Resection of a giant intraspinal and extraspinal schwannoma with cystic change using a two-step surgery: a case report.

BACKGROUND: Schwannomas originating from the intravertebral canal rarely extend into the paravertebral region or form large masses. There are few reports on such medical cases, and their clinical diagnosis and management are poorly understood. Here, we report a case of an intraspinal schwannoma with a giant extraspinal mass in a middle-aged Chinese woman and the clinical implications of the symptoms, diagnosis, and treatment of thoracic vertebral schwannoma. CASE PRESENTATION: A 59-year-old female patient who presented with sudden lower limb numbness and difficulty in walking was referred to our department. Magnetic resonance imaging (MRI) revealed a tumor compressing the T11-T12 spinal canal and extensively invading the left thoracic cavity to form a giant paravertebral mass. Schwannoma was diagnosed after intraoperative pathological examination, in which tumor cells were immunoreactive to S100 and Sox10 but negative for smooth muscle actin (SMH). Intraspinal mass resection through the posterior approach and extraspinal chest mass resection under video-assisted thoracoscopy through the left lateral approach were performed simultaneously, and instrumentation was used to maintain thoracic spinal stability. CONCLUSION: In patients with large schwannomas, customized treatment plans are crucial. Tailoring the approach to an individual's specific condition by considering factors such as tumor size and location is essential for optimal outcomes.

Modic changes in patients with lumbar disc herniation followed more than 1 year after lumbar discectomy: a systematic review and meta-analysis.

Background: Modic changes (MCs) are identified as an independent risk factor for low back pain. Different subtypes of MCs vary in their impact on postoperative pain relief. However, consensus on the transformation of postoperative MC fractions in patients with distinct MC subtypes is lacking. Methods: This comprehensive systematic review and meta-analysis searched English-language articles in PubMed, Cochrane Library, Web of Science, and Embase databases until January 2024. Studies included focused on patients transitioning between various microcrack subtypes post-discectomy. The primary outcome measure was the transformation between different postoperative microcrack fractions. Results: Eight studies with 689 participants were analyzed. Overall, there is moderate to high-quality evidence indicating differences in the incidence of MC conversion across MC subtypes. The overall incidence of MC conversion was 27.7%, with rates of 37.0%, 20.5%, and 19.1% for MC0, MC1, and MC2 subtypes, respectively. Thus, postoperative MC type transformation, particularly from preoperative MC0 to MC1 (17.7%) or MC2 (13.1%), was more common, with MC1 transformation being predominant. Patients with preoperative comorbid MC1 types (19.0%) exhibited more postoperative transitions than those with MC2 types (12.4%). Conclusion: This study underscores the significance of analyzing post-discectomy MCs in patients with lumbar disc herniation, revealing a higher incidence of MCs post-lumbar discectomy, particularly from preoperative absence of MC to MC1 or MC2. Preoperative MC0 types were more likely to undergo postoperative MC transformation than combined MC1 or MC2 types. These findings are crucial for enhancing surgical outcomes and postoperative care.

Comparison of Lumbosacral Fusion Grade in Patients after Transforaminal and Anterior Lumbar Interbody Fusion with Minimum 2-Year Follow-Up.

OBJECTIVE: Generally, anterior lumbar interbody fusion (ALIF) was believed superior to transforaminal lumbar interbody fusion (TLIF) in induction of fusion. However, many studies have reported comparable results in lumbosacral fusion rate between the two approaches. This study aimed to evaluate the realistic lumbosacral arthrodesis rates following ALIF and TLIF in patients with degenerative spondylolisthesis as measured by CT and radiology. METHODS: Ninety-six patients who underwent single-level L5-S1 fusion through ALIF (n = 48) or TLIF (n = 48) for degenerative spondylolisthesis at the Spine Center, University of California San Francisco, between October 2014 and December 2017 were retrospectively evaluated. Fusion was independently evaluated and categorized as solid fusion, indeterminate fusion, or pseudarthroses by two radiologists using the modified Brantigan-Steffee-Fraser (mBSF) grade. Clinical data on sex, age, body mass index, Meyerding grade, smoking status, follow-up times, complications, and radiological parameters including disc height, disc angle, segmental lordosis, and overall lumbar lordosis were collected. The fusion results and clinical and radiographic data were statistically compared between the ALIF and TLIF groups by using t-test or chi-square test. RESULTS: The mean follow-up period was 37.5 (ranging from 24 to 51) months. Clear, solid radiographic fusions were higher in the ALIF group compared with the TLIF group at the last follow-up (75% vs 47.9%, p = 0.006). Indeterminate fusion occurred in 20.8% (10/48) of ALIF cases and in 43.8% (21/48) of TLIF cases (p = 0.028). Radiographic pseudarthrosis was not significantly different between the TLIF and ALIF groups (16.7% vs 8.3%; p = 0.677). In subgroup analysis of the patients without bone morphogenetic protein (BMP), the solid radiographic fusion rate was significantly higher in the ALIF group than that in the TLIF group (78.6% vs 45.5%; p = 0.037). There were no differences in sex, age, body mass index, Meyerding grade, smoking status, or follow-up time between the two groups (p > 0.05). The ALIF group had more improvement in disc height (7.8 mm vs 4.7 mm), disc angle (5.2° vs 1.5°), segmental lordosis (7.0° vs 2.5°), and overall lumbar lordosis (4.7° vs 0.7°) compared with the TLIF group (p < 0.05). Overall complication rates were similar between the TLIF and ALIF groups (10.4% vs 8.33%; p > 0.999). CONCLUSIONS: With a minimum 2-year radiographic analysis of arthrodesis at lumbosacral level by radiologists, the rate of solid radiographic fusions was higher in the ALIF group compared with the TLIF group, whereas the TLIF group had a higher rate of indeterminate fusion. Radiographic pseudarthrosis did not differ significantly between the TLIF and ALIF groups.

LncRNA TSIX knockdown restores spinal cord injury repair through miR-30a/SOCS3 axis.

Spinal cord injury (SCI) is a serious injury to the central nervous system. Previous studies have discovered that the development of SCI is associated with gene expression. The purpose of this study was to explore the significance of lncRNA TSIX in SCI and its underlying mechanism involved. An in vivo SCI mice model and an in vitro hypoxia-treated HT22 cells model were applied in this study. TSIX and SOCS3 expression in SCI tissues was measured by qRT-PCR, western blot and FISH assay. LV-sh-TSIX was injected into SCI mice intrathecally or subjected to HT22 cells to access the consequent alteration in inflammation response, cell apoptosis and functional recovery through ELISA, immunohistochemistry, TUNEL, flow cytometry assays and BMS scores. Then, the underlying mechanism of TSIX was analyzed by bioinformatics analysis and then confirmed by RIP, RNA pull-down and dual-luciferase reporter assay. It was identified that TSIX was up-regulated in HT22 cells under hypoxia operation and spinal cord tissues of SCI mice. TSIX knockdown improved the lesion size and BMS score and inhibited inflammation and cell apoptosis. MiR-30a was identified as a target for TSIX and SOCS3, and TSIX binds to miR-30a by competing with SOCS3, thereby counteracting miR-30a-mediated SOCS3 inhibition. In addition, LV-sh-TSIX effects were significantly overturned by miR-30a inhibition or SOCS3 over-expression. Knockdown of TSIX improved functional recovery and attenuated the inflammation response and cell apoptosis via miR-30a/SOCS3 axis. These results may provide a potential novel insight for SCI treatment.

Posterior Displacement of L1 May be a Risk Factor for Proximal Junctional Kyphosis After Adult Spinal Deformity Correction.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: Overcorrection in adult spinal deformity (ASD) surgery may lead to proximal junctional kyphosis (PJK) because of posterior spinal displacement. The aim of this paper is to determine if the L1 position relative to the gravity line (GL) is associated with PJK. METHODS: ASD patients fused from the lower thoracic spine to sacrum by 4 spine surgeons at our hospital were retrospectively studied. Lumbar-only and upper thoracic spine fusions were excluded. Spinopelvic parameters, the L1 plumb line (L1PL), L1 distance to the GL (L1-GL), and Roussouly type were measured. RESULTS: One hundred fourteen patients met inclusion criteria (63 patients with PJK, 51 without). Mean age and follow up was 65.51 and 3.39 years, respectively. There was no difference between the PJK and the non-PJK groups in baseline demographics, pre-operative and immediate post-operative pelvic incidence-lumbar lordosis mismatch, sagittal vertical axis, or coronal Cobb. The immediate postoperative L1-GL was -7.24 cm in PJK and -3.45 cm in non-PJK (P < 0.001), L1PL was 1.71 cm in PJK and 3.07 cm in non-PJK (P = 0.004), and PT (23.76° vs 18.90°, P = 0.026) and TK (40.56° vs 31.39°, P < 0.001) were larger in PJK than in non-PJK. After univariate and multivariate analyses, immediate postoperative TK and immediate postoperative L1-GL were independent risk factors for PJK without collinearity. CONCLUSIONS: A dorsally displaced L1 relative to the GL was associated with an increased risk of PJK after ASD surgery. The postoperative L1-GL distance may be a factor to consider during ASD surgery.

Epithelial to Mesenchymal Transition Relevant Subtypes with Distinct Prognosis and Responses to Chemo- or Immunotherapies in Osteosarcoma.

Objective: Currently, clinical classification of osteosarcoma cannot accurately predict the survival outcomes and responses to chemo- or immunotherapies. Our goal was to classify osteosarcoma patients into clinical/biological subtypes based on EMT molecules. Methods: This study retrospectively curated the RNA expression profiling of osteosarcoma patients from the TARGET and GSE21257 cohorts. Consensus clustering analyses were conducted in accordance with the expression profiling of prognostic EMT genes derived from univariate analyses. Immunological features were evaluated through immune cell infiltration, immune checkpoint expression, and activity of cancer immunity cycle. Drug sensitivity was estimated with the GDSC database. WGCNA approach was adopted to determine the EMT-derived genes. Following univariate analyses, a multivariate cox regression model was developed and externally verified. Predictive independency was evaluated with uni- and multivariate analyses. GSEA was presented to uncover relevant molecular mechanisms. Results: Prognostic EMT genes across osteosarcoma patients were stratified into distinct subtypes, namely, subtypes A and B. Patients in subtype B presented desirable prognosis, high immune activation, and enhanced sensitivity to cisplatin. Meanwhile, patients in subtype A were more sensitive to gemcitabine. In total, 86 EMT-derived hub genes were determined, and an EMT score was conducted for osteosarcoma prognosis. Following external verification, this EMT score was reliably and independently predictive of patients' survival outcomes. Additionally, it was positively linked to steroid biosynthesis. Conclusion: Overall, our findings proposed EMT-relevant molecular subtypes and signatures for predicting prognosis and therapeutic responses, contributing to personalized treatment and clinical implication for osteosarcoma.

Osteotomized debridement versus curetted debridement in posterior approach in treating thoracolumbar tuberculosis: a comparative study.

PURPOSE: This study aimed to compare osteotomized debridement (OD) with traditional curetted debridement (CD) in treating thoracolumbar tuberculosis (TB). METHODS: A total of 188 patients were diagnosed with active thoracolumbar TB and underwent one-stage posterior surgery at our institution. Of the 188 patients, 85 patients were treated with OD, and 103 patients were treated with traditional CD. The patient information, laboratory results, imaging findings, and clinical effectiveness were, respectively, compared between the two groups. RESULTS: Group OD consumed less operation time and blood loss than group CD (P < 0.05 for both values). No significant difference in hospitalization time was found between the two groups (P > 0.05). The values of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) in both groups returned to the normal range within one month postoperatively. All patients had significant improvement in visual analog scale (VAS) and oswestry disability index (ODI) postoperatively. The mean fusion time in group OD was shorter than that in group CD (P < 0.05). There was no statistically significant difference in preoperative kyphotic angle between the two groups (P > 0.05), but group OD showed less correction loss than group CD at the final follow-up (P < 0.05). The rate of recurrence and surgery-related complications in group OD was lower than group CD. CONCLUSIONS: Posterior OD, reconstruction with titanium mesh cages (TMCs), and instrumentation is feasible and effective in treating thoracolumbar TB. Compared with the traditional CD, OD can achieve radical lesion removal, more effective kyphosis correction, lower recurrence rate, and fewer complications.

Revision Surgery for Adjacent Segment Degeneration After Fusion for Lumbar Spondylolisthesis: Is there a Correlation with Roussouly Type?

STUDY DESIGN: Retrospective study. OBJECTIVE: The aim of this study was to investigate whether there is an association between revision surgery rates for adjacent segment degeneration (ASD) and Roussouly type after L4-5 transforaminal lumbar interbody fusion (TLIF) for spondylolisthesis. SUMMARY OF BACKGROUND DATA: Revision surgery for ASD is known to occur after spinal fusion; however, it is unclear whether rates of ASD are associated with certain Roussouly types. METHODS: Patients who underwent L4-5 TLIF for spondylolisthesis at the University of California San Francisco from January 2006 to December 2016 with minimum 2-year follow-up were retrospectively analyzed by Roussouly type. Revision surgery for ASD was noted and correlated by Roussouly type. Spinopelvic parameters were also measured for correlation. A value of P < 0.05 was significant. RESULTS: There were 174 patients who met inclusion criteria, (59 males and 115 females). The average age was 62.3 (25-80) years. A total of 132 patients had grade I spondylolisthesis, and 42 had grade II. Mean follow-up was 45.2 months (24-497). A total of 22 patients (12.6%) underwent revision surgery for ASD after L4-5 TLIF. When classified by Roussouly type, revision surgery rates for ASD were: 1, 14.3%; 2, 22.6%; 3, 4.9%; and 4, 15.6% (P = 0.013). Type 3 spines with normal PI-LL (8.85°â€Š±â€Š6.83°) had the lowest revision surgery rate (4.9%), and type 2 spines with PI-LL mismatch (11.06°â€Š±â€Š8.81°) had the highest revision surgery rate (22.6%), a four-fold difference (P = 0.013). The PI-LL mismatch did not change significantly in each type postoperatively (P > 0.05). CONCLUSION: We found that there may be a correlation between Roussouly type and revision surgery for ASD after L4-5 TLIF for spondylolisthesis, with type 2 spines having the highest rate. Spinopelvic parameters may also correlate with revision surgery for ASD after L4-5 TLIF.Level of Evidence: 4.

Upper instrumented vertebra-femoral angle and correlation with proximal junctional kyphosis in adult spinal deformity.

INTRODUCTION: Although matching lumbar lordosis (LL) with pelvic incidence (PI) is an important surgical goal for adult spinal deformity (ASD), there is concern that overcorrection may lead to proximal junctional kyphosis (PJK). We introduce the upper instrumented vertebra-femoral angle (UIVFA) as a measure of appropriate postoperative position in the setting of lower thoracic to pelvis surgical correction for patients with sagittal imbalance. We hypothesize that a more posterior UIV position in relation to the center of the femoral head is associated with an increased risk of PJK given compensatory hyperkyphosis above the UIV. METHODS: In this retrospective cohort study, adult patients undergoing lower thoracic (T9-T12) to pelvis correction of ASD with a minimum of 2-year follow-up were included. UIVFA was measured as the angle subtended by a line from the UIV centroid to the femoral head center to the vertical axis. Patients who developed PJK and those who did not were compared with preoperative and postoperative UIVFA as well as change between postoperative and preoperative UIVFA (deltaUIVFA). RESULTS: Of 119 patients included with an average 3.6-year follow-up, 51 (42.9%) had PJK and 24 (20.2%) had PJF. Patients with PJK had significantly higher postoperative UIVFA (12.6 ± 4.8° vs. 9.4 ± 6.6°, p = 0.04), deltaUIVFA (6.1 ± 7.6° vs. 2.1 ± 5.6°, p < 0.01), postoperative pelvic tilt (27.3 ± 9.2 vs. 23.3 ± 11, p = 0.04), postoperative lumbar lordosis (47.7 ± 13.9° vs. 42.4 ± 13.1, p = 0.04) and postoperative thoracic kyphosis (44.9 ± 13.2 vs. 31.6 ± 18.8) than patients without PJK. With multivariate logistic regression, postoperative UIVFA and deltaUIVFA were found to be independent risk factors for PJK (p < 0.05). DeltaUIVFA was found to be an independent risk factor for PJF (p < 0.05). A receiver operating characteristic (ROC) curve for UIVFA as a predictor for PJK was established with an area under the curve of 0.67 (95% CI 0.59-0.76). Per the Youden index, the optimal UIVFA cut-off value is 11.5 degrees. CONCLUSION: The more posterior the UIV is from the femoral head center after lower thoracic to pelvis surgical correction for ASD, the more patients are at risk for PJK. The greater the magnitude of posterior translation of the UIV from the femoral head center from preop to postop, the greater the likelihood for PJF.

Does transforaminal lumbar interbody fusion induce lordosis or kyphosis? Radiographic evaluation with a minimum 2-year follow-up.

OBJECTIVE: Conflicting reports exist about whether transforaminal lumbar interbody fusion (TLIF) induces lordosis or kyphosis, ranging from decreasing lordosis by 3.71° to increasing it by 18.8°. In this study, the authors' aim was to identify factors that result in kyphosis or lordosis after TLIF. METHODS: A single-center, retrospective study of open TLIF without osteotomy for spondylolisthesis with a minimum 2-year follow-up was undertaken. Preoperative and postoperative clinical and radiographic parameters and cage specifics were collected. TLIFs were considered to be "lordosing" if postoperative induction of lordosis was > 0° and "kyphosing" if postoperative induction of lordosis was ≤ 0°. RESULTS: A total of 137 patients with an average follow-up of 52.5 months (range 24-130 months) were included. The overall postoperative disc angle (DA) and segmental lordosis (SL) increased by 1.96° and 1.88° (p = 0.003 and p = 0.038), respectively, whereas overall lumbar lordosis remained unchanged (p = 0.133). Seventy-nine patients had lordosing TLIFs with a mean SL increase of 5.72° ± 3.97°, and 58 patients had kyphosing TLIFs with a mean decrease of 3.02° ± 2.98°. Multivariate analysis showed that a lower preoperative DA, lower preoperative SL, and anterior cage placement were correlated with the greatest increase in postoperative SL (p = 0.040, p < 0.001, and p = 0.035, respectively). There was no difference in demographics, cage type or height, or spinopelvic parameters between the groups (p > 0.05). Linear regression showed that the preoperative DA and SL correlated with SL after TLIF (R2 = 0.198, p < 0.001; and R2 = 0.2931, p < 0.001, respectively). CONCLUSIONS: Whether a TLIF induces kyphosis or lordosis depends on the preoperative DA, preoperative SL, and cage position. Less-lordotic segments became more lordotic postoperatively, and highly lordotic segments may lose lordosis after TLIF. Cages placed more anteriorly were associated with more lordosis.

MicroRNA­487b­3p inhibits osteosarcoma chemoresistance and metastasis by targeting ALDH1A3.

Metastasis and chemoresistance indicate poor prognosis in patients with osteosarcoma (OS). In the present study, the expression level of microRNA(miR)­487b­3p in OS specimens and cell lines was found to be decreased, and the expression level of miR­487b­3p was associated with overall survival in patients with OS. The inhibition of miR­487b­3p stimulated OS cell migration and contributed to the development of chemoresistance. In contrast, the overexpression of miR­487b­3p significantly inhibited OS cell migration and enhanced the sensitivity of OS cells to doxorubicin treatment. In addition, the results from the present study revealed that the suppression of miR­487b­3p stimulates OS stemness, while the overexpression of miR­487b­3p suppresses OS stemness. Notably, in vivo experiments also revealed that the overexpression of miR­487b­3p inhibited cancer stem cell (CSC)­induced tumor formation, and the combination treatment of miR­487b­3p and doxorubicin significantly inhibited CSC­induced tumor growth. Furthermore, miR­487b­3p exerts its anticancer role by targeting aldehyde dehydrogenase 1 family member A3 in OS. Taken together, the results from the present study suggests that miR­487b­3p is a tumor suppressor and that the overexpression of miR­487b­3p is a novel strategy to inhibit tumor metastasis and chemoresistance in OS.

Is the Goutallier grade of multifidus fat infiltration associated with adjacent-segment degeneration after lumbar spinal fusion?

OBJECTIVE: The aim of this study was to investigate whether fat infiltration of the lumbar multifidus (LM) muscle affects revision surgery rates for adjacent-segment degeneration (ASD) after L4-5 transforaminal lumbar interbody fusion (TLIF) for degenerative spondylolisthesis. METHODS: A total of 178 patients undergoing single-level L4-5 TLIF for spondylolisthesis (2006 to 2016) were retrospectively analyzed. Inclusion criteria were a minimum 2-year follow-up, preoperative MR images and radiographs, and single-level L4-5 TLIF for degenerative spondylolisthesis. Twenty-three patients underwent revision surgery for ASD during the follow-up. Another 23 patients without ASD were matched with the patients with ASD. Demographic data, Roussouly curvature type, and spinopelvic parameter data were collected. The fat infiltration of the LM muscle (L3, L4, and L5) was evaluated on preoperative MRI using the Goutallier classification system. RESULTS: A total of 46 patients were evaluated. There were no differences in age, sex, BMI, or spinopelvic parameters with regard to patients with and those without ASD (p > 0.05). Fat infiltration of the LM was significantly greater in the patients with ASD than in those without ASD (p = 0.029). Fat infiltration was most significant at L3 in patients with ASD than in patients without ASD (p = 0.017). At L4 and L5, there was an increasing trend of fat infiltration in the patients with ASD than in those without ASD, but the difference was not statistically significant (p = 0.354 for L4 and p = 0.077 for L5). CONCLUSIONS: Fat infiltration of the LM may be associated with ASD after L4-5 TLIF for spondylolisthesis. Fat infiltration at L3 may also be associated with ASD at L3-4 after L4-5 TLIF.

Obesity may be associated with adjacent-segment degeneration after single-level transforaminal lumbar interbody fusion in spinopelvic-mismatched patients with a minimum 2-year follow-up.

OBJECTIVE: In this study, the authors' aim was to investigate whether obesity affects surgery rates for adjacent-segment degeneration (ASD) after transforaminal lumbar interbody fusion (TLIF) for spondylolisthesis. METHODS: Patients who underwent single-level TLIF for spondylolisthesis at the University of California, San Francisco, from 2006 to 2016 were retrospectively analyzed. Inclusion criteria were a minimum 2-year follow-up, single-level TLIF, and degenerative lumbar spondylolisthesis. Exclusion criteria were trauma, tumor, infection, multilevel fusions, non-TLIF fusions, or less than a 2-year follow-up. Patient demographic data were collected, and an analysis of spinopelvic parameters was performed. The patients were divided into two groups: mismatched, or pelvic incidence (PI) minus lumbar lordosis (LL) ≥ 10°; and balanced, or PI-LL < 10°. Within the two groups, the patients were further classified by BMI (< 30 and ≥ 30 kg/m2). Patients were then evaluated for surgery for ASD, matched by BMI and PI-LL parameters. RESULTS: A total of 190 patients met inclusion criteria (72 males and 118 females, mean age 59.57 ± 12.39 years). The average follow-up was 40.21 ± 20.42 months (range 24-135 months). In total, 24 patients (12.63% of 190) underwent surgery for ASD. Within the entire cohort, 82 patients were in the mismatched group, and 108 patients were in the balanced group. Within the mismatched group, adjacent-segment surgeries occurred at the following rates: BMI < 30 kg/m2, 2.1% (1/48); and BMI ≥ 30 kg/m2, 17.6% (6/34). Significant differences were seen between patients with BMI ≥ 30 and BMI < 30 (p = 0.018). A receiver operating characteristic curve for BMI as a predictor for ASD was established, with an AUC of 0.69 (95% CI 0.49-0.90). The optimal BMI cutoff value determined by the Youden index is 29.95 (sensitivity 0.857; specificity 0.627). However, in the balanced PI-LL group (108/190 patients), there was no difference in surgery rates for ASD among the patients with different BMIs (p > 0.05). CONCLUSIONS: In patients who have a PI-LL mismatch, obesity may be associated with an increased risk of surgery for ASD after TLIF, but in obese patients without PI-LL mismatch, this association was not observed.

The combination of forskolin and VPA increases gene expression efficiency to the hypoxia/neuron-specific system.

BACKGROUND: Spinal cord injury (SCI) tends to damage neural tissue and generate a hypoxic environment. Studies have confirmed that single therapy with gene or stem cells is inefficient, but research into combining stem cells and gene therapy in treating tissue damage has been undertaken to overcome the related limitations, which include low gene delivery efficiency and therapeutic outcome. Thus, a combination of stem cells, gene therapy, and a hypoxia-specific system may be useful for the reconstruction of SCI. METHODS: To synergistically treat SCI, a combined platform using a hypoxia/neuron-inducible gene expression system (HNIS) and human induced-neural stem cells (hiNSCs) produced by direct reprogramming was designed. Sox2- or nestin-positive hiNSCs were differentiated to Tuj1-, MAP2-, or NeuN-positive neurons. RESULTS: HNIS showed consistent hypoxia/neuron-specific gene expression in hiNSCs cultured under hypoxia. In particular, the HNIS-hiNSC combined platform revealed a complex pattern with higher gene expression compared with a single platform. In addition, we found that an optimal combination of small molecules, such as CHIR99021, valproic acid (VPA), glycogen synthase kinase-3ß (GSK3ß), and histone deacetylase (HDAC) inhibitors, could significantly enhance gene expression with HNIS-hiNSCs in the hypoxic environment. CONCLUSIONS: This experiment demonstrated that HNIS-hiNSCs combined with GSK3 and HDAC inhibitors may present another promising strategy in the treatment of SCI.

The association between lower Hounsfield units of the upper instrumented vertebra and proximal junctional kyphosis in adult spinal deformity surgery with a minimum 2-year follow-up.

OBJECTIVE: Patients undergoing long-segment fusions from the lower thoracic (LT) spine to the sacrum for adult spinal deformity (ASD) correction are at risk for proximal junctional kyphosis (PJK). One mechanism of PJK is fracture of the upper instrumented vertebra (UIV) or higher (UIV+1), which may be related to bone mineral density (BMD). Because Hounsfield units (HUs) on CT correlate with BMD, the authors evaluated whether HU values were correlated with PJK after long fusions for ASD. METHODS: The authors performed a retrospective study of patients older than 50 years who had undergone ASD correction from the LT spine to the sacrum in the period from October 2007 to January 2018 and had a minimum 2-year follow-up. Demographic and spinopelvic parameters were measured. HU values were measured on preoperative CT at the UIV, UIV+1, and UIV+2 (2 levels above the UIV) levels and were assessed for correlations with PJK. RESULTS: The records of 127 patients were reviewed. Fifty-four patients (19 males and 35 females) with a mean age of 64.91 years and mean follow-up of 3.19 years met the study inclusion criteria; there were 29 patients with PJK and 25 patients without. There was no statistically significant difference in demographics or follow-up between these two groups. Neither was there a difference between the groups with regard to postoperative pelvic incidence (PI), sacral slope (SS), lumbar lordosis (LL), PI minus LL (PI-LL), thoracic kyphosis (TK), or sagittal vertical axis (SVA; all p > 0.05). Postoperative pelvic tilt (p = 0.003) and T1 pelvic angle (p = 0.014) were significantly higher in patients with PJK than in those without. Preoperative HUs at UIV, UIV+1, and UIV+2 were 120.41, 124.52, and 129.28 in the patients with PJK, respectively, and 152.80, 155.96, and 160.00 in the patients without PJK, respectively (p = 0.011, 0.02, and 0.018). Three receiver operating characteristic (ROC) curves for preoperative HU values at the UIV, UIV+1, and UIV+2 as a predictor for PJK were established, with areas under the ROC curve of 0.710 (95% CI 0.574-0.847), 0.679 (95% CI 0.536-0.821), and 0.681 (95% CI 0.539-0.824), respectively. The optimal HU value by Youden index was 104 HU at the UIV (sensitivity 0.840, specificity 0.517), 113 HU at the UIV+1 (sensitivity 0.720, specificity 0.517), and 110 HU at the UIV+2 (sensitivity 0.880, specificity 0.448). CONCLUSIONS: In patients undergoing long-segment fusions from the LT spine to the sacrum for ASD, PJK was associated with lower HU values on CT at the UIV, UIV+1, and UIV+2. The measurement of HU values on preoperative CTs may be a useful adjunct for ASD surgery planning.

Anterior Lumbar Interbody Fusion (ALIF): Technique Video: 2-Dimensional Operative Video.

This surgical video demonstrates the technique of an anterior lumbar interbody fusion (ALIF). This video demonstrates the surgical approach, technical nuances of ALIF, and pearls. The main surgical anatomy and approach-related risks are discussed. The video demonstrates the nuances of ALIF, discussing the importance of the release of the disc space to allow for height restoration and lordosis, endplate preparation to enhance arthrodesis, and choice of implant size. The incision is made via a left paramedian approach with a retroperitoneal dissection and mobilization of the vasculature for access to the disc space. The ALIF provides direct access to the ventral surface of the exposed disc, allowing for an incision of the anterior longitudinal ligament, bilateral release of the annulus fibrosus, and access to a large surface area of the vertebral endplate. This anterior access allows for the placement of implants with a greater surface area for fusion, and this facilitates restoration of segmental lordosis, disc height improvement, and foraminal height increase. We have received informed consent from this patient for the video of this case.

Recurrent giant cell tumour of the thoracic spine managed by total en bloc spondylectomy and denosumab therapy: a case report.

BACKGROUND: Giant cell tumour (GCT) of the bone is a rare, invasive benign bone tumour, which typically originates in the metaphyseal ends of long bones and rarely in the spine. Here, we report a rare case of recurrent GCT of the thoracic vertebra, which was managed by three-level total en bloc spondylectomy (TES) after denosumab therapy. CASE PRESENTATION: A 50-year-old woman presented with a 2-month history of progressive lower back pain. Magnetic resonance imaging revealed destruction of the T11 vertebra and a soft tissue mass. The patient underwent tumour resection. Computed tomography at the 2-year follow-up revealed relapse of the resected tumour, which had spread to the T12 vertebral body. Subsequently, denosumab therapy was administered to the patient for 1 year. The growth of the tumour was controlled, and its boundary line was clear. Thereafter, TES for the T10-T12 vertebrae was performed, and spinal reconstruction was completed through a one-stage single posterior approach. The patient's condition improved postoperatively, and no evidence of recurrence of GCT of the bone or spinal deformity was observed at the 32-month follow-up. CONCLUSIONS: Denosumab therapy contributed to tumour regression. Three-level TES may be an effective and feasible strategy for managing large recurrent GCTs of the spine after denosumab therapy.

Restoration of osteochondral defects by implanting bilayered poly(lactide-co-glycolide) porous scaffolds in rabbit joints for 12 and 24 weeks.

BACKGROUND: With the ageing of the population and the increase of sports injuries, the number of joint injuries has increased greatly. Tissue engineering or tissue regeneration is an important method to repair articular cartilage defects. While it has recently been paid much attention to use bilayered porous scaffolds to repair both cartilage and subchondral bone, it is interesting to examine to what extent a bilayer scaffold composed of the same kind of the biodegradable polymer poly(lactide-co-glycolide) (PLGA) can restore an osteochondral defect. Herein, we fabricated bilayered PLGA scaffolds and used a rabbit model to examine the efficacy of implanting the porous scaffolds with or without bone marrow mesenchymal stem cells (BMSCs). The present manuscript reports the regenerative potential up to 24 weeks. METHODS: The osteochondral defect, 4 mm in diameter and 5 mm in depth, was created in the medial condyle of each knee in 23 rabbits. The bilayered PLGA scaffolds with a pore size of 100-200 µm in the chondral layer and a pore size of 300-450 µm in the osseous layer, seeded with or without BMSCs in the chondral layer, were then transplanted into the osteochondral defect of each knee. The osteochondral defect created in the same manner was untreated to act as the control. At 12 and 24 weeks postoperatively, condyles were harvested and analyzed using histology, immunohistochemistry, real-time polymerase chain reaction, and biomechanical testing to evaluate the efficacy of osteochondral repair. RESULTS: No joint erosion, inflammation, swelling, or deformity was observed, and all animals maintained a full range of motion. Compared with the untreated blank group, the groups implanting the bilayered scaffolds with or without cells exhibited much better resurfacing, similar to the surrounding normal tissue. The histological scores of neotissues repaired by the scaffold with cells were closer to that of normal tissue. Although the biomechanical properties of neotissues were not as good as the normal tissue, no significant difference was found between the gene levels of neotissues repaired by the scaffold with or without cells and that of the normal tissue. The repair of the osteochondral defect tends to be stable 12 weeks after implantation. CONCLUSIONS: Our bilayered PLGA porous scaffold supports long-term osteochondral repair via in vivo tissue engineering or regeneration, and its effect can be further facilitated under the scaffold seeded with allogenic BMSCs. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: The bilayered PLGA porous scaffold can facilitate the repair of osteochondral defects and has potential for application in osteochondral tissue engineering.

Postoperative Cervical Sagittal Realignment Improves Patient-Reported Outcomes in Chronic Atlantoaxial Anterior Dislocation.

BACKGROUND: Chronic atlantoaxial anterior dislocation (AAD) not only results in myelopathy, but dislocation-related kyphosis also results in cervical malalignment, which permanently affects neck function and patient-reported outcomes (PROs). OBJECTIVE: To investigate the effect of kyphotic correction on realigning cervical spine and independent cervical alignment parameters, which may be correlated with an improvement of PROs. METHODS: The study included 21 patients with chronic AAD-related kyphosis who underwent C1-2 reduction and correction surgery. Radiographic parameters were measured to assess cervical realignment preoperatively and postoperatively. Neck disability index (NDI), short form 12 physical component summary (SF-12 PCS), and Japanese Orthopaedic Association (JOA) scores were recorded to reveal changes in PROs. The independent parameters correlated with the improvements of PROs were analyzed. RESULTS: Of the radiographic parameters, the C1-2 Cobb angle, the C2-7 Cobb angle, thoracic inlet angle, cervical tilt, and T1 slope were significantly changed from -4.0° ± 16.2°, -29.2° ± 11.2°, 73.1° ± 13.3°, 30.4° ± 8.5°, and 29.1° ± 8.8° preoperatively to -13.5° ± 8.1° (P = .005), -18.0° ± 12.0° (P < .001), 67.1° ± 11.6° (P = .042), 23.1° ± 10.3° (P = .007), and 24.0° ± 7.0° (P = .011) at last follow-up, respectively. NDI, JOA, and SF-12 PCS scores were significantly improved postoperatively. The C1-2 Cobb angle was an independent parameter correlated with the improvements in SF-12 PCS, NDI, and JOA scores. CONCLUSION: Correction and reduction surgery can realign cervical spine in chronic AAD patients. The C1-2 Cobb angle was an independent parameter correlated with the improvements of PROs.

Bilayered PLGA/PLGA-HAp Composite Scaffold for Osteochondral Tissue Engineering and Tissue Regeneration.

This study is aimed at investigation of the osteochondral regeneration potential of bilayered PLGA/PLGA-HAp composite scaffolds with one layer made of biodegradable polymer poly(d,l-lactide-co-glycolide) (PLGA) and another layer made of PLGA polymeric matrix coated by bioactive ceramics hydroxyapatite (HAp). The composite scaffolds were fabricated by compression molding/particle leaching and plasma-treated surface deposition. The pore morphology, mechanical properties, and surface deposition of the scaffold were characterized, and the growth of bone marrow derived mesenchymal stem cells or medicinal signaling cells (MSCs) in the scaffold was verified. Thereafter, rabbit models with an artificial osteochondral defect in joint were randomized into three treatment groups: virgin bilayered scaffold, bilayered scaffold preseeded in vitro with MSCs, and untreated blank control. At 16-week postoperation, both the virgin scaffolds and cell-seeded bilayered scaffolds exhibited osteochondral repair, as verified by biomechanics analysis, histological evaluations, and Western blot. The results highlighted the potentiality of the bilayered PLGA/PLGA-HAp composite scaffold for osteochondral tissue engineering, and in particular tissue regeneration or in situ tissue induction, probably by recruiting the local cells toward chondrogenic and osteogenic differentiation in the porous biomaterials.