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Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_13 | Pages 49 - 49
1 Dec 2022
Charest-Morin R Bailey C McIntosh G Rampersaud RY Jacobs B Cadotte D Fisher C Hall H Manson N Paquet J Christie S Thomas K Phan P Johnson MG Weber M Attabib N Nataraj A Dea N
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In multilevel posterior cervical instrumented fusions, extending the fusion across the cervico-thoracic junction at T1 or T2 (CTJ) has been associated with decreased rate of re-operation and pseudarthrosis but with longer surgical time and increased blood loss. The impact on patient reported outcomes (PROs) remains unclear. The primary objective was to determine whether extending the fusion through the CTJ influenced PROs at 3 and 12 months after surgery. Secondary objectives were to compare the number of patients reaching the minimally clinically important difference (MCID) for the PROs and mJOA, operative time duration, intra-operative blood loss (IOBL), length of stay (LOS), discharge disposition, adverse events (AEs), re-operation within 12 months of the surgery, and patient satisfaction.

This is a retrospective analysis of prospectively collected data from a multicenter observational cohort study of patients with degenerative cervical myelopathy. Patients who underwent a posterior instrumented fusion of 4 levels of greater (between C2-T2) between January 2015 and October 2020 with 12 months follow-up were included. PROS (NDI, EQ5D, SF-12 PCS and MCS, NRS arm and neck pain) and mJOA were compared using ANCOVA, adjusted for baseline differences. Patient demographics, comorbidities and surgical details were abstracted. Percentafe of patient reaching MCID for these outcomes was compared using chi-square test. Operative duration, IOBL, AEs, re-operation, discharge disposittion, LOS and satisfaction were compared using chi-square test for categorical variables and independent samples t-tests for continuous variables.

A total of 206 patients were included in this study (105 patients not crossing the CTJ and 101 crossing the CTJ). Patients who underwent a construct extending through the CTJ were more likely to be female and had worse baseline EQ5D and NDI scores (p> 0.05). When adjusted for baseline difference, there was no statistically significant difference between the two groups for the PROs and mJOA at 3 and 12 months. Surgical duration was longer (p 0.05). Satisfaction with the surgery was high in both groups but significantly different at 12 months (80% versus 72%, p= 0.042 for the group not crossing the CTJ and the group crossing the CTJ, respectively). The percentage of patients reaching MCID for the NDI score was 55% in the non-crossing group versus 69% in the group extending through the CTJ (p= 0.06).

Up to 12 months after the surgery, there was no statistically significant differences in PROs between posterior construct extended to or not extended to the upper thoracic spine. The adverse event profile did not differ significantly, but longer surgical time and blood loss were associated with construct extending across the CTJ.


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_13 | Pages 52 - 52
1 Dec 2022
Moskven E Lasry O Singh S Flexman A Fisher C Street J Boyd M Ailon T Dvorak M Kwon B Paquette S Dea N Charest-Morin R
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En bloc resection for primary bone tumours and isolated metastasis are complex surgeries associated with a high rate of adverse events (AEs). The primary objective of this study was to explore the relationship between frailty/sarcopenia and major perioperative AEs following en bloc resection for primary bone tumours or isolated metastases of the spine. Secondary objectives were to report the prevalence and distribution of frailty and sarcopenia, and determine the relationship between these factors and length of stay (LOS), unplanned reoperation, and 1-year postoperative mortality in this population.

This is a retrospective study of prospectively collected data from a single quaternary care referral center consisting of patients undergoing an elective en bloc resection for a primary bone tumour or an isolated spinal metastasis between January 1st, 2009 and February 28th, 2020. Frailty was calculated with the modified frailty index (mFI) and spine tumour frailty index (STFI). Sarcopenia, determined by the total psoas area (TPA) vertebral body (VB) ratio (TPA/VB), was measured at L3 and L4. Regression analysis produced ORs, IRRs, and HRs that quantified the association between frailty/sarcopenia and major perioperative AEs, LOS, unplanned reoperation and 1-year postoperative mortality.

One hundred twelve patients met the inclusion criteria. Using the mFI, five patients (5%) were frail (mFI ³ 0.21), while the STFI identified 21 patients (19%) as frail (STFI ³ 2). The mean CT ratios were 1.45 (SD 0.05) and 1.81 (SD 0.06) at L3 and L4 respectively. Unadjusted analysis demonstrated that sarcopenia and frailty were not significant predictors of major perioperative AEs, LOS or unplanned reoperation. Sarcopenia defined by the CT L3 TPA/VB and CT L4 TPA/VB ratios significantly predicted 1-year mortality (HR of 0.32 per one unit increase, 95% CI 0.11-0.93, p=0.04 vs. HR of 0.28 per one unit increase, 95% CI 0.11-0.69, p=0.01) following unadjusted analysis. Frailty defined by an STFI score ≥ 2 predicted 1-year postoperative mortality (OR of 2.10, 95% CI 1.02-4.30, p=0.04).

The mFI was not predictive of any clinical outcome in patients undergoing en bloc resection for primary bone tumours or isolated metastases of the spine. Sarcopenia defined by the CT L3 TPA/VB and L4 TPA/VB and frailty assessed with the STFI predicted 1-year postoperative mortality on univariate analysis but not major perioperative AEs, LOS or reoperation. Further investigation with a larger cohort is needed to identify the optimal measure for assessing frailty and sarcopenia in this spine population.


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_12 | Pages 76 - 76
1 Dec 2022
Eltit F Ng T Gokaslan Z Fisher C Dea N Charest-Morin R
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Giant cell tumors of bone (GCTs) are locally aggressive tumors with recurrence potential that represent up to 10% of primary tumors of the bone. GCTs pathogenesis is driven by neoplastic mononuclear stromal cells that overexpress receptor activator of nuclear factor kappa-B/ligand (RANKL). Treatment with specific anti-RANKL antibody (denosumab) was recently introduced, used either as a neo-adjuvant in resectable tumors or as a stand-alone treatment in unresectable tumors. While denosumab has been increasingly used, a percentage of patients do not improve after treatment. Here, we aim to determine molecular and histological patterns that would help predicting GCTs response to denosumab to improve personalized treatment.

Nine pre-treatment biopsies of patients with spinal GCT were collected at 2 centres. In 4 patients denosumab was used as a neo-adjuvant, 3 as a stand-alone and 2 received denosumab as adjuvant treatment. Clinical data was extracted retrospectively. Total mRNA was extracted by using a formalin-fixed paraffin-embedded extraction kit and we determined the transcript profile of 730 immune-oncology related genes by using the Pan Cancer Immune Profiling panel (Nanostring). The gene expression was compared between patients with good and poor response to Denosumab treatment by using the nSolver Analysis Software (Nanostring). Immunohistochemistry was performed in the tissue slides to characterize cell populations and immune response in CGTs.

Two out of 9 patients showed poor clinical response with tumor progression and metastasis. Our analysis using unsupervised hierarchical clustering determined differences in gene expression between poor responders and good responders before denosumab treatment. Poor responding lesions are characterized by increased expression of inflammatory cytokines as IL8, IL1, interferon a and g, among a myriad of cytokines and chemokines (CCL25, IL5, IL26, IL25, IL13, CCL20, IL24, IL22, etc.), while good responders are characterized by elevated expression of platelets (CD31 and PECAM), coagulation (CD74, F13A1), and complement classic pathway (C1QB, C1R, C1QBP, C1S, C2) markers, together with extracellular matrix proteins (COL3A1, FN1,. Interestingly the T-cell response is also different between groups. Poor responding lesions have increased Th1 and Th2 component, but good responders have an increased Th17 component. Interestingly, the checkpoint inhibitor of the immune response PD1 (PDCD1) is increased ~10 fold in poor responders.

This preliminary study using a novel experimental approach revealed differences in the immune response in GCTs associated with clinical response to denosumab. The increased activity of checkpoint inhibitor PD1 in poor responders to denosumab treatment may have implications for therapy, raising the potential to investigate immunotherapy as is currently used in other neoplasms. Further validation using a larger independent cohort will be required but these results could potentially identify the patients who would most benefit from denosumab therapy.


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_13 | Pages 40 - 40
1 Dec 2022
Dandurand C Mashayekhi M McIntosh G Street J Fisher C Jacobs B Johnson MG Paquet J Wilson J Hall H Bailey C Christie S Nataraj A Manson N Phan P Rampersaud RY Thomas K Dea N Soroceanu A Marion T Kelly A Santaguida C Finkelstein J Charest-Morin R
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Prolonged length of stay (LOS) is a significant contributor to the variation in surgical health care costs and resource utilization after elective spine surgery. The primary goal of this study was to identify patient, surgical and institutional variables that influence LOS. The secondary objective is to examine variability in institutional practices among participating centers.

This is a retrospective study of a prospectively multicentric followed cohort of patients enrolled in the CSORN between January 2015 and October 2020. A logistic regression model and bootstrapping method was used. A survey was sent to participating centers to assessed institutional level interventions in place to decrease LOS. Centers with LOS shorter than the median were compared to centers with LOS longer than the median.

A total of 3734 patients were included (979 discectomies, 1102 laminectomies, 1653 fusions). The median LOS for discectomy, laminectomy and fusion were respectively 0.0 day (IQR 1.0), 1.0 day (IQR 2.0) and 4.0 days (IQR 2.0). Laminectomy group had the largest variability (SD=4.4, Range 0-133 days). For discectomy, predictors of LOS longer than 0 days were having less leg pain, higher ODI, symptoms duration over 2 years, open procedure, and AE (p< 0.05). Predictors of longer LOS than median of 1 day for laminectomy were increasing age, living alone, higher ODI, open procedures, longer operative time, and AEs (p< 0.05). For posterior instrumented fusion, predictors of longer LOS than median of 4 days were older age, living alone, more comorbidities, less back pain, higher ODI, using narcotics, longer operative time, open procedures, and AEs (p< 0.05). Ten centers (53%) had either ERAS or a standardized protocol aimed at reducing LOS.

In this study stratifying individual patient and institutional level factors across Canada, several independent predictors were identified to enhance the understanding of LOS variability in common elective lumbar spine surgery. The current study provides an updated detailed analysis of the ongoing Canadian efforts in the implementation of multimodal ERAS care pathways. Future studies should explore multivariate analysis in institutional factors and the influence of preoperative patient education on LOS.