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Objective: This study aimed to elucidate postoperative outcomes in patients with spinal metastases of prostate cancer, with a focus on patient-oriented assessments., Methods: This was a prospective multicenter registry study involving 35 centers. A total of 413 patients enrolled in the Japanese Association for Spine Surgery and Oncology Multicenter Prospective Study of Surgery for Metastatic Spinal Tumors were evaluated for inclusion. The eligible patients were followed for at least 1 year after surgery. The Frankel Classification, Eastern Cooperative Oncology Group Performance Status, visual analog scale for pain, face scale, Barthel Index, vitality index, indications for oral pain medication, and the EQ-5D-5L questionnaire were used for evaluating functional status, activities of daily living, and patient motivation., Results: Of the 413 eligible patients, 41 with primary prostate cancer were included in the study. The patient-oriented assessments indicated that the patients experienced postoperative improvements in quality of life and motivation in most items, with the improvements extending for up to 6 months. More than half of the patients with Frankel classifications B or C showed improved neurological function at 1 month after surgery, and most patients presented maintained or improved their classification at 6 months., Conclusion: Surgical intervention for spinal metastases of prostate cancer significantly improved neurological function, quality of life, and motivation of the patients. Consequently, our results support the validity of surgical intervention for improving the neurological function and overall well-being of patients with spinal metastases of prostate cancer., Competing Interests: Declaration of competing interest The Authors declare that there is no conflict of interest., (Copyright © 2024 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

The resting zone (RZ) in mammalian growth plates is critical for maintaining and regulating chondrocyte turnover during longitudinal bone growth as a control tower and stem cell reservoir. Although recent lineage tracing studies have identified several markers for stem cells in the RZ, these markers only partially label chondrocytes in the RZ, suggesting that the resting chondrocytes (RCs) are a heterogeneous population with different types of stem cells. Since a comprehensive marker for RCs is still lacking, the RZ is generally determined based on ambiguous histological criteria, such as small and round chondrocytes without columnar formation, which may lead to inconsistencies among researchers. Therefore, in this study, we used single-cell RNA sequencing (scRNAseq) of growth plate chondrocytes followed by validation by fluorescence in situ hybridization (FISH) to precisely annotate cell clusters in scRNAseq and search for a marker of RCs. The scRNAseq analysis revealed that apolipoprotein E ( Apoe ) was the top-hit gene, which was ubiquitously expressed in the RC cluster. FISH confirmed that Apoe was exclusively localized to the histologically defined RZ. In newly generated Apoe -mCherry knock-in mice, we further confirmed that mCherry expression mirrored the distribution of Apoe -expressing chondrocytes in the RZ particularly after the formation of the secondary ossification center. These mCherry + RCs were slow cycling in vivo and exhibited stem cell properties both in vitro and in vivo . Moreover, APOE was detected in human growth plate RCs. These findings suggest that Apoe is a novel pan-RC marker in both mouse and human growth plates., Competing Interests: Conflict of interests The authors declare no competing interest.

Study Design: A retrospective analysis., Objective: This research sought to develop a predictive model for surgical outcomes in patients with cervical ossification of the posterior longitudinal ligament (OPLL) using deep learning and machine learning (ML) techniques., Summary of Background Data: Determining surgical outcomes assists surgeons in communicating prognosis to patients and setting their expectations. Deep learning and ML are computational models that identify patterns from large datasets and make predictions., Methods: Of the 482 patients, 288 patients were included in the analysis. A minimal clinically important difference (MCID) was defined as gain in Japanese Orthopaedic Association (JOA) score of 2.5 points or more. The predictive model for MCID achievement at 1 year post-surgery was constructed using patient background, clinical symptoms, and preoperative imaging features (x-ray, CT, MRI) analyzed via LightGBM and deep learning with RadImagenet., Results: The median preoperative JOA score was 11.0 (IQR: 9.0-12.0), which significantly improved to 14.0 (IQR: 12.0-15.0) at 1 year after surgery (P < 0.001, Wilcoxon signed-rank test). The average improvement rate of the JOA score was 44.7%, and 60.1% of patients achieved the MCID. Our model exhibited an area under the receiver operating characteristic curve of 0.81 and the accuracy of 71.9% in predicting MCID at 1 year. Preoperative JOA score and certain preoperative imaging features were identified as the most significant factors in the predictive models., Conclusion: A predictive ML and deep learning model for surgical outcomes in OPLL patients is feasible, suggesting promising applications in spinal surgery., Level of Evidence: 4., Competing Interests: Authors have no conflict of interest to declare., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Despite the increasing prevalence of cervical odontoid fractures in older adults, the treatment strategy is controversial. The objectives of the current study are to investigate the prognosis and complications of cervical odontoid fractures in elderly patients and to identify factors associated with worsening of ambulation after 6 months., Methods: This multicenter, retrospective study included 167 patients aged 65 years or older with odontoid fractures. Patient demographic and treatment data were investigated and compared according to the treatment strategy. To determine associations with worsening ambulation after 6 months, we focused on the treatment strategies (nonsurgical treatment [collar immobilization or halo vest], conversion to surgery, or initial surgery) and patients' background., Results: Patients who received nonsurgical treatment were significantly older, and patients who underwent surgery had more Anderson-D'Alonzo type 2 fractures. Of the patients initially treated nonsurgically, 26% later underwent surgery. Numbers of complications, including death, and degrees of ambulation after 6 months did not differ significantly among treatment strategies. Patients who had worsened ambulation after 6 months were significantly more likely to be older than 80 years, to have needed assistance with walking before injury, and to have cerebrovascular disease. Multivariable analysis showed that a score of ≥2 on the 5-item modified frailty index (mFI-5) was significantly associated with worsening ambulation., Conclusions: Preinjury mFI-5 scores of ≥2 were significantly associated with worsening ambulation 6 months after treatment of cervical odontoid fractures in older adults., (Copyright © 2023 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: Although pelvic obliquity (PO) is a risk factor for postoperative coronal decompensation in corrective surgery in adolescent idiopathic scoliosis (AIS), especially Lenke 5C, methods of measuring PO are controversial. This study aimed to establish an appropriate measurement method using multiplanar reconstructed computed tomography (MPR-CT) images instead of standing posteroanterior (PA) whole-spine radiographs to evaluate PO in patients with Lenke 5C AIS., Methods: This study was a retrospective cross-sectional study. Twenty-five patients who underwent corrective surgery for AIS in Osaka University Hospital from August 2014 to February 2023 were included. Cobb angle, L5 tilt, C7 plumb line to center sacral vertebral line (C7PL-CSVL), and leg length discrepancy (LLD) were measured on standing PA whole-spine radiographs preoperatively. Sacral obliquity (SO), the slope of the upper endplate of S1, and iliac obliquity (IO), the tilt of the line connecting the iliac crests, were measured on standing PA whole-spine radiographs and MPR-CT (SO/IO-X-ray, SO/IO-CT, respectively). S1 angle and S2 angle were measured on CT., Results: The mean age of the patients was 18.7±3.9 years and all of them were females. SO-X-ray and SO-CT were larger than IO-X-ray and IO-CT, respectively. SO-X-ray was highly correlated with SO-CT (r=0.838, P<0.001). L5 tilt had higher correlation with SO-CT (r=0.884, P<0.001) than with SO-X-ray (r=0.726, P=0.001) and IO-CT (r=0.550, P=0.22). L5 tilt was correlated poorly with IO-X-ray (r=0.104, P=0.69). The S1 angle was 4.5±3.5° meanwhile the S2 angle was 1.2±2.1°, the sacral deformity was mainly due to the S1 vertebral wedging., Conclusions: Given the asymmetric sacral morphology, SO is more appropriate pelvic parameter than IO to represent the sacral tilt of Lenke 5C AIS, especially when measured using CT images to overcome the poor visibility on PA whole-spine radiographs., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jss.amegroups.com/article/view/10.21037/jss-23-138/coif). The authors have no conflicts of interest to declare., (2024 Journal of Spine Surgery. All rights reserved.)

Study Design: Multicenter, prospective registry study., Objective: To clarify minimal clinically important differences (MCIDs) for surgical interventions for spinal metastases, thereby enhancing patient care by integrating quality of life (QoL) assessments with clinical outcomes., Summary of Background Data: Despite its proven usefulness in degenerative spinal diseases and deformities, the MCID remains unexplored regarding surgery for spinal metastases., Methods: This study included 171 (out of 413) patients from the multicenter "Prospective Registration Study on Surgery for Metastatic Spinal Tumors" by the Japan Association of Spine Surgeons. These were evaluated preoperatively and at 6 months postoperatively using the Face scale, EuroQol-5 Dimensions-5 Levels (EQ-5D-5L), including the visual analog scale (VAS), and performance status. The MCIDs were calculated using an anchor-based method, classifying participants into the improved, unchanged, and deteriorated groups based on the Face scale scores. Focusing on the improved and unchanged groups, the change in the EQ-5D-5L values from before to after treatment was analyzed, and the cutoff value with the highest sensitivity and specificity was determined as the MCID through receiver operating characteristic curve analysis. The validity of the MCIDs was evaluated using a distribution-based calculation method for patient-reported outcomes., Results: The improved, unchanged, and deteriorated groups comprised 121, 28, and 22 participants, respectively. The anchor-based MCIDs for the EQ-5D-5L index, EQ-VAS, and domains of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression were 0.21, 15.50, 1.50, 0.50, 0.50, 0.50, and 0.50, respectively; the corresponding distribution-based MCIDs were 0.17, 15,99, 0.77, 0.80, 0.78, 0.60, and 0.70, respectively., Conclusion: We identified MCIDs for surgical treatment of spinal metastases, providing benchmarks for future clinical research. By retrospectively examining whether the MCIDs are achieved, factors favoring their achievement and risks affecting them can be explored. This could aid in decisions on surgical candidacy and patient counseling., Competing Interests: Conflicts of interest: The authors declare that there is no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Study Design: Non-randomized prospective controlled study., Objectives: To compare the safety and perioperative outcomes between patient-specific template-guided and fluoroscopic-assisted freehand techniques in transforaminal lumbar interbody fusion (TLIF) using cortical bone trajectory (CBT)., Methods: The subjects consisted of 94 consecutive patients who underwent single-level TLIF using CBT. The standard trajectory was set so as to start from the pars interarticularis, pass the inferior border of the pedicle, and end around the middle of the vertebral endplate. Template guide technique was performed in 66 patients (Guide group), and fluoroscopic-assisted freehand technique was performed in 28 patients (Freehand group). Intraoperative parameters, screw placement accuracy, and complications were compared between the two techniques., Results: The Guide group had significantly shorter operative and radiation exposure times than the Freehand group (operative time 84.6 ± 16.7 vs 93.0 ± 15.0 minutes; P = .023, radiation exposure time 7.0 ± 6.0 vs 20.4 ± 11.8 seconds; P < .001, respectively). The screw diameter and the screw insertion depth in the vertebra in the Guide group were significantly greater than those in the Freehand group. The degree and incidence of facet joint violation were comparable between the two groups, while the accuracy of screw placement was significantly different, with no perforation rate of 97.7% in the Guide group vs 82.1% in the Freehand group ( P < .001). No significant difference was found in the rate of clinically relevant complications between the two groups., Conclusions: The template-guided technique provided a safe and highly accurate option for CBT screw placement., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflict of interest with respect to the research, authorship, and/or publication of this article: KM, KT, and YA have received speaker and consultant honoraria from Medacta International.

Study Design: Retrospective multicenter study., Objectives: To investigate changes over a 10-years period in the profile of cervical spine and spinal cord injuries among the elderly in Japan., Methods: The current multicenter study was a retrospective analysis of inpatients aged ≥65 years, suffering cervical fracture (CF) and/or cervical spinal cord injury (CSCI). We analyzed 1413 patients' epidemiology (from 2010 to 2019). Moreover, 727 patients who underwent surgical treatment were analyzed in 2 groups: the early (2010-2014) and late period (2015-2019)., Results: Both the number of patients and number of surgical patients showed a significant increasing trend ( P < .001), while the mean age, the distribution of injury levels and paralysis severity, and the proportion of surgical indications remained the same. The number of surgical patients doubled from 228 to 499 from the early to late periods. Posterior surgery was the most common approach (90.4%), instrumentation surgery with screws increased significantly, and the range of fusion was significantly longer in the late period (2.1 vs 2.7 levels, P = .001). Significantly worsening neurological symptoms were recorded in the late period (1.3% vs 5.8%, P = .006), with C5 palsy being the major one. Otherwise, perioperative, major, and other complications, including mortality, did not differ significantly in incidence., Conclusions: Both the number of elderly CF and/or CSCI patients and number of patients undergoing surgery increased dramatically over the decade without any change in profile. Instrumentation surgeries with screws increased, without an increase in systemic complications., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Study Design: A retrospective cohort study using prospectively collected data., Objective: This study primarily aimed to investigate the risk factors for surgery-related complications in primary thoracic spine surgery for degenerative diseases using a surgeon-maintained database. The secondary purpose was to elucidate the characteristics of surgically treated thoracic myelopathy that also required cervical and/or lumbar spine surgery in the study period., Summary of Background Data: Few studies reported surgical complications and the feature of tandem spinal stenosis in thoracic myelopathy in detail because of their rarity., Materials and Methods: This study included 840 thoracic myelopathy patients undergoing primary surgery for degenerative diseases from 2012 to 2021, investigating the effects of diseases, surgical procedures, and patient demographics on postoperative neurological deterioration, dural tear, dural leakage, surgical-site infection, and postoperative hematoma. In thoracic myelopathy patients who were surgically treated and also undergoing cervical and/or lumbar surgery, we investigated the proportion, the effects of diseases, and the order and intervals between surgeries., Results: Multivariate logistic regression revealed that significant risk factors ( P <0.05) for postoperative neurological deterioration were intervertebral disk herniation [odds ratio (OR): 4.59, 95% confidence interval (CI): 1.32-16.0) and degenerative spondylolisthesis (OR: 11.1, 95% CI: 2.15-57.5). Ossification of the ligamentum flavum (OR: 4.12, 95% CI: 1.92-8.86), anterior spinal fusion (OR: 41.2, 95% CI: 4.70-361), and circumferential decompression via a posterior approach (OR: 30.5, 95% CI: 2.27-410) were risk factors for dural tear. In thoracic myelopathy patients surgically treated, 37.0% also underwent degenerative cervical and/or lumbar surgery., Conclusions: Pathologies involving anterior decompression and instability increased the risk of postoperative neurological deterioration. The risk of dural tear was increased when dura mater adhesions were likely to be directly operated upon. It should be recognized that a relatively high proportion (37.0%) of surgically treated thoracic myelopathy patients also underwent cervical and/or lumbar surgery., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

In Japan, the Act on Safety of Regenerative Medicine regulates unapproved regenerative medicine. Other nations market regenerative medicine products, bypassing regulatory approval. To identify unapproved orthopedic regenerative medicine, we have used data based on the Act. Platelet-rich plasma was often used. The common target was the knee. Prices averaged $2,490., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background Context: Bone morphogenetic proteins (BMPs) have potent osteoinductivity and have been applied clinically for challenging musculoskeletal conditions. However, the supraphysiological doses of BMPs used in clinical settings cause various side effects that prevent widespread use, and therefore the BMP dosage needs to be reduced., Purpose: To address this problem, we synthesized 7C, a retinoic acid receptor γ antagonist-loaded nanoparticle (NP), and investigated its potential application in BMP-based bone regeneration therapy using a rat spinal fusion model., Study Design: An experimental animal study., Methods: Fifty-three male 8-week-old Sprague-Dawley rats underwent posterolateral spinal fusion and were divided into the following five treatment groups: (1) no recombinant human (rh)BMP-2 and blank-NP (Control), (2) no rhBMP-2 and 1 μg 7C-NP (7C group), (3) low-dose rhBMP-2 (0.5 μg) and 1 μg blank-NP (L-BMP group), (4) low-dose rhBMP-2 (0.5 μg) and 1 μg 7C-NP (L-BMP + 7C group), and (5) high-dose rhBMP-2 (5.0 μg) and 1 μg blank-NP (H-BMP group). Micro-computed tomography and histologic analysis were performed 2 and 6 weeks after the surgery., Results: The spinal fusion rates of the Control and 7C groups were both 0%, and those of the L-BMP, L-BMP + 7C, and H-BMP groups were 55.6%, 94.4%, and 100%, respectively. The L-BMP + 7C group markedly promoted cartilaginous tissue formation during BMP-induced endochondral bone formation that resulted in a significantly better spinal fusion rate and bone formation than in the L-BMP group. Although spinal fusion was slower in the L-BMP + 7C group, the L-BMP + 7C group formed a spinal fusion mass with better bone quality than the spinal fusion mass in the H-BMP group., Conclusions: The combined use of 7C-NP with rhBMP-2 in a rat posterolateral lumbar fusion model increased spinal fusion rate and new bone volume without deteriorating the quality of newly formed bone., Clinical Significance: 7C-NP potentiates BMP-2-induced bone regeneration and has the potential for efficient bone regeneration with low-dose BMP-2, which can reduce the dose-dependent side effects of BMP-2 in clinical settings., Competing Interests: Declaration of Competing Interest One or more of the authors declare financial or professional relationships on ICMJE-TSJ disclosure forms., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Health-related patient-reported outcomes (HR-PROs) are crucial for assessing the quality of life among individuals experiencing low back pain. However, manual data entry from paper forms, while convenient for patients, imposes a considerable tallying burden on collectors. In this study, we developed a deep learning (DL) model capable of automatically reading these paper forms., Methods: We employed the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire, a globally recognized assessment tool for low back pain. The questionnaire comprised 25 low back pain-related multiple-choice questions and three pain-related visual analog scales (VASs). We collected 1305 forms from an academic medical center as the training set, and 483 forms from a community medical center as the test set. The performance of our DL model for multiple-choice questions was evaluated using accuracy as a categorical classification task. The performance for VASs was evaluated using the correlation coefficient and absolute error as regression tasks., Result: In external validation, the mean accuracy of the categorical questions was 0.997. When outputs for categorical questions with low probability (threshold: 0.9996) were excluded, the accuracy reached 1.000 for the remaining 65 % of questions. Regarding the VASs, the average of the correlation coefficients was 0.989, with the mean absolute error being 0.25., Conclusion: Our DL model demonstrated remarkable accuracy and correlation coefficients when automatic reading paper-based HR-PROs during external validation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Study Design: Retrospective cohort study., Objectives: To define the prognosis and predictive factors for neurological improvement in older patients with incomplete spinal cord injury (SCI) of American Spinal Injury Association Impairment Scale grade C (AIS-C)., Settings: Multi-institutions in Japan., Methods: We included patients aged ≥65 years with traumatic SCI of AIS-C who were treated conservatively or surgically with >3 follow-up months. To identify factors related to neurological improvement, patients were divided into three groups according to their neurological status at the final follow-up, with univariate among-group comparisons of demographics, radiographic, and therapeutic factors. Significant variables were included in the multivariate logistic regression analysis., Results: Overall, 296 older patients with SCI of AIS-C on admission were identified (average age: 75.2 years, average follow-up: 18.7 months). Among them, 190 (64.2%) patients improved to AIS-D and 21 (7.1%) patients improved to AIS-E at final follow-up. There were significant among-group differences in age (p = 0.026), body mass index (p = 0.007), status of pre-traumatic activities of daily living (ADL) (p = 0.037), and serum albumin concentrations (p = 0.011). Logistic regression analysis showed no significant differences in variables in the stratified group of patients who improved to AIS-D. Meanwhile, serum albumin was a significant variable in patients who improved to AIS-E (p = 0.026; OR: 6.20, pre-traumatic ADL was omitted due to data skewness)., Conclusions: Most older patients with incomplete AIS-C SCI demonstrated at least 1 grade of neurological improvement. However, <10% of patients achieved complete recovery. Key predictors of complete recovery were high serum albumin levels on admission and independent pre-traumatic ADL., Sponsorship: No funding was received for this study., (© 2024. The Author(s), under exclusive licence to International Spinal Cord Society.)

This retrospective cohort study established malnutrition's impact on mortality and neurological recovery of older patients with cervical spinal cord injury (SCI). It included patients aged ≥ 65 years with traumatic cervical SCI treated conservatively or surgically. The Geriatric Nutritional Risk Index was calculated to assess nutritional-related risk. Overall, 789 patients (mean follow-up: 20.1 months) were examined and 47 had major nutritional-related risks on admission. One-year mortality rate, median survival time, neurological recovery, and activities of daily living (ADL) at 1 year post-injury were compared between patients with major nutrition-related risk and matched controls selected using 1:2 propensity score matching to adjust for age, pre-traumatic neurological impairment, and activity. In the Kaplan-Meier analysis, the median survival times were 44.9 and 76.5 months for patients with major nutrition-related risk and matched controls, respectively (p = 0.015). Matched controls had more individuals with a neurological improvement of American Spinal Injury Association Impairment Scale ≥ 1 grade (p = 0.039) and independence in ADL at 1 year post-injury than patients with major nutrition-related risk (p < 0.05). In conclusion, 6% of older patients with cervical SCI had major nutrition-related risks; they showed a significantly higher 1 year mortality rate, shorter survival time, poorer neurological improvement, and lower ADL at 1 year post-injury than matched controls., (© 2024. The Author(s).)

Background: Although previous studies have demonstrated the advantages of early surgery for traumatic spinal cord injury (SCI), the appropriate surgical timing for cervical SCIs (CSCIs) without bone injury remains controversial. Here, we investigated the influence of relatively early surgery within 48 h of injury on the neurological recovery of elderly patients with CSCI and no bone injury., Methods: In this retrospective multicenter study, we reviewed data from 159 consecutive patients aged ≥65 years with CSCI without bone injury who underwent surgery in participating centers between 2010 and 2020. Patients were followed up for at least 6 months following CSCI. We divided patients into relatively early (≤48 h after CSCI, n = 24) and late surgery (>48 h after CSCI, n = 135) groups, and baseline characteristics and neurological outcomes were compared between them. Multivariate analysis was performed to identify factors associated with neurological recovery., Results: The relatively early surgery group demonstrated a lower prevalence of cardiac disease, poorer baseline American Spinal Injury Association (ASIA) impairment scale grade, and lower baseline ASIA motor score (AMS) than those of the late surgery group (P < 0.030, P < 0.001, and P < 0.001, respectively). Although the AMS was lower in the relatively early surgery group at 6 months following injury (P = 0.001), greater improvement in this score from baseline to 6-months post injury was observed (P = 0.010). Multiple linear regression analysis revealed that relatively early surgery did not affect postoperative improvement in AMS, rather, lower baseline AMS was associated with better AMS improvement (P < 0.001). Delirium (P = 0.006), pneumonia (P = 0.030), and diabetes mellitus (P = 0.039) negatively influenced postoperative improvement., Conclusions: Although further validation by future studies is required, relatively early surgery did not show a positive influence on neurological recovery after CSCI without bone injury in the elderly., (Copyright © 2023 The Japanese Orthopaedic Association. All rights reserved.)

Study Design: Retrospective multicenter study., Objectives: The effectiveness of early surgery for cervical spinal injury (CSI) has been demonstrated. However, whether early surgery improves outcomes in the elderly remains unclear. This study investigated whether early surgery for CSI in elderly affects complication rates and neurological outcomes., Methods: This retrospective multicenter study included 462 patients. We included patients with traumatic acute cervical spinal cord injury aged ≥65 years who were treated surgically, whereas patients with American Spinal Injury Association (ASIA) Impairment Scale E, those with unknown operative procedures, and those waiting for surgery for >1 month were excluded. The minimum follow-up period was 6 months. Sixty-five patients (early group, 14.1%) underwent surgical treatment within 24 hours, whereas the remaining 397 patients (85.9%) underwent surgery on a standby basis (delayed group). The propensity score-matched cohorts of 63 cases were compared., Results: Patients in the early group were significantly younger, had significantly more subaxial dislocations (and fractures), tetraplegia, significantly lower ASIA motor scores, and ambulatory abilities 6 months after injury. However, no significant differences in the rate of complications, ambulatory abilities, or ASIA Impairment Scale scores 6 months after injury were observed between the matched cohorts. At 6 months after injury, 61% of the patients in the early group (25% unsupported and 36% supported) and 53% of the patients in the delayed group (34% unsupported and 19% supported) were ambulatory., Conclusions: Early surgery is possible for CSI in elderly patients as the matched cohort reveals no significant difference in complication rates and neurological or ambulatory recovery between the early and delayed surgery groups., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Adult spinal deformity (ASD) is a complex condition that combines scoliosis, kyphosis, pain, and postoperative range of motion limitation. The lack of a scale that can successfully capture this complex condition is a clinical challenge. We aimed to develop a disease-specific scale for ASD. The study included 106 patients (mean age; 68 years, 89 women) with ASD. We selected 29 questions that could be useful in assessing ASD and asked the patients to answer them. The factor analysis found two factors: the main symptom and the collateral symptom. The main symptom consisted of 10 questions and assessed activity of daily living (ADL), pain, and appearance. The collateral symptom consisted of five questions to assess ADL due to range of motion limitation. Cronbach's alpha was 0.90 and 0.84, respectively. The Spearman's correlation coefficient between the change of main symptom and satisfaction was 0.48 (p < 0.001). The effect size of Cohen's d for comparison between preoperative and postoperative scores was 1.09 in the main symptom and 0.65 in the collateral symptom. In conclusion, we have developed a validated disease-specific scale for ASD that can simultaneously evaluate the benefits and limitations of ASD surgery with enough responsiveness in clinical practice., (© 2024. The Author(s).)

Study Design: Retrospective Cohort Study., Objective: The purpose of this study was to investigate the prognosis of respiratory function in elderly patients with cervical spinal cord injury (SCI) and to identify predictive factors., Methods: We included 1353 cases of elderly cervical SCI patients collected from 78 institutions in Japan. Patients who required early tracheostomy and ventilator management and those who developed respiratory complications were defined as the respiratory disability group. Patients' background characteristics, injury mechanism, injury form, neurological disability, complications, and treatment methods were compared between the disability and non-disability groups. Multiple logistic regression analysis was used to examine the independent factors. Patients who required respiratory management for 6 months or longer after injury and those who died of respiratory complications were classified into the severe disability group and were compared with minor cases who were weaned off the respirator., Results: A total of 104 patients (7.8%) had impaired respiratory function. Comparisons between the disabled and non-disabled groups and between the severe and mild injury groups yielded distinct trends. In multiple logistic regression analysis, age, blood glucose level, presence of ossification of posterior longitudinal ligament (OPLL), anterior vertebral hematoma, and critical paralysis were selected as independent risk factors., Conclusion: Age, OPLL, severe paralysis, anterior vertebral hematoma, hypoalbuminemia, and blood glucose level at the time of injury were independent factors for respiratory failure. Hyperglycemia may have a negative effect on respiratory function in this condition., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Cervicobrachial pain frequently affects the quality of life (QOL) of the general public and has a significant economic impact on the health care systems of various countries. There are a number of treatment options for this disease, including widely-used drug therapy, but the effectiveness of each option is indeterminate, and there have been no published cost-effectiveness analysis studies so far. This prospective observational study aimed to examine the cost-effectiveness of drug treatment for cervicobrachial symptoms., Methods: A 6-month medication regimen for each of five frequently-prescribed drugs for cervicobrachial symptoms was administered to 322 patients at 24 centers in Japan. Outcome measures, including of the EuroQol Group 5D, Short Form-8, and Visual Analog Scale (VAS), were investigated at baseline and every month thereafter. Incremental cost-effectiveness ratios (ICERs) of the drug cost to quality-adjusted life years (QALYs) were calculated. A stratified analysis of patient characteristics was also performed to identify baseline factors potentially affecting cost-effectiveness., Results: The ICER of entire drug treatment for cervicobrachial symptoms was 7,491,640 yen. Compared with the reference willingness-to-pay, the ICER was assumed to not be cost-effective. A certain number of QALYs were gained during the first 3 months after the treatment intervention, but almost no QALYs were gained during the following 3 months. Stratified analysis showed that cost-effectiveness was extremely low for patients with high baseline VAS and high QOL., Conclusions: The available medications for cervicobrachial symptoms did not have excellent cost-effectiveness. Although a certain number of QALYs were gained during the first 3 months after medication, no QALYs were gained in the latter half of the study period, suggesting that it is not advisable to continue the medication needlessly., Level of Evidence: II, prospective cohort study., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest relevant to this work., (Copyright © 2023 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Study Design: Retrospective multicenter study., Objectives: To investigate the treatments of the geriatric population with hangman's fractures using a multicenter database under the Japan Association of Spine Surgeons with Ambition (JASA)., Methods: The multicenter database included data from 1512 patients. We employed the Levine and Edwards classification for categorizing hangman's fractures. The study incorporated epidemiological data, including the prevalence of hangman's fractures, patient age, and follow-up duration. Bony fusion rates and length of hospitalization were recorded for Type I and Type II fractures, and the degree of neurological impairment was assessed., Results: Hangman's fractures represented 62 cases, accounting for 7.4% of all cervical spine injuries. The patients had an average age of 76.6 ± 6.5 years, and the mean duration of follow-up was 21.5 ± 23.6 months. The study found that the bony fusion rate for hangman's fractures in the geriatric population was 88.9%. Surgical treatment was associated with a shorter hospitalization period for Type II fractures compared to conservative treatment. Thirteen cases of hangman's fractures in the geriatric population, accounting for 21%, were complicated by spinal cord injury., Conclusions: This is the largest study to date on hangman's fractures in geriatric population ≥65 years. Type I and Type II fractures, according to the Levine and Edwards classification, had a bony fusion rate of up to 90%. In patients with Type II fractures, surgical treatment led to a shorter initial hospital stay. Geriatric patients are at risk of spinal cord injury due to hangman's fractures., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: Postoperative complication prediction helps surgeons to inform and manage patient expectations. Deep learning, a model that finds patterns in large samples of data, outperform traditional statistical methods in making predictions. This study aimed to create a deep learning-based model (DLM) to predict postoperative complications in patients with cervical ossification of the posterior longitudinal ligament (OPLL)., Methods: This prospective multicenter study was conducted by the 28 institutions, and 478 patients were included in the analysis. Deep learning was used to create two predictive models of the overall postoperative complications and neurological complications, one of the major complications. These models were constructed by learning the patient's preoperative background, clinical symptoms, surgical procedures, and imaging findings. These logistic regression models were also created, and these accuracies were compared with those of the DLM., Results: Overall complications were observed in 127 cases (26.6%). The accuracy of the DLM was 74.6 ± 3.7% for predicting the overall occurrence of complications, which was comparable to that of the logistic regression (74.1%). Neurological complications were observed in 48 cases (10.0%), and the accuracy of the DLM was 91.7 ± 3.5%, which was higher than that of the logistic regression (90.1%)., Conclusion: A new algorithm using deep learning was able to predict complications after cervical OPLL surgery. This model was well calibrated, with prediction accuracy comparable to that of regression models. The accuracy remained high even for predicting only neurological complications, for which the case number is limited compared to conventional statistical methods., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Study Design: Retrospective study., Objective: The primary aim of this study was to investigate the predictors of severe complications in patients following surgery for pyogenic spondylodiscitis (PS) using a surgeon-maintained database. The secondary aim was to investigate the predictors of early recovery., Methods: We introduced a surgeon-maintained database of prospectively collected multicenter data that mainly focused on perioperative complications in 2012. Our surgeon-maintained database allows the retrospective collection of detailed data. We analyzed 143 patients who underwent surgery for PS from the 19,056 patients in the prospective surgeon-maintained database at 27 affiliated institutions between 2013 and 2017. Data relating to preoperative patient factors, infection factors, surgical factors, and pre- and postoperative blood tests was retrospectively collected. We performed multivariate regression analysis to evaluate the predictors of postoperative severe complications and early recovery in patients with PS., Results: High updated Charlson comorbidity index (uCCI), chronic pulmonary disease, diabetes, Gram-negative bacteria, pyogenic osteoarthritis, high preoperative white blood cell count, and low preoperative platelet count were significantly associated with severe complications in patients undergoing surgery for PS. A high uCCI was the sole independent negative predictor on early recovery., Conclusion: Careful perioperative management is necessary if surgery is performed on patients who are at a high risk of life-threatening events.

Purpose: To investigate the impact of early post-injury respiratory dysfunction for neurological and ambulatory ability recovery in patients with cervical spinal cord injury (SCI) and/or fractures., Methods: We included 1,353 elderly patients with SCI and/or fractures from 78 institutions in Japan. Patients who required early tracheostomy and ventilator management and those who developed respiratory complications were included in the respiratory dysfunction group, which was further classified into mild and severe respiratory groups based on respiratory weaning management. Patient characteristics, laboratory data, neurological impairment scale scores, complications at injury, and surgical treatment were evaluated. We performed a propensity score-matched analysis to compare neurological outcomes and mobility between groups., Results: Overall, 104 patients (7.8%) had impaired respiratory function. In propensity score-matched analysis, the respiratory dysfunction group had a lower home discharge and ambulation rates (p = 0.018, p = 0.001, respectively), and higher rate of severe paralysis (p < 0.001) at discharge. At the final follow-up, the respiratory dysfunction group had a lower ambulation rate (p = 0.004) and higher rate of severe paralysis (p < 0.001). Twenty-six patients with severe disability required respiratory management for up to 6 months post-injury and died of respiratory complications. The mild and severe respiratory dysfunction groups had a high percentage of severe paraplegic cases with low ambulatory ability; there was no significant difference between them. The severe respiratory dysfunction group tended to have a poorer prognosis., Conclusion: Respiratory dysfunction in elderly patients with SCI and/or cervical fracture in the early post-injury period reflects the severity of the condition and may be a useful prognostic predictor., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Study Design: A prospective multicenter study., Objective: To investigate the effect of preoperative symptom duration on neurological recovery for the treatment of cervical ossification of the posterior longitudinal ligament (OPLL)., Summary of Background Data: The optimal timing to perform surgery in the setting of cervical OPLL remains unknown. It is important to know the influence of symptom duration on postoperative outcomes to facilitate discussions regarding the timing of surgery., Patients and Methods: The study included 395 patients (291 men and 104 women; mean age, 63.7 ± 11.4 yr): 204 were treated with laminoplasty, 90 with posterior decompression and fusion, 85 with anterior decompression and fusion, and 16 with other procedures. The Japanese Orthopedic Association (JOA) score and patient-reported outcomes of the JOA Cervical Myelopathy Evaluation Questionnaire were used to assess clinical outcomes preoperatively and 2 years after surgery. Logistic regression analysis was used to identify factors associated with the achievement of minimum clinically important difference (MCID) after surgery., Results: The recovery rate was significantly lower in the group with symptom duration of ≥5 years compared with the groups with durations of <0.5 years, 0.5 to 1 year, and 1 to 2 years. Improvement of JOA Cervical Myelopathy Evaluation Questionnaire in the upper extremity function score ( P < 0.001), lower extremity function ( P = 0.039), quality of life ( P = 0.053), and bladder function ( P = 0.034) were all decreased when the symptom duration exceeded 2 years. Duration of symptoms ( P = 0.001), age ( P < 0.001), and body mass index ( P < 0.001) were significantly associated with the achievement of MCID. The cutoff value we established for symptom duration was 23 months (area under the curve, 0.616; sensitivity, 67.4%; specificity, 53.5%)., Conclusions: Symptom duration had a significant impact on neurological recovery and patient-reported outcome measures in this series of patients undergoing surgery for cervical OPLL. Patients with symptom duration exceeding 23 months may be at greater risk of failing to achieve MCID after surgery., Level of Evidence: 3., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

We proposed a bimodal artificial intelligence that integrates patient information with images to diagnose spinal cord tumors. Our model combines TabNet, a state-of-the-art deep learning model for tabular data for patient information, and a convolutional neural network for images. As training data, we collected 259 spinal tumor patients (158 for schwannoma and 101 for meningioma). We compared the performance of the image-only unimodal model, table-only unimodal model, bimodal model using a gradient-boosting decision tree, and bimodal model using TabNet. Our proposed bimodal model using TabNet performed best (area under the receiver-operating characteristic curve [AUROC]: 0.91) in the training data and significantly outperformed the physicians' performance. In the external validation using 62 cases from the other two facilities, our bimodal model showed an AUROC of 0.92, proving the robustness of the model. The bimodal analysis using TabNet was effective for differentiating spinal tumors., Competing Interests: Authors declare that they have no competing interests., (© 2023 The Authors.)

Study Design: A prospective multicenter study., Objective: The objective of this study was to investigate the incidence of loss of cervical lordosis after laminoplasty for cervical ossification of the posterior longitudinal ligament (OPLL). We also sought to determine associated risk factors and the relationship with patient-reported outcomes., Summary of Background Data: Loss of cervical lordosis is a sequelae often observed after laminoplasty, which may adversely impact surgical outcomes. Cervical kyphosis, especially in OPLL, is associated with reoperation, but risk factors and relationship to postoperative outcomes remain understudied at this time., Materials and Methods: This study was conducted by the Japanese Multicenter Research Organization for Ossification of the Spinal Ligament. We included 165 patients who underwent laminoplasty and completed Japanese Orthopaedic Association (JOA) score or Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaires (JOACMEQ), as well as Visual Analog Scales (VAS) for pain, with imaging. The participants were divided into two groups: those with loss of cervical lordosis of >10° or 20° after surgery and those without loss of cervical lordosis. A paired t test was applied to evaluate the association between changes in cervical spinal angles, range of motion, and cervical JOA and VAS scores before and at 2 years postoperatively. Mann-Whitney U test was used for JOACMEQ., Results: Postoperative loss of cervical lordosis >10° and >20° was observed in 32 (19.4%) and 7 (4.2%), respectively. JOA, JOACMEQ, and VAS scores were not significantly different between those with, and without, loss of cervical lordosis. Preoperative small extension range of motion (eROM) was significantly associated with postoperative loss of cervical lordosis, and the cutoff values of eROM were 7.4° [area under the curve (AUC): 0.76] and 8.2° (AUC: 0.92) for loss of cervical lordosis >10° and >20°, respectively. A large occupation ratio of OPLL was also associated with loss of cervical lordosis, with a cutoff value of 39.9% (AUC: 0.94). Laminoplasty resulted in functional improvement in most patient-reported outcomes; however, neck pain and bladder function tended to become worse postoperatively in cases with postoperative loss of cervical lordosis >20°., Conclusions: JOA, JOACMEQ, and VAS scores were not significantly different between those with, and without, loss of cervical lordosis. Preoperative small eROM and large OPLL may represent factors associated with loss of cervical lordosis after laminoplasty in patients with OPLL., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Ossification of the posterior longitudinal ligament of the spine (OPLL) is an intractable disease leading to severe neurological deficits. Its etiology and pathogenesis are primarily unknown. The relationship between OPLL and comorbidities, especially type 2 diabetes (T2D) and high body mass index (BMI), has been the focus of attention; however, no trait has been proven to have a causal relationship. We conducted a meta-analysis of genome-wide association studies (GWASs) using 22,016 Japanese individuals and identified 14 significant loci, 8 of which were previously unreported. We then conducted a gene-based association analysis and a transcriptome-wide Mendelian randomization approach and identified three candidate genes for each. Partitioning heritability enrichment analyses observed significant enrichment of the polygenic signals in the active enhancers of the connective/bone cell group, especially H3K27ac in chondrogenic differentiation cells, as well as the immune/hematopoietic cell group. Single-cell RNA sequencing of Achilles tendon cells from a mouse Achilles tendon ossification model confirmed the expression of genes in GWAS and post-GWAS analyses in mesenchymal and immune cells. Genetic correlations with 96 complex traits showed positive correlations with T2D and BMI and a negative correlation with cerebral aneurysm. Mendelian randomization analysis demonstrated a significant causal effect of increased BMI and high bone mineral density on OPLL. We evaluated the clinical images in detail and classified OPLL into cervical, thoracic, and the other types. GWAS subanalyses identified subtype-specific signals. A polygenic risk score for BMI demonstrated that the effect of BMI was particularly strong in thoracic OPLL. Our study provides genetic insight into the etiology and pathogenesis of OPLL and is expected to serve as a basis for future treatment development., Competing Interests: YK, MT, MN, NO, HS, XL, TE, SI, KK, TK, SK, MK, HS, TT, TM, HI, TY, MK, HN, KA, YT, KT, SI, KT, KH, YI, YK, SM, HN, KM, AS, SF, TK, KW, TT, KK, SK, MT, KY, HT, HL, SN, KO, YM, AO, MM, NI, CT, SI No competing interests declared, YK Consulting fees from Medacta International, MY representatives of Japanese Organization of the Study for Ossification of Spinal Ligament, (© 2023, Koike, Takahata, Nakajima et al.)

Study Design: Retrospective multicenter study., Objective: The purpose of this study was to compare the prognosis of elderly patients with injuries related to cervical diffuse idiopathic skeletal hyperostosis (cDISH) to matched control for each group, with and without fractures., Methods: The current multicenter study was a retrospective analysis of 140 patients aged 65 years or older with cDISH-related cervical spine injuries; 106 fractures and 34 spinal cord injuries without fracture were identified. Propensity score-matched cohorts from 1363 patients without cDISH were generated and compared. Logistic regression analysis was performed to determine the risk of early mortality for patients with cDISH-related injury., Results: Patients with cDISH-related injuries with fracture did not differ significantly in the incidence of each complication and ambulation or severity of paralysis compared to matched controls. In patients with cDISH-related injury without fracture, those who were nonambulatory at discharge comprised 55% vs 34% of controls, indicating significantly poorer ambulation in those with cDISH-related injuries ( P = .023). There was no significant difference in the incidence of complications and ambulation or paralysis severity at 6 months as compared with controls. Fourteen patients died within 3 months. Logistic regression analysis identified complete paralysis (odds ratio [OR] 36.99) and age (OR 1.24) as significant risk factors for mortality., Conclusions: The current study showed no significant differences in the incidence of complications, ambulation outcomes between patients with cDISH-related injury with fracture and matched controls, and that the ambulation at discharge for patients with cDISH-related injury without fractures were significantly inferior to those of matched controls., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Study Design: A prospective multi-institutional observational study., Objective: To investigate and identify risk factors for residual neuropathic pain after surgery in patients with cervical ossification of posterior longitudinal ligament (c-OPLL)., Summary of Background Data: Patients with c-OPLL often require surgery for numbness and paralysis of the extremities; however, postoperative neuropathic pain can considerably deteriorate their quality of life., Methods: Out of 479 patients identified from multicenter c-OPLL registries between 2014 and 2017, 292 patients who could be followed up for 2 years postoperatively were reviewed, after excluding patients with nervous system comorbidities. Demographic details; medical history; radiographic factors including the K-line, spinal canal occupancy rate of OPLL, cervical kyphosis angle, and presence of spinal cord myelomalacia; preoperative Japanese Orthopaedic Association (JOA) score; surgical procedure (fusion or decompression surgery); postoperative neurological deterioration; and the visual analogue scale for pain and numbness in the upper extremities (U/E) or trunk/lower extremities (L/E) at baseline and at 2 years postoperatively were assessed. Patients were grouped into residual and non-residual groups based on a postoperative visual analogue scale ≥40 mm. Risk factors for residual neuropathic pain were evaluated by multiple logistic regression analysis., Results: The prevalence of U/E and L/E residual pain in postoperative c-OPLL patients was 51.7% and 40.4%, respectively. The U/E residual group had a poor preoperative JOA score and longer illness duration, and fusion surgery was more common in the residual group than in non-residual group. The L/E residual group was older with a poorer preoperative JOA score. On multivariate analysis, risk factors for U/E residual pain were long illness duration and poor preoperative JOA score, whereas those for L/E residual pain were age and poor preoperative JOA score., Conclusions: The risk factors for residual spinal neuropathic pain after c-OPLL surgery were age, long duration of illness, and poor preoperative JOA score., Level of Evidence: IV., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To determine the optimal level for the measurement of psoas cross-sectional area and examine the correlation with short-term functional outcomes of posterior lumbar surgery., Methods: Patients who underwent minimally invasive posterior lumbar surgery were included in this study. The cross-sectional area of psoas muscle was measured at each intervertebral level on T2-weighted axial images of preoperative MRI. Normalized total psoas area (NTPA) (mm 2 /m 2 ) was calculated as total psoas area normalized to patient height. Intraclass Correlation Coefficient (ICC) was calculated for the analysis of inter-rater reliability. Patient reported outcome measures including Oswestry disability index (ODI), visual analog scale (VAS), short form health survey (SF-12) and patient-reported outcomes measurement information system were collected. A multivariate analysis was performed to elucidate independent predictors associated with failure to reach minimal clinically important difference (MCID) in each functional outcome at 6 months., Results: The total of 212 patients were included in this study. ICC was highest at L3/4 [0.992 (95% CI: 0.987-0.994)] compared to the other levels [L1/2 0.983 (0.973-0.989), L2/3 0.991 (0.986-0.994), L4/5 0.928 (0.893-0.952)]. Postoperative PROMs were significantly worse in patients with low NTPA. Low NTPA was an independent predictor of failure to reach MCID in ODI (OR = 2.68; 95% CI: 1.26-5.67; p = 0.010) and VAS leg (OR = 2.43; 95% CI: 1.13-5.20; p = 0.022)., Conclusion: Decreased psoas cross-sectional area on preoperative MRI correlated with functional outcomes after posterior lumbar surgery. NTPA was highly reliable, especially at L3/4., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Study Design: A prospective multicenter study., Objective: The objective of this study is to compare the surgical outcomes of anterior and posterior fusion surgeries in patients with K-line (-) cervical ossification of the posterior longitudinal ligament (OPLL)., Summary of Background Data: Although laminoplasty is effective for patients with K-line (+) OPLL, fusion surgery is recommended for those with K-line (-) OPLL. However, whether the anterior or posterior approach is preferable for this pathology has not been effectively determined., Materials and Methods: A total of 478 patients with myelopathy due to cervical OPLL from 28 institutions were prospectively registered from 2014 to 2017 and followed up for two years. Of the 478 patients, 45 and 46 with K-line (-) underwent anterior and posterior fusion surgeries, respectively. After adjusting for confounders in baseline characteristics using a propensity score-matched analysis, 54 patients in both the anterior and posterior groups (27 patients each) were evaluated. Clinical outcomes were assessed using the cervical Japanese Orthopaedic Association and the Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire., Results: Both approaches showed comparable neurological and functional recovery. The cervical range of motion was significantly restricted in the posterior group because of the large number of fused vertebrae compared with the anterior group. The incidence of surgical complications was comparable between the cohorts, but the posterior group demonstrated a higher frequency of segmental motor paralysis, whereas the anterior group more frequently reported postoperative dysphagia., Conclusions: Clinical improvement was comparable between anterior and posterior fusion surgeries for patients with K-line (-) OPLL. The ideal surgical approach should be informed based on the balance between the surgeon's technical preference and the risk of complications., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Adolescent idiopathic scoliosis (AIS) is a disorder with a three-dimensional spinal deformity and is a common disease affecting 1-5% of adolescents. AIS is also known as a complex disease involved in environmental and genetic factors. A relation between AIS and body mass index (BMI) has been epidemiologically and genetically suggested. However, the causal relationship between AIS and BMI remains to be elucidated., Material and Methods: Mendelian randomization (MR) analysis was performed using summary statistics from genome-wide association studies (GWASs) of AIS (Japanese cohort, 5,327 cases, 73,884 controls; US cohort: 1,468 cases, 20,158 controls) and BMI (Biobank Japan: 173430 individual; meta-analysis of genetic investigation of anthropometric traits and UK Biobank: 806334 individuals; European Children cohort: 39620 individuals; Population Architecture using Genomics and Epidemiology: 49335 individuals). In MR analyses evaluating the effect of BMI on AIS, the association between BMI and AIS summary statistics was evaluated using the inverse-variance weighted (IVW) method, weighted median method, and Egger regression (MR-Egger) methods in Japanese., Results: Significant causality of genetically decreased BMI on risk of AIS was estimated: IVW method (Estimate (beta) [SE] = -0.56 [0.16], p = 1.8 × 10 -3 ), weighted median method (beta = -0.56 [0.18], p = 8.5 × 10 -3 ) and MR-Egger method (beta = -1.50 [0.43], p = 4.7 × 10 -3 ), respectively. Consistent results were also observed when using the US AIS summary statistic in three MR methods; however, no significant causality was observed when evaluating the effect of AIS on BMI., Conclusions: Our Mendelian randomization analysis using large studies of AIS and GWAS for BMI summary statistics revealed that genetic variants contributing to low BMI have a causal effect on the onset of AIS. This result was consistent with those of epidemiological studies and would contribute to the early detection of AIS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Otomo, Khanshour, Koido, Takeda, Momozawa, Kubo, Kamatani, Herring, Ogura, Takahashi, Minami, Uno, Kawakami, Ito, Sato, Watanabe, Kaito, Yanagida, Taneichi, Harimaya, Taniguchi, Shigematsu, Iida, Demura, Sugawara, Fujita, Yagi, Okada, Hosogane, Kono, Nakamura, Chiba, Kotani, Sakuma, Akazawa, Suzuki, Nishida, Kakutani, Tsuji, Sudo, Iwata, Inami, Wise, Kochi, Matsumoto, Ikegawa, Watanabe and Terao.)

This study is nationwide retrospective multi-center study to investigate the incidence and characteristics of blunt cerebrovascular injury (BCVI) in elderly Japanese patients with traumatic cervical spine injuries (CSI) including spinal cord injury (SCI) without major bone injury. The study enrolled 1512 patients (average age: 75.8 ± 6.9 years; 1007 males, 505 females) from 33 nationwide institutions, and 391 (26%) of the participants had digital subtraction angiography and/or computed tomography angiography. Fifty-three patients were diagnosed as having BCVI by angiography. We assessed neurological evaluation, comorbidities and classification of CSI in the elderly patients with/without BCVI and collected 6-month follow-up data on treatment, complications, and patient outcome. We also statistically analyzed the relative risk (RR) and relationship between BCVI and other factors. Significant differences were identified between BCVI (+) ( n  = 53) and (-) ( n  = 1459) patients with American Spinal Injury Association Impairment Scale (ASIA) A, C, D, cervical fracture, C3-7 injury level (AO type F and/or C), cervical dislocation, spinal surgery for CSI, tetraplegia type of SCI, and/or head injury. Fifty-three (3.5%) elderly patients had CSI complicated by BCVI including 10 (19%) cases of Denver grade I, four (7%) of grade II, 1 (2%) of grade III, 29 (55%) of grade IV, and nine (17%) of grade V. Sixteen cases were treated by interventional radiology. Rates of mortality and brain infarction from BCVI were 0.13% and 0.40%, respectively. RR of BCVI was significantly higher in the elderly cervical injury patients with head injury, severe neurological deficit, ASIA A (RR: 4.33), cervical fracture at the C3-7 level (RR: 7.39), and cervical dislocation at the C1-6 level (RR: 3.06-7.18). In conclusion, 53 (3.5%) elderly patients were complicated with BCVI. BCVI more frequently complicated head injury, severe neurological deficit (ASIA A or tetraplegia), AO type F, and/or C fractures and cervical dislocation in these patients. Six patients (11%) suffered brain infarction and two patients died from BCVI.

Background: Bone morphogenetic protein 2 (BMP2) can enhance posterolateral spinal fusion (PLSF). The minimum effective dose that may stimulate mesenchymal stem cells however remains unknown. Nano-hydroxyapatite (nHAp) polyethylene glycol (PEG)/polylactic acid (PLA) was combined with recombinant human BMP2 (rhBMP2). We in vitro evaluated proliferation, differentiation, and osteogenic genes of human bone marrow mesenchymal stem cells with 0.5, 1.0, and 3.0 μg/mL rhBMP2 doses in this study., Methods: In vitro experimental study was designed to proliferation by a real-time quantitative cell analysis system and the osteogenic differentiation by alkaline phosphatase (ALP) activity and osteogenic marker (Runx2, OPN, and OCN) gene expressions of human derived bone marrow mesenchymal stem cells (hBMMSCs). nHAp was produced by wet chemical process and characterized by Fourier transform infrared spectrophotometer, scanning electron microscopy, and energy-dispersive x-ray spectroscopy. PEG/PLA polymer was produced at a 51:49 molar ratio. 0.5, 1.0, and 3.0 μg/mL rhBMP2 and nHAp was combined with the polymers. hBMMSCs were characterized by multipotency assays and surface markers were assessed by flow cytometer. The hBMMSC-rhBMP2 containing nHAp-PEG/PLA composite interaction was evaluated by transmission electron microscopy. Proliferative effect was evaluated by real-time proliferation analysis, and osteogenic capacity was evaluated by ALP activity assay and qPCR., Results: hBMMSC proliferation in the 0.5 μg/mL rhBMP2 + nHAp-PEG/PLA and the 1.0 μg/mL rhBMP2 + nHAp-PEG/PLA groups were higher compared to control. 1.0 μg/mL rhBMP2 + nHAp-PEG/PLA and 3.0 μg/mL rhBMP2 + nHAp-PEG/PLA containing composites induced ALP activity on days 3 and 10. 0.5 μg/mL rhBMP2 + nHAp-PEG/PLA application stimulated Runx2 and OPN gene expressions., Conclusion: rhBMP2 + nHAp-PEG/PLA composites stimulate hBMMSC proliferation and differentiation. The nHAp-PEG/PLA composite with low dose of rhBMP2 may enhance bone formation in future clinical PLSF applications., Competing Interests: Takashi Kaito is an Editorial Board member of JOR Spine and a co‐author of this article. To minimize bias, they were excluded from all editorial decision‐making related to the acceptance of this article for publication. [Correction added on 23 June 2023, after first online publication: Conflict of Interest statement was revised], (© 2023 The Authors. JOR Spine published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

Objective: The nucleus pulposus (NP) comprises notochordal NP cells (NCs) and chondrocyte-like NP cells (CLCs). Although morphological similarities between CLCs and chondrocytes have been reported, interactions between CLCs and NCs remain unclear. In this study, we aimed to clarify regulatory mechanisms of cells in the NP and chondrocytes. Design: We performed single-cell RNA sequencing (scRNA-seq) analysis of the articular cartilage (AC) and NP of three-year-old cynomolgus monkeys in which NCs were present. We then performed immunohistochemical analysis of NP and distal femur. We added sonic hedgehog (SHH) to primary chondrocyte culture. Results: The scRNA-seq analysis revealed that CLCs and some articular chondrocytes had similar gene expression profiles, particularly related to GLI1, the nuclear mediator of the hedgehog pathway. In the NP, cell-cell interaction analysis revealed SHH expression in NCs, resulting in hedgehog signaling to CLCs. In contrast, no hedgehog ligands were expressed by chondrocytes in AC samples. Immunohistochemical analysis of the distal end of femur indicated that SHH and Indian hedgehog (IHH) were expressed around the subchondral bone that was excluded from our scRNA-seq sample. scRNA-seq data analysis and treatment of primary chondrocytes with SHH revealed that hedgehog proteins mediated an increase in hypoxia-inducible factor 1-alpha (HIF-1α) levels. Conclusion: CLCs and some articular chondrocytes have similar transcriptional profiles, regulated by paracrine hedgehog proteins secreted from NCs in the NP and from the subchondral bone in the AC to promote the HIF-1α pathway., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hagizawa, Koyamatsu, Okada, Kaito and Tsumaki.)

Background Context: Although autologous bone grafting is widely considered as an ideal source for interbody fusion, it still carries a risk of nonunion. The influence of the intervertebral device should not be overlooked. Requirements for artificial spinal devices are to join the vertebrae together and recover the original function of the spine rapidly. Ordered mineralization of apatite crystals on collagen accelerates bone functionalization during the healing process. Particularly, the stable spinal function requires the ingrowth of an ordered collagen and apatite matrix which mimics the intact intervertebral microstructure. This collagen and apatite ordering is imperative for functional bone regeneration, which has not been achieved using classical autologous grafting., Purpose: We developed an intervertebral body device to achieve high stability between the host bone and synthesized bone by controlling the ordered collagen and apatite microstructure., Study Design: This was an in vivo animal study., Methods: Intervertebral spacers with a through-pore grooved surface structure, referred to as a honeycomb tree structure, were produced using metal 3D printing. These spacers were implanted into normal sheep at the L2-L3 or L4-L5 disc levels. As a control group, grafting autologous bone was embedded. The mechanical integrity of the spacer/bone interface was evaluated through push-out tests., Results: The spacer with honeycomb tree structure induced anisotropic trabecular bone growth with textured collagen and apatite orientation in the through-pore and groove directions. The push-out load of the spacer was significantly higher than that of the conventional autologous graft spacer. Moreover, the load was significantly correlated with the anisotropic texture of the newly formed bone matrix., Conclusions: The developed intervertebral spacer guided the regenerated bone matrix orientation of collagen and apatite, resulting in greater strength at the spacer/host bone interface than that obtained using a conventional gold-standard autologous bone graft., Clinical Significance: Our results provide a foundation for designing future spacers for interbody fusion in human., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

The number of elderly patients with cervical trauma is increasing. Such patients are considered to be at high risk for delirium, which is an acute neuropsychological disorder that reduces the patient's capacity to interact with their environment due to impairments in cognition. This study aimed to establish a risk score that predicts delirium in elderly patients with cervical SCI and/or cervical fracture regardless of treatment type. This retrospective cohort study included 1512 patients aged ≥65 years with cervical SCI and/or cervical fracture. The risk factors for delirium according to treatment type (surgical or conservative) were calculated using multivariate logistic regression. A delirium risk score was established as the simple arithmetic sum of points assigned to variables that were significant in the multivariate analyses. Based on the statistical results, the delirium risk score was defined using six factors: old age (≥80 years), hypoalbuminemia, cervical fracture, major organ injury, dependence on pre-injury mobility, and comorbid diabetes. The score's area under the curve for the prediction of delirium was 0.66 ( p < 0.001). Although the current scoring system must be validated with an independent dataset, the system remains beneficial because it can be used after screening examinations upon hospitalization and before deciding the treatment strategy.

Ossification of the posterior longitudinal ligament (OPLL) is a heterotopic ossification that may cause spinal cord compression. With the recent development of computed tomography (CT) imaging, it is known that patients with OPLL often have complications related to ossification of other spinal ligaments, and OPLL is now considered part of ossification of the spinal ligaments (OSL). OSL is known to be a multifactorial disease with associated genetic and environmental factors, but its pathophysiology has not been clearly elucidated. To elucidate the pathophysiology of OSL and develop novel therapeutic strategies, clinically relevant and validated animal models are needed. In this review, we focus on animal models that have been reported to date and discuss their pathophysiology and clinical relevance. The purpose of this review is to summarize the usefulness and problems of existing animal models and to help further the development of basic research on OSL.

We aimed to retrospectively investigate the demographic characteristics and short-term outcomes of traumatic cervical spine injuries in patients with dementia. We enrolled 1512 patients aged ≥ 65 years with traumatic cervical injuries registered in a multicenter study database. Patients were divided into two groups according to the presence of dementia, and 95 patients (6.3%) had dementia. Univariate analysis revealed that the dementia group comprised patients who were older and predominantly female and had lower body mass index, higher modified 5-item frailty index (mFI-5), lower pre-injury activities of daily living (ADLs), and a larger number of comorbidities than patients without dementia. Furthermore, 61 patient pairs were selected through propensity score matching with adjustments for age, sex, pre-injury ADLs, American Spinal Injury Association Impairment Scale score at the time of injury, and the administration of surgical treatment. In the univariate analysis of the matched groups, patients with dementia had significantly lower ADLs at 6 months and a higher incidence of dysphagia up to 6 months than patients without dementia. Kaplan-Meier analysis revealed that patients with dementia had a higher mortality than those without dementia until the last follow-up. Dementia was associated with poor ADLs and higher mortality rates after traumatic cervical spine injuries in elderly patients.

Although the incidence of cervical spinal cord injury (CSCI) with ossification of the posterior longitudinal ligament (OPLL) has increased in older adults, its etiology and neurological outcomes remain unknown. We identified OPLL characteristics and determined whether they influence neurological severity and improvement of CSCI in older patients. This multicenter retrospective cohort study identified 1512 patients aged ≥ 65 years diagnosed with CSCI on admission during 2010-2020. We analyzed CSCI etiology in OPLL patients. We performed propensity score-adjusted analyses to compare neurological outcomes between patients with and without OPLL. Cases were matched based on variables influencing neurological prognosis. The primary neurological outcome was rated according to the American Spine Injury Association (ASIA) impairment scale (AIS) and ASIA motor score (AMS). In 332 OPLL patients, the male-to-female ratio was approximately 4:1. Half of all patients displayed low-energy trauma-induced injury and one-third had CSCI without a bony injury. Propensity score matching created 279 pairs. There was no significant difference in the AIS grade and AMS between patients with and without OPLL during hospitalization, 6 months, and 12 months following injury. OPLL patients tended to exhibit worse neurological findings during injury; nevertheless, OPLL was not associated with poor neurological improvement in older CSCI patients., (© 2023. The Author(s).)

This study developed a system to quantify the lumbar spine's bone mineral density (BMD) in two and three dimensions for osteoporosis screening using quantitative CT images. Measuring the two-dimensional BMD could reproduce the BMD measurement performed in dual-energy X-ray absorptiometry, and an accurate diagnosis of osteoporosis was possible., Purpose: To date, the assessment of bone mineral density (BMD) using CT images has been made in three dimensions, leading to errors in detecting osteoporosis based on the two-dimensional assessments of BMD using dual-energy X-ray absorptiometry (DXA-BMD). Herein, we aimed to develop a system that measures two- and three-dimensional lumbar BMD from quantitative CT images and validated the accuracy of the system in diagnosing osteoporosis with regard to the DXA classification., Methods: Fifty-nine pairs of spinal CT and DXA images were analyzed. First, the three-dimensional BMD was measured at the axial slice of the L1 vertebra on CT images (L1-vBMD). Then, the L1-L4 vertebrae were segmented from the CT images to measure the three-dimensional BMD at the trabecular region of the L1-L4 vertebral bodies (CT-vBMD). Lastly, the segmented vertebrae were projected onto the coronal plane to measure the two-dimensional BMD (CT-aBMD). Each parameter was correlated with DXA-BMD, and the receiver operating characteristic (ROC) curve to diagnose osteoporosis was assessed., Results: The correlation coefficients of DXA-BMD with L1-vBMD, CT-vBMD, and CT-aBMD were 0.364, 0.456, and 0.911, respectively (all p < 0.01). In the ROC curve analysis to diagnose osteoporosis, the area under the curve for CT-aBMD (0.941) was significantly higher than those for L1-vBMD (0.582) and CT-vBMD (0.657) (both p < 0.01)., Conclusion: Compared with L1-vBMD and CT-vBMD, CT-aBMD could accurately predict DXA-BMD and detect patients with osteoporosis. Given that our method can quantify BMD in both two and three dimensions, it could be used to screen for osteoporosis from quantitative CT images., (© 2023. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

For older patients with decreased reserve function, traumatic cervical spine injuries frequently lead to early mortality. However, the prognostic factors for early mortality remain unclear. This study included patients aged ≥65 years and hospitalized for treatment of traumatic cervical spine injuries in 78 hospitals between 2010 and 2020. Early mortality was defined as death within 90 days after injury. We evaluated the relationship between early mortality and the following factors: age, sex, body mass index, history of drinking and smoking, injury mechanisms, presence of a cervical spine fracture and dislocation, cervical ossification of the posterior longitudinal ligament, diffuse idiopathic skeletal hyperostosis, American Spinal Injury Association Impairment Scale, concomitant injury, pre-existing comorbidities, steroid administration, and treatment plan. Overall, 1512 patients (mean age, 75.8 ± 6.9 years) were included in the study. The early mortality rate was 4.0%. Multivariate analysis identified older age (OR = 1.1, p < 0.001), male sex (OR = 3.7, p = 0.009), cervical spine fracture (OR = 4.2, p < 0.001), complete motor paralysis (OR = 8.4, p < 0.001), and chronic kidney disease (OR = 5.3, p < 0.001) as risk factors for early mortality. Older age, male sex, cervical spine fracture, complete motor paralysis, and chronic kidney disease are prognostic factors for early mortality in older patients with traumatic cervical spine injuries.

Background: The Japanese Orthopaedic Association (JOA) guideline for the management of lumbar spinal stenosis (LSS) was first published in 2011. Since then, the medical care system for LSS has changed and many new articles regarding the epidemiology and diagnostics of LSS, conservative treatments such as new pharmacotherapy and physical therapy, and surgical treatments including minimally invasive surgery have been published. In addition, various issues need to be examined, such as verification of patient-reported outcome measures, and the economic effect of revised medical management of patients with lumbar spinal disorders. Accordingly, in 2019 the JOA clinical guidelines committee decided to update the guideline and consequently established a formulation committee. The purpose of this study was to describe the formulation we implemented for the revision of the guideline, incorporating the recent advances of evidence-based medicine., Methods: The JOA LSS guideline formulation committee revised the previous guideline based on the method for preparing clinical guidelines in Japan proposed by the Medical Information Network Distribution Service in 2017. Background and clinical questions were determined followed by a literature search related to each question. Appropriate articles based on keywords were selected from all the searched literature. Using prepared structured abstracts, systematic reviews and meta-analyses were performed. The strength of evidence and recommendations for each clinical question was decided by the committee members., Results: Eight background and 15 clinical questions were determined. Answers and explanations were described for the background questions. For each clinical question, the strength of evidence and the recommendation were both decided, and an explanation was provided., Conclusions: The 2021 clinical practice guideline for the management of LSS was completed according to the latest evidence-based medicine. We expect that this guideline will be useful for all medical providers as an index in daily medical care, as well as for patients with LSS., Competing Interests: Declaration of competing interest All guideline formulation committee members confirmed the COI through self-reporting at the time of preparation of this manuscript. Committee members with any COI declined to vote for applicable recommendation decisions. No companies or any other organizations were directly involved in any text pertaining to the guideline, including the recommendations for all CQs and BQs., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Adolescent idiopathic scoliosis (AIS) is a serious health problem affecting 3% of live births all over the world. Many loci associated with AIS have been identified by previous genome wide association studies, but their biological implication remains mostly unclear. In this study, we evaluated the AIS-associated variants in the 7p22.3 locus by combining in silico, in vitro, and in vivo analyses. rs78148157 was located in an enhancer of UNCX, a homeobox gene and its risk allele upregulated the UNCX expression. A transcription factor, early growth response 1 (EGR1), transactivated the rs78148157-located enhancer and showed a higher binding affinity for the risk allele of rs78148157. Furthermore, zebrafish larvae with UNCX messenger RNA (mRNA) injection developed body curvature and defective neurogenesis in a dose-dependent manner. rs78148157 confers the genetic susceptibility to AIS by enhancing the EGR1-regulated UNCX expression. © 2022 American Society for Bone and Mineral Research (ASBMR)., (© 2022 American Society for Bone and Mineral Research (ASBMR).)

Background: Neuropathic pain (NeP) is pain provoked by damage or disease in the nervous system and about one in three Japanese patients with spinal disorders are highly likely to have NeP. The humanistic and economic burden of illness (BOI) of spine-related NeP represents unmet medical needs that should be addressed. The purpose of this targeted literature review was to synthesize the available evidence on the BOI of spine-related NeP in Japanese patients., Methods: PubMed and ICHUSHI were searched for relevant studies published between January 2010 and December 2020, in English or Japanese. The population included patients with one or more of prespecified spinal disorders and NeP, and outcomes of interest were data related to humanistic or economic burden., Results: Out of 32 studies that assessed the BOI of spine-related disorders in Japan, only six specifically assessed spine-related NeP. Among these studies, five different validated questionnaires were used to measure humanistic burden. Spine-related NeP was consistently shown to be related with a poorer health-related quality of life and higher levels of anxiety and depression compared to the general population as well as patients with nociceptive pain. No articles directly evaluating economic burden were identified in this search, so an exploratory analysis was conducted. Reduction in work productivity by people experiencing spine-related NeP in the whole of Japan were estimated to total JPY 172,266,780,480 per year., Conclusions: The humanistic burden of spine-related NeP on Japanese patients is considerable, not only physically but also mentally. Exploratory analysis of the economic burden illustrates the possibility of substantial societal costs associated with NeP. In order to better understand the depth of BOI and the unmet medical need caused by spine-related NeP, further studies on real-world outcomes are recommended., Competing Interests: Declaration of competing interest T Kaito has received consulting fees from Daiichi Sankyo Co., Ltd. K Okuizumi, S Takada, M Yokoyama and K Saito are full-time employees of Daiichi Sankyo Co., Ltd. B Crawford and K Usuba are full-time employees of Syneos Health. Syneos Health received funding from Daiichi Sankyo Co., Ltd. to conduct the data collection, data analysis and manuscript development., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

A retrospective multicenter study. Body mass index (BMI) is recognized as an important determinant of osteoporosis and spinal postoperative outcomes; however, the specific impact of BMI on surgery for osteoporotic vertebral fractures (OVFs) remains inconclusive. This retrospective multicenter study investigated the impact of BMI on clinical outcomes following fusion surgery for OVFs. 237 OVF patients (mean age, 74.3 years; 48 men and 189 women) with neurological symptoms who underwent spinal fusion were included in this study. Patients were grouped by World Health Organization BMI categories: low BMI (<18.5 kg/m2), normal BMI (≥18.5 and <25 kg/m2), and high BMI (≥25 kg/m2). Patients' backgrounds, surgical method, radiological findings, pain measurements, activities of daily living (ADL), and postoperative complications were compared after a mean follow-up period of 4 years. As results, the proportion of patients able to walk independently was significantly smaller in the low BMI group (75.0%) compared with the normal BMI group (89.9%; P = .01) and the high BMI group (94.3%; P = .04). Improvement in the visual analogue scale for leg pain was significantly less in the low BMI group than the high BMI group (26.7 vs 42.8 mm; P = .046). Radiological evaluation, the Frankel classification, and postoperative complications were not significantly different among all 3 groups. Improvement of pain intensity and ADL in the high BMI group was equivalent or non-significantly better for some outcome measures compared with the normal BMI group. Leg pain and independent walking ability after fusion surgery for patients with OVFs improved less in the low versus the high BMI group. Surgeons may want to carefully evaluate at risk low BMI patients before fusion surgery for OVF because poor clinical results may occur., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)