and intra-aortic balloon pump in 1 (3%). The left ventricular ejection fraction normalized in 95% of those with a depressed ejection fraction. All patients were discharged home with median duration of pediatric intensive care unit stay of 4.7 days (IQR, 4-8 days) and a hospital stay of 7.8 days (IQR, 6.0-10.1 days). One patient (3%) died after withdrawal of care secondary to stroke while on extracorporeal membrane oxygenation.
Critically ill children with coronavirus disease-2019-associated MIS-C have a spectrum of severity broader than described previously but still require careful supportive intensive care. Rapid, complete clinical and myocardial recovery was almost universal.
Abstract
The management of patients with glioma usually requires multimodality treatment including surgery, radiotherapy, and systemic therapy. Accurate neuroimaging plays a central role for ...radiotherapy planning and follow-up after radiotherapy completion. In order to maximize the radiation dose to the tumor and to minimize toxic effects on the surrounding brain parenchyma, reliable identification of tumor extent and target volume delineation is crucial. The use of positron emission tomography (PET) for radiotherapy planning and monitoring in gliomas has gained considerable interest over the last several years, but Class I data are not yet available. Furthermore, PET has been used after radiotherapy for response assessment and to distinguish tumor progression from pseudoprogression or radiation necrosis. Here, the Response Assessment in Neuro-Oncology (RANO) working group provides a summary of the literature and recommendations for the use of PET imaging for radiotherapy of patients with glioma based on published studies, constituting levels 1-3 evidence according to the Oxford Centre for Evidence-based Medicine.
We present a detailed study of the faint Milky Way satellite Draco II (Dra II) from deep CFHT/MegaCam broad-band g and i photometry and narrow-band metallicity-sensitive CaHK observations, along with ...follow-up Keck II/DEIMOS multi-object spectroscopy. Forward modelling of the deep photometry allows us to refine the structural and photometric properties of Dra II: the distribution of stars in colour-magnitude space implies Dra II is old (13.5 ± 0.5 Gyr), very metal-poor, very faint (L_V = 180 ^{+124}_{-72} { L_⊙}), and at a distance d = 21.5 ± 0.4 { kpc}. The narrow-band, metallicity-sensitive CaHK Pristine photometry confirms this very low metallicity (Fe/H = -2.7 ± 0.1 dex). Even though our study benefits from a doubling of the spectroscopic sample size compared to previous investigations, the velocity dispersion of the system is still only marginally resolved (σ _{vr}< 5.9 { km s^{-1}} at the 95 per cent confidence level) and confirms that Dra II is a dynamically cold stellar system with a large recessional velocity (< vr> = -342.5^{+1.1}_{-1.2}{ km s^{-1}}). We further show that the spectroscopically confirmed members of Dra II have a mean proper motion of (μ _α ^*,μ _δ)=(1.26 ± 0.27,0.94 ± 0.28) { mas/yr} in the Gaia DR2 data, which translates to an orbit with a pericentre and an apocentre of 21.3 ^{+0.7}_{-1.0} and 153.8 ^{+56.7}_{-34.7} { kpc}, respectively. Taken altogether, these properties favour the scenario of Dra II being a potentially disrupting dwarf galaxy. The low-significance extra-tidal features we map around the satellite tentatively support this scenario.
Brain metastases (BM) from extracranial cancer are associated with significant morbidity and mortality. Effective local treatment options are stereotactic radiotherapy, including radiosurgery or ...fractionated external beam radiotherapy, and surgical resection. The use of systemic treatment for intracranial disease control also is improving. BM diagnosis, treatment planning, and follow-up is most often based on contrast-enhanced magnetic resonance imaging (MRI). However, anatomic imaging modalities including standard MRI have limitations in accurately characterizing posttherapeutic reactive changes and treatment response. Molecular imaging techniques such as positron emission tomography (PET) characterize specific metabolic and cellular features of metastases, potentially providing clinically relevant information supplementing anatomic MRI. Here, the Response Assessment in Neuro-Oncology working group provides recommendations for the use of PET imaging in the clinical management of patients with BM based on evidence from studies validated by histology and/or clinical outcome.
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