Publications by authors named "Scott Paquette"

49 Publications

Characterization of Hyperacute Neuropathic Pain after Spinal Cord Injury: A Prospective Study.

J Pain 2021 Jul 21. Epub 2021 Jul 21.

International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, British Columbia, Canada; Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, British Columbia, Canada; Hugill Centre for Anesthesia, Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address:

There is currently a lack of information regarding neuropathic pain in the very early stages of spinal cord injury (SCI). In the present study, neuropathic pain was assessed using the Douleur Neuropathique 4 Questions (DN4) for the patient's worst pain within the first 5 days of injury (i.e., hyperacute) and on follow-up at 3, 6, and 12 months. Within the hyperacute time-frame (i.e., 5 days), at- and below level neuropathic pain were reported as the worst pain in 23% (n=18) and 5% (n=4) of individuals with SCI, respectively. Compared to the neuropathic pain observed in this hyperacute setting, late presenting neuropathic pain was characterized by more intense painful electrical and cold sensations, but less itching sensations. Phenotypic differences between acute and late neuropathic pain support the incorporation of timing into a mechanism-based classification of neuropathic pain after SCI. The diagnosis of acute neuropathic pain after SCI is challenged by the presence of nociceptive and neuropathic pains, with the former potentially masking the latter. This may lead to an underestimation of the incidence of neuropathic pain during the very early, hyperacute time points post-injury. Trial registration: ClinicalTrials.gov (Identifier: NCT01279811) Perspective: This article presents distinct pain phenotypes of hyperacute and late presenting neuropathic pain after spinal cord injury and highlights the challenges of pain assessments in the acute phase after injury. This information may be relevant to clinical trial design and broaden our understanding of neuropathic pain mechanisms after spinal cord injury.
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http://dx.doi.org/10.1016/j.jpain.2021.06.013DOI Listing
July 2021

Accuracy of hospital-based surveillance systems for surgical site infection after adult spine surgery: A Bayesian latent class analysis.

J Hosp Infect 2021 Jul 14. Epub 2021 Jul 14.

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

Background: Surgical site infections (SSIs) of the spine are morbid and costly complications. An accurate surveillance system is required to properly describe the disease burden and the impact of interventions that mitigate SSI risk. Unfortunately, uniform approaches to conducting SSI surveillance are lacking because of varying SSI case definitions, the lack of a perfect reference case definition and heterogeneous data sources.

Aim: We assessed the accuracy of 4 independent data sources that capture SSIs after spine surgery, with estimation of a measurement error-adjusted SSI incidence.

Methods: A Bayesian latent class model assessed the sensitivity/specificity of each data source to identify SSI and to estimate a measurement-error adjusted incidence. The four data sources used were: the discharge abstract database (DAD), the National Surgical Quality Improvement Program (NSQIP) database, the Infection Prevention and Control Canada (IPAC) database, and the Spine Adverse Events Severity database.

Findings: A total of 904 patients underwent spine surgery in 2017. The most sensitive data source was DAD (0.799, 95% CrI 0.597, 0.943), while the least sensitive was NSQIP (0.497, 95% CrI 0.308, 0.694). The most specific data source was IPAC (0.997, 95% CrI 0.993, 1.000) and the least specific was DAD (0.969, 95% CrI 0.956, 0.981). The measurement error-adjusted SSI incidence was 0.030 (95% CrI 0.019, 0.045). The crude incidence using the DAD over-estimated the incidence, and the 3 other data sources under-estimated it.

Conclusion: SSI surveillance in the spine surgery population is feasible using several data sources, provided that measurement error is considered.
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http://dx.doi.org/10.1016/j.jhin.2021.07.005DOI Listing
July 2021

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

Patient perspective: diagnosis and prognosis of acute spinal cord injuries.

Spinal Cord 2021 Jun 3. Epub 2021 Jun 3.

Combined Neurosurgical and Orthopaedic Spine Program, Blusson Spinal Cord Centre, Vancouver General Hospital, Vancouver, British Columbia, Canada.

Study Design: Qualitative study.

Objectives: The purpose of this study is to understand the patient perspective after diagnosis of an acute traumatic spinal cord injury (tSCI). Discussing the diagnosis and prognosis of a tSCI with a patient can be a challenging experience for both the patient and the physician. As such, this paper attempts to better understand the patient experience to improve communication when discussing this life-altering injury.

Setting: Vancouver General Hospital, Vancouver, British Columbia, Canada.

Methods: This study is a qualitative study utilizing grounded theory and semi-structured interviews. The interview transcripts were manually coded using manifest and latent content analysis. Major and minor codes were identified and discussed.

Results: In total, 17 interviews were conducted, fifteen individuals with tSCI who received acute care at Vancouver General Hospital (VGH) and eleven family members were interviewed. Patient participants were interviewed individually or in a paired interview with a participating family member. Patient participants had varying spinal cord injuries from AIS A-D. Two major themes were identified from the interviews. The first major theme was physician demeanor (general approach and attitude towards patients) and the second major theme was delivery of information (content, timing, and source).

Conclusions: This study summarizes the preferences of patients who sustained a tSCI discussions regarding their diagnosis and prognosis in the acute care setting. The goal of this study is to help guide physician interactions at this difficult and vulnerable time for patients with hopes to improve patient care through effective communication.
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http://dx.doi.org/10.1038/s41393-021-00641-5DOI Listing
June 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

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

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

Advancing spinal fellowship training: an international multi-centre educational perspective.

Eur Spine J 2019 Nov 12;28(11):2437-2443. Epub 2019 Aug 12.

Department of Surgery, University of Toronto, Toronto, Canada.

Purpose: The purpose of this article is to review the importance of contemporary spine surgery fellowships and educational strategies to assist with fellowship design and delivery.

Methods: Spine surgery fellowship includes trainees from orthopaedic and neurosurgical backgrounds and is increasingly indicated for individuals wishing to pursue spine surgery as a career, recognizing how spinal surgery evolved significantly in scope and complexity. We combine expert opinion with a review of the literature and international experience to expound spine fellowship training.

Results: Contemporary learning techniques include boot camps at the start of fellowship which may reinforce previous clinical learning and help prepare fellows for their new clinical roles. There is good evidence that surgical specialty training boot camps improve clinical skills, knowledge and trainee confidence prior to embarking upon new clinical roles with increasing levels of responsibility. Furthermore, as simulation techniques and technologies take on an increasing role in medical and surgical training, we found evidence that trainees' operative skills and knowledge can improve with simulated operations, even if just carried out briefly. Finally, we found evidence to suggest a role for establishing competence-based objectives for training in specific operative and technical procedures. Competence-based objectives are helpful for trainees and trainers to highlight gaps in a trainee's skill set that may then be addressed during training.

Conclusions: Spinal fellowships may benefit from certain contemporary strategies that assist design and delivery of training in a safe environment. Interpersonal factors that promote healthy teamwork may contribute to an environment conducive to learning. These slides can be retrieved under Electronic Supplementary Material.
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http://dx.doi.org/10.1007/s00586-019-06098-8DOI Listing
November 2019

Decision tree analysis to better control treatment effects in spinal cord injury clinical research.

J Neurosurg Spine 2019 Jun 14:1-9. Epub 2019 Jun 14.

4International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver; and.

Objective: The aim of this study was to use decision tree modeling to identify optimal stratification groups considering both the neurological impairment and spinal column injury and to investigate the change in motor score as an example of a practical application. Inherent heterogeneity in spinal cord injury (SCI) introduces variation in natural recovery, compromising the ability to identify true treatment effects in clinical research. Optimized stratification factors to create homogeneous groups of participants would improve accurate identification of true treatment effects.

Methods: The analysis cohort consisted of patients with acute traumatic SCI registered in the Vancouver Rick Hansen Spinal Cord Injury Registry (RHSCIR) between 2004 and 2014. Severity of neurological injury (American Spinal Injury Association Impairment Scale [AIS grades A-D]), level of injury (cervical, thoracic), and total motor score (TMS) were assessed using the International Standards for Neurological Classification of Spinal Cord Injury examination; morphological injury to the spinal column assessed using the AOSpine classification (AOSC types A-C, C most severe) and age were also included. Decision trees were used to determine the most homogeneous groupings of participants based on TMS at admission and discharge from in-hospital care.

Results: The analysis cohort included 806 participants; 79.3% were male, and the mean age was 46.7 ± 19.9 years. Distribution of severity of neurological injury at admission was AIS grade A in 40.0% of patients, grade B in 11.3%, grade C in 18.9%, and grade D in 29.9%. The level of injury was cervical in 68.7% of patients and thoracolumbar in 31.3%. An AOSC type A injury was found in 33.1% of patients, type B in 25.6%, and type C in 37.8%. Decision tree analysis identified 6 optimal stratification groups for assessing TMS: 1) AOSC type A or B, cervical injury, and age ≤ 32 years; 2) AOSC type A or B, cervical injury, and age > 32-53 years; 3) AOSC type A or B, cervical injury, and age > 53 years; 4) AOSC type A or B and thoracic injury; 5) AOSC type C and cervical injury; and 6) AOSC type C and thoracic injury.

Conclusions: Appropriate stratification factors are fundamental to accurately identify treatment effects. Inclusion of AOSC type improves stratification, and use of the 6 stratification groups could minimize confounding effects of variable neurological recovery so that effective treatments can be identified.
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http://dx.doi.org/10.3171/2019.3.SPINE18993DOI Listing
June 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

The Importance of Determining Trainee Perspectives on Procedural Competencies During Spine Surgery Clinical Fellowship.

Global Spine J 2019 Feb 10;9(1):18-24. Epub 2018 May 10.

Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.

Study Design: Longitudinal survey.

Objective: It remains important to align competence-based objectives for training as deemed important by clinical fellows to those of their fellowship supervisors and program educators. The primary aim of this study was to determine trainee views on the relative importance of specific procedural training competencies. Secondarily, we aimed to evaluate self-perceived confidence in procedural performance at the commencement and completion of fellowship.

Methods: Questionnaires were administered to 68 clinical fellows enrolled in the AOSNA fellowship program during the 2015-2016 academic year. A Likert-type scale was used to quantify trainee perspectives on the relative importance of specific procedural competencies to their training base on an established curriculum including 53 general and 22 focused/advanced procedural competencies. We measured trainee self-perceived confidence in performing procedures at the commencement and completion of their program. Statistical analysis was performed on fellow demographic data and procedural responses.

Results: Our initial survey response rate was 82% (56/68) and 69% (47/68) for the follow-up survey. Although most procedural competencies were regarded of high importance, we did identify several procedures of high importance yet low confidence among fellows (ie, upper cervical, thoracic discectomy surgery), which highlights an educational opportunity. Overall procedural confidence increased from an average Likert score of 4.2 (SD = 1.3) on the initial survey to 5.4 (SD = 0.8) by follow-up survey ( < .0001).

Conclusions: Understanding trainee goals for clinical fellowship remains important. Identification of areas of low procedural confidence and high importance to training experience will better guide fellowship programs and supervisors in the strategic delivery of the educational experience.
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http://dx.doi.org/10.1177/2192568217747574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6362552PMC
February 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

The use of vacuum-assisted closure in spinal wound infections with or without exposed dura.

Eur Spine J 2018 10 25;27(10):2536-2542. Epub 2018 Apr 25.

Vancouver General Hospital, Vancouver, BC, Canada.

Introduction: The treatment of postoperative deep spinal wound infection involves debridement and intravenous antibiotics. Authors have previously reported success in a small series of patients treated with vacuum-assisted closure (VAC) therapy, but its use over exposed dura is controversial and the outcome has not been reported in large series.

Purpose: To review the outcomes following the treatment of postoperative spinal infections with VAC therapy, particularly those with exposed dura.

Methods: This is a review of prospectively collected data in 42 patients, all of whom had deep postoperative spinal infections. 30 of these patients had exposed dura. All patients had an initial debridement followed by application of VAC Whitefoam (with exposed dura) or grey Granufoam (where no dura was exposed). Pressure was set at 50 mmHg with exposed dura or 125 mmHg where no dura was exposed. All patients underwent a minimum 6 week course of antibiotics. We report on the number of visits to theatre required for dressing changes and debridement and the eventual outcomes.

Results: Five patients required a flap reconstruction. Two patients died before definitive final closure due to other complications (pneumonia and stroke). In all the other patients, their wounds healed fully. A mean of 2.3 infection surgeries were required to eradicate infection and achieve wound closure.

Conclusions: This is one of the largest studies which confirms the safety and efficacy of VAC dressings in patients with spinal wound infections, even when the dura is exposed. These slides can be retrieved under Electronic Supplementary Material.
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http://dx.doi.org/10.1007/s00586-018-5612-2DOI Listing
October 2018

Do intraoperative radiographs predict final lumbar sagittal alignment following single-level transforaminal lumbar interbody fusion?

J Neurosurg Spine 2018 05 16;28(5):486-491. Epub 2018 Feb 16.

OBJECTIVE The study aimed to determine if the intraoperative segmental lordosis (as calculated on a cross-table lateral radiograph following a single-level transforaminal lumbar interbody fusion [TLIF] for degenerative spondylolisthesis/low-grade isthmic spondylolisthesis) is maintained at discharge and at 6 months postsurgery. METHODS The authors reviewed images and medical records of patients ≥ 16 years of age with a diagnosis of an isolated single-level, low-grade spondylolisthesis (degenerative or isthmic) with symptomatic spinal stenosis treated between January 2008 and April 2014. Age, sex, surgical level, surgical approach, and facetectomy (unilateral vs bilateral) were recorded. Upright standardized preoperative, early, and 6-month postoperative radiographs, as well as intraoperative lateral radiographs, were analyzed for the pelvic incidence, segmental lumbar lordosis (SLL) at the TILF level, and total LL (TLL). In addition, the anteroposterior position of the cage in the disc space was documented. Data are presented as the mean ± SD; a p value < 0.05 was considered significant. RESULTS Eighty-four patients were included in the study. The mean age of patients was 56.8 ± 13.7 years, and 46 patients (55%) were men. The mean pelvic incidence was 59.7° ± 11.9°, and a posterior midline approach was used in 47 cases (56%). All TLIF procedures were single level using a bullet-shaped cage. A bilateral facetectomy was performed in 17 patients (20.2%), and 89.3% of procedures were done at the L4-5 and L5-S1 segments. SLL significantly improved intraoperatively from 15.8° ± 7.5° to 20.9° ± 7.7°, but the correction was lost after ambulation. Compared with preoperative values, at 6 months the change in SLL was modest at 1.8° ± 6.7° (p = 0.025), whereas TLL increased by 4.3° ± 9.6° (p < 0.001). The anteroposterior position of the cage, approach, level of surgery, and use of a bilateral facetectomy did not significantly affect postoperative LL. CONCLUSIONS Following a single-level TLIF procedure using a bullet-shaped cage, the intraoperative improvement in SLL is largely lost after ambulation. The improvement in TLL over time is probably due to the decompression part of the procedure. The approach, level of surgery, bilateral facetectomy, and position of the cage do not seem to have a significant effect on LL achieved postoperatively.
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http://dx.doi.org/10.3171/2017.8.SPINE161231DOI Listing
May 2018

Pseudarthrosis in adult and pediatric spinal deformity surgery: a systematic review of the literature and meta-analysis of incidence, characteristics, and risk factors.

Neurosurg Rev 2019 Jun 6;42(2):319-336. Epub 2018 Feb 6.

Department of Orthopaedics, University of British Columbia, Vancouver, BC, Canada.

We conducted a systematic review with meta-analysis and qualitative synthesis. This study aims to characterize pseudarthrosis after long-segment fusion in spinal deformity by identifying incidence rates by etiology, risk factors for its development, and common features. Pseudarthrosis can be a painful and debilitating complication of spinal fusion that may require reoperation. It is poorly characterized in the setting of spinal deformity. The MEDLINE, EMBASE, and Cochrane databases were searched for clinical research including spinal deformity patients treated with long-segment fusions reporting pseudarthrosis as a complication. Meta-analysis was performed on etiologic subsets of the studies to calculate incidence rates for pseudarthrosis. Qualitative synthesis was performed to identify characteristics of and risk factors for pseudarthrosis. The review found 162 articles reporting outcomes for 16,938 patients which met inclusion criteria. In general, the included studies were of medium to low quality according to recommended reporting standards and study design. Meta-analysis calculated an incidence of 1.4% (95% CI 0.9-1.8%) for pseudarthrosis in adolescent idiopathic scoliosis, 2.2% (95% CI 1.3-3.2%) in neuromuscular scoliosis, and 6.3% (95% CI 4.3-8.2%) in adult spinal deformity. Risk factors for pseudarthrosis include age over 55, construct length greater than 12 segments, smoking, thoracolumbar kyphosis greater than 20°, and fusion to the sacrum. Choice of graft material, pre-operative coronal alignment, post-operative analgesics, and sex have no significant impact on fusion rates. Older patients with greater deformity requiring more extensive instrumentation are at higher risk for pseudarthrosis. Overall incidence of pseudarthrosis requiring reoperation is low in adult populations and very low in adolescent populations.
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http://dx.doi.org/10.1007/s10143-018-0951-3DOI Listing
June 2019

Predicting Injury Severity and Neurological Recovery after Acute Cervical Spinal Cord Injury: A Comparison of Cerebrospinal Fluid and Magnetic Resonance Imaging Biomarkers.

J Neurotrauma 2018 02 6;35(3):435-445. Epub 2017 Nov 6.

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

Biomarkers of acute human spinal cord injury (SCI) could provide a more objective measure of spinal cord damage and a better predictor of neurological outcome than current standardized neurological assessments. In SCI, there is growing interest in establishing biomarkers from cerebrospinal fluid (CSF) and from magnetic resonance imaging (MRI). Here, we compared the ability of CSF and MRI biomarkers to classify injury severity and predict neurological recovery in a cohort of acute cervical SCI patients. CSF samples and MRI scans from 36 acute cervical SCI patients were examined. From the CSF samples taken 24 h post-injury, the concentrations of inflammatory cytokines (interleukin [IL]-6, IL-8, monocyte chemotactic protein-1), and structural proteins (tau, glial fibrillary acidic protein, and S100β) were measured. From the pre-operative MRI scans, we measured intramedullary lesion length, hematoma length, hematoma extent, CSF effacement, cord expansion, and maximal spinal cord compression. Baseline and 6-month post-injury assessments of American Spine Injury Association Impairment Scale (AIS) grade and motor score were conducted. Both MRI measures and CSF biomarker levels were found to correlate with baseline injury grade, and in combination they provided a stronger model for classifying baseline AIS grade than CSF or MRI biomarkers alone. For predicting neurological recovery, the inflammatory CSF biomarkers best predicted AIS grade conversion, whereas structural biomarker levels best predicted motor score improvement. A logistic regression model utilizing CSF biomarkers alone had a 91.2% accuracy at predicting AIS conversion, and was not strengthened by adding MRI features or even knowledge of the baseline AIS grade. In a direct comparison of MRI and CSF biomarkers, the CSF biomarkers discriminate better between different injury severities, and are stronger predictors of neurological recovery in terms of AIS grade and motor score improvement. These findings demonstrate the utility of measuring the acute biological responses to SCI as biomarkers of injury severity and neurological prognosis.
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http://dx.doi.org/10.1089/neu.2017.5357DOI Listing
February 2018

Spinal cord perfusion pressure predicts neurologic recovery in acute spinal cord injury.

Neurology 2017 Oct 15;89(16):1660-1667. Epub 2017 Sep 15.

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

Objective: To determine whether spinal cord perfusion pressure (SCPP) as measured with a lumbar intrathecal catheter is a more predictive measure of neurologic outcome than the conventionally measured mean arterial pressure (MAP).

Methods: A total of 92 individuals with acute spinal cord injury were enrolled in this multicenter prospective observational clinical trial. MAP and CSF pressure (CSFP) were monitored during the first week postinjury. Neurologic impairment was assessed at baseline and at 6 months postinjury. We used logistic regression, systematic iterations of relative risk, and Cox proportional hazard models to examine hemodynamic patterns commensurate with neurologic outcome.

Results: We found that SCPP (odds ratio 1.039, = 0.002) is independently associated with positive neurologic recovery. The relative risk for not recovering neurologic function continually increased as individuals were exposed to SCPP below 50 mm Hg. Individuals who improved in neurologic grade dropped below SCPP of 50 mm Hg fewer times than those who did not improve ( = 0.012). This effect was not observed for MAP or CSFP. Those who were exposed to SCPP below 50 mm Hg were less likely to improve from their baseline neurologic impairment grade ( = 0.0056).

Conclusions: We demonstrate that maintaining SCPP above 50 mm Hg is a strong predictor of improved neurologic recovery following spinal cord injury. This suggests that SCPP (the difference between MAP and CSFP) can provide useful information to guide the hemodynamic management of patients with acute spinal cord injury.
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http://dx.doi.org/10.1212/WNL.0000000000004519DOI Listing
October 2017

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

Factors predictive of topographical accuracy in spine level localization.

J Spine Surg 2017 Mar;3(1):23-30

University of British Columbia, Vancouver, BC, Canada.

Background: Pre-operative spine level localization by palpation of anatomical landmarks (ribs, spinous processes) in posterior approaches for surgeries from T4 to L2 is often inaccurate. This can lead to ineffective utilization of procedural time, increased radiation dose, potentially longer skin incision and wrong level surgery. Factors affecting topographical accuracy includes body mass index (BMI) of the patient, congenital or acquired deformity and knowledge of topographical anatomy.

Methods: All patients had the presumed location of their pathology marked on the skin using anatomical landmarks prior to application of the Target Tape (Vancouver, BC, Canada) and verification using an anterior-posterior radiograph. Potential factors predictive of accurate pre-operative spine level localization such as age, gender, BMI, palpable deformity, pathology related interspinous distance (ISPD) and pathology related skin to spinous process distance were evaluated.

Results: A prospective study was performed with 30 consecutive patients undergoing posterior spine surgery (T4 to L2). Accuracy of pathology related spine level localization using anatomical landmarks was only 40%. Pathology related ISPDs of more than 10 mm and palpable deformity was significantly correlated with successful determination of spine levels using anatomical landmarks.

Conclusions: This study showed that poor spine level localization using anatomical landmarks was associated with pathology related ISPDs of less than 10 mm. Conversely, patients with palpable spinal deformity have their levels easily localized.
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http://dx.doi.org/10.21037/jss.2017.02.06DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5386898PMC
March 2017

A Targeted Proteomics Analysis of Cerebrospinal Fluid after Acute Human Spinal Cord Injury.

J Neurotrauma 2017 06 7;34(12):2054-2068. Epub 2017 Apr 7.

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

Efforts to validate novel therapies in acute clinical trials for spinal cord injury (SCI) are impeded by the lack of objective quantitative measures that reflect injury severity and accurately predict neurological recovery. Therefore, a strong rationale exists for establishing neurochemical biomarkers that objectively quantify injury severity and predict outcome. Here, we conducted a targeted proteomics analysis of cerebrospinal fluid (CSF) samples derived from 29 acute SCI patients (American Spinal Injury Association Impairment Scale [AIS] A, B, or C) acquired at 24, 48, and 72 h post-injury. From a total of 165 proteins, we identified 27 potential biomarkers of injury severity (baseline AIS A, B, or C), with triosephosphate isomerase having the strongest relationship to AIS grade. The majority of affected proteins (24 of 27) were more abundant in samples from AIS A patients than in those from AIS C patients, suggesting that for the most part, these proteins are released into the CSF more readily with more severe trauma to the spinal cord. We then analyzed the relationship between CSF protein abundance and neurological recovery. For AIS grade improvement over 6 months, we identified 34 proteins that were associated with AIS grade conversion (p < 0.05); however, these associations were not statistically significant after adjusting for multiple comparisons. For total motor score (TMS) recovery over 6 months, after adjusting for baseline neurological injury level, we identified 46 proteins with a statistically significant association with TMS recovery. Twenty-two of these proteins were among the 27 proteins that were related to baseline AIS grade, consistent with the notion that protein markers that reflect a more severe injury also appropriately predict a poorer recovery of motor function. In summary, this study provides a description of the CSF proteome changes that occur after acute human SCI, and reveals a number of protein candidates for further validation as potential biomarkers of injury severity.
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http://dx.doi.org/10.1089/neu.2016.4879DOI Listing
June 2017

Parallel Metabolomic Profiling of Cerebrospinal Fluid and Serum for Identifying Biomarkers of Injury Severity after Acute Human Spinal Cord Injury.

Sci Rep 2016 12 14;6:38718. Epub 2016 Dec 14.

Department of Chemistry, University of Alberta, Edmonton, AB, T6G2G2, Canada.

Suffering an acute spinal cord injury (SCI) can result in catastrophic physical and emotional loss. Efforts to translate novel therapies in acute clinical trials are impeded by the SCI community's singular dependence upon functional outcome measures. Therefore, a compelling rationale exists to establish neurochemical biomarkers for the objective classification of injury severity. In this study, CSF and serum samples were obtained at 3 time points (~24, 48, and 72 hours post-injury) from 30 acute SCI patients (10 AIS A, 12 AIS B, and 8 AIS C). A differential chemical isotope labeling liquid chromatography mass spectrometry (CIL LC-MS) with a universal metabolome standard (UMS) was applied to the metabolomic profiling of these samples. This method provided enhanced detection of the amine- and phenol-containing submetabolome. Metabolic pathway analysis revealed dysregulations in arginine-proline metabolism following SCI. Six CSF metabolites were identified as potential biomarkers of baseline injury severity, and good classification performance (AUC > 0.869) was achieved by using combinations of these metabolites in pair-wise comparisons of AIS A, B and C patients. Using the UMS strategy, the current data set can be expanded to a larger cohort for biomarker validation, as well as discovering biomarkers for predicting neurologic outcome.
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http://dx.doi.org/10.1038/srep38718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5155264PMC
December 2016

Mean Arterial Blood Pressure Management of Acute Traumatic Spinal Cord Injured Patients during the Pre-Hospital and Early Admission Period.

J Neurotrauma 2017 03 13;34(6):1271-1277. Epub 2017 Jan 13.

3 Department of Orthopaedics, Vancouver Spine Surgery Institute, University of British Columbia , Blusson Spinal Cord Centre, Vancouver, British Columbia, Canada .

The optimization and maintenance of mean arterial blood pressure (MAP) and the general avoidance of systemic hypotension for the first 5-7 days following acute traumatic spinal cord injury (tSCI) is considered to be important for minimizing secondary spinal cord ischemic damage. The characterization of hemodynamic parameters in the immediate post-injury stage prior to admission to a specialized spine unit has not been previously reported. Here we describe the blood pressure management of 40 acute tSCI patients in the early post-injury phases of care prior to their arrival in a specialized spinal injury high dependency unit (HDU), intensive care unit (ICU), or operating room (OR). This study found that a significant proportion of these patients experience periods of relative hypotension prior to their admission to a specialized spinal unit. In particular, the mean calculated MAP was 78.8 mm Hg, with 52% of MAP measurements <80 mm Hg at primary receiving hospitals. Despite having a mean calculated MAP of 83.3 mm Hg in the emergency room of the tertiary hospital, 40% of the MAP measurements were <80 mm Hg. Although stringent monitoring and management of MAP may be facilitated and adhered to in a spinal HDU, ICU, or OR, it is important to recognize that acute traumatic SCI patients may experience many periods of relative hypotension prior to their arrival in such specialized units. This study highlights the need for education and awareness to optimize the hemodynamic management of acute SCI patients during the immediate post-injury period.
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http://dx.doi.org/10.1089/neu.2016.4689DOI Listing
March 2017

Cerebrospinal Fluid Biomarkers To Stratify Injury Severity and Predict Outcome in Human Traumatic Spinal Cord Injury.

J Neurotrauma 2017 02 15;34(3):567-580. Epub 2016 Aug 15.

1 Department of Orthopedics, Vancouver Spine Surgery Institute , Vancouver, British Columbia, Canada .

Neurologic impairment after spinal cord injury (SCI) is currently measured and classified by functional examination. Biological markers that objectively classify injury severity and predict outcome would greatly facilitate efforts to evaluate acute SCI therapies. The purpose of this study was to determine how well inflammatory and structural proteins within the cerebrospinal fluid (CSF) of acute traumatic SCI patients predicted American Spinal Injury Association Impairment Scale (AIS) grade conversion and motor score improvement over 6 months. Fifty acute SCI patients (29 AIS A, 9 AIS B, 12 AIS C; 32 cervical, 18 thoracic) were enrolled and CSF obtained through lumbar intrathecal catheters to analyze interleukin (IL)-6, IL-8, monocyte chemotactic protein (MCP)-1, tau, S100β, and glial fibrillary acidic protein (GFAP) at 24 h post-injury. The levels of IL-6, tau, S100β, and GFAP were significantly different between patients with baseline AIS grades of A, B, or C. The levels of all proteins (IL-6, IL-8, MCP-1, tau, S100β, and GFAP) were significantly different between those who improved an AIS grade over 6 months and those who did not improve. Linear discriminant analysis modeling was 83% accurate in predicting AIS conversion. For AIS A patients, the concentrations of proteins such as IL-6 and S100β correlated with conversion to AIS B or C. Motor score improvement also was strongly correlated with the 24-h post-injury CSF levels of all six biomarkers. The analysis of CSF can provide valuable biological information about injury severity and recovery potential after acute SCI. Such biological markers may be valuable tools for stratifying individuals in acute clinical trials where variability in spontaneous recovery requires large recruitment cohorts for sufficient power.
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http://dx.doi.org/10.1089/neu.2016.4435DOI Listing
February 2017

A comparison of the Wiltse versus midline approaches in degenerative conditions of the lumbar spine.

J Neurosurg Spine 2016 Sep 22;25(3):332-8. Epub 2016 Apr 22.

Vancouver Spine Surgery Institute and Department of Orthopaedics, University of British Columbia, Vancouver, British Columbia;

OBJECTIVE The objective of this study was to determine if there is a significant difference in surgical site infection (SSI) when comparing the Wiltse and midline approaches for posterior instrumented interbody fusions of the lumbar spine and, secondarily, to evaluate if the reoperation rates and specific causes for reoperation were similar for both approaches. METHODS A total of 358 patients who underwent 1- or 2-level posterior instrumented interbody fusions for degenerative lumbar spinal pathology through either a midline or Wiltse approach were prospectively followed between March 2005 and January 2011 at a single tertiary care facility. A retrospective analysis was performed primarily to evaluate the incidence of SSI and the incidence and causes for reoperation. Secondary outcome measures included intraoperative complications, blood loss, and length of stay. A matched analysis was performed using the Fisher's exact test and a logistic regression model. The matched analysis controlled for age, sex, comorbidities, number of index levels addressed surgically, number of levels fused, and the use of bone grafting. RESULTS All patients returned for follow-up at 1 year, and adverse events were followed for 2 years. The rate of SSI was greater in the midline group (8 of 103 patients; 7.8%) versus the Wiltse group (1 of 103 patients; 1.0%) (p = 0.018). Fewer additional surgical procedures were performed in the Wiltse group (p = 0.025; OR 0.47; 95% CI 0.23-0.95). Proximal adjacent segment failure requiring reoperation occurred more frequently in the midline group (15 of 103 patients; 14.6%) versus the Wiltse group (6 of 103 patients; 5.8%) (p = 0.048). Blood loss was significantly lower in the Wiltse group (436 ml) versus the midline group (703 ml); however, there was no significant difference between the 2 groups in intraoperative complications or length of stay. CONCLUSIONS The patients who underwent the Wiltse approach had a decreased risk of wound breakdown and infection, less blood loss, and fewer reoperations than the midline patients. The risk of adjacent segment failure in short posterior constructs is lower with a Wiltse approach.
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http://dx.doi.org/10.3171/2016.2.SPINE151018DOI Listing
September 2016
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