Benign Brain and Spinal Tumors Originating from Bone or Cartilage.

Benign osseocartilaginous tumors of the spine are overall uncommon, representing between 1 and 13% of all primary bone tumors and less than 10% of all spinal tumors. Tumors in this category include osteoblastic lesions such as the related osteoid osteoma and osteoblastoma, and cartilage-forming lesions including osteochondroma, chondroma, and chondroblastoma. Aneurysmal bone cysts, giant cell tumors of bone, and eosinophilic granulomas also comprise benign tumors of the spine arising from bone. There is significant heterogeneity in the epidemiology, molecular biology, imaging features, and optimal treatment of these lesions. For example, osteoid osteoma is characterized by high expression of the cyclooxygenase enzymes, making it amenable to treatment with anti-inflammatory drugs initially, whereas other lesions such as osteoblastoma may require intralesional curettage or en bloc resection sooner. Generally, en bloc resection is preferred when possible to minimize risk of recurrence. Further, some tumors may arise in the setting of syndromic conditions, such as multiple chondromas arising in Ollier disease or Maffucci syndrome, or as part of genetic disorders, such as osteochondromas in the context of hereditary multiple exostosis. These lesions may present with local pain, cause neurological compromise or be discovered incidentally on routine imaging. The Enneking classification and Weinstein-Boriani-Biagini system are routinely used to classify lesions and assist in surgical planning. More novel techniques such as radiofrequency ablation and laser photocoagulation have been applied for the treatment of osteoid osteoma and may have utility in the treatment of other lesion types. A multidisciplinary approach is critical in the management of benign lesions of the spine, and both chemotherapeutic and surgical approaches are routinely used.

Radiographic alignment outcomes after the single-position prone transpsoas approach: a multi-institutional retrospective review of 363 cases.

OBJECTIVE: The aim of this paper was to evaluate the changes in radiographic spinopelvic parameters in a large cohort of patients undergoing the prone transpsoas approach to the lumbar spine. METHODS: A multicenter retrospective observational cohort study was performed for all patients who underwent lateral lumber interbody fusion via the single-position prone transpsoas (PTP) approach. Spinopelvic parameters from preoperative and first upright postoperative radiographs were collected, including lumbar lordosis (LL), pelvic incidence (PI), and pelvic tilt (PT). Functional indices (visual analog scale score), and patient-reported outcomes (Oswestry Disability Index) were also recorded from pre- and postoperative appointments. RESULTS: Of the 363 patients who successfully underwent the procedure, LL after fusion was 50.0° compared with 45.6° preoperatively (p < 0.001). The pelvic incidence-lumbar lordosis mismatch (PI-LL) was 10.5° preoperatively versus 2.9° postoperatively (p < 0.001). PT did not significantly change (0.2° ± 10.7°, p > 0.05). CONCLUSIONS: The PTP approach allows significant gain in lordotic augmentation, which was associated with good functional results at follow-up.

Dehydrated human amnion/chorion membrane use in emergent craniectomies shows minimal dural adhesions.

Decompressive craniectomies (DCs) are routinely performed neurosurgical procedures to emergently treat increased intracranial pressure secondary to multiple aetiologies, such as subdural haematoma, epidural haematoma, or malignant oedema in the setting of acute infarction. The DC procedure typically induces epidural fibrosis post-cranial resection, resulting in adherence of the dura to both the brain internally and skin flap externally. This becomes especially problematic in the setting of skull flap replacement for cranioplasty as adherences can lead to bridging vein tear, damage to the underlying brain cortex, and other postoperative complications. Dural adjuvants, which can contribute to decreased rate of adherence formation, can thereby reduce both postoperative cranioplasty complications and operative duration. Dehydrated human amnion/chorion membrane (DHACM) allografts (AMNIOFIX, MIMEDX Group Inc., US) have been shown to reduce the rate of dural scar tissue formation in re-exploration of posterior lumbar interbody fusion operations which require entry into the epidural space. The purpose of this study was to evaluate whether or not the use of DHACM in the setting of emergent craniectomies decreased the rate of dural adhesion formation and subsequent cranioplasty complications. Patients (n=7) who underwent emergent craniectomy and intraoperative placement of DHACM were evaluated during replacement of either an autologous skull cap or a custom-made implant, at which point the degree of adhesions was qualitatively assessed. Placement of DHACM below and on top of the dura resulted in negligible adhesion being found during the defect exposure, and there were no intraoperative complications during cranioplasties. Reported estimated blood loss across the seven patients averaged 64.2ml, total operative time averaged 79.2 minutes, and time dedicated to exposing defect for bone flap placement was <3 minutes.

Low-Intensity Pulsed Ultrasound as a Potential Adjuvant Therapy to Promote Spinal Fusion: Systematic Review and Meta-analysis of the Available Data.

Despite extensive research, nonunion continues to affect a nontrivial proportion of patients undergoing spinal fusion. Recently, preclinical studies have suggested that low-intensity pulsed ultrasound (LIPUS) may increase rates of spinal fusion. In this study, we summarized the available in vivo literature evaluating the effect of LIPUS on spinal fusion and performed a meta-analysis of the available data to estimate the degree to which LIPUS may mediate higher fusion rates. Across 13 preclinical studies, LIPUS was associated with a 9-fold increase in the odds of successful spinal fusion. Future studies are necessary to establish the benefit of LIPUS on spinal fusion in clinical populations.

Systematic review of charged-particle therapy for chordomas and sarcomas of the mobile spine and sacrum.

OBJECTIVE: Long-term local control in patients with primary chordoma and sarcoma of the spine and sacrum is increasingly reliant upon en bloc resection with negative margins. At many institutions, adjuvant radiation is recommended; definitive radiation is also recommended for the treatment of unresectable tumors. Because of the high off-target radiation toxicities associated with conventional radiotherapy, there has been growing interest in the use of proton and heavy-ion therapies. The aim of this study was to systematically review the literature regarding these therapies. METHODS: The PubMed, OVID, Embase, and Web of Science databases were queried for articles describing the use of proton, combined proton/photon, or heavy-ion therapies for adjuvant or definitive radiotherapy in patients with primary sarcoma or chordoma of the mobile spine and sacrum. A qualitative synthesis of the results was performed, focusing on overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), and disease-specific survival (DSS); local control; and postradiation toxicities. RESULTS: Of 595 unique articles, 64 underwent full-text screening and 38 were included in the final synthesis. All studies were level III or IV evidence with a high risk of bias; there was also significant overlap in the reported populations, with six centers accounting for roughly three-fourths of all reports. Five-year therapy outcomes were as follows: proton-only therapies, OS 67%-82%, PFS 31%-57%, and DFS 52%-62%; metastases occurred in 17%-18% and acute toxicities in 3%-100% of cases; combined proton/photon therapy, local control 62%-85%, OS 78%-87%, PFS 90%, and DFS 61%-72%; metastases occurred in 12%-14% and acute toxicities in 84%-100% of cases; and carbon ion therapy, local control 53%-100%, OS 52%-86%, PFS (only reported for 3 years) 48%-76%, and DFS 50%-53%; metastases occurred in 2%-39% and acute toxicities in 26%-48%. There were no studies directly comparing outcomes between photon and charged-particle therapies or comparing outcomes between radiation and surgical groups. CONCLUSIONS: The current evidence for charged-particle therapies in the management of sarcomas of the spine and sacrum is limited. Preliminary evidence suggests that with these therapies local control and OS at 5 years are comparable among various charged-particle options and may be similar between those treated with definitive charged-particle therapy and historical surgical cohorts. Further research directly comparing charged-particle and photon-based therapies is necessary.

Role of the Pubic Symphysis in Osseous Pelvic Development: A Novel Model of Bladder Exstrophy in Rabbits.

BACKGROUND: It has been posited that the osseous pelvic anomalies seen in patients with classic bladder exstrophy (CBE) result from disruption of the pubic symphysis. This hypothesis, however, has not been tested. In the present animal study, our objective was to determine whether the tension of the pubic symphysis helps maintain the shape of the pelvic ring, or whether the growing bones maintain a ring shape even without the tension of the symphysis. METHODS: In total, 12 neonatal New Zealand White rabbits underwent pubic symphysiotomy (experimental group, n=9) or sham surgery (control group, n=3) on days 3 or 4 of life. Rabbits were scanned with cone-beam computed tomography at 1, 4, 12, and 20 weeks postoperatively to monitor changes in the following pelvic parameters, which are known to be altered in CBE: anterior segment angle, anterior segment length, intertriradiate distance, interpubic distance, and posterior segment angle. Changes within the experimental and control groups were evaluated using repeated-measures analysis of variance and post hoc Tukey honest significant difference testing. Two-tailed t tests were used to compare treatment groups at each time point. RESULTS: Both groups showed increases in anterior segment length and intertriradiate distance during the study period; rabbits in the experimental group also showed a steady increase in interpubic distance (F=43.9; P<0.001). Experimental rabbits had significantly larger mean values for anterior segment angle, intertriradiate distance, interpubic distance, and posterior segment angle than did control rabbits at all time points. We found no difference in mean anterior segment length between control and experimental groups at any time point. The difference in interpubic distance was particularly pronounced by 20 weeks (experimental group, 13±2.7 mm; control group, 1.1±0.1 mm; P<0.001). CONCLUSIONS: The pubic symphysis is essential for normal pelvic development. Its absence led to early pelvic angulation and progressive pubic separation in a rabbit model. However, we found no significant difference in the mean anterior segment length, and it is likely that other factors are also implicated in the growth disturbance seen in CBE. LEVEL OF EVIDENCE: Level V.

Propensity for different vascular distributions and cerebral edema of intraparenchymal brain metastases from different primary cancers.

PURPOSE: This study seeks to ascertain whether different primary tumor types have a propensity for brain metastases (BMs) in different cerebral vascular territories and cerebral edema. METHODS: Consecutive adult patients who underwent surgical resection of a BM at a tertiary care institution between 2001 and 2011 were retrospectively reviewed. Only patients with the most common primary cancers (lung, breast, skin-melanoma, colon, and kidney) were included. Preoperative MRIs were reviewed to classify all tumors by cerebral vascular territory (anterior cerebral artery-ACA, lenticulostriate, middle cerebral artery-MCA, posterior cerebral artery-PCA, posterior fossa, and watershed), and T2-weighted FLAIR widths were measured. Chi square analyses were performed to determine differences in cerebral vascular distribution by primary tumor type, and one-way ANOVA analyses were performed to determine FLAIR signal differences. RESULTS: 669 tumors from 388 patients were classified from lung (n = 316 BMs), breast (n = 144), melanoma (n = 119), renal (n = 47), and colon (n = 43). BMs from breast cancer were less likely to be located in PCA territory (n = 18 [13%]; χ2 = 6.10, p = 0.01). BMs from melanoma were less likely to be located in cerebellar territory (n = 11 [9%]; χ2 = 14.1, p < 0.001), and more likely to be located in lateral (n = 5 [4%]; χ2 = 4.56, p = 0.03) and medial lenticulostriate territories (n = 2 [2%]; χ2 = 6.93, p = 0.009). BMs from breast and melanoma had shorter T2-FLAIR widths, with an average [IQR] of 47.2 [19.6-69.2] mm (p = 0.01) and 41.2 [14.4-62.7] mm (p = 0.002) respectively. Conversely, BMs from renal cancer had longer T2-FLAIR widths (64.2 [43.6-80.8] mm, p = 0.002). CONCLUSIONS: These findings suggest that different primary tumor types could have propensities for different cerebral vascular territories and cerebral edema.

Novel Use of Bilateral Prone Transpsoas Approach for the Treatment of Transforaminal Interbody Fusion Pseudarthrosis and Interbody Cage Subsidence.

BACKGROUND AND OBJECTIVES: Pseudarthrosis is a complication after transforaminal lumbar interbody fusion (TLIF) that leads to recurrent symptoms and potential revision surgery. Subsidence of the interbody adds to the complexity of surgical revision. In addition, we report a novel technique for the treatment of TLIF pseudarthrosis with subsidence and propose an approach algorithm for TLIF cage removal. METHODS: Cases of reoperation for TLIF pseudarthrosis were reviewed. We report a novel technique using a bilateral prone transpsoas (PTP) approach to remove a subsided TLIF cage and place a new lateral cage. An approach algorithm was developed based on the experience of TLIF cage removal. The patient was placed in the prone position with somatosensory evoked potential and electromyography monitoring. A PTP retractor was placed using standard techniques on the ipsilateral side of the previous TLIF. After the discectomy, the subsided TLIF cage was visualized but unable to be removed. The initial dilator was closed, and a second PTP retractor was placed on the contralateral side. After annulotomy and discectomy to circumferentially isolate the subsided cage, a box cutter was used to push and mobilize the TLIF cage from this contralateral side, which could then be pulled out from the ipsilateral side. A standard lateral interbody cage was then placed. RESULTS: Retractor time was less than 10 minutes on each side. The patient's symptoms resolved postoperatively. We review illustrative cases of various approaches for TLIF cage removal spanning the lumbosacral spine and recommend an operative approach based on the lumbar level, degree of subsidence, and mobility of the interbody. CONCLUSION: Bilateral PTP retractors for TLIF cage removal may be effectively used in cases of pseudarthrosis with severe cage subsidence. Careful consideration of various factors, including patient surgical history, body habitus, and intraoperative findings, is essential in determining the appropriate treatment for these complex cases.

In-Human Report of S2 Alar-Iliac Screw Placement Using Augmented Reality Assistance.

BACKGROUND: S2 alar-iliac (S2AI) screws provide spinopelvic fixation with the advantages of minimized dissection, easier rod contouring, and decreased symptomatic screw-head prominence. However, placement of S2AI screws may be challenging because of the anatomy of the lumbosacral junction. Augmented reality is a nascent technology that may enhance placement of S2AI screws. OBJECTIVE: To report the first in-human placement of augmented reality (AR)-assisted S2 alar-iliac screws and evaluate the accuracy of screw placement. METHODS: A retrospective review was performed of patients who underwent AR-assisted S2AI screw placement. All surgeries were performed by 2 neurosurgeons using an AR head-mounted display (Xvision, Augmedics). Screw accuracy was analyzed in a blinded fashion by an independent neuroradiologist using the cortical breach grading scale. RESULTS: Twelve patients underwent AR-assisted S2AI screw placement for a total of 23 screws. Indications for surgery included deformity, degenerative disease, and tumor. Twenty-two screws (95.6%) were accurate-defined as grade 0 or grade 1. Twenty-one screws (91.3%) were classified as grade 0, 1 screw (4.3%) was grade 1, and 1 screw (4.3%) was grade 3. All breaches were asymptomatic. CONCLUSION: AR-assisted S2AI screw placement had an overall accuracy rate of 95.6% (grade 0 and grade 1 screws) in a cohort of 12 patients and 23 screws. This compares favorably with freehand and robotic placement. 1,2 AR enables spine surgeons to both better visualize anatomy and accurately place spinal instrumentation. Future studies are warranted to research the learning curve and cost analysis of AR-assisted spine surgery.

Cerebrospinal Fluid Drainage in Patients with Acute Spinal Cord Injury: A Multi-Center Randomized Controlled Trial.

OBJECTIVE: The secondary phase of spinal cord injury (SCI) is characterized by ischemic injury. Spinal cord perfusion pressure (SCPP), calculated as the difference between mean arterial pressure (MAP) and intrathecal pressure (ITP), has arisen as a therapeutic target for improving outcomes. Cerebrospinal fluid drainage (CSFD) may reduce ITP and thereby increase SCPP. Randomized controlled trial to evaluate the safety and feasibility of CSFD to improve SCPP and outcomes after acute SCI. METHODS: Inclusion criteria included acute cervical SCI within 24 hours of presentation. All patients received lumbar drain placement and appropriate decompressive surgery. Patients randomized to the control group received MAP elevation only. Patients in the experimental group received MAP elevation and CSFD to achieve ITP <10 mmHg for 5 days. ITP and MAP were recorded hourly. Adverse events were documented and patients underwent functional assessments at enrollment, 72 hours, 90 days, and 180 days post-injury. RESULTS: Eleven patients were enrolled; 4 were randomized to receive CSFD. CSFD patients had a mean ITP of 5.3 ± 2.5 mmHg versus. 15 ± 3.0 mmHg in the control group. SCPP improved significantly, from 77 ± 4.5 mmHg in the control group to 101 ± 6.3 mmHg in the CSFD group (P < 0.01). Total motor scores improved by 15 ± 8.4 and 57 ± 24 points in the control and CSFD groups, respectively, over 180 days. No adverse events were attributable to CSFD. CONCLUSIONS: CSFD is a safe, effective mechanism for reducing ITP and improving SCPP in the acute period post-SCI. The favorable safety profile and preliminary efficacy should help drive recruitment in future studies.

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.

Complications of the Prone Transpsoas Lateral Lumbar Interbody Fusion for Degenerative Lumbar Spine Disease: A Multicenter Study.

BACKGROUND AND OBJECTIVES: The prone transpsoas (PTP) approach for lateral lumbar interbody fusion (LLIF) is a novel technique for degenerative lumbar spine disease. However, there is a paucity of information in the literature on the complications of this procedure, with all published data consisting of small samples. We aimed to report the intraoperative and postoperative complications of PTP in the largest study to date. METHODS: A retrospective electronic medical record review was conducted at 11 centers to identify consecutive patients who underwent LLIF through the PTP approach between January 1, 2021, and December 31, 2021. The following data were collected: intraoperative characteristics (operative time, estimated blood loss [EBL], intraoperative complications [anterior longitudinal ligament (ALL) rupture, cage subsidence, vascular and visceral injuries]), postoperative complications, and hospital stay. RESULTS: A total of 365 patients were included in the study. Among these patients, 2.2% had ALL rupture, 0.3% had cage subsidence, 0.3% had a vascular injury, 0.3% had a ureteric injury, and no other visceral injuries were reported. Mean operative time was 226.2 ± 147.9 minutes. Mean EBL was 138.4 ± 215.6 mL. Mean hospital stay was 2.7 ± 2.2 days. Postoperative complications included new sensory symptoms-8.2%, new lower extremity weakness-5.8%, wound infection-1.4%, cage subsidence-0.8%, psoas hematoma-0.5%, small bowel obstruction and ischemia-0.3%, and 90-day readmission-1.9%. CONCLUSION: In this multicenter case series, the PTP approach was well tolerated and associated with a satisfactory safety profile.

Treatment of Spinal Arteriovenous Malformation and Fistula.

With the rapid advancements in endovascular therapy over previous decades, the treatment of spinal arteriovenous malformations (AVMs) continues to evolve. The decision to use endovascular versus surgical therapy largely depends on the type of lesion and its anatomic location. Recent studies demonstrate that endovascular treatment is effective for extradural arteriovenous fistulas (AVFs), intradural ventral (perimedullary) AVMs, and intramedullary spinal AVMs. Treatment of intradural dorsal (dural) AVFs remains largely surgical because of lower recurrence rates, although recent studies demonstrate equivocal outcomes. Extradural-intradural (juvenile) AVMs and conus AVMs remain difficult-to-treat lesions.

Octogenarians Are Independently Associated With Extended LOS and Non-Routine Discharge After Elective ACDF for CSM.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The aim of this study was to determine the impact age has on LOS and discharge disposition following elective ACDF for cervical spondylotic myelopathy (CSM). METHODS: A retrospective cohort study was performed using the National Inpatient Sample (NIS) database from 2016 and 2017. All adult patients >50 years old undergoing ACDF for CSM were identified using the ICD-10-CM diagnosis and procedural coding system. Patients were then stratified by age: 50 to 64 years-old, 65 to 79 years-old, and greater than or equal to 80 years-old. Weighted patient demographics, comorbidities, perioperative complications, LOS, discharge disposition, and total cost of admission were assessed. RESULTS: A total of 14 865 patients were identified. Compared to the 50-64 and 65-79 year-old cohorts, the 80+ years cohort had a significantly higher rate of postoperative complication (50-64 yo:10.2% vs. 65-79 yo:12.6% vs. 80+ yo:18.9%, P = 0.048). The 80+ years cohort experienced significantly longer hospital stays (50-64 yo: 2.0 ± 2.4 days vs. 65-79 yo: 2.2 ± 2.8 days vs. 80+ yo: 2.3 ± 2.1 days, P = 0.028), higher proportion of patients with extended LOS (50-64 yo:18.3% vs. 65-79 yo:21.9% vs. 80+ yo:28.4%, P = 0.009), and increased rates of non-routine discharges (50-64 yo:15.1% vs. 65-79 yo:23.0% vs. 80+ yo:35.8%, P < 0.001). On multivariate analysis, age 80+ years was found to be a significant independent predictor of extended LOS [OR:1.97, 95% CI:(1.10,3.55), P = 0.023] and non-routine discharge [OR:2.46, 95% CI:(1.44,4.21), P = 0.001]. CONCLUSIONS: Our study demonstrates that octogenarian age status is a significant independent risk factor for extended LOS and non-routine discharge after elective ACDF for CSM.

Clinical accuracy and initial experience with augmented reality-assisted pedicle screw placement: the first 205 screws.

OBJECTIVE: Augmented reality (AR) is a novel technology which, when applied to spine surgery, offers the potential for efficient, safe, and accurate placement of spinal instrumentation. The authors report the accuracy of the first 205 pedicle screws consecutively placed at their institution by using AR assistance with a unique head-mounted display (HMD) navigation system. METHODS: A retrospective review was performed of the first 28 consecutive patients who underwent AR-assisted pedicle screw placement in the thoracic, lumbar, and/or sacral spine at the authors' institution. Clinical accuracy for each pedicle screw was graded using the Gertzbein-Robbins scale by an independent neuroradiologist working in a blinded fashion. RESULTS: Twenty-eight consecutive patients underwent thoracic, lumbar, or sacral pedicle screw placement with AR assistance. The median age at the time of surgery was 62.5 (IQR 13.8) years and the median body mass index was 31 (IQR 8.6) kg/m2. Indications for surgery included degenerative disease (n = 12, 43%); deformity correction (n = 12, 43%); tumor (n = 3, 11%); and trauma (n = 1, 4%). The majority of patients (n = 26, 93%) presented with low-back pain, 19 (68%) patients presented with radicular leg pain, and 10 (36%) patients had documented lower extremity weakness. A total of 205 screws were consecutively placed, with 112 (55%) placed in the lumbar spine, 67 (33%) in the thoracic spine, and 26 (13%) at S1. Screw placement accuracy was 98.5% for thoracic screws, 97.8% for lumbar/S1 screws, and 98.0% overall. CONCLUSIONS: AR depicted through a unique HMD is a novel and clinically accurate technology for the navigated insertion of pedicle screws. The authors describe the first 205 AR-assisted thoracic, lumbar, and sacral pedicle screws consecutively placed at their institution with an accuracy of 98.0% as determined by a Gertzbein-Robbins grade of A or B.

Ramifications of Postoperative Dysphagia on Health Care Resource Utilization Following Elective Anterior Cervical Discectomy and Interbody Fusion for Cervical Spondylotic Myelopathy.

STUDY DESIGN: This is a retrospective cohort study. OBJECTIVE: The aim of this study was to investigate patient risk factors and health care resource utilization associated with postoperative dysphagia following elective anterior cervical discectomy and fusion (ACDF) for cervical spondylotic myelopathy. SUMMARY OF BACKGROUND DATA: There is a paucity of data on factors predisposing patients to dysphagia and the burden this complication has on health care resource utilization following ACDF. METHODS: A retrospective cohort study was performed using the Nationwide Inpatient Sample (NIS) database from 2016 to 2017. All adult (above 18 y old) patients undergoing ACDF for cervical spondylotic myelopathy were identified using the ICD-10-CM diagnosis and procedural coding system. Patients were then categorized by whether they had a recorded postoperative dysphagia or no dysphagia. Weighted patient demographics, comorbidities, perioperative complications, length of hospital stay (LOS), discharge disposition, and total cost of admission were assessed. A multivariate stepwise logistic regression was used to determine both the odds ratio for risk-adjusted postoperative dysphagia as well as extended LOS. RESULTS: A total of 17,385 patients were identified, of which 1400 (8.1%) experienced postoperative dysphagia. Compared with the No-Dysphagia cohort, the Dysphagia cohort had a greater proportion of patients experiencing a complication (P=0.004), including 1 complication (No-Dysphagia: 2.9% vs. Dysphagia: 6.8%), and >1 complication (No-Dysphagia: 0.3% vs. Dysphagia: 0.4%). The Dysphagia cohort experienced significantly longer hospital stays (No-Dysphagia: 1.9±2.1 d vs. Dysphagia: 4.2±4.3 d, P<0.001), higher total cost of admission (No-Dysphagia: $19,441±10,495 vs. Dysphagia: $25,529±18,641, P<0.001), and increased rates of nonroutine discharge (No-Dysphagia: 16.5% vs. Dysphagia: 34.3%, P<0.001). Postoperative dysphagia was found to be a significant independent risk factor for extended LOS on multivariate analysis, with an odds ratio of 5.37 (95% confidence interval: 4.09, 7.05, P<0.001). CONCLUSION: Patients experiencing postoperative dysphagia were found to have significantly longer hospital LOS, higher total cost of admission, and increased nonroutine discharge when compared with the patients who did not. LEVEL OF EVIDENCE: Level III.

Impact of race on nonroutine discharge, length of stay, and postoperative complications after surgery for spinal metastases.

OBJECTIVE: Previous studies have suggested the possibility of racial disparities in surgical outcomes for patients undergoing spine surgery, although this has not been thoroughly investigated in those with spinal metastases. Given the increasing prevalence of spinal metastases requiring intervention, knowledge about potential discrepancies in outcomes would benefit overall patient care. The objective in the present study was to investigate whether race was an independent predictor of postoperative complications, nonroutine discharge, and prolonged length of stay (LOS) after surgery for spinal metastasis. METHODS: The authors retrospectively examined patients at a single comprehensive cancer center who had undergone surgery for spinal metastasis between April 2013 and April 2020. Demographic information, primary pathology, preoperative clinical characteristics, and operative outcomes were collected. Factors achieving p values < 0.15 on univariate regression were entered into a stepwise multivariable logistic regression to generate predictive models. Nonroutine discharge was defined as a nonhome discharge destination and prolonged LOS was defined as LOS greater than the 75th percentile for the entire cohort. RESULTS: Three hundred twenty-eight patients who had undergone 348 operations were included: 240 (69.0%) White and 108 (31.0%) Black. On univariable analysis, cohorts significantly differed in age (p = 0.02), marital status (p < 0.001), insurance status (p = 0.03), income quartile (p = 0.02), primary tumor type (p = 0.04), and preoperative Karnofsky Performance Scale (KPS) score (p < 0.001). On multivariable analysis, race was an independent predictor for nonroutine discharge: Black patients had significantly higher odds of nonroutine discharge than White patients (adjusted odds ratio [AOR] 2.24, 95% confidence interval [CI] 1.28-3.92, p = 0.005). Older age (AOR 1.06 per year, 95% CI 1.03-1.09, p < 0.001), preoperative KPS score ≤ 70 (AOR 3.30, 95% CI 1.93-5.65, p < 0.001), preoperative Frankel grade A-C (AOR 3.48, 95% CI 1.17-10.3, p = 0.02), insurance status (p = 0.005), being unmarried (AOR 0.58, 95% CI 0.35-0.97, p = 0.04), number of levels (AOR 1.17 per level, 95% CI 1.05-1.31, p = 0.004), and thoracic involvement (AOR 1.71, 95% CI 1.02-2.88, p = 0.04) were also predictive of nonroutine discharge. However, race was not independently predictive of postoperative complications or prolonged LOS. Higher Charlson Comorbidity Index (AOR 1.22 per point, 95% CI 1.04-1.43, p = 0.01), low preoperative KPS score (AOR 1.84, 95% CI 1.16-2.92, p = 0.01), and number of levels (AOR 1.15 per level, 95% CI 1.05-1.27, p = 0.004) were predictive of complications, while insurance status (p = 0.05), income quartile (p = 0.01), low preoperative KPS score (AOR 1.64, 95% CI 1.03-2.72, p = 0.05), and number of levels (AOR 1.16 per level, 95% CI 1.05-1.30, p = 0.004) were predictive of prolonged LOS. CONCLUSIONS: Race, insurance status, age, baseline functional status, and marital status were all independently associated with nonroutine discharge. This suggests that a combination of socioeconomic factors and functional status, rather than medical comorbidities, may best predict postdischarge disposition in patients treated for spinal metastases. Further investigation in a prospective cohort is merited.

Synergy between glutamate modulation and anti-programmed cell death protein 1 immunotherapy for glioblastoma.

OBJECTIVE: Immune checkpoint inhibitors such as anti-programmed cell death protein 1 (anti-PD-1) have shown promise for the treatment of cancers such as melanoma, but results for glioblastoma (GBM) have been disappointing thus far. It has been suggested that GBM has multiple mechanisms of immunosuppression, indicating a need for combinatorial treatment strategies. It is well understood that GBM increases glutamate in the tumor microenvironment (TME); however, the significance of this is not well understood. The authors posit that glutamate upregulation in the GBM TME is immunosuppressive. The authors utilized a novel glutamate modulator, BHV-4157, to determine synergy between glutamate modulation and the well-established anti-PD-1 immunotherapy for GBM. METHODS: C57BL/6J mice were intracranially implanted with luciferase-tagged GL261 glioma cells. Mice were randomly assigned to the control, anti-PD-1, BHV-4157, or combination anti-PD-1 plus BHV-4157 treatment arms, and median overall survival was assessed. In vivo microdialysis was performed at the tumor site with administration of BHV-4157. Intratumoral immune cell populations were characterized with immunofluorescence and flow cytometry. RESULTS: The BHV-4157 treatment arm demonstrated improved survival compared with the control arm (p < 0.0001). Microdialysis demonstrated that glutamate concentration in TME significantly decreased after BHV-4157 administration. Immunofluorescence and flow cytometry demonstrated increased CD4+ T cells and decreased Foxp3+ T cells in mice that received BHV-4157 treatment. No survival benefit was observed when CD4+ or CD8+ T cells were depleted in mice prior to BHV-4157 administration (p < 0.05). CONCLUSIONS: In this study, the authors showed synergy between anti-PD-1 immunotherapy and glutamate modulation. The authors provide a possible mechanism for this synergistic benefit by showing that BHV-4157 relies on CD4+ and CD8+ T cells. This study sheds light on the role of excess glutamate in GBM and provides a basis for further exploring combinatorial approaches for the treatment of this disease.

Hybrid Therapy for Metastatic Disease.

Metastatic spine disease represents a complex clinical entity, requiring a multidisciplinary treatment team to formulate treatment plans that treat disease, palliate symptoms, and give patients the greatest quality-of-life. With the improvement in focused radiation technologies, the role of surgery has changed from a standalone treatment to an adjuvant supporting other treatment modalities. As patients within this population are often exceptionally frail, there has been increased emphasis on the smallest possible surgery to achieve the team's treatment goals. Surgeons have increasingly turned to more minimally invasive techniques for treating spinal metastases. The use of these procedures, called separation surgery, centers around the goal of decompressing the neural elements, creating or maintaining mechanical stability, and allowing enough room for high-dose radiation to minimize cord dose.

Neuroprotective Role of Acidosis in Ischemia: Review of the Preclinical Evidence.

Efforts to develop effective neuroprotective therapies for ischemic stroke have had little success to date. One promising approach to neuroprotection is ischemic postconditioning, which utilizes brief bouts of ischemia after acute ischemic stroke to elicit neuroprotection, although the mechanism is largely unknown. As the primary components of transient ischemia are local hypoxia and acidosis, and hypoxic postconditioning has had little success, it is possible that the acidosis component may be the primary driver. To address the evidence behind this, we performed a systematic review of preclinical studies focused on the neuroprotective role of transient acidosis after ischemia. Animal studies demonstrated that mild-to-moderate acidosis after ischemic events led to better functional neurologic outcomes with reduced infarct volumes, while severe acidosis often led to cerebral edema and worse functional outcomes. In vitro studies demonstrated that mild-to-moderate acidosis improves neuronal survival largely through two means: (1) inhibition of harmful superoxide formation in the excitotoxic pathway and (2) remodeling neuronal mitochondria to allow for efficient ATP production (i.e., oxidative phosphorylation), even in the absence of oxygen. Similar to the animal studies, acidotic postconditioning in humans would entail short cycles of carbon dioxide inhalation, which has already been demonstrated to be safe as part of a hypercapnic challenge when measuring cerebrovascular reactivity. Due to the preclinical efficacy of acidotic postconditioning, its relatively straightforward translation into humans, and the growing need for neuroprotective therapies, future preclinical studies should focus on filling the current knowledge gaps that are currently restricting the development of phase I/II clinical trials.