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 2, 4, and 8 weeks after the procedure. RESULTS: The maximum burst strength of the ApGltn sealant was approximately 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. CONCLUSIONS: The ApGltn sealant had a higher sealing strength than, and comparable effect on dura regeneration with, the fibrin sealant.

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.

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.

How coronal malalignment affects the surgical outcome in corrective spine surgery for adult symptomatic lumbar deformity.

PURPOSE: The importance of coronal alignment is unclear, while the importance of sagittal alignment in the treatment of adult patients with spinal deformities is well described. This study sought to elucidate the impact of global coronal malalignment (GCMA) in surgically treated adult symptomatic lumbar deformity (ASLD) patients. METHODS: A multicentre retrospective analysis of a prospective ASD database. GCMA was defined as GCA (C7PL-CSVL) ≥ 3 cm. GCMA is categorized based on the Obeid-Coronal Malalignment Classification (O-CM). Demographic, surgical, radiographic, HRQOL, and complication data were analysed. The risk for postoperative GCMA was analysed by univariate and multivariate analyses. RESULTS: Of 230 surgically treated ASLD patients, 96 patients showed GCMA preoperatively and baseline GCA was correlated with the baseline SRS-22 pain domain score (r = - 30). Postoperatively, 62 patients (27%, O-CM type 1: 41[18%], type 2: 21[9%]) developed GCMA. The multivariate risk analysis indicated dementia (OR 20.1[1.2-304.4]), diabetes (OR 5.9[1.3-27.3]), and baseline O-CM type 2 (OR 2.1[1.3-3.4]) as independent risk factors for postoperative GCMA. The 2-year SRS-22 score was not different between the 2 groups, while 4 GCMA patients required revision surgery within 1 year after surgery due to coronal decompensation (GCMA+ vs. GCMA- function: 3.6 ± 0.6 vs. 3.7 ± 0.7, pain: 3.7 ± 0.8 vs. 3.8 ± 0.8, self-image: 3.6 ± 0.8 vs. 3.6 ± 0.8, mental health: 3.7 ± 0.8 vs. 3.8 ± 0.9, satisfaction: 3.9 ± 0.9 vs. 3.9 ± 0.8, total: 3.7 ± 0.7 vs. 3.7 ± 0.7). Additionally, the comparisons of 2-yr SRS-22 between GCMA ± showed no difference in any UIV and LIV level or O-CM type. CONCLUSIONS: In ASLD patients with corrective spine surgery, GCMA at 2 years did not affect HRQOL or major complications at any spinal fusion extent or O-CM type of malalignment, whereas GCA correlated with pain intensity before surgery. These findings may warrant further study of the impact of GCMA on HRQOL in the surgical treatment of ASLD patients.

A shift of brain network hub after spinal cord injury.

Background: Spinal cord injury (SCI) causes severe sequelae and significant social loss, depending on the extent of the damage. Most previous studies have focused on the pathology of the spinal cord to develop treatments for SCI. However, it is now known that the brain, which is not directly damaged, also undergoes morphological changes after spinal cord injury, which could affect natural recovery and treatment. In recent years, magnetic resonance imaging (MRI) has been developed to analyze functional changes in the brain. Resting-state functional MRI (rsfMRI), which captures brain activity at rest, can calculate functional connections between brain areas and identify central hubs by network analysis. Purpose: We aim to investigate functional connectivity in the brain using rsfMRI after SCI and to determine how brain-network main hubs change over time. Methods: We evaluated rsfMRI in 10 mice of the contusional SCI model and calculated connectivity using graph theory. We evaluated "centrality," a representative parameter of network analysis. The subtype of centrality was degree centrality, which indicates the hub function of a single area. The five times of rsfMRI were performed in each individual mouse: before injury and at 1, 3, 7, and 14 weeks post-injury. Results: Before the injury, the degree centralities of the primary and secondary motor cortex were high, suggesting that these motor cortices served as main hubs for motor function. After SCI, the hub function of the motor cortices decreased by 14 weeks. In contrast, hub function in the external capsule and the putamen comparatively increased with time after injury, suggesting that the extrapyramidal/subcortical system, which runs the ventral side of the spinal cord and remains after injury in this model, becomes dominant. Conclusion: We demonstrated the shift of the brain network hub after SCI. The results of this study provide basic information for understanding brain network changes after SCI and would be useful for treatment selection and evaluation of its efficacy in SCI patients.

Impact of Surgical Resection Without Spinal Fusion for Thoracic Dumbbell Tumors on Postoperative Global Spinal Sagittal Alignment and Clinical Outcomes.

STUDY DESIGN: A retrospective comparative study. OBJECTIVES: This study investigated radiographical changes in global spinal sagittal alignment (GSSA) and clinical outcomes after tumor resection without spinal fusion in patients with thoracic dumbbell tumors. METHODS: Thirty patients with thoracic dumbbell tumors who were followed up for at least 3 years were included in this study. Variations in the outcome variables were analyzed using individual GSSA parameters measured on radiography. Clinical outcomes were assessed using the modified McCormick scale (MMCS), Japan Orthopaedic Association (JOA) score, and visual analog scale (VAS). To assess the impact of the affected levels on these outcomes, we divided the patients into three groups according to the location of the tumor (upper [T1-4], middle [T5-8], or lower [T9-12] thoracic spine). RESULTS: The GSSA parameters (cervical lordosis, T1 slope, thoracic kyphosis [global, upper, middle, and lower], thoracolumbar kyphosis, lumbar lordosis, sacral slope, pelvic incidence, and pelvic tilt) of all the patients did not change significantly after surgery. Eleven of thirty patients had preoperative gait disturbances but they could walk without support (MMCS grade I or II) at the final follow-up. The JOA score and VAS showed significant postoperative improvements. No statistically significant differences were observed in each postoperative sagittal profile or clinical outcome between the upper, middle, and lower groups. CONCLUSIONS: Tumor resection without spinal fusion did not affect the various GSSA parameters and resulted in satisfactory clinical outcomes, indicating that spinal fusion may not always be necessary when resecting thoracic dumbbell tumors.

Hepatocyte growth factor pretreatment boosts functional recovery after spinal cord injury through human iPSC-derived neural stem/progenitor cell transplantation.

BACKGROUND: Human induced pluripotent stem cell-derived neural stem/progenitor cell (hiPSC-NS/PC)-based cell transplantation has emerged as a groundbreaking method for replacing damaged neural cells and stimulating functional recovery, but its efficacy is strongly influenced by the state of the injured spinal microenvironment. This study evaluates the impact of a dual therapeutic intervention utilizing hepatocyte growth factor (HGF) and hiPSC-NS/PC transplantation on motor function restoration following spinal cord injury (SCI). METHODS: Severe contusive SCI was induced in immunocompromised rats, followed by continuous administration of recombinant human HGF protein into the subarachnoid space immediately after SCI for two weeks. Acute-phase histological and RNA sequencing analyses were conducted. Nine days after the injury, hiPSC-NS/PCs were transplanted into the lesion epicenter of the injured spinal cord, and the functional and histological outcomes were determined. RESULTS: The acute-phase HGF-treated group exhibited vascularization, diverse anti-inflammatory effects, and activation of endogenous neural stem cells after SCI, which collectively contributed to tissue preservation. Following cell transplantation into a favorable environment, the transplanted NS/PCs survived well, facilitating remyelination and neuronal regeneration in host tissues. These comprehensive effects led to substantial enhancements in motor function in the dual-therapy group compared to the single-treatment groups. CONCLUSIONS: We demonstrate that the combined therapeutic approach of HGF preconditioning and hiPSC-NS/PC transplantation enhances locomotor functional recovery post-SCI, highlighting a highly promising therapeutic strategy for acute to subacute SCI.

The Effect of Age-adjusted Sagittal Alignment on the Result of Posterior Decompression Surgery for Lumbar Spinal Canal Stenosis.

STUDY DESIGN: Retrospective case series. OBJECTIVE: The aim of this study was to compare the outcomes of posterior decompression surgery for lumbar spinal canal stenosis (LSS) in patients with preoperative sagittal malalignment to those without, after adjusting for age and sex. SUMMARY OF BACKGROUND DATA: Sagittal balance is an important factor in spine surgery and is thought to affect postoperative outcomes following LSS. However, the relationship between sagittal malalignment and postoperative outcomes has not been thoroughly examined. METHODS: We included 533 patients who underwent surgical treatment for LSS and also achieved two-year follow-up. Patients were categorized into either a malalignment (MA+) group (69 patients) or a matched-alignment (MA-) group (348 patients) based on age-adjusted preoperative sagittal alignment. We compared the baseline and two-year postoperative health-related quality of life (HRQOL) using the Visual Analog Scale and Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) scores. We also calculated clinical efficacy using the minimal clinically important difference (MCID) based on JOABPEQ scores, and age- and sex-adjusted JOABPEQ scores two years after surgery. Differences between groups were examined using the Mann‒Whitney U test and χ 2 analysis, where applicable. RESULTS: Both groups showed an improved HRQOL after decompression surgery. Similar proportions of patients showed substantial improvement, as estimated by the MCID, in four out of five subdomains of the JOABPEQ. A significantly smaller proportion of patients in the MA+ group showed substantial improvement in lumbar function. The age- and sex-adjusted HRQOL scores two years after surgery were lower in the MA+ group, particularly in the lumbar function and social life function subdomains of the JOABPEQ. CONCLUSION: The effects of posterior decompression surgery alone can still be observed at least two years postoperatively for patients with LSS and concomitant sagittal malalignment. Patients with sagittal malalignment may experience lower HRQOL than those without this type of malalignment.

Human Spinal Oligodendrogenic Neural Progenitor Cells Enhance Pathophysiological Outcomes and Functional Recovery in a Clinically Relevant Cervical Spinal Cord Injury Rat Model.

Traumatic spinal cord injury (SCI) results in the loss of neurons, oligodendrocytes, and astrocytes. Present interventions for SCI include decompressive surgery, anti-inflammatory therapies, and rehabilitation programs. Nonetheless, these approaches do not offer regenerative solutions to replace the lost cells, fiber tracts, and circuits. Neural stem/progenitor cell (NPC) transplantation is a promising strategy that aims to encourage regeneration. However, NPC differentiation remains inconsistent, thus, contributing to suboptimal functional recovery. As such, we have previously engineered oligodendrogenically biased NPCs (oNPCs) and demonstrated their efficacy in a thoracic model of SCI. Since the majority of patients with SCI experience cervical injuries, our objective in the current study was to generate human induced pluripotent stem cell-derived oNPCs (hiPSC-oNPCs) and to characterize these cells in vitro and in vivo, utilizing a clinically relevant rodent model of cervical SCI. Following transplantation, the oNPCs engrafted, migrated to the rostral and caudal regions of the lesion, and demonstrated preferential differentiation toward oligodendrocytes. Histopathological evaluations revealed that oNPC transplantation facilitated tissue preservation while diminishing astrogliosis. Moreover, oNPC transplantation fostered remyelination of the spared tissue. Functional analyses indicated improved forelimb grip strength, gait, and locomotor function in the oNPC-transplanted rats. Importantly, oNPC transplantation did not exacerbate neuropathic pain or induce tumor formation. In conclusion, these findings underscore the therapeutic potential of oNPCs in promoting functional recovery and histopathological improvements in cervical SCI. This evidence warrants further investigation to optimize and advance this promising cell-based therapeutic approach.

Radiographical Results of Adolescent Idiopathic Scoliosis with Major Curve at Proximal Thoracic Spine.

Introduction: Adolescent idiopathic scoliosis (AIS) with a major curve at the main thoracic (MT) area is classified as Lenke type 1, 2, or 3 depending on the flexibility of the proximal thoracic (PT) curve and lumbar curve. No definite classification has been established for a major curve at the PT spine. The purpose of this study is to investigate the radiographic characteristics before and after correction surgery for AIS with a major curve at the PT area. Methods: This is a retrospective cohort study at a single academic institution. Twelve patients with a major curve at the PT spine participated in our study and followed for at least two years after surgery. We evaluated the pre- and postoperative Cobb angles of the curve, curve range, location of the apex, sagittal parameters, and shoulder balance-related parameters. All patients were treated by posterior correction and fusion surgery using pedicle screw constructs. Results: The patients were classified as having a double-curve (DC) type, in which the MT curve was structural, or a single-curve (SC) type, in which the MT curve was corrected to less than 25° on supine side-bending films. The mean correction rates for the PT curve were favorable in both groups (DC, 65.7%±9.6%; SC, 39.2%±4.9%). The mean Cobb angle of the lumbar curve improved in the DC group (preoperative, 17.1°±4.0°; postoperative, 5.0°±4.2°) but deteriorated in the SC group (preoperative, 7.1°±1.2°; postoperative, 12.4°±4.4°) after surgery. Conclusions: We illustrated the postoperative radiographical changes of 12 consecutive patients with the major curve at the PT curve. Although posterior correction and fusion surgery corrected the PT curve satisfactorily in both DC and SC patients, the Cobb angle of the lumbar curve deteriorated after surgery in all SC patients. Surgeons need to pay attention to the fusion area, especially LIV, when operating the SC curve type.

A Review of Treatment Methods Focusing on Human Induced Pluripotent Stem Cell-Derived Neural Stem/Progenitor Cell Transplantation for Chronic Spinal Cord Injury.

Cell transplantation therapy using human induced pluripotent stem cell-derived neural stem/progenitor cells (hiPSC-NS/PCs) has attracted attention as a regenerative therapy for spinal cord injury (SCI), and its efficacy in treating the subacute phase of SCI has been reported in numerous studies. However, few studies have focused on treatment in the chronic phase, which accounts for many patients, suggesting that there are factors that are difficult to overcome in the treatment of chronic SCI. The search for therapeutic strategies that focus on chronic SCI is fraught with challenges, and the combination of different therapies is thought to be the key to a solution. In addition, many issues remain to be addressed, including the investigation of therapeutic approaches for more severe injury models of chronic SCI and the acquisition of practical motor function. This review summarizes the current progress in regenerative therapy for SCI and discusses the prospects for regenerative medicine, particularly in animal models of chronic SCI.

Schwann cell-encapsulated chitosan-collagen hydrogel nerve conduit promotes peripheral nerve regeneration in rodent sciatic nerve defect models.

Chitosan has various tissue regeneration effects. This study was designed to investigate the nerve regeneration effect of Schwann cell (SC)-encapsulated chitosan-collagen hydrogel nerve conduit (CCN) transplanted into a rat model of sciatic nerve defect. We prepared a CCN consisting of an outer layer of chitosan hydrogel and an inner layer of collagen hydrogel to encapsulate the intended cells. Rats with a 10-mm sciatic nerve defect were treated with SCs encapsulated in CCN (CCN+), CCN without SCs (CCN-), SC-encapsulated silicone tube (silicone+), and autologous nerve transplanting (auto). Behavioral and histological analyses indicated that motor functional recovery, axonal regrowth, and myelination of the CCN+ group were superior to those of the CCN- and silicone+ groups. Meanwhile, the CCN- and silicone+ groups showed no significant differences in the recovery of motor function and nerve histological restoration. In conclusion, SC-encapsulated CCN has a synergistic effect on peripheral nerve regeneration, especially axonal regrowth and remyelination of host SCs. In the early phase after transplantation, SC-encapsulated CCNs have a positive effect on recovery. Therefore, using SC-encapsulated CCNs may be a promising approach for massive peripheral nerve defects.

Clinical Features of Recurrent Spinal Cord Tumors.

Introduction: Only a few reports have described the clinical features of recurrent spinal cord tumors. This study aimed to report the recurrence rates (RRs), radiographic imaging, and pathological features of various histopathological recurrent spinal cord tumors using a large sample size. Methods: This study adopted the retrospective observational study design using a single-center study setting. We retrospectively reviewed 818 consecutive individuals operated for spinal cord and cauda equina tumors between 2009 and 2018 in a university hospital. We first determined the number of surgeries and then the histopathology, duration to reoperation, number of surgeries, location, degree of tumor resection, and tumor configuration of the recurrent cases. Results: A total of 99 patients (46 men and 53 women) who underwent multiple surgeries were identified. The mean duration between the primary and second surgeries was 94.8 months. A total of 74 patients underwent surgery twice, 18 patients thrice, and 7 patients 4 or more times. The recurrence sites were broadly distributed over the spine, with mainly intramedullary (47.5%) and dumbbell-shaped (31.3%) tumors. The RRs for each histopathology were as follows: schwannoma, 6.8%; meningioma and ependymoma, 15.9%; hemangioblastoma, 15.8%; and astrocytoma, 38.9%. The RRs after total resection were significantly lower (4.4%) than that after partial resection. Neurofibromatosis-associated schwannomas had a higher RR than sporadic schwannomas (p<0.001, odds ratio [OR]=8.54, 95% confidence interval [95% CI]: 3.67-19.93). Among the meningiomas, the RR increased to 43.5% in ventral cases (p<0.001, OR=14.36, 95% CI: 3.66-55.29). Within the ependymomas, partial resection (p<0.001, OR=2.871, 95% CI: 1.37-6.03) was found to be significantly correlated with recurrence. Dumbbell-shaped schwannomas exhibited a higher RR than non-dumbbell-shaped ones. Furthermore, dumbbell-shaped tumors other than schwannoma had a higher RR than dumbbell-shaped schwannomas (p<0.001, OR=16.0, 95% CI: 5.518-46.191). Conclusions: Aiming for total resection is essential to prevent recurrence. Dumbbell-shaped schwannomas and ventral meningiomas exhibited higher RR requiring revision surgery. As for dumbbell-shaped tumors, spinal surgeons should pay attention to the possibilities of non-schwannoma histopathologies.

Preoperative Symptom Duration Influences Neurological Recovery and Patient-Reported Outcome Measures After Surgical Treatment of Cervical Ossification of the Posterior Longitudinal Ligament.

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.