Culture substrate stiffness impacts human myoblast contractility-dependent proliferation and nuclear envelope wrinkling.

Understanding how biophysical and biochemical microenvironmental cues together influence the regenerative activities of muscle stem cells and their progeny is crucial in strategizing remedies for pathological dysregulation of these cues in aging and disease. In this study, we investigated the cell-level influences of extracellular matrix (ECM) ligands and culture substrate stiffness on primary human myoblast contractility and proliferation within 16 h of plating and found that tethered fibronectin led to stronger stiffness-dependent responses compared to laminin and collagen. A proteome-wide analysis further uncovered cell metabolism, cytoskeletal and nuclear component regulation distinctions between cells cultured on soft and stiff substrates. Interestingly, we found that softer substrates increased the incidence of myoblasts with a wrinkled nucleus, and that the extent of wrinkling could predict Ki67 (also known as MKI67) expression. Nuclear wrinkling and Ki67 expression could be controlled by pharmacological manipulation of cellular contractility, offering a potential cellular mechanism. These results provide new insights into the regulation of human myoblast stiffness-dependent contractility response by ECM ligands and highlight a link between myoblast contractility and proliferation.

Comparison of major spine navigation platforms based on key performance metrics: a meta-analysis of 16,040 screws.

PURPOSE: The objective of this meta-analysis is to compare available computer-assisted navigation platforms by key performance metrics including pedicle screw placement accuracy, operative time, neurological complications, and blood loss. METHODS: A systematic review was conducted using major databases for articles comparing pedicle screw accuracy of computer-assisted navigation to conventional (freehand or fluoroscopy) controls via post-operative computed tomography. Outcome data were extracted and pooled by random-effects model for analysis. RESULTS: All navigation platforms demonstrated significant reduction in risk of breach, with Stryker demonstrating the highest accuracy compared to controls (OR 0.16 95% CI 0.06 to 0.41, P < 0.00001, I2 = 0%) followed by Medtronic. There were no significant differences in accuracy or most surgical outcome measures between platforms; however, BrainLab demonstrated significantly faster operative time compared to Medtronic by 30 min (95% CI - 63.27 to - 2.47, P = 0.03, I2 = 74%). Together, there was significantly lower risk of major breach in the navigation group compared to controls (OR 0.42, 95% CI 0.27-0.63, P < 0.0001, I2 = 56%). CONCLUSIONS: When comparing between platforms, Stryker demonstrated the highest accuracy, and Brainlab the shortest operative time, both followed by Medtronic. No significant difference was found between platforms regarding neurologic complications or blood loss. Overall, our results demonstrated a 60% reduction in risk of major breach utilizing computer-assisted navigation, coinciding with previous studies, and supporting its validity. This study is the first to directly compare available navigation platforms offering insight for further investigation and aiding in the institutional procurement of platforms. LEVEL 3 EVIDENCE: Meta-analysis of Level 3 studies.

Health Conditions: Effect on Function, Health-Related Quality of Life, and Life Satisfaction After Traumatic Spinal Cord Injury. A Prospective Observational Registry Cohort Study.

OBJECTIVE: To analyze relations among injury, demographic, and environmental factors on function, health-related quality of life (HRQoL), and life satisfaction in individuals with traumatic spinal cord injury (SCI). DESIGN: Prospective observational registry cohort study. SETTING: Specialized acute and rehabilitation SCI centers. PARTICIPANTS: Participants (N=340) from the Rick Hansen Spinal Cord Injury Registry (RHSCIR) who were prospectively recruited from 2004 to 2014 were included. The model cohort participants were 79.1% men, with a mean age of 41.6±17.3 years. Of the participants, 34.7% were motor/sensory complete (ASIA Impairment Scale [AIS] grade A). INTERVENTIONS: None. MAIN OUTCOME MEASURES: Path analysis was used to determine relations among SCI severity (AIS grade and anatomic level [cervical/thoracolumbar]), age at injury, education, number of health conditions, functional independence (FIM motor score), HRQoL (Medical Outcomes Study 36-Item Short-Form Health Survey [Version 2] Physical Component Score [PCS] and Mental Component Score [MCS]), and life satisfaction (Life Satisfaction-11 [LiSat-11]). Model fit was assessed using recommended published indices. RESULTS: Goodness of fit of the model was supported by all indices, indicating the model results closely matched the RHSCIR data. Higher age, higher severity injuries, cervical injuries, and more health conditions negatively affected FIM motor score, whereas employment had a positive effect. Higher age, less education, more severe injuries (AIS grades A-C), and more health conditions negatively correlated with PCS (worse physical health). More health conditions were negatively correlated with a lower MCS (worse mental health), however were positively associated with reduced function. Being married and having higher function positively affected Lisat-11, but more health conditions had a negative effect. CONCLUSIONS: Complex interactions and enduring effects of health conditions after SCI have a negative effect on function, HRQoL, and life satisfaction. Modeling relations among these types of concepts will inform clinicians how to positively effect outcomes after SCI (eg, development of screening tools and protocols for managing individuals with traumatic SCI who have multiple health conditions).

Effect of older age on treatment decisions and outcomes among patients with traumatic spinal cord injury.

BACKGROUND: Older people are at increased risk of traumatic spinal cord injury from falls. We evaluated the impact of older age (≥ 70 yr) on treatment decisions and outcomes. METHODS: We identified patients with traumatic spinal cord injury for whom consent and detailed data were available from among patients recruited (2004-2013) at any of the 31 acute care and rehabilitation hospitals participating in the Rick Hansen Spinal Cord Injury Registry. Patients were assessed by age group (< 70 v. ≥ 70 yr). The primary outcome was the rate of acute surgical treatment. We used bivariate and multivariate regression models to assess patient and injury-related factors associated with receiving surgical treatment and with the timing of surgery after arrival to a participating centre. RESULTS: Of the 1440 patients included in our study cohort, 167 (11.6%) were 70 years or older at the time of injury. Older patients were more likely than younger patients to be injured by falling (83.1% v. 37.4%; p < 0.001), to have a cervical injury (78.0% v. 61.6%; p = 0.001), to have less severe injuries on admission (American Spinal Injury Association Impairment Scale grade C or D: 70.5% v. 46.9%; p < 0.001), to have a longer stay in an acute care hospital (median 35 v. 28 d; p < 0.005) and to have a higher in-hospital mortality (4.2% v. 0.6%; p < 0.001). Multivariate analysis did not show that age of 70 years or more at injury was associated with a decreased likelihood of surgical treatment (adjusted odds ratio [OR] 0.48, 95% confidence interval [CI] 0.22-1.07). An unplanned sensitivity analysis with different age thresholds showed that a threshold of 65 years was associated with a decreased chance of surgical treatment (OR 0.39, 95% CI 0.19-0.80). Older patients who underwent surgical treatment had a significantly longer wait time from admission to surgery than younger patients (37 v. 19 h; p < 0.001). INTERPRETATION: We found chronological age to be a factor influencing treatment decisions but not at the 70-year age threshold that we had hypothesized. Older patients waited longer for surgery and had a substantially higher in-hospital mortality despite having less severe injuries than younger patients. Further research into the link between treatment delays and outcomes among older patients could inform surgical guideline development.

Improving access to emergent spinal care through knowledge translation: an ethnographic study.

BACKGROUND: For patients and family members, access to timely specialty medical care for emergent spinal conditions is a significant stressor to an already serious condition. Timing to surgical care for emergent spinal conditions such as spinal trauma is an important predictor of outcome. However, few studies have explored ethnographically the views of surgeons and other key stakeholders on issues related to patient access and care for emergent spine conditions. The primary study objective was to determine the challenges to the provision of timely care as well as to identify areas of opportunities to enhance care delivery. METHODS: An ethnographic study of key administrative and clinical care providers involved in the triage and care of patients referred through CritiCall Ontario was undertaken utilizing standard methods of qualitative inquiry. This comprised 21 interviews with people involved in varying capacities with the provision of emergent spinal care, as well as qualitative observations on an orthopaedic/neurosurgical ward, in operating theatres, and at CritiCall Ontario's call centre. RESULTS: Several themes were identified and organized into categories that range from inter-professional collaboration through to issues of hospital-level resources and the role of relationships between hospitals and external organizations at the provincial level. Underlying many of these issues is the nature of the medically complex emergent spine patient and the scientific evidentiary base upon which best practice care is delivered. Through the implementation of knowledge translation strategies facilitated from this research, a reduction of patient transfers out of province was observed in the one-year period following program implementation. CONCLUSIONS: Our findings suggest that competing priorities at both the hospital and provincial level create challenges in the delivery of spinal care. Key stakeholders recognized spinal care as aligning with multiple priorities such as emergent/critical care, medical through surgical, acute through rehabilitative, disease-based (i.e. trauma, cancer), and wait times initiatives. However, despite newly implemented strategies, there continues to be increasing trends over time in the number of spinal CritiCall Ontario referrals. This reinforces the need for ongoing inter-professional efforts in care delivery that take into account the institutional contexts that may constrain individual or team efforts.

Riluzole for Degenerative Cervical Myelopathy: A Secondary Analysis of the CSM-PROTECT Trial.

Importance: The modified Japanese Orthopaedic Association (mJOA) scale is the most common scale used to represent outcomes of degenerative cervical myelopathy (DCM); however, it lacks consideration for neck pain scores and neglects the multidimensional aspect of recovery after surgery. Objective: To use a global statistical approach that incorporates assessments of multiple outcomes to reassess the efficacy of riluzole in patients undergoing spinal surgery for DCM. Design, Setting, and Participants: This was a secondary analysis of prespecified secondary end points within the Efficacy of Riluzole in Surgical Treatment for Cervical Spondylotic Myelopathy (CSM-PROTECT) trial, a multicenter, double-blind, phase 3 randomized clinical trial conducted from January 2012 to May 2017. Adult surgical patients with DCM with moderate to severe myelopathy (mJOA scale score of 8-14) were randomized to receive either riluzole or placebo. The present study was conducted from July to December 2023. Intervention: Riluzole (50 mg twice daily) or placebo for a total of 6 weeks, including 2 weeks prior to surgery and 4 weeks following surgery. Main Outcomes and Measures: The primary outcome measure was a difference in clinical improvement from baseline to 1-year follow-up, assessed using a global statistical test (GST). The 36-Item Short Form Health Survey Physical Component Score (SF-36 PCS), arm and neck pain numeric rating scale (NRS) scores, American Spinal Injury Association (ASIA) motor score, and Nurick grade were combined into a single summary statistic known as the global treatment effect (GTE). Results: Overall, 290 patients (riluzole group, 141; placebo group, 149; mean [SD] age, 59 [10.1] years; 161 [56%] male) were included. Riluzole showed a significantly higher probability of global improvement compared with placebo at 1-year follow-up (GTE, 0.08; 95% CI, 0.00-0.16; P = .02). A similar favorable global response was seen at 35 days and 6 months (GTE for both, 0.07; 95% CI, -0.01 to 0.15; P = .04), although the results were not statistically significant. Riluzole-treated patients had at least a 54% likelihood of achieving better outcomes at 1 year compared with the placebo group. The ASIA motor score and neck and arm pain NRS combination at 1 year provided the best-fit parsimonious model for detecting a benefit of riluzole (GTE, 0.11; 95% CI, 0.02-0.16; P = .007). Conclusions and Relevance: In this secondary analysis of the CSM-PROTECT trial using a global outcome technique, riluzole was associated with improved clinical outcomes in patients with DCM. The GST offered probability-based results capable of representing diverse outcome scales and should be considered in future studies assessing spine surgery outcomes.

Postoperative C5 Palsy after Anterior or Posterior Decompression for Degenerative Cervical Myelopathy: A Subgroup Analysis of the Multicenter, Prospective, Randomized, Phase III, CSM-Protect Clinical Trial.

STUDY DESIGN: Retrospective cohort study of prospectively accrued data. OBJECTIVE: To evaluate a large, prospective, multicentre dataset of surgically-treated DCM cases on the contemporary risk of C5 palsy with surgical approach. SUMMARY OF BACKGROUND DATA: The influence of surgical technique on postoperative C5 palsy after decompression for degenerative cervical myelopathy (DCM) is intensely debated. Comprehensive analyses are needed using contemporary data and accounting for covariates. METHODS: Patients with moderate to severe DCM were prospectively enrolled in the multicenter, randomized CSM-Protect clinical trial and underwent either anterior or posterior decompression between Jan 31, 2012, to May 16, 2017. The primary outcome was the incidence of postoperative C5 palsy, defined as onset of muscle weakness by at least one grade in manual muscle test at the C5 myotome with slight or absent sensory disruption after cervical surgery. Two comparative cohorts were made based on anterior or posterior surgical approach. Multivariate hierarchical mixed-effects logistic regression was used to estimate odds ratios (OR) with 95% confidence intervals (CI) for C5 palsy. RESULTS: A total of 283 patients were included, and 53.4% underwent posterior decompression. The total incidence of postoperative C5 palsy was 7.4% and was significantly higher in patients that underwent posterior decompression compared to anterior decompression (11.26% vs. 3.03%, P=0.008). After multivariable regression, posterior approach was independently associated with greater than four times the likelihood of postoperative C5 palsy (P=0.017). Rates of C5 palsy recovery were comparable between the two surgical approaches. CONCLUSION: The odds of postoperative C5 palsy are significantly higher after posterior decompression compared to anterior decompression for DCM. This may influence surgical decision-making when there is equipoise in deciding between anterior and posterior treatment options for DCM. LEVEL OF EVIDENCE: Therapeutic Level II.

Preoperative carbohydrate loading in patients undergoing coronary artery bypass or spinal surgery.

BACKGROUND: Surgical stress creates a state of insulin resistance which may contribute to the development of hyperglycemia and, subsequently, postoperative complications. Consumption of an oral carbohydrate supplement before surgery may improve insulin sensitivity and reduce hyperglycemia. In this trial, we investigated the effects of carbohydrate supplementation on insulin resistance in coronary artery bypass graft and spinal decompression and fusion surgical patients. METHODS: Twenty-six patients undergoing coronary artery bypass graft and 12 undergoing spine surgery were randomized to receive 800 mL of an oral carbohydrate supplement the evening before and 400 mL 2 hours before surgery (CHO) or to fasting per standard hospital protocol (FAST). Baseline and postoperative measurements of insulin sensitivity were assessed using the short insulin tolerance test and homeostasis model assessment (HOMA). Interleukin-6, C-reactive protein, and free fatty acid levels were determined at baseline, postoperatively, and 24, 48, and 72 hours after surgery. Adiponectin was measured at baseline. Subjective feelings of well-being were measured immediately before surgery, and intra- and postoperative outcomes were documented. RESULTS: Postoperative insulin sensitivity did not differ significantly between the FAST and CHO groups whether measured by the short insulin tolerance test (rate of disappearance of blood glucose: 0.29%/min vs 0.38%/min; 99% confidence interval [CI] for difference, -0.17 to 0.32, P = 0.41) or HOMA (insulin resistance at values >1: 2.3 vs 3.3; 99% CI for difference, -0.8 to 2.8, P = 0.14). Circulating blood glucose levels after surgery in the CHO group, 6.2 mmol/L, tended to be lower than the FAST group, 6.9 mmol/L (99% CI for difference, -1.7 to 0.25, P = 0.05) and postoperative ß-cell function, measured by HOMA-ß (impaired ß-cell function at values <100%), tended to be higher in the CHO group, 87%, vs 47.5% in the FAST group (99% CI for difference, -9.4 to 88.4), but these differences were not significant. Adiponectin levels were not different between groups at baseline, and levels of free fatty acid, interleukin-6 and C-reactive protein were not affected by treatment. CONCLUSIONS: Preoperative carbohydrate loading did not improve postoperative insulin sensitivity. However, the observed postoperative blood glucose levels and ß-cell function as well as secondary outcomes warrant further study to reevaluate traditional fasting practices in surgical patients.

Machine learning models can predict subsequent publication of North American Spine Society (NASS) annual general meeting abstracts.

BACKGROUND CONTEXT: Academic meetings serve as an opportunity to present and discuss novel ideas. Previous studies have identified factors predictive of publication without generating predictive models. Machine learning (ML) presents a novel tool capable of generating these models. As such, the objective of this study was to use ML models to predict subsequent publication of abstracts presented at a major surgical conference. STUDY DESIGN/SETTING: Database study. METHODS: All abstracts from the North American Spine Society (NASS) annual general meetings (AGM) from 2013-2015 were reviewed. The following information was extracted: number of authors, institution, location, conference category, subject category, study type, data collection methodology, human subject research, and FDA approval. Abstracts were then searched on the PubMed, Google Scholar, and Scopus databases for publication. ML models were trained to predict whether the abstract would be published or not. Quality of models was determined by using the area under the receiver operator curve (AUC). The top ten most important factors were extracted from the most successful model during testing. RESULTS: A total of 1119 abstracts were presented, with 553 (49%) abstracts published. During training, the model with the highest AUC and accuracy metrics was the partial least squares (AUC of 0.77±0.05, accuracy of 75.5%±4.7%). During testing, the model with the highest AUC and accuracy was the random forest (AUC of 0.69, accuracy of 67%). The top ten features for the random forest model were (descending order): number of authors, year, conference category, subject category, human subjects research, continent, and data collection methodology. CONCLUSIONS: This was the first study attempting to use ML to predict the publication of complete articles after abstract presentation at a major academic conference. Future studies should incorporate deep learning frameworks, cognitive/results-based variables and aim to apply this methodology to larger conferences across other fields of medicine to improve the quality of works presented.

Patient, clinical, surgical, and institutional factors associated with length of stay in scheduled degenerative thoracolumbar spine surgery: National Multicenter Cohort Analysis from the Canadian Spine Outcomes and Research Network.

OBJECTIVE: Length of stay (LOS) is a contributor to costs and resource utilization. The primary goal of this study was to identify patient, clinical, surgical, and institutional variables that influence LOS after elective surgery for thoracolumbar degenerative pathology. The secondary objective was to examine variability in LOS and institutional strategies used to decrease LOS. METHODS: This is a retrospective study of prospectively collected data from a multicentric cohort enrolled in the Canadian Spine Outcomes and Research Network (CSORN) between January 2015 and October 2020 who underwent elective thoracolumbar surgery (discectomy [1 or 2 levels], laminectomy [1 or 2 levels], and posterior instrumented fusion [up to 5 levels]). Prolonged LOS was defined as LOS greater than the median. Logistic regression models were used to determine factors associated with prolonged LOS for each procedure. A survey was sent to the principal investigators of the participating healthcare institutions to understand institutional practices that are used to decrease LOS. RESULTS: A total of 3700 patients were included (967 discectomies, 1094 laminectomies, and 1639 fusions). The median LOSs for discectomy, laminectomy, and fusion were 0.0 (IQR 1.0), 1.0 (IQR 2.0), and 4.0 (IQR 2.0) days, respectively. On multivariable analysis, predictors of prolonged LOS for discectomy were having more leg pain, higher Oswestry Disability Index (ODI) scores, symptom duration more than 2 years, having undergone an open procedure, occurrence of an adverse event (AE), and treatment at an institution without protocols to reduce LOS (p < 0.05). Predictors of prolonged LOS for laminectomy were increased age, living alone, higher ODI scores, higher BMI, open procedures, longer operative time, AEs, and treatment at an institution without protocols to reduce LOS (p < 0.05). For posterior instrumented fusion, predictors of prolonged LOS were older age, living alone, more comorbidities, higher ODI scores, longer operative time, AEs, and treatment at an institution without protocols to reduce LOS (p < 0.05). The laminectomy group had the largest variability in LOS (SD 4.4 days, range 0-133 days). Three hundred fifty-four patients (22%) had an LOS above the 75th percentile. Ten institutions (53%) had either Enhanced Recovery After Surgery or standardized protocols in place. CONCLUSIONS: Among the factors identified in this study, worse baseline ODI scores, experiencing AEs, and treatment at an institution without protocols aimed at reducing LOS were predictive of prolonged LOS in all surgical groups. The laminectomy group had the largest variability in LOS.

Outcome of spine surgery in patients with depressed mental states: a Canadian spine outcome research network study.

BACKGROUND CONTEXT: Depression is higher among spine patients than among the general population. Some small studies, but not others, have suggested that depression may be a predictor of worse outcome after surgery. PURPOSE: Determination whether there is an association between depression and worse response to surgery among spine patients. STUDY DESIGN/SETTING: The national, prospective, Canadian Spine Outcome Research Network (CSORN) surgical outcome registry. PATIENT SAMPLE: All patients in the CSORN registry who received surgery for thoracic or lumbar degenerative deformity, stenosis, spondylolisthesis, disc disease, or disc herniation with a minimum of 12 months follow-up postoperation (n = 2310). OUTCOME MEASURES: Oswestry Disability Index (ODI), SF12 Physical Component Score (PCS), European Quality of Life (EuroQoL), and pain scales. METHODS: Change in preoperative to 12-month postoperative ODI, and secondary measures, were compared to assess if there was an association between preoperative depression, as measured by PHQ9, and smaller response to surgery. Multivariate regression analysis was used to search for preoperative factors which might interact with PHQ9 to predict ODI outcome. RESULTS: Patients with PHQ9<5, associated with minimal to no depression, had the smallest ODI improvement (-16.8 [95%CI -18.1 to -15.3]) and patients with severe preoperative depression (PHQ9 ≥ 10) had the largest ODI improvement (-22.8 [95%CI -24.1 to -21.5]; p<.00001). Similar findings were found in the EQ5D and PCS. Pain improvement was not different between depression levels. Multivariate modeling found worse baseline PHQ9 and ODI, greater age, nicotine use, more operative levels, and worse American Society of Anesthesiology score was predictive of worse ODI outcomes. CONCLUSIONS: Depressed patients have similar or better relative improvements in disability, quality of life, and pain, when compared to nondepressed patients, although their preoperative and postoperative levels of disability are higher. Surgeons should not be concerned that depression will reduce the patient-reported beneficial response to surgical intervention.

Empirically derived maximal acceptable wait time for surgery to treat adolescent idiopathic scoliosis.

BACKGROUND: Prioritizing patients using empirically derived access targets can help to ensure high-quality care. Adolescent scoliosis can worsen while patients wait for treatment, increasing the risk of adverse events. Our objective was to determine an empirically derived access target for scoliosis surgery and to compare this with consensus-based targets. METHODS: Two-hundred sixteen sequential patients receiving surgery for adolescent idiopathic scoliosis were included in the study. The main outcome was need for additional surgery. Logistic regression modeling was used to evaluate the relation between surgical wait times and adverse events and χ2 analysis was used as the primary analysis for the main outcome. RESULTS: Of the 88 patients who waited longer than six months for surgery, 13 (14.8%) needed additional surgery due to progression of curvature versus 1.6% (2 of 128 patients) who waited less than six months for surgery (χ2 analysis, p=0.0001). Patients who waited longer than six months for surgery had greater progression of curvature, longer surgeries and longer stays in hospital. These patients also had less surgical correction than patients who waited less than six months for surgery (Wilcoxon-Mann-Whitney test, p=0.011). All patients requiring additional surgeries waited longer than three months for their initial surgery. A receiver-operator characteristic curve also suggested a three-month wait as an access target. The adjusted odds ratio for an adverse event for each additional 90 days of waiting from time of consent was 1.81 (95% confidence interval 1.34-2.44). The adjusted odds ratio increased with skeletal immaturity and with the size of the spinal curvature at the time of consent. INTERPRETATION: A prolonged wait for surgery increased the risk of additional surgical procedures and other adverse events. An empirically derived access target of three months for surgery to treat adolescent idiopathic scoliosis could potentially eliminate the need for additional surgery by reducing progression of curvature. This is a shorter access target than the six months determined by expert consensus.

A Comparison of Patient and Surgeon Expectations of Spine Surgical Outcomes.

STUDY DESIGN: Ambispective cohort study. OBJECTIVE: Limited data exists comparing surgeon and patient expectations of outcome following spine surgery. The objective of this study was to elicit whether any differences exist between patient and surgeon expectations for common spine surgeries. METHODS: Ten common age-appropriate clinical scenarios were generated and sent to Canadian spine surgeons to determine surgeon expectations for standard spine surgeries. Patients in the Canadian Spine Outcomes and Research Network (CSORN) registry matching the clinical scenarios were identified. Aggregated patient expectations were compared with surgeon responses for each scenario. A χ2 analysis was then completed to determine discrepancies between surgeon and patient expectations for each scenario. RESULTS: A total of 51 Canadian spine surgeons completed the survey on surgical expectations. A total of 919 patients from multiple centers were identified within the CSORN database that matched the clinical scenarios. Our results demonstrated that patients tend to be more optimistic about the expected outcomes of surgery compared with the treating surgeon. The majority of patients in all clinical scenarios anticipated improvement in back or neck pain after surgery, which differed from surgeon expectations. Results also highlighted the effect of patient age on both patient and surgeon expectations. Discrepancies between patient and surgeon expectations were higher for older patients. CONCLUSION: We present data on patient and surgeon expectations for spine surgeries and show that differences exist particularly concerning the improvement of neck or back pain. Patient age plays a role in the agreement between the treating physicians and patients in regard to surgical expectations. The reasons for the discrepancies remain unclear.

Factors associated with using an interbody fusion device for low-grade lumbar degenerative versus isthmic spondylolisthesis: a retrospective cohort study.

OBJECTIVE: Many studies have utilized a combined cohort of patients with degenerative spondylolisthesis (DS) and isthmic spondylolisthesis (IS) to evaluate indications and outcomes. Intuitively, these are very different populations, and rates, indications, and outcomes may differ. The goal of this study was to compare specific patient characteristics associated with the utilization of a posterior lumbar interbody device between cohorts of patients with DS and IS, as well as to compare rates of interbody device use and patient-rated outcomes at 1 year after surgical treatment. METHODS: The authors included patients who underwent posterior lumbar interbody fusion or instrumented posterolateral fusion for grade I or II DS or IS and had been enrolled in the Canadian Spine Outcomes and Research Network registry from 2009 to 2016. The outcome measures were score on the Oswestry Disability Index, scores for back pain and leg pain on the numeric rating scale, and mental component summary (MCS) score and physical component summary score on the 12-Item Short-Form Health Survey. Descriptive statistics were used to compare spondylolisthesis groups, logistic regression was used to compare interbody device use, and the chi-square test was used to compare the proportions of patients who achieved a minimal clinically important difference (MCID) at 1 year after surgery. RESULTS: In total, 119 patients had IS and 339 had DS. Patients with DS were more commonly women, older, less likely to smoke, and more likely to have neurogenic claudication and comorbidities, whereas patients with IS more commonly had radicular pain, neurological deficits, and worse back pain. Spondylolisthesis was more common at the L4-5 level in patients with DS and at the L5-S1 level in patients with IS. Similar proportions of patients had an interbody device (78.6% of patients with DS vs 82.4% of patients with IS, p = 0.429). Among patients with IS, factors associated with interbody device utilization were BMI ≥ 30 kg/m2 and increased baseline leg pain intensity. Factors associated with interbody device utilization in patients with DS were younger age, increased number of total comorbidities, and lower baseline MCS score. For each outcome measure, similar proportions of patients in the surgical treatment and spondylolisthesis groups achieved the MCID at 1 year after surgery. CONCLUSIONS: Although the demographic and patient characteristics associated with interbody device utilization differed between cohorts, similar proportions of patients attained clinically meaningful improvement at 1 year after surgery.

Low-back pain after lumbar discectomy for disc herniation: what can you tell your patient?

OBJECTIVE: Lumbar discectomy (LD) is frequently performed to alleviate radicular pain resulting from disc herniation. While this goal is achieved in most patients, improvement in low-back pain (LBP) has been reported inconsistently. The goal of this study was to characterize how LBP evolves following discectomy. METHODS: The authors performed a retrospective analysis of prospectively collected patient data from the Canadian Spine Outcomes and Research Network (CSORN) registry. Patients who underwent surgery for lumbar disc herniation were eligible for inclusion. The primary outcome was a clinically significant reduction in the back pain numerical rating scale (BPNRS) assessed at 12 months. Binary logistic regression was used to model the relationship between the primary outcome and potential predictors. RESULTS: There were 557 patients included in the analysis. The chief complaint was radiculopathy in 85%; 55% of patients underwent a minimally invasive procedure. BPNRS improved at 3 months by 48% and this improvement was sustained at all follow-ups. LBP and leg pain improvement were correlated. Clinically significant improvement in BPNRS at 12 months was reported by 64% of patients. Six factors predicted a lack of LBP improvement: female sex, low education level, marriage, not working, low expectations with regard to LBP improvement, and a low BPNRS preoperatively. CONCLUSIONS: Clinically significant improvement in LBP is observed in the majority of patients after LD. These data should be used to better counsel patients and provide accurate expectations about back pain improvement.

The impact of pathoanatomical diagnosis on elective spine surgery patient expectations: a Canadian Spine Outcomes and Research Network study.

OBJECTIVE: Patients undergoing spine surgery generally have high expectations for improvement postoperatively. Little is known about how these expectations are affected by the diagnosis. The purpose of this study was to examine whether preoperative expectations differ based on diagnostic pathoanatomical patterns in elective spine surgery patients. METHODS: Patients with common degenerative cervical/lumbar pathology (lumbar/cervical stenosis, lumbar spondylolisthesis, and cervical/lumbar disc herniation) who had given their consent for surgery were analyzed using the Canadian Spine Outcomes and Research Network (CSORN). Patients reported the changes they expected to experience postoperatively in relation to 7 separate items using a modified version of the North American Spine Society spine questionnaire. Patients were also asked about the most important item that would make them consider the surgery a success. Sociodemographic, lifestyle, and clinical variables were also collected. RESULTS: There were 3868 eligible patients identified within the network for analysis. Patients with lumbar disc herniation had higher expectations for relief of leg pain compared with stenosis and lumbar degenerative spondylolisthesis cohorts within the univariate analysis. Cervical stenosis (myelopathy) patients were more likely to rank general physical capacity as their most important expectation from spine surgery. The multinomial regression analysis showed that cervical myelopathy patients have lower expectations for relief of arm or neck pain from surgery (OR 0.54, 0.34-0.88; p < 0.05). Patient factors, including age, symptoms (pain, disability, depression), work status, and lifestyle factors, were significantly associated with expectation, whereas the diagnoses were not. CONCLUSIONS: Patients with degenerative spinal conditions consenting for spine surgery have high expectations for improvement in all realms of their daily lives. With the exception of patients with cervical myelopathy, patient symptoms rather than diagnoses had a more substantial impact on the dimensions in which patients expected to improve or their most important expected change. Determination of patient expectation should be individualized and not biased by pathoanatomical diagnosis.

Safety and efficacy of riluzole in patients undergoing decompressive surgery for degenerative cervical myelopathy (CSM-Protect): a multicentre, double-blind, placebo-controlled, randomised, phase 3 trial.

BACKGROUND: Degenerative cervical myelopathy represents the most common form of non-traumatic spinal cord injury. This trial investigated whether riluzole enhances outcomes in patients undergoing decompression surgery for degenerative cervical myelopathy. METHODS: This multicentre, double-blind, placebo-controlled, randomised, phase 3 trial was done at 16 university-affiliated centres in Canada and the USA. Patients with moderate-to-severe degenerative cervical myelopathy aged 18-80 years, who had a modified Japanese Orthopaedic Association (mJOA) score of 8-14, were eligible. Patients were randomly assigned (1:1) to receive either oral riluzole (50 mg twice a day for 14 days before surgery and then for 28 days after surgery) or placebo. Randomisation was done using permuted blocks stratified by study site. Patients, physicians, and outcome assessors remained masked to treatment group allocation. The primary endpoint was change in mJOA score from baseline to 6 months in the intention-to-treat (ITT) population, defined as all individuals who underwent randomisation and surgical decompression. Adverse events were analysed in the modified intention-to-treat (mITT) population, defined as all patients who underwent randomisation, including those who did not ultimately undergo surgical decompression. This study is registered with ClinicalTrials.gov, NCT01257828. FINDINGS: From Jan 31, 2012, to May 16, 2017, 408 patients were screened. Of those screened, 300 were eligible (mITT population); 290 patients underwent decompression surgery (ITT population) and received either riluzole (n=141) or placebo (n=149). There was no difference between the riluzole and placebo groups in the primary endpoint of change in mJOA score at 6-month follow-up: 2·45 points (95% CI 2·08 to 2·82 points) versus 2·83 points (2·47 to 3·19), difference -0·38 points (-0·90 to 0·13; p=0·14). The most common adverse events were neck or arm or shoulder pain, arm paraesthesia, dysphagia, and worsening of myelopathy. There were 43 serious adverse events in 33 (22%) of 147 patients in the riluzole group and 34 serious adverse events in 29 (19%) of 153 patients in the placebo group. The most frequent severe adverse events were osteoarthrosis of non-spinal joints, worsening of myelopathy, and wound complications. INTERPRETATION: In this trial, adjuvant treatment for 6 weeks perioperatively with riluzole did not improve functional recovery beyond decompressive surgery in patients with moderate-to-severe degenerative cervical myelopathy. Whether riluzole has other benefits in this patient population merits further study. FUNDING: AOSpine North America.

A 96-well culture platform enables longitudinal analyses of engineered human skeletal muscle microtissue strength.

Three-dimensional (3D) in vitro models of human skeletal muscle mimic aspects of native tissue structure and function, thereby providing a promising system for disease modeling, drug discovery or pre-clinical validation, and toxicity testing. Widespread adoption of this research approach is hindered by the lack of easy-to-use platforms that are simple to fabricate and that yield arrays of human skeletal muscle micro-tissues (hMMTs) in culture with reproducible physiological responses that can be assayed non-invasively. Here, we describe a design and methods to generate a reusable mold to fabricate a 96-well platform, referred to as MyoTACTIC, that enables bulk production of 3D hMMTs. All 96-wells and all well features are cast in a single step from the reusable mold. Non-invasive calcium transient and contractile force measurements are performed on hMMTs directly in MyoTACTIC, and unbiased force analysis occurs by a custom automated algorithm, allowing for longitudinal studies of function. Characterizations of MyoTACTIC and resulting hMMTs confirms the capability of the device to support formation of hMMTs that recapitulate biological responses. We show that hMMT contractile force mirrors expected responses to compounds shown by others to decrease (dexamethasone, cerivastatin) or increase (IGF-1) skeletal muscle strength. Since MyoTACTIC supports hMMT long-term culture, we evaluated direct influences of pancreatic cancer chemotherapeutics agents on contraction competent human skeletal muscle myotubes. A single application of a clinically relevant dose of Irinotecan decreased hMMT contractile force generation, while clear effects on myotube atrophy were observed histologically only at a higher dose. This suggests an off-target effect that may contribute to cancer associated muscle wasting, and highlights the value of the MyoTACTIC platform to non-invasively predict modulators of human skeletal muscle function.

Patients' expectations of spine surgery for degenerative conditions: results from the Canadian Spine Outcomes and Research Network (CSORN).

BACKGROUND: Understanding patient expectations is a critical component of patient-centered care; however, little is known about which expectation(s) are most important to patients as they relate to their sense of postoperative success. PURPOSE: To investigate patient's preoperative expectations of change in symptoms, function, and well-being resulting from surgical intervention and to examine the associations between sociodemographic, lifestyle, health status, and clinical characteristics with patient outcome expectations STUDY DESIGN: Observational cross-sectional study. SAMPLE: Preoperative data from the Canadian Spine Outcomes and Research Network national registry of patients of patients (n=4,333) undergoing surgery for degenerative spinal conditions between 2012 and 2017. OUTCOME MEASURES: Patients reported their expectations as a result of the surgery (0 [no change], 1 [somewhat better], 2 [better] or 3 [much better]) for seven items: leg/arm pain, back/neck pain, independence in everyday activities, sporting activities/recreation, general physical capacity, frequency and quality of social contacts, and mental well-being. Patients also reported the single most important change expected. METHODS: Data on demographic, lifestyles, health status, clinical factors, and reasons for having surgery were also collected. Factor analysis was used to examine the multidimensionality of expectations. Multivariate linear regression was used to examine factors associated with expectations. RESULTS: Over 80% of patients reported expectation for improvements (at least somewhat better) in all items with the exception of social contacts (75.8%). Expectations are multidimensional; a two factor structure emerged indicating two expectation dimensions (pain relief and overall functional well-being). Two expectation scores were calculated corresponding to the two dimensions (0-100), with higher scores reflecting higher expectations. The mean±standard deviation pain relief expectation score was 78.5±24.7 and the mean overall functional well-being expectation score was 69.7±24.4. In multivariate analysis, the variables associated with these dimensions either differed or differed in degree of influence. For example, higher pain and disability scores, thoracolumbar location and diagnosis of spondylolisthesis were associated with higher expectations in both dimensions, while longer disease duration was only associated with lower overall functional well-being expectations. The top three most important expected change items were pain (improvement of leg or arm pain (29.1%)/improvement in back/neck pain (26.0%)), improvement in general capacity/function (21.0%), and improvement of independence in everyday activities (15.9%). Rankings of the most important expected change were similar across sociodemographic, lifestyle, health status, and clinical variables examined. CONCLUSIONS: Our findings highlight the need to identify and address specific individual expectations as part of the shared decision-making and presurgery education process.

Preoperative Factors Predict Postoperative Trajectories of Pain and Disability Following Surgery for Degenerative Lumbar Spinal Stenosis.

STUDY DESIGN: Longitudinal analysis of prospectively collected data. OBJECTIVE: Investigate potential predictors of poor outcome following surgery for degenerative lumbar spinal stenosis (LSS). SUMMARY OF BACKGROUND DATA: LSS is the most common reason for an older person to undergo spinal surgery, yet little information is available to inform patient selection. METHODS: We recruited LSS surgical candidates from 13 orthopedic and neurological surgery centers. Potential outcome predictors included demographic, health, clinical, and surgery-related variables. Outcome measures were leg and back numeric pain rating scales and Oswestry disability index scores obtained before surgery and after 3, 12, and 24 postoperative months. We classified surgical outcomes based on trajectories of leg pain and a composite measure of overall outcome (leg pain, back pain, and disability). RESULTS: Data from 529 patients (mean [SD] age = 66.5 [9.1] yrs; 46% female) were included. In total, 36.1% and 27.6% of patients were classified as experiencing a poor leg pain outcome and overall outcome, respectively. For both outcomes, patients receiving compensation or with depression/depression risk were more likely, and patients participating in regular exercise were less likely to have poor outcomes. Lower health-related quality of life, previous spine surgery, and preoperative anticonvulsant medication use were associated with poor leg pain outcome. Patients with ASA scores more than two, greater preoperative disability, and longer pain duration or surgical waits were more likely to have a poor overall outcome. Patients who received preoperative chiropractic or physiotherapy treatment were less likely to report a poor overall outcome. Multivariable models demonstrated poor-to acceptable (leg pain) and excellent (overall outcome) discrimination. CONCLUSION: Approximately one in three patients with LSS experience a poor clinical outcome consistent with surgical non-response. Demographic, health, and clinical factors were more predictive of clinical outcome than surgery-related factors. These predictors may assist surgeons with patient selection and inform shared decision-making for patients with symptomatic LSS. LEVEL OF EVIDENCE: 2.