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The Global Neurosurgery Committee (GNC) of the World Federation of Neurosurgical Societies (WFNS) launched the Global Action Plan during the 2016 Bogota Declaration on Global Neurosurgery in Colombia in order to coordinate efforts and bring neurosurgeons around the world to address unmet neurosurgical care. The Global Action Plan contains five objectives: Amplify, Align, Advance, Assimilate and Advocate for neurosurgical care. In this paper, we present the goals and the work of the Advance team. The goal of the Advance objective was to “A. Map research output by region and themes, B. Establish one or more Global Neurosurgery research grant and/or award mechanisms, C. Advocate for Global Neurosurgery category/sections in major neurosurgery journals (3 or more by 2021), D. Establish funding mechanisms for training in future leaders in the public health practice of Global Neurosurgery (2 or more by 2021), E. Inclusion of Global Neurosurgery Sessions in major neurosurgery meetings (>75% by 2021), F. Establish a mentoring relationship between editorial board members from HIC and LMICs (>1 by 2021), and G. Establish a mentoring relationship between authors from HIC and LMICs (>1 by 2021).

To elucidate the pathogenesis of vein of Galen malformations (VOGMs), the most common and severe congenital brain arteriovenous malformation, we performed an integrated analysis of 310 VOGM proband-family exomes and 336,326 human cerebrovasculature single-cell transcriptomes. We found the Ras suppressor p120 RasGAP (RASA1) harbored a genome-wide significant burden of loss-of-functionde novovariants (p=4.79×10-7). Rare, damaging transmitted variants were enriched in Ephrin receptor-B4 (EPHB4) (p=1.22×10-5), which cooperates with p120 RasGAP to limit Ras activation. Other probands had pathogenic variants inACVRL1,NOTCH1,ITGB1, andPTPN11.ACVRL1variants were also identified in a multi-generational VOGM pedigree. Integrative genomics defined developing endothelial cells as a key spatio-temporal locus of VOGM pathophysiology. Mice expressing a VOGM-specificEPHB4kinase-domain missense variant exhibited constitutive endothelial Ras/ERK/MAPK activation and impaired hierarchical development of angiogenesis-regulated arterial-capillary-venous networks, but only when carrying a “second-hit” allele. These results illuminate human arterio-venous development and VOGM pathobiology and have clinical implications.

When it comes to surgical subspecialties such as neurological surgery, access to care goes from being a disparity to a complete absencein many cases as access to neurosurgical care is no longer a right but a luxury. To address this need multiple organizations have workedto improve access to neurosurgery, and as global neurosurgical efforts expand a concerted effort is necessary to ensure safe,sustainable and equitable care is provided and efforts by the multiple stakeholders are not duplicated. To that end, the GlobalNeurosurgery Committee (GNC) of the World Federation of Neurosurgical Societies (WFNS) created an action plan for directedcollaboration. We introduce the GNC Action Plan here and describe its guiding principles, divided into five objectives that encompassthe necessary steps to achieve universal access to neurosurgical care: 1) amplifying access to neurosurgical care, 2) aligning globalneurosurgery activities, 3) advancing global neurosurgery research efforts, 4) assimilating neurosurgical capacity building into s urgicalsystems, and 5) advocating for neurosurgical care within Universal Health Coverage.

Introduction 33 million people worldwide face catastrophic health expenditures each year from surgery and anesthesia. This study aims to collate the current literature on out-of-pocket (OOP) costs of Bellwether neurosurgical procedures in low- and middle-income countries (LMICs) to provide a basis for calculations of financial burdens, determine deficits in the literature, and guide further research efforts. Method MEDLINE/PubMed, Embase, Cochrane Library, Google Scholar and Relief Web were searched for articles containing data on OOP costs for neurosurgical Bellwether procedures in LMICs. Of 415 relevant publications that were identified, 4 met inclusion criteria. Results One study from Uganda found median direct medical and non-medical costs to be USD 118.06 and USD 84.33, respectively. A study from Vietnam found the total medical care and surgery for head injury OOP cost to be USD 287.30 and USD 63, respectively. A multi-country study found the cost of neuroimaging to vary by country income level and public/private institutions with a range of USD 14 to USD 286. Discussion There is great variability in OOP expenses for neurosurgical Bellwether procedures, but the average cost to the patient did not exceed USD 300. When assessing patient expenditures, attention should be given to average country income, as the cost of a medical expense may be lower in an LMIC but the impact on the patient greater due to lower income. More studies on OOP costs for neurosurgical interventions in LMICs are needed to provide evidence for policy changes geared towards financial risk protection.

Introduction 33 million people worldwide face catastrophic health expenditures each year from surgery and anesthesia. This study aims to collate the current literature on out-of-pocket (OOP) costs of Bellwether neurosurgical procedures in low- and middle-income countries (LMICs) to provide a basis for calculations of financial burdens, determine deficits in the literature, and guide further research efforts. Methods MEDLINE/PubMed, Embase, Cochrane Library, Google Scholar and Relief Web were searched for articles containing data on OOP costs for neurosurgical Bellwether procedures in LMICs. Of 415 relevant publications that were identified, 4 met inclusion criteria. Results One study from Uganda found median direct medical and non-medical costs to be USD 118.06 and USD 84.33, respectively. A study from Vietnam found the total medical care and surgery for head injury OOP cost to be USD 287.30 and USD 63, respectively. A multi-country study found the cost of neuroimaging to vary by country income level and public/private institutions with a range of USD 14 to USD 286. Discussion There is great variability in OOP expenses for neurosurgical Bellwether procedures, but the average cost to the patient did not exceed USD 300. When assessing patient expenditures, attention should be given to average country income, as the cost of a medical expense may be lower in an LMIC but the impact on the patient greater due to lower income. More studies on OOP costs for neurosurgical interventions in LMICs are needed to provide evidence for policy changes geared towards financial risk protection.

Intracranial abscess in the pediatric population is an overall rare occurrence-4 in a million. The most common predisposing factor is underlying cyanotic congenital heart disease (CCHD), which is associated with ~ 30% of all cases. We present an unusual case of cerebral abscess in a 17-month-old female with partially treated Tetralogy of Fallot and fever of unknown origin without associated neurologic symptoms. We propose a low threshold for intracranial imaging as part of the fever of unknown origin work-up in children with underlying cyanotic congenital heart disease.

Global neurosurgery encompasses the neurosurgical care and public health efforts to ensure timely and safe neurosurgical care accessfor all who need it (1). Over the past several decades, global neurosurgery has been championed by many individuals, which has led toa broader interest in developing larger collaborative, sustainable neurosurgical care efforts. On a national level, neurosurgicaleducational opportunities have grown through courses, online education, and fellowships. Given the growing global burden ofneurosurgical disease, there is a significant opportunity and need for worldwide neurosurgery and neurosurgical education worldwide,especially in low- and middle-income countries (LMICs)

OBJECTIVE Achieving rigid spinal fixation can be challenging in patients with cancer-related instability, as factors such as osteopenia, radiation, and immunosuppression adversely affect bone quality. Augmenting pedicle screws with cement is a strategy to overcome construct failure. This study aimed to assess the safety and efficacy of cement augmentation with fenestrated pedicle screws in patients undergoing posterior, open thoracolumbar surgery for spinal metastases. METHODS A retrospective review was performed for patients who underwent surgery for cancer-related spine instability from 2016 to 2019 at the Massachusetts General Hospital. Patient demographics, surgical details, radiographic characteristics, patterns of cement extravasation, complications, and prospectively collected Patient-Reported Outcomes Measurement Information System Pain Interference and Pain Intensity scores were analyzed using descriptive statistics. Logistic regression was performed to determine factors associated with cement extravasation. RESULTS Sixty-nine patients underwent open posterior surgery with a total of 502 cement-augmented screws (mean 7.8 screws per construct). The median follow-up period for those who survived past 90 days was 25.3 months (IQR 10.8–34.6 months). Thirteen patients (18.8%) either died within 90 days or were lost to follow-up. Postoperative CT was performed to assess the instrumentation and patterns of cement extravasation. There was no screw loosening, pullout, or failure. The rate of cement extravasation was 28.9% (145/502), most commonly through the segmental veins (77/145, 53.1%). Screws breaching the lateral border of the pedicle but with fenestrations within the vertebral body were associated with a higher risk of leakage through the segmental veins compared with screws without any breach (OR 8.77, 95% CI 2.84–29.79; p < 0.001). Cement extravasation did not cause symptoms except in 1 patient who developed a symptomatic thoracic radiculopathy requiring decompression. There was 1 case of asymptomatic pulmonary cement embolism. Patients experienced significant pain improvement at the 3-month follow-up, with decreases in Pain Interference (mean change 15.8, 95% CI 14.5–17.1; p < 0.001) and Pain Intensity (mean change 28.5, 95% CI 26.7–30.4; p < 0.001). CONCLUSIONS Cement augmentation through fenestrated pedicle screws is a safe and effective option for spine stabilization in the cancer population. The risk of clinically significant adverse events from cement extravasation is very low.

info:eu-repo/semantics/published

NMR studies of post-translationally modified proteins are complicated by the lack of an efficient method to produce isotope enriched recombinant proteins in cultured mammalian cells. We show that reducing the glucose concentration and substituting glutamate for glutamine in serum-free medium increased cell viability while simultaneously increasing recombinant protein yield and the enrichment of non-essential amino acids compared to culture in unmodified, serum-free medium. Adding dichloroacetate, a pyruvate dehydrogenase kinase inhibitor, further improves cell viability, recombinant protein yield, and isotope enrichment. We demonstrate the method by producing partially enriched recombinant Thy1 glycoprotein from Lec1 Chinese hamster ovary (CHO) cells using U-¹³C-glucose and ¹⁵N-glutamate as labeled precursors. This study suggests that uniformly ¹⁵N,¹³C-labeled recombinant proteins may be produced in cultured mammalian cells starting from a mixture of labeled essential amino acids, glucose, and glutamate.