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.

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.

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.

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.

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.

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.

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.

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 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.

In-Hospital Mortality for the Elderly with Acute Traumatic Spinal Cord Injury.

As the incidence of traumatic spinal cord injury (tSCI) in the elderly rises, clinicians are increasingly faced with difficult discussions regarding aggressiveness of management, likelihood of recovery, and survival. Our objective was to outline risk factors associated with in-hospital mortality in elderly surgical and non-surgical patients following tSCI and to determine those unlikely to have a favorable outcome. Data from elderly patients (≥ 65 years of age) in the Canadian Rick Hansen SCI Registry from 2004 to 2017 were analyzed using descriptive analysis. Survival and mortality groups in each of the surgical and non-surgical group were compared to explore factors associated with in-hospital mortality and their impact, using logistical regression. Of 1340 elderly patients, 1018 had surgical data with 826 having had surgery. In the surgical group, the median time to death post-injury was 30 days with 75% dying within 50 days compared with 7 days and 20 days, respectively, in the non-surgical group. Significant predictors for in-hospital mortality following surgery are age, comorbidities, neurological injury severity (American Spinal Injury Association [ASIA] Impairment Scale [AIS]), and ventilation status. The odds of dying 50 days post-surgery are six times higher for patients ≥77 years of age versus those 65-76 years of age, five times higher for those with AIS A versus those with AIS B/C/D, and seven times higher for those who are ventilator dependent. An expected probability of dying within 50 days post-surgery was determined using these results. In-hospital mortality in the elderly after tSCI is high. The trend with age and time to death and the significant predictors of mortality identified in this study can be used to inform clinical decision making and discussions with patients and their families.

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.

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.

Patients undergoing surgery for lumbar spinal stenosis experience unique courses of pain and disability: A group-based trajectory analysis.

OBJECTIVE: Identify patient subgroups defined by trajectories of pain and disability following surgery for degenerative lumbar spinal stenosis, and investigate the construct validity of the subgroups by evaluating for meaningful differences in clinical outcomes. METHODS: We recruited patients with degenerative lumbar spinal stenosis from 13 surgical spine centers who were deemed to be surgical candidates. Study outcomes (leg and back pain numeric rating scales, modified Oswestry disability index) were measured before surgery, and after 3, 12, and 24 months. Group-based trajectory models were developed to identify trajectory subgroups for leg pain, back pain, and pain-related disability. We examined for differences in the proportion of patients achieving minimum clinically important change in pain and disability (30%) and clinical success (50% reduction in disability or Oswestry score ≤22) 12 months from surgery. RESULTS: Data from 548 patients (mean[SD] age = 66.7[9.1] years; 46% female) were included. The models estimated 3 unique trajectories for leg pain (excellent outcome = 14.4%, good outcome = 49.5%, poor outcome = 36.1%), back pain (excellent outcome = 13.1%, good outcome = 45.0%, poor outcome = 41.9%), and disability (excellent outcome = 30.8%, fair outcome = 40.1%, poor outcome = 29.1%). The construct validity of the trajectory subgroups was confirmed by between-trajectory group differences in the proportion of patients meeting thresholds for minimum clinically important change and clinical success after 12 postoperative months (p < .001). CONCLUSION: Subgroups of patients with degenerative lumbar spinal stenosis can be identified by their trajectories of pain and disability following surgery. Although most patients experienced important reductions in pain and disability, 29% to 42% of patients were classified as members of an outcome trajectory subgroup that experienced little to no benefit from surgery. These findings may inform appropriate expectation setting for patients and clinicians and highlight the need for better methods of treatment selection for patients with degenerative lumbar spinal stenosis.

Predictive Factors for Discharge Destination Following Posterior Lumbar Spinal Fusion: A Canadian Spine Outcome and Research Network (CSORN) Study.

STUDY DESIGN: Ambispective cohort study. OBJECTIVE: Patients spend on average 3 to 7 days in hospital after lumbar fusion surgery. Patients who are unable to be discharged home may require a prolonged hospital stay while awaiting a bed at a rehabilitation facility, adding cost and imposing a considerable burden on the health care system. Our objective is to identify patient or procedure related predictors of discharge destination for patients undergoing posterior lumbar fusion. METHODS: Analysis of data from the Canadian Spine Outcomes and Research Network. Patients who underwent lumbar fusion for degenerative pathology between 2008 and 2015 were identified. Multivariable logistic regression analysis was used to identify independent predictors of the discharge destination. RESULTS: A total of 643 patients were identified from the database, 87.1% of the patients (N = 560) were discharged home while 12.9% (N = 83) required discharge to nonhome facilities. Using multivariate logistic regression analysis, the predictors for discharge to a facility rather than home were identified including: increasing age (odds ratio [OR] 1.045, 95% confidence interval [CI] 1.017 -1.075, P < .002), increasing body mass index (BMI) (OR 1.069, 95% CI 1.021 -1.118, P < .004), increasing disability score (OR 1.025, 95% CI 1.004 -1.046, P < .02), living alone preoperatively (OR 1.916, 95% CI 1.004-3.654, P < .05), increasing operating time (OR 1.005, 95% CI 1.003 -1.008, P < .0001), need for blood transfusion (OR 3.32, 95% CI 1.687-6.528, P < .001), and multilevel fusion surgery (OR 1.142, 95% CI 1.007 -1.297, P < .04). CONCLUSIONS: Older age, high BMI, living alone, high disability score, extended surgical time, blood transfusion, and multilevel fusion are significant factors that increase the odds of being discharged to facilities other than home. LEVEL OF EVIDENCE: Level 3.

A 3D culture model of innervated human skeletal muscle enables studies of the adult neuromuscular junction.

Two-dimensional (2D) human skeletal muscle fiber cultures are ill-equipped to support the contractile properties of maturing muscle fibers. This limits their application to the study of adult human neuromuscular junction (NMJ) development, a process requiring maturation of muscle fibers in the presence of motor neuron endplates. Here we describe a three-dimensional (3D) co-culture method whereby human muscle progenitors mixed with human pluripotent stem cell-derived motor neurons self-organize to form functional NMJ connections. Functional connectivity between motor neuron endplates and muscle fibers is confirmed with calcium imaging and electrophysiological recordings. Notably, we only observed epsilon acetylcholine receptor subunit protein upregulation and activity in 3D co-cultures. Further, 3D co-culture treatments with myasthenia gravis patient sera shows the ease of studying human disease with the system. Hence, this work offers a simple method to model and evaluate adult human NMJ de novo development or disease in culture.

Effect of preoperative symptom duration on outcome in lumbar spinal stenosis: a Canadian Spine Outcomes and Research Network registry study.

BACKGROUND CONTEXT: Lumbar degenerative stenosis is one of the most common spine pathologies for which surgical intervention is indicated. There is some evidence that a prolonged duration of neurological compression could lead to a failure of surgery to alleviate symptoms. PURPOSE: Determination of whether longer symptom duration was associated with worse postoperative disability outcomes after decompressive surgery for lumbar degenerative stenosis. STUDY DESIGN/SETTING: The Canadian Spine Outcomes and Research Network (CSORN) prospective database includes pre- and postoperative data from 18 tertiary care hospitals. PATIENT SAMPLE: The CSORN database was queried for all cases of degenerative lumbar stenosis receiving surgical decompression for neurogenic claudication or radiculopathy. Patients with tumor, infection, fracture, or previous surgery were excluded. Patients were divided into groups based on symptom duration (<6 weeks, 6-12 weeks, 3-6 months, 6-12 months, 1-2 years, and >2 years). OUTCOME MEASURES: Change between preoperative and 12-month postoperative Oswestry Disability Index (ODI) was compared between symptom duration groups. Secondary outcomes included SF12 physical component score (PCS), and numeric rating scales for leg and back pain. Outcomes were also assessed at 3 months and 24 months postoperatively. METHODS: Change in ODI, and secondary outcome measures, were compared between different symptom duration groups. Multiple regression analysis was used to identify factors interacting with symptom duration to predict change in ODI. RESULTS: Four hundred and seventy-eight cases of lumbar stenosis with 12-month postoperative data were identified. Longer symptom duration correlated with less improvement in ODI (p<.001). Patients with >1 year of symptoms were less likely to achieve a Minimal Clinically Significant Difference in ODI (54.4% vs. 66.1%; p=.03) and were more likely to experience no improvement or worse disability, postoperatively (22.1% vs. 11.3%; p=.008). Similar results were found at 3- and 24-month timepoints. Smaller postoperative improvements in SF12 PCS and leg pain scales were also correlated with longer symptom duration (p<.05). CONCLUSIONS: Multicenter registry data provides important real-world evidence to guide consent, surgical planning, and health resource management. Longer symptom duration was found to correlate with less improvement in pain and disability after lumbar stenosis surgery suggesting that these patients may benefit from earlier treatment.