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Study Design: Systematic Review., Objectives: While substantial research has explored the impact of osteoporosis on patients undergoing adult spinal deformity (ASD) correction, the literature remains inconclusive. As such, the purpose of this study is to synthesize and analyze existing studies pertaining to osteoporosis as a predictor of postoperative outcomes in ASD surgery., Methods: We performed a systematic review and meta-analysis to determine the effect that a diagnosis of osteoporosis, based on ICD-10 coding, dual-energy X-ray absorptiometry (DEXA) or computed tomography, has on the incidence of adverse outcomes following surgical correction of ASD. Statistical analysis was performed using Comprehensive Meta-Analysis (Version 2) using a random effects model to account for heterogeneity between studies., Results: After application of inclusion and exclusion criteria, 36 and 28 articles were included in the systematic review and meta-analysis, respectively. The meta-analysis identified greater rates of screw loosening amongst osteoporotic patients (70.5% vs 31.9%, P = .009), and decreased bone mineral density in patients who developed proximal junctional kyphosis (PJK) (.69 vs .79 g/cm 2 , P = .001). The systematic review demonstrated significantly increased risk of any complication, reoperation, and proximal junctional failure (PJF) associated with reduced bone density. No statistical difference was observed between groups regarding fusion rates, readmission rates, and patient-reported and/or functional outcome scores., Conclusion: This study demonstrates a higher incidence of screw loosening, PJK, and revision surgery amongst osteoporotic ASD patients. Future investigations should explore outcomes at various follow-up intervals in order to better characterize how risk changes with time and to tailor preoperative planning based on patient-specific characteristics., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Traditional deep fluorescence imaging has primarily focused on red-shifting imaging wavelengths into the near-infrared (NIR) windows or implementation of multi-photon excitation approaches. Here, we combine the advantages of NIR and multiphoton imaging by developing a dual-infrared two-photon microscope to enable high-resolution deep imaging in biological tissues. We first computationally identify that photon absorption, as opposed to scattering, is the primary contributor to signal attenuation. We next construct a NIR two-photon microscope with a 1640 nm femtosecond pulsed laser and a NIR PMT detector to image biological tissues labeled with fluorescent single-walled carbon nanotubes (SWNTs). We achieve spatial imaging resolutions close to the Abbe resolution limit and eliminate blur and background autofluorescence of biomolecules, 300 μm deep into brain slices and through the full 120 μm thickness of a Nicotiana benthamiana leaf. We also demonstrate that NIR-II two-photon microscopy can measure tissue heterogeneity by quantifying how much the fluorescence power law function varies across tissues, a feature we exploit to distinguish Huntington's Disease afflicted mouse brain tissues from wildtype. Our results suggest dual-infrared two-photon microscopy could accomplish in-tissue structural imaging and biochemical sensing with a minimal background, and with high spatial resolution, in optically opaque or highly autofluorescent biological tissues.

Background and Objectives: Adjacent segment disease is a relatively common late complication after lumbar fusion. If symptomatic, certain patients require fusion of the degenerated adjacent segment. Currently, there are no posterior completely minimally invasive techniques described for fusion of the adjacent segment above or below a previous fusion. We describe here a novel minimally invasive technique for both implant removal (MIS-IR) and adjacent level transforaminal lumbar interbody fusion (MIS-TLIF) for lumbar stenosis., Methods: Demographic, surgical, and radiographic outcome data were collected for patients with lumbar stenosis and previous lumbar fusion, who were treated with MIS-IR and MIS-TLIF through the same incision. Radiographic outcomes were assessed postoperatively and complications were assessed at the primary end point of 3 months., Results: A total of 14 patients (7 female and 7 male), with average age 64.6 years (SD 13.4), were included in this case series. Nine patients had single-level MIS-IR with single-level MIS-TLIF. Three patients had 2-level MIS-IR with single-level MIS-TLIF. Two patients had single-level MIS-IR with 2-level MIS-TLIF. Only 1 patient had a postoperative complication-hematoma requiring same-day evacuation. There were no other complications at the primary end point and no fusion failure at the hardware removal levels to date (average follow-up, 11 months). Average increases in posterior disk height and foraminal height after MIS-TLIF were 4.44, and 2.18 mm, respectively., Conclusion: Minimally invasive spinal IR can be successfully completed along with adjacent level TLIF through the same incisions, via an all-posterior approach., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Background: Risk assessment is critically important in elective and high-risk interventions, particularly spine surgery. This narrative review describes the evolution of risk assessment from the earliest instruments focused on general surgical risk stratification, to more accurate and spine-specific risk calculators that quantified risk, to the current era of big data., Methods: The PubMed and SCOPUS databases were queried on October 11, 2023 using search terms to identify risk assessment tools (RATs) in spine surgery. A total of 108 manuscripts were included after screening with full-text review using the following inclusion criteria: 1) study population of adult spine surgical patients, 2) studies describing validation and subsequent performance of preoperative RATs, and 3) studies published in English., Results: Early RATs provided stratified patients into broad categories and allowed for improved communication between physicians. Subsequent risk calculators attempted to quantify risk by estimating general outcomes such as mortality, but then evolved to estimate spine-specific surgical complications. The integration of novel concepts such as invasiveness, frailty, genetic biomarkers, and sarcopenia led to the development of more sophisticated predictive models that estimate the risk of spine-specific complications and long-term outcomes., Conclusions: RATs have undergone a transformative shift from generalized risk stratification to quantitative predictive models. The next generation of tools will likely involve integration of radiographic and genetic biomarkers, machine learning, and artificial intelligence to improve the accuracy of these models and better inform patients, surgeons, and payers., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: We evaluated the contributions of chronological age, comorbidity burden, and/or frailty in predicting 90-day readmission in patients undergoing degenerative scoliosis surgery., Methods: Patients were identified through the Healthcare Cost and Utilization Project Nationwide Readmissions Database. Frailty was assessed using the Johns Hopkins Adjusted Clinical Groups frailty-defining indicator. Comorbidity was assessed using the Elixhauser Comorbidity Index (ECI). Generalized linear mixed-effects models were created to predict readmission using age, frailty, and/or ECI. Area under the curve (AUC) was compared using DeLong's test., Results: A total of 8104 patients were identified. Readmission rate was 9.8%, with infection representing the most common cause (3.5%). Our first model utilized chronological age, ECI, and/or frailty as primary predictors. The combination of ECI + frailty + age performed best, but the inclusion of chronological age did not significantly improve performance compared to ECI + frailty alone (AUC 0.603 vs. 0.599, P = 0.290). A second model using only chronological age and frailty as primary predictors performed better, however the inclusion of chronological age worsened performance when compared to frailty alone (AUC 0.747 vs. 0.743, P = 0.043)., Conclusions: These data support frailty as a predictor of 90-day readmission within a nationally representative sample. Frailty alone performed better than combinations of ECI and age. Interestingly, the integration of chronological age did not dramatically improve the model's performance. Limitations include the use of a national registry and a single frailty index. This provides impetus to explore biological age, rather than chronological age, as a potential tool for surgical risk assessment., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Internationally, the United States (U.S.) cites the highest cost burden of low back pain (LBP). The cost continues to rise, faster than the rate of inflation and overall growth of health expenditures. We performed a comprehensive literature review of peer-reviewed and non- peer-reviewed literature from PubMed, Scopus, and Google Scholar for contemporary data on prevalence, cost, and projected future costs. Policymakers in the U.S. have long attempted to address the high-cost burden of LBP through limiting low-value services and early imaging. Despite these efforts, costs (~$40 billion; ~$2,000/patient/yr) continue to rise with increasing rates of unindicated imaging, high rates of surgery, and subsequent revision surgery without proper trial of non-pharmacologic measures and no corresponding reduction in LBP prevalence. Globally, the overall prevalence of LBP continues to rise largely secondary to a growing aging population. Cost containment methods should focus on careful and comprehensive clinical assessment of patients to better understand when more resource-intensive interventions are indicated.

Objective: Surgery for spinal deformity has the potential to improve pain, disability, function, self-image, and mental health. These surgical procedures carry significant risk and require careful selection, optimization, and risk assessment. Epigenetic clocks are age estimation tools derived by measuring the methylation patterns of specific DNA regions. The study of biological age in the adult deformity population has the potential to shed insight onto the molecular basis of frailty and to improve current risk assessment tools., Methods: Adult patients who underwent deformity surgery were prospectively enrolled. Preoperative whole blood samples were used to assess epigenetic age and telomere length. DNA methylation patterns were quantified and processed to extract 4 principal component (PC)-based epigenetic age clocks (PC Horvath, PC Hannum, PC PhenoAge, and PC GrimAge) and the instantaneous pace of aging (DunedinPACE). Telomere length was assessed using both quantitative polymerase chain reaction (telomere to single gene [T/S] ratio) and a methylation-based telomere estimator (PC DNAmTL). Patient demographic and surgical data included age, BMI, American Society of Anesthesiologists Physical Status Classification System class, and scores on the Charlson Comorbidity Index, adult spinal deformity frailty index (ASD-FI), Edmonton Frail Scale (EFS), Oswestry Disability Index, and Scoliosis Research Society-22r questionnaire (SRS-22r). Medical or surgical complications within 90 days of surgery were collected. Spearman correlations and beta coefficients (β) from linear regression, adjusted for BMI and sex, were calculated., Results: Eighty-three patients were enrolled with a mean age of 65 years, and 45 were women (54%). All patients underwent posterior fusion with a mean of 11 levels fused and 33 (40%) 3-column osteotomies were performed. Among the epigenetic clocks adjusted for BMI and sex, DunedinPACE showed a significant association with ASD-FI (β = 0.041, p = 0.002), EFS (β = 0.696, p = 0.026), and SRS-22r (β = 0.174, p = 0.013) scores. PC PhenoAge showed associations with ASD-FI (β = 0.029, p = 0.028) and SRS-22r (β = 0.159, p = 0.018) scores. PC GrimAge showed associations with ASD-FI (β = 0.029, p = 0.037) and SRS-22r (β = 0.161, p = 0.025) scores. Patients with postoperative complications were noted to have shorter telomere length (T/S 0.790 vs 0.858, p = 0.049), even when the analysis controlled for BMI and sex (OR = 1.71, 95% CI 1.07-2.87, p = 0.031)., Conclusions: Epigenetic clocks showed significant associations with markers of frailty and disability, while patients with postoperative complications had shorter telomere length. These data suggest a potential role for aging biomarkers as components of surgical risk assessment. Integrating biological age into current risk calculators may improve their accuracy and provide valuable information for patients, surgeons, and payers.

Background: For transforaminal lumbar interbody fusion (TLIF), there are equally good open and minimally invasive surgery (MIS) options., Objective: To determine if frailty has a differential effect on outcome for open vs MIS TLIF., Methods: We performed a retrospective review of 115 TLIF surgeries (1-3 levels) for lumbar degenerative disease performed at a single center; 44 MIS transforaminal interbody fusions and 71 open TLIFs were included. All patients had at least a 2-year follow up, and any revision surgery during that time was recorded. The Adult Spinal Deformity Frailty Index (ASD-FI) was used to separate patients into nonfrail (ASD-FI < 0.3) and frail (ASD-FI > 0.3) cohorts. The primary outcome variables were revision surgery and discharge disposition. Univariate analyses were performed to reveal associations in demographic, radiographic, and surgical data with the outcome variables. Multivariate logistic regression was used to assess independent predictors of outcome., Results: Frailty uniquely predicted both reoperation (odds ratio 8.1, 95% CI 2.5-26.1, P = .0005) and discharge to a location other than home (odds ratio 3.9, 95% CI 1.2-12.7, P = .0239). Post hoc analysis indicated that frail patients undergoing open TLIF had a higher revision surgery rate (51.72%) compared with frail patients undergoing MIS-TLIF (16.7%). Nonfrail patients undergoing open and MIS TLIF had a revision surgery rate of 7.5% and 7.7%, respectively., Conclusion: Frailty was associated with increased revision rate and increased probability to discharge to a location other than home after open transforaminal interbody fusions, but not MIS transforaminal interbody fusions. These data suggest that patients with high frailty scores may benefit from MIS-TLIF procedures., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Adult spinal deformity (ASD) surgery is still associated with high surgical risks. Machine learning algorithms applied to multicenter databases have been created to predict outcomes and complications, optimize patient selection, and improve overall results. However, the multiple data points currently used to create these models allow for 70% of accuracy in prediction. We need to find new variables that can capture the spectrum of probability that is escaping from our control. These proposed variables are based on patients' biological dimensions, such as frailty, sarcopenia, muscle and bone (tissue) sampling, serological assessment of cellular senescence, and circulating biomarkers that can measure epigenetics, inflammaging, and -omics. Many of these variables are proven to be modifiable and could be improved with proper nutrition, toxin avoidance, endurance exercise, and even surgery. The purpose of this manuscript is to describe the different future data points that can be implemented in ASD assessment to improve modeling prediction, allow monitoring their response to prerehabilitation programs, and improve patient counseling., Competing Interests: Declaration of Conflicting Interests : The authors report no conflicts of interest in this work., (This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2023 ISASS. To see more or order reprints or permissions, see http://ijssurgery.com.)

Study Design: Retrospective database study., Objective: To compare outcomes between 1-, 2-, 3-, and 4- level anterior cervical discectomy and fusions (ACDF) and posterior cervical fusions (PCF) procedures using a national database., Summary of Background Data: Surgical outcomes involving 3- or 4-level ACDF and PCF cases are not well-described. As there are situations where both ACDF and PCF can be employed, it is important to compare the risks and benefits of both procedures., Materials and Methods: Patients who underwent ACDF or PCF between 2010 and 2020 were identified in PearlDiver using current procedural terminology codes. Surgeries done for infectious, traumatic, or neoplastic etiologies were excluded. 2-year reoperations and 90-day readmissions were queried. Surgical complications and transfusions were compiled using ICD-9/10 billing codes. ACDF and PCF procedures were then matched by age, sex, Charlson Comorbidity Index, and a number of levels fused, and the above outcomes were compared., Results: In all, 31,301 PCFs and 110,526 ACDFs were identified. After matching for age, sex, and Charlson Comorbidity Index, a total of 30,353 ACDF and PCF procedures were compared. Three-level and 4-level PCFs had higher rates of 90-day postoperative surgical complications compared with ACDF (OR=2.4 and 2.87, respectively; P <0.001). In addition, higher rates of 90-day readmissions were noted in 3-level PCF compared with 3-level ACDF (OR=1.24, P <0.001). Ninety-day postoperative transfusions were higher in both 3- and 4-level PCFs (OR=2.44 and 18.27, respectively; P <0.001). Two-year reoperations rates were higher for 3-level PCF procedures than 3-level ACDF (OR=1.22; P =0.01)., Conclusions: Patients who underwent 3-4-level ACDF had lower rates of readmission, blood transfusions, and postoperative complications compared with 3-4-level PCF. This data suggests that in cases of 3-4-level pathology with clinical equipoise regarding approach, ACDF may be associated with less short-term morbidity, however, data on fusion rates and adjacent level disease are needed., Competing Interests: P.H.: Royalty agreements with Medtronics, Nuvasive, and Zimmer Biomet. J.L.: MD: Board member for NASS; Former consultant to Viseon. No royalties. Z.B.: consultancy: Cerapedics (past); Research Support: SeaSpine (past, paid to the institution), Next Science (paid directly to institution), Medical Metrics (past, paid directly to institution), NIH SBIR Subaward (paid to institution); North American Spine Society: committee member; Lumbar Spine Society: Co-chair Educational Committee, AOSpine Knowledge Forum Degenerative: Associate member; AOSNA Research committee- committee member: Patents (issued): Biomarkers for painful intervertebral disks and methods of use thereof. The remaining authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The Publisher regrets that this article is an accidental duplication of an article that has already been published, http://doi.org/10.1016/j.wneu.2023.02.011. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/policies/article-withdrawal., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Risk stratification is a critical element of surgical planning. Early tools were fairly crude, while newer instruments incorporate disease-specific elements and markers of frailty. It is unknown if discrepancies between chronological and cellular age can guide surgical planning or treatment. Telomeres are DNA-protein complexes that serve an important role in protecting genomic DNA. Their shortening is a consequence of aging and environmental exposures, with well-established associations with diseases of aging and mortality. There are compelling data to suggest that telomere length can provide insight toward overall health. The authors sought to determine potential associations between telomere length and postoperative complications., Methods: Adults undergoing elective surgery for spinal deformity were prospectively enrolled. Telomere length was measured from preoperative whole blood using quantitative polymerase chain reaction and expressed as the ratio of telomere (T) to single-copy gene (S) abundance (T/S ratio), with higher T/S ratios indicating longer telomere length. Demographic and patient data included age, BMI, and results for the following rating scales: the Adult Spinal Deformity Frailty Index (ASD-FI), Oswestry Disability Index (ODI), Scoliosis Research Society-22r (SRS-22r), American Society of Anesthesiology (ASA) classification, and Charlson Comorbidity Index (CCI). Operative and postoperative complication data (medical or surgical within 90 days) were also collected., Results: Forty-three patients were enrolled, including 31 women (53%), with a mean age of 66 years and a mean BMI of 28.5. The mean number of levels fused was 11, with 21 (48.8%) combined anterior-posterior approaches. Twenty-two patients (51.2%) had a medical or surgical complication. Patients with a postoperative complication had a significantly lower T/S ratio (0.712 vs 0.813, p = 0.008), indicating shorter telomere length, despite a mild difference in age compared with patients without a postoperative complication (68 vs 63 years, p = 0.069). Patients with complications also had higher CCI scores than patients without complications (2.3 vs 3.8, p = 0.004). There were no significant differences in sex, BMI, ASD-FI score, ASA class, preoperative ODI and SRS-22r scores, number of levels fused, or use of three-column osteotomies. In a multivariate model including age, frailty, ASA class, use of an anterior-posterior approach, CCI score, and telomere length, the authors found that short telomere length was significantly associated with postoperative complications. Patients whose telomere length fell in the shortest quartile had the highest risk (OR 18.184, p = 0.030)., Conclusions: Short telomere length was associated with an increased risk of postoperative complications despite only a mild difference in chronological age. Increasing comorbidity scores also trended toward significance. Larger prospective studies are needed; however, these data provide a compelling impetus to investigate the role of biological aging as a component of surgical risk stratification.

Study Design: Literature review., Objective: The aim of this review is to summarize recent literature on adult spinal deformity (ASD) treatment failure as well as prevention strategies for these failure modes., Summary of Background Data: There is substantial evidence that ASD surgery can provide significant clinical benefits to patients. The volume of ASD surgery is increasing, and significantly more complex procedures are being performed, especially in the aging population with multiple comorbidities. Although there is potential for significant improvements in pain and disability with ASD surgery, these procedures continue to be associated with major complications and even outright failure., Methods: A systematic search of the PubMed database was performed for articles relevant to failure after ASD surgery. Institutional review board approval was not needed., Results: Failure and the potential need for revision surgery generally fall into 1 of 4 well-defined phenotypes: clinical failure, radiographic failure, the need for reoperation, and lack of cost-effectiveness. Revision surgery rates remain relatively high, challenging the overall cost-effectiveness of these procedures., Conclusion: By consolidating the key evidence regarding failure, further research and innovation may be stimulated with the goal of significantly improving the safety and cost-effectiveness of ASD surgery., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Spinal meningiomas pose unique challenges based on the location of their dural attachment. However, there is a paucity of literature investigating the role of dural attachment location on outcomes after posterior-based approach for spinal meningioma resection. The aim of this study was to investigate any differences in outcomes between dural attachment location subgroups in spinal meningioma patients who underwent posterior-based resection., Methods: This was a single-institution review of patients who underwent resection of a spinal meningioma from 1997 to 2017. Surgical, oncological, and neurological outcomes were compared between patients with varying dural attachments. Multivariate analysis was utilized., Results: A total of 141 patients were identified. The mean age was 62 years, and 110 women were included. The sites of dural attachments were as follows: 16 (11.3%) dorsal, 31 (22.0%) dorsolateral, 17 (12.1%) lateral, 40 (28.4%) ventral, and 37 (26.2%) ventrolateral. Most meningiomas were WHO grade I (92.2%) and in the thoracic spine (61.0%). All patients underwent a posterior approach for tumor resection. There were no differences between subgroups in terms of largest diameter of tumor resected (p = 0.201), gross-total resection (GTR) or subtotal resection (p = 0.362), Simpson grade of resection, perioperative complications (p = 0.116), long-term neurological deficit (p = 0.100), or postoperative radiation therapy (p = 0.971). Cervical spine location was associated with reduced incidence of GTR (OR 0.271, 95% CI 0.108-0.684, p = 0.006) on multivariate analysis. The overall incidence of recurrence/progression was 4.6%, with no difference (p = 0.800) between subgroups. Similarly, the average length of follow-up was 28.1 months, with no difference between subgroups (p = 0.413)., Conclusions: Posterior-based approaches for resection of spinal meningiomas are safe and effective, regardless of dural attachment location, with similar surgical, oncological, and neurological outcomes. Comparison of long-term recurrence rates between dural attachment subgroups is required.

Background: Dorsal intradural arteriovenous fistulas (DI-AVFs) represent 80% of spinal AVFs. Microsurgical clip occlusion is a durable treatment that uses preoperative and postoperative digital subtraction angiography (DSA) as standard practice. Intraoperative indocyanine green videoangiography (ICG-VA) is a valuable intraoperative adjunct in these cases. Intraoperative ICG-VA findings have not been compared with postoperative DSA findings., Objective: To assess the diagnostic value of intraoperative ICG-VA vs postoperative DSA for spinal DI-AVFs., Methods: A multi-institutional database of vascular malformations was queried for all surgically managed cases of DI-AVF. Patients with both intraoperative ICG-VA and postoperative DSA were included. Demographic and radiologic data, intraoperative findings, and surgical outcomes data were retrospectively analyzed., Results: Forty-five patients with DI-AVF were identified (male sex, 32; mean age, 61.9 [range, 26-85] years). All DI-AVFs were treated with interruption of the fistula with clip occlusion of the draining vein. Intraoperative ICG-VA showed complete obliteration in all patients. Postoperative DSA was performed for 40 patients and confirmed complete obliteration in all patients. The negative predictive value of ICG-VA confirming complete occlusion of the DI-AVFs was 100%. Eighteen patients (47%) experienced clinical improvement, and 16 (42%) experienced no change in condition., Conclusion: ICG-VA is useful for intraoperative identification of DI-AVFs and confirmation of complete microsurgical occlusion. Correlation between intraoperative ICG-VA and postoperative DSA findings demonstrates the diagnostic power of ICG-VA. This finding suggests that postoperative DSA is unnecessary when intraoperative ICG-VA confirms complete occlusion of the DI-AVF, which will spare patients the procedural risk and cost of this invasive procedure., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Background and Importance: Superior laryngeal nerve (SLN) injury after high cervical dissection can result in changes in vocal pitch due to cricothyroid denervation and dysphagia with aspiration risk because of decreased sensation of the supraglottic larynx., Clinical Presentation: We describe a 69-year-old singer with cervical spondylotic myelopathy who underwent elective C3/4 and C4/5 anterior cervical diskectomy and fusion. Postoperatively, the patient reported changes in his voice, most noticeable with higher registers. A number of studies confirmed severe right superior laryngeal neuropathy. A cadaveric description included to highlight anatomic relationships critical in minimizing risk of SLN injury during an anterior cervical diskectomy and fusion approach., Conclusion: The SLN is a critical structure vulnerable to iatrogenic injury during high cervical dissections for anterior approaches to the spine. Therefore, it is critical for spine surgeons to have a firm understanding of SLN anatomy for these approaches., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Background: Lumbosacral deformities are caused by high-grade spondylolisthesis, fractures, iatrogenic flat back, and other etiologies. The S1 pedicle subtraction osteotomy (PSO) can facilitate reduction of spondylolisthesis and lower the pelvic incidence. There are limited reports on the indications and outcomes of this technique., Objective: To present a technical description and literature review of the S1 PSO with video summary., Methods: This was a retrospective review of a single case to highlight the use of S1 PSO for the treatment of high-grade spondylolisthesis. A literature review was performed in accordance with STROBE guidelines., Results: A 47-year-old woman presented with back and right leg pain related to grade 4 spondylolisthesis at L5-S1 with sagittal imbalance and lumbosacral kyphosis. She was taken for an L2-pelvis instrumented fusion with S1 PSO. Three days later, she was taken for an L4-5 and L5-S1 anterior lumbar interbody fusion with the L5-S1 segmental plate. Her postoperative course was notable for right foot drop that resolved in 6 weeks. Postoperative x-rays showed successful reduction of spondylolisthesis with normal alignment and sagittal balance. Based on 6 studies involving 22 true sacral PSOs in the literature, the procedure carries a 27% risk of neurological deficit, typically in the form of L5 palsy., Conclusion: The S1 PSO is a technically challenging operation that has a unique role in the treatment of high-grade spondylolisthesis. It carries a significant risk of L5 palsy and should be reserved for surgeons with experience performing complex 3-column osteotomies., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Background: The kickstand rod has been described for the treatment of severe coronal imbalance. We present a modified description that combines an asymmetric pedicle subtraction osteotomy (PSO) for correction of severe kyphoscoliosis., Objective: To describe the use of a temporary kickstand rod., Methods: Type 1 osteotomies were performed across the main and fractional curves. An asymmetric PSO was performed at the apex of the main curve, and a kickstand rod placed on the concavity anchored from the ilium to a temporary connector above the main curve. Distraction was applied across the kickstand rod because the PSO was closed on the convexity. A permanent rod was placed contralateral to the kickstand, followed by replacement of the kickstand with a permanent rod and bilateral accessory rods., Results: A 66-year-old man presented with kyphoscoliosis causing severe coronal and sagittal imbalance. He underwent L4-S1 anterior lumbar interbody fusion followed by T4-pelvis instrumented fusion the following day. Type 1 osteotomies were performed from T6-T12 to L3-S1 and an asymmetric PSO at L2. A temporary kickstand rod was used to distract across the concavity because the PSO was closed on the convexity. The patient achieved excellent clinical and radiographical results., Conclusion: When used in conjunction with appropriate osteotomies, the kickstand rod can aid in correction of severe coronal imbalance. Use of a temporary kickstand rod is technically easier and allows for correction of the main and fractional curves when used with an asymmetric PSO., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Nanomaterials are the subject of a range of biomedical, commercial, and environmental investigations involving measurements in living cells and tissues. Accurate quantification of nanomaterials, at the tissue, cell, and organelle levels, is often difficult, however, in part due to their inhomogeneity. Here, we propose a method that uses the distinct optical properties of a heterogeneous nanomaterial preparation in order to improve quantification at the single-cell and organelle level. We developed "hyperspectral counting", which employs diffraction-limited imaging via hyperspectral microscopy of a diverse set of fluorescent nanomaterials to estimate particle number counts in live cells and subcellular structures. A mathematical model was developed, and Monte Carlo simulations were employed, to improve the accuracy of these estimates, enabling quantification with single-cell and single-endosome resolution. We applied this nanometrology technique with single-walled carbon nanotubes and identified an upper limit of the rate of uptake into cells─approximately 3,000 nanotubes endocytosed within 30 min. In contrast, conventional region-of-interest counting results in a 230% undercount. The method identified significant heterogeneity and a broad non-Gaussian distribution of carbon nanotube uptake within cells. For example, while a particular cell contained an average of 1 nanotube per endosome, the heterogeneous distribution resulted in over 7 nanotubes localizing within some endosomes, substantially changing the accounting of subcellular nanoparticle concentration distributions. This work presents a method to quantify the cellular and subcellular concentrations of a heterogeneous carbon nanotube reference material, with implications for the nanotoxicology, drug/gene delivery, and nanosensor fields.

Glioblastoma (GBM) is the most common primary brain tumor with a median survival under two years. Using in silico and in vitro techniques, we demonstrate heterogeneous expression of CD97, a leukocyte adhesion marker, in human GBM. Beyond its previous demonstrated role in tumor invasion, we show that CD97 is also associated with upregulation of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/Erk) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathways in GBM. While CD97 knockout decreased Akt activation, CD97 targeting did not alter MAPK/Erk activation, did not slow GBM cell proliferation in culture, and increased levels of glycolytic and oxidative phosphorylation metabolites. Treatment with a soluble CD97 inhibitor did not alter activation of the MAPK/Erk and PI3K/Akt pathways. Tumors with high CD97 expression were associated with immune microenvironment changes including increased naïve macrophages, regulatory T cells, and resting natural killer (NK) cells. These data suggest that, while CD97 expression is associated with conflicting effects on tumor cell proliferative and metabolic pathways that overall do not affect tumor cell proliferation, CD97 exerts pro-tumoral effects on the tumor immune microenvironment, which along with the pro-invasive effects of CD97 we previously demonstrated, provides impetus to continue exploring CD97 as a therapeutic target in GBM., (© 2022. The Author(s).)

Introduction Posterior cervical foraminotomy and anterior cervical discectomy and fusion (ACDF) are the mainstay treatments for cervical radiculopathy. A recent alternative or adjunct involves the placement of interfacet spacers, which promote indirect decompression by increasing foraminal height. Cervical interfacet spacers have been shown to be safe options for indirect decompression and improve short-term clinical outcomes in patients with cervical spine pathologies. However, no previous data regarding malpositioned spacers and their management have been reported. Given this paucity of data, we aim to present examples of malpositioned interfacet spacers and their management. Methods This was a retrospective single-center review. Results Twenty-five patients were identified in which interfacet spacers were used at a single level in 19 cases, two levels in five cases, and three levels in one case. The cohort had a mean follow-up of 14.4 months. Among 60 total spacers placed, two required repositioning (3.3%). The first underwent bilateral placement at C4/5 and developed a unilateral deltoid palsy postoperatively. She was taken back to the operating room the same day for implant removal. A second patient underwent removal after a malpositioned implant at C4/5 was identified on an intraoperative CT scan. A third patient had spacers placed at a referring hospital and presented with progressive neck pain and radiculopathy. She underwent successful removal with a resolution of her symptoms. Conclusions Interfacet spacers represent a novel technique for the treatment of cervical radiculopathy, however, there are limited data on their utilization. We present the first reports of malpositioned spacers and their management. Patients with small facet joints and lateral masses may be at increased risk for malposition, and intraoperative fluoroscopy may not adequately confirm implant placement. Surgeons should use caution when implementing new technology with a low threshold for intraoperative CT to confirm the appropriate placement of these devices., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2021, Garcia et al.)

Traditional iliac screws and S2-alar iliac (S2-AI) screws are common methods used for pelvic fixation, and many surgeons advocate pelvic fixation for long-segment fixation to the sacrum. However, in patients without severe deformities and only degenerative conditions, many surgeons may choose S1 screws only. Moreover, even with S2-AI screws, there is more muscular dissection than with using S1 screws, and the rod connection can be cumbersome in both S2-AI fixation and placing iliac screws. Using a surgical video, artist's illustration, and intraoperative photographs, the authors describe the S1-AI screw fixation technique that allows for single-screw sacral and iliac fixation, requires less distal dissection of the sacrum, allows for easier rod connection, and may be an option in degenerative conditions needing pelvic fixation. However, this is a preliminary feasibility study, and in long fusion constructs, this type of fixation has only been used in conjunction with L5-S1 anterior lumbar interbody fusion (ALIF), and there are no long-term data on the use of this screw fixation technique without ALIF. In short-segment revision fusions, this technique may be considered for salvage in cases of large halos in the sacrum from loosened S1 screw fixation.

Objective: Proximal junctional kyphosis (PJK) and proximal junctional failure (PJF) are well-recognized complications of long-segment spinal fusion. Previous studies have suggested that ligament augmentation can decrease rates of PJF by reducing junctional stress and strengthening upper instrumented vertebrae (UIVs) and adjacent segments. However, there is a paucity of long-term data on the efficacy of ligament augmentation in preventing PJF. In this study, the authors sought to determine the effect of ligament augmentation on rates of PJF in a cohort of adult spinal deformity patients with at least 1 year of follow-up., Methods: They conducted a retrospective analysis of ligament augmentation in a consecutive series of surgical patients with adult spinal deformity. Data on patient demographics, surgical characteristics, and surgery for PJF were collected. The minimum follow-up was 12 months. Univariate and multivariate analyses were performed to identify factors associated with reoperation for PJF., Results: The authors identified a total of 242 patients (166 women [68.6%]) with ligament augmentation whose mean age was 66 years. The mean number of fused levels was 10, with a UIV distribution as follows: 90 upper thoracic UIVs (37.2%) and 152 lower thoracic UIVs (62.8%). Compared to a historical cohort of 77 patients treated before implementation of ligament augmentation, reoperation for PJF was significantly lower with ligament augmentation (15.6% vs 3.3%, p < 0.001). In a multivariate model, only ligament augmentation (OR 0.184, 95% CI 0.071-0.478, p = 0.001) and number of fused levels (OR 0.762, 95% CI 0.620-0.937, p = 0.010) were associated with reductions in reoperation for PJF., Conclusions: Ligament augmentation was associated with significant reductions in the rate of reoperation for PJF at 12 months in a cohort of adult spinal deformity patients. The most dramatic reduction was seen among patients with lower thoracic UIV. These data suggest that in appropriately selected patients, ligament augmentation may be a valuable adjunct for PJF reduction; however, long-term follow-up is needed.

Metastases cause 90% of human cancer deaths. The metastatic cascade involves local invasion, intravasation, extravasation, metastatic site colonization, and proliferation. Although individual mediators of these processes have been investigated, interactions between these mediators remain less well defined. We previously identified a complex between receptor tyrosine kinase c-Met and β1 integrin in metastases. Using cell culture and in vivo assays, we found that c-Met/β1 complex induction promoted intravasation and vessel wall adhesion in triple-negative breast cancer cells, but did not increase extravasation. These effects may have been driven by the ability of the c-Met/β1 complex to increase mesenchymal and stem cell characteristics. Multiplex transcriptomic analysis revealed upregulated Wnt and hedgehog pathways after c-Met/β1 complex induction. A β1 integrin point mutation that prevented binding to c-Met reduced intravasation. OS2966, a therapeutic antibody disrupting c-Met/β1 binding, decreased breast cancer cell invasion and mesenchymal gene expression. Bone-seeking breast cancer cells exhibited higher levels of c-Met/β1 complex than parental controls and preferentially adhered to tissue-specific matrix. Patient bone metastases demonstrated higher c-Met/β1 complex than brain metastases. Thus, the c-Met/β1 complex drove intravasation of triple-negative breast cancer cells and preferential affinity for bone-specific matrix. Pharmacological targeting of the complex may have prevented metastases, particularly osseous metastases.

Objective: The use of telemedicine has dramatically increased due to the coronavirus disease 2019 pandemic. Many neurosurgeons are now using telemedicine technologies for preoperative evaluations and routine outpatient visits. Our goal was to standardize the telemedicine motor neurologic examination, summarize the evidence surrounding clinical use of telehealth technologies, and discuss financial and legal considerations., Methods: We identified a 12-member panel composed of spine surgeons, fellows, and senior residents at a single institution. We created an initial telehealth strength examination protocol based on published data and developed 10 agree/disagree statements summarizing the protocol. A blinded Delphi method was utilized to build consensus for each statement, defined as > 80% agreement and no significant disagreement using a 2-way binomial test (significance threshold of p < 0.05). Any statement that did not meet consensus was edited and iteratively resubmitted to the panel until consensus was achieved. In the final round, the panel was unblinded and the protocol was finalized., Results: After the first round, 4/10 statements failed to meet consensus ( < 80% agreement, and p = 0.031, p = 0.031, p = 0.003, and p = 0.031 statistical disagreement, respectively). The disagreement pertained to grading of strength of the upper (3/10 statements) and lower extremities (1/10 statement). The amended statements clarified strength grading, achieved consensus ( > 80% agreement, p > 0.05 disagreement), and were used to create the final telehealth strength examination protocol., Conclusion: The resulting protocol was used in our clinic to standardize the telehealth strength examination. This protocol, as well as our summary of telehealth clinical practice, should aid neurosurgical clinics in integrating telemedicine modalities into their practice.

The ongoing SARS-CoV-2 pandemic has highlighted the importance of the rapid development of vaccines and antivirals. However, the potential for the emergence of antibiotic resistances due to the increased use of antibacterial cleaning products and therapeutics presents an additional, underreported threat. Most antibacterial cleaners contain simple quaternary ammonium compounds (QACs); however, these compounds are steadily becoming less effective as antibacterial agents. QACs are extensively used in SARS-CoV-2-related sanitization in clinical and household settings. Similarly, due to the danger of secondary infections, antibiotic therapeutics are increasingly used as a component of COVID-19 treatment regimens, even in the absence of a bacterial infection diagnosis. The increased use of antibacterial agents as cleaners and therapeutics is anticipated to lead to novel resistances in the coming years., Competing Interests: W.M.W. has intellectual property covering novel quaternary ammonium compounds. A.L.F. is a member of the Editorial Advisory Board of iScience., (© 2021 The Authors.)

Adult cervical deformity management is complex and is a growing field with many recent advancements. The cervical spine functions to maintain the position of the head and plays a pivotal role in influencing subjacent global spinal alignment and pelvic tilt as compensatory changes occur to maintain horizontal gaze. There are various types of cervical deformity and a variety of surgical options available. The major advancements in the management of cervical deformity have only been around for a few years and continue to evolve. Therefore, the goal of this article is to provide a comprehensive review of cervical alignment parameters, deformity classification, clinical evaluation, and surgical treatment of adult cervical deformity. The information presented here may be used as a guide for proper preoperative evaluation and surgical treatment in the adult cervical deformity patient., (© Congress of Neurological Surgeons 2021.)

Objective: In patients with new primary intradural spinal tumors, the best screening strategy for additional central nervous system (CNS) lesions is unclear. The goal of this study was to document the rate of additional CNS tumors in these patients., Methods: Adults with primary intradural spinal tumors were retrospectively reviewed. Imaging strategy at diagnosis was classified as focused spine (cervical, thoracic, or lumbar), total spine, or complete neuraxis (brain and total spine). Tumor pathology, genetic syndromes, and presence of additional CNS lesions at diagnosis or follow-up were collected., Results: The study comprised 319 patients with mean age of 51 years and mean follow-up of 41 months. In 151 patients with focused spine imaging, 3 (2.0%) were found to have new lesions with 2 (1.4%) requiring treatment. In 35 patients with total spine imaging, there were no additional lesions. In 133 patients with complete neuraxis imaging, 4 (3.0%) were found to have new lesions with 2 (1.5%) requiring treatment. There was no difference in the identification of new lesions (P = 0.542) or new lesions requiring treatment (P = 0.772) across imaging strategies. Among patients without genetic syndromes, rates of new lesions requiring treatment were 1.4% for focused spine, 0% for total spine, and 2.2% for complete neuraxis (P = 0.683). There were no cases of delayed identification causing risk to life or neurological function. Complete neuraxis imaging carried an increased charge of $4420 per patient., Conclusions: Among patients without an underlying genetic syndrome, the likelihood of identifying additional CNS lesions requiring treatment is low. In appropriate cases, focused spine imaging may be a more cost-effective strategy., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Spinal arteriovenous malformations (AVMs) are rare disease entities with significant morbidity if untreated. Risk factors of complications, hospitalization and costs-of-care remain in need of characterization., Methods: Using the National Inpatient Sample years 2002-2014, adult subjects with spinal AVMs who underwent either laminectomy with lesion excision or endovascular embolization were extracted using ICD-9-CM diagnostic code 747.82. Predictors of inpatient complications, hospital length of stay (HLOS), and discharge home were evaluated using multivariable regression. Cost was evaluated using inflation-adjusted healthcare cost [charge*(cost/charge ratio)]. Mean differences (B), odds ratios (OR) and 95% CIs are reported. Significance was assessed at P<0.001., Results: In 2546 weighted admissions, age was 54.4±16.5-years (laminectomy: 70.0%, embolization: 30.0%). Fifteen percent suffered inpatient complications. Cost of hospitalization was $ 41216±38511 and was elevated for subjects with complications ($67571±2636, vs. no complications: $36562±723, P<0.001). Increased costs for categories of complications ranged from $ 16525 (renal/urinary) to $62246 (thromboembolism). In surgical subjects, complications were more costly ($ 69761±2896, vs. no complications: 36520±809, P<0.001). On multivariable analysis, major/extreme disease severity and major/extreme mortality risk were associated with increased complications and HLOS (P<0.001). Elective admissions had shorter HLOS (B=-4.3-days, [-4.8, -3.8], P<0.001) and higher odds of discharge home (OR=2.6 [2.1-3.2], P<0.001). Laminectomy (vs. embolization) was associated with complications (OR=2.6, 95% CI [1.7-3.8], P<0.001), HLOS (B=3.4-days [2.9-4.0], P<0.001), and decreased discharge home (OR=0.3 [0.2-0.4], P<0.001)., Conclusions: In spinal AVMs, high disease severity, non-elective admissions, and surgery are associated with complications, HLOS, and discharge to a non-home facility. Costs are elevated in patients suffering complications. Future studies are warranted.

Background: Anterior cervical discectomy and fusion (ACDF) are increasingly performed at ambulatory surgical centers (ASCs). Academic centers lacking dedicated ASCs must perform these at large university hospitals, which pose unique challenges to cost savings and efficiency., Objective: To describe the safety and cost of outpatient ACDF at a major academic medical center without a dedicated ASC., Methods: ACDFs performed from 2015 to 2018 were retrospectively reviewed. Cases were performed at the major tertiary university hospital or a satellite university hospital dedicated to outpatient surgery. Patient demographics, surgical characteristics, perioperative complications, fusion at 12 months, and cost were collected., Results: A total of 470 patients were included. The mean age was 56 years, with 255 women (54.3%). When comparing same-day discharge, overnight observation, or inpatient admission, there were no differences in age, gender, or number of levels fused. Same-day and overnight observation cases were associated with shorter procedure duration and less estimated blood loss. There were no differences in perioperative complications, 30-day readmissions, or fusion at 12 months. Direct and total costs were lowest for same-day cases, followed by overnight observation and inpatient admissions (P < 0.001)., Conclusion: Academic centers without dedicated ASCs can safely perform ACDF as a same-day or overnight observation procedure with significant reductions in cost. The lack of a dedicated ASC should not preclude academic centers from allocating appropriately selected patients into same-day or overnight observation care pathways. This strategy can improve resource utilization and preserve precious hospital resources for the most critically ill patients while also allowing these centers to build viable outpatient spine practices., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Lumbar decompressions are increasingly performed at ambulatory surgery centers (ASCs). We sought to compare costs of open and minimally invasive (MIS) lumbar decompressions performed at a university without dedicated ASCs., Methods: Lumbar decompressions performed at a tertiary academic hospital or satellite university hospital dedicated to outpatient surgery were retrospectively reviewed. Care pathways were same-day, overnight observation, or inpatient admission. Patient demographics, American Society of Anesthesiologists classification, Charlson Comorbidity Index, surgical characteristics, 30-day readmission, and costs were collected. A systematic review of lumbar decompression cost literature was performed., Results: A total of 354 patients, mean age 55 years with 128 women (36.2%), were reviewed. There was no significant difference in age, gender, body mass index, American Society of Anesthesiologists classification, or Charlson Comorbidity Index between patients treated with open and minimally invasive surgery. Open decompression was associated with higher total cost ($21,280 vs. $14,407; P < 0.001); however, this was driven by care pathway and length of stay. When stratifying by care pathway, there was no difference in total cost between open versus minimally invasive surgery among same-day ($10,609 vs. $11,074; P = 0.556), overnight observation ($14,097 vs. $13,992; P = 0.918), or inpatient admissions ($24,507 vs. $27,929; P = 0.311)., Conclusions: When accounting for care pathway, the cost of open and MIS decompression were no different. Transition from a tertiary academic hospital to a university hospital specializing in outpatient surgery was not associated with lower costs. Academic departments may consider transitioning lumbar decompressions to a dedicated ASC to maximize cost savings; however, additional studies are needed., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The treatment of pseudarthrosis after transforaminal lumbar interbody fusion (TLIF) can be challenging, particularly when anterior column reconstruction is required. There are limited data on TLIF cage removal through an anterior approach., Objective: To assess the safety and efficacy of anterior lumbar interbody fusion (ALIF) as a treatment for pseudarthrosis after TLIF., Methods: ALIFs performed at a single academic medical center were reviewed to identify cases performed for the treatment of pseudarthrosis after TLIF. Patient demographics, surgical characteristics, perioperative complications, and 1-yr radiographic data were collected., Results: A total of 84 patients were identified with mean age of 59 yr and 37 women (44.0%). A total of 16 patients (19.0%) underwent removal of 2 interbody cages for a total of 99 implants removed with distribution as follows: 1 L2/3 (0.9%), 6 L3/4 (5.7%), 37 L4/5 (41.5%), and 55 L5/S1 (51.9%). There were 2 intraoperative venous injuries (2.4%) and postoperative complications were as follows: 7 ileus (8.3%), 5 wound-related (6.0%), 1 rectus hematoma (1.1%), and 12 medical complications (14.3%), including 6 pulmonary (7.1%), 3 cardiac (3.6%), and 6 urinary tract infections (7.1%). Among 58 patients with at least 1-yr follow-up, 56 (96.6%) had solid fusion. There were 5 cases of subsidence (6.0%), none of which required surgical revision. Two patients (2.4%) required additional surgery at the level of ALIF for pseudarthrosis., Conclusion: ALIF is a safe and effective technique for the treatment of TLIF cage pseudarthrosis with a favorable risk profile., (Copyright © 2020 by the Congress of Neurological Surgeons.)

Objective: Anterior lumbar interbody fusion (ALIF) is a powerful technique that provides wide access to the disc space and allows for large lordotic grafts. When used with posterior spinal fusion (PSF), the procedures are often staged within the same hospital admission. There are limited data on the perioperative risk profile of ALIF-first versus PSF-first circumferential fusions performed within the same hospital admission. In an effort to understand whether these procedures are associated with different perioperative complication profiles, the authors performed a retrospective review of their institutional experience in adult patients who had undergone circumferential lumbar fusions., Methods: The electronic medicals records of patients who had undergone ALIF and PSF on separate days within the same hospital admission at a single academic center were retrospectively analyzed. Patients carrying a diagnosis of tumor, infection, or traumatic fracture were excluded. Demographics, surgical characteristics, and perioperative complications were collected and assessed., Results: A total of 373 patients, 217 of them women (58.2%), met the inclusion criteria. The mean age of the study cohort was 60 years. Surgical indications were as follows: degenerative disease or spondylolisthesis, 171 (45.8%); adult deformity, 168 (45.0%); and pseudarthrosis, 34 (9.1%). The majority of patients underwent ALIF first (321 [86.1%]) with a mean time of 2.5 days between stages. The mean number of levels fused was 2.1 for ALIF and 6.8 for PSF. In a comparison of ALIF-first to PSF-first cases, there were no major differences in demographics or surgical characteristics. Rates of intraoperative complications including venous injury were not significantly different between the two groups. The rates of postoperative ileus (11.8% vs 5.8%, p = 0.194) and ALIF-related wound complications (9.0% vs 3.8%, p = 0.283) were slightly higher in the ALIF-first group, although the differences did not reach statistical significance. Rates of other perioperative complications were no different., Conclusions: In patients undergoing staged circumferential fusion with ALIF and PSF, there was no statistically significant difference in the rate of perioperative complications when comparing ALIF-first to PSF-first surgeries.

Background: The spine is the most common site of bony metastases. Associated pathological fractures can result in pain, neurological deficit, biomechanical instability, and deformity., Objective: To present a minimally invasive technique for indirect decompression by ligamentotaxis in pathological fractures., Methods: A minimally invasive approach was utilized to perform percutaneous pedicle screw fixation in patients who required stabilization for pathological fractures. Preoperative and postoperative computed tomography and magnetic resonance imaging were used to compare spinal canal area and midsagittal canal diameter., Results: Two patients with newly diagnosed pathological fractures underwent minimally invasive treatment. Each presented with minimal epidural disease and a chief complaint of intractable back pain without neurological deficit. They underwent minimally invasive pedicle screw fixation with indirect decompression by ligamentotaxis. In each case, postoperative imaging demonstrated an increase in spinal canal area and midsagittal canal diameter by an independent neuroradiologist. There were no perioperative complications, and each patient was neurologically stable without evidence of hardware failure at their 5- and 6-mo follow-up visits., Conclusion: Minimally invasive percutaneous fixation can be used to stabilize pathological fractures and provide indirect decompression by ligamentotaxis. This procedure is associated with minimal blood loss, low morbidity, and rapid initiation of radiation therapy. Only patients with minimal epidural disease, stenosis caused primarily by bony retropulsion, and mild-to-moderate deformity should be considered candidates for this approach., (Copyright © 2020 by the Congress of Neurological Surgeons.)

Adult spinal deformity (ASD) has gained significant attention over the past decade with improvements in diagnostic tools, classification schemes, and surgical technique. The demographics of the aging population in the United States are undergoing a fundamental shift as medical care advances and life expectancy increases. The "baby boomers" represent the fastest growing demographic in the United States and by 2050, the number of individuals 65 yr and older is projected to reach 89 million, more than double its current size. Based on current prevalence estimates there are approximately 27.5 million elderly individuals with some form of spinal deformity, which will place a significant burden on our health care systems. Rates of surgery for ASD and case complexity are both increasing, with concomitant increase in the cost of deformity care. At the same time, patients are more medically complex with increasing number of comorbidities that result in increased surgical risk and complication profiles. This review aims to highlight recent trends in the epidemiology and socioeconomic patterns in surgery for ASD., (Copyright © 2019 by the Congress of Neurological Surgeons.)

Objective: Primary sacral tumors pose unique challenges because of their complex radiographic appearances, diverse pathologic entities, and dramatically different treatment paradigms based on tumor type. Magnetic resonance imaging and computed tomography (CT) can provide valuable information; however, sacral lesions can possess unique radiographic features and pose diagnostic dilemmas. CT-guided percutaneous needle biopsy is a critical component of the diagnostic workup. However, limited data are available on its efficacy for primary sacral tumors., Methods: The data from patients with newly diagnosed primary sacral lesions during a 12-year period at our hospital were analyzed. The preoperative magnetic resonance imaging findings, biopsy results, and pathological data for patients who required surgery were analyzed. Unique cases in which the final pathologic result was unexpected from the preoperative imaging findings have been highlighted., Results: Of 38 patients who underwent percutaneous needle biopsy, diagnostic tissue was obtained on the first attempt for 31 (82%). Five of the remaining 7 obtained diagnostic tissue on the second attempt, yielding 95% diagnosis, with only two requiring open biopsies. In 2 patients with diagnostic tissue on CT-guided biopsy, an open biopsy was still recommended because of the clinical scenario. In both patients, the open biopsy results matched those of the CT-guided biopsy. For the 18 patients who required surgery, we found 100% correlation between the percutaneous needle biopsy findings and the final pathological diagnosis. No biopsy-induced complications or extraspinal tumor seeding occurred., Conclusions: CT-guided biopsy is a safe and effective technique. It represents a critical component of the diagnostic algorithm, given the diverse pathological findings of primary sacral lesions and dramatic differences in treatment., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Anterior approaches to the lumbar spine provide wide exposure that facilitates placement of large grafts with high fusion rates. There are limited data on the effects of obesity on perioperative complications., Methods: Data from consecutive patients undergoing anterior lumbar interbody fusion (ALIF) from 2007 to 2016 at a single academic center were analyzed. The primary outcome was any perioperative complication. Complications were divided into those occurring intraoperatively and those occurring postoperatively. Multivariate logistic regression was used to assess the association of obesity and other variables with these complications. An estimation table was used to identify a body mass index (BMI) threshold associated with increased risk of postoperative complication., Results: A total of 938 patients were identified, and the mean age was 57 years; 511 were females (54.5%). The mean BMI was 28.7 kg/m2, with 354 (37.7%) patients classified as obese (BMI ≥ 30 kg/m2). Forty patients (4.3%) underwent a lateral transthoracic approach, while the remaining 898 (95.7%) underwent a transabdominal retroperitoneal approach. Among patients undergoing transabdominal retroperitoneal ALIF, complication rates were higher for obese patients than for nonobese patients (37.0% vs 28.7%, p = 0.010), a difference that was driven primarily by postoperative complications (36.1% vs 26.0%, p = 0.001) rather than intraoperative complications (3.2% vs 4.3%, p = 0.416). Obese patients had higher rates of ileus (11.7% vs 7.2%, p = 0.020), wound complications (11.4% vs 3.4%, p < 0.001), and urinary tract infections (UTI) (5.0% vs 2.5%, p = 0.049). In a multivariate model, age, obesity, and number of ALIF levels fused were associated with an increased risk of postoperative complication. An estimation table including 19 candidate cut-points, odds ratios, and adjusted p values found a BMI ≥ 31 kg/m2 to have the highest association with postoperative complication (p = 0.012)., Conclusions: Obesity is associated with increased postoperative complications in ALIF, including ileus, wound complications, and UTI. ALIF is a safe and effective procedure. However, patients with a BMI ≥ 31 kg/m2 should be counseled on their increased risks and warrant careful preoperative medical optimization and close monitoring in the postoperative setting.

Cervical radiculopathy is a common spinal condition associated with pain, sensory disturbances, and motor weakness. Symptoms often can be attributable to either disc herniation and/or bony foraminal stenosis due to uncinate hypertrophy. Posterior cervical foraminotomy and conventional anterior cervical discectomy and fusion (ACDF) represent the mainstay of treatment. In patients with severe bony foraminal stenosis, posterior foraminotomy and standard ACDF without complete resection of uncinate process may result in incomplete decompression. ACDF with uncinectomy allows for complete and direct decompression of the exiting nerve root, and may lead to improved clinical outcome in appropriately selected patients. We describe the technique for ACDF with uncinectomy and report the clinical outcome in a consecutive series of patients., Competing Interests: Conflicts of Interest: The series “Advanced Techniques in Complex Cervical Spine Surgery” was commissioned by the editorial office without any funding or sponsorship. LAT serves as the unpaid editorial board member of Journal of Spine Surgery from Jan. 2019 to Jan. 2021 and served as the unpaid Guest Editor of the series. The other authors have no conflicts of interest to declare., (2020 Journal of Spine Surgery. All rights reserved.)

Rigid deformities of the cervical spine can be associated with significant pain, disability, and impaired quality of life. Historical treatments generally utilized posterior approaches including the opening wedge osteotomy and pedicle subtraction osteotomy (PSO). Translation can occur during osteoclasis of the opening wedge osteotomy, making it inherently less stable than a PSO. The PSO is limited to lower cervical or upper thoracic levels due to the vertebral artery and sensitivity of cervical nerve roots to compression during osteotomy closure. The anterior osteotomy, defined as an osteotomy through the cervical disc space and uncovertebral joints back to the level of the transverse foramen bilaterally, is a powerful correction technique that can be applied throughout the cervical spine. It can also be used to correct deformities in the coronal plane. This review will summarize the technical nuances of the anterior osteotomy including patient selection, preoperative planning, and surgical technique., Competing Interests: Conflicts of Interest: The series “Advanced Techniques in Complex Cervical Spine Surgery” was commissioned by the editorial office without any funding or sponsorship. LAT serves as the unpaid editorial board member of Journal of Spine Surgery from Jan. 2019 to Jan. 2021 and served as the unpaid Guest Editor of the series. The other authors have no conflicts of interest to declare., (2020 Journal of Spine Surgery. All rights reserved.)

Posterior cervical osteotomies are powerful techniques for the correction of rigid cervical deformity. These include a variety of subtypes including partial facet joint resection, complete facet joint resection, opening wedge osteotomy (OWO), and closing wedge osteotomy (CWO). The partial facet joint resection provides limited lordosis but can be applied across multiple levels and provides bony surface for fusion. Complete facet joint resection can also be performed across multiple segments for a cumulative effect and like the partial facet joint resection requires mobility of the anterior column. The OWO is traditionally performed at C7 and involves complete a complete laminectomy, facetectomy, and pediculectomy with special care to fully decompress the C8 nerve roots prior to osteotomy closure. The osteotomy utilizes a fulcrum of rotation in the middle column with shortening of the posterior column and lengthening of the anterior column with an osteoclastic fracture that must be performed with significant care. The CWO is similar to an OWO with the addition of an osteotomy into the vertebral body that is closed like a pedicle subtraction osteotomy (PSO). The goal of this review article is to summarize posterior osteotomy techniques for cervical deformity correction., Competing Interests: Conflicts of Interest: The series “Advanced Techniques in Complex Cervical Spine Surgery” was commissioned by the editorial office without any funding or sponsorship. LAT serves as the unpaid editorial board member of Journal of Spine Surgery from Jan. 2019 to Jan. 2021. LAT served as the unpaid Guest Editor of the series. The other authors have no conflicts of interest to declare., (2020 Journal of Spine Surgery. All rights reserved.)

Background: Thoracolumbar pathology can result in compression of neural elements, instability, and deformity. Circumferential decompression with anterior column reconstruction is often required to restore biomechanical stability and minimize the risk of implant failure., Objective: To assess the safety and viability of wide-footprint rectangular cages for vertebral column resection (VCR)., Methods: We performed VCR with wide-footprint rectangular endplate cages, which were designed for transthoracic or retroperitoneal approaches. We present our technique using a single-stage posterior approach., Results: A total of 45 patients underwent VCR with rectangular endplate cages. Mean age was 58 yr. Diagnoses included 23 tumors (51%), 14 infections (31%), and 8 deformities (18%). VCRs were performed in 10 upper thoracic, 17 middle thoracic, 14 lower thoracic, and 4 lumbar levels. Twenty-four cases involved a single level VCR (53%) with 18 two-level (40%) and 3 three-level (7%) VCRs. Average procedure duration was 264 min with mean estimated blood loss of 1900 ml. Neurological outcomes were stable in 27 cases (60%), improved in 16 (36%), and worse in 2 (4%). There were 7 medical and 7 surgical complications in 11 patients. There were significant decreases in postoperative thoracic kyphosis (47° vs 35°, P = .022) and regional kyphosis (34° vs 10°, P < .001). There were 2 cases of cage subsidence due to intraoperative endplate violation, neither of which progressed on CT scan at 14 and 35 mo., Conclusion: Posterior VCR with rectangular footprint cages is safe and feasible. This provides improved biomechanical stability without the morbidity of a lateral transthoracic or retroperitoneal approach., (Copyright © 2019 by the Congress of Neurological Surgeons.)

Noncovalent hybrids of single-stranded DNA and single-walled carbon nanotubes (SWCNTs) have demonstrated applications in biomedical imaging and sensing due to their enhanced biocompatibility and photostable, environmentally responsive near-infrared (NIR) fluorescence. The fundamental properties of such DNA-SWCNTs have been studied to determine the correlative relationships between oligonucleotide sequence and length, SWCNT species, and the physical attributes of the resultant hybrids. However, intracellular environments introduce harsh conditions that can change the physical identities of the hybrid nanomaterials, thus altering their intrinsic optical properties. Here, through visible and NIR fluorescence imaging in addition to confocal Raman microscopy, we show that the oligonucleotide length controls the relative uptake, intracellular optical stability, and retention of DNA-SWCNTs in mammalian cells. Although the absolute NIR fluorescence intensity of DNA-SWCNTs in murine macrophages increases with increasing oligonucleotide length (from 12 to 60 nucleotides), we found that shorter oligonucleotide DNA-SWCNTs undergo a greater magnitude of spectral shift and are more rapidly internalized and expelled from the cell after 24 h. Furthermore, by labeling the DNA with a fluorophore that dequenches upon removal from the SWCNT surface, we found that shorter oligonucleotide strands are displaced from the SWCNT within the cell, altering the physical identity and changing the fate of the internalized nanomaterial. Finally, through a pharmacological inhibition study, we identified the mechanism of SWCNT expulsion from the cells as lysosomal exocytosis. These findings provide a fundamental understanding of the interactions between SWCNTs and live cells as well as evidence suggesting the ability to control the biological fate of the nanomaterials merely by varying the type of DNA wrapping.

Single-walled carbon nanotubes (SWCNTs) have recently been utilized as fillers that reduce the flammability and enhance the strength and thermal conductivity of material composites. Enhancing the thermal stability of SWCNTs is crucial when these materials are applied to high temperature applications. In many instances, SWCNTs are applied to composites with surface coatings that are toxic to living organisms. Alternatively, single-stranded DNA, a naturally occurring biological polymer, has recently been utilized to form singly-dispersed hybrids with SWCNTs as well as suppress their known toxicological effects. These hybrids have shown unrivaled stabilities in both aqueous suspension or as a dried material. Furthermore, DNA has certain documented flame-retardant effects due to the creation of a protective char upon heating in the presence of oxygen. Herein, using various thermogravimetric analytical techniques, we find that single-stranded DNA has a significant flame-retardant effect on the SWCNTs, and effectively enhances their thermal stability. Hybridization with DNA results in the elevation of the thermal decomposition temperature of purified SWCNTs in excess of 200 °C. We translate this finding to other carbon nanomaterials including multi-walled carbon nanotubes (MWCNTs), reduced graphene oxide (RGO) and fullerene (C 60 ), and show similar effects upon complexation with DNA. The rate of thermal decomposition of the SWCNTs was also explored and found to significantly depend upon the sequence of DNA that was used.

Objective: Interfacility neurosurgical transfers to tertiary care centers are driven by a number of variables, including lack of on-site coverage, limited available technology, insurance factors, and patient preference. The authors sought to assess the timing and necessity of surgery and compared transfers to their institution from emergency departments (ED) and inpatient units at other hospitals., Methods: Adult neurosurgical patients who were transferred to a single tertiary care center were analyzed over 12 months. Patients with traumatic injuries or those referred from skilled nursing facilities or rehabilitation centers were excluded., Results: A total of 504 transferred patients were included, with mean age 55 years (range 19-92 years); 53% of patients were women. Points of origin were ED in 54% cases and inpatient hospital unit in 46%, with a mean distance traveled for most patients of 119 miles. Broad diagnosis categories included brain tumors (n = 142, 28%), vascular lesions, including spontaneous and hypertensive intracerebral hemorrhage (n = 143, 28%), spinal lesions (n = 126, 25%), hydrocephalus (n = 45, 9%), wound complications (n = 29, 6%), and others (n = 19, 4%). Patients transferred from inpatient units had higher rates of surgical intervention (75% vs 57%, p < 0.001), whereas patients transferred from the ED had higher rates of urgent surgery (20% vs 8%, p < 0.001) and shorter mean time to surgery (3 vs 5 days, p < 0.001). Misdiagnosis rates were higher among ED referrals (11% vs 4%, p = 0.008). Across the same timeframe, patients undergoing elective admission (n = 1986) or admission from the authors' own ED (n = 248) had significantly shorter lengths of stay (p < 0.001) and ICU days (p < 0.001) than transferred patients, as well as a significantly lower total cost ($44,412, $46,163, and $72,175, respectively; p < 0.001)., Conclusions: The authors present their 12-month experience from a single tertiary care center without Level I trauma designation. In this cohort, 65% of patients required surgery, but the rates were higher among inpatient referrals, and misdiagnosis rates were higher among ED transfers. These data suggest that admitting nonemergency patients to local hospitals may improve diagnostic accuracy of patients requiring urgent care, more precisely identify patients in need of transfer, and reduce costs. Referring facilities may lack necessary resources or expertise, and the Emergency Medical Treatment and Active Labor Act (EMTALA) obligates tertiary care centers to accept these patients under those circumstances. Telemedicine and integration of electronic medical records may help guide referring hospitals to pursue additional workup, which may eliminate the need for unnecessary transfer and provide additional cost savings.

Objective: The benefits and utility of routine neuromonitoring with motor and somatosensory evoked potentials during lumbar spine surgery remain unclear. This study assesses measures of performance and utility of transcranial motor evoked potentials (MEPs) during lumbar pedicle subtraction osteotomy (PSO)., Methods: This is a retrospective study of a single-surgeon cohort of consecutive adult spinal deformity (ASD) patients who underwent lumbar PSO from 2006 to 2016. A blinded neurophysiologist reviewed individual cases for MEP changes. Multivariate analysis was performed to determine whether changes correlated with neurological deficits. Measures of performance were calculated., Results: A total of 242 lumbar PSO cases were included. MEP changes occurred in 38 (15.7%) cases; the changes were transient in 21 cases (55.3%) and permanent in 17 (44.7%). Of the patients with permanent changes, 9 (52.9%) had no recovery and 8 (47.1%) had partial recovery of MEP signals. Changes occurred at a mean time of 8.8 minutes following PSO closure (range: during closure to 55 minutes after closure). The mean percentage of MEP signal loss was 72.9%. The overall complication rate was 25.2%, and the incidence of new neurological deficits was 4.1%. On multivariate analysis, MEP signal loss of at least 50% was not associated with complication (p = 0.495) or able to predict postoperative neurological deficits (p = 0.429). Of the 38 cases in which MEP changes were observed, the observation represented a true-positive finding in only 3 cases. Postoperative neurological deficits without MEP changes occurred in 7 cases. Calculated measures of performance were as follows: sensitivity 30.0%, specificity 84.9%, positive predictive value 7.9%, and negative predictive value 96.6%. Regarding the specific characteristics of the MEP changes, only a signal loss of 80% or greater was significantly associated with a higher rate of neurological deficit (23.0% vs 0.0% for loss of less than 80%, p = 0.021); changes of less than 80% were not associated with postoperative deficits., Conclusions: Neuromonitoring has a low positive predictive value and low sensitivity for detecting new neurological deficits. Even when neuromonitoring is unchanged, patients can still have new neurological deficits. The utility of transcranial MEP monitoring for lumbar PSO remains unclear but there may be advantages to its use.

Objective: Anterior communicating artery (ACoA) aneurysms are common intracranial aneurysms. Despite advances in endovascular therapy, microsurgical clipping remains an important treatment for aneurysms with broad necks, large size, intraluminal thrombus, complex branches, or previous coiling. Anatomical triangles identify safe corridors for aneurysm access. The authors introduce the A1-A2 junctional triangle and the A1-A1 precommunicating triangle and examine relationships between dome projection, triangular corridors of access, and surgical outcomes., Methods: Preoperative catheter and CT angiograms were evaluated to characterize aneurysm dome projection. Aneurysm projection was categorized into quadrants and octants. Preoperative, intraoperative, and postoperative factors were correlated to aneurysm dome projection and patient outcomes using univariate and multivariate analyses., Results: A total of 513 patients with microsurgically treated ACoA aneurysms were identified over a 13-year period, and 400 had adequate imaging and follow-up data for inclusion. Surgical clipping was performed on 271 ruptured and 129 unruptured aneurysms. Good outcomes were observed in 91% of patients with unruptured aneurysms and 86% of those with ruptured aneurysms, with a mortality rate < 1% among patients with unruptured aneurysms. Increasing age (p < 0.01), larger aneurysm size (p = 0.03), and worse preoperative modified Rankin Scale score (p < 0.01) affected outcomes adversely. Aneurysms projecting superiorly and posteriorly required dissection in the junctional triangle, and multivariate analysis demonstrated worse clinical outcomes in these patients (p < 0.01)., Conclusions: Anteriorly and inferiorly projecting aneurysms involve only the precommunicating triangle, are simpler to treat microsurgically, and have more favorable outcomes. Superior and posterior dome projections make ACoA aneurysms more difficult to visualize and require opening the junctional triangle. Added visualization through the junctional triangle is recommended for these aneurysms in order to facilitate dissection of efferent branch arteries, careful clip application, and perforator preservation. Dome projection can be determined preoperatively from images and can help anticipate dissection routes through the junctional triangle.

Objective: Bone morphogenetic protein (BMP) is associated with reduced rates of pseudarthrosis and has the potential to decrease the need for revision surgery. There are limited data evaluating the cost-benefit of BMP for pseudarthrosis-related prevention surgery in adult spinal deformity., Methods: The authors performed a single-center retrospective review of 200 consecutive patients with adult spinal deformity. Demographic data and costs of BMP, primary surgery, and revision surgery for pseudarthrosis were collected. Patients with less than 12 months of follow-up or with infection, tumor, or neuromuscular disease were excluded., Results: One hundred fifty-one patients (107 [71%] women) with a mean age of 65 years met the inclusion criteria. The mean number of levels fused was 10; BMP was used in 98 cases (65%), and the mean follow-up was 23 months. Fifteen patients (10%) underwent surgical revision for pseudarthrosis; BMP use was associated with an 11% absolute risk reduction in the rate of reoperation (17% vs 6%, p = 0.033), with a number needed to treat of 9.2. There were no significant differences in age, sex, upper instrumented vertebra, or number of levels fused in patients who received BMP. In a multivariate model including age, sex, number of levels fused, and the upper instrumented vertebra, only BMP (OR 0.250, 95% CI 0.078-0.797; p = 0.019) was associated with revision surgery for pseudarthrosis. The mean direct cost of primary surgery was $87,653 ± $19,879, and the mean direct cost of BMP was $10,444 ± $4607. The mean direct cost of revision surgery was $52,153 ± $26,985. The authors independently varied the efficacy of BMP, cost of BMP, and cost of reoperation by ± 50%; only reductions in the cost of BMP resulted in a cost savings per 100 patients. Using these data, the authors estimated a price point of $5663 in order for BMP to be cost-neutral., Conclusions: Use of BMP was associated with a significant reduction in the rates of revision surgery for pseudarthrosis. At its current price, the direct in-hospital costs for BMP exceed the costs associated with revision surgery; however, this likely underestimates the true value of BMP when considering the savings associated with reductions in rehabilitation, therapy, medication, and additional outpatient costs.

Single-walled carbon nanotubes (SWCNTs) functionalized with short single-stranded DNA have been extensively studied within the last decade for biomedical applications due to the high dispersion efficiency and intrinsic biocompatibility of DNA as well as the photostable and tunable fluorescence of SWCNTs. Characterization of their physical properties, particularly their length distribution, is of great importance regarding their application as a bioengineered research tool and clinical diagnostic agent. Conventionally, atomic force microscopy (AFM) has been used to quantify the length of DNA-SWCNTs by depositing the hybrids onto an electrostatically charged flat surface. Here, we demonstrate that hybrids of DNA-SWCNTs with different oligomeric DNA sequences ((GT) 6 and (GT) 30 ) differentially deposit on the AFM substrate, resulting in significant inaccuracies in the reported length distributions of the parent solutions. Using a solution-based surfactant exchange technique, we placed both samples into a common surfactant wrapping and found identical SWCNT length distributions upon surface deposition. Additionally, by spin-coating the surfactant-wrapped SWCNTs onto a substrate, thus mitigating effects of electrostatic interactions, we found length distributions that did not depend on DNA sequence but were significantly longer than electrostatic deposition methods, illuminating the inherent bias of the surface deposition method. Quantifying the coverage of DNA molecules on each SWCNT through both absorbance spectroscopy and direct observation, we found that the density of DNA per SWCNT was significantly higher in short (GT) 6 -SWCNTs (length < 100 nm) compared to long (GT) 6 -SWCNTs (length > 100 nm). In contrast, we found no dependence of the DNA density on SWCNT length in (GT) 30 -SWCNT hybrids. Thus, we attribute differences in the observed length distributions of DNA-SWCNTs to variations in electrostatic repulsion induced by sequence-dependent DNA density.