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Background and Objectives: Augmented reality head-mounted display (AR-HMD) is a novel technology that provides surgeons with a real-time CT-guided 3-dimensional recapitulation of a patient's spinal anatomy. In this case series, we explore the use of AR-HMD alongside more traditional robotic assistance in surgical spine trauma cases to determine their effect on operative costs and perioperative outcomes. Materials and Methods: We retrospectively reviewed trauma patients who underwent pedicle screw placement surgery guided by AR-HMD or robotic-assisted platforms at an academic tertiary care center between 1 January 2021 and 31 December 2022. Outcome distributions were compared using the Mann–Whitney U test. Results: The AR cohort (n = 9) had a mean age of 66 years, BMI of 29.4 kg/m2, Charlson Comorbidity Index (CCI) of 4.1, and Surgical Invasiveness Index (SII) of 8.8. In total, 77 pedicle screws were placed in this cohort. Intra-operatively, there was a mean blood loss of 378 mL, 0.78 units transfused, 398 min spent in the operating room, and a 20-day LOS. The robotic cohort (n = 13) had a mean age of 56 years, BMI of 27.1 kg/m2, CCI of 3.8, and SII of 14.2. In total, 128 pedicle screws were placed in this cohort. Intra-operatively, there was a mean blood loss of 432 mL, 0.46 units transfused units used, 331 min spent in the operating room, and a 10.4-day LOS. No significant difference was found between the two cohorts in any outcome metrics. Conclusions: Although the need to address urgent spinal conditions poses a significant challenge to the implementation of innovative technologies in spine surgery, this study represents an initial effort to show that AR-HMD can yield comparable outcomes to traditional robotic surgical techniques. Moreover, it highlights the potential for AR-HMD to be readily integrated into Level 1 trauma centers without requiring extensive modifications or adjustments. [ABSTRACT FROM AUTHOR]

Although bone marrow‐derived mesenchymal stem cells (BMCs) have been widely used in spinal fusion procedures, adipose‐derived stem cells (ASCs) offer a number of advantages as an alternative clinical cell source. This study directly compares the efficacy of ASCs and BMCs from the same donor animals to achieve successful fusion when combined with a clinical‐grade bone graft substitute in a rat lumbar fusion model. ASCs and BMCs were isolated from the same Lewis donor rats and grown to passage 2 (P2). Single‐level bilateral posterolateral intertransverse process lumbar fusion surgery was performed on syngeneic rats divided into three experimental groups: clinical‐grade bone graft substitute alone (CBGS); CBGS+ rat ASCs (rASC); and, CBGS+ rat BMCs (rBMC). Eight weeks postoperatively, fusion was evaluated via micro‐CT, manual palpation and histology. In vitro analysis of the osteogenic capacity of rBMCs and rASCs was also performed. Results indicated that the average fusion volume in the rASC group was the largest and was significantly larger than the CBGS group. Although the rASC group displayed the highest fusion rates via micro‐CT and manual palpation, this difference was not statistically significant. Cell‐seeded grafts showed more histological bone formation than cell‐free grafts. P2 rASCs and rBMCs displayed similar in vitro osteogenic differentiation capacities. Overall, this study showed that, when combined with a clinical‐grade bone graft substitute in a rat model, rASCs cells yielded the largest fusion masses and comparable fusion results to rBMCs. These results add to growing evidence that ASCs provide an attractive alternative to BMCs for spinal fusion procedures. [ABSTRACT FROM AUTHOR]

Vascularization is critical for skull development, maintenance, and healing. Yet, there remains a significant knowledge gap in the relationship of blood vessels to cranial skeletal progenitors during these processes. Here, we introduce a quantitative 3D imaging platform to enable the visualization and analysis of high-resolution data sets (>100 GB) throughout the entire murine calvarium. Using this technique, we provide single-cell resolution 3D maps of vessel phenotypes and skeletal progenitors in the frontoparietal cranial bones. Through these high-resolution data sets, we demonstrate that CD31hiEmcnhi vessels are spatially correlated with both Osterix+ and Gli1+ skeletal progenitors during postnatal growth, healing, and stimulated remodeling, and are concentrated at transcortical canals and osteogenic fronts. Interestingly, we find that this relationship is weakened in mice with a conditional knockout of PDGF-BB in TRAP+ osteoclasts, suggesting a potential role for osteoclasts in maintaining the native cranial microvascular environment. Our findings provide a foundational framework for understanding how blood vessels and skeletal progenitors spatially interact in cranial bone, and will enable more targeted studies into the mechanisms of skull disease pathologies and treatments. Additionally, our technique can be readily adapted to study numerous cell types and investigate other elusive phenomena in cranial bone biology. Vascularization is critical for cranial bone growth, maintenance, and healing, but it remains unknown how blood vessels are spatially distributed in the calvarium, and how they interact with skeletal progenitors during these processes. Here, the authors apply a quantitative light-sheet imaging platform to visualize and analyze the relationship between blood vessels and skeletal progenitors throughout the murine calvarium. [ABSTRACT FROM AUTHOR]

Astrocytoma is the most common type of primary brain tumor. The risk factors for astrocytoma are poorly understood; however, germline genetic variants account for 25% of the risk of developing gliomas. In this study, we assessed the risk of astrocytoma associated with variants in AGT, known by its role in angiogenesis, TP53, a well-known tumor suppressor and the DNA repair gene MGMT in a Mexican population. A case–control study was performed in 49 adult Mexican patients with grade II–IV astrocytoma. Sequencing of exons and untranslated regions of AGT, MGMT, and TP53 from was carried in an Ion Torrent platform. Individuals with Mexican Ancestry from the 1000 Genomes Project were used as controls. Variants found in our cohort were then assessed in a The Cancer Genome Atlas astrocytoma pan-ethnic validation cohort. Variants rs1926723 located in AGT (OR 2.74, 1.40–5.36 95% CI), rs7896488 in MGMT (OR 3.43, 1.17–10.10 95% CI), and rs4968187 in TP53 (OR 2.48, 1.26–4.88 95% CI) were significantly associated with the risk of astrocytoma after multiple-testing correction. This is the first study where the AGT rs1926723 variant, TP53 rs4968187, and MGMT rs7896488 were found to be associated with the risk of developing an astrocytoma. [ABSTRACT FROM AUTHOR]

Background: Despite widespread use of femoral-sourced allografts in clinical spinal fusion procedures and the increasing interest in using femoral reamer–irrigator–aspirator (RIA) autograft in clinical bone grafting, few studies have examined the efficacy of femoral grafts compared to iliac crest grafts in spinal fusion. The objective of this study was to directly compare the use of autologous iliac crest with syngeneic femoral and iliac allograft bone in the rat model of lumbar spinal fusion. Methods: Single-level bilateral posterolateral intertransverse process lumbar spinal fusion surgery was performed on Lewis rats divided into three experimental groups: iliac crest autograft, syngeneic iliac crest allograft, and syngeneic femoral allograft bone. Eight weeks postoperatively, fusion was evaluated via microCT analysis, manual palpation, and histology. In vitro analysis of the colony-forming and osteogenic capacity of bone marrow cells derived from rat femurs and hips was also performed to determine whether there was a correlation with the fusion efficacy of these graft sources. Results: Although no differences were observed between groups in CT fusion mass volumes, iliac allografts displayed an increased number of radiographically fused fusion masses and a higher rate of bilateral fusion via manual palpation. Histologically, hip-derived grafts showed better integration with host bone than femur derived ones, likely associated with the higher concentration of osteogenic progenitor cells observed in hip-derived bone marrow. Conclusions: This study demonstrates the feasibility of using syngeneic allograft bone in place of autograft bone within inbred rat fusion models and highlights the need for further study of femoral-derived grafts in fusion. [ABSTRACT FROM AUTHOR]

Background: Local, intrawound use of antibiotic powder, such as vancomycin and tobramycin, in spinal fusion surgery has become an increasingly common prophylactic measure in an attempt to reduce rates of postsurgical infection. However, the effects of localized antibiotic delivery on fusion remain unclear. The objective of this study was to examine the in vivo effects of intraoperative local delivery of 2 antibiotics commonly used in bone-grafting surgery on spinal fusion outcomes in a rat model. Methods: Single-level (L4-L5), bilateral posterolateral intertransverse process lumbar fusion surgery was performed on 60 female Lewis rats (6 to 8 weeks of age) using syngeneic iliac crest allograft mixed with clinical bone-graft substitute and varying concentrations of antibiotics (n = 12 each): (1) control without any antibiotics, (2) low-dose vancomycin (14.3 mg/kg), (3) high-dose vancomycin (71.5 mg/kg), (4) low-dose tobramycin (28.6 mg/kg), and (5) high-dose tobramycin (143 mg/kg). Eight weeks postoperatively, fusion was evaluated via micro-computed tomography ([micro]CT), manual palpation, and histological analysis, with blinding to treatment group. In the [micro]CT analysis, fusion-mass volumes were measured for each rat. Each spine specimen (L4-L5) was rated (manual palpation score) on a scale of 2 to 0 (2 = fused, 1 = partially fused, and 0 = non-fused). Results: The mean fusion-mass volume on [micro]CT (mm3) was as follows: control, 29.3 +/- 6.2; low-dose vancomycin, 26.3 +/- 8.9; high-dose vancomycin, 18.8 +/- 7.9; low-dose tobramycin, 32.7 +/- 9.0; and high-dose tobramycin, 43.8 +/- 11.9 (control versus high-dose vancomycin, p < 0.05; and control versus high-dose tobramycin, p < 0.05). The mean manual palpation score for each group was as follows: control, 1.46 +/- 0.58; low-dose vancomycin, 0.86 +/- 0.87; high-dose vancomycin, 0.68 +/- 0.62; low-dose tobramycin, 1.25 +/- 0.71; and high-dose tobramycin, 1.32 +/- 0.72 (control versus high-dose vancomycin, p < 0.05). The histological analyses demonstrated a similar trend with regard to spinal fusion volume. Conclusions: Intraoperative local application of vancomycin, particularly at a supraphysiological dosage, may have detrimental effects on fusion-mass formation. No inhibitory effect of tobramycin on fusion-mass formation was observed. Clinical Relevance: When spine surgeons decide to use intraoperative intrawound antibiotics in spinal fusion surgery, they should weigh the reduction in surgical site infection against a possible inhibitory effect on fusion. [ABSTRACT FROM AUTHOR]

Purpose: Bone marrow aspirate has been successfully used alongside a variety of grafting materials to clinically augment spinal fusion. However, little is known about the fate of these transplanted cells. Herein, we develop a novel murine model for the in vivo monitoring of implanted bone marrow cells (BMCs) following spinal fusion.Methods: A clinical-grade scaffold was implanted into immune-intact mice undergoing spinal fusion with or without freshly isolated BMCs from either transgenic mice which constitutively express the firefly luciferase gene or syngeneic controls. The in vivo survival, distribution and proliferation of these luciferase-expressing cells was monitored via bioluminescence imaging over a period of 8 weeks and confirmed via immunohistochemistry. MicroCT imaging was performed 8 weeks to assess fusion.Results: Bioluminescence imaging indicated transplanted cell survival and proliferation over the first 2 weeks, followed by a decrease in cell numbers, with transplanted cell survival still evident at the end of the study. New bone formation and increased fusion mass volume were observed in mice implanted with cell-seeded scaffolds.Conclusions: By enabling the tracking of transplanted bone marrow-derived cells during spinal fusion in vivo, this mouse model will be integral to developing a deeper understanding of the biological processes underlying spinal fusion in future studies. These slides can be retrieved under Electronic Supplementary Material. [ABSTRACT FROM AUTHOR]

Introduction: Renin-angiotensin system (RAS) in brain cancer represents a scarcely explored field in neuro-oncology. Recently, some pre- and clinical studies have reported that RAS components play a relevant role in the development and behavior of gliomas. The angiotensinogen (AGT) rs5050 genetic variant has been identified as a crucial regulator of the transcription of AGT mRNA, which makes it a logical and promising target of research. The aim of this study was to determine the relationship between the AGT rs5050 genetic variant in blood with prognosis in astrocytoma. Methods: A prospective pilot study was performed on forty-eight astrocytoma patients, who received the standard-of-care treatment. Blood samples were taken prior to surgery and DNA was sequenced using Ion Torrent next-generation sequencing and analyzed by Ion Reporter software. Descriptive, bivariate, multivariate, and survival analyses were performed using SPSS v21, STATA 12 and GraphPad Prism 7. Results: Median follow-up was 41 months (range 1–48). Survival analysis showed a significant difference between the rs5050 genotypes (p = .05). We found lower survival rates in individuals with the GG-genotype of rs5050 AGT compared to patients with the TT- and TG-genotype (2 months vs. 11.5 months, respectively [p = .01]). In bivariate and multivariate analyses, GG-genotype was negatively associated with survival. Conclusions: In patients with astrocytoma, AGT rs5050 GG-genotype was associated with poor prognosis. We propose this germline genetic variant as a complementary biomarker, which can be detected practically and safely in blood samples or saliva. [ABSTRACT FROM AUTHOR]

Gliomas are the most common primary intrinsic tumor in the brain and are classified as low- or high-grade according to the World Health Organization (WHO). Patients with high-grade gliomas (HGG) who undergo surgical resection with adjuvant therapy have a mean overall survival of 15 months and 100% recurrence. The renin-angiotensin system (RAS), the primary regulator of cardiovascular circulation, exhibits local action and works as a paracrine system. In the context of this local regulation, the expression of RAS peptides and receptors has been detected in different kinds of tumors, including gliomas. The dysregulation of RAS components plays a significant role in the proliferation, angiogenesis, and invasion of these tumors, and therefore in their outcomes. The study and potential application of RAS peptides and receptors as biomarkers in gliomas could bring advantages against the limitations of current tumoral markers and should be considered in the future. The targeting of RAS components by RAS blockers has shown potential of being protective against cancer and improving immunotherapy. In gliomas, RAS blockers have shown a broad spectrum for beneficial effects and are being considered for use in treatment protocols. This review aims to summarize the background behind how RAS plays a role in gliomagenesis and explore the evidence that could lead to their use as biomarkers and treatment adjuvants. [ABSTRACT FROM AUTHOR]

Background The CYP11A1 gene encodes the cytochrome P450 side-chain cleavage enzyme, which is essential for steroid formation. Recessive variants in this gene can lead to impairment of sexual differentiation caused by a complete or partial loss of steroid hormone production. The phenotypic spectrum in affected 46 XY males may vary from surgically repairable defects including cryptorchidism and hypospadias to complete feminization of external gonads, accompanied by symptoms of adrenal dysfunction. Methods Whole-exome sequencing ( WES) of a 12-year-old male proband and his parents was performed after a protracted diagnostic odyssey failed to uncover the cause of his primary adrenal insufficiency. Of note, the proband had early symptomatology and corrective surgery for hypospadias, raising suspicion for a disorder of steroidogenesis. Results WES identified compound heterozygous variants in CYP11A1 including a novel canonical splice site variant (c.425+1G>A) and a previously reported p.E314K variant, which were consistent with a diagnosis of congenital adrenal insufficiency with partial 46 XY sex reversal. Conclusion Congenital adrenal insufficiency with 46 XY sex reversal is a rare disorder that is characterized by dysregulation of steroid hormone synthesis, leading to adrenal and gonadal dysfunction. In this report, we describe a patient with adrenal insufficiency, hypospadias, and skin hyperpigmentation who was found to have a novel c.425+1G>A variant in trans with the p.E314K variant in CYP11A1. We performed structural analyses to examine the effect of the p.E314K variant on protein function and show that it falls in the core of the protein may disrupt cholesterol binding in the active site. [ABSTRACT FROM AUTHOR]