Publications by authors named "Raphaele Charest-Morin"

30 Publications

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Proteomic Portraits Reveal Evolutionarily Conserved and Divergent Responses to Spinal Cord Injury.

Mol Cell Proteomics 2021 Jun 12;20:100096. Epub 2021 Jun 12.

Division of Neurosurgery, University of British Columbia, Vancouver, British Columbia, Canada.

Despite the emergence of promising therapeutic approaches in preclinical studies, the failure of large-scale clinical trials leaves clinicians without effective treatments for acute spinal cord injury (SCI). These trials are hindered by their reliance on detailed neurological examinations to establish outcomes, which inflate the time and resources required for completion. Moreover, therapeutic development takes place in animal models whose relevance to human injury remains unclear. Here, we address these challenges through targeted proteomic analyses of cerebrospinal fluid and serum samples from 111 patients with acute SCI and, in parallel, a large animal (porcine) model of SCI. We develop protein biomarkers of injury severity and recovery, including a prognostic model of neurological improvement at 6 months with an area under the receiver operating characteristic curve of 0.91, and validate these in an independent cohort. Through cross-species proteomic analyses, we dissect evolutionarily conserved and divergent aspects of the SCI response and establish the cerebrospinal fluid abundance of glial fibrillary acidic protein as a biochemical outcome measure in both humans and pigs. Our work opens up new avenues to catalyze translation by facilitating the evaluation of novel SCI therapies, while also providing a resource from which to direct future preclinical efforts.
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http://dx.doi.org/10.1016/j.mcpro.2021.100096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260874PMC
June 2021

Feasibility of achieving planned surgical margins in primary spine tumor: a PTRON study.

Neurosurg Focus 2021 05;50(5):E16

1Combined Neurosurgical and Orthopaedic Spine Program, University of British Columbia, Vancouver, British Columbia, Canada.

Objective: Oncological resection of primary spine tumors is associated with lower recurrence rates. However, even in the most experienced hands, the execution of a meticulously drafted plan sometimes fails. The objectives of this study were to determine how successful surgical teams are at achieving planned surgical margins and how successful surgeons are in intraoperatively assessing tumor margins. The secondary objective was to identify factors associated with successful execution of planned resection.

Methods: The Primary Tumor Research and Outcomes Network (PTRON) is a multicenter international prospective registry for the management of primary tumors of the spine. Using this registry, the authors compared 1) the planned surgical margin and 2) the intraoperative assessment of the margin by the surgeon with the postoperative assessment of the margin by the pathologist. Univariate analysis was used to assess whether factors such as histology, size, location, previous radiotherapy, and revision surgery were associated with successful execution of the planned margins.

Results: Three hundred patients were included. The surgical plan was successfully achieved in 224 (74.7%) patients. The surgeon correctly assessed the intraoperative margins, as reported in the final assessment by the pathologist, in 239 (79.7%) patients. On univariate analysis, no factor had a statistically significant influence on successful achievement of planned margins.

Conclusions: In high-volume cancer centers around the world, planned surgical margins can be achieved in approximately 75% of cases. The morbidity of the proposed intervention must be balanced with the expected success rate in order to optimize patient management and surgical decision-making.
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http://dx.doi.org/10.3171/2021.2.FOCUS201091DOI Listing
May 2021

Characterization of Cerebrospinal Fluid Ubiquitin C-Terminal Hydrolase L1 (UCH-L1) as a Biomarker of Human Acute Traumatic Spinal Cord Injury.

J Neurotrauma 2021 May 3. Epub 2021 May 3.

International Collaboration on Repair Discoveries (ICORD), Blusson Spinal Cord Center, University of British Columbia, Vancouver, British Columbia, Canada.

A major obstacle for translational research in acute spinal cord injury (SCI) is the lack of biomarkers that can objectively stratify injury severity and predict outcome. Ubiquitin C-terminal hydrolase L1 (UCH-L1) is a neuron-specific enzyme that shows promise as a diagnostic biomarker in traumatic brain injury (TBI), but has not been studied in SCI. In this study, cerebrospinal fluid (CSF) and serum samples were collected over the first 72-96 h post-injury from 32 acute SCI patients who were followed prospectively to determine neurological outcomes at 6 months post-injury. UCH-L1 concentration was measured using the Quanterix Simoa platform (Quanterix, Billerica, MA) and correlated to injury severity, time, and neurological recovery. We found that CSF UCH-L1 was significantly elevated by 10- to 100-fold over laminectomy controls in an injury severity- and time-dependent manner. Twenty-four-hour post-injury CSF UCH-L1 concentrations distinguished between American Spinal Injury Association Impairment Scale (AIS) A and AIS B, and AIS A and AIS C patients in the acute setting, and predicted who would remain "motor complete" (AIS A/B) at 6 months with a sensitivity of 100% and a specificity of 86%. AIS A patients who did not improve their AIS grade at 6 months post-injury were characterized by sustained elevations in CSF UCH-L1 up to 96 h. Similarly, the failure to gain >8 points on the total motor score at 6 months post-injury was associated with higher 24-h CSF UCH-L1. Unfortunately, serum UCH-L1 levels were not informative about injury severity or outcome. In conclusion, CSF UCH-L1 in acute SCI shows promise as a biomarker to reflect injury severity and predict outcome.
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http://dx.doi.org/10.1089/neu.2020.7352DOI Listing
May 2021

Lumbar degenerative spondylolisthesis: factors associated with the decision to fuse.

Spine J 2021 05 26;21(5):821-828. Epub 2020 Nov 26.

Division of Orthopaedics, Department of Surgery, Western University /London Health Sciences Centre, London, Ontario, Canada; Lawson Health Research Institute /London Health Sciences Centre, E4-120, 800 Commissioners Road, East, London, Ontario N6A 4G5, Canada. Electronic address:

Background Context: The indication to perform a fusion and decompression surgery as opposed to decompression alone for lumbar degenerative spondylolisthesis (LDS) remains controversial. A variety of factors are considered when deciding on whether to fuse, including patient demographics, radiographic parameters, and symptom presentation. Likely surgeon preference has an important influence as well.

Purpose: The aim of this study was to assess factors associated with the decision of a Canadian academic spine surgeon to perform a fusion for LDS.

Study Design/setting: This study is a retrospective analysis of patients prospectively enrolled in a multicenter Canadian study that was designed to evaluate the assessment and surgical management of LDS.

Patient Sample: Inclusion criteria were patients with: radiographic evidence of LDS and neurogenic claudication or radicular pain, undergoing posterior decompression alone or posterior decompression and fusion, performed in one of seven, participating academic centers from 2015 to 2019.

Outcome Measures: Patient demographics, patient-rated outcome measures (Oswestry Disability Index [ODI], numberical rating scale back pain and leg pain, SF-12), and imaging parameters were recorded in the Canadian Spine Outcomes Research Network (CSORN) database. Surgeon factors were retrieved by survey of each participating surgeon and then linked to their specific patients within the database.

Methods: Univariate analysis was used to compare patient characteristics, imaging measures, and surgeon variables between those that had a fusion and those that had decompression alone. Multivariate backward logistic regression was used to identify the best combination of factors associated with the decision to perform a fusion.

Results: This study includes 241 consecutively enrolled patients receiving surgery from 11 surgeons at 7 sites. Patients that had a fusion were younger (65.3±8.3 vs. 68.6±9.7 years, p=.012), had worse ODI scores (45.9±14.7 vs. 40.2±13.5, p=.007), a smaller average disc height (6.1±2.7 vs. 8.0±7.3 mm, p=.005), were more likely to have grade II spondylolisthesis (31% vs. 14%, p=.008), facet distraction (34% vs. 60%, p=.034), and a nonlordotic disc angle (26% vs. 17%, p=.038). The rate of fusion varied by individual surgeon and practice location (p<.001, respectively). Surgeons that were fellowship trained in Canada more frequently fused than those who fellowship trained outside of Canada (76% vs. 57%, p=.027). Surgeons on salary fused more frequently than surgeons remunerated by fee-for-service (80% vs. 64%, p=.004). In the multivariate analysis the clinical factors associated with an increased odds of fusion were decreasing age, decreasing disc height, and increasing ODI score; the radiographic factors were grade II spondylolisthesis and neutral or kyphotic standing disc type; and the surgeon factors were fellowship location, renumeration type and practice region. The odds of having a fusion surgery was more than two times greater for patients with a grade II spondylolisthesis or neutral and/or kyphotic standing disc type (opposed to lordotic standing disc type). Patients whose surgeon completed their fellowship in Canada, or whose surgeon was salaried (opposed to fee-for-service), or whose surgeon practiced in western Canada had twice the odds of having fusion surgery.

Conclusions: The decision to perform a fusion in addition to decompression for LDS is multifactorial. Although patient and radiographic parameters are important in the decision-making process, multiple surgeon factors are associated with the preference of a Canadian spine surgeon to perform a fusion for LDS. Future work is necessary to decrease treatment variability between surgeons and help facilitate the implementation of evidence-based decision making.
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http://dx.doi.org/10.1016/j.spinee.2020.11.010DOI Listing
May 2021

Back pain in surgically treated degenerative lumbar spondylolisthesis: what can we tell our patients?

Spine J 2020 12 19;20(12):1940-1947. Epub 2020 Aug 19.

Combined Neurosurgery and Orthopaedic Spine Program, University of British Columbia, Vancouver, British Columbia, Canada.

Of Background Data: Surgery for degenerative lumbar spondylolisthesis (DLS) has traditionally been indicated for patients with neurogenic claudication. Surgery improves patients' disability and lower extremity symptoms, but less is known about the impact on back pain.

Objective: To evaluate changes in back pain after surgery and identify factors associated with these changes in surgically-treated DLS.

Study Design: Retrospective review of prospectively collected data.

Methods: There were 486 consecutive patients with surgically-treated DLS who were enrolled in the Canadian Spine Outcomes Research Network prospective registry and identified for this study. Patients had demographic data, clinical information, disability (Oswestry Disability Index), and back pain rating scores collected prospectively at baseline, and 12 months follow-up RESULTS: Of the 486 DLS patients, 376 (77.3%) were successfully followed at 12 months. Mean age at baseline was 66.7 (standard deviation [SD] 9.2) years old, and 63% were female. Back pain improved significantly at 12 months, compared with baseline (p<.001). Improvement in Numeric Rating Scale (NRS)-back pain ratings was on average 2.97 (SD 2.5) points at one year and clinically significant improvement in back pain was observed in 75% of patients (minimal clinically important difference (MCID) NRS-Pain 1.2 points). Multivariable logistic regression revealed five factors associated with meeting MCID NRS-back pain at 12 month follow up: higher baseline back pain, better baseline physical function (higher SF-12 Physical Component Score), symptoms duration less than 1 to 2 years, and having no intraoperative adverse events.

Conclusions: Back pain improved significantly for patients treated surgically for DLS at 1-year follow-up.
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http://dx.doi.org/10.1016/j.spinee.2020.08.009DOI Listing
December 2020

Effectiveness of silver alloy-coated silicone urinary catheters in patients with acute traumatic cervical spinal cord injury: Results of a quality improvement initiative.

J Clin Neurosci 2020 Aug 11;78:135-138. Epub 2020 Jun 11.

Combined Neurosurgical and Orthopaedic Spine Program, Department of Orthopaedic Surgery, University of British Columbia, Vancouver Spine Surgery Institute, Blusson Spinal Cord Centre, 818 West 10th Avenue, Vancouver, BC V5Z 1M9, Canada. Electronic address:

Patients with acute traumatic cervical spinal cord injury (ATCSCI) have an increased risk of catheter-associated urinary tract infection (CAUTI). The effectiveness of silver alloy-coated silicone urinary catheters (SACC) in preventing CAUTI in ATCSCI is unknown and was the objective of this study. We performed a quality improvement initiative in an attempt to reduce CAUTI in patients undergoing spine surgery at a single quaternary center. Prior to July 2015, all patients received a latex indwelling catheter (LIC). All patients with ATCSCI with limited hand function (AIS A,B, or C) received a SACC. Incidence of CAUTI, microbiology, duration of infection, antibiotic susceptibility, and catheter-associated adverse events were recorded prospectively. We studied 3081 consecutive patients over the three years, of whom 302 (9.8%) had ATCSCI; 63% of ATCSCI patients were ASIA Impairment Scale (AIS) A or B. The overall rate of CAUTI was 19% (585/3081), and was 38% (116/302) in patients with ATCSCI. Of 178 ATCSCI patients with LIC, 100 (56%) developed a CAUTI compared with 28 of 124 (23%) patients with SACC (p < 0.05). Poly-microbial and gram-positive infection was more common in LIC than in SACC (p < 0.05). Median duration of infection was 9 days in SACC group and 12 days in LIC group (p = 0.08). Resistance to trimethoprim (p < 0.001) and ciprofloxacin (p < 0.05) were more common in LIC group. There was no difference in catheter-associated adverse events or length of stay between the groups. This quality improvement initiative illustrates the effectiveness of antiseptic silver alloy-coated silicone urinary catheters in patients with ATCSCI. In our population, the use of SACC reduces the incidence and the complexity of CAUTI.
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http://dx.doi.org/10.1016/j.jocn.2020.05.036DOI Listing
August 2020

Correction: The influence of neurological examination timing within hours after acute traumatic spinal cord injuries: an observational study.

Spinal Cord 2020 Feb;58(2):255

Division of Spine, University of British Columbia, 6400-818 West 10th Avenue, Vancouver, BC, V5Z 1M9, Canada.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41393-020-0413-yDOI Listing
February 2020

Metastatic Spine Disease: Should Patients With Short Life Expectancy Be Denied Surgical Care? An International Retrospective Cohort Study.

Neurosurgery 2020 08;87(2):303-311

Division of Spine Surgery, Department of Orthopaedics, Vancouver General Hospital, University of British Columbia, Vancouver, Canada.

Background: Despite our inability to accurately predict survival in many cancer patients, a life expectancy of at least 3 mo is historically necessary to be considered for surgical treatment of spinal metastases.

Objective: To compare health-related quality of life (HRQOL) in patients surviving <3 mo after surgical treatment to patients surviving >3 mo to assess the validity of this inclusion criteria.

Methods: Patients who underwent surgery for spinal metastases between August 2013 and May 2017 were retrospectively identified from an international cohort study. HRQOL was evaluated using generic and disease-specific outcome tools at baseline and at 6 and 12 wk postsurgery. The primary outcome was the HRQOL at 6 wk post-treatment measured by the Spine Oncology Study Group Outcomes Questionnaire (SOSGOQ).

Results: A total of 253 patients were included: 40 patients died within the first 3 mo after surgery and 213 patients survived more than 3 mo. Patients surviving <3 mo after surgery presented with lower baseline performance status. Adjusted analyses for baseline performance status did not reveal a significant difference in HRQOL between both groups at 6 wk post-treatment. No significant difference in patient satisfaction at 6 wk with regard to their treatment could be detected between both groups.

Conclusion: When controlled for baseline performance status, quality of life 6 wk after surgery for spinal metastasis is independent of survival. To optimize improvement in HRQOL for this patient population, baseline performance status should take priority over expected survival in the surgical decision-making process.
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http://dx.doi.org/10.1093/neuros/nyz472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360875PMC
August 2020

The influence of neurological examination timing within hours after acute traumatic spinal cord injuries: an observational study.

Spinal Cord 2020 Feb 8;58(2):247-254. Epub 2019 Oct 8.

Division of Spine, University of British Columbia, 6400-818 West 10th Avenue, Vancouver, BC, V5Z 1M9, Canada.

Study Design: Cohort study.

Objectives: It is widely accepted that the prediction of long-term neurologic outcome after traumatic spinal cord injury (SCI) can be done more accurately with neurological examinations conducted days to weeks post injury. However, modern clinical trials of neuroprotective interventions often require patients be examined and enrolled within hours. Our objective was to determine whether variability in timing of neurological examinations within 48 h after SCI is associated with differences in observations of follow-up neurologic recovery.

Setting: Level I trauma hospital.

Methods: An observational analysis testing for differences in AIS conversion rates and changes in total motor scores by neurological examination timing, controlling for potential confounders with multivariate stepwise regression.

Results: We included 85 patients, whose mean times from injury to baseline and follow-up examinations were 11.8 h (SD 9.8) and 208.2 days (SD 75.2), respectively. AIS conversion by 1+ grade was significantly more likely in patients examined at ≤4 h in comparison with later examination (78% versus 47%, RR = 1.66, p = 0.04), even after controlling for timing of surgery, age, and sex (OR 5.0, 95% CI 1.1-10, p = 0.04). We failed to identify any statistically significant associations for total motor score recovery in unadjusted or adjusted analyses.

Conclusions: AIS grade conversion was significantly more likely in those examined ≤4 h of injury; the effect of timing on motor scores remains uncertain. Variability in neurological examination timing within hours after acute traumatic SCI may influence observations of long-term neurological recovery, which could introduce bias or lead to errors in interpretation of studies of therapeutic interventions.
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http://dx.doi.org/10.1038/s41393-019-0359-0DOI Listing
February 2020

Perioperative adverse events following surgery for primary bone tumors of the spine and en bloc resection for metastases.

J Neurosurg Spine 2019 Sep 27:1-8. Epub 2019 Sep 27.

1Combined Neurosurgical and Orthopedic Spine Program, Department of Orthopedic Surgery, and.

Objective: Surgical treatment of primary bone tumors of the spine and en bloc resection for isolated metastases are complex and challenging. Operative care is fraught with complications, though the true incidence and predictors of adverse events (AEs), length of stay (LOS), and mortality in this population remain poorly understood. The primary objective of this study was to describe the incidence and predictors of perioperative AEs in these patients. Secondary objectives included the determination of the incidence and predictors of admission to the intensive care unit (ICU), unanticipated reoperation during the same admission, hospital LOS, and mortality.

Methods: In this retrospective analysis of prospectively collected data, the authors included consecutive patients at a single quaternary care referral center (January 1, 2009, to September 30, 2018) who underwent either surgery for a primary bone tumor of the spine or an en bloc resection for an isolated spinal metastasis. Information on perioperative AEs, demographic data, primary tumor histology, neurological status, surgical variables, pathological margins, Enneking appropriateness, LOS, ICU stay, reoperation during the same admission period, and in-hospital mortality was collected prospectively in the institutional database. The modified frailty score was extracted retrospectively.

Results: One hundred thirteen patients met the inclusion criteria: 98 with primary bone tumors and 15 with isolated metastases. The cohort was 59% male, and the mean age was 49 years (SD 19 years). Overall, 79% of the patients experienced at least 1 AE. The median number of AEs per patient was 2 (IQR 0-4 AEs), and the median LOS was 16 days (IQR 9-32 days). No in-hospital deaths occurred in the cohort. Thirty-two patients (28%) required an ICU stay and 19% underwent an unanticipated second surgery during their admission. A longer surgical duration was associated with a higher likelihood of AEs (OR 1.21/hour, 95% CI 1.06-1.37, p = 0.005), longer ICU stay (OR 1.35/hour, 95% CI 1 1.20-1.52, p < 0.001), and reoperation (OR 1.001/hour, 95% CI 1.0003-1.003, p = 0.012). Longer hospital LOS was independently predicted by older age, female sex, upper cervical and sacral location of the tumor, surgical duration, preoperative neurological deficit, presence of AEs, and higher modified frailty index score.

Conclusions: Surgeries for primary bone tumors and en bloc resection for metastatic tumors are associated with a high incidence of perioperative AEs. Surgical duration predicts complications, reoperation, LOS, and ICU stay.
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http://dx.doi.org/10.3171/2019.6.SPINE19587DOI Listing
September 2019

Sarcopenia, but not frailty, predicts early mortality and adverse events after emergent surgery for metastatic disease of the spine.

Spine J 2020 01 1;20(1):22-31. Epub 2019 Sep 1.

Vancouver General Hospital, Vancouver Spine Surgery Institute, 818 west 10th Avenue, Vancouver, British Columbia, V5Z 1M9 Canada.

Background Context: Frailty and sarcopenia variably predict adverse events (AEs) in a number of surgical populations.

Purpose: The aim of this study was to investigate the ability of frailty and sarcopenia to independently predict early mortality and AEs following urgent surgery for metastatic disease of the spine.

Study Design: A single institution, retrospective cohort study.

Patient Sample: One hundred eight patients undergoing urgent surgery for spinal metastases from 2009 to 2015.

Outcome Measures: The incidence of AEs including 1- and 3-month mortality.

Methods: Sarcopenia was defined using the L3 Total Psoas Area/Vertebral body Area (L3-TPA/VB) technique on CT. The modified Frailty Index (mFI), Metastatic Frailty Index (MSTFI) and the Bollen prognostic scales were calculated for each patient. Additional data included demographics, tumor type and burden, neurological status, the extent of surgical treatment and the use of radiation-therapy. Spearman correlation test, logistic regression and Kaplan-Meier were used to study the relation between the outcomes measures and potential predictors (L3-TPA/VB, MSTFI, mFI, and the Bollen prognostic scales).

Results: Eighty-five percent of patients had at least one acute AE. Sarcopenia predicted the occurrence of at least one postop AE (L3-TPA/VB, 1.07±0.40 vs. 1.25±0.52; p=.031). Sarcopenia (L3-TPA/VB) and the degree of neurological impairment were predictive of postoperative AE but MFI or MSTFI were not. Sarcopenia predicted 3-month mortality, independent of primary tumor type (L3-TPA/VB: 0.86±0.27 vs. 1.12±0.41; p<.001). Kaplan-Meyer analysis showed L3-TPA/VB and the Bollen Scale to significantly discriminate patient survival.

Conclusions: Sarcopenia, easily measured by the L3-TPA/VB on conventional CT, predicts both early postoperative mortality and adverse events in patients undergoing urgent surgery for spinal metastasis, thus providing a practical tool for timely therapeutic decision-making in this complex patient population.
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http://dx.doi.org/10.1016/j.spinee.2019.08.012DOI Listing
January 2020

Empirical targets for acute hemodynamic management of individuals with spinal cord injury.

Neurology 2019 09 13;93(12):e1205-e1211. Epub 2019 Aug 13.

From the International Collaboration on Repair Discoveries (J.W.S., C.R.W., B.K.K.); MD/PhD Training Program (J.W.S.), School of Kinesiology (C.R.W.), and Department of Orthopaedics (R.C.-M., J.S., T.A., S. Paquette, N.D., C.G.F., M.F.D.), University of British Columbia; Vancouver Spine Program (L.M.B., A.T., L.R.), Vancouver General Hospital, British Columbia; Department of Surgery (J.-M.M.-T., S. Parent), Hôpital du Sacré-Coeur de Montréal, and Chu Sainte-Justine (S.C.), Department of Surgery, Université de Montréal, Quebec; Division of Orthopaedic Surgery (C.B.), London Health Sciences Centre, University of Western Ontario, Canada; Department of Neurological Surgery (S.D.), University of California, San Francisco; Vancouver Spine Surgery Institute (R.C.-M., J.S., T.A., S. Paquette, N.D., C.G.F., M.F.D., B.K.K.); and Division of Neurosurgery (B.K.K.), University of British Columbia, Blusson Spinal Cord Centre, Vancouver, Canada.

Objective: To determine the hemodynamic conditions associated with optimal neurologic improvement in individuals with acute traumatic spinal cord injury (SCI) who had lumbar intrathecal catheters placed to measure CSF pressure (CSFP).

Methods: Ninety-two individuals with acute SCI were enrolled in this multicenter prospective observational clinical trial. We monitored mean arterial pressure (MAP) and CSFP during the first week after injury and assessed neurologic function at baseline and 6 months after injury. We used relative risk iterations to determine transition points at which the likelihood of either improving neurologically or remaining unchanged neurologically was equivalent. These transition points guided our analyses in which we examined the linear relationships between time spent within target hemodynamic ranges (i.e., clinical adherence) and neurologic recovery.

Results: Relative risk transition points for CSFP, MAP, and spinal cord perfusion pressure (SCPP) were linearly associated with neurologic improvement and directed the identification of key hemodynamic target ranges. Clinical adherence to the target ranges was positively and linearly related to improved neurologic outcomes. Adherence to SCPP targets, not MAP targets, was the best indicator of improved neurologic recovery, which occurred with SCPP targets of 60 to 65 mm Hg. Failing to maintain the SCPP within the target ranges was an important detrimental factor in neurologic recovery, particularly if the target range is set lower.

Conclusion: We provide an empirical, data-driven approach to aid institutions in setting hemodynamic management targets that accept the real-life challenges of adherence to specific targets. Our results provide a framework to guide the development of widespread institutional management guidelines for acute traumatic SCI.
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http://dx.doi.org/10.1212/WNL.0000000000008125DOI Listing
September 2019

Effect of Frailty on Outcome after Traumatic Spinal Cord Injury.

J Neurotrauma 2020 03 8;37(6):839-845. Epub 2019 Nov 8.

Vancouver Spine Surgery Institute, Department of Orthopaedics, University of British Columbia, Vancouver, British Columbia, Canada.

Frailty negatively affects outcome in elective spine surgery populations. This study sought to determine the effect of frailty on patient outcome after traumatic spinal cord injury (tSCI). Patients with tSCI were identified from our prospectively collected database from 2004 to 2016. We examined effect of patient age, admission Total Motor Score (TMS), and Modified Frailty Index (mFI) on adverse events (AEs), acute length of stay (LOS), in-hospital mortality, and discharge destination (home vs. other). Subgroup analysis (for three age groups: <60, 61-75, and 76+ years), and multi-variable analysis was performed to investigate the impact of age, TMS, and mFI on outcome. For the 634 patients, the mean age was 50.3 years, 77% were male, and falls were the main cause of injury (46.5%). On bivariate analysis, mFI, age at injury, and TMS were predictors of AEs, acute LOS, and in-hospital mortality. After statistical adjustment, mFI was a predictor of LOS ( = 0.0375), but not of AEs ( = 0.1428) or in-hospital mortality ( = 0.1245). In patients <60 years of age, mFI predicted number of AEs, acute LOS, and in-hospital mortality. In those aged 61-75, TMS predicted AEs, LOS, and mortality. In those 76+ years of age, mFI no longer predicted outcome. Age, mFI, and TMS on admission are important determinants of outcome in patients with tSCI. mFI predicts outcomes in those <75 years of age only. The inter-relationship of advanced age and decreased physiological reserve is complex in acute tSCI, warranting further study. Identifying frailty in younger patients with tSCI may be useful for peri-operative optimization, risk stratification, and patient counseling.
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http://dx.doi.org/10.1089/neu.2019.6581DOI Listing
March 2020

Clinical presentation, management and outcomes of sacral metastases: a multicenter, retrospective cohort study.

Ann Transl Med 2019 May;7(10):214

Department of Orthopaedics, Division of Spine, University of British Columbia and Vancouver General Hospital, Vancouver, BC, Canada.

Background: Sacral metastases are rare and literature regarding their management is sparse. This multicenter, prospective, observational study aimed to determine health related-quality of life (HRQOL) and pain in patients treated for sacral metastases with surgery and/or radiation therapy (RT). The secondary objectives were to describe the adverse event (AE) profile and change in neurologic function in this population.

Methods: Twenty-three patients presenting with symptomatic sacral metastases were identified from the Epidemiology, Process and Outcomes of Spine Oncology (EPOSO) dataset, a prospective multicenter study on spinal metastases. Patients requiring surgery and/or RT between August 2013 and February 2017 were prospectively enrolled. HRQOL, assessed by the Spine Oncology Study Group Outcomes Questionnaire (SOSGOQv2.0), the Short Form-36 version 2 (SF-36v2), and the EuroQol-5Dimension (EQ-5D) was documented at baseline, 6 weeks, 3 and 6 months post-treatment. Pain numeric rating scale (NRS), AEs, lower extremities motor score (ASIA), and bowel and bladder function were also recorded.

Results: Eight patients underwent surgery ± RT and 15 patients underwent RT alone. Mean age was 59.3 (SD 11.7) years and 13 patients were female. At 6 months, 3 (37.5%) surgical patients and 2 (13.3%) RT patients were deceased. There was a trend showing that surgical patients had worse baseline HRQOL and pain. Pain NRS, EQ-5D, SOSGOQv2.0, and the mental component of the SF-36v2 showed improvement, irrespective of treatment (P>0.05). Ten AEs occurred in the surgical cohort, dominated by wound complications (n=3). Bowel and bladder function improved at 6 weeks in both groups.

Conclusions: Surgical treatment and RT are both valid treatment options for symptomatic sacral metastases. Improvement in HRQOL can be expected with an acceptable AE rate.
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http://dx.doi.org/10.21037/atm.2019.04.88DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6595205PMC
May 2019

Treatment of Mild Cervical Myelopathy: Factors Associated With Decision for Surgical Intervention.

Spine (Phila Pa 1976) 2019 Nov;44(22):1606-1612

Combined Neurosurgery and Orthopaedic Spine Program, University of British Columbia, Vancouver, British Columbia.

Study Design: Prospective Cohort OBJECTIVE.: The aim of this study was to evaluate which demographic, clinical, or radiographic factors are associated with selection for surgical intervention in patients with mild cervical spondylotic myelopathy (CSM).

Summary Of Background Data: Surgery has not been shown superior to best conservative management in mild CSM comparative studies; trials of conservative management represent an acceptable alternative to surgical decompression. It is unknown what patients benefit from surgery.

Methods: This is a prospective study of patients with mild CSM, defined as modified Japanese Orthopaedic Association Score (mJOA) ≥15. Patients were recruited from seven sites contributing to the Canadian Spine Outcomes Research Network. Demographic, clinical, radiographic and health related quality of life data were collected on all patients at baseline. Multivariate logistic regression modeling was used to identify factors associated with surgical intervention.

Results: There were 122 patients enrolled, 105 (86.0%) were treated surgically, and 17 (14.0%) were treated nonoperatively. Overall mean age was 54.8 years (SD 12.6) with 80 (65.5%) males. Bivariate analysis revealed no statistically significant differences between surgical and nonoperative groups with respect to age, sex, BMI, smoking status, number of comorbidities and duration of symptoms; mJOA scores were significantly higher in the nonoperative group (16.8 [SD 0.99] vs. 15.9 [SD 0.89], P < 0.001). There was a statistically significant difference in Neck Disability Index, SF12 Physical Component, SF12 Mental Component Score, EQ5D, and PHQ-9 scores between groups; those treated surgically had worse baseline questionnaire scores (P < 0.05). There was no difference in radiographic parameters between groups. Multivariable analysis revealed that lower quality of life scores on EQ5D were associated with selection for surgical management (P < 0.018).

Conclusion: Patients treated surgically for mild cervical myelopathy did not differ from those treated nonoperatively with respect to baseline demographic or radiographic parameters. Patients with worse EQ5D scores had higher odds of surgical intervention.

Level Of Evidence: 3.
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http://dx.doi.org/10.1097/BRS.0000000000003124DOI Listing
November 2019

The impact of frailty and sarcopenia on patient outcomes after complex spine surgery.

Curr Opin Anaesthesiol 2019 Oct;32(5):609-615

Combined Neurosurgical and Orthopedic Spine Program, Department of Orthopedic Surgery, University of British Columbia.

Purpose Of Review: Frailty and sarcopenia represent a state of increased fragility and decreased reserve, and both have been associated with worse outcomes after surgery. The present review focuses on the definitions and measurement tools used to assess frailty and sarcopenia in patients with spinal disorder, and the relationships between frailty, sarcopenia, and postoperative outcomes in patients undergoing complex spine surgery.

Recent Findings: Complex spine surgery is associated with a high rate of adverse events when using a validated, prospective data collection system. Recent studies have demonstrated that patients with spine surgery with frailty and sarcopenia have a higher risk of adverse events, although this relationship varies depending on the measurement tool and specific population studied. Both general and specific frailty assessment tools have been used in the spine surgery population, however the optimal tool is not known. Spinal disorders such as lumbar stenosis contribute to the frailty phenotype, and may be reversible with surgery.

Summary: Frailty and sarcopenia are increasingly recognized as important predictors of adverse outcomes after complex spine surgery. The optimal tool to measure frailty and sarcopenia in patients with spinal disorders remains unclear, and the role of surgery as an intervention to reverse frailty requires further investigation.
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http://dx.doi.org/10.1097/ACO.0000000000000759DOI Listing
October 2019

Primary Bone Tumor of the Spine-An Evolving Field: What a General Spine Surgeon Should Know.

Global Spine J 2019 May 8;9(1 Suppl):108S-116S. Epub 2019 May 8.

University of British Columbia, Vancouver, British Columbia, Canada.

Study Design: A narrative review of the literature.

Objective: This article reviews the general principles of treatment and investigation for primary bone tumors of the spine. Furthermore, it explores the emerging alternatives.

Methods: A review was performed using Medline, Embase, and Cochrane databases.

Results: Primary bone tumors of the spine are rare entities that general spine surgeons may encounter only a few times in their career. The treatment algorithm of these complex tumors is filled with nuances and is evolving constantly. For these reasons, patients should be referred to experienced tertiary or quaternary centers who can offer a comprehensive multidisciplinary approach. For most malignant spinal bone tumors, surgery remains the cornerstone of treatment. Respecting oncologic principles has been associated with improved survival and decreased local recurrence in multiple settings. However, even in experienced centers, these surgeries carry a significant risk of adverse events and possible long-term neurologic impairment. The associated morbidity of these procedures and the challenges of local recurrence have encouraged professionals caring for these patients to explore alternatives or adjuncts to surgical treatment.

Conclusions: Over the past few years, several advances have occurred in medical oncology, radiation oncology and interventional radiology, changing the treatment paradigm for some tumors. Other advances still need to be refined before being applied in a clinical setting.
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http://dx.doi.org/10.1177/2192568219828727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512194PMC
May 2019

Consultation and Surgical Wait Times in Cervical Spondylotic Myelopathy.

Can J Neurol Sci 2019 07 3;46(4):430-435. Epub 2019 May 3.

Combined Neurosurgery and Orthopaedic Spine Program,University of British Columbia,Vancouver, British Columbia,Canada.

Background: Cervical spondylotic myelopathy (CSM) is the leading cause of spinal cord impairment. In a public healthcare system, wait times to see spine specialists and eventually access surgical treatment for CSM can be substantial. The goals of this study were to determine consultation wait times (CWT) and surgical wait times (SWT), and identify predictors of wait time length.

Methods: Consecutive patients enrolled in the Canadian Spine Outcomes and Research Network (CSORN) prospective and observational CSM study from March 2015 to July 2017 were included. A data-splitting technique was used to develop and internally validate multivariable models of potential predictors.

Results: A CSORN query returned 264 CSM patients for CWT. The median was 46 days. There were 31% mild, 35% moderate, and 33% severe CSM. There was a statistically significant difference in median CWT between moderate and severe groups; 207 patients underwent surgical treatment. Median SWT was 42 days. There was a statistically significant difference in SWT between mild/moderate and severe groups. Short symptom duration, less pain, lower BMI, and lower physical component score of SF-12 were predictive of shorter CWT. Only baseline pain and medication duration were predictive of SWT. Both CWT and SWT were shorter compared to a concurrent cohort of lumbar stenosis patients (p <0.001).

Conclusions: Patients with shorter duration (either symptoms or medication) and less neck pain waited less to see a spine specialist in Canada and to undergo surgical treatment. This study highlights some of the obstacles to overcome in expedited care for this patient population.
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http://dx.doi.org/10.1017/cjn.2019.34DOI Listing
July 2019

MicroRNA Biomarkers in Cerebrospinal Fluid and Serum Reflect Injury Severity in Human Acute Traumatic Spinal Cord Injury.

J Neurotrauma 2019 08 14;36(15):2358-2371. Epub 2019 May 14.

1International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, British Columbia, Canada.

Spinal cord injury (SCI) is a devastating condition with variability in injury mechanisms and neurologic recovery. Spinal cord impairment after SCI is measured and classified by a widely accepted standard neurological examination. In the very acute stages post-injury, however, this examination is extremely challenging (and often impossible) to conduct and has modest prognostic value in terms of neurological recovery. The lack of objective tools to classify injury severity and predict outcome is a barrier for clinical trials and thwarts development of therapies for those with SCI. Biological markers (biomarkers) represent a promising, complementary approach to these challenges because they represent an unbiased approach to classify injury severity and predict neurological outcome. Identification of a suitable panel of molecular biomarkers would comprise a fundamental shift in how patients with acute SCI are evaluated, stratified, and treated in clinical trials. MicroRNA are attractive biomarker candidates in neurological disorders for several reasons, including their stability in biological fluids, their conservation between humans and model mammals, and their tissue specificity. In this study, we used next-generation sequencing to identify microRNA associated with injury severity within the cerebrospinal fluid (CSF) and serum of human patients with acute SCI. The CSF and serum samples were obtained 1-5 days post-injury from 39 patients with acute SCI (24 American Spinal Injury Association Impairment Scale [AIS] A, 8 AIS B, 7 AIS C) and from five non-SCI controls. We identified a severity-dependent pattern of change in microRNA expression in CSF and identified a set of microRNA that are diagnostic of baseline AIS classification and prognostic of neurological outcome six months post-injury. The data presented here provide a comprehensive description of the CSF and serum microRNA expression changes that occur after acute human SCI. This data set reveals microRNA candidates that warrant further evaluation as biomarkers of injury severity after SCI and as key regulators in other neurological disorders.
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http://dx.doi.org/10.1089/neu.2018.6256DOI Listing
August 2019

'After-hours' non-elective spine surgery is associated with increased perioperative adverse events in a quaternary center.

Eur Spine J 2019 04 6;28(4):817-828. Epub 2018 Dec 6.

Department of Orthopedic Surgery, Blusson Spinal Cord Centre, University of British Columbia, 6th Floor, 818 West 10th Avenue, Vancouver, BC, V5Z 1M9, Canada.

Purpose: 'After-hours' non-elective spinal surgeries are frequently necessary, and often performed under sub-optimal conditions. This study aimed (1) to compare the characteristics of patients undergoing non-elective spine surgery 'After-hours' as compared to 'In-hours'; and (2) to compare the perioperative adverse events (AEs) between those undergoing non-elective spine surgery 'after-hours' as compared to 'in-hours'.

Methods: In this retrospective study of a prospective non-elective spine surgery cohort performed in a quaternary spine center, surgery was defined as 'in-hours' if performed between 0700 and 1600 h from Monday to Friday or 'after-hours' if more than 50% of the operative time occurred between 1601 and 0659 h, or if performed over the weekend. The association of 'after-hours' surgery with AEs, surgical duration, intraoperative estimated blood loss (IOBL), length of stay and in-hospital mortality was analyzed using stepwise multivariate logistic regression.

Results: A total of 1440 patients who underwent non-elective spinal surgery between 2009 and 2013 were included in this study. A total of 664 (46%) procedures were performed 'after-hours'. Surgical duration and IOBL were similar. About 70% of the patients operated 'after-hours' experienced at least one AE compared to 64% for the 'in-hours' group (p = 0.016). 'After-hours' surgery remained an independent predictor of AEs on multivariate analysis [adjusted OR 1.30, 95% confidence interval (CI) 1.02-1.66, p = 0.034]. In-hospital mortality increased twofold in patients operated 'after-hours' (4.4% vs. 2.1%, p = 0.013). This association lost significance on multivariate analysis (adjusted OR 1.99, 95% CI 0.98-4.06, p = 0.056).

Conclusion: Non-elective spine surgery performed 'after-hours' is independently associated with increased risk of perioperative adverse events, length of stay and possibly, mortality. Research is needed to determine the specific factors contributing to poorer outcomes with 'after-hours' surgery and strategies to minimize this risk. These slides can be retrieved under Electronic Supplementary Material.
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http://dx.doi.org/10.1007/s00586-018-5848-xDOI Listing
April 2019

Current treatment strategy for newly diagnosed chordoma of the mobile spine and sacrum: results of an international survey.

J Neurosurg Spine 2018 10;30(1):119-125

19Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts.

OBJECTIVEThe purpose of this study was to investigate the spectrum of current treatment protocols for managing newly diagnosed chordoma of the mobile spine and sacrum.METHODSA survey on the treatment of spinal chordoma was distributed electronically to members of the AOSpine Knowledge Forum Tumor, including neurosurgeons, orthopedic surgeons, and radiation oncologists from North America, South America, Europe, Asia, and Australia. Survey participants were pre-identified clinicians from centers with expertise in the treatment of spinal tumors. The suvey responses were analyzed using descriptive statistics.RESULTSThirty-nine of 43 (91%) participants completed the survey. Most (80%) indicated that they favor en bloc resection without preoperative neoadjuvant radiation therapy (RT) when en bloc resection is feasible with acceptable morbidity. The main area of disagreement was with the role of postoperative RT, where 41% preferred giving RT only if positive margins were achieved and 38% preferred giving RT irrespective of margin status. When en bloc resection would result in significant morbidity, 33% preferred planned intralesional resection followed by RT, and 33% preferred giving neoadjuvant RT prior to surgery. In total, 8 treatment protocols were identified: 3 in which en bloc resection is feasible with acceptable morbidity and 5 in which en bloc resection would result in significant morbidity.CONCLUSIONSThe results confirm that there is treatment variability across centers worldwide for managing newly diagnosed chordoma of the mobile spine and sacrum. This information will be used to design an international prospective cohort study to determine the most appropriate treatment strategy for patients with spinal chordoma.
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http://dx.doi.org/10.3171/2018.6.SPINE18362DOI Listing
October 2018

The impact of frailty and sarcopenia on postoperative outcomes in adult spine surgery. A systematic review of the literature.

Spine J 2018 12 24;18(12):2354-2369. Epub 2018 Jul 24.

Vancouver Spine Surgery Institute and Department of Orthopaedics, University of British Columbia, Vancouver, BC, Canada.

Study Design: Systematic review.

Objectives: To identify currently used measures of frailty and sarcopenia in the adult spine surgery literature. To assess their ability to predict postoperative outcomes including mortality, morbidity, in-hospital length of stay (LOS), and discharge disposition. To determine which is the best clinical measure of frailty and sarcopenia in predicting outcome after spine surgery.

Summary Of Background Data: Frailty and sarcopenia have been identified as predictors of mortality and adverse-events (AEs) in numerous nonsurgical and nonspine populations. This topic is an emerging area of interest and study in patients undergoing spinal surgery.

Methods: A systematic literature review using the PRISMA methodology of MEDLINE, PubMed, Ovid, EMBASE, and Cochrane databases was performed from January 1950 to August 2017. Included studies consisted of those that examined measures of frailty or sarcopenia in adult patients undergoing any spinal surgery. The literature was synthesized and recommendations are proposed based on the GRADE system.

Results: The initial search yielded 210 results, 11 of which met our complete inclusion criteria. Seven reported on measures of frailty and four reported on measures of sarcopenia. Frailty, assessed using a variety of measurement tools, was a consistent predictor of mortality, major and minor morbidity, prolonged in-hospital LOS, and discharge to a center of higher care for adult patients undergoing spinal surgery. The relationship between sarcopenia and postoperative outcomes was inconsistent due to the lack of consensus regarding the definition, measurement tools, and wide variability in sarcopenia measured in the spinal population.

Conclusions: Frailty is predictive of AEs, mortality, in-hospital LOS, and discharge disposition in a number of distinct spinal surgery populations. The impact of sarcopenia on postoperative outcomes is equivocal given the current state of the literature. The relationship between spinal pathology, frailty, sarcopenia, and how they interact to yield outcome remains to be clarified. Frailty and sarcopenia are potentially useful tools for risk stratification of patients undergoing spinal surgery. This systematic review was registered with PROSPERO, registration number 85096.
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http://dx.doi.org/10.1016/j.spinee.2018.07.008DOI Listing
December 2018

Ewing Sarcoma of the Spine: Prognostic Variables for Survival and Local Control in Surgically Treated Patients.

Spine (Phila Pa 1976) 2018 05;43(9):622-629

Department of Neurosurgery, MD Anderson Cancer Center, University of Texas, Houston, TX.

Study Design: Multicenter, ambispective observational study.

Objective: To quantify mortality and local recurrence after surgical treatment of spinal Ewing sarcoma (ES) and to determine whether an Enneking appropriate procedure and surgical margins (en bloc resection with wide/marginal margins) are associated with improved prognosis.

Summary Of Background Data: Treatment of primary ES of the spine is complex. Ambiguity remains regarding the role and optimal type of surgery in the treatment of spinal ES.

Methods: The AOSpine Knowledge Forum Tumor developed a multicenter database including demographics, diagnosis, treatment, mortality, and recurrence rate data for spinal ES. Patients were stratified based on surgical margins and Enneking appropriateness. Survival and recurrence were analyzed using Kaplan-Meier curves and log-rank tests.

Results: Fifty-eight patients diagnosed with primary spinal ES underwent surgery. Enneking appropriateness of surgery was known for 55 patients; 24 (44%) treated Enneking appropriately (EA) and 31 (56%) treated Enneking inappropriately (EI). A statistically significant difference in favor of EA-treated patients was found with regards to survival (P = 0.034). Neoadjuvant and postoperative chemotherapy was significantly associated with increased survival (P = 0.008). Local recurrence occurred in 22% (N = 5) of patients with an EA procedure versus 38% (N = 11) of patients with an EI procedure. The timing of chemotherapy treatment was significantly different between the Enneking cohorts (P < 0.001) and all EA-treated patients received chemotherapy treatment. Although, local recurrence was not significantly different between Enneking cohorts (P = 0.140), intralesional surgical margins and patients who received a previous spine tumor operation were associated with increased local recurrence (P = 0.025 and P = 0.018, respectively).

Conclusion: Surgery should be undertaken when an en bloc resection with wide/marginal margins is feasible. An EA surgery correlates with improved survival, but the impact of other prognostic factors needs to be evaluated. En bloc resection with wide/marginal margins is associated with local control.

Level Of Evidence: 3.
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http://dx.doi.org/10.1097/BRS.0000000000002386DOI Listing
May 2018

Frailty and sarcopenia do not predict adverse events in an elderly population undergoing non-complex primary elective surgery for degenerative conditions of the lumbar spine.

Spine J 2018 02 12;18(2):245-254. Epub 2017 Jul 12.

Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver General Hospital, Room 2449 JPP 899 West 12th Ave, Vancouver, BC V5Z 1M9, Canada.

Background Context: Sarcopenia measured by normalized total psoas area (NTPA) has been shown to predict mortality and adverse events (AEs) in numerous surgical populations. The relationship between sarcopenia and postoperative outcomes after surgery for degenerative spine disease (DSD) has not been investigated.

Purpose: This study aimed to determine the relationships between sarcopenia, frailty, and postoperative AEs in the elderly DSD population. Secondary objectives were to describe the distribution and predictors of NTPA and to determine the relationship between sarcopenia, frailty, and length of stay, discharge to a facility, and in-hospital mortality.

Study Design: This is an ambispective study from a quaternary care academic center.

Patient Sample: A total of 102 patients over 65 years old who underwent elective thoracolumbar surgery for DSD between 2009 and 2013 were included in this study.

Outcome Measures: The primary outcome was a composite of perioperative AEs; the secondary outcomes were length of stay, discharge disposition, and in-hospital mortality.

Methods: Total psoas area (TPA) at mid-L3 level on preoperative computed tomography scan adjusted for height (NTPA) defined sarcopenia. The modified frailty index (mFI) of 11 clinical variables defined frailty. The distribution and predictors of sarcopenia (NTPA) were determined. The association of NTPA with AEs, length of stay, discharge disposition to care facility, and mortality was analyzed, including adjusting for known and suspected confounders using multivariate regression.

Results: Median Spine Surgical Invasiveness Index was 8 (interquartile range 2-10), and mean NTPA was 674 mm/m (293.21-1636.25). Using the mFI, 20.6% were pre-frail and 19.6% were frail. Inter- and intraobserver reliability for determining NTPA were near perfect with kappa 0.95-0.97 and 0.94-1.00, respectively. The NTPA was independently associated with patient gender and body mass index (BMI) but not frailty (mFI). Age, BMI, mFI, and American Anesthesiologists' Society score were not associated with incidence of postoperative AEs. The NTPA did not predict the occurrence of AE (odds ratio [OR] 1.06 per 100 mm/m, 95% confidence interval [CI] 0.91-1.23, p=.45). Similarly, NTPA was not predictive of length of stay (rho=-0.04, p=.67), discharge home (OR 0.95 (95% CI 0.76-1.20) per 100 mm/m, p=.70), or death (OR 1.12 (95% CI 0.83-1.53) per 100 mm/m, p=.47). In contrast, increasing mFI was associated with increased risk of mortality (OR 3.12 (95% CI 1.21-8.03) per 0.1 increase in frailty score, p=.006).

Conclusions: In contrast to other surgical groups, sarcopenia (NTPA) or frailty (mFI) did not predict acute care complications in a selected population of elderly patients undergoing simple lumbar spine surgery for DSD. Although NTPA can be reliably measured in this population, it may be an inappropriate surrogate for sarcopenia given its anatomical relationship to spinal function.
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http://dx.doi.org/10.1016/j.spinee.2017.07.003DOI Listing
February 2018

Spine Stereotactic Body Radiotherapy: Indications, Outcomes, and Points of Caution.

Global Spine J 2017 Apr 6;7(2):179-197. Epub 2017 Apr 6.

Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.

Study Design: A broad narrative review.

Objectives: The objective of this article is to provide a technical review of spine stereotactic body radiotherapy (SBRT) planning and delivery, indications for treatment, outcomes, complications, and the challenges of response assessment. The surgical approach to spinal metastases is discussed with an overview of emerging minimally invasive techniques.

Methods: A comprehensive review of the literature was conducted on the techniques, outcomes, and developments in SBRT and surgery for spinal metastases.

Results: The optimal management of patients with spinal metastases is complex and requires multidisciplinary assessment from an oncologic team that is familiar with the shifting paradigm as a consequence of evolving techniques in surgery and stereotactic radiation, as well as new developments in systemic agents. The Spinal Instability Neoplastic Score and the epidural spinal cord compression (Bilsky) grading system are useful tools that facilitate communication among oncologic team members and can direct management by providing a baseline assessment of risks prior to therapy. The combined multimodality approach with "separation surgery" followed by postoperative spine SBRT achieves thecal sac decompression, improves tumor control, and avoids complications that may be associated with more extensive surgery.

Conclusion: Spine SBRT is a highly effective treatment that is capable of delivering ablative doses to the target while sparing the critical organs-at-risk, chiefly the critical neural tissues, within a short and manageable schedule. At the same time, surgery occupies an important role in select patients, particularly with the expanding availability and expertise in minimally invasive techniques. With rapid adoption of spine SBRT in centers outside of the academic setting, it is imperative for the practicing oncologist to understand the relevance and application of these evolving concepts.
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http://dx.doi.org/10.1177/2192568217694016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5415159PMC
April 2017

En Bloc Resection Versus Intralesional Surgery in the Treatment of Giant Cell Tumor of the Spine.

Spine (Phila Pa 1976) 2017 Sep;42(18):1383-1390

Department of Degenerative and Oncological Spine Surgery, Rizzoli Institute Bologna, Bologna, Italy.

Study Design: Multicenter, ambispective observational study.

Objective: The aim of this study was to quantify local recurrence (LR) and mortality rates after surgical treatment of spinal giant cell tumor and to determine whether en bloc resection with wide/marginal margins is associated with improved prognosis compared to an intralesional procedure.

Summary Of Background Data: Giant cell tumor (GCT) of the spine is a rare primary bone tumor known for its local aggressiveness. Optimal surgical treatment remains to be determined.

Methods: The AOSpine Knowledge Forum Tumor developed a comprehensive multicenter database including demographics, presentation, diagnosis, treatment, mortality, and recurrence rate data for GCT of the spine. Patients were analyzed based on surgical margins, including Enneking appropriateness.

Results: Between 1991 and 2011, 82 patients underwent surgery for spinal GCT. According to the Enneking classification, 59 (74%) tumors were classified as S3-aggressive and 21 (26%) as S2-active. The surgical margins were wide/marginal in 27 (36%) patients and intralesional in 48 (64%) patients. Thirty-nine of 77 (51%) underwent Enneking appropriate (EA) treatment and 38 (49%) underwent Enneking inappropriate (EI) treatment. Eighteen (22%) patients experienced LR. LR occurred in 11 (29%) EI-treated patients and six (15%) EA-treated patients (P = 0.151). There was a significant difference between wide/marginal margins and intralesional margins for LR (P = 0.029). Seven (9%) patients died. LR is strongly associated with death (Relative Risk 8.9, P < 0.001). Six (16%) EI-treated patients and one (3%) EA-treated patients died (P = 0.056). With regards to surgical margins, all patients who died underwent intralesional resection (P = 0.096).

Conclusion: En bloc resection with wide/marginal margins should be performed when technically feasible because it is associated with decreased LR. Intralesional resection is associated with increased LR, and mortality correlates with LR.

Level Of Evidence: 3.
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http://dx.doi.org/10.1097/BRS.0000000000002094DOI Listing
September 2017

Optimizing the Adverse Event and HRQOL Profiles in the Management of Primary Spine Tumors.

Spine (Phila Pa 1976) 2016 Oct;41 Suppl 20:S212-S217

Department of Neurosurgery, University of California-San Francisco Medical Center, San Francisco, CA.

Study Design: Systematic literature review.

Objective: To investigate if evidence-based principles of oncologic resection for primary spinal tumors are correlated with an acceptable morbidity and mortality profile and satisfactory health-related quality of life (HRQOL) measures.

Summary Of Background Data: Respecting oncologic principles for primary spinal tumor surgery is correlated with lower recurrence rates. These interventions are, however, often highly morbid.

Methods: A systematic literature review was performed to address the objectives by searching MEDLINE and EBMR databases. Articles that met our inclusion criteria were reviewed. GRADE guidelines were used for recommendation formulation.

Results: A total of 25 articles addressing the morbidity and mortality profile of primary spinal tumor surgery were identified. For sacral tumors, complication rates of up to 100% have been reported and complication-related death ranged from 0% to 27%. Mobile spine tumor complication rates varied from 13% to 73.7% and complication-related death ranged from 0% to 7.7%. Seven articles examining HRQOL for this patient population were identified. The limited literature showed comparable patient HRQOL profiles to those with benign conditions such as degenerative disc disease.

Conclusion: Respecting oncologic principles for primary spinal tumors are correlated with high adverse event rates. We recommend that primary spinal tumor surgeries be performed in experienced centers with multidisciplinary support teams and that prospective adverse event collection be promoted (strong recommendation/very low certainty of the evidence). Oncologic resection of primary tumors of the spine is associated with HRQOL that more closely approximates normative values with increasing duration of follow-up, but decreases with disease recurrence. We recommend primary spinal tumor surgery be performed with a curative intent whenever possible, even at the expense of greater initial morbidity to optimize long-term HRQOL (strong recommendation/very low certainty of the evidence).

Level Of Evidence: N/A.
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http://dx.doi.org/10.1097/BRS.0000000000001821DOI Listing
October 2016

Benign Tumors of the Spine: Has New Chemotherapy and Interventional Radiology Changed the Treatment Paradigm?

Spine (Phila Pa 1976) 2016 Oct;41 Suppl 20:S178-S185

Department of Neurosurgery, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX.

Study Design: Clinically based systematic review.

Objective: To determine the role of (A) medical treatment and (B) interventional radiology as either adjuvant or stand-alone treatment in primary benign bone tumors of the spine.

Methods: A multidisciplinary panel of spine surgeons, radiation oncologists, and medical oncologists elaborated specific focused questions regarding aneurysmal bone cyst, giant cell tumor, and osteoid osteoma. Denosumab, bisphosphonate, interferon, bone marrow aspirate, doxycycline, thermal ablation, and selective arterial embolization were identified as areas of interest for the article. A systematic review was performed through MEDLINE and EMBASE. Recommendations based on the literature review and clinical expertise were issued using the GRADE system.

Results: The overall quality of the literature is very low with few multicenter prospective studies. For giant cell tumor, combination with Denosumab identified 14 pertinent articles with four multicenter prospective studies. Nine studies were found on bisphosphonates and six for selective arterial embolization. The search on aneurysmal bone cyst and selective arterial embolization revealed 12 articles. Combination with Denosumab, Doxycycline, and bone marrow aspirate identified four, two, and three relevant articles respectively. Eleven focused articles were selected on the role of thermal ablation in osteoid osteoma.

Conclusion: Alternative and adjuvant therapy for primary benign bone tumors have emerged. Their ability to complement or replace surgery is now being scrutinized and they may impact significantly the algorithm of treatment of these tumors. Most of the data are still emerging and further research is desirable. Close collaboration between the different specialists managing these pathologies is crucial.

Level Of Evidence: N/A.
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http://dx.doi.org/10.1097/BRS.0000000000001818DOI Listing
October 2016

Frailty and postoperative outcomes in patients undergoing surgery for degenerative spine disease.

Spine J 2016 11 30;16(11):1315-1323. Epub 2016 Jun 30.

Division of Respirology, Department of Medicine, St. Paul's Hospital, University of British Columbia, Ward 8B, 1081 Burrard Street, Vancouver, BC, Canada, V6Z 1Y6.

Background Context: Frailty is defined as a state of decreased reserve and susceptibility to stressors. The relationship between frailty and postoperative outcomes after degenerative spine surgery has not been studied.

Purpose: This study aimed to (1) determine prevalence of frailty in the degenerative spine population; (2) describe patient characteristics associated with frailty; and (3) determine the association between frailty and postoperative complications, mortality, length of stay, and discharge disposition.

Study Design: This is a retrospective analysis on a prospectively collected cohort from the National Surgical Quality Improvement Program (NSQIP).

Patient Sample: A total of 53,080 patients who underwent degenerative spine surgery between 2006 and 2012 were included in the study.

Outcome Measures: A modified frailty index (mFI) with 11 variables derived from the NSQIP dataset was used to determine prevalence of frailty and its correlation with a composite outcome of perioperative complications as well as hospital length of stay, mortality, and discharge disposition.

Methods: After calculating the mFI for each patient, the prevalence and predictors of frailty were determined for our cohort. The association of frailty with postoperative outcomes was determined after adjusting for known and suspected confounders using multivariate logistic regression.

Results: Frailty was present in 2,041 patients within the total population (4%) and in 8% of patients older than 65 years. Frailty severity increased with increasing age, male sex, African American race, higher body mass index, recent weight loss, paraplegia or quadriplegia, American Society of Anesthesiologists (ASA) score, and preadmission residence in a care facility. Frailty severity was an independent predictor of major complication (OR 1.15 for every 0.10 increase in mFI, 95%CI 1.09-1.21, p<.0005) and specifically predicted reoperation for postsurgical infection (OR 1.3, 95%CI 1.16-1.46, p<.0005). Prolonged length of stay and discharge to a new facility were also independently predicted by frailty severity (p<.0005). Frailty severity predicted 30-day mortality on unadjusted (OR 2.05, 95%CI 1.70-2.48, p<.0005) and adjusted analyses (OR 1.48, 95%CI 1.18-1.86, p<.0005).

Conclusions: Frailty is an important predictor of postoperative outcomes following degenerative spine surgery. Preoperative recognition of frailty may be useful for perioperative optimization, risk stratification, and patient counseling.
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http://dx.doi.org/10.1016/j.spinee.2016.06.017DOI Listing
November 2016

Health-Related Quality of Life After Spine Surgery for Primary Bone Tumour.

Curr Treat Options Oncol 2016 Feb;17(2)

Division of Spine, Department of Orthopaedics, The Combined Neurosurgical and Orthopaedic Spine Program at Vancouver Coastal Health, Blusson Spinal Cord Centre, 6th Floor, 818 West 10th Avenue, Vancouver, BC, Canada, V5Z 1M9.

Opinion Statement: Treatment of primary bone tumours (PBT) of the spine is complex, often involving numerous surgical and oncology disciplines. Surgical en bloc resection with oncologically appropriate margins is the modality of choice when treating malignant PBT. En bloc resection with wide or marginal margins appears to offer better local and systemic control of the disease. This type of surgical resection can also be considered when treating benign aggressive tumours such as aneurysmal bone cyst, giant cell tumour and osteoblastoma. Although these surgeries respect oncologic principles, significant morbidity and mortality are associated. Adverse event collection is highly variable in the literature and mostly from retrospective studies. Wound complication, neurologic deficit and significant blood loss are encountered with surgical resection of PBT of the mobile spine and especially, the sacrum. The adverse event profile of these surgeries is high even in experienced quaternary referral centres. Therefore, primary spinal tumour resection is best performed in experienced centre with adequate multidisciplinary support. Furthermore, prospective and systematic adverse event data collection should be developed to ensure accurate data. The impact of such extensive and potentially impairment producing procedures on health-related quality of life (HRQOL) is another critically valuable piece of information in the era of shared treatment decision making. At the present time, there is paucity of published data regarding HRQOL following these surgeries. Nonetheless, in theory, it seems that health-related quality of life after surgery for PBT is acceptable given the curative intent of the treatment. However, a decision-making process should be tailored to each patient and his or her expectations. Comprehensive discussions should be held preoperatively with the patient, family and other related allied health professionals if the informed consent and decision-making process is to be optimal.
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http://dx.doi.org/10.1007/s11864-015-0383-zDOI Listing
February 2016
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