Medical Device Advances in the Treatment of Glioblastoma.

Despite decades of research and the growing emergence of new treatment modalities, Glioblastoma (GBM) frustratingly remains an incurable brain cancer with largely stagnant 5-year survival outcomes of around 5%. Historically, a significant challenge has been the effective delivery of anti-cancer treatment. This review aims to summarize key innovations in the field of medical devices, developed either to improve the delivery of existing treatments, for example that of chemo-radiotherapy, or provide novel treatments using devices, such as sonodynamic therapy, thermotherapy and electric field therapy. It will highlight current as well as emerging device technologies, non-invasive versus invasive approaches, and by doing so provide a detailed summary of evidence from clinical studies and trials undertaken to date. Potential limitations and current challenges are discussed whilst also highlighting the exciting potential of this developing field. It is hoped that this review will serve as a useful primer for clinicians, scientists, and engineers in the field, united by a shared goal to translate medical device innovations to help improve treatment outcomes for patients with this devastating disease.

Unravelling the potential of graphene in glioblastoma therapy.

Glioblastoma multiforme (GBM) is one of the most malignant types of central nervous system tumours. Despite advances in treatment modalities, it remains largely incurable with an extremely poor prognosis. Treatment of GBM is associated with several difficulties such as the risk of damaging healthy brain tissues during surgery, drug resistance and inadequate drug delivery across the blood brain barrier. The new nanomaterial graphene, has recently attracted great attention due to its unique physico-chemical characteristics, good biocompatibility, specific targeting and small size. Starting from simple drug delivery systems, the application of graphene-based nanomaterials has been extended to a versatile platform of multiple therapeutic modalities, including immunotherapy, gene therapy, photothermal therapy and photodynamic therapy. Graphene-based materials can also be engineered to integrate multiple functions into a single platform for combination therapy for enhanced anticancer activity and reduced side effects. This review aims to discuss the state-of-the-art applications of graphene-based materials in GBM diagnosis and therapy. In addition, future challenges and prospects regarding this promising field are discussed, which may pave the way towards improving the safety and efficacy of graphene-based therapeutics.

Pre-emptive intrathecal vancomycin therapy reduces external ventricular drain infection: a single centre retrospective case-control study.

OBJECTIVES: External ventricular drain (EVD)-related infection is a significant source of morbidity in neurosurgical patients. Recently, there has been a drive to adopt new catheters with bactericidal properties to reduce infection rates. We propose that the use of standard catheters combined with pre-emptive intrathecal vancomycin (ITV) 10 mg daily provides an effective alternative. DESIGN: Retrospective study of all patients with EVDs between 2010 and 2012, comparing infection rates in those who did and did not receive pre-emptive ITV. All EVDs were of the standard silicon catheter type. CSF infection was defined, as per Centre for Disease Control (CDC) guidelines, as clinical suspicion ± positive CSF gram stain/culture or leucocytosis. Infection rates were compared using Pearson's chi-squared test. RESULTS: 262 EVDs were included in the study, of which 111 were managed with pre-emptive ITV. The infection rate was 2.7% in the vancomycin group and 11.9% in the control group (p<.01). There were no cases of vancomycin-resistant infection in either group. CONCLUSION: The use of pre-emptive ITV is associated with a significantly lower EVD infection rate. This compares favourably with those reported in the literature for bactericidal catheters.

Dopamine Activation Preserves Visual Motion Perception Despite Noise Interference of Human V5/MT.

UNLABELLED: When processing sensory signals, the brain must account for noise, both noise in the stimulus and that arising from within its own neuronal circuitry. Dopamine receptor activation is known to enhance both visual cortical signal-to-noise-ratio (SNR) and visual perceptual performance; however, it is unknown whether these two dopamine-mediated phenomena are linked. To assess this, we used single-pulse transcranial magnetic stimulation (TMS) applied to visual cortical area V5/MT to reduce the SNR focally and thus disrupt visual motion discrimination performance to visual targets located in the same retinotopic space. The hypothesis that dopamine receptor activation enhances perceptual performance by improving cortical SNR predicts that dopamine activation should antagonize TMS disruption of visual perception. We assessed this hypothesis via a double-blinded, placebo-controlled study with the dopamine receptor agonists cabergoline (a D2 agonist) and pergolide (a D1/D2 agonist) administered in separate sessions (separated by 2 weeks) in 12 healthy volunteers in a William's balance-order design. TMS degraded visual motion perception when the evoked phosphene and the visual stimulus overlapped in time and space in the placebo and cabergoline conditions, but not in the pergolide condition. This suggests that dopamine D1 or combined D1 and D2 receptor activation enhances cortical SNR to boost perceptual performance. That local visual cortical excitability was unchanged across drug conditions suggests the involvement of long-range intracortical interactions in this D1 effect. Because increased internal noise (and thus lower SNR) can impair visual perceptual learning, improving visual cortical SNR via D1/D2 agonist therapy may be useful in boosting rehabilitation programs involving visual perceptual training. SIGNIFICANCE STATEMENT: In this study, we address the issue of whether dopamine activation improves visual perception despite increasing sensory noise in the visual cortex. We show specifically that dopamine D1 (or combined D1/D2) receptor activation enhances the cortical signal-to-noise-ratio to boost perceptual performance. Together with the previously reported effects of dopamine upon brain plasticity and learning (Wolf et al., 2003; Hansen and Manahan-Vaughan, 2014), our results suggest that combining rehabilitation with dopamine agonists could enhance both the saliency of the training signal and the long-term effects on brain plasticity to boost rehabilitation regimens for brain injury.

Eye Movements during Auditory Attention Predict Individual Differences in Dorsal Attention Network Activity.

The neural mechanisms supporting auditory attention are not fully understood. A dorsal frontoparietal network of brain regions is thought to mediate the spatial orienting of attention across all sensory modalities. Key parts of this network, the frontal eye fields (FEF) and the superior parietal lobes (SPL), contain retinotopic maps and elicit saccades when stimulated. This suggests that their recruitment during auditory attention might reflect crossmodal oculomotor processes; however this has not been confirmed experimentally. Here we investigate whether task-evoked eye movements during an auditory task can predict the magnitude of activity within the dorsal frontoparietal network. A spatial and non-spatial listening task was used with on-line eye-tracking and functional magnetic resonance imaging (fMRI). No visual stimuli or cues were used. The auditory task elicited systematic eye movements, with saccade rate and gaze position predicting attentional engagement and the cued sound location, respectively. Activity associated with these separate aspects of evoked eye-movements dissociated between the SPL and FEF. However these observed eye movements could not account for all the activation in the frontoparietal network. Our results suggest that the recruitment of the SPL and FEF during attentive listening reflects, at least partly, overt crossmodal oculomotor processes during non-visual attention. Further work is needed to establish whether the network's remaining contribution to auditory attention is through covert crossmodal processes, or is directly involved in the manipulation of auditory information.

Surgical and Biomechanical Perspectives on Osteoarthritis and the ACL Deficient Knee: A Critical Review of the Literature.

This review was undertaken to better understand the debate regarding the issue of osteoarthritis associated with anterior cruciate ligament (ACL) injuries, from a surgical and biomechanical standpoint. Much of the current debate focuses on contributory surgical factors and their relative roles in increasing or decreasing the risk of future osteoarthritis development, primarily highlighting the controversy over whether reconstructive surgery itself is necessarily protective. This review addresses the evolution of ACL reconstruction techniques over time, and with a view to thoroughly examine the role of surgery, outcome differences in procedural technique are reviewed, with a focus on open versus arthroscopic methods, graft choice and the use of a double versus single bundle reconstruction technique. Moreover, other potentially important contributory factors are identified and discussed, such as intrinsic biomechanical alterations sustained at the time of initial injury, and how these may have a more significant role with regard to future osteoarthritic changes in the knee than previously attributed.