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.

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.

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.

Despite the current trend favoring surgical treatment of displaced intra-articular calcaneal fractures (DIACFs), studies have not been able to demonstrate superior functional outcomes when compared to non-operative treatment. These fractures are notoriously difficult to reduce. Studies investigating surgical fixation often lack information about the quality of reduction even though it may play an important role in the success of this procedure. We wanted to establish if, amongst surgically treated DIACF, an anatomic reduction led to improved functional outcomes at 12 months.

From July 2011 to December 2020, at a level I trauma center, 84 patients with an isolated DIACF scheduled for surgical fixation with plate and screws using a lateral extensile approach were enrolled in this prospective cohort study and followed over a 12-month period. Post-operative computed tomography (CT) imaging of bilateral feet was obtained to assess surgical reduction using a combination of pre-determined parameters: Böhler's angle, calcaneal height, congruence and articular step-off of the posterior facet and calcaneocuboid (CC) joint. Reduction was judged anatomic when Böhler's angle and calcaneal height were within 20% of the contralateral foot while the posterior facet and CC joint had to be congruent with a step-off less than 2 mm. Several functional scores related to foot and ankle pathology were used to evaluate functional outcomes (American Orthopedic Foot and Ankle Score - AOFAS, Lower Extremity Functional Score - LEFS, Olerud and Molander Ankle Score - OMAS, Calcaneal Functional Scoring System - CFSS, Visual Analog Scale for pain - VAS) and were compared between anatomic and nonanatomic DIAFCs using Student's t-test. Demographic data and information about injury severity were collected for each patient.

Among the 84 enrolled patients, 6 were excluded while 11 were lost to follow-up. Thirty-nine patients had a nonanatomic reduction while 35 patients had an anatomic reduction (47%). Baseline characteristics were similar in both groups. When we compared the injury severity as defined by the Sanders’ Classification, we did not find a significant difference. In other words, the nonanatomic group did not have a greater proportion of complex fractures. Anatomically reduced DIACFs showed significantly superior results at 12 months for all but one scoring system (mean difference at 12 months: AOFAS 3.97, p = 0.12; LEFS 7.46, p = 0.003; OMAS 13.6, p = 0.002, CFSS 7.5, p = 0.037; VAS −1.53, p = 0.005). Univariate analyses did not show that smoking status, worker's compensation or body mass index were associated with functional outcomes. Moreover, fracture severity could not predict functional outcomes at 12 months

This study showed superior functional outcomes in patients with a DIACF when an anatomic reduction is achieved regardless of the injury severity.

One out of nine Canadian males would suffer prostate cancer (PC) during his lifetime. Life expectancy of males with PC has increased with modern therapy and 90% live >10 years. However, 20% of PC-affected males would develop incurable metastatic diseases. Bone metastases (BM) are present in ~80% of metastatic PC patients, and are the most severe complication of PC, generating severe pain, fractures, spinal cord compression, and death. Interestingly, PC-BMs are mostly osteoblastic. However, the structure of this newly formed bone and how it relates to pain and fracture are unknown. Due to androgen antagonist treatment, different PC phenotypes develop with differential dependency on androgen receptor (AR) signaling: androgen-dependent (AR+), double negative (AR-) and neuroendocrine. How these phenotypes are related to changes in bone structure has not been studied. Here we show a state-of-the-art structural characterization of PCBM and how PC phenotypes are associated to abnormal bone formation in PCBM.

Cadaveric samples (n=14) obtained from metastases of PC in thoracic or lumbar vertebrae (mean age 74yo) were used to analyze bone structure. We used micro-computed tomography (mCT) to analyze the three-dimensional structure of the bone samples. After imaging, the samples were sectioned and one 3mm thick section was embedded in epoxy-resin, ground and polished. Scanning electron microscopy (SEM)/energy-dispersive X-ray spectroscopy (EDS) and quantitative backscattering electron (qBSE) imaging were used to determine mineral morphology and composition. Another section was used for histological analysis of the PC-affected bone. Collagen structure, fibril orientation and extracellular matrix composition were characterized using histochemistry. Additionally, we obtained biopsies of 3 PCBM patients undergoing emergency decompression surgery following vertebral fracture and used them for immunohistological characterization.

By using mCT, we observed three dysmorphic bone patterns: osteolytic pattern with thinned trabecula of otherwise well-organized structures, osteoblastic pattern defined as accumulation of disorganized matrix deposited on pre-existing trabecula, and osteoblastic pattern with minimum residual trabecula and bone space dominated by accumulation of disorganized mineralized matrix. Comparing mCT data with patho/clinical parameters revealed a trend for higher bone density in males with larger PSA increase. Through histological sections, we observed that PC-affected bone, lacks collagen alignment structure, have a higher number of lacunae and increased amount of proteoglycans as decorin.

Immunohistochemistry of biopsies revealed that PC-cells inside bone organize into two manners: i) glandular-like structures where cells maintain their polarization in the expression of prostate markers, ii) diffuse infiltrate that spreads along bone surfaces, with loss of cell polarity. These cells take direct contact with osteoblasts in the surface of trabecula. We define that PCBM are mostly composed by AR+ with some double negative cells. We did not observe neuroendocrine phenotype cells.

PCBMs generate predominantly osteoblastic lesions that are characterized by high lacunar density, lack of collagen organization and elevated proteoglycan content. These structural changes are associated with the infiltration of PC cells that are mostly androgen-dependent but have lost their polarization and contact directly with osteoblasts, perhaps altering their function. These changes could be associated with lower mechanical properties that led to fracture and weakness of the PCBM affected bone.

Despite the current trend favoring surgical treatment of displaced intra-articular calcaneal fractures (DIACFs), studies have not been able to demonstrate superior functional outcomes when compared to non-operative treatment. These fractures are notoriously difficult to reduce. Studies investigating surgical fixation often lack information about the quality of reduction even though it may play an important role in the success of this procedure. We wanted to establish if, amongst surgically treated DIACF, an anatomic reduction led to improved functional outcomes at 12 months.

From July 2011 to December 2020, at a level I trauma center, 84 patients with an isolated DIACF scheduled for surgical fixation with plate and screws using a lateral extensile approach were enrolled in this prospective cohort study and followed over a 12-month period. Post-operative computed tomography (CT) imaging of bilateral feet was obtained to assess surgical reduction using a combination of pre-determined parameters: Böhler's angle, calcaneal height, congruence and articular step-off of the posterior facet and calcaneocuboid (CC) joint. Reduction was judged anatomic when Böhler's angle and calcaneal height were within 20% of the contralateral foot while the posterior facet and CC joint had to be congruent with a step-off less than 2 mm. Several functional scores related to foot and ankle pathology were used to evaluate functional outcomes (American Orthopedic Foot and Ankle Score - AOFAS, Lower Extremity Functional Score - LEFS, Olerud and Molander Ankle Score - OMAS, Calcaneal Functional Scoring System - CFSS, Visual Analog Scale for pain – VAS) and were compared between anatomic and nonanatomic DIAFCs using Student's t-test. Demographic data and information about injury severity were collected for each patient.

Among the 84 enrolled patients, 6 were excluded while 11 were lost to follow-up. Thirty-nine patients had a nonanatomic reduction while 35 patients had an anatomic reduction (47%). Baseline characteristics were similar in both groups. When we compared the injury severity as defined by the Sanders’ Classification, we did not find a significant difference. In other words, the nonanatomic group did not have a greater proportion of complex fractures. Anatomically reduced DIACFs showed significantly superior results at 12 months for all but one scoring system (mean difference at 12 months: AOFAS 3.97, p = 0.12; LEFS 7.46, p = 0.003; OMAS 13.6, p = 0.002, CFSS 7.5, p = 0.037; VAS −1.53, p = 0.005). Univariate analyses did not show that smoking status, worker's compensation or body mass index were associated with functional outcomes. Moreover, fracture severity could not predict functional outcomes at 12 months.

This study showed superior functional outcomes in patients with a DIACF when an anatomic reduction is achieved regardless of the injury severity.

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.

Frailty has been shown to be a risk predictor for peri-operative adverse events (AEs) in patients undergoing various type of spine surgery. However, its relationship with Patient Related Outcome Measures (PROMS) remains unknown. The primary objective of this study was to determine the impact of frailty on PROMS in patients undergoing surgery for thoraco-lumbar degenerative conditions. The secondary objective was to determine the association between frailty and baseline PROMS.

This is a retrospective study of a prospective cohort of patients >55 years old who underwent surgery between 2012 and 2018. Patient data and PROMS (EQ-5D, SF-12, ODI, back and leg pain NRS) were extracted from the Canadian Spine Outcomes and Research Network registry for a single academic centre. Frailty was retrospectively calculated using the modified frailty index (mFI) and patient were classified as frail, pre-frail and non-frail. Patient characteristics and outcomes were analyzed using ANOVA or Kruskal-Wallis test for continuous variables and Chi square or Fisher's exact test for proportions. A generalized estimating equations (GEEs) regression model was used to assess the association between patients' baseline frailty status and PROMs measures at three and 12 months.

293 patients were included with a mean age of 67 ± 7 years. Twenty-two percent of the patients (n= 65) were frail, 59 % (n=172) were pre-frail and 19% (n=56) were non-frail. At baseline, the three groups had similar PROMS, except for the PCS which was worse in the frail group (mean difference [95% CI], −4.9 [−8.6;-1.1], p= 0.0083). The improvement in the EQ-5D, PCS, MCS, ODI, back and leg pain NRS scores was not significantly different between the three groups (p> 0.05). The was no difference in the evolution of the PROMS at three and 12 months between the three groups (p> 0.05).

Although frailty is a known predictor of AEs, it does not predict worse PROMS after spine surgery in that population. At baseline, non-frail, pre-frail and frail patients have similar PROMS.