Objective
The prevalence of epilepsy in World Health Organization (WHO) grade 2 glioma is high, with seizures being the presenting symptom in 60%–90%. We explore the epidemiology of seizures in this ...patient population in a regional neurosurgical center.
Methods
Electronic health records of patients with histologically‐proven WHO grade 2 glioma (n = 228) were reviewed between 1997 and 2021, with data collected including patient demographics, epilepsy prevalence, and seizure semiology. The influence of seizure type on overall survival was calculated using a Cox proportional hazards model.
Results
Overall, 197 of 228 patients (86.4%) were diagnosed with epilepsy—either at presentation or during the course of their disease. Male patients were more likely than female patients to be diagnosed with epilepsy (91.1% vs 77.1%, p = .003) and, in those with epilepsy, more likely to experience at least one focal to bilateral tonic–clonic seizure (69.4% vs 54.1%, p = .05). Patients with left‐sided tumors were twice as likely to have experienced a focal to bilateral tonic–clonic seizure (p = .02, odds ratio OR = .47). Predominantly experiencing seizures with motor activity appeared to confer better overall survival, with a 65% decrease in the risk of death 10 years post diagnosis (hazard ratio HR = .35, p = .02). This is despite accounting for previously described prognostic markers including tumor histology/genetics, time from diagnosis to surgery, and the extent of tumor resection.
Significance
Motor seizure activity is a frequent feature in WHO grade 2 glioma and appears to confer a survival benefit regardless of histology or surgical factors. Seizures due to dominant hemisphere tumors may be more likely to propagate and cause bilateral tonic–clonic activity.
Objective
The high seizure burden seen in World Health Association (WHO) grade 2 gliomas is well documented. This study aims to identify factors that influence the probability of seizure freedom (12 ...months of seizure remission) and treatment failure (antiseizure medication ASM cessation or introduction of an alternative) in patients with WHO grade 2 glioma.
Methods
This is a retrospective observational analysis of patients from a regional UK neurosurgical center with histologically proven (n = 146) WHO grade 2 glioma and brain tumor related epilepsy. Statistical analyses using both Kaplan‐Meier and Cox proportional hazards models were undertaken, with a particular focus on treatment outcomes when the commonly prescribed ASM levetiracetam (n = 101) is used as first line.
Results
Treatment with levetiracetam as a first‐line ASM resulted in a significant increase in the probability of seizure freedom (p < .05) at 2 years compared with treatment with an alternative ASM. Individuals presenting with focal seizures without bilateral tonic‐clonic progression were between 39% and 42% significantly less likely to reach seizure freedom within 10 years (p < .05) and 132% more likely to fail treatment by 5 years (p < .01) when compared to individuals who had seizures with progression to bilateral tonic‐clonic activity. ASM choice did not significantly affect treatment failure rates.
Significance
More than two‐thirds of patients with WHO grade 2 glioma related epilepsy treated with levetiracetam first line achieve seizure freedom within 2 years and it is a reasonable first‐choice agent. Experiencing mainly focal seizures without progression infers a significant long‐term reduction in the chance of seizure freedom. Further studies are needed to inform ASM selection.
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Porous silica nanoparticles (PSiNPs) have long attracted interest in drug delivery research. However, conventional synthesis methods for sub-100 nm, functionalised PSiNPs typically ...give poor monodispersity, reproducibility, or involve complex synthetic protocols. We report a facile, reproducible, and cost-effective one-pot method for the synthesis of cancer targeting and pH responsive PSiNPs in this size range, without the need for post-synthetic modification. This was achieved by using monodisperse l-arginine (Arg)/ poly(acrylic acid) (PAA) polyelectrolyte complexes (PECs) as soft templates for silane hydrolysis and condensation. Highly uniform PSiNPs with tunable size control between 42 and 178 nm and disordered pore structure (1.1–2.7 nm) were obtained. Both PAA and Arg were retained within the PSiNPs, which enabled a high doxorubicin hydrochloride (Dox) loading capacity (22% w/w) and a 4-fold increase in drug release under weakly acidic pH compared to physiological pH. The surface presentation of Arg conferred significantly higher intracellular accumulation of Arg/PAA-PSiNPs in patient-derived glioblastoma cells compared to non-tumorigenic neural progenitor cells, which effectively translated to lower IC50 values for Dox-loaded Arg/PAA-PSiNPs than non-functionalised PSiNPs. This work brings forward new insights for the development of monodisperse PSiNPs with highly desirable built-in functionalities for biomedical applications.
Diffuse intrinsic pontine glioma (DIPG) is a deadly paediatric brain cancer. Transient response to radiation, ineffective chemotherapeutic agents and aggressive biology result in rapid progression of ...symptoms and a dismal prognosis. Increased availability of tumour tissue has enabled the identification of histone gene aberrations, genetic driver mutations and methylation changes, which have resulted in molecular and phenotypic subgrouping. However, many of the underlying mechanisms of DIPG oncogenesis remain unexplained. It is hoped that more representative
and preclinical models-using both xenografted material and genetically engineered mice-will enable the development of novel chemotherapeutic agents and strategies for targeted drug delivery. This review provides a clinical overview of DIPG, the barriers to progress in developing effective treatment, updates on drug development and preclinical models, and an introduction to new technologies aimed at enhancing drug delivery.
Independent robotic manipulation of two large permanent magnets, in the form of the dual External Permanent Magnet (dEPM) system has demonstrated the possibility for enhanced magnetic control by ...allowing for actuation up to eight magnetic degrees of freedom (DOFs) at clinically relevant scales. This precise off-board control has facilitated the use of magnetic agents as medical devices, including catheter-like soft continuum robots (SCRs). The use of multiple robotically actuated permanent magnets poses the risk of collision between the robotic arms, the environment, and the patient. Furthermore, unconstrained transitions between actuation inputs can lead to undesired spikes in magnetic fields potentially resulting in unsafe manipulator deformation. This paper presents a hybrid approach to trajectory planning for the dEPM platform. This is performed by splitting the planning problem in two: first finding a collision-free physical path for the two robotically actuated permanent magnets before combining this with a path in magnetic space, which permits for a smooth change in magnetic fields and gradients. This algorithm was characterized by actuating each of the eight magnetic DOFs sequentially, eliminating any potential collisions and reducing the maximum undesired actuation value by 203.7 mT for fields and by 418.7 mT/m for gradients. The effect of this planned magnetic field actuation on a SCR was then examined through two case studies. First, a tip-driven SCR was moved to set points within a confined area. Actuation using the proposed planner reduced movement outside the restricted area by an average of 41.3%. Lastly, the use of the proposed magnetic planner was shown to be essential in navigating a multi-segment magnetic SCR to the site of an aneurysm within a silicone brain phantom.
ABSTRACT
Background
Hospital waste adds to the ecological footprint of the healthcare system, whereas inattention to recyclables may increase costs. The primary objective of this study was to assess ...the amount of recyclable and nonrecyclable intraoperative waste produced across representative otolaryngology surgical procedures.
Methods
Representative surgical cases across four otolaryngology subspecialties at a tertiary care military medical institution were prospectively identified. Waste was collected, divided, and weighed across two categories: recyclable and nonrecyclable. This study was performed in conjunction with a hospital-approved quality improvement project.
Results
The study included 22 otolaryngology surgeries performed across four otolaryngology subspecialties: facial plastics, pediatrics, otology, and head and neck oncology. Overall, 197.4 kg of waste was collected of which 40.2 kg (20%) was recyclable and 157.2 kg (80%) was nonrecyclable. An average of 1.8 kg of recyclable materials and 7.1 kg of nonrecyclable materials were collected per case.
Conclusion
This study supports that otolaryngology surgical procedures generate a significant amount of waste, a large component of which is recyclable. It highlights the need for proper disposal of this waste and the implementation of a recycling program at our institution with the potential for both ecologic and economic benefits.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Immune checkpoint inhibitors, including those targeting programmed cell death protein 1 (PD-1), are reshaping cancer therapeutic strategies. Evidence suggests, however, that tumor response and ...patient survival are determined by tumor programmed death ligand 1 (PD-L1) expression. We hypothesized that preconditioning of the tumor immune microenvironment using targeted, virus-mediated interferon (IFN) stimulation would up-regulate tumor PD-L1 protein expression and increase cytotoxic T cell infiltration, improving the efficacy of subsequent checkpoint blockade. Oncolytic viruses (OVs) represent a promising form of cancer immunotherapy. For brain tumors, almost all studies to date have used direct intralesional injection of OV, because of the largely untested belief that intravenous administration will not deliver virus to this site. We show, in a window-of-opportunity clinical study, that intravenous infusion of oncolytic human
(referred to herein as reovirus) leads to infection of tumor cells subsequently resected as part of standard clinical care, both in high-grade glioma and in brain metastases, and increases cytotoxic T cell tumor infiltration relative to patients not treated with virus. We further show that reovirus up-regulates IFN-regulated gene expression, as well as the PD-1/PD-L1 axis in tumors, via an IFN-mediated mechanism. Finally, we show that addition of PD-1 blockade to reovirus enhances systemic therapy in a preclinical glioma model. These results support the development of combined systemic immunovirotherapy strategies for the treatment of both primary and secondary tumors in the brain.
Both phenotypic and genotypic variations now underpin glioma classification, thus helping to more accurately guide their clinical management. However, WHO Grade III anaplastic astrocytoma (AA) ...remains an unpredictable, heterogeneous entity; displaying a variable prognosis, clinical course and treatment response. This study aims to examine whether additional tumour characteristics influence either overall survival (OS) or 3-year survival in AA.
Data were collected on all newly diagnosed cases of AA between 2003 and 2014, followed up for a minimum of 3 years. Molecular information was obtained from case records and if missing, was re-analysed. Histological slides were independently examined for Ki-67 proliferation index, cellularity and number of mitotic figures. Kaplan-Meier and Cox regression analyses were used to assess OS.
In total, 50 cases were included with a median OS of 14.5 months (range: 1-150 months). Cumulative 3-year survival was 31.5%. Median age was 50 years (range: 24 − 77). Age, IDH1 mutation status, lobar location, oncological therapy and surgical resection were significant independent prognostic indicators for OS. In cases demonstrating an OS ≥ 3 years (n
= 15), Ki-67 index, number of mitotic figures and percentage areas of 'high cellularity' were significantly reduced, i.e. more characteristic of lower-grade/WHO Grade II glioma.
IDH1 status, age, treatment and location remain the most significant prognostic indicators for patients with AA. However, Ki-67 index, mitotic figures and cellularity may help identify AA cases more likely to survive < 3 years, i.e. AA cases more similar to glioblastoma and those cases more likely to survive > 3 years, i.e. more similar to a low-grade glioma.
ObjectivesPostoperative mortality is a widely used quality indicator, but it may be unreliable when procedure numbers and/or mortality rates are low, due to insufficient statistical power. The ...objective was to investigate the statistical validity of postoperative 30-day mortality as a quality metric for neurosurgical practice across healthcare providers.DesignRetrospective cohort study.SettingHospital Episode Statistics data from all neurosurgical units in England.ParticipantsPatients who underwent neurosurgical procedures between April 2013 and March 2018. Procedures were grouped using the National Neurosurgical Audit Programme classification.Outcomes measuredNational 30-day postoperative mortality rates were calculated for elective and non-elective neurosurgical procedural groups. The study estimated the proportion of neurosurgeons and NHS trusts in England that performed sufficient procedures in 3-year and 5-year periods to detect unusual performance (defined as double the national rate of mortality). The actual difference in mortality rates that could be reliably detected based on procedure volumes of neurosurgeons and units over a 5-year period was modelled.ResultsThe 30-day mortality rates for all elective and non-elective procedures were 0.4% and 6.1%, respectively. Only one neurosurgeon in England achieved the minimum sample size (n=2402) of elective cases in 5 years needed to detect if their mortality rate was double the national average. All neurosurgical units achieved the minimum sample sizes for both elective (n=2402) and non-elective (n=149) procedures. In several neurosurgical subspecialties, approximately 80% of units (or more) achieved the minimum sample sizes needed to detect if their mortality rate was double the national rate, including elective neuro-oncology (baseline mortality rate=2.3%), non-elective neuro-oncology (rate=5.7%), neurovascular (rate=6.7%) and trauma (rate=11%).ConclusionPostoperative mortality lacks statistical power as a measure of individual neurosurgeon performance. Neurosurgical units in England performed sufficient procedure numbers overall and in several subspecialty areas to support the use of mortality as a quality indicator.
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