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Fusions for lumbar spine diseases are widely performed and have a growing incidence, especially in elderly population. The goal of this study was to assess national trends of lumbar spinal fusions and examine the risk for reoperations after a lumbar fusion with a focus on 'epidemiologic transition' relating to age. The prospectively collected Korean Health Insurance Review and Assessment Service (HIRA) nationwide cohort database was retrospectively reviewed. The total 278,815 patients who underwent lumbar spinal fusions for degenerative spine diseases between 2010 and 2018 were reviewed and used to assess trends in operative incidence. The 37,050 patients who underwent lumbar fusions between 1/2010 and 12/2011 were enrolled to determine 8-year reoperation rates. The overall number of lumbar spinal fusions were analyzed for the national annual trend. Demographic data, reoperation rates, and confounding clinical factors were evaluated. The overall number of lumbar spinal fusions was analyzed to determine the national annual trend of operative incidence. For the reoperation rate analysis, the primary outcome measured was the cumulative incidence of revision operations within a minimum 8-year follow-up period. Additional outcomes included comparative analyses of the reoperation rate with respect to age, sex, or other underlying comorbidities. Over time, elderly patients comprised a larger portion of the cohort (2010:24.2%; 2018:37.6%), while operations in younger patients decreased over time (2010:40.3%; 2018:27.0%). In the cohort of patients with a minimum 8-year follow-up (n=37,050), rates of reoperation peaked in patients aged 60–69 years (17.6 per 1000 person-years [HR 2.20 compared to <40years]) and decreased for more elderly patients (14.3 per 1000 person-years [HR 1.80 compared to <40years]). Age was the most significant risk factor for reoperation. Osteoporosis was also a risk factor for reoperation in postmenopausal females. Increasing incidence of lumbar fusions in elderly patients was seen however the risk of reoperation decreased in patients aged 70 or more. Lumbar fusion for elderly patients should not be hesitated in the decision-making process because of concerns about reoperation. [ABSTRACT FROM AUTHOR]

With the aging population, osteoporosis, which leads to poor fusion, has become a common challenge for lumbar surgery. In addition, most people with osteoporosis are elderly individuals with poor surgical tolerance, and poor bone quality can also weaken the stability of internal fixation. This study compared the fixation strength of the bilateral traditional trajectory screw structure (TT-TT), the bilateral cortical bone trajectory screw structure (CBT-CBT), and the hybrid CBT-TT (CBT screws at the cranial level and TT screws at the caudal level) structure under different bone mineral density conditions. A finite element (FE) analysis study. Above all, we established a healthy adult lumbar spine model. Second, under normal and osteoporotic conditions, three transforaminal lumbar interbody fusion (TLIF) models were established: bilateral traditional trajectory (TT-TT) screw fixation, bilateral cortical bone trajectory (CBT-CBT) screw fixation, and hybrid cortical bone trajectory screw and traditional trajectory screw (CBT-TT) fixation. Finally, a 500-N compression load with a torque of 10 N/m was applied to simulate flexion, extension, lateral bending, and axial rotation. We compared the range of motion (ROM), adjacent disc stress, cage stress, and posterior fixation stress of the different fusion models. Under different bone mineral density conditions, the range of motion of the fusion segment was significantly reduced. Compared to normal bone conditions, the ROM of the L4–L5 segment, the stress of the adjacent intervertebral disc, the surface stress of the cage, and the maximum stress of the posterior fixation system were all increased in osteoporosis. Under most loads, the ROM and surface stress of the cage and the maximum stress of the posterior fixation system of the TT-TT structure are the lowest under normal bone mineral density conditions. However, under osteoporotic conditions, the fixation strength of the CBT-CBT and CBT-TT structures are higher than that of the TT-TT structures under certain load conditions. At the same time, the surface stress of the intervertebral fusion cage and the maximum stress of the posterior fixation system for the two structures are lower than those of the TT-TT structure. Under normal bone mineral density conditions, transforaminal lumbar interbody fusion combined with TT-TT fixation provides the best biomechanictability. However, under osteoporotic conditions, CBT-CBT and CBT-TT structures have higher fixed strength compared to TT-TT structures. The hybrid CBT-TT structure exhibits advantages in minimal trauma and fixation strength. Therefore, this seems to be an alternative fixation method for patients with osteoporosis and degenerative spinal diseases. This study provides biomechanical support for the clinical application of hybrid CBT-TT structure for osteoporotic patients undergoing TLIF surgery. [ABSTRACT FROM AUTHOR]

Intraoperative blood loss is a significant concern in patients with metastatic spinal disease. Early identification of patients at high risk of experiencing massive intraoperative blood loss is crucial as it allows for the development of appropriate surgical plans and facilitates timely interventions. However, accurate prediction of intraoperative blood loss remains limited based on prior studies. The purpose of this study was to develop and validate a web-based artificial intelligence (AI) model to predict massive intraoperative blood loss during surgery for metastatic spinal disease. An observational cohort study. Two hundred seventy-six patients with metastatic spinal tumors undergoing decompressive surgery from two hospitals were included for analysis. Of these, 200 patients were assigned to the derivation cohort for model development and internal validation, while the remaining 76 were allocated to the external validation cohort. The primary outcome was massive intraoperative blood loss defined as an estimated blood loss of 2,500 cc or more. Data on patients' demographics, tumor conditions, oncological therapies, surgical strategies, and laboratory examinations were collected in the derivation cohort. SMOTETomek resampling (which is a combination of Synthetic Minority Oversampling Technique and Tomek Links Undersampling) was performed to balance the classes of the dataset and obtain an expanded dataset. The patients were randomly divided into two groups in a proportion of 7:3, with the most used for model development and the remaining for internal validation. External validation was performed in another cohort of 76 patients with metastatic spinal tumors undergoing decompressive surgery from a teaching hospital. The logistic regression (LR) model, and five machine learning models, including K-Nearest Neighbor (KNN), Decision Tree (DT), XGBoosting Machine (XGBM), Random Forest (RF), and Support Vector Machine (SVM), were used to develop prediction models. Model prediction performance was evaluated using area under the curve (AUC), recall, specificity, F1 score, Brier score, and log loss. A scoring system incorporating 10 evaluation metrics was developed to comprehensively evaluate the prediction performance. The incidence of massive intraoperative blood loss was 23.50% (47/200). The model features were comprised of five clinical variables, including tumor type, smoking status, Eastern Cooperative Oncology Group (ECOG) score, surgical process, and preoperative platelet level. The XGBM model performed the best in AUC (0.857 [95% CI: 0.827, 0.877]), accuracy (0.771), recall (0.854), F1 score (0.787), Brier score (0.150), and log loss (0.461), and the RF model ranked second in AUC (0.826 [95% CI: 0.793, 0.861]) and precise (0.705), whereas the AUC of the LR model was only 0.710 (95% CI: 0.665, 0.771), the accuracy was 0.627, the recall was 0.610, and the F1 score was 0.617. According to the scoring system, the XGBM model obtained the highest total score of 55, which signifies the best predictive performance among the evaluated models. External validation showed that the AUC of the XGBM model was also up to 0.809 (95% CI: 0.778, 0.860) and the accuracy was 0.733. The XGBM model, was further deployed online, and can be freely accessed at https://starxueshu-massivebloodloss-main-iudy71.streamlit.app/. The XGBM model may be a useful AI tool to assess the risk of intraoperative blood loss in patients with metastatic spinal disease undergoing decompressive surgery. [ABSTRACT FROM AUTHOR]

Although the risk of postoperative venous thromboembolism (VTE) in patients who undergo surgery for degenerative spinal disease has received attention, patients experiencing prolonged pain and disability while awaiting or considering surgery have not received adequate attention regarding the risk of VTE. To investigate the epidemiology of preoperative VTE in patients undergoing surgery for degenerative spinal disease. Retrospective cohort study using a nationwide database. Patients who underwent surgery for degenerative spinal disease. Preoperative occurrence of VTE. Data from 2014 to 2018 were obtained from the Korean National Health Insurance claims database. The occurrence of preoperative VTE within a 1-year period divided into 12 time intervals of 30 days each was investigated. The patients were categorized into two groups based on the presence of preoperative VTE. Multivariable logistic regression analysis was conducted to identify the factors associated with preoperative VTE. To validate the relationship between degenerative spinal disease and preoperative VTE, the diagnostic trends of preoperative VTE were analyzed in accordance with the identified risk factors. The overall incidence of preoperative VTE was 50 per 10,000 individuals. Multivariable analysis revealed that VTE occurred more frequently in older patients with specific medical comorbidities, particularly in those with a lumbar spinal lesion accompanied by arthritis of the hip, knee, or shoulder. We also found that the incidence rates of preoperative VTE, as well as the gradient of their increase, began to rise approximately 2 to 3 months prior to the index surgery, peaking just before the index surgery. This diagnostic trend was consistently observed in all patients irrespective of the presence of other risk factors. The incidence of preoperative VTE in patients with degenerative spinal disease exhibited a sharp increase immediately before surgery, with similar rates to those of postoperative VTE. Clinicians managing patients with degenerative spinal disease should be vigilant for preoperative as well as postoperative VTE. [ABSTRACT FROM AUTHOR]

Metastatic spinal disease is an advanced stage of cancer patients and often suffer from terrible psychological health status; however, the ability to estimate the risk probability of this adverse outcome using current available data is very limited. The goal of this study was to propose a precise model based on machine learning techniques to predict psychological status among cancer patients with spinal metastatic disease. A prospective cohort study. A total of 1043 cancer patients with spinal metastatic disease were included. The main outcome was severe psychological distress. The total of patients was randomly divided into a training dataset and a testing dataset on a ratio of 9:1. Patients' demographics, lifestyle choices, cancer-related features, clinical manifestations, and treatments were collected as potential model predictors in the study. Five machine learning algorithms, including XGBoosting machine, random forest, gradient boosting machine, support vector machine, and ensemble prediction model, as well as a logistic regression model were employed to train and optimize models in the training set, and their predictive performance was assessed in the testing set. Up to 21.48% of all patients who were recruited had severe psychological distress. Elderly patients (p<0.001), female (p =0.045), current smoking (p=0.002) or drinking (p=0.003), a lower level of education (p<0.001), a stronger spiritual desire (p<0.001), visceral metastasis (p=0.005), and a higher Eastern Cooperative Oncology Group (ECOG) score (p<0.001) were significantly associated with worse psychological health. With an area under the curve (AUC) of 0.865 (95% CI: 0.788–0.941) and an accuracy of up to 0.843, the gradient boosting machine algorithm performed best in the prediction of the outcome, followed by the XGBooting machine algorithm (AUC: 0.851, 95% CI: 0.768–0.934; Accuracy: 0.826) and ensemble prediction (AUC: 0.851, 95% CI: 0.770–0.932; Accuracy: 0.809) in the testing set. In contrast, the AUC of the logistic regression model was only 0.836 (95% CI: 0.756–0.916; Accuracy: 0.783). Machine learning models have greater predictive power and can offer useful tools to identify individuals with spinal metastatic disease who are experiencing severe psychological distress. [ABSTRACT FROM AUTHOR]

• Patients with cervical spine disease suffer from upper limb functional impairment. • No clinical benchmarks exist that define meaningful improvement in the upper limb function following cervical spine surgery. • Disabilities of arm, shoulder, and hand (DASH) is a validated outcome measure indicating upper limb disability. • This study aimed to establish minimal clinical important difference (MCID) and substantial clinical benefit (SCB) of the DASH score following cervical spine surgery. • The MCID of the DASH was –8 points and the SCB was –18 points. These metrics can be used to evaluate minimal and substantial improvement in the upper limb function following cervical spine surgery. Patients with cervical spine disease suffer from upper limb disability. At present, no clinical benchmarks exist for clinically meaningful change in the upper limb function following cervical spine surgery. Primary: to establish clinically meaningful metrics; the minimal clinically important difference (MCID) and substantial clinical benefit (SCB) of upper limb functional improvement in patients following cervical spine surgery. Secondary: to identify the prognostic factors of MCID and SCB of upper limb function following cervical spine surgery. Retrospective cohort study. Adult patients ≥18 years of age who underwent cervical spine surgery from 2012 to 2016. Patient-reported outcomes: Neck disability index (NDI) and Disabilities of Arm, Shoulder, and Hand (DASH). MCID was defined as minimal improvement and SCB as substantial improvement in the DASH score at last follow-up. The anchor-based methods (ROC analyses) defined optimal MCID and SCB thresholds with area under curve (AUC) in discriminating improved vs. non-improved patients. The MCID was also calculated by distribution-based methods: half standard-deviation (0.5-SD) and standard error of the mean (SEM) method. A multivariable logistic regression evaluated the impact of baseline factors in achieving the MCID and SCB in DASH following cervical spine surgery. Between 2012 and 2016, 1,046 patients with average age of 57±11.3 years, 53% males, underwent cervical spine surgery. Using the ROC analysis, the threshold for MCID was –8 points with AUC of 0.73 (95% CI: 0.67–0.79) and the SCB was –18 points with AUC of 0.88 (95% confidence interval [CI]: 0.85–0.91). The MCID was –11 points by 0.5–SD and –12 points by SEM-method. On multivariable analysis, patients with myelopathy had lower odds of achieving MCID and SCB, whereas older patients and those with ≥6 months duration of symptoms had lower odds of achieving DASH MCID and SCB respectively. In patients undergoing cervical spine surgery, MCID of –8 points and SCB of –18 points in DASH improvement may be considered clinically significant. These metrics may enable evaluation of minimal and substantial improvement in the upper extremity function following cervical spine surgery. [ABSTRACT FROM AUTHOR]

Background Context: Patient reported outcome measures (PROMs) are of utmost importance to clinical practice as they permit a patient-focused evaluation of surgical outcomes. However, recall bias can limit an adequate interpretation of PROMs.Purpose: To assess the impact of recall bias of preoperative status on postoperative PROMs of patients submitted to surgery due to degenerative spine disease.Study Design/ Setting: Randomized controlled trial in a tertiary care neurosurgical unit in Portugal PATIENT SAMPLE: All patients submitted to surgery at our institution from January 2019 to April 2020 due to degenerative lumbar or cervical spine disease with valid PROMs questionnaires were enrolled, and two computer generated randomized groups were created.Outcome Measures: The study´s primary endpoint was the median postoperative Core Outcome Measure Index (COMI) score.Methods: The intervention group was sent postoperative questionnaires including preoperative answers, while patients in the control group were sent the same PROMs without the preoperative answers.Results: Randomization was applied to 236 patients (118 for each group) and valid results were obtained for 147 patients (81 lumbar, 44 from the intervention group; and 66 cervical, 29 from the intervention group), from which 88 (60%) were females, with a median age of 58 years. Both groups shared similar baseline clinical characteristics and preoperative scores. Median postoperative COMI scores and interquartile ranges (IQR) were 4.20 (IQR: 2.30-6.00) and 5.45 (IQR: 3.75-7.40) for the intervention and control groups, respectively (Wilcoxon, p=0.02). This difference was reached mainly due to cervical spine patients as median postoperative COMI score was 3.95 (IQR: 2.20-5.32) in the intervention group and 5.1 (IQR: 4.0-8.4) in the control group (Wilcoxon, p=0.01). No significant difference was reached for lumbar patients.Conclusions: Better PROMs scores were obtained for degenerative cervical spine patients to whom the preoperative results were provided. Therefore, providing preoperative scores to patients upon postoperative PROMs fulfilment might influence postoperative results. Further research is necessary to increase the reliability of PROMs in clinical practice. [ABSTRACT FROM AUTHOR]

Background Context: Cage subsidence following transforaminal lumbar interbody fusion (TLIF) has been associated with poor bone quality. Current evidence suggests that the magnetic resonance imaging (MRI)-based vertebral bone quality (VBQ) score correlates with poor bone quality.Purpose: To our knowledge, this is the first study to assess whether the VBQ score can predict the occurrence of postoperative cage subsidence after TLIF surgery.Design/setting: Retrospective single-center cohort.Patient Sample: Patients undergoing single-level TLIF for degenerative spine disease between February 2014 and October 2021.Outcome Measures: Extent of subsidence.Methods: Demographic, procedure-related, and radiographic data were collected for study patients. VBQ scores were determined from preoperative T1-weighted MRI. Subsidence was defined as ≥2 mm of migration of the cage into the superior or inferior end plate or both. Univariate and multivariate logistic regression were used to determine the correlation between potential risk factors for subsidence and actual subsidence rates.Results: Subsidence was observed among 42 of the 74 study patients. The mean VBQ scores were 2.9±0.5 for patients with subsidence and 2.5±0.5 for patients without subsidence. The difference among groups was significant (p=.003). On multivariate logistic regression, a higher VBQ score was significantly associated with an increased risk of subsidence (OR=1.5, 95% CI=1.160-1.973, p=.004) and was the only significant independent predictor of subsidence after TLIF.Conclusion: We found that a higher VBQ score was significantly associated with cage subsidence following TLIF. The MRI-VBQ score may be a valuable tool for assisting in identifying patients at risk of cage subsidence following TLIF. [ABSTRACT FROM AUTHOR]

Background Context: Intervertebral disc degeneration represents one of multiple potential trigger factors for reduced passive spinal mobility and back pain. The effects of age-related degenerative intervertebral disc changes on spinal flexibility were however mainly investigated for the lumbar spine in the past, while intervertebral disc degeneration is also highly prevalent in the thoracic spine.Purpose: To evaluate the effect of the degeneration grade on the range of motion and neutral zone of the thoracic spine.Study Design: Experimental study including combined radiological grading of intervertebral disc degeneration and biomechanical testing of 95 human thoracic functional spinal units (min. n=4 per level from T1-T2 to T11-T12) from 33 donors (15 female / 18 male, mean age 56 years, age range 37-80 years).Methods: Degeneration grades of the intervertebral discs were assessed using the validated x-ray grading scheme of Liebsch et al. (0=no, 1=mild, 2=moderate, 3=severe degeneration). Motion segments were loaded with pure moments in flexion/extension, lateral bending, and axial rotation to determine range of motion and neutral zone at 5 Nm.Results: All tested specimens exhibited degeneration grades between zero and two. Range of motion significantly decreased for grades one and two compared with grade zero in any motion direction (p<.05), showing the strongest decrease in extension comparing grade two with grade zero (-42%), while no significant differences were detected between grades one and two. Similar trends were found for the neutral zone with the strongest decrease in extension also comparing grade two with grade zero (-47%). Donor age did not significantly affect the range of motion, whereas the range of motion was significantly reduced in specimens from male donors due to the significantly higher degeneration grade in this study.Conclusions: Even mild intervertebral disc degeneration reduces the range of motion and neutral zone of the thoracic spine in any motion plane, whereas progressing degeneration does not further affect its flexibility. This is in contrast to the lumbar spine, where a more gradual decrease of flexibility was found in prior studies, which might be explained by differences between thoracic and lumbar intervertebral disc morphologies.Clinical Significance: Thoracic intervertebral disc degeneration should be considered as one of multiple potential causal factors in patients showing reduced passive mobility and middle back pain. [ABSTRACT FROM AUTHOR]

The Oswestry Disability Index (ODI) and Patient Reported Outcomes Measurement Information Systems (PROMIS) domains are common patient-reported assessment tools used in the evaluation of spine interventions. Previous studies have aided in developing crosswalks between ODI and the different PROMIS domains. The aim of this study is to determine correlation of measures preoperatively (preop) in patients undergoing spinal fusion for degenerative lumbar disease and determine any patterns in demographics that could contribute to establishing benchmarking data that could aid in preoperative counseling and surgical decision making. Retrospective study. A total of 140 adult lumbar spine patients. Patient reported outcomes. Retrospective data collection and analysis of patients completing preop ODI and PROMIS Physical Function (PF), Pain Interference (PI) and Satisfaction in Social Roles (SR) prior to lumbar fusion for degenerative spine disease. In total, 140 patients charts were reviewed. Three cohorts were created based on the distribution of the ODI score (< 25th, 25th-75th and > 75th percentiles): Group I (ODI <36), Group II (36≥ODI≤58), and Group III (ODI>58). Group I consisted of 37 patients with a mean age 66.4 ± 11.9 years and 50% female; Group II had 69 patients with a mean age of 68.1 ± 9.6 years and 58% female; Group III had 34 patients with a mean age of 59.5 ± 11.3 years and 50% female. Mean age of Group III was significantly younger than Groups I and II (p=0.023). In addition to the higher ODI scores, Group III had lowest mean PF (28.4± 4.4) and SR (31.6± 5.0) PROMIS scores as well as highest mean PI (72.4± 4.7) scores. Negative correlations existed, as expected, across all Groups between ODI vs PF, and ODI vs SR, whereas a positive correlation was observed between ODI vs PI across all groups as well. Patients with the highest self-reported disability and pain interference scores, were significantly younger than patients with lower ODI and PI scores. These younger patients also reported lower physical function and dissatisfaction in social roles than the other patients. This study supports the observation that higher self-reported pain scores are increasingly being seen in younger spine populations. This abstract does not discuss or include any applicable devices or drugs. [ABSTRACT FROM AUTHOR]

Recently, a 2024 TSJ article by Shi et al. described the development of a machine learning (ML) model for predicting massive (>2500mL) intraoperative blood loss during posterior decompressive surgery for spinal metastasis. Surgery included en-bloc or partial resection of vertebrae with stabilization or palliative decompression with stabilization. The model was developed in a Chinese cohort (n = 200) and performed well in an external validation cohort (n = 76) within the same region. We sought to validate the ML model across two new geographical areas (North America and Europe) and patient cohorts. N/A N/A N/A N/A We retrospectively included patients across two institutions between 2016 and 2022. Inclusion and exclusion criteria were consistent with the development study, with additional inclusion of (1) patients undergoing palliative decompression without stabilization, (2) patients with multiple myeloma and lymphoma, and (3) patients who continued anticoagulants perioperatively. Massive intraoperative blood loss was defined as >2500mL and in addition to the Gross formula used in the development study, we quantified this outcome using 6 other methods as there is no gold standard for estimating blood loss. ML model predictions were compared against all intraoperative blood loss quantification methods. A sub-analysis, excluding the additional patient groups, assessed the ML model's performance with the same in- and exclusion criteria as the development cohort. Missing values were imputed using missForest in R. In total, 539 patients were included. There were notable differences in baseline characteristics between our cohort and the development cohort. We included more patients with partial or en-bloc resection, suggesting higher risk of blood loss, and lower Eastern Cooperative Oncology Group (ECOG) scores. However, depending on the method used, massive intraoperative blood loss incidence ranged from 7.7% (p <0.01) to 23% (p >0.999), which is less or equal to the development study respectively. The ML model scored poorly on performance metrics and overestimated the intraoperative blood loss across all outcome methods with the best performance using the Lopez-Picado nadir formula (specificity: 0.352, precision: 0.261), overall performance (F1 Score: 0.394, accuracy: 0.453, Brier score: 0.298, log loss: 0.848), and discriminatory ability (AUC: 0.634 [CI: 0.578, 0.690]), except for recall (0.875). Sub-analysis (n = 421) showed consistent poor performance. To our knowledge, this is the first external ML model validation within spine surgery demonstrating poor performance. The ML model displayed a strong tendency to overestimate massive intraoperative blood loss risk in our cohort. This overestimation might be attributed to a distributional shift as our cohort had key differences in variables used by the ML model to predict massive intraoperative blood loss, such as ECOG scores and surgery type. Overall, our results emphasize the importance of external validation and the development of ML algorithms in multiple geographical areas with varying baseline characteristic distributions, before implementing them in clinical practice. This abstract does not discuss or include any applicable devices or drugs. [ABSTRACT FROM AUTHOR]

Background Context: With improvements in surgical techniques and perioperative management, transfusion rates after spine surgery have decreased over time. Given this trend, routine preoperative ABO/Rh type and antibody screen (T&S) laboratory testing may not be warranted in all patients undergoing spine surgery.Purpose: The aim of the current study is to evaluate risk factors for intra/postoperative transfusion in patients undergoing a variety of spine procedures and to develop an algorithm for selectively ordering preoperative T&S testing in appropriate patients.Study Design/setting: This is a single institution, retrospective observational study of patients undergoing emergent or elective spine surgery. External validation of the algorithm was performed on a national sample of patients undergoing spine surgery from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) national database.Patient Sample: A total of 5,947 surgeries from January 1, 2016 to December 31, 2019 at a single institution, and 166,113 surgeries from the 2016 to 2018 ACS-NSQIP database.Outcome Measures: The primary outcome measure was performance of intraoperative or postoperative transfusion.Methods: Using the institutional sample, univariate statistics (chi-square tests, fisher's exact test, 2-sided independent sample tests) were performed to compare demographics, comorbidities, and surgical details (case type, number of levels treated, etc.) between patients who did and did not require intra- or postoperative transfusion. Transfusion rates were calculated and compared across procedure types. Multivariate logistic regression was performed to identify independent predictors of transfusion and the model's accuracy was evaluated using the area under the curve (AUC) of the receiver operating characteristics (ROC) curve. A risk-based algorithm suggesting no preoperative T&S in low transfusion risk procedures, routine preoperative T&S in high-risk procedures, and further assessment in medium risk thoracolumbar fusion procedures was created. The algorithm's sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were evaluated when it was applied to both the institutional and national samples. Potential cost savings from reducing T&S orders were calculated.Results: In the institutional sample, 120 patients (2.0%) required intraoperative or postoperative transfusion. The highest rates of transfusion were found in corpectomy (10.5%) and anterior/posterior cervical fusion (6.9%) procedures. In the multivariate logistic regression model, the presence of a preoperative coagulation defect or hemorrhagic condition (OR: 7.149, p<.001) and 6+ level surgery (OR: 7.511, p<.001) were the strongest predictors of transfusion. Overall, the model generated an AUC of 0.882, indicating excellent predictive accuracy. When applied to the institutional cohort, the risk-based algorithm had a sensitivity of 78.3%, specificity of 80.5%, PPV of 7.6%, and NPV of 99.4% for evaluating likelihood of transfusion. Using the algorithm 4,717 T&S tests would have been eliminated (79.3%), resulting in a cost savings of $179,246. Application of the model to the ACS-NSQIP cohort resulted in a sensitivity of 61.9%, specificity of 84.6%, PPV of 15.6%, and NPV of 98.0%.Conclusions: The routine use of preoperative ABO/Rh type and antibody screen testing does not appear to be warranted in patients undergoing spine surgery. A risk-based approach to preoperative type and screen testing may eliminate unnecessary tests and generate significant cost savings with minimal disruption to clinical care. [ABSTRACT FROM AUTHOR]

Background Context: Facet joint degeneration (FJD) and disc degeneration (DD) with associated endplate (EP) changes, specifically Modic 1 changes, might occur concurrently and therefore pose a challenge in the treatment of lower back pain (LBP).Purpose: The aim of the present study was to investigate if the presence of active EP changes (Modic 1) would alter the effect of facet joint infiltrations (FJI) for the treatment of concurrent FJD.Study Design: Prospective cohort study, Level III.Patient Sample: 42 patients (Male:20, Female:22) with an average of 58±14 years with FJD on conventional magnetic resonance imaging (MRI) receiving a FJI for treatment of lower back pain were included.Outcome Measures: The pain score at baseline, 15 min, 1 day, 1 week and 1 month following FJI as well as the reduction of pain were analyzed. Furthermore, active EP changes on conventional MRI and increased EP metabolic activity on PET/MRI were evaluated and compared.Methods: All the patients underwent a (18F)-NaF PET/MRI, conventional MRI and FJI for symptomatic FJD. Active EP changes on conventional MRI and increased EP metabolic activity on PET/MR were analyzed for conformity. The pain score as well as the pain reduction at the above-mentioned time points were compared between patients with and without increased EP metabolic activity in PET/MRI.Results: The LBP reduction was significantly different between patients with (n=20) and without (n=22) active EP changes at 15 minutes (1.3±2.4 vs. 2.9±2.4, p=.03) and 1 month (0.9±2.3 vs. 2.8±2.9, p<.001) following FJI. The minimal clinically important difference for LBP reduction was reached significantly more often in the absence of active EP changes (73%) compared with patients with active EP changes (35%) 1 month following FJI (p=.03).Conclusions: FJI is less effective in LBP reduction of patients with FJD and concurrent active EP changes (eg Modic 1). [ABSTRACT FROM AUTHOR]

Background Context: The importance of bone status assessment in spine surgery is well recognized. The current gold standard for assessing bone mineral density is dual-energy X-ray absorptiometry (DEXA). However, DEXA has been shown to overestimate BMD in patients with spinal degenerative disease and obesity. Consequently, alternative radiographic measurements using data routinely gathered during preoperative evaluation have been explored for the evaluation of bone quality and fracture risk. Opportunistic quantitative computed tomography (QCT) and more recently, the MRI-based vertebral bone quality (VBQ) score, have both been shown to correlate with DEXA T-scores and predict osteoporotic fractures. However, to date the direct association between VBQ and QCT has not been studied.Purpose: The objective of this study was to evaluate the correlation between VBQ and spine QCT BMD measurements and assess whether the recently described novel VBQ score can predict the presence of osteopenia/osteoporosis diagnosed with QCT.Study Design/setting: Cross-sectional study using retrospectively collected data.Patient Sample: Patients undergoing lumbar fusion from 2014-2019 at a single, academic institution with available preoperative lumbar CT and T1-weighted MRIs were included.Outcome Measures: Correlation of the VBQ score with BMD measured by QCT, and association between VBQ score and presence of osteopenia/osteoporosis.Methods: Asynchronous QCT measurements were performed. The average L1-L2 BMD was calculated and patients were categorized as either normal BMD (>120 mg/cm3) or osteopenic/osteoporotic (≤120 mg/cm3). The VBQ score was calculated by dividing the median signal intensity of the L1-L4 vertebral bodies by the signal intensity of the cerebrospinal fluid on midsagittal T1-weighted MRI images. Inter-observer reliability testing of the VBQ measurements was performed. Demographic data and the VBQ score were compared between the normal and osteopenic/osteoporotic group. To determine the area-under-curve (AUC) of the VBQ score as a predictor of osteopenia/osteoporosis receiver operating characteristic (ROC) analysis was performed. VBQ scores were compared with QCT BMD using the Pearson's correlation.Results: A total of 198 patients (53% female) were included. The mean age was 62 years and the mean BMI was 28.2 kg/m2. The inter-observer reliability of the VBQ measurements was excellent (ICC of 0.90). When comparing the patients with normal QCT BMD to those with osteopenia/osteoporosis, the patients with osteopenia/osteoporosis were significantly older (64.9 vs. 56.7 years, p<.0001). The osteopenic/osteoporotic group had significantly higher VBQ scores (2.6 vs. 2.2, p<.0001). The VBQ score showed a statistically significant negative correlation with QCT BMD (correlation coefficient = -0.358, 95% CI -0.473 - -0.23, p<.001). Using a VBQ score cutoff value of 2.388, the categorical VBQ score yielded a sensitivity of 74.3% and a specificity of 57.0% with an AUC of 0.7079 to differentiate patients with osteopenia/osteoporosis and with normal BMD.Conclusions: We found that the VBQ score showed moderate diagnostic ability to differentiate patients with normal BMD versus osteopenic/osteoporotic BMD based on QCT. VBQ may be an interesting adjunct to clinically performed bone density measurements in the future. [ABSTRACT FROM AUTHOR]

Background Context: Sacroiliac (SI) joint pain causes significant disability and impairment to quality of life (QOL). Minimally invasive SI joint fusion is increasingly used to relieve chronic SI joint pain among patients who do not respond to nonsurgical treatment.Purpose: To systematically review the existing literature to assess the effectiveness and safety of minimally invasive SI joint fusion.Study Design/setting: Systematic review.Data Sources: PubMed, Embase, Cochrane, and a clinical trial registry from database inception to June 30, 2021.Study Selection: Eligible studies were primary research studies published in the English language, enrolled adults with SI joint pain, and compared SI joint fusion to nonsurgical interventions or alternative minimally invasive procedures. We included randomized controlled trials (RCTs) or controlled cohort studies (CCSs) that reported effectiveness (pain, physical function, QOL, opioid use) or safety outcomes (adverse events [AEs], revision surgeries) and uncontrolled studies that reported safety outcomes.Data Abstraction and Synthesis: Data were abstracted into structured forms; two independent reviewers assessed risk of bias using standard instruments; certainty of evidence was rated using GRADE.Results: Forty studies (2 RCTs, 3 CCSs, and 35 uncontrolled studies) were included. Minimally invasive SI joint fusion with the iFuse Implant System appeared to result in larger improvements in pain (two RCTs: mean difference in visual analog scale -40.5 mm, 95% CI, -50.1 to -30.9; -38.1 mm, p<.0001) and larger improvements in physical function (mean difference in Oswestry Disability Index -25.4 points, 95% CI, -32.5 to -18.3; -19.8 points, p<.0001) compared to conservative management at 6 months. Improvements in pain and physical function for the RCTs appeared durable at 1- and 2-year follow-up. Findings were similar in one CCS. The two RCTs also found significant improvements in QOL at 6 months and 1 year. Opioid use may be improved at 6 months and 1 to 2 years. AEs appeared higher in the fusion group at 6 months. The incidence of revision surgery varied by study; the highest was 3.8% at 2 years. Two CCSs compared the effectiveness of alternative minimally invasive fusion procedures. One CCS compared iFuse to the Rialto SI Fusion System and reported no differences in pain, function, QOL, and revision surgeries from 6 months to 1 year. One CCS compared iFuse to percutaneous screw fixation and reported significantly fewer revisions among iFuse participants (mean difference -61.0%, 95% CI, -78.4% to -43.5%). The 35 uncontrolled studies had serious limitations and reported heterogeneous safety outcomes. Two of the larger studies reported a 13.2% incidence of complications from minimally invasive SI joint fusion at 90 days using an insurance claims database and a 3.1% incidence of revision surgery over 2.5 years using a postmarket surveillance database.Conclusions: Among patients meeting diagnostic criteria for SI joint pain and who have not responded to conservative care, minimally invasive SI joint fusion is probably more effective than conservative management for reducing pain and opioid use and improving physical function and QOL. Fusion with iFuse and Rialto appear to have similar effectiveness. AEs appear to be higher for minimally invasive SI joint fusion than conservative management through 6 months. Based on evidence from uncontrolled studies, serious AEs from minimally invasive SI joint fusion may be higher in usual practice compared to what is reported in trials. The incidence of revision surgery is likely no higher than 3.8% at 2 years. Limited evidence is available that compares different minimally invasive devices. [ABSTRACT FROM AUTHOR]

Background Context: Arthrodesis is important for the success of posterior cervical fusion (PCF), however, there exists limited data regarding the safety and efficacy of bone morphogenic protein (BMP) in PCF.Purpose: The primary objective was to evaluate early postoperative complications associated with BMP in PCF and determine whether BMP leads to adverse early clinical outcomes. A secondary objective was to determine the optimal location for BMP sponge placement, within the facet joint (IF) or elsewhere, and the optimal dosage/level.Design: Retrospective, consecutive case-control study.Patient Sample: Seven hundred sixty-five patients who underwent PCF OUTCOME MEASURES: Patient-reported outcomes (PROs), complications, arthrodesis, optimum dose/level of BMP METHODS: Surgical data, including preoperative diagnosis, levels fused, type of bone graft, BMP dose (when used), and fusion technique were recorded. Complications were assessed by reviewing the medical record encompassing the first 6-weeks postoperative. These included medical, neurological, and wound-related complications and reoperation. Neurological complications were defined as any new weakness, radicular pain, or numbness. PROs were collected, including SF36, VAS, EQ-5D, and NDI scores. To determine the optimal dosage and location for BMP placement, a sub-analysis was performed.Results: There were no significant differences between the BMP and no BMP group with regards to wound complications, neurological complications, or reoperation. There were no differences in PROs between BMP and no BMP. Placement of BMP for IF and at a dose of 0.87 mg/level minimized wound-related complications. The BMP group had a higher fusion rate compared to the no BMP group (96% vs. 91%, p=.02) when assessed 1 year post-operatively.Conclusion: BMP was not associated with a higher rate of early complications after PCF when the dose was minimized. Complications thought to be associated with BMP, such as compressive seroma, radiculitis, and wound-related complications were not seen at a higher rate. PROs at early follow-up were similar. Placement of BMP for IF and at lower doses than previously reported may minimize complications. [ABSTRACT FROM AUTHOR]

Background Context: Despite concerted efforts toward quality improvement in high-volume spine surgery, there remains concern that increases in case load may compromise the efficient and safe delivery of surgical care. There is a paucity of evidence to describe the effects of spine case order and operating room (OR) team structure on measures of intraoperative timing and OR efficiency.Purpose: This study aims to determine if intraoperative staff changes and surgical case order independently predict extensions in intraoperative timing after spinal surgery for spondylotic diseases.Study Design/ Setting: Retrospective cohort analysis PATIENT SAMPLE: All patients over age 18 who underwent primary or revision decompression and/or fusion for degenerative spinal diseases between 2017 to 2019 at a single academic institution were retrospectively identified. Exclusion criteria included absence of descriptive data and intraoperative timing parameters as well as surgery for traumatic injury, infection, and malignancy.Outcome Measures: Intraoperative timing metrics including total theater time, wheels in to induction, induction start to cut, cut to close, and close to wheels out. Postoperative outcomes included length of hospital stay and 90-day hospital readmissions.Methods: Surgical case order and intraoperative changes in staff (circulator and surgical scrub nurse or technician) were determined. Patient demographics, surgical factors, intraoperative timing and postoperative outcomes were recorded. Extensions in each operative stage were determined as a ratio of the actual duration of the parameter divided by the predicted duration of the parameter. Univariate and multivariate analyses were performed to compare outcomes within case order and staff change groups.Results: A total of 1,108 patients met the inclusion criteria. First, second, and third start cases differed significantly in intraoperative extensions of total theater time, wheels in to induction, induction start to cut, cut to close, and close to wheels out. On regression, decreasing case order predicted extension in wheels in to induction time. Surgeries with intraoperative staff changes were associated with increases in total theater time, induction start to cut time, cut to close time, close to wheels out time, and length of hospital stay. Switch in primary circulator predicted extended theater time and cut to close time. Relief of primary circulator or scrub predicted extended total theater time, induction start to cut time, cut to close time, and close to wheels out time.Conclusions: Intraoperative staff change in spine surgery independently predicted extended operative duration. However, higher case order was not significantly associated with procedural time. [ABSTRACT FROM AUTHOR]

Background Context: Frailty as a concept is not yet fully understood, and is not the same as comorbidity. It is associated with an increased risk of adverse events and mortality after surgery, which makes its preoperative assessment significant. Despite its relevance, it still remains unclear which scales are appropriate for use in patients with spinal pathology.Purpose: To evaluate the feasibility and measurement properties of frailty scales for spine patients, specifically with adult spinal deformity (ASD), and to propose adequate scales for primary triage to prevent surgery in too frail patients and for preoperative assessment to modify patients' condition and surgical plans.Study Design/setting: Systematic review.Methods: Systematic search was performed between 2010 and 2021 including terms relating to spinal disorders, frailty scales, and methodological quality. Characteristics of the studies and frailty scales and data describing relation to treatment outcomes were extracted. The risk of bias was determined with the QAREL score.Results: Of the 1993 references found, 88 original studies were included and 23 scales were identified. No prospective interventional study was found where the preoperative frailty assessment was implemented. Predictive value of scales for surgical outcomes varied, dependent on spinal disorders, type of surgeries, patients' age and frailty at baseline, and outcomes. Seventeen studies reported measurement properties of eight scales but these studies were not free of bias. In 30 ASD studies, ASD-Frailty Index (ASD-FI, n=14) and 11-item modified Frailty Index (mFI-11, n=11) were most frequently used. These scales were mainly studied in registry studies including young adult population, and carry a risk of sample bias and make their validity in elderly population unclear. ASD-FI covers multidisciplinary concepts of frailty with 40 items but its feasibility in clinical practice is questionable due to its length. The Risk Analysis Index, another multidisciplinary scale with 14 items, has been implemented for preoperative assessment in other surgical domains and was proven to be feasible and effective in interventional prospective studies. The FRAIL is a simple questionnaire with five items and its predictive value was confirmed in prospective cohort studies in which only elderly patients were included.Conclusions: No adequate scale was identified in terms of methodological quality and feasibility for daily practice. Careful attention should be paid when choosing an adequate scale, which depends on the setting of interest (eg triage or preoperative work-up). We recommend to further study a simple and predictive scale such as FRAIL for primary triage and a comprehensive and feasible scale such as Risk Analysis Index for preoperative assessment for patients undergoing spine surgery, as their adequacy has been shown in other medical domains. [ABSTRACT FROM AUTHOR]

Background Context: It is controversial whether lumbar spinal stenosis (LSS) itself contributes to low back pain (LBP). Lower truncal skeletal muscle mass, spinopelvic malalignment, intervertebral disc degeneration, and endplate abnormalities are thought to be related to LBP. However, whether these factors cause LBP in patients with LSS is unclear.Purpose: To identify factors associated with LBP in patients with LSS.Study Design/setting: Cross-sectional design.Patient Sample: A total of 260 patients (119 men and 141 women, average age 72.8 years) with neurogenic claudication caused by LSS, as confirmed by magnetic resonance imaging (MRI).Outcome Measures: Ratings of LBP, buttock and leg pain, and numbness on a numerical rating scale (NRS), 36-Item Short Form Survey (SF-36) scores, muscle mass measured by bioelectrical impedance analysis, and radiographic measurements including slippage and lumbopelvic alignment. The severity of LSS, endplate defects, Modic endplate changes, intervertebral disc degeneration, and facet joint osteoarthritis were assessed on MRI.Methods: The presence of LBP was defined as an NRS score ≥3. The demographic data, patient-reported outcomes, and radiological and MRI findings were compared between patients with and without LBP. Multivariate logistic regression analysis was used to identify the factors that were independently associated with the presence of LBP.Results: There were significant differences between patients with and without LBP for buttock and leg pain and numbness on the NRS, general health on the SF-36, presence of endplate defects, presence of Modic changes, disc degeneration grading, and disc height grading (all p < .05). Multivariate logistic regression analysis showed significant associations between LBP and diabetes (OR 2.43; 95% CI 1.07-5.53), buttock and leg numbness on the NRS (OR 1.34; 95% CI 1.17-1.52), general health on the SF-36 (OR 0.97; 95% CI 0.95-0.99), and the presence of erosive endplate defects (OR 3.04; 95% CI 1.51-6.11) (all p < .05).Conclusions: These results suggest that LBP in patients with LSS should be carefully assessed not only for spinal stenosis but also clinical factors and endplate defects. [ABSTRACT FROM AUTHOR]

Background: Increasing kyphosis of the spine in a human is a well-recognized clinical phenomenon that has been associated with back pain, poor physical performance and disability. The pathophysiology of age-related kyphosis is complex and has been associated with physiological changes in vertebrae, intervertebral disc (IVD) and paraspinal musculature, which current cross-sectional studies are unable to demonstrate. Creating an in vivo, paraspinal myopathic animal model for longitudinal study of these changes under controlled conditions is thus warranted.Purpose: To confirm the TSC1 gene knockout effect on paraspinal muscle musculature; to analyze the development of spinal kyphosis, IVD degeneration and vertebra structural changes in a longitudinal manner to gain insights into the relationship between these processes.Study Design: A prospective cohort study of 28 female mice, divided into 4 groups-9-month-old TSC1mKO (n=7), 9-month-old control (n=4), 12-month-old TSC1mKO (n=8), and 12-month-old controls (n=9).Methods: High resolution micro-computed tomography was used to measure sagittal spinal alignment (Cobb's angle), vertebral height, vertebral body wedging, disc height index (DHI), disc wedge index (DWI), histomorphometry of trabecular bone and erector spinae muscle cross-sectional area. Paraspinal muscle specimens were harvested to assess for myopathic features with H&E stain, muscle fiber size, density of triangular fiber and central nucleus with WGA/DAPI stain, and percentage of fibers with PGC-1α stain. Intervertebral discs were evaluated for disc score using FAST stain.Results: Compared to controls, paraspinal muscle sections revealed features of myopathy in TSC1mKO mice similar to human sarcopenic paraspinal muscle. While there was significantly greater presence of small triangular fiber and density of central nucleus in 9-and 12-month-old TSC1mKO mice, significantly larger muscle fibers and decreased erector spinae muscle cross-sectional area were only found in 12-month-old TSC1mKO mice compared to controls. TSC1mKO mice developed accelerated thoracolumbar kyphosis, with significantly larger Cobb angles found only at 12 months old. Structural changes to the trabecular bone in terms of higher bone volume fraction and quality, as well as vertebral body wedging were observed only in 12-month-old TSC1mKO mice when compared to controls. Disc degeneration was observed as early as 9 months in TSC1mKO mice and corresponded with disc wedging. However, significant disc height loss was only observed when comparing 12-month-old TSC1mKO mice with controls.Conclusions: This study successfully shows the TSC1 gene knockout effect on the development of paraspinal muscle myopathy in a mouse which is characteristic of sarcopenia. The TSC1mKO mice is by far the best model available to study the pathological consequence of sarcopenia on mice spine. With paraspinal muscle myopathy established as early as 9 months, TSC1mKO mice developed disc degeneration and disc wedging. This is followed by kyphosis of the spine at 12 months with concomitant disc height loss and vertebral body wedging due to bone remodeling. Age-related bone loss was not found in our study, suggesting osteoporosis and myopathy-induced vertebral body wedging are likely two independent processes.Clinical Significance: This is the first study to provide key insights on the early and late consequences of paraspinal myopathy on intervertebral disc degeneration, spinal kyphosis, and vertebral body changes. With this new understanding, future studies evaluating therapies for spinal degeneration may be performed to develop time-sensitive interventions. [ABSTRACT FROM AUTHOR]

Background Context: Cervical total disc arthroplasty (TDA) is an alternative procedure to anterior cervical discectomy and fusion that facilitates neural decompression while both preserving motion of the spinal unit and decreasing the risk for degenerative changes at adjacent segments. However, due to its more recent introduction in clinical practice and low complication rates, the modes by which TDA may fail remain to be described.Purpose: This study sought to identify the modes and frequencies of cervical TDA failure in order to propose a novel classification system.Study Design: Retrospective cohort and systematic review.Patient Sample: Patients who underwent single or two-level TDA for cervical radiculopathy or myelopathy at a single institution and in the literature of medium and large prospective studies.Outcome Measures: Cervical TDA failure, defined as subsequent surgical intervention at the index segment.Methods: This study retrospectively reviewed patients who underwent single or two-level TDA for cervical radiculopathy or myelopathy at a single institution to identify the potential implant failure modes. A systematic review and meta-analysis of prospective data in the literature was then performed to further supplement failure mode identification and to describe the rates at which the various failure types occurred. Statistical analysis included between-group comparisons of Non-Failed and Failed patients and frequencies of each failure type among Failed patients.Results: A retrospective review at our institution of 169 patients (201 levels) identified eight failures, for a failure rate of 4.7%. Additionally, seven patients were revised who had the primary surgery at an outside institution. The systematic review of 3976 patients (4525 levels) identified 165 (4.1%) additional failures. Using this data, six primary failure types were classified, with several subtypes. These include recurrent or persistent index-level stenosis (Type I); migration (Type II) presenting as gross extrusion (A) or endplate failure with subsidence/acute fracture (B); instability (Type III) due to mechanical loosening (A), septic loosening (B), or device fracture (C); device motion loss (Type IV) such as "locking" of the device in kyphosis; implantation error (Type V) due to malposition (A) or improper sizing (B); and wear (Type VI) either without osteolysis (A) or with wear-particle-induced osteolysis (B). Stenosis (Type I) was the most common mode of failure found both through retrospective review and in the literature.Conclusions: Cervical TDA fails through six primary mechanisms. While rates of certain failures requiring subsequent surgical intervention are low, it is possible that these complications may become more prevalent upon further longitudinal observation. Thus, future application and validation of this classification system is warranted to evaluate how failure frequencies change over time and with larger patient samples. [ABSTRACT FROM AUTHOR]

Background Context: Low back pain is one of the most common musculoskeletal disorders. Although, the pathology of intervertebral disc (IVD) degeneration has been modeled using various biological methods, these models are inadequate for simulating similar pathologic states in humans.Purpose: This study investigated whether monosodium iodoacetate (MIA) injection into the IVD of rats could generate a reliable model of IVD degeneration.Study Design/settings: In vivo animal study.Methods: MIA was injected into two-disc spaces (L4-5 and L5-6) of Sprague-Dawley rats. Their behaviors were examined by measuring weight load shifts from hind to forefoot, rearing, and von Frey tests. We examined the inhibition of pain behavior through intraperitoneal morphine injection and measured cyclooxygenase-2 (COX-2) and transcription factor nuclear factor-kappa B (NF-κB) levels in the IVD and dorsal root ganglion (DRG) by Western blot. Bone alterations were assessed by microfocus computed tomography (micro-CT), and IVD and/or cartilage changes were evaluated by hematoxylin and eosin and safranin-O staining and inducible nitric oxide synthase (iNOS) immunohistochemistry. The other authors declare no conflicts of interest. This project funded by the Memorial Fund and the National Research Foundation of Korea (NRF).Results: We observed increased weight load shifts to the forefoot and decreased rearing. Morphine-injected rats showed reduced pain. NF-κB and COX-2 expression increased in the IVD and left and/or right DRG. Micro-CT analyses suggested progressive bone deformation. Histologic examination showed decreased IVD width and nucleus pulposus area. Cartilaginous changes indicated epiphyseal growth plate loss. Finally, iNOS expression was increased in the subchondral endplate.Conclusions: These results suggest that low back pain (LBP) models can be developed by MIA injection into the IVDs of rats and that an animal model is useful for exploring degenerative alterations in the affected discs. Therefore, MIA injection may be a useful model for the study of changes in the IVD to elucidate the mechanisms underlying clinical symptoms, such as LBP, in patients with IVD degeneration.Clinical Significance: This model in which MIA was injected into the disc better represented the human histologic and behavioral characteristics than the existing puncture model. [ABSTRACT FROM AUTHOR]

Background Context: Minimally invasive surgical transforaminal lumbar interbody fusion (MIS-TLIF) was developed in addition to open-TLIF to minimize iatrogenic soft-tissue damage. A potential disadvantage of MIS-TLIF is inadequate visualization, which may lead to incomplete neural decompression and a less robust arthrodesis. This may cause long-term problems and result in decreased patient satisfaction.Purpose: To evaluate the long-term clinical outcome, measured by patient-reported outcomes (PROMs), of patients with degenerative lumbar diseases treated with single-level TLIF (open vs. minimally invasive) with a minimum follow-up of 2-years.Study Design: Meta-analysis.Methods: The systematic review was conducted according to the PRISMA guidelines. Relevant studies were identified from Pubmed, MEDLINE, EMBASE, Scopus, Web of Science, and CENTRAL from the date of inception to August 2019. The inclusion criteria were (1) longitudinal comparative studies of MIS-TLIF versus open-TLIF approach for degenerative spine disease (2) outcomes reported as PROMs, (3) minimum follow-up of 2-years.Results: Sixteen studies were included in the analysis. In total, 1,321 patients were included (660 MIS-TLIF& 661 open-TLIF). The following PROMS were analyzed: EQ-5D, SF, ODI, and VAS. Both techniques resulted in significant improvement in PROM, which remained significant at 2-years follow-up. However, no significant differences were found in all PROMs at 2-years follow-up. Both treatments resulted in a high rate of spinal fusion (80.5% vs. 91.1%; p=.29) and low rate of reoperation (3.0% vs. 2.4%; p=.50) or adjacent segment disease (12.6% vs. 12.40%; p=.50).Conclusions: MIS-TLIF and open-TLIF have comparable long-term clinical outscomes. Both operations can significantly reduce pain and positively improve PROMs. No significant differences were found between both treatments in clinical outcomes at a follow-up of minimal 2-years. Therefore, MIS-TLIF seems to be an effective and safe alternative to traditional open-TLIF in the long-term. [ABSTRACT FROM AUTHOR]

Background Context: Spondylodiscitis is the most common spinal infection of which the incidence has increased and the peak prevalence is between 50 and 70 years of age. Spondylodiscitis is often a complication of a distant infection. Early diagnosis can be challenging, and although improvements in diagnostic techniques and modern therapy have diminished the mortality of the disease, current literature about the outcome of spondylodiscitis is scarce.Purpose: To evaluate the long-term clinical outcome of patients who suffered from spondylodiscitis.Study Design: A two-center cross-sectional study.Patient Sample: Patients with spondylodiscitis in two large teaching hospitals in the Netherlands between 2003 and 2017.Outcome Measures: Visual Analogue Scale (VAS) for back pain, Oswestry Disability Index (ODI) for function, and Short Form 36 (SF-36) for general quality of life of spondylodiscitis patients.Method: Eligible patients were identified from electronic patient databases and completed multiple patient reported outcome measures after obtaining informed consent. General demographic and clinical information (age, sex, medical history) were extracted from the patient records. SF-36 domain scores of spondylodiscitis patients were compared with a nationwide population sample.Results: 183 patients were treated for spondylodiscitis; additional questionnaires were received from 82 patients. After a median follow-up of 63 months, the overall mortality was 28%. The mean VAS for back pain was 3.5, and the mean ODI score was 22. In all SF-36 domains a significantly lower score was found in the spondylodiscitis group compared with a normative national Dutch cohort. There was a strong correlation between back pain and ODI scores (ρ=0.81, p<.05).Conclusions: Our study confirms that spondylodiscitis is a disease causing a profound impact on back pain, function and quality of life. The results suggest that chronic back pain is a debilitating problem, as it has an extensive influence on daily activities and social and psychological well-being, causing significant disability. [ABSTRACT FROM AUTHOR]

Background Context: Chronic low back pain (LBP) is a multifactorial disorder with complex underlying mechanisms, including associations with intervertebral disc (IVD) degeneration in some individuals. It has been demonstrated that epigenetic processes are involved in the pathology of IVD degeneration. Epigenetics refers to several mechanisms, including DNA methylation, that have the ability to change gene expression without inducing any change in the underlying DNA sequence. DNA methylation can alter the entire state of a tissue for an extended period of time and thus could potentially be harnessed for long-term pain relief. Lifestyle factors, such as physical activity, have a strong influence on epigenetic regulation. Exercise is a commonly prescribed treatment for chronic LBP, and sex-specific epigenetic adaptations in response to endurance exercise have been reported. However, whether exercise interventions that attenuate LBP are associated with epigenetic alterations in degenerating IVDs has not been evaluated.Purpose: We hypothesize that the therapeutic efficacy of physical activity is mediated, at least in part, at the epigenetic level. The purpose of this study was to use the SPARC-null mouse model of LBP associated with IVD degeneration to clarify (1) if IVD degeneration is associated with altered expression of epigenetic regulatory genes in the IVDs, (2) if epigenetic regulatory machinery is sensitive to therapeutic environmental intervention, and (3) if there are sex-specific differences in (1) and/or (2).Study Design: Eight-month-old male and female SPARC-null and age-matched control (WT) mice (n=108) were assigned to exercise (n=56) or sedentary (n=52) groups. Deletion of SPARC is associated with progressive IVD degeneration and behavioral signs of LBP. The exercise group received a circular plastic home cage running wheel on which they could run freely. The sedentary group received an identical wheel secured in place to prevent rotation. After 6 months, the results obtained in each group were compared.Methods: After 6 months of exercise, LBP-related behavioral indices were determined, and global DNA methylation (5-methylcytosine) and epigenetic regulatory gene mRNA expression in IVDs were assessed. This project was supported by the Canadian Institutes for Health Research. The authors have no conflicts of interest.Results: Lumbar IVDs from WT sedentary and SPARC-null sedentary mice had similar levels of global DNA methylation (%5-mC) and comparable mRNA expression of epigenetic regulatory genes (Dnmt1,3a,b, Mecp2, Mbd2a,b, Tet1-3) in both sexes. Exercise attenuated LBP-related behaviors, decreased global DNA methylation in both WT (p<.05) and SPARC-null mice (p<.01) and reduced mRNA expression of Mecp2 in SPARC-null mice (p<.05). Sex-specific effects of exercise on expression of mRNA were also observed.Conclusions: Exercise alleviates LBP in a mouse model. This may be mediated, in part, by changes in the epigenetic regulatory machinery in degenerating IVDs. Epigenetic alterations due to a lifestyle change could have a long-lasting therapeutic impact by changing tissue homeostasis in IVDs.Clinical Significance: This study confirmed the therapeutic benefits of exercise on LBP and suggests that exercise results in sex-specific alterations in epigenetic regulation in IVDs. Elucidating the effects of exercise on epigenetic regulation may enable the discovery of novel gene targets or new strategies to improve the treatment of chronic LBP. [ABSTRACT FROM AUTHOR]

Background Context: Although highlighted in joint arthroplasty studies, long-term outcomes between differing biomaterial composites, such as metal-on-metal (MoM) and metal-on-plastic (MoP) in anterior cervical disc replacement (ACDR) have not been thoroughly investigated.Purpose: The purpose of this study was to evaluate the patient-reported clinical outcomes, overall reoperation rates, complications, and rates of ASD of MoM versus MoP artificial discs in two-level ACDR for the treatment of cervical DDD.Study Design/setting: Meta-analysis and systematic review.Patient Sample: Nine hundred eighty patients (442 MoM, 538 MoP) across seven studies.Outcome Measures: Patient reported clinical outcomes (NDI, VAS-n, VAS-a), overall reoperation rates, complications, and rates of ASD.Methods: A systematic search strategy of three electronic databases (PubMed, CINAHL Plus, and SCOPUS) was conducted utilizing terms related to two-level ACDR. All studies included had a sample size of >10 patients, had a minimum 5-year follow-up, and reported data on adjacent segment disease. Cadaver studies, non-English manuscripts, articles with less than 5-year follow-up and studies in which only single-level ACDR was investigated were excluded. A total of seven studies were included in this analysis. Studies were analyzed for demographic data, clinical outcome scores (NDI, VAS-neck, and VAS-arm), overall reoperation rates, complications, and rates of ASD. A random-effects model of meta-analysis was used for groups that were determined to be heterogenous and a fixed-effects model was utilized for groups that were not. An overlap of 95% confidence intervals suggests no statistically significant difference at the p<.05 level.Results: Seven studies were included with data on 980 patients (442 MoM, 538 MoP). The study population was 52.84% female, with a mean age of 48.01 years, and a mean follow-up of 85.66 months. The mean improvement in NDI was 34.42 (95% CI, 32.49-36.36) and 29.72 (95% CI, 27.15-32.29) for the MoM and MoP groups, respectively. The mean improvement in VAS-neck was 11.20 (95% CI, 10.69-11.70) and 8.78 (95% CI, 7.81-9.74) for the MoM and MoP groups, respectively. The mean improvement in VAS-arm was 10.73 (95% CI, 9.83-11.63) and 8.49 (95% CI, 7.59-9.39) for the MoM and MoP groups, respectively. 3.85% (95% CI, 2.40-6.10) of patients who underwent ACDR with a MoM implant required reoperation compared to 5.33% (95% CI, 3.68-7.65) of patients with a MoP implant. Heterotopic ossification and dysphagia were the most common complications in both groups. The MoM cohort showed a higher incidence of HO (72.62% vs. 21.07%), but a lower incidence of dysphagia (0.96% vs. 16.31%) compared to the MoP cohort. The MoM cohort had a larger proportion of patients with ASD who underwent subsequent surgery at an adjacent level (7.89% MoM versus 1.91% MoP).Conclusions: Our present meta-analysis suggests that the use of MoM artificial discs in two-level ACDR results in superior clinical outcome score improvement, but higher rates of ASD requiring secondary surgery compared to MoP discs after a follow-up period of 5 years or more. [ABSTRACT FROM AUTHOR]

Background: After non-contact co-culture of bone marrow mesenchymal stem cells (BMSCs) with nucleus pulposus cells (NPCs), exosomes secreted by BMSCs were able to ameliorate the degree of disc degeneration. The reason for this is, at least in part, that exosomes from BMSCs achieve by affecting the level of autophagy in NPCs, while the components in exosomes are diverse and their specific mechanism of action is still unclear.Purpose: Here, we aimed to explore the therapeutic effect of co-culture of BMSCs and NPCs on NPCs and explore its specific mechanism of action.Study Design/setting: In vitro study.Methods: Rat NPCs and BMSCs were isolated and cultured in vitro. The serum deprivation experiment (using oxygen, glucose, and serum deprivation [OGD]) simulates the pathological state of low blood supply of the intervertebral disc in vivo. We used apoptotic cell staining and flow cytometry to study the effect of BMSCs on the apoptosis rate of rat NPCs, and the apoptotic proteins active-caspase-3, active-caspase-9, autophagy marker proteins LC3 and Beclin 1 were further detected using Western blot analysis. The expression levels of the pro-apoptotic protein Bax and the apoptosis-inhibiting protein Bcl2 were measured. The differentially expressed miRNAs were screened in a gene expression profiling chip. Then qRT-PCR was used to detect the effect of different treatment methods on miR-155 expression. The effect of anti-miR-155 antibodies on autophagy was studied by flow cytometry and transmission electron microscopy. A luciferase reporter assay was used to study the direct interaction between miR-155 and BACH1 mRNA, which was analyzed by TargetScan software, and the results were verified by Western blotting.Results: Compared with the OGD group, the expression level of miR-155 and the NPC autophagy level significantly increased; the HO-1 protein expression increased; and the Bach1 protein expression, degeneration index, and apoptosis index all significantly decreased in the co-culture group. After BMSCs transfected with anti-miR-155 were co-cultured with NPCs, the miR-155 expression in the cells was significantly reduced, the HO-1 protein expression and the level of cell autophagy was reduced. However, Bach1 protein expression, NPC degeneration index, and apoptosis index increased. After being inhibited by the autophagy inhibitor wortmannin, the cell degeneration index and apoptosis rate significantly improved.Conclusion: In the OGD model, BMSCs can significantly increase the viability, the level of autophagy, and reduce the level of apoptosis in rat NPCs. BMSC exosomes increase miR-155 expression in NPCs, which targets Bach1 and in turn upregulates HO-1 expression, activates autophagy in NPCs, inhibits the apoptosis level, and improves intervertebral disc degeneration.Clinical Significance: Our experiment shows that it is maybe feasible to treat disc degeneration with drugs. At the same time, compared with BMSC injection method of treatment, side effects of drug therapy are smaller, and can be controlled, it also provides a new way for intervertebral disc degeneration drug treatment. [ABSTRACT FROM AUTHOR]

Background Context: High quality evidence is difficult to generate, leaving substantial knowledge gaps in the treatment of spinal conditions. Appropriate use criteria (AUC) are a means of determining appropriate recommendations when high quality evidence is lacking.Purpose: Define appropriate use criteria (AUC) of cervical fusion for treatment of degenerative conditions of the cervical spine.Study Design/setting: Appropriate use criteria for cervical fusion were developed using the RAND/UCLA appropriateness methodology. Following development of clinical guidelines and scenario writing, a one-day workshop was held with a multidisciplinary group of 14 raters, all considered thought leaders in their respective fields, to determine final ratings for cervical fusion appropriateness for various clinical situations.Outcome Measures: Final rating for cervical fusion recommendation as either "Appropriate," "Uncertain" or "Rarely Appropriate" based on the median final rating among the raters.Methods: Inclusion criteria for scenarios included patients aged 18 to 80 with degenerative conditions of the cervical spine. Key modifiers were defined and combined to develop a matrix of clinical scenarios. The median score among the raters was used to determine the final rating for each scenario. The final rating was compared between modifier levels. Spearman's rank correlation between each modifier and the final rating was determined. A multivariable ordinal regression model was fit to determine the adjusted odds of an "Appropriate" final rating while adjusting for radiographic diagnosis, number of levels and symptom type. Three decision trees were developed using decision tree classification models and variable importance for each tree was computed.Results: Of the 263 scenarios, 47 (17.9 %) were rated as rarely appropriate, 66 (25%) as uncertain and 150 (57%) were rated as appropriate. Symptom type was the modifier most strongly correlated with the final rating (adjusted ρ2 = 0.58, p<.01). A multivariable ordinal regression adjusting for symptom type, diagnosis, and number of levels and showed high discriminative ability (C statistic = 0.90) and the adjusted odds ratio (aOR) of receiving a final rating of "Appropriate" was highest for myelopathy (aOR, 7.1) and radiculopathy (aOR, 4.8). Three decision tree models showed that symptom type and radiographic diagnosis had the highest variable importance.Conclusions: Appropriate use criteria for cervical fusion in the setting of cervical degenerative disorders were developed. Symptom type was most strongly correlated with final rating. Myelopathy or radiculopathy were most strongly associated with an "Appropriate" rating, while axial pain without stenosis was most associated with "Rarely Appropriate." [ABSTRACT FROM AUTHOR]

Background Context: Bertolotti Syndrome is a diagnosis given to patients with lower back pain arising from a lumbosacral transitional vertebra (LSTV). These patients can experience symptomatology similar to common degenerative diseases of the spine, making Bertolotti Syndrome difficult to diagnose with clinical presentation alone. Castellvi classified the LSTV seen in this condition and specifically in types IIa and IIb, a "pseudoarticulation" is present between the fifth lumbar transverse process and the sacral ala, resulting in a semi-mobile joint with cartilaginous surfaces.Treatment outcomes for Bertolotti Syndrome are poorly understood but can involve diagnostic and therapeutic injections and ultimately surgical resection of the pseudoarticulation (pseudoarthrectomy) or fusion of surrounding segments.Purpose: To examine spine and regional injection patterns and clinical outcomes for patients with diagnosed and undiagnosed Bertolotti Syndrome.Design: Retrospective observational cohort study of patients seen at a single institution's tertiary spine center over a 10-year period.Patient Sample: Cohort consisted of 67 patients with an identified or unidentified LSTV who were provided injections or surgery for symptoms related to their chronic low back pain and radiculopathy.Outcome Measures: Self-reported clinical improvement following injections and pseudoarthrectomy.Methods: Patient charts were reviewed. Identification of a type II LSTV was confirmed through provider notes and imaging. Variables collected included demographics, injection history and outcomes, and surgical history for those who underwent pseudoarthrectomy.Results: A total of 22 out of 67 patients (33%) had an LSTV that was not identified by their provider. Diagnosed patients underwent fewer injections for their symptoms than those whose LSTV was never previously identified (p = 0.031). Only those diagnosed received an injection at the LSTV pseudoarticulation, which demonstrated significant symptomatic improvement at immediate follow up compared to all other injection types (p = 0.002). Patients who responded well to pseudoarticulation injections were offered a pseudoarthrectomy, which was more likely to result in symptom relief at most recent follow up than patients who underwent further injections without surgery (p < 0.001).Conclusions: Undiagnosed patients are subject to a higher quantity of injections at locations less likely to provide relief than pseudoarticulation injections. These patients in turn cannot be offered a pseudoarthrectomy which can result in significant relief compared to continued injections alone. Proper and timely identification of an LSTV dramatically alters the clinical course of these patients as they can only be offered treatment directed towards the LSTV once it is identified. [ABSTRACT FROM AUTHOR]

Bertolotti Syndrome is a diagnosis given to patients experiencing pain caused by the presence of a lumbosacral transitional vertebra (LSTV), which is characterized by enlargement of the L5 transverse process(es), with potential pseudoarticulation or fusion with the sacrum. The Castellvi classification system is commonly utilized to grade LSTVs based on the degree of contact between the L5 transverse process(es) and the sacrum. LSTVs present a diagnostic dilemma to the treating clinician, as they may remain unidentified on plain x-rays and even advanced imaging; additionally, even if the malformation is identified, patients with a LSTV may be asymptomatic or have nonspecific symptoms, such as low back pain with or without radicular symptoms. With low back pain being extremely prevalent in the general population; it can be difficult to implicate the LSTV as the source of this pain. Care should be taken however, to exclude Bertolotti Syndrome in patients under 30 years old presenting with persisting low back pain given its congenital origin. If a LSTV is identified, typically with acquisition of a MRI or CT scan of the lumbosacral spine, and there is an absence of a more compelling or obvious source for the patient's symptoms, a conservative, step-wise management plan is recommended. This may include assessing for improvement in symptoms with injections prior to proceeding with surgical intervention. Additional concerns arise from the biomechanical alterations that a LSTV induces in adjacent spinal levels, predisposing this patient population to a more rapid-onset of adjacent segment disease, raising the question as to the most appropriate surgery (resection of LSTV pseudoarticulation with or without fusion). Postoperative outcome data for patients undergoing surgical treatment is limited in the literature with promising, but variable, results. More large-scale, controlled studies must be performed to gain further insight into the ideal work-up and management of this pathology. [ABSTRACT FROM AUTHOR]

Background Context: The ligamentum flavum (LF), the inter- and supraspinous ligament (ISL&SSL) and the intertransverse ligament (ITL) are relevant spinal structures for segmental stability. The biomechanical effect of degeneration and aging on their biomechanical properties remains largely unknown.Purpose: The aim of this study was to assess the material properties of the ITL, ISL&SSL and LF and to correlate parameters of biomechanical function with LF-thickness, intervertebral disc (IVD) degeneration and age.Study Design: Biomechanical cadaveric study.Methods: MRI- and CT-scans of 50 human lumbar segments (Th12-L5) were used to assess the ISL (acc. to Keorochana), the grade of IVD degeneration (acc. to Pfirrmann) and to quantify LF-thickness. The ITL, ISL&SSL and LF were resected in the neutral position of the spinal segment with a specifically developed method to conserve initial strain. Ramp to failure testing was performed (0.5 mm/s) to record initial tension, slack length, stiffness and ultimate strength. The relationship between the biomechanical characteristics and age and radiological parameters were analyzed. There are no study-specific conflicts of interest and no external funding was received for this study.Results: With aging, a significant reduction in initial tension (r=-0.5, p<.01) and ultimate strength (r=-0.41, p<.01) of the LF was observed, while the effect on LF-stiffness and the characteristics of the other ligaments was non-significant. IVD-degeneration was correlated with a significant reduction in stiffness (r=-0.47, p=.001; r=-0.36, p=.01) and ultimate strength (r=-0.3, p=.04; r=-0.36, p=.01) of the LF and ISL&SSL respectively and a significant reduction in initial tension (r=-0.4, p<.01) of the LF. For the ITL, no significant correlation was observed. Comparing Pfirrman 2 to 5, this reduction was 40% to 80% for stiffness 60% to 70% for ultimate strength and 88% for initial tension of the LF. ISL&SSL-stiffness between Kerorochana grade A and D differed significantly (p=.03), while all other comparisons were non-significant (p>.05). LF-thickness did not correlate with the biomechanical properties of the LF (p>.05).Conclusions: Aging is primarily related to biomechanical changes to the LF. IVD-degeneration is related to a relevant reduction in stiffness and ultimate strength of the LF and ISL&SSL, with a similar trend for the ITL. The ISL-specific Keorochana grading system provides only minimal biomechanical information and LF-thickness does not provide biomechanical information.Clinical Significance: Patient age and the degenerative state of the IVD can be used to evaluate the biomechanical characteristics of the dorsal spinal ligaments, which can be helpful in selecting the optimal surgical procedure (e.g. in decompression surgery) for a specific situation. [ABSTRACT FROM AUTHOR]

Background Context: Low back pain is commonly attributed to intervertebral disc (IVD) degeneration. IVD resembles articular cartilage in its biochemical and cellular composition in many ways. For articular cartilage, degeneration stage-specific characteristic spatial chondrocyte patterns have recently been described.Purpose: This study addresses how spatial chondrocyte organization in the IVD changes from early embryonic development to end stage degeneration.Study Design: Ex vivo immunohistochemical analysis.Methods: We immunohistochemically investigated bovine IVD-tissue (n=72) from early embryonic development to early disc degeneration and human adult IVD-tissue (n=25) operated for trauma or degeneration for cellular density and chondrocyte spatial organization. IVD samples were sectioned along the main collagen fiber orientation. Nuclei were stained with DAPI and their number and spatial patterns were analyzed in an area of 250,000 µm² for each tissue category.Results: The initially very high cellular density in the early embryonic bovine disc (11,431 cells/mm²) steadily decreases during gestation, growth and maturation to about 71 cell/mm² in the fully grown cattle. Interestingly, in human degenerative discs, a new increase in this figure could be noted (184 cells/mm). The IVD chondrocytes appear to be predominantly present as single cells. Especially in the time after birth, string-formations represent up to 32% of all cells in the anulus fibrosus, although single cells are the predominant spatial pattern (>50%) over the entire time. With increasing degeneration, the relative proportion of single cells in human IVDs continuously decreases (12%). At the same time, the share of cells organized in clusters increases (70%).Conclusion: Similar to articular cartilage, spatial chondrocyte organization appears to be a strong indicator for local tissue degeneration in the IVD.Clinical Significance: In the future these findings may be important for the detection and therapy of IVD degeneration in early stages. [ABSTRACT FROM AUTHOR]

Background Context: Computer-assisted navigation (CAN) has emerged in spine surgery as an approach to improve patient outcomes. While there is substantial evidence demonstrating improved pedicle screw accuracy in CAN as compared to conventional spinal fusion (CONV), there is limited data regarding clinical outcomes and utilization trends in the United States.Purpose: The purpose of this study was to determine the utilization rates of CAN in the United States, identify patient and hospital trends associated with both techniques, and to compare their results.Study Design: Retrospective review of national database.Patient Sample: Nationwide Inpatient Sample (NIS), United States national database.Outcome Measures: CAN utilization, mortality, medical complications, neurologic complications, discharge destination, length of hospital stay, cost of hospital stay.Methods: The NIS database was queried to identify patients undergoing spinal fusion with CAN or CONV. CAN and CONV utilization were tracked by year and anatomic location (cervical, thoracic, lumbar/lumbosacral). Patient demographics, hospital characteristics, index length of stay (LOS), and cost of stay (COS) were compared between the cohorts. After multivariate adjustment, index hospitalization clinical outcomes were compared.Results: A total of 4,275,413 patients underwent spinal fusion surgery during the study period (2004 to 2014). CONV was performed in 98.4% (4,208,068) of cases and CAN was performed in 1.6% (67,345) of cases. The utilization rate of CAN increased from 0.04% in 2004 to 3.3% in 2014. Overall, CAN was performed most commonly in the lumbar/lumbosacral region (70.4%) compared to the cervical (20.4%) or thoracic (9.2%) regions. When normalized to region-specific rates of fusion with any technique, the proportional utilization of CAN was highest in the thoracic spine (2.7%), followed by the lumbar/lumbosacral (2.2%) and cervical (0.9%) regions. CAN utilization was positively correlated with patient factors including increasing age and number of medical comorbidities. Multivariate adjusted clinical outcomes demonstrated that compared to CONV, CAN was associated with a statistically significant decreased risk of mortality (0.28% vs 0.31%, OR=0.67, 95% CI: 0.46-0.97, p=.035) and increased risk of blood transfusions (9.1% vs 6.7%, OR=1.19, 95% CI: 1.02-1.39, p=.032). However, there was no difference in risk of neurologic complications. CAN patients had an increased average LOS (4.44 days vs. 3.97 days, p<.0001) and average COS ($34,669.49 vs $26,784.62, p<.0001) compared to CONV patients.Conclusions: CAN utilization increased in the United States from 2004-2014. Use of CAN was proportionately higher in the thoracic and lumbar/lumbosacral regions and in older patients with more comorbidities. Given the continued trend towards increased CAN utilization, large-scale studies are needed to determine the impact of this technology on long-term clinical outcomes. [ABSTRACT FROM AUTHOR]

Background Context: Outcomes of treatment in care of patients with spinal disorders are directly related to patient selection and treatment indications. However, for many disorders, there is absence of consensus for precise indications. With the increasing emphasis on quality and value in spine care, it is essential that treatment recommendations and decisions are optimized.Purpose: The purpose of the North American Spine Society Appropriate Use Criteria was to determine the appropriate (ie reasonable) multidisciplinary treatment recommendations for patients with degenerative spondylolisthesis across a spectrum of more common clinical scenarios.Study Design: A Modified Delphi process was used.Methods: The methodology was based on the Appropriate Use Criteria development process established by the Research AND Development Corporation. The topic of degenerative spondylolisthesis was selected by the committee, key modifiers determined, and consensus reached on standard definitions. A literature search and evidence analysis were completed by one work group simultaneously as scenarios were written, reviewed, and finalized by another work group. A separate multidisciplinary rating group was assembled. Based on the literature, provider experience, and group discussion, each scenario was scored on a nine-point scale on two separate occasions, once without discussion and then a second time following discussion based on the initial responses. The median rating for each scenario was then used to determine if indications were rarely appropriate (1 - 3), uncertain (4-6), or appropriate (7-9). Consensus was not mandatory.Results: There were 131 discrete scenarios. These addressed questions on bone grafting, imaging, mechanical instability, radiculopathy with or without neurological deficits, obesity, and yellow flags consisting of psychosocial and medical comorbidities. For most of these, appropriateness was established for physical therapy, injections, and various forms of surgical intervention. The diagnosis of spondylolisthesis should be determined by an upright x-ray. Scenarios pertaining to bone grafting suggested that patients should quit smoking prior to surgery, and that use of BMP should be reserved for patients who had risk factors for non-union. Across all clinical scenarios, physical therapy (PT) had an adjusted mean of 7.66, epidural steroid injections 5.76, and surgery 4.52. Physical therapy was appropriate in most scenarios, and most appropriate in patients with back pain and no neurological deficits. Epidural steroid injections were most appropriate in patients with radiculopathy. Surgery was generally more appropriate for patients with neurological deficits, higher disability scores, and dynamic spondylolisthesis. Mechanical back pain and presence of yellow flags tended to be less appropriate, and obesity in general had relatively little influence on decision making. Decompression alone was more strongly considered in the presence of static versus dynamic spondylolisthesis. On average, posterior fusion with or without interbody fusion was similarly appropriate, and generally more appropriate than stand-alone interbody fusion which was in turn more appropriate than interspinous spacers.Conclusions: Multidisciplinary appropriate treatment criteria were generated based on the Research AND Development methodology. While there were consistent and significant differences between surgeons and non-surgeons, these differences were generally very small. This document provides comprehensive evidence-based recommendations for evaluation and treatment of degenerative spondylolisthesis. The document in its entirety will be found on the North American Spine Society website (https://www.spine.org/Research-Clinical-Care/Quality-Improvement/Appropriate-Use-Criteria). [ABSTRACT FROM AUTHOR]

Background Context: Back and neck pain secondary to disc degeneration is a major public health burden. There is a need for therapeutic treatments to restore intervertebral disc (IVD) composition and function.Purpose: To quantify ALK3, BMP-2, pSMAD1/5/8 and MMP-13 expression in IVD specimens collected from patients undergoing surgery for disc degeneration, to correlate ALK3, BMP-2, pSMAD1/5/8 and MMP-13 expression in IVD specimens to the 5-level Pfirrmann MRI grading system, and to compare ALK3, BMP-2, pSMAD1/5/8 and MMP-13 expression between cervical and lumbar degenerative disc specimens.Study Design: An immunohistochemical study assessing ALK3, BMP-2, pSMAD1/5/8, and MMP-13 expression levels in human control and degenerative IVD specimens.Methods: Human IVD specimens were collected from surgical patients who underwent discectomy and interbody fusion at our institution between 1/2015 and 8/2017. Each patient underwent MRI prior to surgery. The degree of disc degeneration was measured according to the 5-level Pfirrmann MRI grading system. Patients were categorized into either the 1) control group (Pfirrmann grades I-II) or 2) degenerative group (Pfirrmann grades III-V). Histology slides of the collected IVD specimens were prepared and immunohistochemical staining was performed to assess ALK3, BMP-2, pSMAD1/5/8, and MMP-13 expression levels in the control and degenerative specimens. Expression levels were also correlated to the Pfirrmann criteria. Lastly, the degenerative specimens were stratified according to their vertebral level and expression levels between the degenerative lumbar and cervical discs were compared.Results: Fifty-two patients were enrolled; however, 2 control and 2 degenerative patients were excluded due to incomplete data sets. Of the remaining 48 patients, there were 12 control and 36 degenerative specimens. Degenerative specimens had increased expression levels of BMP-2 (p=.0006) and pSMAD1/5/8 (p<.0001). Pfirrmann grade 3 (p=.0365) and grade 4 (p=.0008) discs had significantly higher BMP-2 expression as compared to grade 2 discs. Pfirrmann grade 4 discs had higher pSMAD1/5/8 expression as compared to grade 2 discs (p<.0001). There were no differences in ALK3 or MMP-13 expression between the control and degenerative discs (p>.05). Stratifying the degenerative specimens according to their vertebral level showed no significant differences in expression levels between the lumbar and cervical discs (p>.05).Conclusions: BMP-2 and pSMAD1/5/8 signaling activity was significantly upregulated in the human degenerative specimens, while ALK3 and MMP-13 expression were not significantly changed. The expression levels of BMP-2 and pSMAD1/5/8 correlate positively with the degree of disc degeneration measured according to the Pfirrmann MRI grading system.Clinical Significance: BMP-SMAD signaling represents a promising therapeutic target to restore IVD composition and function in the setting of disc degeneration. [ABSTRACT FROM AUTHOR]

Background Context: The reoperation rate following TDR (Total Disc replacement) has been established at short- and mid-term time points through the Food and Drug Administration Investigational Device Exemption (FDA IDE) trials. However, these trials include highly selected centers and surgeons with strict governance of indications. The utilization of TDR throughout the community needs further analysis.Purpose: To identify the risk factors for lumbar spine reoperation in patients undergoing lumbar total disc replacement (TDR) at short-, mid-, and long-term follow-up.Study Design/setting: This study is a multi-center retrospective cohort study utilizing the New York Statewide Planning and Research Cooperative System database.Patient Sample: We identified 1,368 patients who underwent an elective primary lumbar TDR in New York State between January 1, 2005 and September 30, 2013.Outcome Measures: The primary functional outcome of interest was lumbar reoperation, specifically the evaluation of independent risk factors for lumbar reoperation at a minimum of 2 years, with sub-analyses performed at 5 and ten years.Methods: International Classification of Diseases, Ninth revision codes were utilized to identify patients undergoing a primary lumbar TDR. We excluded patients with primary/revision lumbar fusion procedures and revision disc replacement procedures. Hospital academic status was determined by the Accreditation Council for Graduate Medical Education. Unique encrypted patient identifiers allowed for longitudinal follow-up for reoperation. Logistic regression models compared reoperation and no-reoperation cohorts, and were performed on sub-analyses for significant univariate predictors of reoperation.Results: Between January 2005 and September 2013, 1368 patients underwent a primary lumbar TDR. Reoperation occurred in 8.8% by 2 years, 15.8% by 5 years, and 19.5% by ten years. Diabetics were more likely to have reoperations (7.5% vs 3.8%, p=.013). Teaching hospitals experienced a decreased reoperation rate compared to nonteaching hospitals at 2-year (5.0% vs 10.5%, p=.002), 5-year (10.7% vs 17.9%, p=.002) and 10-year (11.7% vs 21.9%, p=.045) follow-up. Lumbar fusion was the most common reoperation (14.2%).Conclusion: We identified an 8.8% reoperation rate after inpatient lumbar TDR at 2-years, 15.8% at 5-years, and 19.5% at 10-years. When stratifying by teaching status, reoperation rates at teaching centers align with those reported in FDA IDE studies. Diabetes was the only patient factor influencing reoperation rate. There is a growing consensus that lumbar TDR is a durable and appropriate surgical option for lumbar degenerative disc disease. Proper indications are crucial to obtaining good outcomes with lumbar TDR. [ABSTRACT FROM AUTHOR]

The aim of this manuscript is to describe knowledge gaps in the literature, future directions, and emerging applications of gait and balance analysis in spine surgery with regard to functional outcomes measurement. Functional outcome measurement has been established as a useful clinical and research investigational tool in musculoskeletal disease. Evidence currently supports its use in the diagnosis, treatment, and outcome measurement of multiple musculoskeletal disease states, including spinal disease, and its usefulness continues to grow as literature develops. Gait and balance analysis has proven to be broadly applicable, but most clinicians remain unfamiliar and untrained in its usage. The logistical and communication barriers are also described with the potential solutions that are on the near horizon of research. This article describes our methodology for improving conveyance of functional outcome measures in spine surgery. Additionally, we provide a case example of an adult patient with spinal deformity who is examined pre and post operatively using our methodology. [ABSTRACT FROM AUTHOR]

Background Context: Annular repair devices offer a solution to recurrent disc herniations by closing an annular defect and lowering the risk of reherniation. Given the significant risk of neurologic injury from device failure it is imperative that a reliable preclinical model exists to demonstrate a high load to failure for the disc repair devices.Purpose: To establish a preclinical model for disc herniation and demonstrate how changes in species, intervertebral disc height and Pfirrmann classification impacts failure load on an injured disc. We hypothesized that: (1) The force required for disc herniation would be variable across disc morphologies and species, and (2) for human discs the force to herniation would inversely correlate with the degree of disc degeneration.Study Design: Animal and human cadaveric biomechanical model of disc herniation.Methods: We tested calf lumbar spines, bovine tail segments and human lumbar spines. We first divided individual lumbar or tail segments to include the vertebral bodies and disc. We then hydrated the specimens by placing them in a saline bath overnight. A magnetic resonance images were acquired from human specimens and a Pfirrmann classification was made. A stab incision measuring 25% of the diameter of the disc was then done to each specimen along the posterior intervertebral disc space. Each specimen was placed in custom test fixtures on a servo-hydraulic test frame (MTS, Eden Prarie, MN) such that the superior body was attached to a 10,000 lb load cell and the inferior body was supported on the piston. A compressive ramping load was placed on the specimen in load control at 4 MPa/sec stopping at 75% of the disc height. Load was recorded throughout the test and failure load calculated. Once the test was completed each specimen was sliced through the center of the disc and photos were taken of the cut surface.Results: Fifteen each of calf, human, and bovine tail segments were tested. The failure load varied significantly between specimens (p<.001) with human specimens having the highest average failure load (8154±2049 N). Disc height was higher for lumbar/bovine tail segments as compared to calf specimens (p<.001) with bovine tails having the highest disc height (7.1±1.7 mm). Similarly, human lumbar discs had a cross sectional area that was greater than both bovine tail/calf lumbar spines (p<.001). There was no correlation between disc height and failure load within each individual species (p>.05). Cross sectional area and failure load did not correlate with failure load for human lumbar spine and bovine tails (p>.05) but did correlate with calf spine (r=0.53, p=.04). There was a statistically significant inverse correlation between disc height and Pfirrmann classification for human lumbar spines (r=-0.84, p<.001). There was also a statistically significant inverse relationship between Pfirrmann classification and failure load (r=-0.58, p=.02).Conclusions: We have established a model for disc herniation and have shown how results of this model vary between species, disc morphology, and Pfirrmann classification. Both hypotheses were accepted: The force required for disc herniation was variable across species, and the force to herniation for human spines was inversely correlated with the degree of disc degeneration. We recommend that models using human intervertebral discs should include data on Pfirrmann classification, while biomechanical models using calf spines should report cross sectional area. Failure loads do not vary based on dimensions for bovine tails.Clinical Significance: Our analysis of models for disc herniation will allow for quicker, reliable comparisons of failure forces required to induce a disc herniation. Future work with these models may facilitate rapid testing of devices to repair a torn/ruptured annulus. [ABSTRACT FROM AUTHOR]

Background Context: Manual contouring of spinal rods is often required intraoperatively for proper alignment of the rods within the pedicle screw heads. Residual misalignments are frequently reduced by using dedicated reduction devices. The forces exerted by these devices, however, are uncontrolled and may lead to excessive reaction forces. As a consequence, screw pullout might be provoked and surrounding tissue may experience unfavorable biomechanical loads. The corresponding loads and induced tissue deformations are however not well identified. Additionally, whether the forced reduction alters the biomechanical behavior of the lumbar spine during physiological movements postoperatively, remains unexplored.Purpose: To predict whether the reduction of misaligned posterior instrumentation might result in clinical complications directly after reduction and during a subsequent physiological flexion movement.Study Design: Finite element analysis.Methods: A patient-specific, total lumbar (L1-S1) spine finite element model was available from previous research. The model consists of poro-elastic intervertebral discs with Pfirrmann grade-dependent material parameters, with linear elastic bone tissue with stiffness values related to the local bone density, and with the seven major ligaments per spinal motion segment described as nonlinear materials. Titanium instrumentation was implemented in this model to simulate a L4, L5, and S1 posterolateral fusion. Next, coronal and sagittal misalignments of 6 mm each were introduced between the rod and the screw head at L4. These misalignments were computationally reduced and a physiological flexion movement of 15° was prescribed. Non-instrumented and well-aligned instrumented models were used as control groups.Results: Pulling forces up to 1.0 kN were required to correct the induced misalignments of 6 mm. These forces affected the posture of the total lumbar spine, as motion segments were predicted to rotate up to 3 degrees and rotations propagated proximally to and even affect the L1-2 level. The facet contact pressures in the corrected misaligned models were asymmetrical suggesting non-physiological joint loading in the misaligned models. In addition, the discs and vertebrae experienced abnormally high forces as a result of the correction procedure. These effects were more pronounced after a 15° flexion movement following forced reduction.Conclusions: The results of this study indicate that the correction of misaligned posterior instrumentation can result in high forces at the screws consistent with those reported to cause screw pullout, and may cause high-tissue strains in adjacent and downstream spinal segments.Clinical Significance: Proper alignment of spinal posterior instrumentation may reduce clinical complications secondary to unfavorable biomechanics. [ABSTRACT FROM AUTHOR]

Background Context: Pseudarthrosis after attempted spinal fusion is yet not sufficiently understood and presents a surgical challenge. Occult infections are sometimes observed in patients with pseudarthrosis and no inflammatory signs of infection. The prevalence of such occult infection and its association with patient demographics and inflammatory markers are largely unknown.Purpose: To determine the prevalence of unexpected low-grade infection in spinal pseudarthrosis revision surgery, and to evaluate whether such infection is associated with patient demographics and inflammatory markers.Study Design: Retrospective observational study.Patient Sample: One-hundred-and-twenty-eight patients who underwent thoracolumbar revision surgery due to presumed aseptic pseudarthrosis after spinal instrumentation.Outcome Measures: Culture-positive infections or noninfectious pseudarthrosis.Methods: Samples were routinely taken for microbiological examination from all adults (n=152) who underwent revision surgery for presumed aseptic thoracolumbar pseudarthrosis between 2014 and 2019. A full intraoperative microbiological workup (at least three intraoperative tissue samples) was done for 128 (84%) patients, and these patients were included in further analyses. Patient characteristics, medical history, inflammatory markers, and perioperative data were compared between those with and without microbiologically-confirmed infection based on samples obtained during pseudarthrosis revision.Results: The microbiological workup confirmed infection in 13 of 128 cases (10.2%). The predominant pathogen was Cutibacterium acnes (46.2%), followed by coagulase-negative staphylococci (38.5%). The presence of infection was associated with the body mass index (30.9±4.7 kg/m2 [infected] vs. 28.2±5.6 kg/m2 [controls], p=.049), surgery in the thoracolumbar region (46% vs. 18%, p=.019), and a slightly higher serum C-reactive protein level on admission (9.4±8.0 mg/L vs. 5.7±7.1 mg/L, p=.031). Occult infection was not associated with age, sex, prior lumbar surgeries, number of fused lumbar levels, American Society of Anesthesiologist score, Charlson Comorbidity Index, presence of diabetes mellitus, and smoking status.Conclusions: Occult infections were found in 10% of patients undergoing pseudarthrosis revision after spinal fusion, even without preoperative clinical suspicion. Occult infection was associated with higher body mass index, fusions including the thoracolumbar junction, and slightly higher C-reactive protein levels. Intraoperative microbiological samples should be routinely obtained to exclude or identify occult infection in all revision surgeries for symptomatic pseudarthrosis of the spine, as this information can be used to guide postoperative antibiotic treatment. [ABSTRACT FROM AUTHOR]

Background Context: Several spinal abnormalities have been studied using magnetic resonance imaging (MRI). However, in children these studies were sparsely performed in general populations. Examining young children's spines is important since the shape of the bone is largely determined during the growth spurt. Furthermore, it is so far unknown if associations between weight status and spinal abnormalities, which are known for adolescents and adults, are already present in young children.Purpose: We aimed to present the prevalence of structural abnormalities in the prepubertal pediatric spine on MRI and their association with measures of the children's body weight and body composition.Study Design: Cross-sectional study embedded in a prospective population-based birth cohort study.Patient Sample: For this study, participants from the Generation R Study were selected based on the availability of MRI data of the lumbar spine and accelerometry data at the age of 9 years.Outcome Measures: The presence of structural abnormalities of intervertebral discs and vertebrae was scored on MRI. The body mass index-standard deviation [BMI-SD] score was calculated from objectively measured weight and height, and body composition measurements were obtained by a dual-energy X-ray absorptiometry scan.Methods: A semiquantitative scoring tool to assess the intervertebral discs and vertebrae of the lumbar spine on conventional MRI was designed for this purpose. Proportions of children with spinal abnormalities on at least one lumbar vertebral level were presented. Logistic regression was used to analyze associations between abnormalities and weight and body composition. We declare not to have any financial conflicts of interests.Results: We included 559 children (median age of 9.88 years (interquartile range 6.74-10.02), 48.5% boys). Most frequently observed abnormalities of the intervertebral discs were abnormal signal intensity (24.9%), decreased or collapsed disc height (37.6%), disc bulging (73.3%), and abnormal nuclear shape (29.1%). Vertebral endplate irregularities and lumbosacral transitional vertebrae were seen in respectively 40% and 9.3% of the participants. Except for disc bulging, all abnormalities were predominantly present at the L5 level. Only the presence of endplate irregularities was associated with a higher body weight (BMI SD score (odds ratio [OR] 1.50 [95% confidence interval [CI] 1.21-1.86]) and BMI SD change (OR 1.48 [95% CI 1.07-2.03])) and increased body mass values in body composition measurements (% body fat (OR 1.05 [95% CI 1.02-1.09), fat mass index (OR 1.23 [95% CI 1.09-1.39]), and fat-free mass index (OR 1.30 [95% CI 1.06-1.59])) in adjusted analyses.Conclusions: Structural spinal abnormalities, especially disc bulging, endplate irregularities, and an abnormal disc height, are already present in children aged 9 years from a Dutch population-based cohort. Of those abnormalities, endplate irregularities are associated with various weight and body composition measurements. [ABSTRACT FROM AUTHOR]

Background Context: Various designs of total disc replacement (TDR) devices have been compared to anterior cervical discectomy and fusion (ACDF) with favorable outcomes in FDA-approved investigational device exemption trials. The design of M6-C with a compressible viscoelastic nuclear core and an annular structure is substantially different than prior designs and has previously demonstrated favorable kinematics and clinical outcomes in small case series.Purpose: To evaluate the safety and effectiveness of the novel M6-C compressible artificial cervical disc compared with ACDF for subjects with single-level degenerative cervical radiculopathy.Study Design/setting: Prospective, multicenter, concurrently and historically controlled, FDA-approved investigational device exemption clinical trial.Patient Sample: Subjects with one-level symptomatic degenerative cervical radiculopathy were enrolled and assigned to receive M6-C or ACDF.Outcome Measures: Pain and function (Neck Disability Index, VAS), quality of life (SF-36), safety, neurologic, and radiographic assessments of motion (both flexion extension and lateral bending) were performed. The primary clinical endpoint was composite clinical success (CCS) at 24 months.Methods: Using propensity score subclassification to control for selection bias, 160 M6-C subjects were compared to a matched subset of 189 ACDF controls (46 concurrent and 143 historical controls).Results: Both ACDF and M6-C subjects reported significant improvements in patient-reported outcomes at all time points over baseline. Overall SF-36 Physical Component Score and neck and arm pain scores were significantly improved for M6-C as compared to ACDF treatment. CCS and mean Neck Disability Index improvements were similar between M6-C and ACDF. Correspondingly, there were significantly fewer subjects that utilized pain medication or opioids following M6-C treatment at 24 months relative to baseline. Range of motion was maintained in subjects treated with M6-C. Subsequent surgical interventions, dysphagia rates, and serious adverse events were comparable between groups.Conclusions: M6-C treatment demonstrated both safety and effectiveness for the treatment of degenerative cervical radiculopathy. Treatment with M6-C demonstrated noninferiority for the primary endpoint, indicating a similar ability to achieve CCS at 24 months. However, for the secondary endpoints, M6-C subjects demonstrated significantly improved pain and function compared to ACDF subjects, while maintaining range of motion, improving quality of life, and decreasing analgesic and opioid usage at 2 years postoperatively relative to baseline. [ABSTRACT FROM AUTHOR]

Background Context: Cervical disc arthroplasty (CDA) has been advocated as an alternative to anterior cervical discectomy and fusion (ACDF) with the added potential to reduce the risk of adjacent level disc degeneration and segmental instability. However, the long-term adverse events of arthroplasty have yet to be fully reported.Purpose: To investigate the 10-year follow-up adverse events rates between CDA and ACDF.Study Design/setting: The study was a randomized, prospective, multicenter Investigational Device Exemption (IDE) trial and its continued follow-up as a postapproval study (PAS). Single level surgeries were performed for cervical disc pathologies between May 2002 and October 2004.Patient Sample: n=463 patients.Outcome Measures: Adverse events comparison of CDA and ACDF from self-reported and physiologic measures.Methods: At each evaluation time point, subjects were queried for adverse events since their last visit; and all adverse events were documented, regardless of whether or not they appeared related to the surgery or device. Adverse events were recorded, categorized, and assessed for severity and relationship to the study device and/or surgical procedure. The 10-year cumulative rates for each type of adverse events were summarized using a life-table method for the time-to-event analysis. A log-rank test was used to compare the two treatment groups.Results: A total of 242 patients received CDA and 221 patients received ACDF. At 10-year follow-up, 54% (130/242) of CDA patients and 47% (104/221) of the ACDF subjects were evaluated. At up to 10-year follow-up, 231 patients in the CDA group (cumulative rate 98.4%) and 199 patients in the ACDF group (cumulative rate 98.7%) had at least one adverse event. Overall, the difference in the cumulative rate of all adverse events over 10 years was not statistically different (p=0.166). The cumulative rates of the following adverse events were not different between the two groups for cancer, cardiovascular, death, dysphonia/dysphagia, gastrointestinal, infection, urogenital, respiratory, implant displacement/loosening, implant malposition, neck and arm pain, neurological, other pain, spinal events, and intraoperative vascular injury. However, there were more adverse events in the CDA group resulting from trauma (p=.012) and more spinal events at the index level (p=.006). The ACDF group had significantly more nonunion events (p=.019), and nonunion outcome pending (p=.034), adjacent level spinal events (p=.033), and events that fell into the "other" category (p=.015).Conclusions: The cumulative rates of patients who had any adverse events were not different between the artificial cervical disc and the anterior cervical arthrodesis groups. In addition, the cumulative rates were not different between the two groups for the majority of categories as well. [ABSTRACT FROM AUTHOR]

Background Context Purpose: Evaluate the safety and efficacy of a single intradiscal injection of STRO-3+ adult allogeneic mesenchymal precursor cells (MPCs) combined with hyaluronic acid (HA) in subjects with chronic low back pain (CLBP) associated with degenerative disc disease (DDD) through 36-month follow-up.Study Design/setting: A multicenter, randomized, controlled study conducted at 13 clinical sites (12 in the United States and 1 in Australia).Subject Sample: A total of 100 subjects with chronic low back pain associated with moderate DDD (modified Pfirrmann score of 3-6) at one level from L1 to S1 for at least 6 months and failing 3 months of conservative treatment, including physical therapy were randomized in a 3:3:2:2 ratio to receive 6 million MPCs with HA, 18 million MPCs with HA, HA vehicle control, or saline control (placebo) treatment.Outcome Measures: Subjects were clinically and radiographically evaluated at 1, 3, 6, 12, 24, and 36 months postinjection. Subject-reported outcomes including adverse events, LBP on a Visual Analog Scale (VAS), Oswestry Disability Index (ODI), SF-36 and Work Productivity and Activity Index were collected.Methods: Clinical and radiographic measures were collected at each visit. All randomized subjects were included in the safety assessments and analyzed based on the treatment received. Safety assessments included assessments of AEs, physical and radiographic examinations and laboratory testing. Efficacy assessments evaluated changes in VAS, ODI, and modified Pfirrmann (MP) scores between all active and control groups, respectively. Assessments included least squares mean (Mean), LS mean change from baseline (Mean Change) and responder analyses in order to assess the clinical significance of observed changes from baseline. The population for efficacy assessments was adjusted for the confounding effects of post-treatment interventions (PTIs). This study was conducted under an FDA Investigational New Drug application sponsored and funded by Mesoblast.Results: There were significant differences between the control and MPC groups for improvement in VAS and ODI. The PTI-corrected VAS and ODI Means and Mean Change analyses; the proportion of subjects with VAS ≥30% and ≥50% improvement from baseline; absolute VAS score ≤20; and ODI reduction ≥10 and ≥15 points from baseline showed MPC therapy superior to controls at various time points through 36 months. Additionally, the proportion of subjects achieving the minimally important change and clinically significant change composite endpoints for the MPC groups was also superior compared with controls at various time points from baseline to 36 months. There were no significant differences in change in MP score from baseline across the groups. There were also no statistically significant differences in change in modified MP score at the level above or below the level treated between study arms. Both the procedure and treatment were well tolerated and there were no clinical symptoms of immune reaction to allogeneic MPCs. There was a low rate of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events, and the rates of these events in the MPC groups were not significantly different from the control groups. One TEAE of severe back pain was possibly related to study agent and one TEAE of implantation site infection was considered to be related to the study procedure.Conclusions: Results provide evidence that intradiscal injection of MPCs could be a safe, effective, durable, and minimally invasive therapy for subjects who have CLBP associated with moderate DDD. [ABSTRACT FROM AUTHOR]

Background: Low-tension traction is more effective than high-tension traction in restoring the height and rehydration of a degenerated disc and to some extent the bony endplate. This might better reshape the microenvironment for disc regeneration and repair. However, the repair of the combination of endplate sclerosis, osteophyte formation, and even collapse leading to partial or nearly complete occlusion of the nutrient channel is greatly limited.Purpose: To evaluate the effectiveness of low-intensity extracorporeal shock wave therapy (ESWT) combined with low tension traction for regeneration and repair of moderately and severely degenerated discs; to explore the possible mechanism of action.Study Design: Animal study of a rat model of degenerated discs.Methods: A total of thirty-five 6-month old male Sprague-Dawley rats were randomly assigned to one of five groups (n=7, each group). In Group A (model group), caudal vertebrae were immobilized using a custom-made external device to fix four caudal vertebrae (Co7-Co10) whereas Co8-Co9 underwent 4 weeks of compression to induce moderate disc degeneration. In Group B (experimental control group), as in Group A, disc degeneration was successfully induced after which the fixed device was removed for 8 weeks of self-recovery. The remaining three groups of rats represented the intervention Groups (C-E): after successful generation of disc degeneration in Group C (com - 4w/tra - 4w) and Group D (com - 4w/ESWT), as described for group A, low-tension traction (in-situ traction) or low-energy ESWT was administered for 4 weeks (ESWT parameters: intensity: 0.15 Mpa; frequency: 1 Hz; impact: 1,000 each time; once/week, 4 times in total); Group E (com - 4w/tra - 4w/ESWT): disc degeneration as described for group A, low-tension traction combined with low-energy ESWT was conducted (ESWT parameters as Group D). After experimentation, caudal vertebrae were harvested and disc height, T2 signal intensity, disc morphology, total glycosaminoglycan (GAG) content, gene expression, structure of the Co8-Co9 bony endplates and elastic moduli of the discs were measured.Results: After continuous low-tension traction, low energy ESWT intervention or combined intervention, the degenerated discs effectively recovered their height and became rehydrated. However, the response in Group D was weaker than in the other intervention groups in terms of restoration of intervertebral disc (IVD) height, whereas Group E was superior in disc rehydration. Tissue regeneration was evident in Groups C to E using different interventions. No apparent tissue regeneration was observed in the experimental control group (Group B). The histological scores of the three intervention groups (Groups C-E) were lower than those of Groups A or B (p<.0001), and the scores of Groups C and E were significantly lower than those of Group D (p<.05), but not Group C versus Group E (p>.05). Compared with the intervention groups (Groups C-E), total GAG content of the nucleus pulposus (NP) in Group B did not increase significantly (p>.05). There was also no significant difference in the total GAG content between Groups A and B (p>.05). Of the three intervention groups, the recovery of NP GAG content was greatest in Group E. The expression of collagen I and II, and aggrecan in the annulus fibrosus (AF) was up-regulated (p<.05), whereas the expression of MMP-3, MMP-13, and ADAMTS-4 was down-regulated (p<.05). Of the groups, Group E displayed the greatest degree of regulation. The trend in regulation of gene expression in the NP was essentially consistent with that of the AF, of which Group E was the greatest. In the intervention groups (Groups C-E), compared with Group A, the pore structure of the bony endplate displayed clear changes. The number of pores in the endplate in Groups C to E was significantly higher than in Group A (p<.0001), among which Group C versus Group D (p=.9724), and Group C versus Group E (p=.0116). There was no significant difference between Groups A and B (p=.5261). In addition, the pore diameter also increased, the trend essentially the same as that of pore density. There was no significant difference between the three intervention groups (p=.7213). It is worth noting that, compared with Groups A and B, peripheral pore density and size in Groups D and E of the three intervention groups recovered significantly. The elastic modulus and diameter of collagen fibers in the AF and NP varied with the type of intervention. Low tension traction combined with ESWT resulted in the greatest impact on the diameter and modulus of collagen fibers.Conclusions: Low energy ESWT combined with low tension traction provided a more stable intervertebral environment for the regeneration and repair of moderate and severe degenerative discs. Low energy ESWT promoted the regeneration of disc matrix by reducing MMP-3, MMP-13, and ADAMTS-4 resulting in inhibition of collagen degradation. Although axial traction promoted the recovery of height and rehydration of the IVD, combined with low energy ESWT, the micro-nano structure of the bony endplate underwent positive reconstruction, tension in the annulus of the AF and nuclear stress of the NP declined, and the biomechanical microenvironment required for IVD regeneration and repair was reshaped. [ABSTRACT FROM AUTHOR]

Background Context: The diagnosis of discogenic low back pain (LBP) from disc degeneration of the lumbar spine is often evaluated with discography. Noninvasive, simple screening methods other than invasive discography are useful, as evidence supporting clinical findings and magnetic resonance imaging (MRI) have come to the forefront.Purpose: To investigate disc height (DH) discrepancy between supine and standing positions on simple radiography to clarify its clinical screening value in individuals with discogenic LBP.Study Design/settings: Retrospective matched cohort design.Patient Sample: Ninety-two patients with early to middle stage disc degeneration (Pfirrmann grade II, III, or IV).Outcome Measures: Each subject underwent simple radiographs and MRI. Baseline characteristics, including demographic data and MRI findings, and radiological findings, including DH discrepancy, segmental angle, and sagittal balance, were analyzed. DH discrepancy ratio was calculated as (1 - [calibrated DH on standing radiography/calibrated DH on supine radiography]) × 100%.Methods: We matched LBP group of 46 patients with intractable discogenic pain (≥7 of visual analog scale scores) confirmed by discography with control group of 46 patients with similar stage disc degeneration with mild LBP (≤4 of visual analog scale scores). Binary regression analysis, receiver operating characteristic curve analysis, and cut-off value for diagnosis were used to evaluate and clarify diagnostic value of various factors.Results: There was no significant difference between the two groups in terms of baseline characteristics, including age, sex, body mass index, pathological level, and magnetic resonance findings such as disc degeneration, high intensity zone, and para-spinal muscle volume. Among the various radiological findings, the calibrated mean DH in the standing position (20.87±5.65 [LBP group] vs. 26.95±3.02 [control group], p<.001) and the DH discrepancy ratio (14.55±6.13% [LBP group] vs. 1.47±0.75% [control group], p=.007) were significantly different between the two groups. The cut-off value for DH discrepancy ratio to screen discogenic LBP was ≥6.04%. Additionally, as a compensation for pain, sagittal vertical axis (3.43±2.03 cm [LBP group] vs. -0.54±3.05 cm [control group], p=.002) and pelvic incidence (54.74±6.76° [LBP group] vs. 43.98±8.67° [control group]; p=.006) were different between the two groups.Conclusions: The results suggest that DH discrepancy between the supine and standing positions could be a screening metric for discogenic LBP in early to middle stage disc degeneration of the lumbar spine. [ABSTRACT FROM AUTHOR]

Background Context: Small leucine-rich proteoglycans (SLRPs) play an essential role in extracellular matrix (ECM) organization and function. Recently, dysregulation of SLRPs has been implicated in degenerative disc disease (DDD). An in-depth analysis using high-throughput proteomic sequencing might provide valuable information on their implications in health and disease.Purpose: To utilize proteomics for analyzing the expression of SLRPs in fetal, healthy adult, and degenerated discs, to identify possible molecular targets to halt or reverse the degenerative process.Study Design: Experimental analysis.Methods: Proteomic signatures of 8 magnetic resonance imaging (MRI) normal lumbar discs (ND) [harvested from brain dead alive organ donors] were compared to 8 fetal disc samples (FD) [harvested from fetal spines devoid of congenital anomalies following spontaneous or medical termination of pregnancy] and 8 degenerate discs (DD) [collected from patients undergoing fusion surgery]. The various functional pathways along with the differential expression of SLRPs and the associated changes in collagens, large proteoglycans (LLRPs), matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) have been analyzed further using bioinformatics. This project was self-funded by the Ganga Orthopedic Research and Education Foundation.Results: ESI-LC-MS/MS analysis revealed a total of 1,029 proteins in FD, 1,785 proteins in ND, and 1,775 proteins in DD. Fetal disc proteins were engaged mainly in ribosomal pathways (indicating active proliferation and regenerative potential). The healthy adult discs (ND) primarily participated in ECM maintenance and basic metabolic pathways, whereas the unique proteins of DD group were involved in inflammatory (Complement and coagulation cascades, Systemic Lupus Erythematosus and Leukocyte transendothelial migration) pathways and infective (Staphylococcus aureus infection, Prion diseases, Amoebiasis, Pertussis, and Legionellosis) channels which favor the recent concepts of inflammaging and subclinical infection as causes of DDD. Analysis of SLRPs revealed the upregulation of Biglycan in FDs and downregulation of Lumican, Decorin, Prolargin, and Chondroadherin in the DD group. The universal decrease in the abundance of SLRPs in the DD group was associated with an increase in MMPs and a reduction in TIMPs, collagen and LLRP content.Conclusions: Our study documents the influence of SLRPs in the maintenance of disc health and also the need for future research in using them for disc regeneration.Clinical Significance: The various SLRPs that we identified are all known to have a beneficial influence on ECM integrity and a negative effect on the degenerative process at different stages in the evolution of degeneration. Biglycan, which is abundantly present in a fetus, may be suitable for regenerative therapy, and the other SLRPs like Lumican, Prolargin, Decorin, and Chondroadherin may serve the same purpose and/or as biomarkers. [ABSTRACT FROM AUTHOR]

Up to 1.8 million people in the United States will be diagnosed with cancer every year, and up to 40% of those cancer patients will go on to develop spinal metastases at some point in their lifetime. Radiation therapy continues to be a standard part of treatment in many cases. However, it is known that some tumors will respond better than others to this therapy, and certain patients may tolerate radiotherapy better than others. To date, there is no reliable method of predicting or measuring of the effects of radiation therapy on metastatic tumors. Such a tool would be useful in monitoring tumor treatment in real time and could enable tailoring of treatment to individual patients and tumors with hope of maximizing treatment effect and minimizing adverse effects. Circulating tumor DNA (ctDNA) is cell-free DNA shed by all tumors into the bloodstream. It has been shown that ctDNA is a more specific and sensitive biomarker than standard tumor biomarkers. Previous work established correlation between ctDNA levels and tumor volume, metastatic burden, and response to chemotherapy. Because of its sensitivity and short half-life, ctDNA may be able to function as a biomarker that may predict response to radiation therapy. Our study's aim is to determine if ctDNA can be used as a reliable biomarker for spinal metastases and thus used to tailor radiation therapy to individual tumor response. Our first goal is to assess feasibility of measuring ctDNA levels in mouse model of metastatic disease undergoing radiation therapy. Our second goal is to determine how ctDNA levels vary in relation to radiation therapy and assess the difference in ctDNA levels after radiation in both radiosensitive and radioresistant tumors. Athymic nude mice were implanted with 5x106 LS174T human colorectal tumor cells in the flank. Tumors were allowed to grow for 9 days before initiation of radiation therapy. Mice were treated with 20 Gy stereotactic radiation in 5 fractions, given on serial days. Tumor volumes (LxW2/2) were measured with calipers every other day. Six mice per group were randomized based on pretreatment tumor volume. To obtain enough blood to measure ctDNA, mice were anesthetized with isoflurane and a terminal blood draw via cardiac puncture was performed. Group 1 was sacrificed on day 1 (first dose) of radiation, group 2 on day 3 (middle dose) of radiation, group 3 on day 5 (last dose) of radiation, and group 4 was sacrificed in delayed fashion 10 days after last radiation dose. Blood was drawn into ctDNA specific Streck tube and spun down to extract plasma per standard protocol. Plasma was frozen until all samples collected. ctDNA was extracted via qiagen protocol. Because we used human tumors implanted in mice, we used the human LINE-1 retrotransposon as a tumor specific ctDNA and performed ddPCR with primers designed for this sequence. These results demonstrate that tumor size and radiation dynamically effect the release of ctDNA in mice. Our results demonstrated that radiation decreased tumor size by 33% over the 5 days of treatment. During that time, the average percentage of positive ctDNA droplets increased from 28.3% to 50.2%. Interestingly, on day 3 of treatment the average percentage of ctDNA was 70.8%. After 14 days post treatment, the average percentage of positive ctDNA was 53.1%. We also utilized linear and logistical modeling to measure the association of ctDNA and tumor size within groups. Within group 1 and group 4, logistic models measured a strong, positive association of R2 = 0.98 and R2 = 0.98 between tumor size and ctDNA, but this relationship was lost for group 2 (R2 = 0.33) and group 3 (R2 = 0.43). We see that ctDNA of human tumors is measurable in a mouse model of metastasis. We confirm that ctDNA levels correlate with tumor volume; however, while radiation therapy appears to halt tumor growth, ctDNA levels seem to peak during radiation therapy, suggesting a radiation specific effect. Giving subtherapeutic dose of radiation seems to paradoxically increase amount of tumor DNA shed when receiving radiation. We also show that persistent tumor after radiation continues to shed ctDNA, which could be used to tailor treatment (ie, more radiation). We next plan to repeat this study with the radiosensitive tumor, as well as radioresistant cell lines, in comparison to nontreated controls. We also plan to compare these effects in flank metastasis model to spinal metastasis model. Our preliminary results are promising and, while there is still more to accomplish, this work is readily translatable to human studies and may provide the basis of a future clinical trial. This abstract does not discuss or include any applicable devices or drugs. [ABSTRACT FROM AUTHOR]

Background Context: Pre-existing comorbid psychiatric mood disorders are a known risk factor for impaired health-related quality of life and poor long-term outcomes after spine surgery.Purpose: The purpose of this study was to investigate the effect of preexisting mood disorders on (1) pre- and postoperative patient-reported outcomes, (2) complications, and (3) pre- and postoperative opioid consumption in patients undergoing elective cervical or lumbar spine surgery.Study Design/setting: Retrospective review at a single academic institution from 2014 to 2017.Patient Sample: Consecutive adult patients who underwent cervical or lumbar surgery.Outcome Measures: Quantitative measurements of pain (visual analog scale [VAS]) and spinal region-specific disability scores (Neck Disability Index [NDI] and Oswestry Disability Index [ODI]).Methods: This is a retrospective review of 435 consecutive patients (179 cervical, 256 lumbar) who underwent elective spine surgery at a single academic institution from 2014 to 2017. Patient preoperative diagnosis of psychiatric mood disorder (eg, depression, anxiety, schizophrenia, bipolar, or dementia), baseline characteristics, medical (nonpsychiatric) comorbidities, operative variables, and surgical complications (eg, superficial and deep infection, wound complication, emergency department [ED] visits, readmissions, and repeat operations) were recorded. Additionally, preoperative ED visits, pre- and postoperative opioid requirements, total opioid prescription quantities and most recent dateof opioid prescription were collected. VAS, NDI, and ODI scores were recorded preoperatively and at 2, 6, and 12 weeks after surgery. Continuous variables were compared between those with and without diagnosed psychiatric comorbidity using two-tailed independent t test, and categorical variables were compared using chi-square or Fisher's exact tests. Analyses of variance and analysis of covariance were used to compare patient-reported outcomes between groups. A multivariate approach was taken to account for contribution of potential covariates in significant findings. Multiple linear regressions were used to determine variables associated with the number of postoperative opioid prescriptions.Results: Of the cervical and lumbar cohorts, 78 (43.6%) and 113 (44.1%), respectively, had a preoperative diagnosis of comorbid psychiatric mood disorder. Cervical patients with mood disorders received a significantly higher total number of opioid prescriptions post-operatively (4.6±5.2 vs. 2.8±3.9; p=.002). Patients with mood disorders had worse NDI scores at all time points (p=.04), however there were no differences in VAS pain scores (p=.5). There were no statistical differences between patients with and without mood disorders regarding baseline characteristics, medical (nonpsychiatric) comorbidities, operative variables, surgical complications, preoperative ED visits or prior opioid use (p>.05). For lumbar patients, patients with mood disorders were more commonly females (p=.04), tobacco users (p=.003), alcohol dependent (p=.01) and illicit-drug abusers (p=.03). There were no differences regarding surgical complications or opioid consumption. Tobacco use (p<.001) was the sole contributor to postoperative VAS pain scores. Patients with mood disorders had significantly higher VAS values both before and 3 months following surgery (p=.01), but there was no difference in ODI scores.Conclusions: Patients with preoperative psychiatric mood disorders undergoing elective cervical surgery had worse NDI scores and received more opioid prescriptions, despite similar VAS scores as those without mood disorders. Lumbar surgery patients with mood disorders were demographically different than those without mood disorders and had worse pain before and after surgery, though ODI scores were not different. Tobacco use was the sole contributor to postoperative VAS pain scores. This information can be useful in counseling patients with mood disorders before elective spinal surgery. [ABSTRACT FROM AUTHOR]