Publications by authors named "Tamir Ailon"

66 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

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

The Effect of Perioperative Adverse Events on Long-Term Patient-Reported Outcomes After Lumbar Spine Surgery.

Neurosurgery 2021 01;88(2):420-427

Department of Surgery, Vancouver General Hospital/University of British Columbia, Vancouver, Canada.

Background: Perioperative adverse events (AEs) lead to patient disappointment and greater costs. There is a paucity of data on how AEs affect long-term outcomes.

Objective: To examine perioperative AEs and their impact on outcome after lumbar spine surgery.

Methods: A total of 3556 consecutive patients undergoing surgery for lumbar degenerative disorders enrolled in the Canadian Spine Outcomes and Research Network were analyzed. AEs were defined using the validated Spine AdVerse Events Severity system. Outcomes at 3, 12, and 24 mo postoperatively included the Owestry Disability Index (ODI), 12-Item Short-Form Health Survey (SF-12) Physical (PCS) and Mental (MCS) Component Summary scales, visual analog scale (VAS) leg and back, EuroQol-5D (EQ5D), and satisfaction.

Results: AEs occurred in 767 (21.6%) patients, and 85 (2.4%) patients suffered major AEs. Patients with major AEs had worse ODI scores and did not reach minimum clinically important differences at 2 yr (no AE: 25.7 ± 19.2, major: 36.4 ± 19.1, P < .001). Major AEs were associated with worse ODI scores on multivariable linear regression (P = .011). PCS scores were lower after major AEs (43.8 ± 9.5, vs 37.7 ± 20.3, P = .002). On VAS leg and back and EQ5D, the 2-yr outcomes were significantly different between the major and no AE groups (<0.01), but these differences were small (VAS leg: 3.4 ± 3.0 vs 4.0 ± 3.3; VAS back: 3.5 ± 2.7 vs 4.5 ± 2.6; EQ5D: 0.75 ± 0.2 vs 0.64 ± 0.2). SF12 MCS scores were not different. Rates of satisfaction were lower after major AEs (no AE: 84.6%, major: 72.3%, P < .05).

Conclusion: Major AEs after lumbar spine surgery lead to worse functional outcomes and lower satisfaction. This highlights the need to implement strategies aimed at reducing AEs.
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http://dx.doi.org/10.1093/neuros/nyaa427DOI Listing
January 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

Development of a Novel Cervical Deformity Surgical Invasiveness Index.

Spine (Phila Pa 1976) 2020 Jan;45(2):116-123

Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA.

Study Design: Retrospective review.

Objective: The aim of this study was to develop a novel surgical invasiveness index for cervical deformity (CD) surgery that incorporates CD-specific parameters.

Summary Of Background Data: There has been a surgical invasiveness index for general spine surgery and adult spinal deformity, but a CD index has not been developed.

Methods: CD was defined as at least one of the following: C2-C7 Cobb >10°, cervical lordosis (CL) >10°, cervical sagittal vertical axis (cSVA) >4 cm, chin brow vertical angle >25°. Consensus from experienced spine and neurosurgeons selected weightings for each variable that went into the invasiveness index. Binary logistic regression predicted high operative time (>338 minutes), estimated blood loss (EBL) (>600 mL), or length of stay (LOS) >5 days) based on the median values of operative time, EBL, and LOS. Multivariable regression modeling was utilized to construct a final model incorporating the strongest combination of factors to predict operative time, LOS, and EBL.

Results: Eighty-five CD patients were included (61 years, 66% females). The variables in the newly developed CD invasiveness index with their corresponding weightings were: history of previous cervical surgery (3), anterior cervical discectomy and fusion (2/level), corpectomy (4/level), levels fused (1/level), implants (1/level), posterior decompression (2/level), Smith-Peterson osteotomy (2/level), three-column osteotomy (8/level), fusion to upper cervical spine (2), absolute change in T1 slope minus cervical lordosis, cSVA, T4-T12 thoracic kyphosis (TK), and sagittal vertical axis (SVA) from baseline to 1-year. The newly developed CD-specific invasiveness index strongly predicted long LOS (R = 0.310, P < 0.001), high EBL (R = 0.170, P = 0.011), and extended operative time (R = 0.207, P = 0.031). A second analysis used multivariable regression modeling to determine which combination of factors in the newly developed index were the strongest determinants of operative time, LOS, and EBL. The final predictive model included: number of corpectomies, levels fused, decompression, combined approach, and absolute changes in SVA, cSVA, and TK. This model predicted EBL (R = 0.26), operative time (R = 0.12), and LOS (R = 0.13).

Conclusion: Extended LOS, operative time, and high blood loss were strongly predicted by the newly developed CD invasiveness index, incorporating surgical factors and radiographic parameters clinically relevant for patients undergoing CD corrective surgery.

Level Of Evidence: 4.
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http://dx.doi.org/10.1097/BRS.0000000000003175DOI Listing
January 2020

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

Clinical outcomes research in spine surgery: what are appropriate follow-up times?

J Neurosurg Spine 2018 12;30(3):397-404

1Department of Surgery, Vancouver General Hospital/University of British Columbia, Vancouver, British Columbia.

In BriefThe time course required for the patient-reported outcomes of pain, physical function, and mental health to reach a recovery plateau after elective lumbar spine surgery was assessed utilizing a prospectively maintained multicenter registry. The work is important as it demonstrates that specific health dimensions follow different recovery plateaus and it provides evidence that a 2-year postoperative follow-up is not required to accurately assess the treatment effect of established surgeries for lumbar spinal pathologies.
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http://dx.doi.org/10.3171/2018.8.SPINE18715DOI Listing
December 2018

'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

Patient-reported outcomes following surgery for degenerative spondylolitshtesis: comparison of a universal and multitier health care system.

Spine J 2019 01 10;19(1):24-33. Epub 2018 Oct 10.

University of British Columbia, Vancouver, British Columbia, Canada; Canadian Spine Outcomes and Research Network, Canada.

Study Design: Retrospective review of results from a prospectively collected Canadian cohort in comparison to published literature.

Objectives: (1) To investigate whether patients in a universal health care system have different outcomes than those in a multitier health care system in surgical management of degenerative spondylolisthesis (DS). (2) To identify independent factors predictive of outcome in surgical DS patients.

Summary Of Background Data: Canada has a national health insurance program with unique properties. It is a single-payer system, coverage is universal, and access to specialist care requires referral by the primary care physician. The United States on the other hand is a multitier public/private payer system with more rapid access for insured patients to specialist care.

Methods: Surgical DS patients treated between 2013 and 2016 in Canada were identified through the Canadian Spine Outcome Research Network (CSORN) database, a national registry that prospectively enrolls consecutive patients with spinal pathology from 16 tertiary care academic hospitals. This population was compared with the surgical DS arm of patients treated in the Spine Patients Outcome Research Trial (SPORT) study. We compared baseline demographics, spine-related, and health-related quality of life (HRQOL) outcomes at 3 months and 1 year. Multivariate analysis was used to identify factors predictive of outcome in surgical DS patients.

Results: The CSORN cohort of 213 patients was compared with the SPORT cohort of 248 patients. Patients in the CSORN cohort were younger (mean age 60.1 vs. 65.2; p<.001), comprised fewer females (60.1% vs. 67.7%; p=.09), and had a higher proportion of smokers (23.3% vs. 8.9%; p<.001). The SPORT cohort had more patients receiving compensation (14.6% vs. 7.7%; p<.001). The CSORN cohort consisted of patients with slightly greater baseline disability (Oswestry disability index scores: 47.7 vs. 44.0; p=.008) and had more patients with symptom duration of greater than 6 months (93.7% vs. 62.1%; p<.001). The CSORN cohort showed greater satisfaction with surgical results at 3 months (91.1% vs. 66.1% somewhat or very satisfied; p<.01) and 1 year (88.2% vs. 71.0%, p<.01). Improvements in back and leg pain were similar comparing the two cohorts. On multivariate analysis, duration of symptoms, treatment group (CSORN vs. SPORT) or insurance type (public/Medicare/Medicaid vs. Private/Employer) predicted higher level of postoperative satisfaction. Baseline depression was also associated with worse Oswestry disability index at 1-year postoperative follow-up in both cohorts.

Conclusions: Surgical DS patients treated in Canada (CSORN cohort) reported higher levels of satisfaction than those treated in the United States (SPORT cohort) despite similar to slightly worse baseline HRQOL measures. Symptom duration and insurance type appeared to impact satisfaction levels. Improvements in other patient-reported health-related quality of life measures were similar between the cohorts.
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http://dx.doi.org/10.1016/j.spinee.2018.10.005DOI Listing
January 2019

Development of a Preoperative Predictive Model for Reaching the Oswestry Disability Index Minimal Clinically Important Difference for Adult Spinal Deformity Patients.

Spine Deform 2018 Sep - Oct;6(5):593-599

Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94131, USA.

Study Design: Retrospective review of prospective multicenter adult spinal deformity (ASD) database.

Objective: To create a model based on baseline demographic, radiographic, health-related quality of life (HRQOL), and surgical factors that can predict patients meeting the Oswestry Disability Index (ODI) minimal clinically important difference (MCID) at the two-year postoperative follow-up.

Summary Of Background Data: Surgical correction of ASD can result in significant improvement in disability as measured by ODI, with the goal of reaching at least one MCID. However, a predictive model for reaching MCID following ASD correction does not exist.

Methods: ASD patients ≥18 years and baseline ODI ≥ 30 were included. Initial training of the model comprised forty-three variables including demographic data, comorbidities, modifiable surgical variables, baseline HRQOL, and coronal/sagittal radiographic parameters. Patients were grouped by whether or not they reached at least one ODI MCID at two-year follow-up. Decision trees were constructed using the C5.0 algorithm with five different bootstrapped models. Internal validation was accomplished via a 70:30 data split for training and testing each model, respectively. Final predictions from the models were chosen by voting with random selection for tied votes. Overall accuracy, and the area under a receiver operating characteristic curve (AUC) were calculated.

Results: 198 patients were included (MCID: 109, No-MCID: 89). Overall model accuracy was 86.0%, with an AUC of 0.94. The top 11 predictors of reaching MCID were gender, Scoliosis Research Society (SRS) activity subscore, back pain, sagittal vertical axis (SVA), pelvic incidence-lumbar lordosis mismatch (PI-LL), primary version revision, T1 spinopelvic inclination angle (T1SPI), American Society of Anesthesiologists (ASA) grade, T1 pelvic angle (T1PA), SRS pain, SRS total.

Conclusions: A successful model was built predicting ODI MCID. Most important predictors were not modifiable surgical parameters, indicating that baseline clinical and radiographic status is a critical factor for reaching ODI MCID.

Level Of Evidence: Level II.
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http://dx.doi.org/10.1016/j.jspd.2018.02.010DOI Listing
January 2019

Patients with Adult Spinal Deformity with Previous Fusions Have an Equal Chance of Reaching Substantial Clinical Benefit Thresholds in Health-Related Quality of Life Measures but Do Not Reach the Same Absolute Level of Improvement.

World Neurosurg 2018 Aug 9;116:e354-e361. Epub 2018 May 9.

Department of Neurosurgery, University of California-San Francisco, San Francisco, California.

Background: Substantial clinical benefit (SCB) represents a threshold above which patients recognize substantial improvement and represents a rational target for defining clinical success. In adult spinal deformity (ASD) surgery, previous fusions may impact outcomes after deformity correction.

Objective: To investigate the impact of previous spinal fusion on the likelihood of reaching SCB thresholds for 2-year health-related quality of life (HRQOL) after ASD surgery.

Methods: We conducted a retrospective review comparing baseline demographic, HRQOL, and radiographic features for patients with ASD undergoing primary versus revision procedures. The primary outcome measure was reaching SCB threshold in Oswestry Disability Index (ODI), SF-36 Physical Component Summary (PCS), and back and leg pain (numeric rating scale). Secondary outcomes included absolute and change scores in ODI, PCS, and back and leg pain.

Results: In total, 332 patients achieved 2-year follow-up (228 primary; 104 revision cases). Those undergoing revision surgery had similar demographic features (age 58.3/55.9, female 80.8%/82.9%) to patients undergoing primary surgery. They had worse baseline HRQOL (ODI 48.5/41.2, PCS 29.5/33.4, back 7.5/7.0, and leg pain 4.9/4.3; P < 0.001) and radiographic deformity (sagittal vertical axis 111.4/45.1, lumbopelvic mismatch 26.7/11.0, pelvic tilt 29.5/21.0; P < 0.0001). Nevertheless, the number of patients who reached SCB for ODI (38.3/36.3%), PCS (48.5/53.4%), back (53.1/60.5%), and leg pain numeric rating scale (28.6/36.9%) did not significantly differ. Revision patients had worse 2-year HRQOL for all measures.

Conclusions: Patients undergoing revision surgery have worse baseline HRQOL and deformity. Although they do not achieve the same absolute level of 2-year HRQOL outcome, they have a similar likelihood of reaching SCB threshold for improvement in 2-year HRQOL.
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http://dx.doi.org/10.1016/j.wneu.2018.04.204DOI Listing
August 2018

Radiographic Fusion Grade Does Not Impact Health-Related Quality of Life in the Absence of Instrumentation Failure for Patients Undergoing Posterior Instrumented Fusion for Adult Spinal Deformity.

World Neurosurg 2018 Sep 27;117:e1-e7. Epub 2018 Apr 27.

Swedish Neurosciences Institute, Seattle, Washington, USA.

Background: Pseudarthrosis and rod fracture (RF) remain significant concerns after fusion for adult spinal deformity (ASD). Although a radiographic system of fusion grade has been proposed, the correlation between fusion grade and health-related quality of life measures (HRQoL) is not known.

Methods: In a retrospective review of a prospectively collected clinical database, patients that underwent ≥5-level posterior instrumented arthrodesis for ASD were evaluated. Fusion grade was determined on plain films using the Lenke criteria. Patients were grouped as 1) complete fusion (grade I or II at all levels), 2) incomplete fusion (grade 3 or 4 at any level), 3) rod fracture without revision (RF), and 4) rod fracture with revision (RFR). Outcome measures were the Oswestry Disability Index, Medical Outcomes Study 36-Item Short-Form Health Survey Physical and Mental Component Summaries, Scoliosis Research Society-22r total, and Lumbar Stiffness and Disability Index.

Results: There were 205 (85%) patients who achieved the minimum 2-year follow-up and were included. Complete fusion was achieved in 115 patients (56.1%), 55% patients (26.8%) had incomplete fusion, and 35% patients (17.1%) had RF. Of the 35 patients with RF, 19 (17.1%; 19/205) underwent revision while 16 (7.8%; 16/205) had RF without revision. HRQoL measures were significantly worse in the RFR group, whereas no significant differences were found between groups 1, 2, and 3.

Conclusions: Radiographic fusion grade after ASD surgery did not significantly impact HRQoL in the absence of RF. RFR was associated with significantly worse clinical outcomes. Fusion grade may be less predictive of clinical outcomes than the occurrence of RF.
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http://dx.doi.org/10.1016/j.wneu.2018.04.127DOI Listing
September 2018

Predictive Modeling of Length of Hospital Stay Following Adult Spinal Deformity Correction: Analysis of 653 Patients with an Accuracy of 75% within 2 Days.

World Neurosurg 2018 Jul 17;115:e422-e427. Epub 2018 Apr 17.

Department of Neurological Surgery, University of California San Francisco, San Francisco, California, USA.

Background: Length of stay (LOS) after surgery for adult spinal deformity (ASD) is a critical period that allows for optimal recovery. Predictive models that estimate LOS allow for stratification of high-risk patients.

Methods: A prospectively acquired multicenter database of patients with ASD was used. Patients with staged surgery or LOS >30 days were excluded. Univariable predictor importance ≥0.90, redundancy, and collinearity testing were used to identify variables for model building. A generalized linear model was constructed using a training dataset developed from a bootstrap sample; patients not randomly selected for the bootstrap sample were selected to the training dataset. LOS predictions were compared with actual LOS to calculate an accuracy percentage.

Results: Inclusion criteria were met by 653 patients. The mean LOS was 7.9 ± 4.1 days (median 7 days; range, 1-28 days). Following bootstrapping, 893 patients were modeled (653 in the training model and 240 in the testing model). Linear correlations for the training and testing datasets were 0.632 and 0.507, respectively. The prediction accuracy within 2 days of actual LOS was 75.4%.

Conclusions: Our model successfully predicted LOS after ASD surgery with an accuracy of 75% within 2 days. Factors relating to actual LOS, such as rehabilitation bed availability and social support resources, are not captured in large prospective datasets. Predictive analytics will play an increasing role in the future of ASD surgery, and future models will seek to improve the accuracy of these tools.
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http://dx.doi.org/10.1016/j.wneu.2018.04.064DOI Listing
July 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

Frailty and Health-Related Quality of Life Improvement Following Adult Spinal Deformity Surgery.

World Neurosurg 2018 Apr 31;112:e548-e554. Epub 2018 Jan 31.

International Spine Study Group Foundation, Brighton, Colorado, USA.

Background: Although the Adult Spinal Deformity Frailty Index (ASD-FI) predicts major complications and prolonged hospital length of stay after adult spinal deformity surgery, the impact of frailty on postoperative changes in health-related quality of life (HRQoL) is unknown.

Methods: Patients who underwent instrumented fusion of ≥4 levels for adult spinal deformity with minimum 2-year follow-up were stratified by Adult Spinal Deformity Frailty Index score into 3 groups: nonfrail, frail, and severely frail. Baseline and follow-up demographics, HRQoL measures, and radiographic parameters were analyzed. Primary outcome measures included proportion of patients who achieved substantial clinical benefit (SCB) in terms of Oswestry Disability Index, 36-Item Short Form Health Survey Physical Component Summary, and numeric back and leg pain scores.

Results: Inclusion criteria were met by 332 patients (135 nonfrail, 175 frail, 22 severely frail). Frail and severely frail patients were older and had more comorbidities, worse baseline HRQoL and pain scores, and worse radiographic deformity than nonfrail patients (P < 0.05). At 2-year follow-up, all outcome scores were worse in frail and severely frail patients compared with nonfrail patients. Frail patients improved more than nonfrail patients and were more likely to reach SCB for Oswestry Disability Index (43.7% vs. 29.3%; P = 0.025), 36-Item Short Form Health Survey Physical Component Summary (56.9% vs. 51.2%; P = 0.03), and leg pain (45.8% vs. 23.0%; P = 0.03) scores, but not back pain (57.5% vs. 63.4%; P = 0.045) score.

Conclusions: Despite higher risk stratification and worse baseline HRQoL, frail patients were more likely to reach SCB for most HRQoL measures compared with nonfrail patients. Severely frail patients were the least likely to reach SCB for most HRQoL measures.
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http://dx.doi.org/10.1016/j.wneu.2018.01.079DOI Listing
April 2018

Outcomes of Operative Treatment for Adult Cervical Deformity: A Prospective Multicenter Assessment With 1-Year Follow-up.

Neurosurgery 2018 11;83(5):1031-1039

Department of Neurological Surgery, University of California, San Francisco, San Francisco, California.

Background: Despite the potential for profound impact of adult cervical deformity (ACD) on function and health-related quality of life (HRQOL), there are few high-quality studies that assess outcomes of surgical treatment for these patients.

Objective: To determine the impact of surgical treatment for ACD on HRQOL.

Methods: We conducted a prospective cohort study of surgically treated ACD patients eligible for 1-yr follow-up. Baseline deformity characteristics, surgical parameters, and 1-yr HRQOL outcomes were assessed.

Results: Of 77 ACD patients, 55 (71%) had 1-yr follow-up (64% women, mean age of 62 yr, mean Charlson Comorbidity Index of 0.6, previous cervical surgery in 47%). Diagnoses included cervical sagittal imbalance (56%), cervical kyphosis (55%), proximal junctional kyphosis (7%) and coronal deformity (9%). Posterior fusion was performed in 85% (mean levels = 10), and anterior fusion was performed in 53% (mean levels = 5). Three-column osteotomy was performed in 24% of patients. One year following surgery, ACD patients had significant improvement in Neck Disability Index (50.5 to 38.0, P < .001), neck pain numeric rating scale score (6.9 to 4.3, P < .001), EuroQol 5 dimension (EQ-5D) index (0.51 to 0.66, P < .001), and EQ-5D subscores: mobility (1.9 to 1.7, P = .019), usual activities (2.2 to 1.9, P = .007), pain/discomfort (2.4 to 2.1, P < .001), anxiety/depression (1.8 to 1.5, P = .014).

Conclusion: Based on a prospective multicenter series of ACD patients, surgical treatment provided significant improvement in multiple measures of pain and function, including Neck Disability Index, neck pain numeric rating scale score, and EQ-5D. Further follow-up will be necessary to assess the long-term durability of these improved outcomes.
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http://dx.doi.org/10.1093/neuros/nyx574DOI Listing
November 2018

An assessment of frailty as a tool for risk stratification in adult spinal deformity surgery.

Neurosurg Focus 2017 Dec;43(6):E3

Department of Neurosurgery, University of California San Francisco School of Medicine, San Francisco, California.

OBJECTIVE The goal of this study was to analyze the value of an adult spinal deformity frailty index (ASD-FI) in preoperative risk stratification. Preoperative risk assessment is imperative before procedures known to have high complication rates, such as ASD surgery. Frailty has been associated with risk of complications in trauma surgery, and preoperative frailty assessments could improve the accuracy of risk stratification by providing a comprehensive analysis of patient factors that contribute to an increased risk of complications. METHODS Using 40 variables, the authors calculated frailty scores with a validated method for 417 patients (enrolled between 2010 and 2014) with a minimum 2-year follow-up in an ASD database. On the basis of these scores, the authors categorized patients as not frail (NF) (< 0.3 points), frail (0.3-0.5 points), or severely frail (SF) (> 0.5 points). The correlation between frailty category and incidence of complications was analyzed. RESULTS The overall mean ASD-FI score was 0.33 (range 0.0-0.8). Compared with NF patients (n = 183), frail patients (n = 158) and SF patients (n = 109) had longer mean hospital stays (1.2 and 1.6 times longer, respectively; p < 0.001). The adjusted odds of experiencing a major intraoperative or postoperative complication were higher for frail patients (OR 2.8) and SF patients ( 4.1) compared with NF patients (p < 0.01). For frail and SF patients, respectively, the adjusted odds of developing proximal junctional kyphosis (OR 2.8 and 3.1) were higher than those for NF patients. The SF patients had higher odds of developing pseudarthrosis (OR 13.0), deep wound infection (OR 8.0), and wound dehiscence (OR 13.4) than NF patients (p < 0.05), and they had 2.1 times greater odds of reoperation (p < 0.05). CONCLUSIONS Greater patient frailty, as measured by the ASD-FI, was associated with worse outcome in many common quality and value metrics, including greater risk of major complications, proximal junctional kyphosis, pseudarthrosis, deep wound infection, wound dehiscence, reoperation, and longer hospital stay.
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http://dx.doi.org/10.3171/2017.10.FOCUS17472DOI Listing
December 2017

Assessment of a Novel Adult Cervical Deformity Frailty Index as a Component of Preoperative Risk Stratification.

World Neurosurg 2018 Jan 26;109:e800-e806. Epub 2017 Oct 26.

Department of Neurosurgery, University of California San Francisco School of Medicine, San Francisco, California, USA.

Objective: To determine the value of a novel adult cervical deformity frailty index (CD-FI) in preoperative risk stratification.

Methods: We reviewed a prospective, multicenter database of adults with cervical spine deformity. We selected 40 variables to construct the CD-FI using a validated method. Patients were categorized as not frail (NF) (<0.2), frail (0.2-0.4), or severely frail (SF) (>0.4) according to CD-FI score. We performed multivariate logistic regression to determine the relationships between CD-FI score and incidence of complications, length of hospital stay, and discharge disposition.

Results: Of 61 patients enrolled from 2009 to 2015 with at least 1 year of follow-up, the mean CD-FI score was 0.26 (range 0.25-0.59). Seventeen patients were categorized as NF, 34 as frail, and 10 as SF. The incidence of major complications increased with greater frailty, with a gamma correlation coefficient of 0.25 (asymptotic standard error, 0.22). The odds of having a major complication were greater for frail patients (odds ratio 4.4; 95% confidence interval 0.6-32) and SF patients (odds ratio 43; 95% confidence interval 2.7-684) compared with NF patients. Greater frailty was associated with a greater incidence of medical complications and had a gamma correlation coefficient of 0.30 (asymptotic standard error, 0.26). Surgical complications, discharge disposition, and length of hospital stay did not correlate significantly with frailty.

Conclusions: Greater frailty was associated with greater risk of major complications for patients undergoing cervical spine deformity surgery. The CD-FI may be used to improve the accuracy of preoperative risk stratification and allow for adequate patient counseling.
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http://dx.doi.org/10.1016/j.wneu.2017.10.092DOI Listing
January 2018

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
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