Publications by authors named "Ethan Cottrill"

58 Publications

Interrater and Intra-rater Reliability of the Vertebral Bone Quality Score.

World Neurosurg 2021 Jul 9. Epub 2021 Jul 9.

Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD USA 21287; Department of Neurosurgery, Zucker School of Medicine at Hofstra, Long Island Jewish Medical Center and North Shore University Hospital, Northwell Health, Manhasset, NY USA 11030. Electronic address:

Background: Vertebral bone quality had a significant impact on postoperative outcomes in spinal fusion surgery. New MRI-based measures, such as the Vertebral Bone Quality (VBQ) score may allow for bone quality assessment without the radiation associated with conventional testing. In the present study, we sought to assess the intra- and interrater reliability of VBQ scores calculated by medical professionals and trainees.

Methods: Thirteen reviewers of various specialties and levels of training were recruited and asked to calculate VBQ scores for 30 patients at two time points separated by 2-months. Scored volumes were acquired from patients treated for both degenerative and oncologic indications. Intra-rater and interrater agreement, quantified by intraclass correlation coefficient (ICC), was assessed using two-way random effects modeling. Square-weight Cohen's κ and Kendall's Tau-b were used to determine whether raters assigned similar scores during both evaluations.

Results: All raters showed moderate to excellent reliability for VBQ score (ICC 0.667-0.957; κ0.648-0.921) and excellent reliability for all constituent components used to calculate VBQ score (ICC all ≥0.97). Interrater reliability was also found to be good for VBQ score on both the first (ICC=0.818) and second (ICC=0.800) rounds of assessment; scores for the constituent component all had ICC values ≥0.97 for the constituent components.

Conclusions: The VBQ score appears to have both good intra-rater and interrater reliability. Additionally, there appeared to be no correlation between score reliability and level of training. External validation and further investigations of its ability to accurately model bone biomechanical properties are necessary.
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http://dx.doi.org/10.1016/j.wneu.2021.07.020DOI Listing
July 2021

Removal of instrumentation for postoperative spine infection: systematic review.

J Neurosurg Spine 2021 Jul 9:1-13. Epub 2021 Jul 9.

Objective: Currently, no consensus exists as to whether patients who develop infection of the surgical site after undergoing instrumented fusion should have their implants removed at the time of wound debridement. Instrumentation removal may eliminate a potential infection nidus, but removal may also destabilize the patient's spine. The authors sought to summarize the existing evidence by systematically reviewing published studies that compare outcomes between patients undergoing wound washout and instrumentation removal with outcomes of patients undergoing wound washout alone. The primary objectives were to determine 1) whether instrumentation removal from an infected wound facilitates infection clearance and lowers morbidity, and 2) whether the chronicity of the underlying infection affects the decision to remove instrumentation.

Methods: PRISMA guidelines were used to review the PubMed/MEDLINE, Embase, Cochrane Library, Scopus, Web of Science, and ClinicalTrials.gov databases to identify studies that compared patients with implants removed and patients with implants retained. Outcomes of interest included mortality, rate of repeat wound washout, and loss of correction.

Results: Fifteen articles were included. Of 878 patients examined in these studies, 292 (33%) had instrumentation removed. Patient populations were highly heterogeneous, and outcome data were limited. Available data suggested that rates of reoperation, pseudarthrosis, and death were higher in patients who underwent instrumentation removal at the time of initial washout. Three studies recommended that instrumentation be uniformly removed at the time of wound washout. Five studies favored retaining the original instrumentation. Six studies favored retention in early infections but removal in late infections.

Conclusions: The data on this topic remain heterogeneous and low in quality. Retention may be preferred in the setting of early infection, when the risk of underlying spine instability is still high and the risk of mature biofilm formation on the implants is low. However, late infections likely favor instrumentation removal. Higher-quality evidence from large, multicenter, prospective studies is needed to reach generalizable conclusions capable of guiding clinical practice.
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http://dx.doi.org/10.3171/2020.12.SPINE201300DOI Listing
July 2021

Impact of Multidisciplinary Intraoperative Teams on Thirty-Day Complications After Sacral Tumor Resection.

World Neurosurg 2021 Aug 16;152:e558-e566. Epub 2021 Jun 16.

Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. Electronic address:

Objective: To evaluate the impact of multidisciplinary intraoperative teams on surgical complications in patients undergoing sacral tumor resection.

Methods: We reviewed all patients with primary or metastatic sacral tumors managed at a single comprehensive cancer center over a 7-year period. Perioperative complication rates were compared between those treated by an unassisted spinal oncologist and those treated with the assistance of at least 1 other surgical specialty. Statistical analysis involved univariable and stepwise multivariable logistic regression models to identify predictors of multidisciplinary management and 30-day complications.

Results: A total of 107 patients underwent 132 operations for sacral tumors; 92 operations involved multidisciplinary teams, including 54% of metastatic tumor operations and 74% of primary tumor operations. Patients receiving multidisciplinary management had higher body mass indexes (29.8 vs. 26.3 kg/m; P = 0.008), larger tumors (258 vs. 55 cm³; P < 0.001), and higher American Society of Anesthesiologists scores (3 vs. 2; P = 0.049). Only larger tumor volume (odds ratio [OR], 1.007 per cm³; P < 0.001) and undergoing treatment for a malignant primary versus a metastatic tumor (OR, 23.4; P < 0.001) or benign primary tumor (OR, 29.3; P < 0.001) were predictive of multidisciplinary management. Although operations involving multidisciplinary teams were longer (467 vs. 231 minutes; P < 0.001) and had higher blood loss (1698 vs. 774 mL; P = 0.004), 30-day complication rates were similar (37 vs. 27%; P = 0.39). On multivariable analysis, only larger tumor volume (OR, 1.004 per cm³; P = 0.005) and longer surgical duration (OR, 1.002 per minute; P = 0.03) independently predicted higher 30-day complications.

Conclusions: Although patients managed with multidisciplinary teams had larger tumors and worse baseline health, 30-day complications were similar. This finding suggests that the use of multidisciplinary teams may help to mitigate surgical morbidity in those with high baseline risk.
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http://dx.doi.org/10.1016/j.wneu.2021.06.040DOI Listing
August 2021

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

J Orthop Res 2021 Jun 3. Epub 2021 Jun 3.

Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Although bone marrow-derived mesenchymal stem cells (BMCs) have been widely used in spinal fusion procedures, adipose-derived stem cells (ASCs) offer a number of advantages as an alternative clinical cell source. This study directly compares the efficacy of ASCs and BMCs from the same donor animals to achieve successful fusion when combined with a clinical-grade bone graft substitute in a rat lumbar fusion model. ASCs and BMCs were isolated from the same Lewis donor rats and grown to passage 2 (P2). Single-level bilateral posterolateral intertransverse process lumbar fusion surgery was performed on syngeneic rats divided into three experimental groups: clinical-grade bone graft substitute alone (CBGS); CBGS+ rat ASCs (rASC); and, CBGS+ rat BMCs (rBMC). Eight weeks postoperatively, fusion was evaluated via micro-CT, manual palpation and histology. In vitro analysis of the osteogenic capacity of rBMCs and rASCs was also performed. Results indicated that the average fusion volume in the rASC group was the largest and was significantly larger than the CBGS group. Although the rASC group displayed the highest fusion rates via micro-CT and manual palpation, this difference was not statistically significant. Cell-seeded grafts showed more histological bone formation than cell-free grafts. P2 rASCs and rBMCs displayed similar in vitro osteogenic differentiation capacities. Overall, this study showed that, when combined with a clinical-grade bone graft substitute in a rat model, rASCs cells yielded the largest fusion masses and comparable fusion results to rBMCs. These results add to growing evidence that ASCs provide an attractive alternative to BMCs for spinal fusion procedures.
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http://dx.doi.org/10.1002/jor.25111DOI Listing
June 2021

Fenestrated pedicle screws for thoracolumbar instrumentation in patients with poor bone quality: Case series and systematic review of the literature.

Clin Neurol Neurosurg 2021 Jul 11;206:106675. Epub 2021 May 11.

Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Neurosurgery, Zucker School of Medicine at Hofstra, Long Island Jewish Medical Center and North Shore University Hospital, Northwell Health, Manhasset, NY 11030, USA. Electronic address:

Objective: To describe the results of a single-surgeon series and systematically review the literature on cement-augmented instrumented fusion with fenestrated pedicle screws.

Methods: All patients treated by the senior surgeon using fenestrated screws between 2017 and 2019 with a minimum of 6-months of clinical and radiographic follow-up were included. For the systematic review, we used PRISMA guidelines to identify all prior descriptions of cement-augmented instrumented fusion with fenestrated pedicle screws in the English literature. Endpoints of interest included hardware loosening, cement leakage, and pulmonary cement embolism (PCE).

Results: Our series included 38 patients (mean follow-up 14.8 months) who underwent cement-augmented instrumentation for tumor (47.3%), deformity/degenerative disease (39.5%), or osteoporotic fracture (13.2%). Asymptomatic screw lucency was seen in 2.6%, cement leakage in 445, and pulmonary cement embolism (PCE) in 5.2%. Our literature review identified 23 studies (n = 1526 patients), with low reported rates of hardware loosening (0.2%) and symptomatic PCE (1.0%). Cement leakage, while common (55.6%), produced symptoms in fewer than 1% of patients. Indications for cement-augmentation in this cohort included: spine metastasis with or without pathologic fracture (n = 18; 47.3%), degenerative spine disease or fixed deformity with poor underlying bone quality (n = 15; 39.5%), and osteoporotic fracture (n = 5; 13.2%).

Conclusion: Cement-augmented fusion with fenestrated screws appears to be a safe, effective means of treating patients with poor underlying bone quality secondary to tumor or osteoporosis. High-quality evidence with direct comparisons to non-augmented patients is needed.
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http://dx.doi.org/10.1016/j.clineuro.2021.106675DOI Listing
July 2021

Sacrectomy for sacral tumors: Perioperative outcomes in a large-volume comprehensive cancer center.

Spine J 2021 May 14. Epub 2021 May 14.

Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Neurosurgery, Zucker School of Medicine at Hofstra, Long Island Jewish Medical Center and North Shore University Hospital, Northwell Health, Manhasset, NY 11030, USA. Electronic address:

Background Context: Sacral tumors are incredibly rare lesions affecting fewer than one in every 10,000 persons. Reported perioperative morbidity rates range widely, varying from 30% to 70%, due to the relatively low volumes seen by most centers. Factors affecting perioperative outcome following sacrectomy remain ill-defined.

Purpose: To characterize perioperative outcomes of sacral tumor patients undergoing sacrectomy and identify independent risk factors of perioperative morbidity STUDY DESIGN/SETTING: Retrospective cohort study at a single comprehensive cancer center PATIENT SAMPLE: Consecutively treated sacral tumor patients (primary or metastatic) undergoing sacrectomy for oncologic resection between April 2013 and April 2020 OUTCOME MEASURES: Perioperative complications, hospital length of stay, non-home discharge, 30-day readmission, and 30-day reoperation METHODS: Details were gathered about tumor pathology and morphology, surgery performed, baseline medical comorbidities, preoperative lab data, and patient demographics. Stepwise multivariable regressions were conducted to identify independent risk factors of perioperative outcomes while evaluating predictive accuracy.

Results: 57 sacral tumor patients were included (mean age 55.5±13.0 years; 60% female). The complication, non-home discharge, 30-day readmission, and 30-day reoperation rates were 39%, 56%, 16%, and 14%, respectively. Independent predictors of perioperative complications included ASA>2 (OR=10.7; 95%CI [1.3, 86.0]; p=0.026), radicular pain (OR=10.9; p=0.014), platelet count (OR=0.989 per 10³/μL; p=0.049), and instrumentation (OR=10.7; p=0.009). Independent predictors of length of stay included iliac vessel involvement (β=15.8; p=0.005), larger tumor volume (β=0.027 per cm³; p<0.001), a staged procedure (β=10.0; p=0.018), and S1 nerve root sacrifice (OR=15.8; p=.011). The optimal model predictive of non-home discharge included bilateral S3-S5 or higher nerve root sacrifice (OR=3.9; p=0.054), instrumentation (OR=8.6; p=0.005), and vertical rectus abdominis musculocutaneous flap closure (OR=5.3; p=0.067). 30-day readmission was independently predicted by history of chronic kidney disease (OR=26.7; p=0.021), radicular pain (OR=8.1; p=0.039), and preoperative saddle anesthesia (OR=12.6; p=0.026). All multivariable models achieved good discrimination (AUC>0.8 and R>0.7).

Conclusion: Clinical and operative factors were important predictors of complications and 30-day readmission, while tumor-related and operative factors accounted for most of the variability in length of stay and non-home discharge.
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http://dx.doi.org/10.1016/j.spinee.2021.05.004DOI Listing
May 2021

Effects of Single-Dose Versus Hypofractionated Focused Radiation on Vertebral Body Structure and Biomechanical Integrity: Development of a Rabbit Radiation-Induced Vertebral Compression Fracture Model.

Int J Radiat Oncol Biol Phys 2021 May 11. Epub 2021 May 11.

Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address:

Purpose: Vertebral compression fracture is a common complication of spinal stereotactic body radiation therapy. Development of an in vivo model is crucial to fully understand how focal radiation treatment affects vertebral integrity and biology at various dose fractionation regimens. We present a clinically relevant animal model to analyze the effects of localized, high-dose radiation on vertebral microstructure and mechanical integrity. Using this model, we test the hypothesis that fractionation of radiation dosing can reduce focused radiation therapy's harmful effects on the spine.

Methods And Materials: The L5 vertebra of New Zealand white rabbits was treated with either a 24-Gy single dose of focused radiation or 3 fractionated 8-Gy doses over 3 consecutive days via the Small Animal Radiation Research Platform. Nonirradiated rabbits were used as controls. Rabbits were euthanized 6 months after irradiation, and their lumbar vertebrae were harvested for radiologic, histologic, and biomechanical testing.

Results: Localized single-dose radiation led to decreased vertebral bone volume and trabecular number and a subsequent increase in trabecular spacing and thickness at L5. Hypofractionation of the radiation dose similarly led to reduced trabecular number and increased trabecular spacing and thickness, yet it preserved normalized bone volume. Single-dose irradiated vertebrae displayed lower fracture loads and stiffness compared with those receiving hypofractionated irradiation and with controls. The hypofractionated and control groups exhibited similar fracture load and stiffness. For all vertebral samples, bone volume, trabecular number, and trabecular spacing were correlated with fracture loads and Young's modulus (P < .05). Hypocellularity was observed in the bone marrow of both irradiated groups, but osteogenic features were conserved in only the hypofractionated group.

Conclusions: Single-dose focal irradiation showed greater detrimental effects than hypofractionation on the microarchitectural, cellular, and biomechanical characteristics of irradiated vertebral bodies. Correlation between radiologic measurements and biomechanical properties supported the reliability of this animal model of radiation-induced vertebral compression fracture, a finding that can be applied to future studies of preventative measures.
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http://dx.doi.org/10.1016/j.ijrobp.2021.04.050DOI Listing
May 2021

Dataset of the first report of pharmacogenomics profiling in an outpatient spine setting.

Data Brief 2021 Apr 3;35:106832. Epub 2021 Feb 3.

Department of Neurosurgery, Johns Hopkins University School of Medicine, 600 N. Wolfe St., Meyer 7-113, Baltimore, MD 21287, USA.

Here we describe the dataset of the first report of pharmacogenomics profiling in an outpatient spine setting with the primary aims to catalog: 1) the genes, alleles, and associated rs Numbers (accession numbers for specific single-nucleotide polymorphisms) analysed and 2) the genotypes and corresponding phenotypes of the genes involved in metabolizing 37 commonly used analgesic medications. The present description applies to analgesic medication-metabolizing enzymes and may be especially valuable to investigators who are exploring strategies to optimize pharmacologic pain management (e.g., by tailoring analgesic regimens to the genetically identified sensitivities of the patient). Buccal swabs were used to acquire tissue samples of 30 adult patients who presented to an outpatient spine clinic with the chief concern of axial neck and/or back pain. Array-based assays were then used to detect the alleles of genes involved in the metabolism of pain medications, including all common (wild type) and most rare variant alleles with known clinical significance. Both CYP450 isozymes - including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5 - and the phase II enzyme UDP-glucuronosyltransferase-2B7 (UGT2B7) were examined. Genotypes/phenotypes were then used to evaluate each patient's relative ability to metabolize 37 commonly used analgesic medications. These medications included both non-opioid analgesics (i.e., aspirin, diclofenac, nabumetone, indomethacin, meloxicam, piroxicam, tenoxicam, lornoxicam, celecoxib, ibuprofen, flurbiprofen, ketoprofen, fenoprofen, naproxen, and mefenamic acid) and opioid analgesics (i.e., morphine, codeine, dihydrocodeine, ethylmorphine, hydrocodone, hydromorphone, oxycodone, oxymorphone, alfentanil, fentanyl, sufentanil, meperidine, ketobemidone, dextropropoxyphene, levacetylmethadol, loperamide, methadone, buprenorphine, dextromethorphan, tramadol, tapentadol, and tilidine). The genes, alleles, and associated rs Numbers that were analysed are provided. Also provided are: 1) the genotypes and corresponding phenotypes of the genes involved in metabolizing 37 commonly used analgesic medications and 2) the mechanisms of metabolism of the analgesic medications by primary and ancillary pathways. In supplemental spreadsheets, the raw and analysed pharmacogenomics data for all 30 patients evaluated in the primary research article are additionally provided. Collectively, the presented data offer significant reuse potential in future investigations of pharmacogenomics for pain management.
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http://dx.doi.org/10.1016/j.dib.2021.106832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893444PMC
April 2021

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

J Ultrasound Med 2020 Dec 8. Epub 2020 Dec 8.

Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Despite extensive research, nonunion continues to affect a nontrivial proportion of patients undergoing spinal fusion. Recently, preclinical studies have suggested that low-intensity pulsed ultrasound (LIPUS) may increase rates of spinal fusion. In this study, we summarized the available in vivo literature evaluating the effect of LIPUS on spinal fusion and performed a meta-analysis of the available data to estimate the degree to which LIPUS may mediate higher fusion rates. Across 13 preclinical studies, LIPUS was associated with a 9-fold increase in the odds of successful spinal fusion. Future studies are necessary to establish the benefit of LIPUS on spinal fusion in clinical populations.
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http://dx.doi.org/10.1002/jum.15587DOI Listing
December 2020

Posterior Vertebral Column Subtraction Osteotomy for Recurrent Tethered Cord Syndrome: A Multicenter, Retrospective Analysis.

Neurosurgery 2021 02;88(3):637-647

Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona.

Background: Few have explored the safety and efficacy of posterior vertebral column subtraction osteotomy (PVCSO) to treat tethered cord syndrome (TCS).

Objective: To evaluate surgical outcomes after PVCSO in adults with TCS caused by lipomyelomeningocele, who had undergone a previous detethering procedure(s) that ultimately failed.

Methods: This is a multicenter, retrospective analysis of a prospectively collected cohort. Patients were prospectively enrolled and treated with PVCSO at 2 institutions between January 1, 2011 and December 31, 2018. Inclusion criteria were age ≥18 yr, TCS caused by lipomyelomeningocele, previous detethering surgery, and recurrent symptom progression of less than 2-yr duration. All patients undergoing surgery with a 1-yr minimum follow-up were evaluated.

Results: A total of 20 patients (mean age: 36 yr; sex: 15F/5M) met inclusion criteria and were evaluated. At follow-up (mean: 23.3 ± 7.4 mo), symptomatic improvement/resolution was seen in 93% of patients with leg pain, 84% in back pain, 80% in sensory abnormalities, 80% in motor deficits, 55% in bowel incontinence, and 50% in urinary incontinence. Oswestry Disability Index improved from a preoperative mean of 57.7 to 36.6 at last follow-up (P < .01). Mean spinal column height reduction was 23.4 ± 2.7 mm. Four complications occurred: intraoperative durotomy (no reoperation), wound infection, instrumentation failure requiring revision, and new sensory abnormality.

Conclusion: This is the largest study to date assessing the safety and efficacy of PVCSO in adults with TCS caused by lipomyelomeningocele and prior failed detethering. We found PVCSO to be an excellent extradural approach that may afford definitive treatment in this particularly challenging population.
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http://dx.doi.org/10.1093/neuros/nyaa491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884146PMC
February 2021

Experience with an Enhanced Recovery After Spine Surgery protocol at an academic community hospital.

J Neurosurg Spine 2020 Dec 25:1-8. Epub 2020 Dec 25.

Departments of1Neurosurgery.

Objective: Enhanced Recovery After Surgery (ERAS) protocols have rapidly gained popularity in multiple surgical specialties and are recognized for their potential to improve patient outcomes and decrease hospitalization costs. However, they have only recently been applied to spinal surgery. The goal in the present work was to describe the development, implementation, and impact of an Enhanced Recovery After Spine Surgery (ERASS) protocol for patients undergoing elective spine procedures at an academic community hospital.

Methods: A multidisciplinary team, drawing on prior publications and spine surgery best practices, collaborated to develop an ERASS protocol. Patients undergoing elective cervical or lumbar procedures were prospectively enrolled at a single tertiary care center; interventions were standardized across the cohort for pre-, intra-, and postoperative care using standardized order sets in the electronic medical record. Protocol efficacy was evaluated by comparing enrolled patients to a historic cohort of age- and procedure-matched controls. The primary study outcomes were quantity of opiate use in morphine milligram equivalents (MMEs) on postoperative day (POD) 1 and length of stay. Secondary outcomes included frequency and duration of indwelling urinary catheter use, discharge disposition, 30-day readmission and reoperation rates, and complication rates. Multivariable linear regression was used to determine whether ERASS protocol use was independently predictive of opiate use on POD 1.

Results: In total, 97 patients were included in the study cohort and were compared with a historic cohort of 146 patients. The patients in the ERASS group had lower POD 1 opiate use than the control group (26 ± 33 vs 42 ± 40 MMEs, p < 0.001), driven largely by differences in opiate-naive patients (16 ± 21 vs 38 ± 36 MMEs, p < 0.001). Additionally, patients in the ERASS group had shorter hospitalizations than patients in the control group (51 ± 30 vs 62 ± 49 hours, p = 0.047). On multivariable regression, implementation of the ERASS protocol was independently predictive of lower POD 1 opiate consumption (β = -7.32, p < 0.001). There were no significant differences in any of the secondary outcomes.

Conclusions: The authors found that the development and implementation of a comprehensive ERASS protocol led to a modest reduction in postoperative opiate consumption and hospital length of stay in patients undergoing elective cervical or lumbar procedures. As suggested by these results and those of other groups, the implementation of ERASS protocols may reduce care costs and improve patient outcomes after spine surgery.
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http://dx.doi.org/10.3171/2020.7.SPINE20358DOI Listing
December 2020

Predicting postoperative quality-of-life outcomes in patients with metastatic spine disease: who benefits?

J Neurosurg Spine 2020 Dec 18:1-7. Epub 2020 Dec 18.

Symptomatic spinal metastasis occurs in around 10% of all cancer patients, 5%-10% of whom will require operative management. While postoperative survival has been extensively evaluated, postoperative health-related quality-of-life (HRQOL) outcomes have remained relatively understudied. Available tools that measure HRQOL are heterogeneous and may emphasize different aspects of HRQOL. The authors of this paper recommend the use of the EQ-5D and Spine Oncology Study Group Outcomes Questionnaire (SOSGOQ), given their extensive validation, to capture the QOL effects of systemic disease and spine metastases. Recent studies have identified preoperative QOL, baseline functional status, and neurological function as potential predictors of postoperative QOL outcomes, but heterogeneity across studies limits the ability to derive meaningful conclusions from the data. Future development of a valid and reliable prognostic model will likely require the application of a standardized protocol in the context of a multicenter study design.
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http://dx.doi.org/10.3171/2020.7.SPINE201136DOI Listing
December 2020

Clinical utility of enhanced recovery after surgery pathways in pediatric spinal deformity surgery: systematic review of the literature.

J Neurosurg Pediatr 2020 Nov 20:1-14. Epub 2020 Nov 20.

Departments of1Neurosurgery and.

Objectives: More than 7500 children undergo surgery for scoliosis each year, at an estimated annual cost to the health system of $1.1 billion. There is significant interest among patients, parents, providers, and payors in identifying methods for delivering quality outcomes at lower costs. Enhanced recovery after surgery (ERAS) protocols have been suggested as one possible solution. Here the authors conducted a systematic review of the literature describing the clinical and economic benefits of ERAS protocols in pediatric spinal deformity surgery.

Methods: The authors identified all English-language articles on ERAS protocol use in pediatric spinal deformity surgery by using the following databases: PubMed/MEDLINE, Web of Science, Cochrane Reviews, EMBASE, CINAHL, and OVID MEDLINE. Quantitative analyses of comparative articles using random effects were performed for the following clinical outcomes: 1) length of stay (LOS); 2) complication rate; 3) wound infection rate; 4) 30-day readmission rate; 5) reoperation rate; and 6) postoperative pain scores.

Results: Of 950 articles reviewed, 7 were included in the qualitative analysis and 6 were included in the quantitative analysis. The most frequently cited benefits of ERAS protocols were shorter LOS, earlier urinary catheter removal, and earlier discontinuation of patient-controlled analgesia pumps. Quantitative analyses showed ERAS protocols to be associated with shorter LOS (mean difference -1.12 days; 95% CI -1.51, -0.74; p < 0.001), fewer postoperative complications (OR 0.37; 95% CI 0.20, 0.68; p = 0.001), and lower pain scores on postoperative day (POD) 0 (mean -0.92; 95% CI -1.29, -0.56; p < 0.001) and POD 2 (-0.61; 95% CI -0.75, -0.47; p < 0.001). There were no differences in reoperation rate or POD 1 pain scores. ERAS-treated patients had a trend toward higher 30-day readmission rates and earlier discontinuation of patient-controlled analgesia (both p = 0.06). Insufficient data existed to reach a conclusion about cost differences.

Conclusions: The results of this systematic review suggest that ERAS protocols may shorten hospitalizations, reduce postoperative complication rates, and reduce postoperative pain scores in children undergoing scoliosis surgery. Publication biases exist, and therefore larger, prospective, multicenter data are needed to validate these results.
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http://dx.doi.org/10.3171/2020.7.PEDS20444DOI Listing
November 2020

Radiographic and clinical outcomes of silicate-substituted calcium phosphate (SiCaP) bone grafts in spinal fusion: Systematic review and meta-analysis.

J Clin Neurosci 2020 Nov 23;81:353-366. Epub 2020 Oct 23.

Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address:

Pseudarthrosis continues to affect a nontrivial proportion of spine fusion patients. Given its ties to poorer patient outcomes and high reoperation rates, there remains great interest in interventions aimed at reducing the rates of nonunion. Recently, silicate-substituted calcium phosphate (SiCaP) bone grafts have been suggested to improve fusion rates, yet there exists no systematic review of the body of evidence for SiCaP grafts. Here, we present the first such review along with a meta-analysis of the effect of SiCaP bone grafts on fusion rates. Using the PubMed, Embase, and Web of Science databases, we queried the English-language literature for all studies examining the effect of SiCaPs on spinal fusion. Primary endpoints were: 1) radiographic fusion rate at last follow-up and 2) postoperative improvements in Visual Analog Scale (VAS) pain scores and Oswestry Disability Index (ODI) at last follow-up. Meta-analyses were performed for each endpoint using random effects. Ten articles (694 patients treated with SiCaP bone grafts) were included. Among SiCaP-treated patients, 93% achieved radiographic fusion (range: 79-100%), with comparable rates across subgroups. Meta-analysis of the three randomized controlled trials demonstrated no difference in fusion rates between SiCaP-treated patients and patients receiving grafts with recombinant human bone morphogenetic protein-2 (rhBMP-2) (OR: 1.11; p = 0.83). Patients treated with SiCaP bone grafts experienced significant improvements in VAS back pain (-3.3 points), VAS leg pain (-4.8 points), and ODI (-31.6 points) by last follow-up (p < 0.001 for each). Additional high-quality research is needed to evaluate the relative cost-effectiveness of SiCaP bone grafts in spinal fusion.
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http://dx.doi.org/10.1016/j.jocn.2020.09.073DOI Listing
November 2020

Systematic review and meta-analysis of the clinical utility of Enhanced Recovery After Surgery pathways in adult spine surgery.

J Neurosurg Spine 2020 Nov 6:1-23. Epub 2020 Nov 6.

Objective: Spine surgery has been identified as a significant source of healthcare expenditures in the United States. Prolonged hospitalization has been cited as one source of increased spending, and there has been drive from providers and payors alike to decrease inpatient stays. One strategy currently being explored is the use of Enhanced Recovery After Surgery (ERAS) protocols. Here, the authors review the literature on adult spine ERAS protocols, focusing on clinical benefits and cost reductions. They also conducted a quantitative meta-analysis examining the following: 1) length of stay (LOS), 2) complication rate, 3) wound infection rate, 4) 30-day readmission rate, and 5) 30-day reoperation rate.

Methods: Using the PRISMA guidelines, a search of the PubMed/Medline, Web of Science, Cochrane Reviews, Embase, CINAHL, and OVID Medline databases was conducted to identify all full-text articles in the English-language literature describing ERAS protocol implementation for adult spine surgery. A quantitative meta-analysis using random-effects modeling was performed for the identified clinical outcomes using studies that directly compared ERAS protocols with conventional care.

Results: Of 950 articles reviewed, 34 were included in the qualitative analysis and 20 were included in the quantitative analysis. The most common protocol types were general spine surgery protocols and protocols for lumbar spine surgery patients. The most frequently cited benefits of ERAS protocols were shorter LOS (n = 12), lower postoperative pain scores (n = 6), and decreased complication rates (n = 4). The meta-analysis demonstrated shorter LOS for the general spine surgery (mean difference -1.22 days [95% CI -1.98 to -0.47]) and lumbar spine ERAS protocols (-1.53 days [95% CI -2.89 to -0.16]). Neither general nor lumbar spine protocols led to a significant difference in complication rates. Insufficient data existed to perform a meta-analysis of the differences in costs or postoperative narcotic use.

Conclusions: Present data suggest that ERAS protocol implementation may reduce hospitalization time among adult spine surgery patients and may lead to reductions in complication rates when applied to specific populations. To generate high-quality evidence capable of supporting practice guidelines, though, additional controlled trials are necessary to validate these early findings in larger populations.
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http://dx.doi.org/10.3171/2020.6.SPINE20795DOI Listing
November 2020

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

J Pediatr Orthop 2021 Feb;41(2):e181-e187

Departments of Orthopaedic Surgery.

Background: It has been posited that the osseous pelvic anomalies seen in patients with classic bladder exstrophy (CBE) result from disruption of the pubic symphysis. This hypothesis, however, has not been tested. In the present animal study, our objective was to determine whether the tension of the pubic symphysis helps maintain the shape of the pelvic ring, or whether the growing bones maintain a ring shape even without the tension of the symphysis.

Methods: In total, 12 neonatal New Zealand White rabbits underwent pubic symphysiotomy (experimental group, n=9) or sham surgery (control group, n=3) on days 3 or 4 of life. Rabbits were scanned with cone-beam computed tomography at 1, 4, 12, and 20 weeks postoperatively to monitor changes in the following pelvic parameters, which are known to be altered in CBE: anterior segment angle, anterior segment length, intertriradiate distance, interpubic distance, and posterior segment angle. Changes within the experimental and control groups were evaluated using repeated-measures analysis of variance and post hoc Tukey honest significant difference testing. Two-tailed t tests were used to compare treatment groups at each time point.

Results: Both groups showed increases in anterior segment length and intertriradiate distance during the study period; rabbits in the experimental group also showed a steady increase in interpubic distance (F=43.9; P<0.001). Experimental rabbits had significantly larger mean values for anterior segment angle, intertriradiate distance, interpubic distance, and posterior segment angle than did control rabbits at all time points. We found no difference in mean anterior segment length between control and experimental groups at any time point. The difference in interpubic distance was particularly pronounced by 20 weeks (experimental group, 13±2.7 mm; control group, 1.1±0.1 mm; P<0.001).

Conclusions: The pubic symphysis is essential for normal pelvic development. Its absence led to early pelvic angulation and progressive pubic separation in a rabbit model. However, we found no significant difference in the mean anterior segment length, and it is likely that other factors are also implicated in the growth disturbance seen in CBE.

Level Of Evidence: Level V.
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http://dx.doi.org/10.1097/BPO.0000000000001698DOI Listing
February 2021

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

Spine (Phila Pa 1976) 2021 May;46(10):631-637

Johns Hopkins University School of Medicine, Department of Neurosurgery, Baltimore, MD.

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.
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http://dx.doi.org/10.1097/BRS.0000000000003709DOI Listing
May 2021

Comparing the efficacy of syngeneic iliac and femoral allografts with iliac crest autograft in a rat model of lumbar spinal fusion.

J Orthop Surg Res 2020 Sep 15;15(1):410. Epub 2020 Sep 15.

Department of Neurosurgery, The Johns Hopkins University, School of Medicine, Baltimore, MD, USA.

Background: Despite widespread use of femoral-sourced allografts in clinical spinal fusion procedures and the increasing interest in using femoral reamer-irrigator-aspirator (RIA) autograft in clinical bone grafting, few studies have examined the efficacy of femoral grafts compared to iliac crest grafts in spinal fusion. The objective of this study was to directly compare the use of autologous iliac crest with syngeneic femoral and iliac allograft bone in the rat model of lumbar spinal fusion.

Methods: Single-level bilateral posterolateral intertransverse process lumbar spinal fusion surgery was performed on Lewis rats divided into three experimental groups: iliac crest autograft, syngeneic iliac crest allograft, and syngeneic femoral allograft bone. Eight weeks postoperatively, fusion was evaluated via microCT analysis, manual palpation, and histology. In vitro analysis of the colony-forming and osteogenic capacity of bone marrow cells derived from rat femurs and hips was also performed to determine whether there was a correlation with the fusion efficacy of these graft sources.

Results: Although no differences were observed between groups in CT fusion mass volumes, iliac allografts displayed an increased number of radiographically fused fusion masses and a higher rate of bilateral fusion via manual palpation. Histologically, hip-derived grafts showed better integration with host bone than femur derived ones, likely associated with the higher concentration of osteogenic progenitor cells observed in hip-derived bone marrow.

Conclusions: This study demonstrates the feasibility of using syngeneic allograft bone in place of autograft bone within inbred rat fusion models and highlights the need for further study of femoral-derived grafts in fusion.
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http://dx.doi.org/10.1186/s13018-020-01936-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490887PMC
September 2020

To operate, or not to operate? Narrative review of the role of survival predictors in patient selection for operative management of patients with metastatic spine disease.

J Neurosurg Spine 2020 Sep 11:1-15. Epub 2020 Sep 11.

Accurate prediction of patient survival is an essential component of the preoperative evaluation of patients with spinal metastases. Over the past quarter of a century, a number of predictors have been developed, although none have been accurate enough to be instituted as a staple of clinical practice. However, recently more comprehensive survival calculators have been published that make use of larger data sets and machine learning to predict postoperative survival among patients with spine metastases. Given the glut of calculators that have been published, the authors sought to perform a narrative review of the current literature, highlighting existing calculators along with the strengths and weaknesses of each. In doing so, they identify two "generations" of scoring systems-a first generation based on a priori factor weighting and a second generation comprising predictive tools that are developed using advanced statistical modeling and are focused on clinical deployment. In spite of recent advances, the authors found that most predictors have only a moderate ability to explain variation in patient survival. Second-generation models have a greater prognostic accuracy relative to first-generation scoring systems, but most still require external validation. Given this, it seems that there are two outstanding goals for these survival predictors, foremost being external validation of current calculators in multicenter prospective cohorts, as the majority have been developed from, and internally validated within, the same single-institution data sets. Lastly, current predictors should be modified to incorporate advances in targeted systemic therapy and radiotherapy, which have been heretofore largely ignored.
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http://dx.doi.org/10.3171/2020.6.SPINE20707DOI Listing
September 2020

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

World Neurosurg 2021 01 8;145:e21-e31. Epub 2020 Sep 8.

Department of Neurosurgery, Johns Hopkins School of Medicine, Baltimore, Maryland, USA. Electronic address:

Objective: Pharmacogenomics may help personalize medicine and improve therapeutic selection. This is the first study investigating how pharmacogenomic testing may inform analgesic selection in patients with spine disease. We profile pharmacogenetic differences in pain medication-metabolizing enzymes across patients presenting at an outpatient spine clinic and provide preliminary evidence that genetic polymorphisms may help explain interpatient differences in preoperative pain refractory to conservative management.

Methods: Adults presenting to our outpatient spine clinic with chief symptoms of neck and/or back pain were prospectively enrolled over 9 months. Patients completed the Wong-Baker FACES and numeric pain rating scales for their chief pain symptom and provided detailed medication histories and cheek swab samples for genomic analysis.

Results: Thirty adults were included (mean age, 60.6 ± 15.3 years). The chief concern was neck pain in 23%, back pain in 67%, and combined neck/back pain in 10%. At enrollment, patient analgesic regimens comprised 3 ± 1 unique medications, including 1 ± 1 opioids. After genomic analysis, 14/30 patients (47%) were identified as suboptimal metabolizers of ≥1 medications in their analgesic regimen. Of these patients, 93% were suboptimal metabolizers of their prescribed opioid analgesic. Nonetheless, pain scores were similar between optimal and suboptimal metabolizer groups.

Conclusions: This pilot study shows that a large proportion of the spine outpatient population may use pain medications for which they are suboptimal metabolizers. Further studies should assess whether these pharmacogenomic differences indicate differences in odds of receiving therapeutic benefit from surgery or if they can be used to generate more effective postoperative analgesic regimens.
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http://dx.doi.org/10.1016/j.wneu.2020.09.007DOI Listing
January 2021

Oxysterols as promising small molecules for bone tissue engineering: Systematic review.

World J Orthop 2020 Jul 18;11(7):328-344. Epub 2020 Jul 18.

Department of Neurosurgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States.

Background: Bone tissue engineering is an area of continued interest within orthopaedic surgery, as it promises to create implantable bone substitute materials that obviate the need for autologous bone graft. Recently, oxysterols - oxygenated derivatives of cholesterol - have been proposed as a novel class of osteoinductive small molecules for bone tissue engineering. Here, we present the first systematic review of the evidence describing the potential therapeutic utility of oxysterols for bone tissue engineering.

Aim: To systematically review the available literature examining the effect of oxysterols on bone formation.

Methods: We conducted a systematic review of the literature following PRISMA guidelines. Using the PubMed/MEDLINE, Embase, and Web of Science databases, we queried all publications in the English-language literature investigating the effect of oxysterols on bone formation. Articles were screened for eligibility using PICOS criteria and assessed for potential bias using an expanded version of the SYRCLE Risk of Bias assessment tool. All full-text articles examining the effect of oxysterols on bone formation were included. Extracted data included: Animal species, surgical/defect model, description of therapeutic and control treatments, and method for assessing bone growth. Primary outcome was fusion rate for spinal fusion models and percent bone regeneration for critical-sized defect models. Data were tabulated and described by both surgical/defect model and oxysterol employed. Additionally, data from all included studies were aggregated to posit the mechanism by which oxysterols may mediate bone formation.

Results: Our search identified 267 unique articles, of which 27 underwent full-text review. Thirteen studies (all preclinical) met our inclusion/exclusion criteria. Of the 13 included studies, 5 employed spinal fusion models, 2 employed critical-sized alveolar defect models, and 6 employed critical-sized calvarial defect models. Based upon SYRCLE criteria, the included studies were found to possess an overall "unclear risk of bias"; 54% of studies reported treatment randomization and 38% reported blinding at any level. Overall, seven unique oxysterols were evaluated: 20()-hydroxycholesterol, 22()-hydroxycholesterol, 22()-hydroxycholesterol, Oxy4/Oxy34, Oxy18, Oxy21/Oxy133, and Oxy49. All had statistically significant osteoinductive properties, with Oxy4/Oxy34, Oxy21/Oxy133, and Oxy49 showing a dose-dependent effect in some cases. In the eight studies that directly compared oxysterols to rhBMP-2-treated animals, similar rates of bone growth occurred in the two groups. Biochemical investigation of these effects suggests that they may be primarily mediated by direct activation of Smoothened in the Hedgehog signaling pathway.

Conclusion: Present preclinical evidence suggests oxysterols significantly augment bone formation. However, clinical trials are necessary to determine which have the greatest therapeutic potential for orthopaedic surgery patients.
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http://dx.doi.org/10.5312/wjo.v11.i7.328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7453739PMC
July 2020

Assessing underlying bone quality in spine surgery patients: a narrative review of dual-energy X-ray absorptiometry (DXA) and alternatives.

Spine J 2021 02 2;21(2):321-331. Epub 2020 Sep 2.

Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Electronic address:

Poor bone quality and low bone mineral density (BMD) have been previously tied to higher rates of postoperative mechanical complications in patients undergoing spinal fusion. These include higher rates of proximal junctional kyphosis, screw pullout, pseudoarthrosis, and interbody subsidence. For these reasons, accurate preoperative assessment of a patient's underlying bone quality is paramount for all elective procedures. Dual-energy X-ray absorptiometry (DXA) is currently considered to be the gold standard for assessing BMD. However, a growing body of research has suggested that in vivo assessments of BMD using DXA are inaccurate and have, at best, moderate correlations to postoperative mechanical complications. Consequently, there have been investigations into using alternative methods for assessing in vivo bone quality, including using computed tomography (CT) and magnetic resonance imaging (MRI) volumes that are commonly obtained as part of surgical evaluation. Here we review the data regarding the accuracy of DXA for the evaluation of spine bone quality and describe the alternative imaging modalities currently under investigation.
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http://dx.doi.org/10.1016/j.spinee.2020.08.020DOI Listing
February 2021

A novel predictive model of intraoperative blood loss in patients undergoing elective lumbar surgery for degenerative pathologies.

Spine J 2020 12 27;20(12):1976-1985. Epub 2020 Jun 27.

Department of Neurosurgery, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA. Electronic address:

Background Context: Intraoperative blood loss (IOBL) is unavoidable during surgery; however, high IOBL is associated with increased morbidity and increased risk for requiring allogenic blood transfusion, itself associated with poorer outcomes.

Purpose: Here we sought to develop and validate a predictive calculator for IOBL that could be used by surgeons to estimate likely blood loss.

Study Design/setting: Retrospective cohort.

Patient Sample: Series of consecutive patients who underwent elective lumbar spine surgery for degenerative pathologies over a 27-month period at a single tertiary care center.

Outcome Measures: Primary outcome was IOBL. Secondary outcome was the occurrence of "major intraoperative bleeding," defined as IOBL exceeding 1 L.

Methods: Charts of included patients were reviewed for medical comorbidities, preoperative laboratory data, surgical plan, and anesthesia records. Univariate linear regressions were performed to find significant predictors of IOBL, which were then subjected to a multivariate analysis to identify the final model. Model training was performed using 70% of the included cohort and external validation was performed using 30% of the cohort. Results of the model were deployed as a freely available online calculator.

Results: We identified 1,281 patients who met inclusion/exclusion criteria. Mean age was 60±15 years, mean Charlson Comorbidity score was 1.1±1.6, and 51.8% were male. There were no significant differences between the training and validation cohorts with regard to any of the demographic variables or intraoperative variables; tranexamic acid use and surgical invasiveness were also similar in both cohorts. Multivariate analysis identified body mass index (βₙ=7.14; 95% confidence interval [3.15, 11.13]; p<.001), surgical invasiveness (βₙ=29.18; [24.62, 33.74]; p<.001), tranexamic acid use (βₙ=-0.093; [-0.171, -0.014]; p=.02), and surgical duration (βₙ=2.13; [1.75, 2.51]; p<.001) as significant predictors of IOBL. The model had an overall fit of r=0.693 in the validation cohort. Construction of a receiver-operating curve for predicting major IOBL showed a C-statistic of 0.895 within the validation cohort.

Conclusion: Here we identify and validate a model for predicting IOBL in patients undergoing lumbar spine surgery. The model was a moderately strong predictor of absolute IOBL and was demonstrated to predict the occurrence of major IOBL with a high degree of accuracy. We propose it may have future utility when counseling patients about surgical morbidity and the probability of requiring transfusion.
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http://dx.doi.org/10.1016/j.spinee.2020.06.019DOI Listing
December 2020

Interventions to minimize blood loss and transfusion risk in spine surgery: A narrative review.

Clin Neurol Neurosurg 2020 09 18;196:106004. Epub 2020 Jun 18.

Department of Neurosurgery, Johns Hopkins School of Medicine, Baltimore, MD, 21287, United States. Electronic address:

Blood loss is an inevitable reality of spine surgery. Excessive loss is associated with increased morbidity and mortality and is frequently combated with allogeneic blood transfusions. Transfusions themselves are associated with increased morbidity, including circulatory overload, lung injury, and acute kidney injury. It is therefore incumbent upon the practicing spine surgeon to be aware of evidence-based interventions capable of reducing blood loss and the risk of transfusion. Here we review the available literature and make recommendation based upon the available evidence.
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http://dx.doi.org/10.1016/j.clineuro.2020.106004DOI Listing
September 2020

Vertebral bone quality score predicts fragility fractures independently of bone mineral density.

Spine J 2021 01 28;21(1):20-27. Epub 2020 May 28.

Department of Neurosurgery, Johns Hopkins University School of Medicine, 600 N. Wolfe St, Meyer 5-185A, Baltimore, MD 21287, USA. Electronic address:

Background: Current evidence suggests that dual-energy x-ray absorptiometry (DXA) scans, the conventional method defining osteoporosis, is underutilized and, when used, may underestimate patient risk for skeletal fragility. It has recently been suggested that other imaging modalities may better estimate bone quality, such as the magnetic resonance imaging (MRI)-based vertebral bone quality (VBQ) score which also may assess vertebral compression fracture risk in patients with spine metastases.

Purpose: To evaluate whether VBQ score is predictive of fragility fractures in a population with pre-existing low bone density and at high-risk for fracture.

Study Design/setting: Retrospective single-center cohort.

Patient Sample: Patients followed at a metabolic bone clinic for osteopenia and/or osteoporosis.

Outcome Measures: Radiographically-documented new-onset fragility fracture.

Methods: Patients with a DXA and MRI scans at the time of consultation and ≥2-year follow-up were included. Details were gathered about patient demographics, health history, current medication use, and serological studies of kidney function and bone turnover. For each patient, VBQ score was calculated using T1-weighted lumbar MRI images. Univariable and multivariable analyses were used to identify the independent predictors of a new fragility fracture. To support the construct validity of VBQ, patient VBQ scores were compared to those in a cohort of 45 healthy adults.

Results: Seventy-two (39.1%) study participants suffered fragility fractures, the occurrence of which was associated with higher VBQ score (3.50 vs. 3.01; p<.001), chronic glucocorticoid use (30.6% vs. 15.2%; p=.014), and a history of prior fragility fracture (36.1% vs. 21.4%; p=.030). Mean VBQ score across all patients in the study cohort was significantly higher than the mean VBQ score in the healthy controls (p<.001). In multivariable analysis, new-onset fracture was independently associated with history of prior fracture (OR=6.94; 95% confidence interval [2.48-19.40]; p<.001), higher VBQ score (OR=2.40 per point; [1.30-4.44]; p=.003), higher body mass index (OR=1.09 per kg/m²; [1.01-1.17]; p=.03), and chronic glucocorticoid use (OR=2.89; [1.03-8.17]; p=0.043). Notably, DXA bone mineral density (BMD) was not found to be significantly predictive of new-onset fractures in the multivariable analysis (p=.081).

Conclusions: Here we demonstrate the novel, MRI-derived VBQ score is both an independent predictor of fragility fracture in at-risk patients and a superior predictor of fracture risk than DXA-measured BMD. Given the frequency with which MRIs are obtained by patients undergoing spine surgery consultation, we believe the VBQ score could be a valuable tool for estimating bone quality in order to optimize the management of these patients.
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http://dx.doi.org/10.1016/j.spinee.2020.05.540DOI Listing
January 2021

Three-dimensional assessment of robot-assisted pedicle screw placement accuracy and instrumentation reliability based on a preplanned trajectory.

J Neurosurg Spine 2020 May 29:1-10. Epub 2020 May 29.

1Department of Neurosurgery, Johns Hopkins School of Medicine.

Objective: Robotic spine surgery systems are increasingly used in the US market. As this technology gains traction, however, it is necessary to identify mechanisms that assess its effectiveness and allow for its continued improvement. One such mechanism is the development of a new 3D grading system that can serve as the foundation for error-based learning in robot systems. Herein the authors attempted 1) to define a system of providing accuracy data along all three pedicle screw placement axes, that is, cephalocaudal, mediolateral, and screw long axes; and 2) to use the grading system to evaluate the mean accuracy of thoracolumbar pedicle screws placed using a single commercially available robotic system.

Methods: The authors retrospectively reviewed a prospectively maintained, IRB-approved database of patients at a single tertiary care center who had undergone instrumented fusion of the thoracic or lumbosacral spine using robotic assistance. Patients with preoperatively planned screw trajectories and postoperative CT studies were included in the final analysis. Screw accuracy was measured as the net deviation of the planned trajectory from the actual screw trajectory in the mediolateral, cephalocaudal, and screw long axes.

Results: The authors identified 47 patients, 51% male, whose pedicles had been instrumented with a total of 254 screws (63 thoracic, 191 lumbosacral). The patients had a mean age of 61.1 years and a mean BMI of 30.0 kg/m2. The mean screw tip accuracies were 1.3 ± 1.3 mm, 1.2 ± 1.1 mm, and 2.6 ± 2.2 mm in the mediolateral, cephalocaudal, and screw long axes, respectively, for a net linear deviation of 3.6 ± 2.3 mm and net angular deviation of 3.6° ± 2.8°. According to the Gertzbein-Robbins grading system, 184 screws (72%) were classified as grade A and 70 screws (28%) as grade B. Placement of 100% of the screws was clinically acceptable.

Conclusions: The accuracy of the discussed robotic spine system is similar to that described for other surgical systems. Additionally, the authors outline a new method of grading screw placement accuracy that measures deviation in all three relevant axes. This grading system could provide the error signal necessary for unsupervised machine learning by robotic systems, which would in turn support continued improvement in instrumentation placement accuracy.
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http://dx.doi.org/10.3171/2020.3.SPINE20208DOI Listing
May 2020

Vertebral Bone Quality Score and Postoperative Lumbar Lordosis Associated with Need for Reoperation After Lumbar Fusion.

World Neurosurg 2020 08 13;140:e247-e252. Epub 2020 May 13.

Department of Neurosurgery, Johns Hopkins School of Medicine, Baltimore, Maryland, USA. Electronic address:

Background: Poor bone quality is a known risk factor for hardware failure and adjacent segment disease after lumbar fusion. One new method of analyzing bone quality is the vertebral bone quality (VBQ) score, which can be obtained from preoperative lumbar magnetic resonance imaging (MRI) scans. We decided to evaluate whether patients' VBQ scores were associated with reoperation after lumbar fusion.

Methods: We queried records of patients who underwent elective lumbar fusion for degenerative conditions between 2012 and 2017. Patients who required reoperations after lumbar fusions because of symptomatic hardware failure or adjacent segment disease were combined into a case group and compared with a matched control group.

Results: Of the 46 patients who underwent elective lumbar fusions and required reoperation, 30 met the inclusion criteria. A 2:1 control group of 60 individually age-, body mass index-, and sex-matched patients who did not require reoperation was then created. The reoperation group had significantly lower degrees of postoperative lumbar lordosis. There were no significant differences regarding other spinopelvic parameters, adjacent Pfirrmann scores, or dual energy x-ray absorptiometry (DXA) T scores. There was, however, a significant difference in VBQ scores between the groups, with the reoperation group having a higher VBQ score.

Conclusions: This study found that bone quality, according to the VBQ score rather than the DXA T score, is an important risk factor for reoperation after lumbar fusion surgery. Therefore, this MRI-based tool may be used to assist surgeons in preoperative planning for spine surgeries with the goal of reducing the risk of requiring reoperation.
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http://dx.doi.org/10.1016/j.wneu.2020.05.020DOI Listing
August 2020

Incidental durotomy: predictive risk model and external validation of natural language process identification algorithm.

J Neurosurg Spine 2020 May 1:1-7. Epub 2020 May 1.

1Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland; and.

Objective: Incidental durotomy is a common complication of elective lumbar spine surgery seen in up to 11% of cases. Prior studies have suggested patient age and body habitus along with a history of prior surgery as being associated with an increased risk of dural tear. To date, no calculator has been developed for quantifying risk. Here, the authors' aim was to identify independent predictors of incidental durotomy, present a novel predictive calculator, and externally validate a novel method to identify incidental durotomies using natural language processing (NLP).

Methods: The authors retrospectively reviewed all patients who underwent elective lumbar spine procedures at a tertiary academic hospital for degenerative pathologies between July 2016 and November 2018. Data were collected regarding surgical details, patient demographic information, and patient medical comorbidities. The primary outcome was incidental durotomy, which was identified both through manual extraction and the NLP algorithm. Multivariable logistic regression was used to identify independent predictors of incidental durotomy. Bootstrapping was then employed to estimate optimism in the model, which was corrected for; this model was converted to a calculator and deployed online.

Results: Of the 1279 elective lumbar surgery patients included in this study, incidental durotomy occurred in 108 (8.4%). Risk factors for incidental durotomy on multivariable logistic regression were increased surgical duration, older age, revision versus index surgery, and case starts after 4 pm. This model had an area under curve (AUC) of 0.73 in predicting incidental durotomies. The previously established NLP method was used to identify cases of incidental durotomy, of which it demonstrated excellent discrimination (AUC 0.97).

Conclusions: Using multivariable analysis, the authors found that increased surgical duration, older patient age, cases started after 4 pm, and a history of prior spine surgery are all independent positive predictors of incidental durotomy in patients undergoing elective lumbar surgery. Additionally, the authors put forth the first version of a clinical calculator for durotomy risk that could be used prospectively by spine surgeons when counseling patients about their surgical risk. Lastly, the authors presented an external validation of an NLP algorithm used to identify incidental durotomies through the review of free-text operative notes. The authors believe that these tools can aid clinicians and researchers in their efforts to prevent this costly complication in spine surgery.
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http://dx.doi.org/10.3171/2020.2.SPINE20127DOI Listing
May 2020

The effect of bioactive glasses on spinal fusion: A cross-disciplinary systematic review and meta-analysis of the preclinical and clinical data.

J Clin Neurosci 2020 Aug 21;78:34-46. Epub 2020 Apr 21.

Department of Neurosurgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address:

Pseudarthrosis following spinal fusion is correlated with poorer patient outcomes and consequently is an area of continued interest within spinal research. Recently, bioactive glasses have been proposed as a means of augmenting fusion rates. Here, we present the first systematic review and meta-analysis of the existing preclinical and clinical literature on the effect of bioactive glasses on spinal fusion. Using the MEDLINE, Embase, and Web of Science databases, we queried all publications in the English-language literature examining the effect of bioactive glasses on spinal fusion. The primary endpoint was fusion rate at last follow-up and the secondary endpoint for clinical studies was the rate of deep wound infection. Random-effects meta-analyses were performed independently for the preclinical and clinical data. Twelve preclinical studies (267 animals) and 12 clinical studies (396 patients) evaluating a total of twelve unique bioactive glass formulations were included. Across clinical studies, fusion was seen in 84% treated with bioactive glass. On sub-analysis, fusion rates were similar for standalone autograft (91.6%) and bioactive glass-local autograft mixtures (89.6%). Standalone bioactive glass substrates produced inferior fusion rates relative to autograft alone (33.6% vs. 98.8%; OR 0.01, p < 0.02). Rates of deep wound infection did not differ between the bioactive glass and autograft groups (3.1%). The preclinical data similarly showed comparable rates of fusion between autograft and bioactive glass-treated animals. The available data suggest that bioactive glass-autograft mixtures confer similar rates of spinal fusion relative to standalone autograft without altering the risk of deep wound infection.
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http://dx.doi.org/10.1016/j.jocn.2020.04.035DOI Listing
August 2020
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