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.

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.

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.

Does the degree of preoperative gait disturbance remain after tumor resection in patients with intradural extramedullary spinal cord tumors?

STUDY DESIGN: Retrospective comparative study. OBJECTIVE: This study aimed to determine whether the degree of preoperative gait disturbance remains following surgical resection in patients with intradural extramedullary spinal cord tumors (IDEMSCTs), and to investigate any factors that may influence poor improvement in postoperative gait disturbance. SETTING: The single institution in Japan. METHODS: In total, 78 IDEMSCTs patients who required surgical excision between 2010 and 2019 were included. According to the degree of preoperative gait disturbance using modified McCormick scale (MMCS) grade, they were divided into the Mild and Severe groups. The mean postoperative follow-up period was 50.7 ± 17.9 months. Data on demographic and surgical characteristics were compared between the two groups. RESULTS: There was no significant difference in terms of age at surgery, sex, tumor size, surgical time, estimated blood loss, tumor histopathology, and postoperative follow-up period between the Mild and Severe groups. At the final follow-up, 84.6% of IDEMSCTs patients were able to walk without support. Gait disturbance improved after surgery in most of the patients with preoperative MMCS grades II-IV, but remained in approximately half of patients with preoperative MMCS grade V. Age at surgery was correlated with poor improvement in postoperative gait disturbance in the Severe group. CONCLUSIONS: Regardless of the degree of preoperative gait disturbance, it improved after tumor resection in most of the IDEMSCTs patients. However, in the preoperative MMCS grade III-V cases, older age at surgery would be an important factor associated with poor improvement in postoperative gait disturbance.

Effects of Bone Cross-Link Bridging on Fracture Mechanism and Surgical Outcomes in Elderly Patients with Spine Fractures.

STUDY DESIGN: This study adopted a cross-sectional study design. PURPOSE: This study was designed to investigate the effects of bone cross-link bridging on fracture mechanism and surgical outcomes in vertebral fractures using the maximum number of vertebral bodies with bony bridges between adjacent vertebrae without interruption (maxVB). OVERVIEW OF LITERATURE: The complex interplay of bone density and bone bridging in the elderly can complicate vertebral fractures, necessitating a better understanding of fracture mechanics. METHODS: We examined 242 patients (age >60 years) who underwent surgery for thoracic to lumbar spine fractures from 2010 to 2020. Subsequently, the maxVB was classified into three groups: maxVB (0), maxVB (2-8), and maxVB (9-18), and parameters, including fracture morphology (new Association of Osteosynthesis classification), fracture level, and neurological deficits were compared. In a sub-analysis, 146 patients with thoracolumbar spine fractures were classified into the three aforementioned groups based on the maxVB and compared to determine the optimal operative technique and evaluate surgical outcomes. RESULTS: Regarding the fracture morphology, the maxVB (0) group had more A3 and A4 fractures, whereas the maxVB (2-8) group had less A4 and more B1 and B2 fractures. The maxVB (9-18) group exhibited an increased frequency of B3 and C fractures. Regarding the fracture level, the maxVB (0) group tended to have more fractures in the thoracolumbar transition region. Furthermore, the maxVB (2-8) group had a higher fracture frequency in the lumbar spine area, whereas the maxVB (9-18) group had a higher fracture frequency in the thoracic spine area than the maxVB (0) group. The maxVB (9-18) group had fewer preoperative neurological deficits but a higher reoperation rate and postoperative mortality than the other groups. CONCLUSIONS: The maxVB was identified as a factor influencing fracture level, fracture type, and preoperative neurological deficits. Thus, understanding the maxVB could help elucidate fracture mechanics and assist in perioperative patient management.

Resection of Cervical Dumbbell-Shaped Schwannoma Using Posterior Unilateral Approach: Impact on Postoperative Cervical Function and Clinical Outcomes.

STUDY DESIGN: A retrospective comparative study. OBJECTIVES: This study aimed to evaluate the radiographical changes in cervical sagittal alignment (CSA) and clinical outcomes after tumor resection using a posterior unilateral approach without spinal fixation for patients with cervical dumbbell-shaped schwannoma (DS). METHODS: Seventy-three patients with DS who were followed up for at least 2 years were included. The Eden classification was used to designate the types of DS. The CSA and range of motion (ROM) were analyzed using radiographs. The clinical outcomes were assessed using the Japanese Orthopaedic Association (JOA) score and JOA cervical myelopathy questionnaire. RESULTS: The CSA in the neutral, flexion, and extension position and cervical ROM were not significantly reduced in the follow-up period. The JOA scores showed significant improvement after surgery. The postoperative radiographic parameters and clinical outcomes of Eden type II or III DS, which needed facetectomy for the resection, did not show any statistically significant difference compared with those of Eden type I tumor, which was resected without facetectomy. Fifty-two cases (71.2%) achieved gross total resection, whereas 21 cases (28.8%) remained in partial resection (PR). One case underwent reoperation due to the regrowth of the remnant tumor whose margin was at the entrance of the intervertebral foramen. CONCLUSIONS: Tumor resection using the posterior unilateral approach preserved CSA and resulted in favorable clinical outcomes in patients with DS. When the resection ends in PR, the proximal margin of the remnant tumor should be located distally away from the entrance of the foramen to prevent regrowth.

Incidence and predictive factors of shoulder imbalance after selective anterior spinal fusion surgery in Lenke type 5C adolescent idiopathic scoliosis.

Background: No study has assessed the incidence or predictors of postoperative shoulder imbalance (PSI) in patients with Lenke type 5C adolescent idiopathic scoliosis (AIS) who underwent selective anterior spinal fusion (ASF). This study evaluated the incidence and predictors of shoulder imbalance after selective ASF for Lenke type 5C AIS. Methods: In total, 62 patients with Lenke type 5C AIS (4 men and 58 women, mean age at surgery of 15.5 ± 1.5 years) were included and divided into the following two groups according to the radiographic shoulder height (RSH) at the final follow-up: PSI and non-PSI groups. All patients in this study underwent a whole-spine radiological evaluation. Various spinal coronal and sagittal profiles on radiographs were compared between the 2 groups. The clinical outcomes were assessed using the Scoliosis Research Society (SRS)-22 questionnaires. Results: The mean final follow-up duration was 8.6 ± 2.7 years. PSI was observed in 10 patients (16.1%) immediately after surgery; however, in the long-term follow-up period, PSI improved in 3 patients spontaneously, whereas the remaining 7 patients had residual PSI. The preoperative RSH and correction rates of the major curve immediately after surgery or at the final follow-up were significantly larger in the PSI group than in the non-PSI group (p=.001, p=.023, and p=.019, respectively). Receiver operating characteristic curve analysis indicated that the cutoff values for preoperative RSH and the correction rates immediately after surgery and at the final follow-up were 11.79 mm (p=.002; area under the curve [AUC], 0.948), 71.0% (p=.026; AUC, 0.822), and 65.4% (p=.021; AUC, 0.835), respectively. No statistically significant difference was observed in the preoperative and final follow-up SRS-22 scores in any domain between the PSI and non-PSI groups. Conclusions: Paying attention to the preoperative RSH and avoiding excessive correction of the major curve can prevent the occurrence of shoulder imbalance after selective ASF for Lenke type 5C AIS.

Spinous Process-Splitting Laminectomy Approach for Tumor Excision at Conus Medullaris or Cauda Equina Level Results in Satisfactory Clinical Outcomes Without Affecting Global Spinal Sagittal Alignment.

STUDY DESIGN: Retrospective comparative study. OBJECTIVES: The present study investigated radiographical changes in global spinal sagittal alignment (GSSA) and clinical outcomes following tumor resection using spinous process-splitting laminectomy (SPSL) approach without fixation in patients with conus medullaris (CM) or cauda equina (CE) tumor. METHODS: Forty-one patients with CM or CE tumor (19 males, 22 females, mean age at surgery of 52.9 ± 13.0 years) were included in this study. The variations of outcome variables were analyzed in various GSSA profiles using radiographic outcomes. The clinical outcomes were assessed using Japan Orthopaedic Association (JOA) score and JOA back pain evaluation questionnaire (JOABPEQ). RESULTS: In all cases, the various GSSA parameters (sagittal vertical axis, C2-7 lordosis, T1 slope, thoracic kyphosis, T10-L2 kyphosis, lumbar lordosis [LL; upper, middle, and lower], sacral slope, pelvic incidence, and pelvic tilt) did not significantly change in the 2-years postoperative period. Moreover, age at surgery, the number of resected laminae, preoperative T12-L2 kyphosis, or LL did not affect the postoperative changes in T12-L2 kyphosis or LL, and had no statistically significant correlation among them. The scores of each postoperative JOA domain and the Visual Analogue Scale included in the JOABPEQ were significantly improved. There was no statistical significant group difference in each sagittal profile or clinical outcomes between CM and CE groups postoperatively. CONCLUSIONS: Tumor resection using SPSL approach did not affected the various GSSA parameters examined and resulted in satisfactory clinical outcomes, indicating that SPSL approach is a suitable surgical technique for patients with CM or CE tumor.

Imaging Characteristics and Surgical Outcomes in Patients With Intraspinal Solitary Fibrous Tumor/Hemangiopericytoma: A Retrospective Cohort Study.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: Intraspinal solitary fibrous tumor (SFT)/hemangiopericytoma (HPC) is often misdiagnosed preoperatively as schwannoma or meningioma because its imaging characteristics are not well understood. As postoperative prognosis differs among the 3 lesions, predicting the probability of SFT/HPC preoperatively is essential. Thus, this study investigates the imaging characteristics of SFT/HPC compared with those of schwannoma or meningioma and evaluates surgical outcomes. METHODS: The preoperative imaging findings, tumor resection extent, recurrence and regrowth rates, and neurological improvement were compared between 10 patients with SFT/HPC and 42 patients with schwannoma or 40 patients with meningioma. RESULTS: Most patients with SFT/HPC showed isointensity on both T1- and T2-weighted images compared with patients with schwannoma (P = 0.011 and 0.029, respectively) and no significant difference compared with patients with meningioma (P = 0.575 and 0.845, respectively). Almost all patients with SFT/HPC showed highly uniformizing enhancement patterns, similar to those with meningioma (P = 0.496). Compared with meningioma, SFT/HPC lacked the dural tail sign and intratumoral calcification and exhibited irregular shape. Of the 5 patients who underwent partial resection, 60% exhibited tumor recurrence and regrowth following surgery. CONCLUSIONS: Complete en bloc surgical resection should be attempted in patients with intraspinal SFT/HPC to prevent postoperative recurrence or regrowth. As this tumor is often preoperatively misdiagnosed, we recommend that the imaging findings exhibited in this study should be used to positively suspect SFT/HPC. This will enhance patient outcomes by enabling more appropriate preoperative surgical planning.

Normal pressure hydrocephalus due to an iatrogenic giant lumbar pseudomeningocele after posterior lumbar interbody fusion: illustrative case.

BACKGROUND: Iatrogenic pseudomeningocele incidence after lumbar surgery is 0.068%-2%, and most lumbar pseudomeningoceles are smaller than 5 cm; however, in rare cases, "giant" pseudomeningoceles greater than 8 cm in size may develop. Normal pressure hydrocephalus (NPH) is another rare condition in which the ventricles expand despite the presence of normal intracranial pressure. To date, pseudomeningocele associated with NPH has not been reported. OBSERVATIONS: An 80-year-old woman underwent L3-5 laminectomy and posterior lumbar interbody fusion, and her symptoms improved after surgery. However, dementia appeared 1 month after surgery. Repeated brain computed tomography showed ventricular enlargement, and lumbar magnetic resonance imaging showed a long pseudomeningocele in the subcutaneous tissues at the L4 level. Here, the authors report a rare case of an iatrogenic giant pseudomeningocele accompanied by NPH after lumbar surgery. The symptoms of NPH in the present case occurred after spinal surgery and recovered after dural repair surgery, indicating that the changes in cerebrospinal fluid circulation and/or pressure due to pseudomeningoceles may cause NPH. LESSONS: The prevention of dural tears through precise surgical technique and primary repair of dural tears are the best approaches to prevent pseudomeningocele incidence and subsequent events.

Cervical sagittal alignment is influenced by changes in thoracic and lumbar sagittal alignments after correction surgery in patients with lenke type 6 adolescent idiopathic scoliosis.

Background: Few studies have examined the changes in cervical sagittal alignment (CSA) and its relationship with other sagittal alignments in AIS patients with major thoracolumbar/lumbar (TL/L) curve who underwent correction surgery. This study investigated the radiographical changes in CSA after correction surgery in patients with Lenke type 6 adolescent idiopathic scoliosis (AIS) and assess any possible factors affecting postoperative CSA. Methods: Forty-four patients with Lenke type 6 AIS (3 males and 41 females, mean age at surgery of 15.6 ± 2.8 years) who could be followed up for 3 years after correction surgery were included in this study. Variations of outcome variables were analyzed in various spinal sagittal parameters using radiographic outcomes. Univariate correlation analyses were used to evaluate possible factors influencing the postoperative CSA. The Scoliosis Research Society (SRS)-22 questionnaires and the Oswestry Disability Index (ODI) were used for clinical evaluation, and the changes between pre- and 3-year post-operation were compared. Results: The Cobb angle of the major and minor curve was significantly improved after correction surgery. Furthermore, CSA, such as C2-7 angle and T1 slope, changed significantly postoperatively. The magnitude of coronal curve correction did not affect CSA postoperatively, while the postoperative TK, T10-L2 kyphosis and LL were significantly correlated with the postoperative C2-7 angle, respectively. None of the patients in this study complained of neck or low back pain during the period up 3 years after the operation. Comparing each domain of SRS-22 or ODI score, these were unchanged between pre-, 1-year, and 3-year post-operation, with no statistically significant differences. Conclusions: CSA changed significantly after correction surgery, and cervical kyphosis indicated a tendency to decrease in Lenke type 6 AIS patients, which was associated with an improvement in thoracic and lumbar sagittal alignment, not correction for coronal deformity.

Selective Anterior Fusion Surgery Does Not Influence Global Spinal Sagittal Alignment in Lenke Type 5 Adolescent Idiopathic Scoliosis Patients.

STUDY DESIGN: Retrospective comparative study. OBJECTIVE: The aim of this study was to evaluate the changes in global spinal sagittal alignment (GSSA) following selective anterior spinal fusion (ASF) in patients with Lenke type 5 adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: Few studies have assessed the changes in postoperative GSSA, including cervical, thoracic, and lumbosacral sagittal alignment in AIS patients with major thoracolumbar/lumbar (TL/L) curve who underwent selective ASF. METHODS: Fifty-two patients with Lenke type 5 AIS (two males and 50 females, mean age at surgery of 16.4 ±â€Š3.1 years) were included in this study. The average final follow-up was 8.3 ±â€Š3.1 years after surgery. The variations of outcome variables were analyzed in various spinal sagittal profiles using radiographic outcomes (pre-operation, immediate post-operation, and final follow-up). The clinical outcomes at the final follow-up were assessed using Scoliosis Research Society (SRS)-22 and Oswestry Disability Index (ODI) questionnaires. RESULTS: The mean Cobb angle of the main TL/L and minor thoracic curve was significantly improved after selective ASF, which was maintained up to the final follow-up. However, in all cases, the various sagittal parameters examined (sagittal vertical axis [SVA], C2-7 SVA, C2-7 lordosis, T1 slope, thoracic kyphosis, T10-L2 kyphosis, lumbar lordosis, pelvic incidence, pelvic tilt, and sacral slope), did not significantly change in the immediate postoperative period, and all GSSA parameters were maintained up to the final follow-up. Furthermore, the magnitude of coronal curve correction and fused levels did not affect each GSSA parameter postoperatively. During the period up to the final follow-up, no significant clinical symptoms were observed. The final SRS-22 global score was 4.5 ±â€Š0.3, and ODI scored 0.8 ±â€Š2.4. CONCLUSION: Selective ASF did not influence various GSSA parameters postoperatively and could maintain excellent correction for coronal deformity with satisfactory final functional and clinical outcomes confirmed by long-term follow-up.Level of Evidence: 4.

First-in-human clinical trial of transplantation of iPSC-derived NS/PCs in subacute complete spinal cord injury: Study protocol.

INTRODUCTION: Our group has conducted extensive basic and preclinical studies of the use of human induced pluripotent cell (iPSC)-derived neural stem/progenitor cell (hiPSC-NS/PC) grafts in models of spinal cord injury (SCI). Evidence from animal experiments suggests this approach is safe and effective. We are preparing to initiate a first-in-human clinical study of hiPSC-NS/PC transplantation in subacute SCI. SETTING: NS/PCs were prepared at a Good Manufacturing Practice-grade cell processing facility at Osaka National Hospital using a clinical-grade integration-free hiPSC line established by the iPSC Stock Project organized by the Kyoto University Center for iPS Cell Research and Application. After performing all quality checks, the long-term safety and efficacy of cells were confirmed using immunodeficient mouse models. METHODS: The forthcoming clinical study uses an open-label, single-arm design. The initial follow-up period is 1 year. The primary objective is to assess the safety of hiPSC-NS/PC transplantation in patients with subacute SCI. The secondary objective is to obtain preliminary evidence of its impact on neurological function and quality-of-life outcomes. Four patients with C3/4-Th10 level, complete subacute (within 24 days post-injury) SCI will be recruited. After obtaining consent, cryopreserved cells will be thawed and prepared following a multi-step process including treatment with a γ-secretase inhibitor to promote cell differentiation. A total of 2 × 106 cells will be transplanted into the injured spinal cord parenchyma 14-28 days post-injury. Patients will also receive transient immunosuppression. This study protocol has been reviewed and approved by the Certified Committee for Regenerative Medicine and the Japanese Ministry of Health, Labor and Welfare (University Hospital Medical Information Network Clinical Trials Registry [UMIN-CTR] number, UMIN000035074; Japan Registry of Clinical Trials [jRCT] number, jRCTa031190228). DISCUSSION/CONCLUSION: We plan to start recruiting a patient as soon as the COVID-19 epidemic subsides. The primary focus of this clinical study is safety, and the number of transplanted cells may be too low to confirm efficacy. After confirming safety, a dose-escalation study is planned.

Does Selective Posterior Correction and Fusion Surgery Influence Cervical Sagittal Alignment in Patient with Lenke Type 5 Adolescent Idiopathic Scoliosis?-A 5-year Follow-up Retrospective Cohort Study.

STUDY DESIGN: A retrospective comparative study. OBJECTIVE: The aim of this study was to examine the changes in cervical sagittal alignment (CSA) following surgical correction in a patient with Lenke type 5 adolescent idiopathic scoliosis (AIS) and evaluate any possible factors influencing postoperative CSA. SUMMARY OF BACKGROUND DATA: Few studies have assessed the association between CSA and thoracic or lumbar sagittal alignment in AIS patients with major thoracolumbar/lumbar curve who underwent posterior correction and fusion surgery. METHODS: Sixty-six patients with Lenke type 5 AIS (two males and 64 females, the mean age at surgery of 16.2 years) were included in this study. They were followed up for minimum 5 years after surgery. Multiple linear regression analysis was used to evaluate possible factors influencing the postoperative CSA. To determine the influence of upper end vertebra (UEV) level on postoperative CSA, the subjects were divided into two groups according to UEV level of ≥T9 or ≤T10. The outcome variables were compared between the two groups and analyzed for changes in various spinal sagittal profiles using radiographic outcomes. RESULTS: Multiple linear regression analysis revealed that preoperative T10-L2 kyphosis and LL were significantly correlated with postoperative C2-7 lordosis. However, CSA did not significantly change at 5 years after surgery. Sub-analysis of the cohort revealed that in the UEV ≥T9 group, the mean thoracic kyphosis significantly increased from 20.3°â€Š±â€Š10.6° to 24.0°â€Š±â€Š8.9° and the mean C2-7 lordosis also significantly increased from -12.5°â€Š±â€Š8.3° to -4.3°â€Š±â€Š10.3° at 5-year postoperatively. SRS-22 outcomes were comparable between the groups. CONCLUSION: We indicated that the CSA was not influenced by surgical correction in most Lenke type 5 AIS patients. However, in a patient whose UEV was located at T9 or higher levels, CSA was influenced through the changes in thoracic kyphosis following posterior correction surgery.Level of Evidence: 4.

A robust culture system to generate neural progenitors with gliogenic competence from clinically relevant induced pluripotent stem cells for treatment of spinal cord injury.

Cell-based therapy targeting spinal cord injury (SCI) is an attractive approach to promote functional recovery by replacing damaged tissue. We and other groups have reported the effectiveness of transplanting neural stem/progenitor cells (NS/PCs) derived from human induced pluripotent stem cells (hiPSCs) in SCI animal models for neuronal replacement. Glial replacement is an additional approach for tissue repair; however, the lack of robust procedures to drive iPSCs into NS/PCs which can produce glial cells has hindered the development of glial cell transplantation for the restoration of neuronal functions after SCI. Here, we established a method to generate NS/PCs with gliogenic competence (gNS/PCs) optimized for clinical relevance and utilized them as a source of therapeutic NS/PCs for SCI. We could successfully generate gNS/PCs from clinically relevant hiPSCs, which efficiently produced astrocytes and oligodendrocytes in vitro. We also performed comparison between gNS/PCs and neurogenic NS/PCs based on single cell RNA-seq analysis and found that gNS/PCs were distinguished by expression of several transcription factors including HEY2 and NFIB. After gNS/PC transplantation, the graft did not exhibit tumor-like tissue formation, indicating the safety of them as a source of cell therapy. Importantly, the gNS/PCs triggered functional recovery in an SCI animal model, with remyelination of demyelinated axons and improved motor function. Given the inherent safety of gNS/PCs and favorable outcomes observed after their transplantation, cell-based medicine using the gNS/PCs-induction procedure described here together with clinically relevant iPSCs is realistic and would be beneficial for SCI patients.

Treatment with a Gamma-Secretase Inhibitor Promotes Functional Recovery in Human iPSC- Derived Transplants for Chronic Spinal Cord Injury.

Treatment involving regenerative medicine for chronic spinal cord injury (SCI) is difficult due to phase-dependent changes in the intraspinal environment. We previously reported that treatment with a gamma-secretase inhibitor (GSI), which inhibits Notch signaling, promotes the differentiation into mature neurons in human induced pluripotent stem cell-derived neural stem/progenitor cell (hiPSC-NS/PC) transplantation for subacute SCI. Here, we evaluated the efficacy of GSI-treated hiPSC-NS/PC transplantation in treating chronic SCI, which resulted in significantly enhanced axonal regrowth, remyelination, inhibitory synapse formation with the host neural circuitry, and reticulo spinal tract fiber formation. Interestingly, inhibiting Notch signaling with GSI caused phosphorylation of p38 MAPK, which is a key molecule required to promote axonal regeneration. These favorable outcomes contributed to motor function improvement. Therefore, treating cells with GSI provides a beneficial effect after transplantation, even in the chronic phase following SCI.

Pretreatment with a γ-Secretase Inhibitor Prevents Tumor-like Overgrowth in Human iPSC-Derived Transplants for Spinal Cord Injury.

Neural stem/progenitor cells (NS/PCs) derived from human induced pluripotent stem cells (hiPSCs) are considered to be a promising cell source for cell-based interventions that target CNS disorders. We previously reported that transplanting certain hiPSC-NS/PCs in the spinal cord results in tumor-like overgrowth of hiPSC-NS/PCs and subsequent deterioration of motor function. Remnant immature cells should be removed or induced into more mature cell types to avoid adverse effects of hiPSC-NS/PC transplantation. Because Notch signaling plays a role in maintaining NS/PCs, we evaluated the effects of γ-secretase inhibitor (GSI) and found that pretreating hiPSC-NS/PCs with GSI promoted neuronal differentiation and maturation in vitro, and GSI pretreatment also reduced the overgrowth of transplanted hiPSC-NS/PCs and inhibited the deterioration of motor function in vivo. These results indicate that pretreatment with hiPSC-NS/PCs decreases the proliferative capacity of transplanted hiPSC-NS/PCs, triggers neuronal commitment, and improves the safety of hiPSC-based approaches in regenerative medicine.

Antianxiety-like effects of Chimpi (dried citrus peels) in the elevated open-platform test.

Dried citrus peels (Chimpi) is one of the most common natural medicines with qi (energy flow) rectifying and shi (dampness) drying actions, which originates from Citrus unshiu, and/or C. reticulata according to the definition of the pharmacopoeiae of Japan and China. In this study, the pharmacological effects of their extracts and major chemical constituents hesperidin and its aglycone hesperetin on anxiety were examined with an anxiety model of elevated open-platform test using ICR male mice (6-week-old) and total duration of freezing was decreased in fluoxetine-treated mice, which is a simple and highly sensitive to the effects of serotonergic anxiolytics. Moreover, yokukansankachimpihange (YKH), a combination of yokukansan with Chimpi and Hange (Pinellia) was also examined because Chimpi is considered to play a crucial part in this formula against anxious symptoms in dementia patients. The results showed that Chimpi and YKH possess a significant anxiolytic-like effect similar to that of fluoxetine, suggesting that they might be similar to fluoxetine in their pharmacological actions through the serotonergic neurotransmission pathway. Moreover, it also suggested that the major chemical constituent, hesperidin could be an active principle attributed to the antianxiety-like effects with a direct and indirect role via its aglycone hesperetin.

A Kampo formula, saikokaryukotsuboreito, improves serum testosterone levels of castrated mice and its possible mechanism.

The term "late-onset hypogonadism (LOH)" is recommended to express the symptoms in middle-aged males with decreased testosterone. Although androgen replacement therapy (ART) might be an effective way to manage LOH, the risk of testosterone supplementation in elderly men is still concerned. On the other hand, to avoid adverse effects of ART, Kampo medicine (traditional Chinese-Japanese medicine) is often a first choice to treat LOH in Japan. However, their pharmacological studies are few. In this study, castrated mice was used as an LOH animal model for examining the pharmacological effects of a Kampo formula, saikokaryukotsuboreito (shortly SKRBT) on serum testosterone levels and seminal vesicles weights. Furthermore, an attempt to elucidate its pharmacological mechanism, inhibition of SKRBT and its components against aromatase were also examined with the enzyme-based assay. As a result, SKRBT improved significantly both the decline of serum testosterone levels and decrease of seminal vesicles weight of castrated mice at a dose of 125 mg/kg with a non dose-dependent manner. SKRBT and two components Scutellariae radix and Rhei rhizoma exhibited inhibitory activities with the IC(50) values of 145, 29.2 and 29.7 µg/ml, respectively. These results suggested that the aromatase inhibitory activity of SKRBT may contribute, to a different extent, to the improvement of serum testosterone levels.

Effects of keishibukuryoganryokayokuinin (gui-zhi-fu-ling-wanliao-jia-yiyiren) on the epidermal pigment cells from DBA/2 mice exposed to ultraviolet B (UVB) and/or progesterone.

The production of melanin is not only activated by external factors such as sunlight or UV-exposure, but is also considered to be triggered by hormonal factors, particularly sex hormones such as ovarian hormones. Previously, keishibukuryoganryokayokuinin (KBY) was reported to increase the pigmentation and moisture content of dermis in women during the luteal phase of the menstrual cycle, thus suggesting that progesterone could play a critical role in the development of skin pigmentation. In the present study, female DBA/2 mice, a dilute brown strain, were used to examine the effects of KBY on the increase in epidermal pigment cells in mice exposed to ultraviolet B (UVB) radiation or progesterone in an attempt to elucidate its mechanism. An increase in epidermal pigment cells was observed in mice exposed to progesterone. To the best of our knowledge, this is the first study to demonstrate that progesterone causes pigmentation in vivo. Furthermore, administration of KBY to progesterone-exposed mice significantly reduced the number of epidermal pigment cells. However, KBY had no such effects on UVB-induced pigmentation. Another important finding was the gain in body weight in progesterone-exposed mice, while body weight gain was reduced by KBY. The body weight gain was believed to be due to sodium and fluid retention, a kind of adverse effect of progesterone, which may further affect the intracellular pH of melanosomes, which synthesize melanin, in turn, leading to melanin production because tyrosinase activity is linked to the intracellular pH environment. This may help explain the mechanism of the role of KBY in pigmentation.