Effects of Palliative Surgical Treatment for Spinal Metastases on the Patient's Quality of Life With a Focus on the Segment of the Metastasis: A Prospective Multicenter Study.

STUDY DESIGN: Prospective multicenter study. OBJECTIVES: Palliative surgery is crucial for maintaining the quality of life (QOL) in patients with spinal metastases. This study aimed to compare the short-term outcomes of QOL after palliative surgery between patients with metastatic spinal tumors at different segments. METHODS: We prospectively compared the data of 203 patients with spinal metastases at 2-3 consecutive segments who were divided into the following three groups: cervical, patients with cervical spine lesions; thoracic, patients with upper-middle thoracic spine lesions; and TL/L/S, patients with lesions at the thoracolumbar junction and lumbar and sacral regions. Preoperative and postoperative EuroQol 5-dimension (EQ5D) 5-level were compared. RESULTS: All groups exhibited improvement in the Frankel grade, performance status, pain, Barthel index, EQ5D health state utility value (HSUV), and EQ5D visual analog scale (VAS) postoperatively. Although preoperative EQ5D HSUVs did not significantly differ between the groups (cervical, 0.461 ± 0.291; thoracic, 0.321 ± 0.292; and TL/L/S, 0.376 ± 0.272), the thoracic group exhibited significantly lower postoperative EQ5D HSUVs than the other two groups (cervical, 0.653 ± 0.233; thoracic, 0.513 ± 0.252; and TL/L/S, 0.624 ± 0.232). However, postoperative EQ5D VAS was not significantly different between the groups (cervical, 63.4 ± 25.8; thoracic, 54.7 ± 24.5; and TL/L/S, 61.7 ± 21.9). CONCLUSIONS: Palliative surgery for metastatic spinal tumors provided comparable QOL improvement, irrespective of the spinal segment involved. Patients with upper and middle thoracic spinal metastases had poorer QOL outcomes than those with metastases in other segments; however, sufficient QOL improvement was achieved.

Does the presence or absence of preoperative lower extremity neurologic symptoms influence postoperative clinical outcome in patients with cervical intradural extramedullary tumors?: a single-center retrospective comparative study.

STUDY DESIGN: Retrospective comparative study OBJECTIVES: To investigate whether the presence or absence of preoperative lower extremities neurological symptoms (LENS) influences clinical outcomes following tumor resection in patients with cervical intradural extramedullary (IDEM) tumors. SETTING: The single institution in Japan. METHODS: Ninety-two patients with cervical IDEM tumors requiring surgical resection were included. Based on the degree of preoperative LENS assessed using the modified McCormick scale (MMCS), patients were categorized into LENS (-) and (+) groups. Demographic and surgical characteristics were compared between both groups. RESULTS: There were no significant differences observed in sex, tumor location, tumor size, surgical time, estimated blood loss, approach for tumorectomy, or tumor histopathology between the two groups. Additionally, the overall surgical outcomes were favorable for both groups. At the final follow-up, 91.1% of the patients in the LENS (+) group were able to walk without support. Improvement in LENS was observed after surgery in most patients with preoperative MMCS II-IV, but it persisted in approximately 40% of patients with preoperative MMCS V. In the LENS (+) group, there were no significant differences in demographic or surgical data between the patients with MMCS I and II-III at the final follow-up. CONCLUSIONS: Regardless of the presence or absence of preoperative LENS, clinical improvement was observed after tumor resection in most patients with cervical IDEM tumors. These findings suggest that neurological status is likely to improve sufficiently if tumor resection is performed before preoperative LENS deteriorates to an extremely severe stage as MMCS V.

Clinical Implications of Surgical Resection without Spinal Fixation in Lumbar Dumbbell Tumors: Evaluating Postoperative Lumbar Alignment and Patient Outcomes.

OBJECTIVES: This study examined radiographic changes in local and global spinal alignments and clinical outcomes following tumor resection without spinal fixation in patients with lumbar dumbbell tumors (LDTs). METHODS: We included 28 patients with LDTs who were followed for at least two years after surgery. We analyzed variations in the outcome variables by measuring individual coronal and sagittal parameters from radiographs. Clinical outcomes were assessed using the modified McCormick scale (MMCS), the Japanese Orthopaedic Association (JOA) score, and the visual analog scale (VAS). To evaluate the impact of tumor location on these outcomes, we categorized the patients into three groups based on tumor location: Upper (T12-L1), Middle (L2-3), or Lower (L4-S1) group. RESULTS: The local and global spinal parameters (including Cobb angle, cervical lordosis, T1 slope, thoracic kyphosis, thoracolumbar kyphosis, lumbar lordosis [global, upper, middle, lower], sacral slope, pelvic incidence, pelvic tilt) did not show significant changes after surgery. Preoperatively, all patients experienced gait disturbances, but at the final follow-up, nearly all of them (27 cases, 96.4%) could walk without support. The JOA score and VAS demonstrated significant postoperative improvements. There were no statistically significant group differences in postoperative coronal and sagittal profiles or clinical outcomes among the upper, middle, and lower groups. CONCLUSIONS: Tumor resection without spinal fixation had no substantial impact on local and global spinal alignments and led to satisfactory clinical outcomes, suggesting that spinal fixation may not always be necessary when resecting LDTs.

Assessment of the Postoperative Progression in Patients With Intramedullary Spinal Cord Tumors Based on the Severity of Preoperative Gait Disturbance.

STUDY DESIGN: Retrospective comparative study. OBJECTIVES: This study aimed to determine whether the severity of preoperative gait disturbance remains after surgical resection in patients with intramedullary spinal cord tumors (IMSCTs), and to identify any factors influencing poor improvement in postoperative gait disturbance. METHODS: The study included a total of 128 patients with IMSCTs requiring surgical excision between 2006 and 2019. Based on the degree of preoperative gait disturbance assessed by the modified McCormick scale (MMCS) grade, patients were categorized into Mild (I-II) and Severe (III-V) groups. The mean postoperative follow-up period was 55.5 ± 34.3 months, and demographic and surgical characteristics were compared between the two groups. RESULTS: Significant differences were observed in age at surgery, tumor location, tumor size, estimated blood loss, intraoperative motor-evoked potential disappearance, extent of resection, and tumor histopathology between the Mild and Severe groups. In the Mild group, at the final follow-up, only 7.3% of patients experienced improvement, 56.0% showed no changes, and 36.7% experienced deterioration. Conversely, in the Severe group, 26.3% of patients experienced improvement, 31.6% showed no changes, and 42.1% experienced deterioration. Tumor location and age at surgery were identified as factors correlated with poor improvement in postoperative gait disturbance in the Mild group. CONCLUSIONS: Irrespective of the preoperative gait disturbance degree, approximately 40% of patients with IMSCTs experienced deterioration in gait after tumor resection. For preoperative MMCS grade I-II cases, older age at surgery and thoracic IMSCTs would be important factors associated with poor improvement in postoperative gait disturbance.

Does the presence of preoperative neck pain impact clinical outcomes after posterior decompression in patients with cervical ossification of the posterior longitudinal ligament?: Retrospective multicenter cohort study.

STUDY DESIGN: Retrospective multicenter study. OBJECTIVES: To evaluate how preoperative neck pain influences clinical outcomes following posterior decompression for cervical ossification of the posterior longitudinal ligament (OPLL). SETTING: Fourteen medical institutions in Japan. METHODS: We enrolled 90 patients with cervical OPLL who underwent posterior decompression and were followed for a minimum of two years. We collected demographic data, medical history, and imaging findings. Patients were divided into two groups based on preoperative neck pain presence (Pre-op. neck pain (-) and (+) groups), and their outcomes were compared. RESULTS: There were no significant differences in patient demographics between the Pre-op. neck pain (-) and (+) groups. Both groups showed similar distributions of ossification types and K-line positivity. Perioperative complications were comparable between the two groups. Radiographic analysis revealed no significant differences in C2-7 angles or cervical range of motion, pre- and postoperatively. Both groups demonstrated significant improvement in postoperative Japanese orthopedic association (JOA) scores, but there were no significant differences in scores or recovery rates. In the Pre-op. neck pain (-) group, factors associated with appearance of postoperative neck pain included pre- and postoperative lower JOA scores and larger C2-7 angles in neutral and extension positions. CONCLUSIONS: It emerges that lower pre- and postoperative JOA scores or larger C2-7 angles in neutral and extension positions predispose to postoperative neck pain even in those patients without preoperative neck pain. Therefore, this is worth discussing at the time of consenting patients for surgical decompression and fixation.

Pelvic Incidence As a Predictor of Proximal Junctional Kyphosis in Patients with Lenke type 5 Adolescent Idiopathic Scoliosis.

STUDY DESIGN: Retrospective comparative study. OBJECTIVE: To evaluate the relationship between pelvic incidence (PI) and proximal junctional kyphosis (PJK) in patients with Lenke type 5 adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: Although PJK is a common complication of sagittal malalignment after posterior correction and fusion surgery (PSF), few studies have assessed its risk factors. The significance of pelvic morphology in relation to PJK has been suggested but remains unclear in Lenke type 5 AIS patients. METHODS: A total of 92 patients with Lenke type 5 AIS who underwent selective thoracolumbar PSF with a minimum follow-up of two years were included. Patients were divided into PJK and non-PJK groups based on postoperative radiographs. The influence of PI on PJK occurrence was evaluated through binary logistic analysis. Subgroup analysis was performed based on the PI value (low PI,<45°; high PI, ≥ 45°) to identify factors affecting PJK occurrence. RESULTS: PJK was observed in 17.4% of the whole cohort. Binary logistic regression analysis identified low PI and large TL/L curve as a risk factor for PJK (PI, odds ratio, 0.933; TL/L curve, odds ratio, 1.080). Subgroup analysis showed that the postoperative increase in the upper instrumented vertebra slope in PJK cases was comparable in both the low and high PI groups. Meanwhile, lordotic changes in the fused area in the PJK cases were observed only in the low PI group. No difference in the Scoliosis Research Society 22 scores were observed between the two groups. CONCLUSION: From this study a low PI was identified as a risk factor for the occurrence of PJK in Lenke type 5 AIS patients. The occurrence of PJK is influenced by lordotic changes in the fused area and the limited compensatory capacity of the pelvis in patients with a low PI.

Comparison of Surgical Outcomes After Posterior Decompression by Junior or Senior Surgeons for Patients With Cervical Ossification of the Posterior Longitudinal Ligament: Results From Retrospective Multicenter Cohort Study.

STUDY DESIGN: Retrospective multicenter study. OBJECTIVES: To investigate surgical outcomes following posterior decompression for cervical ossification of the posterior longitudinal ligament (OPLL) when performed by board-certified spine (BCS) or non-BCS (NBCS) surgeons. METHODS: We included 203 patients with cervical OPLL who were followed for a minimum of 1 year after surgery. Demographic information, medical history, and imaging findings were collected. Clinical outcomes were assessed preoperatively and at the final follow-up using the Japanese Orthopedic Association (JOA) score and the visual analog scale (VAS) for the neck. We compared outcomes between BCS surgeons, who must meet several requirements, including experience in more than 300 spinal surgeries, and NBCS surgeons. RESULTS: BCS surgeons performed 124 out of 203 cases, while NBCS surgeons were primary in 79 cases, with 73.4% were directly supervised by a BCS surgeon. There was no statistically significant difference in surgical duration, estimated blood loss, and perioperative complication rates between the BCS and NBCS groups. Moreover, no statistically significant group differences were observed in each position of the C2-7 angle and cervical range of motion at preoperation and the final follow-up. Preoperative and final follow-up JOA scores, VAS for the neck, and JOA score recovery rate were comparable between the two groups. CONCLUSIONS: Surgical outcomes, including functional recovery, complication rates, and cervical dynamics, were comparable between the BCS and NBCS groups. Consequently, posterior decompression for cervical OPLL is considered safe and effective when conducted by junior surgeons who have undergone training and supervision by experienced spine surgeons.

Development and Validation of Machine Learning-Based Predictive Model for Prolonged Hospital Stay after Decompression Surgery for Lumbar Spinal Canal Stenosis.

Introduction: Precise prediction of hospital stay duration is essential for maximizing resource utilization during surgery. Existing lumbar spinal stenosis (LSS) surgery prediction models lack accuracy and generalizability. Machine learning can improve accuracy by considering preoperative factors. This study aimed to develop and validate a machine learning-based model for estimating hospital stay duration following decompression surgery for LSS. Methods: Data from 848 patients who underwent decompression surgery for LSS at three hospitals were examined. Twelve prediction models, using 79 preoperative variables, were developed for postoperative hospital stay estimation. The top five models were chosen. Fourteen models predicted prolonged hospital stay (≥14 days), and the most accurate model was chosen. Models were validated using a randomly divided training sample (70%) and testing cohort (30%). Results: The top five models showed moderate linear correlations (0.576-0.624) between predicted and measured values in the testing sample. The ensemble of these models had moderate prediction accuracy for final length of stay (linear correlation 0.626, absolute mean error 2.26 days, standard deviation 3.45 days). The c5.0 decision tree model was the top predictor for prolonged hospital stay, with accuracies of 89.63% (training) and 87.2% (testing). Key predictors for longer stay included JOABPEQ social life domain, facility, history of vertebral fracture, diagnosis, and Visual Analogue Scale (VAS) of low back pain. Conclusions: A machine learning-based model was developed to predict postoperative hospital stay after LSS decompression surgery, using data from multiple hospital settings. Numerical prediction of length of stay was not very accurate, although favorable prediction of prolonged stay was accomplished using preoperative factors. The JOABPEQ social life domain score was the most important predictor.

Influence of slippage reduction and correction of lumbosacral kyphosis by single-level posterior lumbar interbody fusion on spinal alignment in patients with dysplastic spondylolisthesis.

PURPOSE: To investigate the influence of slippage reduction and correction of lumbosacral kyphosis by L5-S1 single-level posterior lumbar interbody fusion (PLIF) on spinal alignment and clinical outcomes including postoperative complications in patients with dysplastic spondylolisthesis (DS). METHODS: Twenty consecutive patients with symptomatic and severe DS who underwent L5-S1 single-level PLIF with a minimum of 2 years of follow-up after surgery were included. Clinical outcomes were evaluated using the Japanese Orthopaedic Association (JOA) and visual analog scale (VAS) scores for low back and leg pain obtained on preoperative and postoperative examinations. Postoperative instrumentation failure and L5 radiculopathy were also evaluated. The preoperative and postoperative spinopelvic parameters were measured. RESULTS: The JOA score significantly improved from 21.5 ± 4.8 (preoperative) to 27.0 ± 2.5 (postoperative), with a mean recovery rate of 75.0% ± 30.4%. The VAS score for low back pain significantly improved from 44.5 ± 30.1 (preoperative) to 11.5 ± 15.9 (postoperative), and that for leg pain significantly improved from 31.0 ± 33.2 (preoperative) to 5.0 ± 10.2 (postoperative). The slip percentage (% slip) significantly improved from 59.6% ± 13.5% (preoperative) to 25.2% ± 15.0% (postoperative). The lumbosacral angle (LSA) significantly improved from 12.3° ± 9.5° (preoperative) to 1.0° ± 4.9° (postoperative). L5-S1 PLIF led to significant improvement of lumbar lordosis (from 52.0° ± 15.9° to 59.7° ± 8.0°) and pelvic incidence - lumbar lordosis mismatch (from 23.9° ± 20.6° to 13.3° ± 10.0°). Correction of lumbosacral kyphosis had a significant positive correlation with postoperative pelvic tilt (PT) (r = 0.50, P = 0.02), while postoperative % slip did not have a significant correlation with postoperative PT. CONCLUSIONS: L5-S1 PLIF for DS provided good clinical outcomes. Correction of lumbosacral kyphosis had a positive impact on regaining ideal spinopelvic balance and may be beneficial in the setting of treating DS.

Clinical application and potential pluripotent effects of hepatocyte growth factor in spinal cord injury regeneration.

INTRODUCTION: Spinal cord injury (SCI) is a condition in which the spinal cord parenchyma is damaged by various factors. The mammalian central nervous system has been considered unable to regenerate once damaged, but recent progress in basic research has gradually revealed that injured neural cells can indeed regenerate. Drug therapy using novel agents is being actively investigated as a new treatment for SCI. One notable treatment method is regeneration therapy using hepatocyte growth factors (HGF). AREA COVERED: HGF has pluripotent neuroregenerative actions, as indicated by its neuroprotective and regenerative effects on the microenvironment and damaged cells, respectively. This review examines these effects in various phases of SCI, from basic research to clinical studies, and the application of this treatment to other diseases. EXPERT OPINION: In regenerative medicine for SCI, drug therapies have tended to be more likely to be developed compared to cell replacement treatment. Nevertheless, there are still challenges to be addressed for these clinical applications due to a wide variety of pathology and animal experimental models of basic study, but HGF could be an effective treatment for SCI with expanded application.

Dysregulation of Inflammatory Pathways in Adult Spinal Deformity Patients with Frailty.

Background/Objectives: An important aspect of the pathophysiology of frailty seems to be the dysregulation of inflammatory pathways and the coagulation system. However, an objective assessment of the impact of frailty on the recovery from surgery is not fully studied. This study sought to assess how frailty affects the recovery of adult spinal deformity (ASD) surgery using blood biomarkers. Methods: 153 consecutive ASD patients (age 64 ± 10 yr, 93% female) who had corrective spine surgery in a single institution and reached 2y f/u were included. The subjects were stratified by frailty using the modified frailty index-11 (robust [R] group or prefrail and frail [F] group). Results of commonly employed laboratory tests at baseline, 1, 3, 7, and 14 post-operative days (POD) were compared. Further comparison was performed in propensity-score matched-39 paired patients between the groups by age, curve type, and baseline alignment. A correlation between HRQOLs, major complications, and biomarkers was performed. Results: Among the propensity-score matched groups, CRP was significantly elevated in the F group at POD1,3(POD1; 5.3 ± 3.1 vs. 7.9 ± 4.7 p = 0.02, POD3; 6.6 ± 4.6 vs. 8.9 ± 5.2 p = 0.02). Transaminase was also elevated in the F group at POD3(ASD: 36 ± 15 vs. 51 ± 58 U/L, p = 0.03, ALT: 32 ± 16 vs. 47 ± 55 U/L, p = 0.04). Interestingly, moderate correlation was observed between transaminase at POD1 and 2 y SRS22 (AST; function r = -0.37, mental health r = -0.39, satisfaction -0.28, total r = -0.40, ALT; function r = -0.37, satisfaction -0.34, total r = -0.39). Conclusions: Frailty affected the serum CRP and transaminase differently following ASD surgery. Transaminase at early POD was correlated with 2 y HRQOLs. These findings support the hypothesis that there is a specific physiological basis to the frailty that is characterized in part by increased inflammation and that these physiological differences persist.

Do Pharmacological Treatments Act in Collaboration with Rehabilitation in Spinal Cord Injury Treatment? A Review of Preclinical Studies.

There is no choice other than rehabilitation as a practical medical treatment to restore impairments or improve activities after acute treatment in people with spinal cord injury (SCI); however, the effect is unremarkable. Therefore, researchers have been seeking effective pharmacological treatments. These will, hopefully, exert a greater effect when combined with rehabilitation. However, no review has specifically summarized the combinatorial effects of rehabilitation with various medical agents. In the current review, which included 43 articles, we summarized the combinatorial effects according to the properties of the medical agents, namely neuromodulation, neurotrophic factors, counteraction to inhibitory factors, and others. The recovery processes promoted by rehabilitation include the regeneration of tracts, neuroprotection, scar tissue reorganization, plasticity of spinal circuits, microenvironmental change in the spinal cord, and enforcement of the musculoskeletal system, which are additive, complementary, or even synergistic with medication in many cases. However, there are some cases that lack interaction or even demonstrate competition between medication and rehabilitation. A large fraction of the combinatorial mechanisms remains to be elucidated, and very few studies have investigated complex combinations of these agents or targeted chronically injured spinal cords.

An Update of a Clinical Practice Guideline for the Management of Patients With Acute Spinal Cord Injury: Recommendations on the Role and Timing of Decompressive Surgery.

STUDY DESIGN: Clinical practice guideline development. OBJECTIVES: Acute spinal cord injury (SCI) can result in devastating motor, sensory, and autonomic impairment; loss of independence; and reduced quality of life. Preclinical evidence suggests that early decompression of the spinal cord may help to limit secondary injury, reduce damage to the neural tissue, and improve functional outcomes. Emerging evidence indicates that "early" surgical decompression completed within 24 hours of injury also improves neurological recovery in patients with acute SCI. The objective of this clinical practice guideline (CPG) is to update the 2017 recommendations on the timing of surgical decompression and to evaluate the evidence with respect to ultra-early surgery (in particular, but not limited to, <12 hours after acute SCI). METHODS: A multidisciplinary, international, guideline development group (GDG) was formed that consisted of spine surgeons, neurologists, critical care specialists, emergency medicine doctors, physical medicine and rehabilitation professionals, as well as individuals living with SCI. A systematic review was conducted based on accepted methodological standards to evaluate the impact of early (within 24 hours of acute SCI) or ultra-early (in particular, but not limited to, within 12 hours of acute SCI) surgery on neurological recovery, functional outcomes, administrative outcomes, safety, and cost-effectiveness. The GRADE approach was used to rate the overall strength of evidence across studies for each primary outcome. Using the "evidence-to-recommendation" framework, recommendations were then developed that considered the balance of benefits and harms, financial impact, patient values, acceptability, and feasibility. The guideline was internally appraised using the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool. RESULTS: The GDG recommended that early surgery (≤24 hours after injury) be offered as the preferred option for adult patients with acute SCI regardless of level. This recommendation was based on moderate evidence suggesting that patients were 2 times more likely to recover by ≥ 2 ASIA Impairment Score (AIS) grades at 6 months (RR: 2.76, 95% CI 1.60 to 4.98) and 12 months (RR: 1.95, 95% CI 1.26 to 3.18) if they were decompressed within 24 hours compared to after 24 hours. Furthermore, patients undergoing early surgery improved by an additional 4.50 (95% 1.70 to 7.29) points on the ASIA Motor Score compared to patients undergoing surgery after 24 hours post-injury. The GDG also agreed that a recommendation for ultra-early surgery could not be made on the basis of the current evidence because of the small sample sizes, variable definitions of what constituted ultra-early in the literature, and the inconsistency of the evidence. CONCLUSIONS: It is recommended that patients with an acute SCI, regardless of level, undergo surgery within 24 hours after injury when medically feasible. Future research is required to determine the differential effectiveness of early surgery in different subpopulations and the impact of ultra-early surgery on neurological recovery. Moreover, further work is required to define what constitutes effective spinal cord decompression and to individualize care. It is also recognized that a concerted international effort will be required to translate these recommendations into policy.

Alaska Pollock-derived Gelatin Sealant has Higher Sealing Strength than, and Comparable Biocompatibility with, Fibrin Sealant in Porcine and Rat Dural Injury Models.

STUDY DESIGN: Burst strength study in porcine dural models and functional and histological study in rat dural models. OBJECTIVE: This study aimed to investigate the sealing strength and biocompatibility of Alaska pollock-derived gelatin (ApGltn) and fibrin sealants in disrupted dural injuries. SUMMARY OF BACKGROUND DATA: Disruption of the dura mater occurs during spine surgery, leading to cerebrospinal fluid leakage. Fibrin sealant is usually applied to ruptured sites; however, it lacks sealing strength. A novel biocompatible sealant composed of ApGltn was recently demonstrated to have good burst strength and biocompatibility in the porcine aorta. METHODS: Ten porcine dura maters with central holes were covered with ApGltn and fibrin sealants (five samples per group). The maximum burst strength of each sealant was measured, and histological examination was performed after burst testing. Twenty-seven dura maters of male Wistar rats were used for functional and histopathological evaluations. The rats were treated with three surgical interventions: defect + ApGltn sealant; defect + fibrin sealant; defect alone (nine rats per group). Macroscopic confirmation of the sealant, hindlimb motor function analysis, and histopathological examination were performed at two, four, and eight weeks after the procedure. RESULTS: The maximum burst strength of the ApGltn sealant was ~4.4 times higher than that of the fibrin sealant (68.1±12.1 vs . 15.6±8.7 mmHg; P <0.001). Histological examination confirmed that the ApGltn sealant showed tight adhesion to the dural surface, whereas a gap was observed between the fibrin sealant and the dura mater. In the rat model, the ApGltn sealant resulted in spinal function and dural histological findings similar to those of the fibrin sealant. CONCLUSION: The ApGltn sealant had a higher sealing strength than, and comparable effect on dura regeneration with, the fibrin sealant.

Novel artificial nerve transplantation of human iPSC-derived neurite bundles enhanced nerve regeneration after peripheral nerve injury.

BACKGROUND: Severe peripheral nerve damage always requires surgical treatment. Autologous nerve transplantation is a standard treatment, but it is not sufficient due to length limitations and extended surgical time. Even with the available artificial nerves, there is still large room for improvement in their therapeutic effects. Novel treatments for peripheral nerve injury are greatly expected. METHODS: Using a specialized microfluidic device, we generated artificial neurite bundles from human iPSC-derived motor and sensory nerve organoids. We developed a new technology to isolate cell-free neurite bundles from spheroids. Transplantation therapy was carried out for large nerve defects in rat sciatic nerve with novel artificial nerve conduit filled with lineally assembled sets of human neurite bundles. Quantitative comparisons were performed over time to search for the artificial nerve with the therapeutic effect, evaluating the recovery of motor and sensory functions and histological regeneration. In addition, a multidimensional unbiased gene expression profiling was carried out by using next-generation sequencing. RESULT: After transplantation, the neurite bundle-derived artificial nerves exerted significant therapeutic effects, both functionally and histologically. Remarkably, therapeutic efficacy was achieved without immunosuppression, even in xenotransplantation. Transplanted neurite bundles fully dissolved after several weeks, with no tumor formation or cell proliferation, confirming their biosafety. Posttransplant gene expression analysis highlighted the immune system's role in recovery. CONCLUSION: The combination of newly developed microfluidic devices and iPSC technology enables the preparation of artificial nerves from organoid-derived neurite bundles in advance for future treatment of peripheral nerve injury patients. A promising, safe, and effective peripheral nerve treatment is now ready for clinical application.

Human-induced pluripotent stem cell-derived neural stem/progenitor cell ex vivo gene therapy with synaptic organizer CPTX for spinal cord injury.

The transplantation of neural stem/progenitor cells (NS/PCs) derived from human induced pluripotent stem cells (hiPSCs) has shown promise in spinal cord injury (SCI) model animals. Establishing a functional synaptic connection between the transplanted and host neurons is crucial for motor function recovery. To boost therapeutic outcomes, we developed an ex vivo gene therapy aimed at promoting synapse formation by expressing the synthetic excitatory synapse organizer CPTX in hiPSC-NS/PCs. Using an immunocompromised transgenic rat model of SCI, we evaluated the effects of transplanting CPTX-expressing hiPSC-NS/PCs using histological and functional analyses. Our findings revealed a significant increase in excitatory synapse formation at the transplantation site. Retrograde monosynaptic tracing indicated extensive integration of transplanted neurons into the surrounding neuronal tracts facilitated by CPTX. Consequently, locomotion and spinal cord conduction significantly improved. Thus, ex vivo gene therapy targeting synapse formation holds promise for future clinical applications and offers potential benefits to individuals with SCI.

Regenerative Medicine for Spinal Cord Injury Using Induced Pluripotent Stem Cells.

Spinal cord injury (SCI) is a devastating injury that causes permanent neurological dysfunction. To develop a new treatment strategy for SCI, a clinical trial of transplantation of human-induced pluripotent stem cell-derived neural precursor cells (NPCs) in patients in the subacute phase of SCI was recently initiated. The formation of synaptic connections with host neural tissues is one of the therapeutic mechanisms of cell transplantation, and this beneficial efficacy has been directly demonstrated using a chemogenetic tool. This research focuses on the establishment of cell therapy for chronic SCI, which is more challenging owing to cavity and scar formation. Thus, neurogenic NPC transplantation is more effective in forming functional synapses with the host neurons. Furthermore, combinatory rehabilitation therapy is useful to enhance the efficacy of this strategy, and a valid rehabilitative training program has been established for SCI animal models that received NPC transplantation in the chronic phase. Therefore, the use of regenerative medicine for chronic SCI is expected to increase.

Chronic Spinal Cord Injury Regeneration with Combined Therapy Comprising Neural Stem/Progenitor Cell Transplantation, Rehabilitation, and Semaphorin 3A Inhibitor.

Spinal cord injury (SCI) often results in various long-term sequelae, and chronically injured spinal cords exhibit a refractory feature, showing a limited response to cell transplantation therapies. To our knowledge, no preclinical studies have reported a treatment approach with results surpassing those of treatment comprising rehabilitation alone. In this study of rats with SCI, we propose a novel combined therapy involving a semaphorin 3A inhibitor (Sema3Ai), which enhances axonal regeneration, as the third treatment element in combination with neural stem/progenitor cell transplantation and rehabilitation. This comprehensive therapeutic strategy achieved significant improvements in host-derived neuronal and oligodendrocyte differentiation at the SCI epicenter and promoted axonal regeneration even in the chronically injured spinal cord. The elongated axons established functional electrical connections, contributing to significant enhancements in locomotor mobility when compared with animals treated with transplantation and rehabilitation. As a result, our combined transplantation, Sema3Ai, and rehabilitation treatment have the potential to serve as a critical step forward for chronic SCI patients, improving their ability to regain motor function.

Influence of thoracolumbar kyphosis on postoperative spinal alignment in patients with Lenke type 5C adolescent idiopathic scoliosis.

PURPOSE: This study aimed to examine the changes in thoracolumbar kyphosis (TLK) following correction surgery in patients with Lenke type 5C adolescent idiopathic scoliosis (AIS) and to evaluate its influence on postoperative spinal alignment and clinical outcomes. METHODS: Sixty-six patients with Lenke type 5C AIS were included and followed up for a minimum of 5 years after surgery. First, the patients were divided into two groups according to the preoperative TLK angle (Study 1; Kyphosis and Lordosis group). The patients were further classified into two groups according to the presence or absence of postoperative changes in TLK (Study 2; Changed and Maintained groups). Finally, the outcome variables were compared between these groups and analyzed for spinal alignment and clinical outcomes. RESULTS: In Study 1, patients demonstrated a significant kyphotic change in the Lordosis group and a significant lordotic change in the Kyphosis group postoperatively. No statistically significant differences were found between the two groups when comparing the pre- and postoperative coronal and sagittal alignment. In Study 2, there were no statistically significant differences between the Changed and the Maintained groups in each spinal alignment pre- and postoperatively. Each domain of the Scoliosis Research Society 22-item questionnaire remained unchanged at 5 years postoperation. CONCLUSION: In many patients with Lenke type 5C AIS, TLK changed significantly and approached 0° after surgery. However, the magnitude of the preoperative TLK and the presence or absence of improvement did not affect postoperative spinal alignment. Furthermore, the patients had satisfactory clinical outcomes irrespective of TLK modification. LEVEL OF EVIDENCE: III.