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Abstract Background The restoration of the functional ability of mesenchymal stem cells (MSCs) using epigenetic modification is very promising for patients with weak osteogenesis ability. This study focused on the acceleration of osteogenesis from MSCs using microRNA (miRNA)2861 and a cell-penetrating peptide (CPP), LK. Methods We performed MSCs penetration test of complex between the LK peptides and miRNA 2861. Three different experiments were performed to investigate the effects of miRNA 2861 on osteogenic differentiation in MSCs: 1) intensity of alizarin red staining, which reflects the status of mineralization by osteoblasts; 2) gene expression related to osteoblast differentiation; and 3) confirmation of corresponding protein translation for comparison with RNA expression levels. Results We found that cLK effectively delivered miRNA 2861 into the cytoplasm of human MSCs and accelerated osteogenic differentiation from MSCs, as well as mineralization. Conclusion The complex of miRNA 2861 with LK may have a positive effect on the osteogenic differentiation from MSCs and mineralization. Therapies using miRNAs combined with LK may be good candidates for the augmentation of osteogenesis in patients.

Abstract Oblique lumbar interbody fusion (OLIF) is a minimally invasive lateral lumbar fusion technique and patients are discharged 1–2 days after surgery. Because OLIF utilizes a retroperitoneal approach close to the superior hypogastric plexus, postoperative urinary retention (POUR) may not be an uncommon problem. The purpose of this study was to present the incidence and outcomes of POUR with a systematic care protocol. The records of 102 consecutive patients (M:F = 34:68; mean age, 68.0 ± 8.4 years) were retrospectively reviewed. After OLIF, the indwelling urinary catheter was immediately removed, and every patient was encouraged to void within 6 h. The POUR care protocol, following a clinical pathway, was based on residual urine (RU), which was monitored with an ultrasound bladder scan after each voiding or every 6 h for 48 h. The incidence rate of POUR was 44% (45/102) at 24 h, 17% (17/102) at 48 h, and 2% (2/102) at 1 month. Preoperative urological symptoms (odds ratio [OR] 3.2) and violation of the protocol (OR 28.3) were risk factors at 24 h. At 48 h, violation of the protocol was the only risk factor (OR 9.6). Identifying risk factors and a preemptive care protocol may reduce permanent POUR.

Abstract We investigated the regulation of histone deacetylases (HDACs) by miR-2861 in the osteoblastic differentiation of human mesenchymal stem cells (MSCs) and miR-2861 binding site by CRISPR activation (CRISPRa). Transfection of miR-2861 into human MSCs was performed and the effect on osteoblast differentiation was analyzed. Using catalytically inactive Cas12a, the CRISPRa system induced targeted overexpression of endogenous miRNA and repressed the luciferase activities of reporters that contained functional miRNA target sites. The delivery of miR-2861 into MSCs enhanced osteoblast differentiation by decreased expressions of the HDAC1, 4 and 5 genes. The mechanism of HDAC5 repression by miR-2861 in humans has not been fully elucidated. To this end, the HDAC5 mRNA sequence was analyzed and a putative primate-specific miR-2861 binding site was identified in the 3’ untranslated region (3’-UTR). CRISPRa was applied to validate the putative binding site and an increase in endogenous miR-2861 was found to repress the expression of a reporter that contained the novel miR-2861 binding site. The delivery of miR-2861 to human MSCs enhanced osteoblast differentiation. In the 3’-UTR, the HDAC5 repression was mediated by the miR-2861 binding site, and miR-2861 promoted osteoblast differentiation via the inhibition of HDAC5 through a primate-specific miRNA binding site. Therefore, miRNAmiR-2861 with the CRISPRa methods might be a good biomaterial for osteogenesis augmentation.

Abstract Background Patients undergo regular clinical follow-up after laminoplasty for cervical myelopathy. However, those whose symptoms significantly improve and remain stable do not need to conform to a regular follow-up schedule. Based on the 1-year postoperative outcomes, we aimed to use a machine-learning (ML) algorithm to predict 2-year postoperative outcomes. Methods We enrolled 80 patients who underwent cervical laminoplasty for cervical myelopathy. The patients’ Japanese Orthopedic Association (JOA) scores (range: 0–17) were analyzed at the 1-, 3-, 6-, and 12-month postoperative timepoints to evaluate their ability to predict the 2-year postoperative outcomes. The patient acceptable symptom state (PASS) was defined as a JOA score ≥ 14.25 at 24 months postoperatively and, based on clinical outcomes recorded up to the 1-year postoperative timepoint, eight ML algorithms were developed to predict PASS status at the 24-month postoperative timepoint. The performance of each of these algorithms was evaluated, and its generalizability was assessed using a prospective internal test set. Results The long short-term memory (LSTM)-based algorithm demonstrated the best performance (area under the receiver operating characteristic curve, 0.90 ± 0.13). Conclusions The LSTM-based algorithm accurately predicted which group was likely to achieve PASS at the 24-month postoperative timepoint. Although this study included a small number of patients with limited available clinical data, the concept of using past outcomes to predict further outcomes presented herein may provide insights for optimizing clinical schedules and efficient medical resource utilization. Trial registration This study was registered as a clinical trial (Clinical Trial No. NCT02487901), and the study protocol was approved by the Seoul National University Hospital Institutional Review Board (IRB No. 1505-037-670).

Objective Classification guides the surgical approach and predicts prognosis. However, existing classifications of spinal schwannomas often result in a high ‘unclassified’ rate. Here, we aim to develop a new comprehensive classification for spinal schwannomas based on their presumed origin. We compared the new classification with the existing classifications regarding the rate of ‘unclassified’. Finally, we assessed the surgical strategies, outcomes, and complications according to each type of the new classification. Methods A new classification with 9 types was created by analyzing the anatomy of spinal nerves and the origin of significant tumor portions and cystic components in preoperative magnetic resonance images. A total of 482 patients with spinal schwannomas were analyzed to compare our new classification with the existing classifications. We defined ‘unclassified’ as the inability to classify a patient with spinal schwannoma using the classification criteria. Surgical approaches and outcomes were also aligned with our new classification. Results Our classification uniquely reported no ‘unclassified’ cases, indicating full applicability. Also, the classification has demonstrated usefulness in predicting the surgical outcome with the approach planned. Gross total removal rates reached 88.0% overall, with type 1 and type 2 tumors at 95.3% and 96.0% respectively. The approach varied with tumor type, with laminectomy predominantly used for types 1, 2, and 9, and facetectomy with posterior fixation used for type 3 tumors. Conclusion The new classification for spinal schwannomas based on presumed origin is applicable to all spinal schwannomas. It could help plan a surgical approach and predict its outcome, compared with existing classifications.

Abstract Dual-position oblique lumbar interbody fusion with fluoroscopy (D-OLIF) requires repositioning the patient to a prone position for pedicle screw insertion. Recently, single-position surgery with navigation has been introduced. However, there are concerns regarding pedicle screw accuracy and achieving appropriate sagittal balance in single-position OLIF with navigation (S-OLIF). The purpose of this study is to evaluate the clinical and radiological outcomes of S-OLIF compared to D-OLIF. A retrospective analysis was conducted on 102 patients who underwent single-level OLIF at a single institution. The patients were divided into two groups: 55 in the S-OLIF group and 47 in the D-OLIF group. The numeric rating scale for back and leg, Oswestry disability index, and walking distance improvements showed no significant difference. However, the EuroQol 5-dimension 5-level index showed higher improvement in the S-OLIF (P = 0.029). The segmental lordosis, lumbar lordosis, and C7 sagittal vertical axis showed no significant difference. S-OLIF had significantly fewer cases of pedicle screw malposition (P = 0.045). Additionally, the surgery time was shorter in the S-OLIF (P = 0.002). In conclusion, S-OLIF exhibited clinical and radiological outcomes comparable to D-OLIF, with the added advantages of reduced surgery time and enhanced accuracy in pedicle screw placement.

Abstract Background Lumbar spinal stenosis (LSS) and spondylolisthesis (SPL) are characterized as degenerative spinal pathologies and share considerable similarities. However, opinions vary on whether to recommend exercise or restrict it for these diseases. Few studies have objectively compared the effects of daily physical activity on LSS and SPL because it is impossible to restrict activities ethnically and practically. We investigated the effect of restricting physical activity due to social distancing (SoD) on LSS and SPL, focusing on the aspect of healthcare burden changes during the pandemic period. Methods We included first-visit patients diagnosed exclusively with LSS and SPL in 2017 and followed them up for two years before and after the implementation of the SoD policy. As controls, patients who first visited in 2015 and were followed for four years without SoD were analyzed. The common data model was employed to analyze each patient’s diagnostic codes and treatments. Hospital visits and medical costs were analyzed by regression discontinuity in time to control for temporal effects on dependent variables. Results Among 33,484 patients, 2,615 with LSS and 446 with SPL were included. A significant decrease in hospital visits was observed in the LSS (difference, -3.94 times/month·100 patients; p = 0.023) and SPL (difference, -3.44 times/month·100 patients; p = 0.026) groups after SoD. This decrease was not observed in the data from the control group. Concerning medical costs, the LSS group showed a statistically significant reduction in median copayment (difference, -$45/month·patient; p

Abstract This study aimed to compare the long-term effects of flexion- and extension-based lumbar exercises on chronic axial low back pain (LBP). This was a 1-year follow-up of a prospective, assessor-blind, randomized controlled trial. Patients with axial LBP (intensity ≥ 5/10) for > 6 months allocated to the flexion or extension exercise group. Patients underwent four sessions of a supervised treatment program and were required to perform their assigned exercises daily at home. Clinical outcomes were obtained at baseline, 1, 3, 6 months, and 1-year. A total of 56 patients (age, 54.3 years) were included, with 27 and 29 in the flexion and extension groups, respectively. Baseline pain and functional scales were similar between both groups. The mean (± standard deviation) baseline average back pain was 6.00 ± 1.00 and 5.83 ± 1.20 in the flexion and extension groups, respectively. At 1-year, the average pain was 3.78 ± 1.40 and 2.26 ± 2.62 (mean between-group difference, 1.52; 95% confidence interval 0.56–2.47; p = 0.002), favoring extension exercise. The extension group tended to have more improvements in current pain, least pain, and pain interference than the flexion group at 1-year. However, there was no group difference in worst pain and functional scales. In this controlled trial involving patients with chronic axial LBP, extension-based lumbar exercise was more effective in reducing pain than flexion-based exercises at 1-year, advocating lumbar extension movement pattern as a component for therapeutic exercise for chronic LBP. Clinical Trial Registration No.: NCT02938689 (Registered on www.clinicaltrial.gov ; first registration date was 19/10/2016).

Abstract Although the role of plain radiographs in diagnosing lumbar spinal stenosis (LSS) has declined in importance since the advent of magnetic resonance imaging (MRI), diagnostic ability of plain radiographs has improved dramatically when combined with deep learning. Previously, we developed a convolutional neural network (CNN) model using a radiograph for diagnosing LSS. In this study, we aimed to improve and generalize the performance of CNN models and overcome the limitation of the single-pose-based CNN (SP-CNN) model using multi-pose radiographs. Individuals with severe or no LSS, confirmed using MRI, were enrolled. Lateral radiographs of patients in three postures were collected. We developed a multi-pose-based CNN (MP-CNN) model using the encoders of the three SP-CNN model (extension, flexion, and neutral postures). We compared the validation results of the MP-CNN model using four algorithms pretrained with ImageNet. The MP-CNN model underwent additional internal and external validations to measure generalization performance. The ResNet50-based MP-CNN model achieved the largest area under the receiver operating characteristic curve (AUROC) of 91.4% (95% confidence interval [CI] 90.9–91.8%) for internal validation. The AUROC of the MP-CNN model were 91.3% (95% CI 90.7–91.9%) and 79.5% (95% CI 78.2–80.8%) for the extra-internal and external validation, respectively. The MP-CNN based heatmap offered a logical decision-making direction through optimized visualization. This model holds potential as a screening tool for LSS diagnosis, offering an explainable rationale for its prediction.

Abstract This study aims to identify healthcare costs indicators predicting secondary surgery for degenerative lumbar spine disease (DLSD), which significantly impacts healthcare budgets. Analyzing data from the National Health Insurance Service-National Sample Cohort (NHIS-NSC) database of Republic of Korea (ROK), the study included 3881 patients who had surgery for lumbar disc herniation (LDH), lumbar spinal stenosis without spondylolisthesis (LSS without SPL), lumbar spinal stenosis with spondylolisthesis (LSS with SPL), and spondylolysis (SP) from 2006 to 2008. Patients were categorized into two groups: those undergoing secondary surgery (S-group) and those not (NS-group). Surgical and interim costs were compared, with S-group having higher secondary surgery costs ($1829.59 vs $1618.40 in NS-group, P = 0.002) and higher interim costs ($30.03; 1.86% of initial surgery costs vs $16.09; 0.99% of initial surgery costs in NS-group, P

Objective Although adult spinal deformity (ASD) surgery aims to restore and maintain alignment, proximal junctional kyphosis (PJK) may occur. While existing scoring systems predict PJK, they predominantly offer a generalized 3-tier risk classification, limiting their utility for nuanced treatment decisions. This study seeks to establish a personalized risk calculator for PJK, aiming to enhance treatment planning precision. Methods Patient data for ASD were sourced from the Korean spinal deformity database. PJK was defined a proximal junctional angle (PJA) of ≥ 20° at the final follow-up, or an increase in PJA of ≥ 10° compared to the preoperative values. Multivariable analysis was performed to identify independent variables. Subsequently, 5 machine learning models were created to predict individualized PJK risk post-ASD surgery. The most efficacious model was deployed as an online and interactive calculator. Results From a pool of 201 patients, 49 (24.4%) exhibited PJK during the follow-up period. Through multivariable analysis, postoperative PJA, body mass index, and deformity type emerged as independent predictors for PJK. When testing machine learning models using study results and previously reported variables as hyperparameters, the random forest model exhibited the highest accuracy, reaching 83%, with an area under the receiver operating characteristics curve of 0.76. This model has been launched as a freely accessible tool at: (https://snuspine.shinyapps.io/PJKafterASD/). Conclusion An online calculator, founded on the random forest model, has been developed to gauge the risk of PJK following ASD surgery. This may be a useful clinical tool for surgeons, allowing them to better predict PJK probabilities and refine subsequent therapeutic strategies.

Abstract Conventional cage and plate (CCP) implants usually used in ACDF surgery, do have limitations such as the development of postoperative dysphagia, adjacent segment degeneration, and soft tissue injury. To reduce the risk of these complications, zero-profile stand-alone cage were developed. We used finite-element modeling to compare the total von Mises stress applied to the bone, disc, endplate, cage and screw when using CCP and ZPSC implants. A 3-dimensional FE (Finite element) analysis was performed to investigate the effects of the CCP implant and ZPSC on the C3 ~ T1 vertebrae. We confirmed that the maximum von Mises stress applied with ZPSC implants was more than 2 times greater in the endplate than that applied with CCP implants. The 3D analysis of the ZPSC model von Mises stress measurements of screw shows areas of higher stress in red. Although using ZPSC implants in ACDF reduces CCP implant-related sequalae such as dysphagia, we have shown that greater von Mises stress is applied to the endplate, and screw when using ZPSC implants. This may explain the higher subsidence rate associated with ZPSC implant use in ACDF. When selecting an implant in ACDF, surgeons should consider patient characteristics and the advantages and disadvantages of each implant type.

Abstract Surgical outcomes of degenerative cervical spinal disease are dependent on the selection of surgical techniques. Although a standardized decision cannot be made in an actual clinical setting, continued education is provided to standardize the medical practice among surgeons. Therefore, it is necessary to supervise and regularly update overall surgical outcomes. This study aimed to compare the rate of additional surgery between anterior and posterior surgeries for degenerative cervical spinal disease using the National Health Insurance Service-National Sample Cohort (NHIS-NSC) nationwide patient database. The NHIS-NSC is a population-based cohort with about a million participants. This retrospective cohort study included 741 adult patients (> 18 years) who underwent their first cervical spinal surgery for degenerative cervical spinal disease. The median follow-up period was 7.3 years. An event was defined as the registration of any type of cervical spinal surgery during the follow-up period. Event-free survival analysis was used for outcome analysis, and the following factors were used as covariates for adjustment: location of disease, sex, age, type of insurance, disability, type of hospital, Charles comorbidity Index, and osteoporosis. Anterior cervical surgery was selected for 75.0% of the patients, and posterior cervical surgery for the remaining 25.0%. Cervical radiculopathy due to foraminal stenosis, hard disc, or soft disc was the primary diagnosis in 78.0% of the patients, and central spinal stenosis was the primary diagnosis in 22.0% of them. Additional surgery was performed for 5.0% of the patients after anterior cervical surgery and 6.5% of the patients after posterior cervical surgery (adjusted subhazard ratio, 0.83; 95% confidence interval, 0.40–1.74). The rates of additional surgery were not different between anterior and posterior cervical surgeries. The results would be helpful in evaluating current practice as a whole and adjusting the health insurance policy.

Abstract Background The endotracheal cuff pressure depends on the airway pressure during positive-pressure ventilation. A high endotracheal cuff pressure may be related to intraoperative coughing, which can be detrimental during neurosurgery. We investigated the incidence of intraoperative coughing and its association with peak inspiratory pressure (PIP) during neurosurgery under general anesthesia without neuromuscular blockade. Methods This retrospective study divided 1656 neurosurgical patients who underwent total intravenous anesthesia without additional neuromuscular blockade after tracheal intubation into high (PIP > 21.6 cmH2O, n = 318) and low (PIP ≤ 21.6 cmH2O, n = 1338) PIP groups. After propensity score matching, 206 patients were selected in each group. Demographic, preoperative, surgical, and anesthetic data were collected retrospectively from electronic medical records and continuous ventilator, infusion pump, and bispectral index data from a data registry. Results Intraoperative coughing occurred in 30 (1.8%) patients, including 9 (0.5%) during the main surgical procedure. Intraoperative coughing was more frequent in the high PIP group than in the low PIP group before (14/318 [4.4%] vs. 16/1338 [1.2%], P

Background: The clinical healing environment after a posterior spinal arthrodesis surgery is one of the most clinically challenging bone-healing environments across all orthopedic interventions due to the absence of a contained space and the need to form de novo bone. Our group has previously reported that sclerostin in expressed locally at high levels throughout a developing spinal fusion. However, the role of sclerostin in controlling bone fusion remains to be established. Methods: We computationally identified two FDA-approved drugs, as well as a single novel small-molecule drug, for their ability to disrupt the interaction between sclerostin and its receptor, LRP5/6. The drugs were tested in several in vitro biochemical assays using murine MC3T3 and MSCs, assessing their ability to (1) enhance canonical Wnt signaling, (2) promote the accumulation of the active (non-phosphorylated) form of β-catenin, and (3) enhance the intensity and signaling duration of BMP signaling. These drugs were then tested subcutaneously in rats as standalone osteoinductive agents on plain collagen sponges. Finally, the top drug candidates (called VA1 and C07) were tested in a rabbit posterolateral spine fusion model for their ability to achieve a successful fusion at 6 wk. Results: We show that by controlling GSK3b phosphorylation our three small-molecule inhibitors (SMIs) simultaneously enhance canonical Wnt signaling and potentiate canonical BMP signaling intensity and duration. We also demonstrate that the SMIs produce dose-dependent ectopic mineralization in vivo in rats as well as significantly increase posterolateral spine fusion rates in rabbits in vivo, both as standalone osteogenic drugs and in combination with autologous iliac crest bone graft. Conclusions: Few if any osteogenic small molecules possess the osteoinductive potency of BMP itself – that is, the ability to form de novo ectopic bone as a standalone agent. Herein, we describe two such SMIs that have this unique ability and were shown to induce de novo bone in a stringent in vivo environment. These SMIs may have the potential to be used in novel, cost-effective bone graft substitutes for either achieving spinal fusion or in the healing of critical-sized fracture defects. Funding: This work was supported by a Veteran Affairs Career Development Award (IK2-BX003845).

Objective Neuropathic pain is a common secondary complication of spinal cord injury (SCI). N-methyl-D-aspartate (NMDA) receptor activation is critical for hypersensitivity in neuropathic pain. This activation requires the binding of both glutamate and the D-serine co-agonist to the NMDA glycine site. We evaluated the effects of D-serine on neuropathic pain after SCI and explored the underlying molecular mechanisms. Methods Anesthetized rats underwent T9 spinal cord contusion (130 kdyn). D-serine (500 and 1,000 mg/kg) and MK-801 hydrogen maleate (2.0 mg/kg) were injected daily for 2 weeks, starting the day after SCI. Functional outcomes were assessed according to the Basso, Beattie, and Bresnahan scale, while histological outcomes were evaluated based on lesion volume and spared tissue area. Mechanical allodynia and thermal hyperalgesia were evaluated by measuring the withdrawal threshold of a von Frey filament and hot/cold plate latency. Western blotting was performed to determine the expression levels of Trpv1, Nav1.9, calcitonin gene-related peptide (CGRP), and β-actin in damaged tissue. Results The withdrawal threshold values and latency of the D-serine group were significantly lower than those of the noninjection group. The MK-801 group showed higher threshold values and latencies than the other groups. Western blotting showed increased Nav1.9 and Trpv1 levels and lower CGRP levels in the D-serine group, whereas the MK-801 group showed the opposite results. Conclusion D-serine increases neuropathic pain after traumatic SCI by mediating the NMDA receptor. NMDA receptor antagonists alleviate neuropathic pain after traumatic SCI.

Objective This study compared the radiological and clinical outcomes with transforaminal lumbar interbody fusion (TLIF) to evaluate the effect of indirect decompression through oblique lumbar interbody fusion (OLIF) as revision surgery. Methods We enrolled patients who underwent single-level fusion with revision surgery at the same level as the previous decompression level. We retrospectively reviewed 25 patients who underwent OLIF from 2017 to 2018 and 25 who received TLIF from 2014 to 2018. Radiologic and clinical outcomes were evaluated by cross-sectional area (CSA) of the spinal canal, thickness and area of ligamentum flavum (LF), subsidence, disc height, fusion rate, Oswestry Disability Index (ODI), and visual analogue scale (VAS). Results Compared with OLIF, the thickness and area of the LF after surgery were significantly less in TLIF, and the resulting CSA extension was also significantly higher. However, both groups showed improvement in ODI and VAS after surgery, and there was no difference between the groups. Complications related to the posterior approach in TLIF were 4 cases, and in OLIF, there were 2 cases that underwent additional posterior decompression surgery and 6 cases of transient paresthesia. Conclusion Since complications associated with the posterior approach can be avoided, OLIF is a safer and useful minimally invasive surgery. Therefore, appropriate indications are applied, OLIF is a good alternative to TLIF when revision surgery is considered.

Objective Oblique lumbar interbody fusion (OLIF) involves inserting large cages into the interbody disc space. This expands the spinal canal and neural foramen by stretching the ligament flavum and releasing the facet joint, resulting in indirect neural decompression. Our objective was to investigate the changes in the spinal canal and ligament flavum over time after OLIF. Methods This was a prospective observational study involving 30 patients who underwent OLIF L4–5 between 2015 and 2018. In total, 27 of the 30 patients underwent preoperative, early follow-up (< 5 days), and late follow-up (10–14 months) magnetic resonance imaging to measure the area of the spinal canal and ligament flavum. Based on the results, the patients were divided into subsidence and nonsubsidence groups for further analysis. Results After OLIF, the spinal canal area gradually increased during the preoperative, early postoperative, and late postoperative periods (p

According to the new 2021 World Health Organization (WHO) classification of tumors of the central nervous system (CNS) the classification of the primary intramedullary spinal cord tumors (IM-SCT) follows that of CNS tumors. However, since the genetics and methylation profile of ependymal tumors depend on the location of the tumor, the ‘spinal (SP)’ should be added for the ependymoma (EPN) and subependymoma (SubEPN). For an evidence-based review, the authors reviewed SCTs in the archives of the Seoul National University Hospital over the past decade. The frequent pathologies of primary IM-SCT were SP-EPN (45.1%), hemangioblastoma (20.0%), astrocytic tumors (17.4%, including pilocytic astrocytoma [4.6%] and diffuse midline glioma, H3 K27-altered [4.0%]), myxopapillary EPN (11.0%), and SP-subEPN (3.0%) in decreasing order. IDH-mutant astrocytomas, oligodendrogliomas, glioneuronal tumors, embryonal tumors, and germ cell tumors can occur but are extremely rare in the spinal cord. Genetic studies should support for the primary IM-SCT classification. In the 2021 WHO classifications, extramedullary SCT did not change significantly but contained several new genetically defined types of mesenchymal tumors. This article focused on primary IM-SCT for tumor frequency, age, sex difference, pathological features, and genetic abnormalities, based on a single-institute experience.

Abstract MRI is the primary diagnostic modality for spinal cord tumors. However, its validity has never been vigorously scrutinized in daily routine clinical practice, where MRI tissue diagnosis is usually not a single one but multiple ones with several differential diagnoses. Here, we aimed to assess the validity of MRI in terms of predicting the pathology and location of the tumor in routine clinical settings. We analyzed 820 patients with primary spinal cord tumors, who have a pathological diagnosis and location in the operation record which were confirmed. We modified traditional measures for validity based upon a set of diagnoses instead of a single diagnosis. Sensitivity and specificity and positive and negative predictabilities were evaluated for the tumor location and pathology. For tumor location, 456 were intradural extramedullary; 165 were intramedullary, and 156 were extradural. The overall sensitivity and specificity were over 90.0%. However, the sensitivity became lower when the tumor resided simultaneously in two spaces such as in the intradural-and-extradural or intramedullary-and-extramedullary space (54.6% and 30.0%, respectively). Most common pathology was schwannoma (n = 416), followed by meningioma (114) and ependymoma (87). Sensitivities were 93.3%, 90.4%, and 89.7%, respectively. Specificities were 70.8%, 82.9%, and 76.0%. In rare tumors such as neurofibromas, and diffuse midline gliomas, the sensitivity was much lower (less than 30%). For common locations and pathologies, the validity of MRI is generally acceptable. However, for rare locations and pathologies, MRI diagnosis still needs some improvement.

Objective Total en bloc spondylectomy (TES) is a curative surgical method for spinal tumors. After resecting the 3 spinal columns, reconstruction is of paramount importance. We present cases of mechanical failure and suggest strategies for salvage surgery. Methods The medical records of 19 patients who underwent TES (9 for primary tumors and 10 for metastatic tumors) were retrospectively reviewed. Previously reported surgical techniques were used, and the surgical extent was 1 level in 16 patients and 2 levels in 3 patients. A titanium-based mesh-type interbody spacer filled with autologous and cadaveric bone was used for anterior support, and a pedicle screw/rod system was used for posterior support. Radiotherapy was performed in 11 patients (pre-TES, 5; post-TES, 6). They were followed up for 59 ± 38 months (range, 11–133 months). Results During follow-up, 8 of 9 primary tumor patients (89%) and 5 of 10 metastatic tumor patients (50%) survived (mean survival time, 124 ± 8 months vs. 51 ± 13 months; p=0.11). Mechanical failure occurred in 3 patients (33%) with primary tumors and 2 patients (20%) with metastatic tumors (p=0.63). The mechanical failure-free time was 94.4 ± 14 months (primary tumors, 95 ± 18 months; metastatic tumors, 68 ± 16 months; p=0.90). Revision surgery was performed in 4 of 5 patients, and bilateral broken rods were replaced with dual cobalt-chromium alloy rods. Repeated rod fractures occurred in 1 of 4 patients 2 years later, and the third operation (with multiple cobalt-chromium alloy rods) was successful for over 6 years. Conclusion Considering the difficulty of reoperation and patients’ suffering, preemptive use of a multiple-rod system may be advisable.

Background and objectivesOblique lumbar interbody fusion (OLIF) procedures involve anterior insertion of interbody cage in lateral position. Following OLIF, insertion of pedicle screws and rod system is performed in a prone position (OLIF-con). The location of the cage is important for restoration of lumbar lordosis and indirect decompression. However, inserting the cage at the desired location is difficult without reduction of spondylolisthesis, and reduction after insertion of interbody cage may limit the amount of reduction. Recent introduction of spinal navigation enabled both surgical procedures in one lateral position (OLIF-one). Therefore, reduction of spondylolisthesis can be performed prior to insertion of interbody cage. The objective of this study was to compare the reduction of spondylolisthesis and the placement of cage between OLIF-one and OLIF-con.MethodsWe retrospectively reviewed 72 consecutive patients with spondylolisthesis for this study; 30 patients underwent OLIF-one and 42 underwent OLIF-con. Spinal navigation system was used for OLIF-one. In OLIF-one, the interbody cage was inserted after reducing spondylolisthesis, whereas in OLIF-con, the cage was inserted before reduction. The following parameters were measured on X-rays: pre- and postoperative spondylolisthesis slippage, reduction degree, and the location of the cage in the disc space.ResultsBoth groups showed significant improvement in back and leg pains (p < .05). Transient motor or sensory changes occurred in three patients after OLIF-con and in two patients after OLIF-one. Pre- and postoperative slips were 26.3±7.7% and 6.6±6.2% in OLIF-one, and 23.1±7.0% and 7.4±5.8% in OLIF-con. The reduction of slippage was 74.4±6.3% after OLIF-one and 65.4±5.7% after OLIF-con, with a significant difference between the two groups (p = .04). The cage was located at 34.2±8.9% after OLIF-one and at 42.8±10.3% after OLIF-con, with a significant difference between the two groups (p = .004).ConclusionSwitching the sequence of surgical procedures with OLIF-one facilitated both the reduction of spondylolisthesis and the placement of the cage at the desired location.

IntroductionFull-endoscopic lumbar discectomy (FELD) is a type of minimally invasive spinal surgery for lumbar disc herniation (LDH). Sufficient evidence exists to recommend FELD as an alternative to standard open microdiscectomy, and some patients prefer FELD due to its minimally invasive nature. However, in the Republic of Korea, the National Health Insurance System (NHIS) controls the reimbursement and use of supplies for FELD, but FELD is not currently reimbursed by the NHIS. Nonetheless, FELD has been performed upon patients' request, but providing FELD for patients' sake is inherently an unstable arrangement in the absence of a practical reimbursement system. The purpose of this study was to conduct a cost-utility analysis of FELD to suggest appropriate reimbursements.MethodThis study was a subgroup analysis of prospectively collected data including 28 patients who underwent FELD. All patients were NHIS beneficiaries and followed a uniform clinical pathway. Quality-adjusted life years (QALYs) were assessed with a utility score using the EuroQol 5-Dimension (EQ-5D) instrument. The costs included direct medical costs incurred at the hospital for 2 years and the price of the electrode ($700), although it was not reimbursed. The costs and QALYs gained were used to calculate the cost per QALY gained.ResultPatients' mean age was 43 years and one-third (32%) were women. L4-5 was the most common surgical level (20/28, 71%) and extrusion was the most common type of LDH (14, 50%). Half of the patients (15, 54%) had jobs with an intermediate level of activity. The preoperative EQ-5D utility score was 0.48±0.19. Pain, disability, and the utility score significantly improved starting 1 month postoperatively. The average EQ-5D utility score during 2 years after FELD was estimated as 0.81 (95% CI: 0.78-0.85). For 2 years, the mean direct costs were $3,459 and the cost per QALY gained was $5,241.ConclusionThe cost-utility analysis showed a quite reasonable cost per QALY gained for FELD. A comprehensive range of surgical options should be provided to patients, for which a practical reimbursement system is a prerequisite.

ObjectivePosterior full-endoscopic cervical foraminotomy (PECF) is one of minimally invasive surgical techniques for cervical radiculopathy. Because of minimal disruption of posterior cervical structures, such as facet joint, cervical kinematics was minimally changed. However, a larger resection of facet joint is required for cervical foraminal stenosis (FS) than disc herniation (DH). The objective was to compare the cervical kinematics between patients with FS and DH after PECF.MethodsConsecutive 52 patients (DH, 34 vs. FS, 18) who underwent PECF for single-level radiculopathy were retrospectively reviewed. Clinical parameters (neck disability index, neck pain and arm pain), and segmental, cervical and global radiological parameters were compared at postoperative 3, 6, and 12 months, and yearly thereafter. A linear mixed-effect model was used to assess interactions between groups and time. Any occurrence of significant pain during follow-up was recorded during a mean follow-up period of 45.5 months (range 24-113 months).ResultsClinical parameters improved after PECF, with no significant differences between groups. Recurrent pain occurred in 6 patients and surgery (PECF, anterior discectomy and fusion) was performed in 2 patients. Pain-free survival rate was 91% for DH and 83% for FS, with no significant difference between the groups (P = 0.29). Radiological changes were not different between groups (P > 0.05). Segmental neutral and extension curvature became more lordotic. Cervical curvature became more lordotic on neutral and extension X-rays, and the range of cervical motion increased. The mismatch between T1-slope and cervical curvature decreased. Disc height did not change, but the index level showed degeneration at postoperative 2 years.ConclusionClinical and radiological outcomes after PECF were not different between DH and FS patients and kinematics were significantly improved. These findings may be informative in a shared decision-making process.

Background: Few studies directly comparing minimally invasive (MI) transforaminal lumbar interbody fusion (TLIF) and open TLIF offering long-term follow-up data have been performed to date. Therefore, we sought to compare mid- to long-term outcomes between these two surgical approaches. Methods: This was a retrospective data analysis of two surgical groups. We analyzed the details of 97 patients with degenerative lumbar disease who were treated with MI TLIF (n = 55) or open TLIF (n = 42) between 2011–2014 and had at least seven years of follow-up data available. Peri- and postoperative outcomes were compared. To evaluate rates of adjacent segment disease (ASD) and revisions, frequencies of radiologic, symptomatic, and operative ASD were analyzed accordingly. Results: In terms of clinical outcome, the Oswestry Disability Index and visual analog scale scores were significantly reduced, with no difference between the groups. However, data for several peri- and postoperative outcomes, including perioperative blood loss, ambulation day, hospital stay, and operation time, varied in a manner favoring the MI TLIF group (P < 0.05). Rates of radiologic ASD and symptomatic ASD were significantly higher in the open TLIF group beginning at five years of follow-up (P < 0.05), while the rate of operative ASD and the revision rate were similar between the groups. Other long-term outcomes, including fusion rate and complications, remained similar between the two groups at 7 years. Conclusion: Patients undergoing MI TLIF showed favorable immediate postoperative outcomes and less radiographic ASD. However, the rates of fusion and operative ASD remained similar between the two groups after 7 years of follow-up.

Background: The clinical healing environment after a posterior spinal arthrodesis surgery is one of the most clinically challenging bone-healing environments across all orthopedic interventions due to the absence of a contained space and the need to form de novo bone. Our group has previously reported that sclerostin in expressed locally at high levels throughout a developing spinal fusion. However, the role of sclerostin in controlling bone fusion remains to be established. Methods: We computationally identified two FDA-approved drugs, as well as a single novel small-molecule drug, for their ability to disrupt the interaction between sclerostin and its receptor, LRP5/6. The drugs were tested in several in vitro biochemical assays using murine MC3T3 and MSCs, assessing their ability to (1) enhance canonical Wnt signaling, (2) promote the accumulation of the active (non-phosphorylated) form of ß-catenin, and (3) enhance the intensity and signaling duration of BMP signaling. These drugs were then tested subcutaneously in rats as standalone osteoinductive agents on plain collagen sponges. Finally, the top drug candidates (called VA1 and C07) were tested in a rabbit posterolateral spine fusion model for their ability to achieve a successful fusion at 6 wk. Results: We show that by controlling GSK3b phosphorylation our three small-molecule inhibitors (SMIs) simultaneously enhance canonical Wnt signaling and potentiate canonical BMP signaling intensity and duration. We also demonstrate that the SMIs produce dose-dependent ectopic mineralization in vivo in rats as well as significantly increase posterolateral spine fusion rates in rabbits in vivo, both as standalone osteogenic drugs and in combination with autologous iliac crest bone graft. Conclusions: Few if any osteogenic small molecules possess the osteoinductive potency of BMP itself - that is, the ability to form de novo ectopic bone as a standalone agent. Herein, we describe two such SMIs that have this unique ability and were shown to induce de novo bone in a stringent in vivo environment. These SMIs may have the potential to be used in novel, cost-effective bone graft substitutes for either achieving spinal fusion or in the healing of critical-sized fracture defects. Funding: This work was supported by a Veteran Affairs Career Development Award (IK2-BX003845). [ABSTRACT FROM AUTHOR]

Objective : Preoperative transarterial embolization (TAE) of tumor feeders in hypervascular spine metastasis is known to reduce intraoperative estimated blood loss (EBL) during surgery. The effect of TAE varies for several reasons, and one controllable factor is the timing between embolization and surgery. However, the adequate timing remains unclear. This study aimed to evaluate the timing and other factors that reduce EBL in spinal metastasis surgery through a meta-analysis. Methods : A comprehensive database search was performed to identify direct comparative studies of EBL stratified by the timing of surgery after TAE for spinal metastasis. EBL was analyzed according to the timing of surgery and other factors. Subgroup analyses were also performed. The difference in EBL was calculated as the mean difference (MD) and 95% confidence interval (CI). Results : Among seven studies, 196 and 194 patients underwent early and late surgery after TAE, respectively. The early surgery was defined as within 1–2 days after TAE, while the late surgery group received surgery later. Overall, the MD in EBL was not different according to the timing of surgery (MD, 86.3 mL; 95% CI, -95.5 to 268.1 mL; p=0.35). A subgroup analysis of the complete embolization group demonstrated that patients who underwent early surgery within 24 hours after TAE had significantly less bleeding (MD, 233.3 mL; 95% CI, 76.0 to 390.5 mL; p=0.004). In cases of partial embolization, EBL was not significantly different regardless of the time interval. Conclusion : Complete embolization followed by early spinal surgery within 24 hours may reduce intraoperative bleeding for the patients with hypervascular spinal metastasis. [ABSTRACT FROM AUTHOR]

Objective : The ossification of the ligamentum flavum (OLF) is one of the major causes of thoracic myelopathy. Surgical decompression with or without instrumented fusion is the mainstay of treatment. However, few studies have reported on the added effect of instrumented fusion. The objective of this study was to compare clinical and radiological outcomes between surgical decompression without instrumented fusion (D-group) and that with instrumented fusion (F-group). Methods : A retrospective review was performed on 28 patients (D-group, n=17; F-group, n=11) with thoracic myelopathy due to OLF. The clinical parameters compared included scores of the Japanese Orthopedic Association (JOA), the Visual analogue scale of the back and leg (VAS-B and VAS-L), and the Korean version of the Oswestry disability index (K-ODI). Radiological parameters included the sagittal vertical axis (SVA), the pelvic tilt (PT), the sacral slope (SS), the thoracic kyphosis angle (TKA), the segmental kyphosis angle (SKA) at the operated level, and the lumbar lordosis angle (LLA; a negative value implying lordosis). These parameters were measured preoperatively, 1 year postoperatively, and 2 years postoperatively, and were compared with a linear mixed model. Results : After surgery, all clinical parameters were significantly improved in both groups, while VAS-L was more improved in the Fgroup than in the D-group (-3.4±2.5 vs. -1.3±2.2, p=0.008). Radiological outcomes were significantly different in terms of changes in TKA, SKA, and LLA. Changes in TKA, SKA, and LLA were 2.3°±4.7°, -0.1°±1.4°, and -1.3°±5.6° in the F-group, which were significantly lower than 6.8°±6.1°, 3.0°±2.8°, and 2.2°±5.3° in the D-group, respectively (p=0.013, p<0.0001, and p=0.037). Symptomatic recurrence of OLF occurred in one patient of the D-group at postoperative 24 months. Conclusion : Clinical improvement was achieved after decompression surgery for OLF regardless of whether instrumented fusion was added. However, adding instrumented fusion resulted in better outcomes in terms of lessening the progression of local and regional kyphosis and improving leg pain. Decompression with instrumented fusion may be a better surgical option for thoracic OLF. [ABSTRACT FROM AUTHOR]

Despite numerous studies, the pathogenesis of ossification of the posterior longitudinal ligament (OPLL) is still unclear. Previous genetic studies proposed variations in genes related to bone and collagen as a cause of OPLL. It is unclear whether the upregulations of those genes are the cause of OPLL or an intermediate result of endochondral ossification process. Causal variations may be in the inflammation-related genes supported by clinical and updated genomic studies. OPLL demonstrates features of genetic diseases but can also be induced by mechanical stress by itself. OPLL may be a combination of various diseases that share ossification as a common pathway and can be divided into genetic and idiopathic. The phenotype of OPLL can be divided into continuous (including mixed) and segmental (including localized) based on the histopathology, prognosis, and appearance. Continuous OPLL shows substantial overexpression of osteoblast-specific genes, frequent upper cervical involvement, common progression, and need for surgery, whereas segmental OPLL shows moderate-to-high expression of these genes and is often clinically silent. Genetic OPLL seems to share clinical features with the continuous type, while idiopathic OPLL shares features with the segmental type. Further genomic studies are needed to elucidate the relationship between genetic OPLL and phenotype of OPLL. [ABSTRACT FROM AUTHOR]

Intervertebral disc degeneration is the main contributor to low back pain, now the leading cause of disability worldwide. Gene transfer, either in a therapeutic attempt or in basic research to understand the mechanisms of disc degeneration, is a fascinating and promising tool to manipulate the complex physiology of the disc. Viral vectors based on the adeno-associated virus (AAV) have emerged as powerful transgene delivery vehicles yet a systematic investigation into their respective tropism, transduction efficiency, and relative toxicity have not yet been performed in the disc in vivo. Herein, we used in vivo bioluminescence imaging to systematically compare multiple AAV serotypes, injection volumes, titers, promoters, and luciferase reporters to determine which result in high transduction efficiency of murine nucleus pulposus (NP) cells in vivo. We find that AAV6 using a CAG promoter to drive transgene expression, delivered into the NP of murine caudal discs at a titer of 1011 GC/mL, provides excellent transduction efficiency/kinetics and low toxicity in vivo. We also show, for the first time, that the transduction of NP cells can be significantly boosted in vivo by the use of small cell permeabilization peptides. Finally, to our knowledge, we are the first to demonstrate the use of optical tissue clearing and three-dimensional lightsheet microscopy in the disc, which was used to visualize fine details of tissue and cell architecture in whole intact discs following AAV6 delivery. Taken together, these data will contribute to the success of using AAV-mediated gene delivery for basic and translational studies of the IVD.