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The aim of this research was to determine whether the proportion of a tumour that enhances (enhancing fraction, EnF) and changes in EnF with enhancement threshold differ between low and high grade glioma. Forty-four patients (45 gliomas comprising 16 grade II, 5 grade III and 24 grade IV) were studied. Imaging included pre- and post-contrast-enhanced T(1)-weighted sequences and T(1)-weighted DCE-MRI. Thresholded enhancement maps were generated for each tumour by using a range of values of the initial area under the contrast concentration curve (IAUC). A plot of EnF versus threshold value was generated. We examined the relationship between tumour grade and enhancement metrics including: EnF (threshold IAUC > 0 mMol s), EnF (threshold IAUC > 2.5 mMol s), initial slope of the EnF/threshold curve (partial differentialEnF), IAUC, and two previously described signal-intensity-based metrics. EnF, defined as the proportion of tumour showing any enhancement (threshold IAUC > 0 mMol s), showed no difference between low and high grade glioma. All other measures demonstrated significant differences between grade II and IV, and low (grade II) and high grade (grades III/ IV) gliomas (p < 0.01). Two measures, partial differentialEnF and Pronin's measure of enhancement, showed differences between grade III and IV (p < 0.05). No measure separated grade II from III. Metrics which describe the enhancing fraction and its variation with enhancement threshold partial differentialEnF show considerably different behaviour in low and high grade tumours. These observations suggest that these metrics may provide important biological information concerning tumour biology and therapeutic responses and encourage further research to characterise and validate these novel biomarkers. [ABSTRACT FROM AUTHOR]

Purpose: Describe clinical practice, inter-disciplinary clinical pathway and core principles of care within a mild traumatic brain injury (mTBI) rehabilitation team., Methods: An observational study examined inter-disciplinary practice, nested within an observational trial investigating team-based mTBI rehabilitation. Data were collected to describe clinical service over 12 months. Activity data quantified clinical sessions per participant, mode of service delivery and content of sessions using custom-designed codes. The clinical team gathered narrative data to confirm the inter-disciplinary clinical pathway and individual discipline practice., Results: 168 participants entered the rehabilitation program during the 12 months. A single Allied Health Screening Assessment identified patient priorities. Occupational Therapy (OT) and Physiotherapy (PT) provided the majority of clinical sessions; the team also comprised Social Work, Rehabilitation Medicine, Speech Pathology and Clinical Psychology. Telehealth was the most common service delivery mode (54%). Median session numbers per participant ranged 1-4 for all disciplines; mean/maximum occasions of service were highest for PT (6.9/44) and OT (6.8/39)., Conclusion: A small proportion of participants received much higher number of sessions, consistent with intractable issues after mTBI. High attendance rates indicate the predominantly telehealth-delivered model was feasible. The clinical approach included early prioritizing of discipline input and follow-up after discharge.

Background: Meningioma is the commonest primary brain tumour. Volumetric post-contrast magnetic resonance imaging (MRI) is recognised as gold standard for delineation of meningioma volume but is hindered by manual processing times. We aimed to investigate the utility of a model-based variational approach in segmenting meningioma., Methods: A database of patients with a meningioma (2007-2015) was queried for patients with a contrast-enhanced volumetric MRI, who had consented to a research tissue biobank. Manual segmentation by a neuroradiologist was performed and results were compared to the mathematical model, using a battery of tests including the Sørensen-Dice coefficient (DICE) and JACCARD index. A publicly available meningioma dataset (708 segmented T1 contrast-enhanced slices) was also used to test the reliability of the model., Results: 49 meningioma cases were included. The most common meningioma location was convexity ( n = 15, 30.6%). The mathematical model segmented all but one incidental meningioma, which failed due to the lack of contrast uptake. The median meningioma volume by manual segmentation was 19.0 cm 3 (IQR 4.9-31.2). The median meningioma volume using the mathematical model was 16.9 cm 3 (IQR 4.6-28.34). The mean DICE score was 0.90 (SD = 0.04). The mean JACCARD index was 0.82 (SD = 0.07). For the publicly available dataset, the mean DICE and JACCARD scores were 0.90 (SD = 0.06) and 0.82 (SD = 0.10), respectively., Conclusions: Segmentation of meningioma volume using the proposed mathematical model was possible with accurate results. Application of this model on contrast-enhanced volumetric imaging may help reduce work burden on neuroradiologists with the increasing number in meningioma diagnoses., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Tectal plate gliomas (TPGs) are a heterogeneous group of uncommon brain tumors. TPGs are considered indolent and are usually managed conservatively but they have the potential to transform into higher-grade tumors. The aims of this study were to investigate the natural history of adult TPG, treatment outcomes, and overall survival., Methods: A retrospective cohort analysis was performed of adult patients with TPG between 1993 and 2021. Baseline clinical, radiologic, and management characteristics were collected. The primary outcome was tumor progression, defined as increasing size on radiologic assessment or new gadolinium contrast enhancement. Secondary outcomes included management and mortality., Results: Thirty-nine patients were included, of whom 23 (52.2%) were men. Median age at diagnosis was 35 years (interquartile range, 27-53). Radiologic tumor progression was observed in 8 patients (20.5%). The 10-year progression-free survival was 72.6% (95% confidence interval [CI], 0.58-0.91). The 10-year overall survival was 86.5% (95% confidence interval, 0.75-1.0). Cerebrospinal fluid diversion procedures were used in 62% of the cohort (n = 24). Seventeen patients (43.6%) underwent at least 1 endoscopic third ventriculostomy, whereas only 6 patients (15.4%) underwent at least 1 ventriculoperitoneal shunt., Conclusions: TPG has an overall favorable clinical prognosis, although progression occurs in 1 in 5 patients. Showing accurate factors by which patients with TPG may be risk stratified should be a key area of further research. A follow-up duration of 10 years would be a reasonable window based on the radiologic progression rates in this study; however, larger cohort studies are needed to answer both questions definitively., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The re-investigation of [Bi 2 O 2 (OH)](NO 3 ), dioxidodibismuth(III) hydroxide nitrate, on the basis of single-crystal X-ray diffraction data revealed an apparent structural phase transition of a crystal structure determined previously (space group Cmc 2 1 at 173 K) to a crystal structure with lower symmetry (space group Pna 2 1 at 100 K). The Cmc 2 1 → Pna 2 1 group-subgroup relationship between the two crystal structures is klassengleiche with index 2. In contrast to the crystal structure in Cmc 2 1 with orientational disorder of the nitrate anion, disorder does not occur in the Pna 2 1 structure. Apart from the disorder of the nitrate anion, the general structural set-up in the two crystal structures is very similar: [Bi 2 O 2 ] 2+ layers extend parallel to (001) and alternate with layers of (OH) - anions above and (NO 3 ) - anions below the cationic layer. Whereas the (OH) - anion shows strong bonds to the Bi III cations, the (NO 3 ) - anion weakly binds to the Bi III cations of the cationic layer. A rather weak O-H⋯O hydrogen-bonding inter-action between the (OH) - anion and the (NO 3 ) - anion links adjacent sheets along [001]., (© Weil et al. 2023.)

Chimeric antigen receptor (CAR)-T cell immunotherapy is a novel treatment that genetically modifies the patients' own T cells to target and kill malignant cells. However, identification of tumour-specific antigens expressed on multiple solid cancer types, remains a major challenge. P2X purinoceptor 7 (P2X7) is a cell surface expressed ATP gated cation channel, and a dysfunctional version of P2X7, named nfP2X7, has been identified on cancer cells from multiple tissues, while being undetectable on healthy cells. We present a prototype -human CAR-T construct targeting nfP2X7 showing potential antigen-specific cytotoxicity against twelve solid cancer types (breast, prostate, lung, colorectal, brain and skin). In xenograft mouse models of breast and prostate cancer, CAR-T cells targeting nfP2X7 exhibit robust anti-tumour efficacy. These data indicate that nfP2X7 is a suitable immunotherapy target because of its broad expression on human tumours. CAR-T cells targeting nfP2X7 have potential as a wide-spectrum cancer immunotherapy for solid tumours in humans., (© 2023. Springer Nature Limited.)

Introduction: Stem cell therapies have been investigated as potential treatment modalities for chronic wounds however there has been limited success to date. Multipotent Adult Progenitor Cells (MAPCs©) have been identified as having potential as an allogenic stem cell product due to their high population doubling number and their characteristic dampening of T-cell proliferation. This helps to prevent autoimmunity and graft/cell rejection. Methods: We have developed a dressing, consisting of medical grade silicone coated with a heptylamine plasma polymer, which supports the growth and transfer of MAPCs to skin. To determine if the dressing can deliver functional stem cells into diabetic wounds, they were loaded with MAPCs and then placed over excisional wounds in both normal and diabetic mice. Results and discussion: Accelerated healing was observed in both the normal and diabetic wounds with wound gape being significantly smaller at day 3 when compared to controls. Wound analysis showed that treatment with the MAPC dressings dampened the inflammatory response with reduced numbers of neutrophils and macrophages observed. Additionally, an increase in pro-angiogenic VEGF and CD31 positive endothelial cells was observed indicating improved new blood vessel formation. The MAPC dressings had no effect on fibrosis with collagen I and III being equally affected in both control and treated wounds. Overall, the functionalized MAPC dressings improve healing responses particularly in diabetic mice with impaired healing responses and therefore, show potential for development as an advanced therapeutic approach for the treatment of chronic diabetic wounds., Competing Interests: AT was employed by the company Athersys Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mills, Kirby, Hofma, Smith, Statham, Vaes, Ting, Short and Cowin.)

The widespread availability and use of brain magnetic resonance imaging and computed tomography has led to an increase in the frequency of incidental meningioma diagnoses. Most incidental meningioma are small, demonstrate indolent behavior during follow-up, and do not require intervention. Occasionally, meningioma growth causes neurological deficits or seizures prompting surgical or radiation treatment. They may cause anxiety to the patient and present a management dilemma for the clinician. The questions for both patient and clinician are "will the meningioma grow and cause symptoms such that it will require treatment within my lifetime?" and "will deferment of treatment result in greater treatment-related risks and lower chance of cure?." International consensus guidelines recommend regular imaging and clinical follow-up, but the duration is not specified. Upfront treatment with surgery or stereotactic radiosurgery/radiotherapy may be recommended but this is potentially an overtreatment, and its benefits must be balanced against the risk of related adverse events. Ideally, treatment should be stratified based on patient and tumor characteristics, but this is presently hindered by low-quality supporting evidence. This review discusses risk factors for meningioma growth, proposed management strategies, and ongoing research in the field., (© The Author(s) 2023. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Purpose: Determine how mobility changes over 6 months in people unable to walk at 8-weeks post-Acquired Brain Injury (ABI); if there is an association over time between postural alignment and mobility post-ABI; and if alignment after ABI becomes closer to healthy alignment over time., Methods: Fourteen adults with ABI, evaluated over 6 months, and a reference sample of 30 healthy adults were studied. The primary measure for changes in mobility was the Clinical Outcome Variables Scale (COVS). Secondary measures were sit-to-stand, timed standing holding rails, independent walking speed and number of testing conditions achieved. The Functional Independence Measure (FIM) was scored at rehabilitation admission and discharge. To analyze postural alignment, participants were recorded in sitting and standing, each repeated holding rails, and walking if able. Three-dimensional kinematic data were used to quantify whole-body postural alignment, equal to mean segment displacements from the base of support in the transverse plane. Associations between three-dimensional kinematic alignment scores and COVS scores were calculated using Linear Mixed-Effects Models., Results: Participants made significant improvements in COVS scores, most secondary mobility scores, and FIM scores over time (p ≤ .001). Relationships between increasing COVS scores and decreasing sitting and standing mal-alignment scores were statistically significant. Visual analysis of graphed segment positions indicated that sitting and standing alignment became more similar to healthy alignment over time; this was not clear for walking., Conclusion: Improvement in postural alignment may be a factor for improving mobility in people with severe impairments after ABI.

Tranexamic Acid (TXA) has been used in medical and surgical practice to reduce haemorrhage. The aim of this review was to evaluate the effect of TXA use on intraoperative and postoperative outcomes of meningioma surgery. A systematic review and meta-analysis was conducted in accordance with the PRISMA statement and registered in PROSPERO (CRD42021292157). Six databases were searched up to November 2021 for phase 2-4 control trials or cohort studies, in the English language, examining TXA use during meningioma surgery. Studies ran outside of dedicated neurosurgical departments or centres were excluded. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Random effects meta-analysis were performed to delineate differences in operative and postoperative outcomes. Four studies (281 patients) were included. TXA use significantly reduced intraoperative blood loss (mean difference 315.7 mls [95% confidence interval [CI] -532.8, -98.5]). Factors not affected by TXA use were transfusion requirement (odds ratio = 0.52; 95% CI 0.27, 0.98), operation time (mean difference = -0.2 h; 95% CI -0.8, 0.4), postoperative seizures (Odds Ratio [OR] = 0.88; 95% CI 0.31, 2.53), hospital stay (mean difference = -1.2; 95% CI -3.4, 0.9) and disability after surgery (OR = 0.50; 95% CI 0.23, 1.06). The key limitations of this review were the small sample size, limited data for secondary outcomes and a lack of standardised method for measuring blood loss. TXA use reduces blood loss in meningioma surgery, but not transfusion requirement or postoperative complications. Larger trials are required to investigate the impact of TXA on patient-reported postoperative outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: After meningioma surgery, approximately 1 in 3 patients will have residual tumor that requires ongoing imaging surveillance. The precise volumetric growth rates of these tumors are unknown., Objective: To identify the volumetric growth rates of residual meningioma, growth trajectory, and factors associated with progression., Methods: Patients with residual meningioma identified at a tertiary neurosurgery center between 2004 and 2020 were retrospectively reviewed. Tumor volume was measured using manual segmentation, after surgery and at every follow-up MRI scan. Growth rates were ascertained using a linear mixed-effects model and nonlinear regression analysis of growth trajectories. Progression was defined according to the Response Assessment in Neuro-Oncology (RANO) criteria (40% volume increase)., Results: There were 236 patients with residual meningioma. One hundred and thirty-two patients (56.0%) progressed according to the RANO criteria, with 86 patients being conservatively managed (65.2%) after progression. Thirteen patients (5.5%) developed clinical progression. Over a median follow-up of 5.3 years (interquartile range, 3.5-8.6 years), the absolute growth rate was 0.11 cm 3 per year and the relative growth rate 4.3% per year. Factors associated with residual meningioma progression in multivariable Cox regression analysis were skull base location (hazard ratio [HR] 1.60, 95% CI 1.02-2.50) and increasing Ki-67 index (HR 3.43, 95% CI 1.19-9.90). Most meningioma exhibited exponential and logistic growth patterns (median R 2 value 0.84, 95% CI 0.60-0.90)., Conclusion: Absolute and relative growth rates of residual meningioma are low, but most meet the RANO criteria for progression. Location and Ki-67 index can be used to stratify adjuvant treatment and surveillance paradigms., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Congress of Neurological Surgeons.)

Introduction: Few studies have evaluated meningioma patients' longer-term health-related quality of life (HRQoL) following diagnosis and treatment, particularly in those with incidental, actively monitored tumours., Methods: A single-center, cross-sectional study was completed. Adult patients with surgically managed or actively monitored meningioma with more than five years of follow-up were included. The patient-reported outcome measures RAND SF-36, EORTC QLQ-C30 and QLQ-BN20 were used to evaluate HRQoL. HRQoL scores were compared to normative population data. Outcome determinants were evaluated using multivariate linear regression analysis., Results: 243 patient responses were analyzed, and the mean time from diagnosis was 9.8 years (range 5.0-40.3 years). Clinically relevant, statistically significant HRQoL impairments were identified across several SF-36 and QLQ-C30 domains. Increasing education level (β = 2.9, 95% CI 0.9 to 4.9), P = .004), employment (β = 7.7, 95% CI 2.2 to 13.1, P = .006) and absence of postoperative complications (β=-6.7, 95% CI -13.2 to (-)0.3, P = .041) were associated with a better QLQ-C30 summary score. Other tumour and treatment variables were not., Conclusion: This study highlights the longer-term disease burden of patients with meningioma nearly one decade after diagnosis or surgery. Patients with actively monitored meningioma have similar HRQoL to operated meningioma patients. Healthcare professionals should be mindful of HRQoL impairments and direct patients to sources of support as needed., (© 2022. The Author(s).)

Background: Sporadic multiple meningioma are uncommon. Population-based data suggests that these patients have a reduced overall survival when compared to patients with solitary meningioma. The aim of this study was to investigate the clinical outcomes in multiple and solitary meningioma., Methods: A single-center matched cohort study (2008-2018) was performed. Patients with synchronous multiple meningioma at presentation, with no history of prior intracranial radiation, concurrent hormone replacement therapy or features of NF2-schwannomatosis were included. Eligible patients were matched 1:1 to patients with solitary meningioma. Outcomes of interest were occurrence of an intervention, recurrence, new meningioma development and mortality., Results: Thirty-four patients harboring 76 meningioma at presentation were included. Mean age was 59.3 years (SD = 13.5). Thirty-one (91.2%) were female. The median number of meningioma per patient was 2 (range 2-6). Eighteen patients (52.9%) were symptomatic at presentation. Median overall follow-up was 80.6 months (IQR 44.1-99.6). Compared to patients with a sporadic meningioma, there was no difference in intervention rates (67.6% vs 70.6%, P = 0.792). Eight patients (34.8%) with a multiple meningioma had a WHO grade 2 meningioma compared to 7 (29.2%) with a solitary meningioma (P = 0.679). Median recurrence-free survival was 89 months (95% CI 76-104) with no difference between the two groups (P = 0.209). Mean overall survival was 132 months (95% CI 127-138) with no difference between the two groups (P = 0.860). One patient with multiple meningioma developed two further new meningioma 36 months following diagnosis., Conclusion: Sporadic multiple meningioma may not have worse clinical outcomes. Management of patients with sporadic multiple meningioma should be tailored towards the symptomatic meningioma or high-risk asymptomatic meningioma., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Tumour Treating Fields (TTF) in combination with standard therapy, prolongs survival in patients with glioblastoma (GBM). The aim of the current study was to assess the feasibility of integrating TTF into a standard UK neuro-oncology service with a focus on patient tolerability, compliance, and treatment delivery., Methods: A prospective study was performed of UK patients with IDH 1 Wild Type, MGMT Unmethylated GBM treated with TTF, in conjunction with conventional therapy. Patient compliance data, device-specific tolerability questions, and an evaluation of disease progression and survival were collected. Monthly quality of life (QoL) questionnaires (EORTC QLQ-C30 with BN-20) examined the trend of global health, psychosocial function, and symptom progression., Results: Nine patients were enrolled with a median age of 47 (seven males; two females). Overall, compliance with TTF was 89% (range 16-97%). Only one patient failed to comply with treatment. Patients tolerated the device with minimal side effects. Eight patients described mild to moderate skin irritation, whilst all patients were keen to recommend the device to other patients (100%). Most patients found the weight and size of the device to be its biggest drawback (72%). Progression-free survival was 5.5 months and median overall survival was 14.9 months., Conclusions: TTF was well-tolerated amongst a small cohort of UK patients, who were able to comply with treatment without any significant complication. QoL questionnaires showed no sustained deterioration in global health, physical and emotional function until the final months of life when the disease burden was greatest.

TLR4 plays a pivotal role in orchestrating inflammation and tissue repair. Its expression has finally been balanced to initiate the early, robust immune response necessary for efficient repair without excessively amplifying and prolonging inflammation, which impairs healing. Studies show Flightless I (Flii) is an immunomodulator that negatively regulates macrophage TLR4 signalling. Using macrophages from Flii +/- , WT, and Flii Tg/Tg mice, we have shown that elevated Flii reduces early TLR4 surface expression, delaying and reducing subsequent TNF secretions. In contrast, reduced Flii increases surface TLR4, leading to an earlier robust TNF peak. In Flii +/- mice, TLR4 levels peak earlier during wound repair, and overall healing is accelerated. Fewer neutrophils, monocytes and macrophages are recruited to Flii +/- wounds, leading to fewer TNF-positive macrophages, alongside an early peak and a robust shift to M2 anti-inflammatory, reparative Ym1 + and IL-10 + macrophages. Importantly, in diabetic mice, high Flii levels are found in plasma and unwounded skin, with further increases observed in their wounds, which have impaired healing. Lowering Flii in diabetic mice results in an earlier shift to M2 macrophages and improved healing. Overall, this suggests Flii regulation of TLR4 reduces early inflammation and decreases the M2 macrophage phenotype, leading to impaired healing.

The endothelial glycocalyx (eGlx) is a critically important structure lining the luminal surface of endothelial cells. There is increasing evidence, in human patients and animal models, for its crucial role in the maintenance of health. Moreover, its damage is associated with the pathogenesis of multiple disease states. This review provides readers with an overview of the eGlx; summarising its structure, essential functions, and evidence for its role in disease. We highlight the lack of studies regarding the eGlx in cats and dogs, particularly in naturally occurring diseases. Importantly, we discuss techniques to aid its study, which can be applied to veterinary species. Finally, we present targeted therapies aimed at preserving, and in some cases, restoring damaged eGlx., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)