Surgeon specialty effect on early outcomes of elective posterior spinal fusion for adolescent idiopathic scoliosis: a propensity-matched analysis of 965 patients.

BACKGROUND AND OBJECTIVE: Comparative effectiveness research plays a vital role in health care delivery. Specialty training is one of these variables; surgeons who are trained in different specialties may have different outcomes performing the same procedure. The objective of this study was to investigate the impact of spine surgeon specialty (neurosurgery vs orthopedic surgery) on early perioperative outcome measures of elective posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS). METHODS: This is a retrospective, 1:4 propensity score-matched cohort study. 5520 AIS patients were reviewed from ACS-NSQIP pediatric database. Propensity score matching was utilized. RESULTS: Patients operated on by orthopedic surgeons were more likely to have shorter operation time (263 min vs 285 min), shorter total hospital stay (95 h vs 118 h), lower rate of return to operating room within the same admission (1.2% vs 3.8%), lower discharge rates after postoperative day 4 (23.8% vs 30.9%), and lower unplanned readmission rate (1.6% vs 4.1%), (p < 0.05). On the other hand, patients operated on by neurosurgeons had lower perioperative blood transfusion rate (62.1% vs 69.8%), (p < 0.05). Other outcome measures and mortality rates were not significantly different between the two cohorts. CONCLUSIONS: This retrospective study found significant differences in early perioperative outcomes of patients undergoing PSF for AIS by neurosurgeons and orthopedic surgeons. Further studies are recommended to corroborate this finding which may trigger changes in the educational curriculum for neurosurgery residents.

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.

Impact of surgery and radiation therapy on spinal high-grade gliomas: a population-based study.

INTRODUCTION: Spinal high-grade gliomas (S-HGGs) is an extremely rare entity in the literature, with only sporadic cases reported. We aim to characterize prognostic factors for post-treatment survival using the SEER database. METHODS: We examined all patients with gliomas located in the spinal cord. WHO-grade was first determined by site-specific factor-1 (WHO-grade), then supplemented by direct review of ICD-O-3 histology. Only grades 3 and 4 were included in this study. Multivariable Cox regression analysis was performed. RESULTS: A total of 158 high-grade spinal cord gliomas were included. Mean age at diagnosis was 36.88 years with 52.8% male. Median survival of all patients was 20 months. A stepwise Akaike information criterion was performed for multivariable Cox regression, with forced inclusion of surgery extent and postoperative radiation therapy (RT). The final model selection added tumor size in addition to these two variables. Tumor size was not related to survival in our study. The extend of surgery had no significant impact on survival of patients, whereas postoperative RT is associated with prolonged survival (HR = 0.55, CI [0.33, 0.93], p = 0.026). CONCLUSION: S-HGGs are rare tumors with aggressive course of disease. We have found that overall median survival of S-HGGs is poor at 24 months, and no demographic or tumor-related factors have been confirmed. Extend of surgery is not associated with improved survival after adjusting for postoperative RT. Postoperative RT is the only factor in our study associated with prolonged survival in S-HGGs.

Aneurysmal bone cysts of the spine: treatment options and considerations.

Aneurysmal bone cysts (ABCs) are benign bone lesions with annual incidences ranging from 1.4 to 3.2 cases per million people. Approximately, 10-30% of ABCs are found in the spine. Such lesions are traditionally treated with curettage or other intralesional techniques. Because ABCs can be locally aggressive, intralesional resection can be incomplete and result in recurrence. This has led to increased use of novel techniques, including selective arterial embolization (SAE). This study aims to: (1) compare outcomes based on extent of surgical resection, and (2) compare the efficacy of SAE versus surgical resection. Clinical data pertaining to 71 cases of spinal ABCs were ambispectively collected from nine institutions in Europe, North America, and Australia. Twenty-two spinal ABCs were treated with surgery, 32 received preoperative embolization and surgery, and 17 were treated with SAE. Most tumors were classified as Enneking stage 2 (n = 29, 41%) and stage 3 (n = 29, 41%). Local recurrence and survival were investigated and a significant difference was not observed between treatment groups. However, all three local recurrences occurred following surgical resection. Surgical resection was further categorized based on Enneking appropriateness. Recurrences only occurred following intralesional Enneking inappropriate (EI) resections (P = 0.10), a classification that characterized 47% of all surgical resections. Furthermore, 56% of intralesional resections were EI, compared to only 10% of en bloc resections (P = 0.01). Although SAE treatment did not result in any local recurrences, 35% involved more than five embolization procedures. Spinal ABCs can be effectively treated with intralesional resection, en bloc resection, or SAE. Preoperative embolization should be considered before intralesional resection to limit intraoperative bleeding. Treatment plans must be guided by lesion characteristics and clinical presentation.

A Bibliometric Analysis of the 20 Most Cited Articles on Sacrococcygeal Chordomas.

This study aims to summarize sacrococcygeal chordoma literature through bibliometric analysis and to offer insights into key studies to guide clinical practices and future research. The Web of Science database was searched using the terms "sacral chordoma", "chordomas of the sacrum", "chordomas of the sacral spine", "chordomas of the sacrococcygeal region", "coccygeal chordoma", and "coccyx chordoma". Articles were analyzed for citation count, authorship, publication date, journal, research area tags, impact factor, and evidence level. The median number of citations was 75 (range: 53-306). The primary publication venue was the International Journal of Radiation Oncology, Biology, Physics. Most works, published between 1999 and 2019, featured a median journal impact factor of 3.8 (range: 2.1-7) and predominantly fell under the research area tag, radiation, nuclear medicine, and imaging. Of these articles, 19 provided clinical data with predominantly level III evidence, and one was a literature review. This review highlights the increasing volume of sacrococcygeal chordoma publications over the past two decades, indicating evolving treatment methods and interdisciplinary patient care. Advances in radiation, particularly intensity-modulated radiation therapy (IMRT) and proton beam therapy, are believed to be propelling research growth, and the lack of level I evidence underscores the need for more rigorous studies to refine treatment protocols for sacrococcygeal chordomas.

Prevalence and Influence of Frailty on Hospital Outcomes After Surgical Resection of Spinal Meningiomas.

OBJECTIVE: Frailty has been shown to affect patient outcomes after medical and surgical interventions. The Hospital Frailty Risk Score (HFRS) is a growing metric used to assess patient frailty using International Classification of Diseases, Tenth Revision codes. The goal of this study was to investigate the impact of frailty, assessed by HFRS, on health care resource utilization and outcomes in patients undergoing surgery for spinal meningiomas. METHODS: A retrospective cohort study was performed using the 2016-2019 National Inpatient Sample database. Adult patients with benign or malignant spinal meningiomas, identified using International Classification of Diseases, Tenth Revision, Clinical Modification codes, were stratified by HFRS: low frailty (HFRS <5) and intermediate-high frailty (HFRS ≥5). Patient demographics, hospital characteristics, comorbidities, procedural variables, adverse events, length of stay (LOS), discharge disposition, and cost of admission were assessed. Multivariate regression analysis was used to identify predictors of increased LOS, discharge disposition, and cost. RESULTS: Of the 3345 patients, 530 (15.8%) had intermediate-high frailty. The intermediate-high cohort was significantly older (P < 0.001). More patients in the intermediate-high cohort had ≥3 comorbidities (P < 0.001). In addition, a greater proportion of patients in the intermediate-high cohort experienced ≥1 perioperative adverse events (P < 0.001). Intermediate-high patients experienced greater mean LOS (P < 0.001) and accrued greater costs (P < 0.001). A greater proportion of intermediate-high patients had nonroutine discharges (P < 0.001). On multivariate analysis, increased HFRS (≥5) was independently associated with extended LOS (adjusted odds ratio [aOR], 3.04; P < 0.001), nonroutine discharge (aOR, 1.98; P = 0.006), and increased costs (aOR, 2.39; P = 0.004). CONCLUSIONS: Frailty may be associated with increased health care resource utilization in patients undergoing surgery for spinal meningiomas.

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.

IFN-gamma primes intact human coronary arteries and cultured coronary smooth muscle cells to double-stranded RNA- and self-RNA-induced inflammatory responses by upregulating TLR3 and melanoma differentiation-associated gene 5.

Atherosclerosis of native coronary arteries and graft arteriosclerosis in transplanted hearts are characterized by activation of innate and adaptive immune responses. Nucleic acids generated by infections or cell death have been detected within arteriosclerotic lesions, and it is known that microbial and synthetic nucleic acids evoke inflammatory responses in cultured vascular cells. In this study, we report that model RNA, but not DNA, instigated robust cytokine and chemokine production from intact human coronary arteries containing both intrinsic vascular cells and resident/infiltrating leukocytes. An ssRNA analog induced TNF-alpha and IFN-gamma-induced protein of 10 kDa secretion by isolated human PBMCs, but not vascular cells. Conversely, synthetic dsRNA induced these inflammatory mediators by vascular cells, but not PBMCs. IFN-gamma, a cytokine linked to atherosclerosis and graft arteriosclerosis, potentiated the inflammatory responses of intact arteries and cultured vascular smooth muscle cells (VSMCs) to polyinosinic:polycytidylic acid [poly(I:C)] and was necessary for inflammatory responses of VSMC to self-RNA derived from autologous cells. IFN-gamma also induced the expression of TLR3, melanoma differentiation-associated gene 5, and retinoic acid-inducible gene I dsRNA receptors. Small interfering RNA knockdown revealed that TLR3 mediated VSMC activation by poly(I:C), whereas melanoma differentiation-associated gene 5 was more important for VSMC stimulation by self-RNA. IFN-gamma-mediated induction of dsRNA receptors and priming for inflammatory responses to poly(I:C) was confirmed in vivo using immunodeficient mice bearing human coronary artery grafts. These findings suggest that IFN-gamma, and by inference adaptive immunity, sensitizes the vasculature to innate immune activators, such as RNA, and activation of IFN-gamma-primed vascular cells by exogenous or endogenous sources of RNA may contribute to the inflammatory milieu of arteriosclerosis.

Mucormycosis of the Spine: A Case Report and Review of the Literature.

Mucormycosis is an extremely rare, invasive infection commonly isolated to patients with known immunosuppressed status. In the present case, a 36-year-old woman, with a history of T-cell acute lymphoblastic leukemia in remission, presented with T4 osteomyelitis and an associated epidural collection. Biopsy was consistent with mucormycosis, and the patient was recommended for surgical debridement. After declining debridement, the patient was successfully managed on a multiagent antifungal regimen consisting of intravenous amphotericin B, micafungin, and oral posaconazole. The patient was alive without clear evidence of disease at eight months, representing one of the first cases of spinal mucormycosis infection successfully treated with medical management alone. We additionally review the previous descriptions of spinal mucormycosis infections to identify those interventions most associated with successful clearance or containment of these infections.

Ventral Spinal Cord Herniation Causing Spinal Intradural Hematoma and Subarachnoid Hemorrhage: A Case Report.

Ventral spinal cord herniation is a rare pathology, caused by a dural defect, that leads to progressive myelopathy. The true prevalence of ventral spinal cord herniation is unknown largely because of underdiagnosis due to its nonspecific symptoms. Though there are theories that attempt to describe how these dural defects are formed, the true causes of these defects are unknown. In this case report, we present a case of a 29-year-old female who had an idiopathic ventral spinal cord herniation causing an intradural hematoma and subarachnoid hemorrhage. This is the first reported case of spinal cord herniation causing hemorrhage.

Early Outcomes of Elective Anterior Cervical Diskectomy and Fusion for Degenerative Spine Disease Correlate With the Specialty of the Surgeon Performing the Procedure.

BACKGROUND: Comparative effectiveness research has a vital role in recent health reform and policies. Specialty training is one of these provider-side variables, and surgeons who were trained in different specialties may have different outcomes on performing the same procedure. OBJECTIVE: To investigate the impact of spine surgeon specialty (neurosurgery vs orthopedic surgery) on early perioperative outcome measures of elective anterior cervical diskectomy and fusion (ACDF) for degenerative spine diseases. METHODS: This was a retrospective, 1:1 propensity score-matched cohort study. In total, 21 211 patients were reviewed from the American College of Surgeons National Surgical Quality Improvement Program database. Propensity score matching and subgroup analysis were performed. RESULTS: In both groups (single-level/multilevel ACDF), patients operated on by neurosurgeons had longer operation time (133 vs 104 min/164 vs 138 min), shorter total hospital stay (24 vs 41 h/25 vs 46 h), and lower rates of return to operating room (0.7% vs 2.1%/0.6% vs 2.4%), nonhome discharge (1.2% vs 4.6%/1.0% vs 4.9%), discharge after postoperative day 1 (6.7% vs 11.9%/10.1% vs 18.9%), perioperative blood transfusion (0.4% vs 2.1%/0.6% vs 3.1%), and sepsis (0.2% vs 0.7%/0.1% vs 0.7%; P < .05). In the single-level ACDF group, patients operated on by neurosurgeons had lower readmission (1.9% vs 4.1%) and unplanned intubation rates (0.1% vs 1.1%; P < .05). Other outcome measures and mortality rates were similar among the 2 cohorts in both groups. CONCLUSION: Our analysis found significant differences in early perioperative outcomes of patients undergoing ACDF by neurosurgeons and orthopedic surgeons. These differences might have significant clinical and cost implications for patients, physicians, program directors, payers, and health systems.

Catheter-directed venography for evaluating internal jugular vein pseudo-occlusion.

The incidence and effects of stenosis of the cerebral venous system are poorly understood. When noninvasive computed tomography venography (CTV) of the head and neck suggests complete internal jugular vein (IJV) occlusion, invasive catheter-directed venography can discordantly show venous patency. We compared CTV vs digital subtraction venography (DSV) in the evaluation of patency/occlusion in the suspected IJV and contralateral IJV. We queried the venous intervention database of our U.S. academic tertiary-care hospital to identify patients with complete or near-complete IJV occlusion per CTV from March 1, 2019 to March 1, 2020. We included patients with both noninvasive and invasive imaging of the target segment and the contralateral IJV. Four patients had suspected occlusion of the IJV at the skull base. Invasive catheter-directed venography consisted of DSV to assess direction of flow and vessel caliber, as well as manometry proximal and distal to areas of suspected stenosis. DSV showed patency in all 4 IJVs for which CTV had shown suspected occlusions. CTV findings of the contralateral IJVs were patency (n = 2), moderate stenosis (n = 1), and severe/critical stenosis (n = 1). Contralateral IJV caliber, measured by DSV, was concordant with CTV findings. Median mean-pressure gradients across the apparent occlusion and contralateral segments were 1 (range, 1-4) mmHg and 0 (range, 0-5) mmHg, respectively. Although noninvasive CTV may suggest absence of or attenuated flow within the IJV, this technique may be insufficient to establish complete occlusion. Catheter-directed venography can be used to evaluate patency, vessel caliber, and mean-pressure gradient.

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.

Risk factors for surgical intervention in patients with primary spinal infection on initial presentation.

OBJECTIVE: Treatment of primary spinal infection includes medical management with or without surgical intervention. The objective of this study was to identify risk factors for the eventual need for surgery in patients with primary spinal infection on initial presentation. METHODS: From January 2010 to July 2019, 275 patients presented with primary spinal infection. Demographic, infectious, imaging, laboratory, treatment, and outcome data were retrospectively reviewed and collected. Thirty-three patients were excluded due to insufficient follow-up (≤ 90 days) or death prior to surgery. RESULTS: The mean age of the 242 patients was 58.8 ± 13.6 years. The majority of the patients were male (n = 130, 53.7%), White (n = 150, 62.0%), and never smokers (n = 132, 54.5%). Fifty-four patients (22.3%) were intravenous drug users. One hundred fifty-four patients (63.6%) ultimately required surgery while 88 (36.4%) never needed surgery during the duration of follow-up. There was no significant difference in age, gender, race, BMI, or comorbidities between the surgery and no-surgery groups. On univariate analysis, the presence of an epidural abscess (55.7% in the no-surgery group vs 82.5% in the surgery group, p < 0.0001), the median spinal levels involved (2 [interquartile range (IQR) 2-3] in the no-surgery group vs 3 [IQR 2-5] in the surgery group, p < 0.0001), and active bacteremia (20.5% in the no-surgery vs 35.1% in the surgery group, p = 0.02) were significantly different. The cultured organism and initial laboratory values (erythrocyte sedimentation rate, C-reactive protein, white blood cell count, creatinine, and albumin) were not significantly different between the groups. On multivariable analysis, the final model included epidural abscess, cervical or thoracic spine involvement, and number of involved levels. After adjusting for other variables, epidural abscess (odds ratio [OR] 3.04, 95% confidence interval [CI] 1.64-5.63), cervical or thoracic spine involvement (OR 2.03, 95% CI 1.15-3.61), and increasing number of involved levels (OR 1.16, 95% CI 1.01-1.35) were associated with greater odds of surgery. Fifty-two surgical patients (33.8%) underwent decompression alone while 102 (66.2%) underwent decompression with fusion. Of those who underwent decompression alone, 2 (3.8%) of 52 required subsequent fusion due to kyphosis. No patient required hardware removal due to persistent infection. CONCLUSIONS: At time of initial presentation of primary spinal infection, the presence of epidural abscess, cervical or thoracic spine involvement, as well as an increasing number of involved spinal levels were potential risk factors for the eventual need for surgery in this study. Additional studies are needed to assess for risk factors for surgery and antibiotic treatment failure.

Does the Specialty of the Surgeon Performing Elective Anterior/Lateral Lumbar Interbody Fusion for Degenerative Spine Disease Correlate with Early Perioperative Outcomes?

BACKGROUND: Comparative effectiveness research has a vital role in health reform and policies. Specialty training is one of these provider-side variables, and surgeons performing the same procedure who were trained in different specialties may have different outcomes. The objective of this study was to investigate the impact of spine surgeon specialty (neurosurgery vs. orthopedic surgery) on early perioperative outcome measures of elective anterior/lateral lumbar interbody fusion (ALIF/LLIF) for degenerative disc diseases. METHODS: In a retrospective, 1:1 propensity score-matched cohort study, 9070 patients were reviewed from the American College of Surgeons National Surgical Quality Improvement Program database. Propensity score matching and subgroup analysis were used. RESULTS: In both groups (single-level and multilevel ALIF/LLIF), patients operated on by neurosurgeons had longer operative time (188 minutes vs. 172 minutes/239 minutes vs. 221 minutes); shorter total hospital stay (71 hours vs. 90 hours/89 hours vs. 96 hours); and lower rates of return to the operating room (2.1% vs. 4.1%/2.4% vs. 4.2%), nonhome discharge (8.7% vs. 11.1%/10.1% vs. 14.9%), discharge after postoperative day 3 (22.0% vs. 30.0%/38.0% vs. 43.9%), and perioperative blood transfusion (2.1% vs. 5.1%/5.0% vs. 9.9%) (P < 0.05). In multilevel ALIF/LLIF, patients operated on by neurosurgeons had lower readmission rates (3.9% vs. 6.9%) (P < 0.05). Other outcome measures and mortality rates were similar between the single-level and multilevel ALIF/LLIF cohorts regardless of surgeon specialty. CONCLUSIONS: Our analysis found significant differences in early perioperative outcomes of patients undergoing ALIF/LLIF by neurosurgeons and orthopedic surgeons. These differences have significant clinical and cost implications for patients, physicians, program directors, payers, and health systems.

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.

Radiomic modeling to predict risk of vertebral compression fracture after stereotactic body radiation therapy for spinal metastases.

OBJECTIVE: In the treatment of spinal metastases with stereotactic body radiation therapy (SBRT), vertebral compression fracture (VCF) is a common and potentially morbid complication. Better methods to identify patients at high risk of radiation-induced VCF are needed to evaluate prophylactic measures. Radiomic features from pretreatment imaging may be employed to more accurately predict VCF. The objective of this study was to develop and evaluate a machine learning model based on clinical characteristics and radiomic features from pretreatment imaging to predict the risk of VCF after SBRT for spinal metastases. METHODS: Vertebral levels C2 through L5 containing metastases treated with SBRT were included if they were naive to prior surgery or radiation therapy, target delineation was based on consensus guidelines, and 1-year follow-up data were available. Clinical features, including characteristics of the patient, disease, and treatment, were obtained from chart review. Radiomic features were extracted from the planning target volume (PTV) on pretreatment CT and T1-weighted MRI. Clinical and radiomic features selected by least absolute shrinkage and selection operator (LASSO) regression were included in random forest classification models, which were trained to predict VCF within 1 year after SBRT. Model performance was assessed with leave-one-out cross-validation. RESULTS: Within 1 year after SBRT, 15 of 95 vertebral levels included in the analysis demonstrated new or progressive VCF. Selected clinical features included BMI, performance status, total prescription dose, dose to 99% of the PTV, lumbar location, and 2 components of the Spine Instability Neoplastic Score (SINS): lytic tumor character and spinal misalignment. Selected radiomic features included 5 features from CT and 3 features from MRI. The best-performing classification model, derived from a combination of selected clinical and radiomic features, demonstrated a sensitivity of 0.844, specificity of 0.800, and area under the receiver operating characteristic (ROC) curve (AUC) of 0.878. This model was significantly more accurate than alternative models derived from only selected clinical features (AUC = 0.795, p = 0.048) or only components of the SINS (AUC = 0.579, p < 0.0001). CONCLUSIONS: In the treatment of spinal metastases with SBRT, a machine learning model incorporating both clinical features and radiomic features from pretreatment imaging predicted VCF at 1 year after SBRT with excellent sensitivity and specificity, outperforming models developed from clinical features or components of the SINS alone. If validated, these findings may allow more judicious selection of patients for prophylactic interventions.

High-dose hypofractionated stereotactic body radiotherapy for spinal chordoma.

OBJECTIVE: Spinal chordoma is locally aggressive and has a high rate of recurrence, even after en bloc resection. Conventionally fractionated adjuvant radiation leads to suboptimal tumor control, and data regarding hypofractionated regimens are limited. The authors hypothesized that neoadjuvant stereotactic body radiotherapy (SBRT) may overcome its intrinsic radioresistance, improve surgical margins, and allow preservation of critical structures during surgery. The purpose of this study is to review the feasibility and early outcomes of high-dose hypofractionated SBRT, with a focus on neoadjuvant SBRT. METHODS: Electronic medical records of patients with spinal chordoma treated using image-guided SBRT between 2009 and 2019 at a single institution were retrospectively reviewed. RESULTS: Twenty-eight patients with 30 discrete lesions (24 in the mobile spine) were included. The median follow-up duration was 20.8 months (range 2.3-126.3 months). The median SBRT dose was 40 Gy (range 15-50 Gy) in 5 fractions (range 1-5 fractions). Seventeen patients (74% of those with newly diagnosed lesions) received neoadjuvant SBRT, of whom 15 (88%) underwent planned en bloc resection, all with negative margins. Two patients (12%) developed surgical wound-related complications after neoadjuvant SBRT and surgery, and 4 (two grade 3 and two grade 2) experienced postoperative complications unrelated to the surgical site. Of the remaining patients with newly diagnosed lesions, 5 received adjuvant SBRT for positive or close surgical margins, and 1 received SBRT alone. Seven recurrent lesions were treated with SBRT alone, including 2 after failure of prior conventional radiation. The 2-year overall survival rate was 92% (95% confidence interval [CI] 71%-98%). Patients with newly diagnosed chordoma had longer median survival (not reached) than those with recurrent lesions (27.7 months, p = 0.006). The 2-year local control rate was 96% (95% CI 74%-99%). Among patients with radiotherapy-naïve lesions, no local recurrence was observed with a biologically effective dose ≥ 140 Gy, maximum dose of the planning target volume (PTV) ≥ 47 Gy, mean dose of the PTV ≥ 39 Gy, or minimum dose to 80% of the PTV ≥ 36 Gy (5-fraction equivalent doses). All acute toxicities from SBRT were grade 1-2, and no myelopathy was observed. CONCLUSIONS: Neoadjuvant high-dose, hypofractionated SBRT for spinal chordoma is safe and does not increase surgical morbidities. Early outcomes at 2 years are promising, although long-term follow-up is pending.

Intraoperative cone-beam and slot-beam CT: 3D image quality and dose with a slot collimator on the O-arm imaging system.

PURPOSE: To characterize the 3D imaging performance and radiation dose for a prototype slot-beam configuration on an intraoperative O-arm™ Surgical Imaging System (Medtronic Inc., Littleton, MA) and identify potential improvements in soft-tissue image quality for surgical interventions. METHODS: A slot collimator was integrated with the O-arm™ system for slot-beam axial CT. The collimator can be automatically actuated to provide 1.2° slot-beam longitudinal collimation. Cone-beam and slot-beam configurations were investigated with and without an antiscatter grid (12:1 grid ratio, 60 lines/cm). Dose, scatter, image noise, and soft-tissue contrast resolution were evaluated in quantitative phantoms for head and body configurations over a range of exposure levels (beam energy and mAs), with reconstruction performed via filtered-backprojection. Qualitative imaging performance across various anatomical sites and imaging tasks was assessed with anthropomorphic head, abdomen, and pelvis phantoms. RESULTS: The dose for a slot-beam scan varied from 0.02-0.06 mGy/mAs for head protocols to 0.01-0.03 mGy/mAs for body protocols, yielding dose reduction by ∼1/5 to 1/3 compared to cone-beam, owing to beam collimation and reduced x-ray scatter. The slot-beam provided an ∼6-7× reduction in scatter-to-primary ratio (SPR) compared to the cone-beam, yielding SPR ∼20-80% for head and body without the grid and ∼7-30% with the grid. Compared to cone-beam scans at equivalent dose, slot-beam images exhibited an ∼2.5× increase in soft-tissue contrast-to-noise ratio (CNR) for both grid and gridless configurations. For slot-beam scans, a further ∼10-30% improvement in CNR was achieved when the grid was removed. Slot-beam imaging could benefit certain interventional scenarios in which improved visualization of soft tissues is required within a fairly narrow longitudinal region of interest ( ± 7 mm in z )--for example, checking the completeness of tumor resection, preservation of adjacent anatomy, or detection of complications (e.g., hemorrhage). While preserving existing capabilities for fluoroscopy and cone-beam CT, slot-beam scanning could enhance the utility of intraoperative imaging and provide a useful mode for safety and validation checks in image-guided surgery. CONCLUSIONS: The 3D imaging performance and dose of a prototype slot-beam CT configuration on the O-arm™ system was investigated. Substantial improvements in soft-tissue image quality and reduction in radiation dose are evident with the slot-beam configuration due to reduced x-ray scatter.

Interleukin-17 and interferon-gamma are produced concomitantly by human coronary artery-infiltrating T cells and act synergistically on vascular smooth muscle cells.

BACKGROUND: Atherosclerosis is an inflammatory disease in which interferon (IFN)-gamma, the signature cytokine of Th1 cells, plays a central role. We investigated whether interleukin (IL)-17, the signature cytokine of Th17 cells, is also associated with human coronary atherosclerosis. METHODS AND RESULTS: Circulating IL-17 and IFN-gamma were detected in a subset of patients with coronary atherosclerosis and in referent outpatients of similar age without cardiac disease but not in young healthy individuals. IL-17 plasma levels correlated closely with those of the IL-12/IFN-gamma/CXCL10 cytokine axis but not with known Th17 inducers such as IL-1beta, IL-6, and IL-23. Both IL-17 and IFN-gamma were produced at higher levels by T cells within cultured atherosclerotic coronary arteries after polyclonal activation than within nondiseased vessels. Combinations of proinflammatory cytokines induced IFN-gamma but not IL-17 secretion. Blockade of IFN-gamma signaling increased IL-17 synthesis, whereas neutralization of IL-17 responses decreased IFN-gamma synthesis; production of both cytokines was inhibited by transforming growth factor-beta1. Approximately 10-fold fewer coronary artery-infiltrating T helper cells were IL-17 producers than IFN-gamma producers, and unexpectedly, IL-17/IFN-gamma double producers were readily detectable within the artery wall. Although IL-17 did not modulate the growth or survival of cultured vascular smooth muscle cells, IL-17 interacted cooperatively with IFN-gamma to enhance IL-6, CXCL8, and CXCL10 secretion. CONCLUSIONS: Our findings demonstrate that IL-17 is produced concomitantly with IFN-gamma by coronary artery-infiltrating T cells and that these cytokines act synergistically to induce proinflammatory responses in vascular smooth muscle cells.