Stress-activated brain-gut circuits disrupt intestinal barrier integrity and social behaviour.

Chronic stress underlies the etiology of both major depressive disorder (MDD) and irritable bowel syndrome (IBS), two highly prevalent and debilitating conditions with high rates of co-morbidity. However, it is not fully understood how the brain and gut bi-directionally communicate during stress to impact intestinal homeostasis and stress-relevant behaviours. Using the chronic social defeat stress (CSDS) model, we find that stressed mice display greater intestinal permeability and circulating levels of the endotoxin lipopolysaccharide (LPS) compared to unstressed control (CON) mice. Interestingly, the microbiota in the colon also exhibit elevated LPS biosynthesis gene expression following CSDS. Additionally, CSDS triggers an increase in pro-inflammatory colonic IFNγ+ Th1 cells and a decrease in IL4+ Th2 cells compared to CON mice, and this gut inflammation contributes to stress-induced intestinal barrier permeability and social avoidance behaviour. We next investigated the role of enteric neurons and identified that noradrenergic dopamine beta-hydroxylase (DBH)+ neurons in the colon are activated by CSDS, and that their ablation protects against gut pathophysiology and disturbances in social behaviour. Retrograde tracing from the colon identified a population of corticotropin-releasing hormone-expressing (CRH+) neurons in the paraventricular nucleus of the hypothalamus (PVH) that innervate the colon and are activated by stress. Chemogenetically activating these PVH CRH+ neurons is sufficient to induce gut inflammation, barrier permeability, and social avoidance behaviour, while inhibiting these cells prevents these effects following exposure to CSDS. Thus, we define a stress-activated brain-to-gut circuit that confers colonic inflammation, leading to impaired intestinal barrier function, and consequent behavioural deficits.

A paracrine circuit of IL-1ß/IL-1R1 between myeloid and tumor cells drives genotype-dependent glioblastoma progression.

Monocytes and monocyte-derived macrophages (MDMs) from blood circulation infiltrate glioblastoma (GBM) and promote growth. Here, we show that PDGFB-driven GBM cells induce the expression of the potent proinflammatory cytokine IL-1ß in MDM, which engages IL-1R1 in tumor cells, activates the NF-κB pathway, and subsequently leads to induction of monocyte chemoattractant proteins (MCPs). Thus, a feedforward paracrine circuit of IL-1ß/IL-1R1 between tumors and MDM creates an interdependence driving PDGFB-driven GBM progression. Genetic loss or locally antagonizing IL-1ß/IL-1R1 leads to reduced MDM infiltration, diminished tumor growth, and reduced exhausted CD8+ T cells and thereby extends the survival of tumor-bearing mice. In contrast to IL-1ß, IL-1α exhibits antitumor effects. Genetic deletion of Il1a/b is associated with decreased recruitment of lymphoid cells and loss-of-interferon signaling in various immune populations and subsets of malignant cells and is associated with decreased survival time of PDGFB-driven tumor-bearing mice. In contrast to PDGFB-driven GBM, Nf1-silenced tumors have a constitutively active NF-κB pathway, which drives the expression of MCPs to recruit monocytes into tumors. These results indicate local antagonism of IL-1ß could be considered as an effective therapy specifically for proneural GBM.

Trends in Immunotherapy Clinical Trials to Treat Glioblastoma: A Look at Progress and Challenges.

PURPOSE: We aimed to catalog past and present clinical trials on immunotherapy treatments for glioblastoma (GBM) and discover relevant trends in this field. METHODS: Former and ongoing clinical trials involving the use of immunotherapy to treat GBM were queried in July 2022 within the clinicaltrials.gov registry (https://clinicaltrials.gov/). Pertinent trials were categorized by variables including immunotherapy classification, tumor type (newly diagnosed versus recurrent), country of origin, start date, clinical phase, study completion status, estimated subject enrollment, design, publication status, and funding source. RESULTS: A list of 173 trials was identified in total. The number of immunotherapy clinical trials to treat GBM has increased over time. The largest proportion of trials were gene therapies (97 studies; 56.1%) and viral therapies (37 studies; 21.4%). Studies were designated as a biologic (45.1%), drug (43.9%), genetic (2.3%), or procedure (1.2%). Trials spanned 19 countries; China, the second largest contributor (5.8%) after the United States (70.0%), has increased clinical trial development in the past years. The average time to completion was 52.3 months. Trials were primarily funded by academic centers; however, one-fourth of the trials were funded by industry and 2 were funded by foundations. One-t of the trials were active and over one-third were linked to publications. CONCLUSIONS: Our findings provide a comprehensive summary of the state of immunotherapy clinical trials for GBM, highlighting the evolving nature and growing scope of this field.

Application of the Robotic-Assisted Digital Exoscope for Resection of Posterior Fossa Tumors in Adults: A Series of 45 Cases.

BACKGROUND AND OBJECTIVES: Complete safe resection is the goal when pursuing surgical treatment for posterior fossa (PF) tumors. Efforts have led to the development of the exoscope that delineates tumors from non-neoplastic brain. This investigation aims to assess patient outcomes where PF tumor resection is performed with the exoscope by a retromastoid or suboccipital approach. METHODS: A retrospective analysis was conducted for patients with PF tumors who underwent exoscope resection from 2017 to 2022. Patient demographics, clinical, operative, and outcome findings were collected. Extent of resection studies were also performed. Associations between perioperative data, discharge disposition, progression-free survival (PFS), and overall survival (OS) were evaluated. RESULTS: A total of 45 patients (22 male patients) with a median age of 57 years were assessed. Eighteen (40%) and 27 patients (60%) were diagnosed with malignant and benign tumors, respectively. Tumor neurovascular involvement was found in 28 patients (62%). Twenty-four (53%) and 20 (44%) tumors formed in the cerebellum and cerebellopontine angle cistern, respectively. One tumor (2%) was found in the cervicomedullary junction. The mean extent of resection was 96.7% for benign and malignant tumors. The PFS and OS rate at 6 months (PFS6, OS6) was 89.7% and 95.5%, respectively. Neurological complications included sensory loss and motor deficit, with 11 patients reporting no postoperative symptoms. Of the neurological complications, 14 were temporary and 9 were permanent. CONCLUSION: The exoscope is an effective intraoperative visualization tool for delineating PF tumors. In our series, we achieved low postoperative tumor volumes and a high gross total resection rate.

Transcranioplasty Ultrasonography Through a Sonolucent Prosthesis: A Review of Feasibility, Safety, and Benefits.

Data on the effectiveness of transcranioplasty ultrasonography through sonolucent cranioplasty (SC) are new and heterogeneous. We performed the first systematic literature review on SC. Ovid Embase, Ovid Medline, and Web of Science Core Collection were systematically searched and published full text articles detailing new use of SC for the purpose of neuroimaging were critically appraised and extracted. Of 16 eligible studies, 6 reported preclinical research and 12 reported clinical experiences encompassing 189 total patients with SC. The cohort age ranged from teens to 80s and was 60% (113/189) female. Sonolucent materials in clinical use are clear PMMA (polymethylmethacrylate), opaque PMMA, polyetheretherketone, and polyolefin. Overall indications included hydrocephalus (20%, 37/189), tumor (15%, 29/189), posterior fossa decompression (14%, 26/189), traumatic brain injury (11%, 20/189), bypass (27%, 52/189), intracerebral hemorrhage (4%, 7/189), ischemic stroke (3%, 5/189), aneurysm and subarachnoid hemorrhage (3%, 5/189), subdural hematoma (2%, 4/189), and vasculitis and other bone revisions (2%, 4/189). Complications described in the entire cohort included revision or delayed scalp healing (3%, 6/189), wound infection (3%, 5/189), epidural hematoma (2%, 3/189), cerebrospinal fluid leaks (1%, 2/189), new seizure (1%, 2/189), and oncologic relapse with subsequent prosthesis removal (<1%, 1/189). Most studies utilized linear or phased array ultrasound transducers at 3-12 MHz. Sources of artifact on sonographic imaging included prosthesis curvature, pneumocephalus, plating system, and dural sealant. Reported findings were mainly qualitative. We, therefore, suggest that future studies should collect quantitative measurement data during transcranioplasty ultrasonography to validate imaging techniques.

YB1 modulates the DNA damage response in medulloblastoma.

Y-box binding protein 1 (YBX1 or YB1) is a therapeutically relevant oncoprotein capable of RNA and DNA binding and mediating protein-protein interactions that drive proliferation, stemness, and resistance to platinum-based therapies. Given our previously published findings, the potential for YB1-driven cisplatin resistance in medulloblastoma (MB), and the limited studies exploring YB1-DNA repair protein interactions, we chose to investigate the role of YB1 in mediating radiation resistance in MB. MB, the most common pediatric malignant brain tumor, is treated with surgical resection, cranio-spinal radiation, and platinum-based chemotherapy, and could potentially benefit from YB1 inhibition. The role of YB1 in the response of MB to ionizing radiation (IR) has not yet been studied but remains relevant for determining potential anti-tumor synergy of YB1 inhibition with standard radiation therapy. We have previously shown that YB1 drives proliferation of cerebellar granular neural precursor cells (CGNPs) and murine Sonic Hedgehog (SHH) group MB cells. While others have demonstrated a link between YB1 and homologous recombination protein binding, functional and therapeutic implications remain unclear, particularly following IR-induced damage. Here we show that depleting YB1 in both SHH and Group 3 MB results not only in reduced proliferation but also synergizes with radiation due to differential response dynamics. YB1 silencing through shRNA followed by IR drives a predominantly NHEJ-dependent repair mechanism, leading to faster γH2AX resolution, premature cell cycle re-entry, checkpoint bypass, reduced proliferation, and increased senescence. These findings show that depleting YB1 in combination with radiation sensitizes SHH and Group 3 MB cells to radiation.

Access to Hepatitis C Treatment during and after Incarceration in New Jersey, United States: A Qualitative Study.

Despite effective antiviral therapy for hepatitis C virus (HCV), people who are incarcerated and those returning to the community face challenges in obtaining HCV treatment. We aimed to explore facilitators and barriers to HCV treatment during and after incarceration. From July-November 2020 and June-July 2021, we conducted 27 semi-structured interviews with residents who were formerly incarcerated in jail or prison. The interviews were audio-recorded and professionally transcribed. We used descriptive statistics to characterize the study sample and analyzed qualitative data thematically using an iterative process. Participants included five women and 22 men who self-identified as White (n = 14), Latinx (n = 8), and Black (n = 5). During incarceration, a key facilitator was having sufficient time to complete HCV treatment, and the corresponding barrier was delaying treatment initiation. After incarceration, a key facilitator was connecting with reentry programs (e.g., halfway house or rehabilitation program) that coordinated the treatment logistics and provided support with culturally sensitive staff. Barriers included a lack of insurance coverage and higher-ranking priorities (e.g., managing more immediate reentry challenges such as other comorbidities, employment, housing, and legal issues), low perceived risk of harm related to HCV, and active substance use. Incarceration and reentry pose distinct facilitators and challenges to accessing HCV treatment. These findings signal the need for interventions to improve engagement in HCV care both during and after incarceration to assist in closing the gap of untreated people living with HCV.

A Nationwide Study Characterizing the Risk and Outcome Profiles of Multilevel Fusion Procedures in Neuromuscular Scoliosis Patients with Neurofibromatosis Type 1.

BACKGROUND: Spine abnormalities are a common manifestation of Neurofibromatosis Type 1 (NF1); however, the outcomes of surgical treatment for NF1-associated spinal deformity are not well explored. The purpose of this study was to investigate the outcome and risk profiles of multilevel fusion surgery for NF1 patients. METHODS: The National Inpatient Sample was queried for NF1 and non-NF1 patient populations with neuromuscular scoliosis who underwent multilevel fusion surgery involving eight or more vertebral levels between 2004 and 2017. Multivariate regression modeling was used to explore the relationship between perioperative variables and pertinent outcomes. RESULTS: Of the 55,485 patients with scoliosis, 533 patients (0.96%) had NF1. Patients with NF1 were more likely to have comorbid solid tumors (P < 0.0001), clinical depression (P < 0.0001), peripheral vascular disease (P < 0.0001), and hypertension (P < 0.001). Following surgery, NF1 patients had a higher incidence of hydrocephalus (0.6% vs. 1.9% P = 0.002), seizures (4.9% vs. 5.7% P = 0.006), and accidental vessel laceration (0.3% vs.1.9% P = 0.011). Although there were no differences in overall complication rates or in-hospital mortality, multivariate regression revealed NF1 patients had an increased probability of pulmonary (OR 0.5, 95%CI 0.3-0.8, P = 0.004) complications. There were no significant differences in utilization, including nonhome discharge or extended hospitalization; however, patients with NF1 had higher total hospital charges (mean -$18739, SE 3384, P < 0.0001). CONCLUSIONS: These findings indicate that NF1 is associated with certain complications following multilevel fusion surgery but does not appear to be associated with differences in quality or cost outcomes. These results provide some guidance to surgeons and other healthcare professionals in their perioperative decision making by raising awareness about risk factors for NF1 patients undergoing multilevel fusion surgery. We intend for this study to set the national baseline for complications after multilevel fusion in the NF1 population.

Comparative Analysis of Early Outcomes and Complications of PSO Among Neurosurgeons and Orthopedic Surgeons.

STUDY DESIGN: Retrospective comparative cohort study using the National Surgical Quality Improvement Program. OBJECTIVE: The aim of this study was to evaluate trends in the annual number of PSOs performed, describe the patient populations associated with each cohort, and compare outcomes between specialties.Summary of Background Data:Pedicle subtraction osteotomies (PSO) are complex and advanced spine deformity surgical procedures performed by neurosurgeons and orthopedic surgeons. Though both sets of surgeons can be equally qualified and credentialed to perform a PSO, it is possible that differences in training and exposure could translate into differences in patient management and outcomes. METHODS: Patients that underwent lumbar PSO from 2005 to 2014 in the American College of Surgeons-National Surgical Quality Improvement Program registry were identified. Relevant demographic, preoperative comorbidity, and postoperative 30-day complications were queried and analyzed. The data was divided into 2 cohorts consisting of those patients who were treated by neurosurgeons versus orthopedic surgeons. Additional data from the Scoliosis Research Society Morbidity and Mortality database was queried and analyzed for comparison. RESULTS: Demographic and comorbidity factors were similar between the neurosurgery and orthopedic surgery cohorts, except there were higher rates of hypertension among orthopedic surgeon-performed PSOs (65.66% vs. 48.67%, P =0.004). Except for 2012, in every year queried, orthopedic surgeons reported more PSOs than neurosurgeons. In patients who underwent lumbar fusion surgery, there was a higher rate of PSOs if the surgery was performed by an orthopedic surgeon (OR 1.7824, 95% CI: 1.4017-2.2665). The incidence of deep vein thrombosis after PSOs was higher for neurosurgery compared with orthopedic surgery (8.85% vs. 1.20%, P =0.004). However, besides deep vein thrombosis, there were no salient differences in surgical complication rates between neurosurgeon-performed PSOs and orthopedic surgeon-performed PSOs. CONCLUSIONS: The number of PSO procedures performed by neurosurgeons and orthopedic surgeons has increased annually. Differences in outcomes between neurosurgeons and orthopedic surgeons suggest an opportunity for wider assessment and alignment of adult spinal deformity surgery exposure and training across specialties.

The Knosp Criteria Revisited: 3-Dimensional Volumetric Analysis as a Predictive Tool for Extent of Resection in Complex Endoscopic Pituitary Surgery.

BACKGROUND: The Knosp criteria have been the historical standard for predicting cavernous sinus invasion, and therefore extent of surgical resection, of pituitary macroadenomas. Few studies have sought to reappraise the utility of this tool after recent advances in visualization and modeling of tumors in complex endoscopic surgery. OBJECTIVE: To evaluate our proposed alternative method, using 3-dimensional (3D) volumetric imaging, and whether it can better predict extent of resection in nonfunctional pituitary adenomas. METHODS: Patients who underwent endoscopic transsphenoidal resection of pituitary macroadenomas at our institution were reviewed. Information was collected on neurological, endocrine, and visual function. Volumetric segmentation was performed using 3D Slicer software. Relationship of tumor volume, clinical features, and Knosp grade on extent of resection was examined. RESULTS: One hundred forty patients were identified who had transsphenoidal resection of nonfunctional pituitary adenomas. Macroadenomas had a median volume of 6 cm 3 (IQR 3.4-8.7), and 17% had a unilateral Knosp grade of at least 3B. On multiple logistic regression, only smaller log-transformed preoperative tumor volume was independently associated with increased odds of gross total resection (GTR; odds ratio: 0.27, 95% CI: 0.07-0.89, P < .05) when controlling for tumor proliferative status, age, and sex (area under the curve 0.67). The Knosp criteria did not independently predict GTR in this cohort ( P > .05, area under the curve 0.46). CONCLUSION: Increasing use of volumetric 3D imaging may better anticipate extent of resection compared with the Knosp grade metric and may have a greater positive predictive value for GTR. More research is needed to validate these findings and implement them using automated methods.

Laser hyperthermia: Past, present, and future.

Magnetic resonance imaging-guided laser interstitial thermal therapy (LITT) is an ablative procedure using heat from a laser to provide cytoreduction in tissue. It is a minimally invasive procedure that has been used in intracranial pathologies such as high-grade gliomas, metastatic lesions, epilepsy, and other lesions. While LITT may offer a more acceptable complication profile compared to open surgery, the role of laser therapy for intracranial lesions in current treatment paradigms continues to evolve. This review will focus on the background and application of LITT, the current evidence for its use, and future directions for the technology.

Neuroimaging through Sonolucent Cranioplasty: A Systematic Scoping Review Protocol.

Cranioplasty is a neurosurgical procedure in which the skull bone is repaired after craniectomy. Recently, studies have suggested that sonolucent synthetic materials are safe and useful for cranioplasty. Sonolucent cranioplasty (SC) implants provide unprecedented opportunity in adult neurosurgery to monitor neuroanatomy, assess hemodynamics, view devices located within the implant, and conduct focused ultrasound treatments. Current research on SC includes proof-of-concept cadaveric studies, patient-related safety and feasibility studies, and case series demonstrating transcranioplasty ultrasonography (TCUS). The purpose of this protocol is to investigate the current literature on SC use and outcomes in TCUS. We will perform a systematic literature search following PRISMA-ScR guidelines. The search will be conducted using Ovid Embase, Ovid Medline, and Web of Science Core Collection databases. Titles, abstracts, and full texts will be screened. Joanna Briggs Institute critical appraisal tools will be utilized. Data extraction points will include subject characteristics, SC implant characteristics, ultrasound characteristics, and sonographic findings. These findings will provide a comprehensive review of the literature on sonolucent cranioplasty and directions for future research.

The Impact of Obstructive Sleep Apnea on Clinical, Perioperative, and Cost Outcomes in Patients Who Underwent Posterior Cervical Decompression and Fusion: A Single-Center Retrospective Analysis From 2008 to 2016.

BACKGROUND: Obstructive sleep apnea (OSA) is a pervasive problem that can result in diminished neurocognitive performance, increased risk of all-cause mortality, and significant cardiovascular disease. While previous studies have examined risk factors that influence outcomes following cervical fusion procedures, to our knowledge, no study has examined the cost or outcome profiles for posterior cervical decompression and fusion (PCDF) procedures in patients with OSA. METHODS: All cases at a single institution between 2008 and 2016 involving a PCDF were included. The primary outcome was prolonged extubation, defined as an extubation that took place outside of the operating room. Secondary outcomes included admission to the intensive care unit (ICU), complications, extended hospitalization, nonhome discharge, readmission within 30 and 90 days, emergency room visit within 30 and 90 days, and higher total costs. RESULTS: We reviewed 1191 PCDF cases, of which 93 patients (7.81%) had a history of OSA. At the univariate level, patients with OSA had higher rates of ICU admissions (33.3% vs 16.8%, P < 0.0001), total complications (29.0% vs 19.0%, P = 0.0202), and respiratory complications (12.9% vs 6.6%, P = 0.0217). Multivariate regression analyses revealed no difference in the odds of a prolonged extubation (P = 0.4773) and showed that history of OSA was not predictive of higher costs. However, a significant difference was observed in the odds of having an ICU admission (P = 0.0046). CONCLUSION: While patients with sleep apnea may be more likely to be admitted to the ICU postoperatively, OSA status a lone is not a risk factor for poor primary and secondary clinical outcomes following posterior cervical fusion procedures. CLINICAL RELEVANCE: Various deformities of the cervical spine can exert extraluminal forces that partially collapse or obstruct the airway, thereby predisposing patients to OSA; however, no study has examined the cost or outcome profiles for PCDF procedures in patients with OSA. Therefore, this investigation highlights the ways in which OSA influences the risks, outcomes, and costs following PCDF using medical data from an institutional registry.

5-Aminolevulinic acid for enhanced surgical visualization of high-grade gliomas: a prospective, multicenter study.

OBJECTIVE: Greater extent of resection (EOR) is associated with longer overall survival in patients with high-grade gliomas (HGGs). 5-Aminolevulinic acid (5-ALA) can increase EOR by improving intraoperative visualization of contrast-enhancing tumor during fluorescence-guided surgery (FGS). When administered orally, 5-ALA is converted by glioma cells into protoporphyrin IX (PPIX), which fluoresces under blue 400-nm light. 5-ALA has been available for use in Europe since 2010, but only recently gained FDA approval as an intraoperative imaging agent for HGG tissue. In this first-ever, to the authors' knowledge, multicenter 5-ALA FGS study conducted in the United States, the primary objectives were the following: 1) assess the diagnostic accuracy of 5-ALA-induced PPIX fluorescence for HGG histopathology across diverse centers and surgeons; and 2) assess the safety profile of 5-ALA FGS, with particular attention to neurological morbidity. METHODS: This single-arm, multicenter, prospective study included adults aged 18-80 years with Karnofsky Performance Status (KPS) score > 60 and an MRI diagnosis of suspected new or recurrent resectable HGG. Intraoperatively, 3-5 samples per tumor were taken and their fluorescence status was recorded by the surgeon. Specimens were submitted for histopathological analysis. Patients were followed for 6 weeks postoperatively for adverse events, changes in the neurological exam, and KPS score. Multivariate analyses were performed of the outcomes of KPS decline, EOR, and residual enhancing tumor volume to identify predictive patient and intraoperative variables. RESULTS: Sixty-nine patients underwent 5-ALA FGS, providing 275 tumor samples for analysis. PPIX fluorescence had a sensitivity of 96.5%, specificity of 29.4%, positive predictive value (PPV) for HGG histopathology of 95.4%, and diagnostic accuracy of 92.4%. Drug-related adverse events occurred at a rate of 22%. Serious adverse events due to intraoperative neurological injury, which may have resulted from FGS, occurred at a rate of 4.3%. There were 2 deaths unrelated to FGS. Compared to preoperative KPS scores, postoperative KPS scores were significantly lower at 48 hours and 2 weeks but were not different at 6 weeks postoperatively. Complete resection of enhancing tumor occurred in 51.9% of patients. Smaller preoperative tumor volume and use of intraoperative MRI predicted lower residual tumor volume. CONCLUSIONS: PPIX fluorescence, as judged by the surgeon, has a high sensitivity and PPV for HGG. 5-ALA was well tolerated in terms of drug-related adverse events, and its application by trained surgeons in FGS for HGGs was not associated with any excess neurological morbidity.

Robotic-Assisted Digital Exoscope for Resection of Cerebral Metastases: A Case Series.

BACKGROUND: Surgical resection is the primary treatment for cerebral metastases with safe complete resection as the goal. The robotically assisted digital surgical exoscope is a novel system with advanced visualization methods with recent applications in neurosurgery. OBJECTIVE: To evaluate the outcomes for patients with cerebral metastases undergoing resection with the surgical exoscope. METHODS: Data were retrospectively collected from patients with cerebral metastases where resection was achieved with using the surgical exoscope from 2016 to 2020. Demographics, clinical, imaging, and operative and outcome findings were collected. The relationship between perioperative data and discharge disposition as well as progression-free survival (PFS) and 12 mo overall survival (OS) was assessed. RESULTS: A total of 31 patients (19 males) with a median patient age 63 yr (range 38-80) were included. Average pre- and postoperative volumes were 18.1 cc and 0.75 cc, respectively. Mean depth of the resected lesions was 0.6 cm (range 0-3.6 cm). Complete resection was achieved in 64.5% of patients. The mean extent of resection was 96.7%, with 71.0% achieving PFS at 6 mo. Overall PFS rate was 58.1% and the OS rate at 12 mo was 83.9%. Neurological complications included motor (35.5%) and sensory (12.9%) deficits, with 12 patients reporting no postoperative symptoms. CONCLUSION: The surgical exoscope can delineate tumor tissues with high resolution, as shown by a gross total resection achieved for the majority of cases in our series. Postoperative complications and patient outcomes were similar to those reported with use of the operative microscope. Use of the exoscope can provide optimal visualization and delineation of cerebral metastases.

Bioelectrical spectroscopy impedance phase angle is not associated with nutritional status in a stable cohort of paediatric inflammatory bowel disease patients.

BACKGROUND & AIMS: Nutritional assessment in paediatric inflammatory bowel disease (IBD) is key to supporting growth whilst minimising adiposity. Bedside assessment using bioelectrical impedance spectroscopy (BIS) has previous identified patients with declining cellular and nutritional health. We aimed to assess BIS measures in stable paediatric IBD patient. METHODS: Stable IBD patients were recruited at routine hospital visits. All patients underwent BIS, anthropometry and disease activity assessment. Multivariable regression and receiver operator curve (ROC) analyses were undertaken to assess the utility of BIS phase angle 50 KHz (PA-50) and 200/5 KHz impedance ratio (IR) in nutritional assessment. RESULTS: There were 140 study visits from 97 patients, mean age 14.49 years, 62.9% Crohn's disease. Mean BMI Z-score (BMIZ) was 0.31 (range -2.97 to 3.99), 33% of patients were overweight (BMIZ>1) and 13.8% of patients were underweight (BMIZ < -1). Crohn's disease patients had a lower mean BMIZ score 0.14, compared to ulcerative colitis, 0.68, p = 0.007. There was no relationship between PA-50 and BMIZ or disease activity. IR was not related to disease activity but was negatively related to BMIZ in a multivariable regression, accounting for age, sex and disease subtype (beta -0.331, p = 0.001). ROC analyses did not identify a clinically useful cut off for either PA-50 or IR to identify patients with active disease, biologic use or BMIZ>1 or < -1. CONCLUSION: BIS appears to have limited added value in nutritional assessment of stable paediatric IBD patients. Nearly 1/3 patients were overweight and personalised approach to supplementation is vital to avoid overnutrition.

Current knowledge on the immune microenvironment and emerging immunotherapies in diffuse midline glioma.

Diffuse midline glioma (DMG) is an incurable malignancy with the highest mortality rate among pediatric brain tumors. While radiotherapy and chemotherapy are the most common treatments, these modalities have limited promise. Due to their diffuse nature in critical areas of the brain, the prognosis of DMG remains dismal. DMGs are characterized by unique phenotypic heterogeneity and histological features. Mutations of H3K27M, TP53, and ACVR1 drive DMG tumorigenesis. Histological artifacts include pseudopalisading necrosis and vascular endothelial proliferation. Mouse models that recapitulate human DMG have been used to study key driver mutations and the tumor microenvironment. DMG consists of a largely immunologically cold tumor microenvironment that lacks immune cell infiltration, immunosuppressive factors, and immune surveillance. While tumor-associated macrophages are the most abundant immune cell population, there is reduced T lymphocyte infiltration. Immunotherapies can stimulate the immune system to find, attack, and eliminate cancer cells. However, it is critical to understand the immune microenvironment of DMG before designing immunotherapies since differences in the microenvironment influence treatment efficacy. To this end, our review aims to overview the immune microenvironment of DMG, discuss emerging insights about the immune landscape that drives disease pathophysiology, and present recent findings and new opportunities for therapeutic discovery.

Fluorescence-Guided High-Grade Glioma Surgery More Than Four Hours After 5-Aminolevulinic Acid Administration.

Background: Fluorescence-guided surgery (FGS) using 5-aminolevulic acid (5-ALA) is a widely used strategy for delineating tumor tissue from surrounding brain intraoperatively during high-grade glioma (HGG) resection. 5-ALA reaches peak plasma levels ~4 h after oral administration and is currently approved by the FDA for use 2-4 h prior to induction to anesthesia. Objective: To demonstrate that there is adequate intraoperative fluorescence in cases undergoing surgery more than 4 h after 5-ALA administration and compare survival and radiological recurrence to previous data. Methods: Retrospective analysis of HGG patients undergoing FGS more than 4 h after 5-ALA administration was performed at two institutions. Clinical, operative, and radiographic pre- and post-operative characteristics are presented. Results: Sixteen patients were identified, 6 of them female (37.5%), with mean (SD) age of 59.3 ± 11.5 years. Preoperative mean modified Rankin score (mRS) was 2 ± 1. All patients were dosed with 20 mg/kg 5-ALA the morning of surgery. Mean time to anesthesia induction was 425 ± 334 min. All cases had adequate intraoperative fluorescence. Eloquent cortex was involved in 12 cases (75%), and 13 cases (81.3%) had residual contrast enhancement on postoperative MRI. Mean progression-free survival was 5 ± 3 months. In the study period, 6 patients died (37.5%), mean mRS was 2.3 ± 1.3, Karnofsky score 71.9 ± 22.1, and NIHSS 3.9 ± 2.4. Conclusion: Here we demonstrate that 5-ALA-guided HGG resection can be performed safely more than 4 h after administration, with clinical results largely similar to previous reports. Relaxation of timing restrictions could improve procedure workflow in busy neurosurgical centers, without additional risk to patients.

Medical Student Publications in Neurosurgery: At Which U.S. Academic Institutions Do Medical Students Publish Most?

BACKGROUND: The neurosurgery residency match is a competitive process. While medical research offers esteemed learning opportunities, productivity is closely evaluated by residency programs. Accordingly, students work diligently to make contributions on projects within their neurosurgery departments. The present study evaluated medical student research productivity for each of the 118 U.S. neurosurgery residency programs. METHODS: A retrospective review of publications for 118 neurosurgery programs from January 1, 2015, to April 1, 2020, was performed. The primary outcome was any publication with a medical student as the first author. Secondary outcomes included number of faculty in each department, department region, and medical school ranking. The number of student first author publications was compared among programs, regions, and medical schools. RESULTS: Mean numbers of medical student first author publications and faculty members per institution were 16.27 and 14.46, respectively. The top 3 neurosurgery departments with the greatest number of student first author publications were Johns Hopkins University, Brigham and Women's Hospital, and University of California, San Francisco. Salient findings included a positive correlation between the number of medical student first author publications from a neurosurgery department and the number of departmental faculty (P < 0.001, R = 0.69). Additionally, the mean number of first author medical student publications at the top 30 programs was higher than the mean for the remaining programs (P < 0.0001). CONCLUSIONS: This study is the first to evaluate neurosurgery medical student productivity in North America. By systematizing first authorships, incoming students who desire to pursue neurosurgery can be informed of institutions with student involvement, and departments that use medical student expertise can be recognized.