Utilization of Augmented Reality Head-Mounted Display for the Surgical Management of Thoracolumbar Spinal Trauma.

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.

Landscape of Germline Genetic Variants in AGT, MGMT, and TP53 in Mexican Adult Patients with Astrocytoma.

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.

A mouse model for the study of transplanted bone marrow mesenchymal stem cell survival and proliferation in lumbar spinal fusion.

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.

Renin angiotensin system and its role in biomarkers and treatment in gliomas.

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.

Synthesis and evaluation of a novel vancomycin-infused, biomimetic bone graft using a rat model of spinal implant-associated infection.

Background: Postoperative infection is a complication of spinal fusion surgery resulting in increased patient morbidity. Strategies including intraoperative application of powdered vancomycin have been proposed to reduce the incidence of infection; however, such antimicrobial effects are short-lived. Methods: Instrumentation of the L4-L5 vertebrae was performed mimicking pedicle screw and rod fixation in 30 rats. Titanium instrumentation inoculated with either PBS or 1×105 CFU bioluminescent MRSA, along with biomimetic bone grafts infused with varying concentrations of vancomycin and 125 µg of rhBMP-2 (BioMim-rhBMP-2-VCM) were implanted prior to closure. Infection was quantified during the six-week postoperative period using bioluminescent imaging. Arthrodesis was evaluated using micro-CT. Results: Infected animals receiving a bone graft infused with low-dose (0.18 mg/g) or high-dose vancomycin (0.89 mg/g) both exhibited significantly lower bioluminescent signal over the six-week postoperative period than control animals inoculated with MRSA and implanted with bone grafts lacking vancomycin (p=.019 and p=.007, respectively). Both low and high-dose vancomycin-infused grafts also resulted in a statistically significant reduction in average bioluminescence when compared to control animals (p=.027 and p=.047, respectively), independent of time. MicroCT analysis of animals from each group revealed pseudoarthrosis only in the control group, suggesting a correlation between infection and pseudoarthrosis. MRSA-inoculated control animals also had significantly less bone volume formation on micro-CT than the PBS-inoculated control cohort (p<.001), the MRSA+low-dose vancomycin-infused bone graft cohort (p<.001), and the MRSA+high-dose vancomycin-infused bone graft cohort (p<.001). Conclusion: BioMim-rhBMP-2-VCM presents a novel tissue engineering approach to simultaneously promoting arthrodesis and antimicrobial prophylaxis in spinal fusion. Despite mixed evidence of potential osteotoxicity of vancomycin reported in literature, BioMim-rhBMP-2-VCM preserved arthrodesis and osteogenesis with increasing vancomycin loading doses due to the graft's osteoinductive composition.

A novel rodent model of chronic spinal implant-associated infection.

BACKGROUND CONTEXT: Bacterial infection of spinal instrumentation is a significant challenge in spinal fusion surgery. Although the intraoperative local application of powdered vancomycin is common practice for mitigating infection, the antimicrobial effects of this route of administration are short-lived. Therefore, novel antibiotic-loaded bone grafts as well as a reliable animal model to permit the testing of such therapies are needed to improve the efficacy of infection reduction practices in spinal fusion surgery. PURPOSE: This study aims to establish a clinically relevant rat model of spinal implant-associated infection to permit the evaluation of antimicrobial bone graft materials used in spinal fusion. STUDY DESIGN: Rodent study of chronic spinal implant-associated infection. METHODS: Instrumentation anchored in and spanning the vertebral bodies of L4 and L5 was inoculated with bioluminescent methicillin-resistant Staphylococcus aureus bacteria (MRSA). Infection was monitored using an in vivo imaging system (IVIS) for 8 weeks. Spines were harvested and evaluated histologically, and colony-forming units (CFUs) were quantified in harvested implants and spinal tissue. RESULTS: Postsurgical analysis of bacterial infection in vivo demonstrated stratification between MRSA and phosphate-buffered saline (PBS) control groups during the first 4 weeks of the 8-week infection period, indicating the successful establishment of acute infection. Over the 8-week chronic infection period, groups inoculated with 1 × 105 MRSA CFU and 1 × 106 MRSA CFU demonstrated significantly higher bioluminescence than groups inoculated with PBS control (p = 0.009 and p = 0.041 respectively). Histological examination at 8 weeks postimplantation revealed the presence of abscesses localized to implant placement in all MRSA inoculation groups, with the most pervasive abscess formation in samples inoculated with 1 × 105 MRSA CFU and 1 × 106 MRSA CFU. Quantification of CFU plated from harvested spinal tissue at 8 weeks post-implantation revealed the 1 × 105 MRSA CFU inoculation group as the only group with a significantly greater average CFU count compared to PBS control (p = 0.017). Further, CFU quantification from harvested spinal tissue was greater than CFU quantification from harvested implants across all inoculation groups. CONCLUSION: Our model demonstrated that the inoculation dosage of 1 × 105 MRSA CFU exhibited the most robust chronic infection within instrumented vertebral bodies. This dosage had the greatest difference in bioluminescence signal from control (p < 0.01), the lowest mortality (0% compared to 50% for samples inoculated with 1 × 106 MRSA CFU), and a significantly higher amount of CFUs from harvested spine samples than CFUs from control harvested spine samples. Further, histological analysis confirmed the reliability of this novel rodent model of implanted-associated infection to establish infection and biofilm formation of MRSA for all inoculation groups. CLINICAL SIGNIFICANCE: This model is intended to simulate the infection of instrumentation used in spinal fusion surgeries concerning implant locality and material. This model may evaluate potential antimicrobial and osteogenic biomaterials and investigate the relationship between implant-associated infection and failed fusion.

Creation and preclinical evaluation of a novel mussel-inspired, biomimetic, bioactive bone graft scaffold: direct comparison with Infuse bone graft using a rat model of spinal fusion.

OBJECTIVE: Infuse bone graft is a widely used osteoinductive adjuvant; however, the simple collagen sponge scaffold used in the implant has minimal inherent osteoinductive properties and poorly controls the delivery of the adsorbed recombinant human bone morphogenetic protein-2 (rhBMP-2). In this study, the authors sought to create a novel bone graft substitute material that overcomes the limitations of Infuse and compare the ability of this material with that of Infuse to facilitate union following spine surgery in a clinically translatable rat model of spinal fusion. METHODS: The authors created a polydopamine (PDA)-infused, porous, homogeneously dispersed solid mixture of extracellular matrix and calcium phosphates (BioMim-PDA) and then compared the efficacy of this material directly with Infuse in the setting of different concentrations of rhBMP-2 using a rat model of spinal fusion. Sixty male Sprague Dawley rats were randomly assigned to each of six equal groups: 1) collagen + 0.2 µg rhBMP-2/side, 2) BioMim-PDA + 0.2 µg rhBMP-2/side, 3) collagen + 2.0 µg rhBMP-2/side, 4) BioMim-PDA + 2.0 µg rhBMP-2/side, 5) collagen + 20 µg rhBMP-2/side, and 6) BioMim-PDA + 20 µg rhBMP-2/side. All animals underwent posterolateral intertransverse process fusion at L4-5 using the assigned bone graft. Animals were euthanized 8 weeks postoperatively, and their lumbar spines were analyzed via microcomputed tomography (µCT) and histology. Spinal fusion was defined as continuous bridging bone bilaterally across the fusion site evaluated via µCT. RESULTS: The fusion rate was 100% in all groups except group 1 (70%) and group 4 (90%). Use of BioMim-PDA with 0.2 µg rhBMP-2 led to significantly greater results for bone volume (BV), percentage BV, and trabecular number, as well as significantly smaller trabecular separation, compared with the use of the collagen sponge with 2.0 µg rhBMP-2. The same results were observed when the use of BioMim-PDA with 2.0 µg rhBMP-2 was compared with the use of the collagen sponge with 20 µg rhBMP-2. CONCLUSIONS: Implantation of rhBMP-2-adsorbed BioMim-PDA scaffolds resulted in BV and bone quality superior to that afforded by treatment with rhBMP-2 concentrations 10-fold higher implanted on a conventional collagen sponge. Using BioMim-PDA (vs a collagen sponge) for rhBMP-2 delivery could significantly lower the amount of rhBMP-2 required for successful bone grafting clinically, improving device safety and decreasing costs.

Rapid Implementation of a 3-Dimensional-Printed Patient-Specific Titanium Sacrum Implant for Severe Neuropathic Spinal Arthropathy and Guide to Compassionate US Regulatory Approval.

BACKGROUND AND OBJECTIVE: Rapid design and production of patient-specific 3-dimensional-printed implants (3DPIs) present a novel opportunity to restore the biomechanically demanding integrity of the lumbopelvic junction. We present a unique case of a 61-year-old patient with severe neuropathic spinal arthropathy (Charcot spine) who initially underwent a T4-to-sacrum spinal fusion. Massive bone destruction led to dissociation of his upper body from his pelvis and legs. Reconstruction of the spinopelvic continuity was planned with the aid of a personalized lumbosacral 3DPI. METHOD: Using high-resolution computed tomography scans, the custom 3DPI was made using additive titanium manufacturing. The unique 3DPI consisted of (1) a sacral platform with iliac screws, (2) modular corpectomy device with rigid connection to the sacral platform, and (3) anterior plate connection with screws for proximal fixation. The procedures to obtain compassionate use Food and Drug Administration approval were followed. The patient underwent debridement of a chronically open wound before undertaking the 3-stage reconstructive procedure. The custom 3DPI and additional instrumentation were inserted as part of a salvage rebuilding procedure. RESULTS: The chronology of the rapid implementation of the personalized sacral 3DPI from decision, design, manufacturing, Food and Drug Administration approval, and surgical execution lasted 28 days. The prosthesis was positioned in the defect according to the expected anatomic planes and secured using a screw-rod system and a vascularized fibular bone strut graft. The prosthesis provided an ideal repair of the lumbosacral junction and pelvic ring by merging spinal pelvic fixation, posterior pelvic ring fixation, and anterior spinal column fixation. CONCLUSION: To the best of our knowledge, this is the first case of a multilevel lumbar, sacral, and sacropelvic neuropathic (Charcot) spine reconstruction using a 3DPI sacral prosthesis. As the prevalence of severe spine deformities continues to increase, adoption of 3DPIs is becoming more relevant to offer personalized treatment for complex deformities.

A biodegradable 3D woven magnesium-based scaffold for orthopedic implants.

Porous Magnesium (Mg) is a promising biodegradable scaffold for treating critical-size bone defects, and as an essential element for human metabolism, Mg has shown sufficient biocompatibility. Its elastic moduli and yield strengths are closer to those of cortical bone than common, inert metallic implants, effectively reducing stress concentrations around host tissue as well as stress shielding. More importantly, Mg can degrade and be absorbed in the human body in a safe and controlled manner, thereby reducing the need for second surgeries to remove implants. The development of porous Mg scaffolds via conventional selective laser melting techniques has been limited due to Mg's low boiling point, high vapor pressures, high reactivity, and non-ideal microstructures in additively manufactured parts. Here we present an exciting alternative to conventional additive techniques: 3D weaving with Mg wires that have controlled chemistries and microstructures. The weaving process offers high throughput manufacturing as well as porous architectures that can be optimized for stiffness and porosity with topology optimization. Once woven, we dip-coat the weaves with polylactic acid to enhance their strength and corrosion resistance. Following fabrication, we characterize their mechanical properties, corrosion behavior, and cell compatibilityin vitro, and we use an intramuscular implantation model to evaluate theirin vivocorrosion behavior and tissue response.

Comparing the efficacy of adipose-derived and bone marrow-derived cells in a rat model of posterolateral lumbar fusion.

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.

Implementation of an Automated Text Message-Based System for Tracking Patient-Reported Outcomes in Spine Surgery: An Overview of the Concept and Our Early Experience.

OBJECTIVE: Text message-based interventions have been demonstrated to be a valuable monitoring tool across various conditions. Here, we aimed to describe our early experience using a newly developed text message-based platform designed to track symptoms in spine surgery patients. METHODS: We used the Informed Mindset Medical (IMM) platform to automatically send text messages with secure and encrypted hyperlinks to enrolled patients. Patient symptoms were monitored using well-standardized functional assessments. Limited patient data and responses were stored on a Health Insurance Portability and Accountability Act-compliant SQL cloud-based server database. RESULTS: In 3 months, 101 patients scheduled for elective spine surgery accepted participation in our pilot study. Overall, 71.2% of the enrolled patients responded to at least 1 preoperative baseline questionnaire. The response rates were similar across attendings, questionnaire bundles (cervical vs. thoracolumbar), genders, and age groups. The overall preoperative IMM pain scores were found to correlate positively with the preoperative electronic medical record pain rates. Similarly, the overall preoperative IMM and electronic medical record pain scores correlated positively with the IMM-collected Neck Disability Index/Oswestry Disability Index scores. From an initial 71.2%, the response rate decreased to 54.9% for the 6-week follow-up questionnaires. CONCLUSIONS: Our preliminary findings support the reliability of this text message-based strategy to monitor symptoms in spine surgery patients. Further studies are warranted to explore strategies to increase the response rate and expand this platform's clinical and research applicability.

Vascular Myelopathy Secondary to Compression of the Artery of Adamkiewicz From an Intrathecal Catheter: A Technical Case Report.

BACKGROUND AND IMPORTANCE: Although catheter-related complications in intrathecal drug delivery systems are relatively common, vascular myelopathy secondary to occlusion of the artery of Adamkiewicz (AoA) from an abutting intrathecal catheter has not yet been reported. In this study, we present a case of this extremely rare presentation, which resolved after decompression of the artery. CLINICAL PRESENTATION: A 39-year-old woman presented with lower extremity weakness and paresthesia. She had a 20-year history of severe chronic back pain and stable sensory disturbances below T8 as sequelae of multiple injuries after a motor vehicle accident. Three years before presentation in our clinic, she underwent baclofen pump placement because of neuropathic pain refractory to oral medication. After pump placement, she gradually developed myelopathic symptoms and dysautonomia. All medications through the pump were discontinued, but her symptoms continued to progress. Workup included a spinal angiogram that showed that her intrathecal catheter was abutting the left side of the AoA at the T12 level. After interdisciplinary evaluation, it was believed that her clinical presentation was attributable to vascular compression, and she underwent surgical removal of the catheter. Three years later, her symptoms have improved and her neurological examination returned to baseline before the catheter placement. CONCLUSION: Meticulous, multidisciplinary neurological and radiological evaluations were essential to diagnose the compression of the AoA as the cause of this patient's myelopathy. Although exceedingly rare, direct compression of the AoA by an intrathecal catheter should be on the differential diagnosis when evaluating for causes of vascular myelopathy.

Porcine Model of Spinal Cord Injury: A Systematic Review.

Spinal cord injury (SCI) is a devastating disease with limited effective treatment options. Animal paradigms are vital for understanding the pathogenesis of SCI and testing potential therapeutics. The porcine model of SCI is increasingly favored because of its greater similarity to humans. However, its adoption is limited by the complexities of care and range of testing parameters. Researchers need to consider swine selection, injury method, post-operative care, rehabilitation, behavioral outcomes, and histology metrics. Therefore, we systematically reviewed full-text English-language articles to evaluate study characteristics used in developing a porcine model and summarize the interventions that have been tested using this paradigm. A total of 63 studies were included, with 33 examining SCI pathogenesis and 30 testing interventions. Studies had an average sample size of 15 pigs with an average weight of 26 kg, and most used female swine with injury to the thoracic cord. Injury was most commonly induced by weight drop with compression. The porcine model is amenable to testing various interventions, including mean arterial pressure augmentation (n = 7), electrical stimulation (n = 6), stem cell therapy (n = 5), hypothermia (n = 2), biomaterials (n = 2), gene therapy (n = 2), steroids (n = 1), and nanoparticles (n = 1). It is also notable for its clinical translatability and is emerging as a valuable pre-clinical study tool. This systematic review can serve as a guideline for researchers implementing and testing the porcine SCI model.

Applications of elastography in operative neurosurgery: A systematic review.

Elastography is an imaging technology capable of measuring tissue stiffness and consistency. The technology has achieved widespread use in the workup and management of diseases of the liver, breast, thyroid, and prostate. Although elastography is increasingly being applied in neurosurgery, it has not yet achieved widespread adoption and many clinicians remain unfamiliar with the technology. Therefore, we sought to summarize the range of applications and elastography modalities available for neurosurgery, report its effectiveness in comparison with conventional imaging methods, and offer recommendations. All full-text English-language manuscripts on the use of elastography for neurosurgical procedures were screened using the PubMed/MEDLINE, Embase, Cochrane Library, Scopus, and Web of Science databases. Thirty-two studies were included with 990 patients, including 21 studies on intracranial tumors, 5 on hydrocephalus, 4 on epilepsy, 1 on spinal cord compression, and 1 on adolescent scoliosis. Twenty studies used ultrasound elastography (USE) whereas 12 used magnetic resonance elastography (MRE). MRE studies were mostly used in the preoperative setting for assessment of lesion stiffness, tumor-brain adherence, diagnostic workup, and operative planning. USE studies were performed intraoperatively to guide resection of lesions, determine residual microscopic abnormalities, assess the tumor-brain interface, and study mechanical properties of tumors. Elastography can assist with resection of brain tissue, detection of microscopic lesions, and workup of hydrocephalus, among other applications under investigation. Its sensitivity often exceeds that of conventional MRI and ultrasound for identifying abnormal tissue and lesion margins.

3D-printed oxygen-releasing scaffolds improve bone regeneration in mice.

Low oxygen (O2) diffusion into large tissue engineered scaffolds hinders the therapeutic efficacy of transplanted cells. To overcome this, we previously studied hollow, hyperbarically-loaded microtanks (µtanks) to serve as O2 reservoirs. To adapt these for bone regeneration, we fabricated biodegradable µtanks from polyvinyl alcohol and poly (lactic-co-glycolic acid) and embedded them to form 3D-printed, porous poly-ε-caprolactone (PCL)-µtank scaffolds. PCL-µtank scaffolds were loaded with pure O2 at 300-500 psi. When placed at atmospheric pressures, the scaffolds released O2 over a period of up to 8 h. We confirmed the inhibitory effects of hypoxia on the osteogenic differentiation of human adipose-derived stem cells (hASCs and we validated that µtank-mediated transient hyperoxia had no toxic impacts on hASCs, possibly due to upregulation of endogenous antioxidant regulator genes. We assessed bone regeneration in vivo by implanting O2-loaded, hASC-seeded, PCL-µtank scaffolds into murine calvarial defects (4 mm diameters × 0.6 mm height) and subcutaneously (4 mm diameter × 8 mm height). In both cases we observed increased deposition of extracellular matrix in the O2 delivery group along with greater osteopontin coverages and higher mineral deposition. This study provides evidence that even short-term O2 delivery from PCL-µtank scaffolds may enhance hASC-mediated bone tissue regeneration.

Impact of international research fellows in neurosurgery: results from a single academic center.

OBJECTIVE: International research fellows have been historically involved in academic neurosurgery in the United States (US). To date, the contribution of international research fellows has been underreported. Herein, the authors aimed to quantify the academic output of international research fellows in the Department of Neurosurgery at The Johns Hopkins University School of Medicine. METHODS: Research fellows with Doctor of Medicine (MD), Doctor of Philosophy (PhD), or MD/PhD degrees from a non-US institution who worked in the Hopkins Department of Neurosurgery for at least 6 months over the past decade (2010-2020) were included in this study. Publications produced during fellowship, number of citations, and journal impact factors (IFs) were analyzed using ANOVA. A survey was sent to collect information on personal background, demographics, and academic activities. RESULTS: Sixty-four international research fellows were included, with 42 (65.6%) having MD degrees, 17 (26.6%) having PhD degrees, and 5 (7.8%) having MD/PhD degrees. During an average 27.9 months of fellowship, 460 publications were produced in 136 unique journals, with 8628 citations and a cumulative journal IF of 1665.73. There was no significant difference in total number of publications, first-author publications, and total citations per person among the different degree holders. Persons holding MD/PhDs had a higher number of citations per publication per person (p = 0.027), whereas those with MDs had higher total IFs per person (p = 0.048). Among the 43 (67.2%) survey responders, 34 (79.1%) had nonimmigrant visas at the start of the fellowship, 16 (37.2%) were self-paid or funded by their country of origin, and 35 (81.4%) had mentored at least one US medical student, nonmedical graduate student, or undergraduate student. CONCLUSIONS: International research fellows at the authors' institution have contributed significantly to academic neurosurgery. Although they have faced major challenges like maintaining nonimmigrant visas, negotiating cultural/language differences, and managing self-sustainability, their scientific productivity has been substantial. Additionally, the majority of fellows have provided reciprocal mentorship to US students.

Quantitative 3D imaging of the cranial microvascular environment at single-cell resolution.

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.

Traumatic sacral dermoid cyst rupture with intracranial subarachnoid seeding of lipid particles: illustrative case.

BACKGROUND: Intracranial deposits of fat droplets are an unusual presentation of a spinal dermoid cyst after spontaneous rupture and are even more uncommon after trauma. Here, the authors present a case with this rare clinical presentation, along with a systematic review of the literature to guide decision making in these patients. OBSERVATIONS: A 54-year-old woman with Lynch syndrome presented with severe headache and sacrococcygeal pain after a traumatic fall. Computed tomography of the head revealed multifocal intraventricular and intracisternal fat deposits, which were confirmed by magnetic resonance imaging (MRI) of the neuroaxis; in addition, a ruptured multiloculated cyst was identified within the sacral canal with proteinaceous/hemorrhagic debris, most consistent with a sacral dermoid cyst with rupture into the cerebrospinal fluid (CSF) space. An unruptured sacral cyst was later noted on numerous previous MRI scans. In our systematic review, we identified 20 similar cases, most of which favored surgical treatment. LESSONS: Rupture of an intraspinal dermoid cyst must be considered when intracranial fat deposits are found in the context of cauda equina syndrome, meningism, or hydrocephalus. Complete tumor removal with close postoperative follow-up is recommended to decrease the risk of complications. CSF diversion must be prioritized if life-threatening hydrocephalus is present.

Comparison of Freshly Isolated Adipose Tissue-derived Stromal Vascular Fraction and Bone Marrow Cells in a Posterolateral Lumbar Spinal Fusion Model.

STUDY DESIGN: Rat posterolateral lumbar fusion model. OBJECTIVE: The aim of this study was to compare the efficacy of freshly isolated adipose tissue-derived stromal vascular fraction (A-SVF) and bone marrow cells (BMCs) cells in achieving spinal fusion in a rat model. SUMMARY OF BACKGROUND DATA: Adipose tissue-derived stromal cells (ASCs) offer advantages as a clinical cell source compared to bone marrow-derived stromal cells (BMSCs), including larger available tissue volumes and reduced donor site morbidity. While pre-clinical studies have shown that ex vivo expanded ASCs can be successfully used in spinal fusion, the use of A-SVF cells better allows for clinical translation. METHODS: A-SVF cells were isolated from the inguinal fat pads, whereas BMCs were isolated from the long bones of syngeneic 6- to 8-week-old Lewis rats and combined with Vitoss (Stryker) bone graft substitute for subsequent transplantation. Posterolateral spinal fusion surgery at L4-L5 was performed on 36 female Lewis rats divided into three experimental groups: Vitoss bone graft substitute only (VO group); Vitoss + 2.5 × 106 A-SVF cells/side; and, Vitoss + 2.5 × 106 BMCs/side. Fusion was assessed 8 weeks post-surgery via manual palpation, micro-computed tomography (µCT) imaging, and histology. RESULTS: µCT imaging analyses revealed that fusion volumes and µCT fusion scores in the A-SVF group were significantly higher than in the VO group; however, they were not significantly different between the A-SVF group and the BMC group. The average manual palpation score was highest in the A-SVF group compared with the BMC and VO groups. Fusion masses arising from cell-seeded implants yielded better bone quality than nonseeded bone graft substitute. CONCLUSION: In a rat model, A-SVF cells yielded a comparable fusion mass volume and radiographic rate of fusion to BMCs when combined with a clinical-grade bone graft substitute. These results suggest the feasibility of using freshly isolated A-SVF cells in spinal fusion procedures.Level of Evidence: N/A.

First Report of Pharmacogenomic Profiling in an Outpatient Spine Setting: Preliminary Results from a Pilot Study.

OBJECTIVE: Pharmacogenomics may help personalize medicine and improve therapeutic selection. This is the first study investigating how pharmacogenomic testing may inform analgesic selection in patients with spine disease. We profile pharmacogenetic differences in pain medication-metabolizing enzymes across patients presenting at an outpatient spine clinic and provide preliminary evidence that genetic polymorphisms may help explain interpatient differences in preoperative pain refractory to conservative management. METHODS: Adults presenting to our outpatient spine clinic with chief symptoms of neck and/or back pain were prospectively enrolled over 9 months. Patients completed the Wong-Baker FACES and numeric pain rating scales for their chief pain symptom and provided detailed medication histories and cheek swab samples for genomic analysis. RESULTS: Thirty adults were included (mean age, 60.6 ± 15.3 years). The chief concern was neck pain in 23%, back pain in 67%, and combined neck/back pain in 10%. At enrollment, patient analgesic regimens comprised 3 ± 1 unique medications, including 1 ± 1 opioids. After genomic analysis, 14/30 patients (47%) were identified as suboptimal metabolizers of ≥1 medications in their analgesic regimen. Of these patients, 93% were suboptimal metabolizers of their prescribed opioid analgesic. Nonetheless, pain scores were similar between optimal and suboptimal metabolizer groups. CONCLUSIONS: This pilot study shows that a large proportion of the spine outpatient population may use pain medications for which they are suboptimal metabolizers. Further studies should assess whether these pharmacogenomic differences indicate differences in odds of receiving therapeutic benefit from surgery or if they can be used to generate more effective postoperative analgesic regimens.