Intermittent administration of PTH for the treatment of inflammatory bone loss does not enhance entheseal pathological new bone formation.

OBJECTIVE: To investigate the effect of intermittent parathyroid hormone (iPTH) administration on pathological new bone formation during treatment of ankylosing spondylitis-related osteoporosis. METHODS: Animal models with pathological bone formation caused by hypothetical AS pathogenesis received treatment with iPTH. We determined the effects of iPTH on bone loss and the formation of pathological new bone with micro-computed tomography (micro-CT) and histological examination. In addition, the tamoxifen-inducible conditional knockout mice (CAGGCre-ERTM; PTHflox/flox, PTH-/-) was established to delete PTH and investigate the effect of endogenous PTH on pathological new bone formation. RESULTS: iPTH treatment significantly improved trabecular bone mass in the modified collagen-induced arthritis (m-CIA) model and unbalanced mechanical loading models. Meanwhile, iPTH treatment did not enhance pathological new bone formation in all types of animal models. Endogenous PTH deficiency had no effects on pathological new bone formation in unbalanced mechanical loading models. CONCLUSION: Experimental animal models of AS treated with iPTH show improvement in trabecular bone density, but not entheseal pathological bone formation，indicating it may be a potential treatment for inflammatory bone loss does in AS.

Piezo1-mediated mechanotransduction promotes entheseal pathological new bone formation in ankylosing spondylitis.

OBJECTIVE: The aim of this study was to identify the role of Piezo1-mediated mechanotransduction in entheseal pathological new bone formation and to explore the underlying molecular mechanism. METHODS: Spinal ligament tissues were collected from 14 patients with ankylosing spondylitis (AS) and 14 non-AS controls and bulk RNA sequencing was conducted. Collagen antibody-induced arthritis models were established to observe pathological new bone formation. Pharmacological inhibition and genetic ablation of Piezo1 was performed in animal models to identify the essential role of Piezo1. Entheseal osteo-chondral lineage cells were collected and in vitro cell culture system was established to study the role and underlying mechanism of Piezo1 in regulation of chondrogenesis, osteogenesis and its own expression. RESULTS: Piezo1 was aberrantly upregulated in ligaments and entheseal tissues from patients with AS and animal models. Pharmaceutical and genetic inhibition of Piezo1 attenuated while activation of Piezo1 promoted pathological new bone formation. Mechanistically, activation of CaMKII (Calcium/calmodulin dependent protein kinase II) signalling was found essential for Piezo1-mediated mechanotransduction. In addition, Piezo1 was upregulated by AS-associated inflammatory cytokines. CONCLUSION: Piezo1-mediated mechanotransduction promotes entheseal pathological new bone formation through CaMKII signalling in AS.

Association between immediate postoperative hypoalbuminemia and surgical site infection after posterior lumbar fusion surgery.

PURPOSE: In this study, we intended to investigate the association between immediate postoperative hypoalbuminemia and surgical site infection (SSI), and determine a threshold value for postoperative hypoalbuminemia that can assist in risk stratification in patients after posterior lumbar fusion surgery. METHODS: From January 2017 to December 2021, 466 consecutive patients who underwent posterior lumbar fusion surgery were selected to analyze the relationship between immediate postoperative hypoalbuminemia and SSI. Multivariate logistic regression analysis was performed to identify the independent risk factors of SSI and postoperative hypoalbuminemia. Receiver Operating Characteristic (ROC) analysis was used to determine the optimal value for postoperative hypoalbuminemia, and subsequent grouping was based on the identified threshold. RESULTS: Of the total 466 patients, 25 patients (5.4%) developed SSI after surgery, and lower postoperative albumin (OR: 0.716, 95% CI: 0.611-0.840, p < 0.001) was independently associated with SSI. ROC analysis showed that the cutoff value of postoperative hypoalbuminemia was 32 g/L with a sensitivity of 0.760, specificity of 0.844, and a Youden index of 0.604. Postoperative SSI was more common in patients with postoperative hypoalbuminemia than in those without (21.6% vs. 1.6%, p < 0.001). Age, gender and operative duration were found to be independent predictors of postoperative hypoalbuminemia. CONCLUSIONS: This study showed that immediate postoperative hypoalbuminemia was an independent risk factor for the development of SSI in patients who underwent posterior lumbar fusion. Even in patients with a normal preoperative serum albumin level, there was an increased risk of SSI when the postoperative albumin within 24 h was < 32 g/L.

Gut-disc axis: A cause of intervertebral disc degeneration and low back pain?

PURPOSE: Low back pain (LBP), a widely prevalent and costly disease around the world, is mainly caused by intervertebral disc (IVD) degeneration (IDD). Although numerous factors may trigger this degenerative process, microbiome dysbiosis has recently been implicated as one of the likely causes. However, the exact relationship between the microbiome and IDD is not well understood. This review summarizes the potential mechanisms and discusses microbiome dysbiosis's possible influence on IDD and LBP. METHODS: Prospective literature review. RESULTS: Alterations in microbiome composition and host responses to the microbiota causing pathological bone development and involution, led to the concept of gut-bone marrow axis and gut-bone axis. Moreover, the concept of the gut-disc axis was also proposed to explain the microbiome's role in IDD and LBP. According to the existing evidence, the microbiome could be an important factor for inducing and aggravating IDD through changing or regulating the outside and inside microenvironment of the IVD. Three potential mechanisms by which the gut microbiota can induce IVD and cause LBP are: (1) translocation of the bacteria across the gut epithelial barrier and into the IVD, (2) regulation of the mucosal and systemic immune system, and (3) regulation of nutrient absorption and metabolites formation at the gut epithelium and its diffusion into the IVD. Furthermore, to investigate whether IVD is initiated by pathogenic bacteria and establish the correlation between the presence of certain microbial groups with the disease in question, microbiome diversity analysis based on16S rRNA data can be used to characterise stool/blood microbiota from IVD patients. CONCLUSION: Future studies on microbiome, fungi and viruses in IDD is necessary to revolutionize our thinking about their possible role in the development of IVD diseases. Furthermore, we believe that inflammation inhibition and interruption of amplification of cascade reaction in IVD by targeting the gut and IVD microbiome is worthwhile for the treatment of IDD and LBP. LEVEL OF EVIDENCE I: Diagnostic: individual cross-sectional studies with the consistently applied reference standard and blinding.

Learning-based fully automated prediction of lumbar disc degeneration progression with specified clinical parameters and preliminary validation.

BACKGROUND: Lumbar disc degeneration (LDD) may be related to aging, biomechanical and genetic factors. Despite the extensive work on understanding its etiology, there is currently no automated tool for accurate prediction of its progression. PURPOSE: We aim to establish a novel deep learning-based pipeline to predict the progression of LDD-related findings using lumbar MRIs. MATERIALS AND METHODS: We utilized our dataset with MRIs acquired from 1,343 individual participants (taken at the baseline and the 5-year follow-up timepoint), and progression assessments (the Schneiderman score, disc bulging, and Pfirrmann grading) that were labelled by spine specialists with over ten years clinical experience. Our new pipeline was realized by integrating the MRI-SegFlow and the Visual Geometry Group-Medium (VGG-M) for automated disc region detection and LDD progression prediction correspondingly. The LDD progression was quantified by comparing the Schneiderman score, disc bulging and Pfirrmann grading at the baseline and at follow-up. A fivefold cross-validation was conducted to assess the predictive performance of the new pipeline. RESULTS: Our pipeline achieved very good performances on the LDD progression prediction, with high progression prediction accuracy of the Schneiderman score (Accuracy: 90.2 ± 0.9%), disc bulging (Accuracy: 90.4% ± 1.1%), and Pfirrmann grading (Accuracy: 89.9% ± 2.1%). CONCLUSION: This is the first attempt of using deep learning to predict LDD progression on a large dataset with 5-year follow-up. Requiring no human interference, our pipeline can potentially achieve similar predictive performances in new settings with minimal efforts.

Tenascin-C-mediated suppression of extracellular matrix adhesion force promotes entheseal new bone formation through activation of Hippo signalling in ankylosing spondylitis.

OBJECTIVES: The aim of this study was to identify the role of tenascin-C (TNC) in entheseal new bone formation and to explore the underlying molecular mechanism. METHODS: Ligament tissue samples were obtained from patients with ankylosing spondylitis (AS) during surgery. Collagen antibody-induced arthritis and DBA/1 models were established to observe entheseal new bone formation. TNC expression was determined by immunohistochemistry staining. Systemic inhibition or genetic ablation of TNC was performed in animal models. Mechanical properties of extracellular matrix (ECM) were measured by atomic force microscopy. Downstream pathway of TNC was analysed by RNA sequencing and confirmed with pharmacological modulation both in vitro and in vivo. Cellular source of TNC was analysed by single-cell RNA sequencing (scRNA-seq) and confirmed by immunofluorescence staining. RESULTS: TNC was aberrantly upregulated in ligament and entheseal tissues from patients with AS and animal models. TNC inhibition significantly suppressed entheseal new bone formation. Functional assays revealed that TNC promoted new bone formation by enhancing chondrogenic differentiation during endochondral ossification. Mechanistically, TNC suppressed the adhesion force of ECM, resulting in the activation of downstream Hippo/yes-associated protein signalling, which in turn increased the expression of chondrogenic genes. scRNA-seq and immunofluorescence staining further revealed that TNC was majorly secreted by fibroblast-specific protein-1 (FSP1)+fibroblasts in the entheseal inflammatory microenvironment. CONCLUSION: Inflammation-induced aberrant expression of TNC by FSP1+fibroblasts promotes entheseal new bone formation by suppressing ECM adhesion forces and activating Hippo signalling.

Perioperative Complications in 255 Patients Who Underwent Lateral Anterior Lumbar Interbody Fusion (LaLIF) Surgery.

PURPOSE: To investigate the perioperative complications of lateral anterior lumbar interbody fusion (LaLIF) surgery. METHODS: The participants were patients who underwent LaLIF surgery for degenerative lumbar diseases between April 2016 and November 2020. The collected data were classified into intraoperative and early-stage postoperative (1 month) complications. Intraoperative complications were subcategorized into nerve root injury, sympathetic chain injury, segmental artery injury, iliolumbar vein injury, peritoneum laceration, temporary psoas injury, endplate damage, and vertebral body fractures. Postoperative complications were subcategorized into surgical site infection, cage migration, cage subsidence and psoas major hematoma. RESULTS: In the 255 included patients, 39 complications (15.3%) were reported. One patient (0.4%) had residual neurological symptoms (numbness) at the last follow-up after conservative management. The most common complications were temporary psoas injury (3.9%), followed by sympathetic chain injury (2.7%) and endplate damage (2.0%). The most frequent postoperative complication was cage migration (1.6%), followed by cage subsidence (1.2%), and surgical site infection (0.8%). CONCLUSION: The complication rates for LaLIF are generally low and comparable to those for conventional OLIF and XLIF that have been reported in other studies. Almost all complications were transient after LaLIF. Severe complications can be avoided by using sufficient muscle relaxant, instruments with the required characteristics and vertical trajectories in multiple steps.

Matching correction of main and compensatory curves is critical for immediate postoperative coronal balance in correction of severe adult idiopathic scoliosis.

PURPOSE: To analyze the correlation between immediate postoperative coronal imbalance and the matching degree of the correction rates of the main curve and compensatory curves in the surgical treatment of severe adult idiopathic scoliosis. METHODS: Patients were categorized into three types based on the preoperative coronal balance status (type A = balance, type B = shifted to cave side and type C = shifted to convex side), and each type was further divided into two subgroups based on the postoperative coronal balance status (balance and imbalance). Different coronal parameters before and after operations were calculated and compared. RESULTS: The rate of postoperative CIB was highest in type C patients (53.8%) and lowest in type A patients (31.5%). To avoid postoperative CIB, the value of the postoperative CRmain should fall within the range of 1.001 × CRcomp ± 2.84% in type A patients, 1.112 × CRcomp + 3.3% ± 5.02% in type B patients and 0.907 × CRcomp - 2.5% ± 4.38% in type C patients. CONCLUSION: Mismatch between the correction rates of the main curve and compensation curves is a critical cause of immediate postoperative CIB. The relatively equal correction of the main curve and compensatory curves is essential for type A patients to achieve postoperative coronal balance, while the correction rate of the main curve should be higher than the compensatory curves in type B patients and vice versa in type C patients. Three formulas for the three different types were developed to provide helpful guidance information for surgical planning.

Correlation study of radiographic characteristics and operative difficulty in lateral-anterior lumbar interbody fusion (LaLIF) at the L4-5 level: a novel classification for case selection.

PURPOSE: To analyze correlations between the realistic surgical difficulty of LaLIF and anatomic characteristics in radiographic images, in order to develop a simple classification to provide guiding information for case selection and evaluate the potential risks of the technique. METHODS: Ninety-six consecutive cases who underwent LaLIF surgeries at the L4-5 level with MR T2-weighted images were analyzed. A novel classification based on the anatomic relationships among the disk, great vessels, and psoas muscle was used for grouping. Clinical outcomes and realistic surgical difficulty parameters were recorded, and comparisons were made among different types of classifications. RESULTS: Of the 96 analyzed cases, the time of surgical exposure was significantly longer for type C than for type B, and both of these were longer than that of type A. The VAS and ODI were significantly improved at a 1-year follow-up. There was no statistically significant difference among the three types. Type C had the highest incidence of complications, while Type A had the lowest. Analyses of another 304 MRI cases obtained in outpatient clinics showed that the distribution of the three types among these cases was consistent with that of the surgical cohort. CONCLUSION: Our novel and simple classification provides useful information for case selection. Type A provided the best indication and is most appropriate for a beginner in this technique. Type C includes the most challenging situations, which may have a high incidence of complications and require sophisticated surgical skills to achieve satisfactory outcomes and avoid approach-related complications.

Wnt4 signaling mediates protective effects of melatonin on new bone formation in an inflammatory environment.

Growing evidence shows that the inhibitory effect of inflammatory cytokines on new bone formation by osteogenic precursor cells is a critical cause of net bone-density reduction. Melatonin has been proven to be a potential therapeutic candidate for osteoporosis. However, whether it is capable of antagonizing the suppressing effect of inflammatory cytokines on osteogenic precursor cells is so far elusive. In this study, using the cell culture system of human bone marrow stromal cells and MC3T3-E1 preosteoblasts, we recorded the following vital observations that provided insights of melatonin-induced bone formation: 1) melatonin induced bone formation in both normal and inflammatory conditions; 2) Wnt4 was essential for melatonin-induced bone formation in inflammatory stimulation; 3) melatonin- and Wnt4-induced bone formation occurred via activation of ß-catenin and p38-JNK MAPK pathways by interaction with a distinct frizzled LDL receptor-related protein complex; 4) melatonin suppressed the inhibitory effect of NF-κB on osteogenesis in a Wnt4-dependent manner; and 5) melatonin induced Wnt4 expression through the ERK1/2-Pax2-Egr1 pathway. In summary, we showed a novel mechanism of melatonin-induced bone formation in an inflammatory environment. Melatonin-induced Wnt4 expression is essential for its osteoinductive effect and the inhibitory effect of NF-κB on bone formation. Our novel findings may provide useful information for its potential translational application.-Li, X., Li, Z., Wang, J., Li, Z., Cui, H., Dai, G., Chen, S., Zhang, M., Zheng, Z., Zhan, Z., Liu, H. Wnt4 signaling mediates protective effects of melatonin on new bone formation in an inflammatory environment.

Comparison of the use of rhBMP-7 versus iliac crest autograft in single-level lumbar fusion: a meta-analysis of randomized controlled trials.

The aim of this study was to evaluate the safety and clinical effectiveness of rhBMP-7 (or osteogenic protein-1) versus that of autogenous iliac crest bone graft (ICBG) in single-level posterolateral fusion (PLF) of the lumbar spine. A systematic search of all articles published through July 1, 2016 was conducted in databases such as PubMed, EMBASE, Scopus, and the Cochrane Collaboration Library. Randomized controlled trials (RCTs) that compared rhBMP-7 with ICBG for the treatment of single-level degenerative spondylolisthesis, provided the fusion rate, clinical success rate, safety and adverse events report, operation time, and hospital stay durations as the outcome were assessed. As a result, a total of five RCTs involving 539 patients met the inclusion criteria. The outcomes of subgroup analysis demonstrated that when compared with autogenous ICBG, rhBMP-7 appear to yield lower fusion rates in instrumented posterolateral fusion patients (RR = 0.76, 95% CI [0.60, 0.98], P = 0.03), despite the test for overall fusion rates suggested that there was no significant difference between the two groups (RR = 0.89, 95% CI [0.78, 1.02], P = 0.09). Patients treated with OP-1 had shorter operation times versus those treated with ICBG (WMD = -16.70,95% CI [-25.83, -7.57], P = 0.0003). Additionally, the outcomes demonstrated a lack of significant differences between rhBMP-7 and ICBG in terms of clinical success of ODI, overall adverse events, revision rates and duration of hospitalization. In conclusion, with the exception of reducing the operation time, our review suggests that the use of the rhBMP-7 instead of ICBG produce no any additional beneficial effect on the fusion rates, clinical success of ODI, overall adverse events, revision rates and duration of hospitalization in single level PLF. On the contrary, it appeared to yield lower fusion rate in the instrumented posterolateral fusion patients and cannot be recommended as an effective tool for this set of patients.

Halo-gravity traction in the treatment of severe spinal deformity: a systematic review and meta-analysis.

PURPOSE: Halo-gravity traction has been reported to successfully assist in managing severe spinal deformity. This is a systematic review of all studies on halo-gravity traction in the treatment of spinal deformity to provide information for clinical practice. METHODS: A comprehensive search was conducted for articles on halo-gravity traction in the treatment of spinal deformity according to the PRISMA guidelines. Appropriate studies would be included and analyzed. Preoperative correction rate of spinal deformity, change of pulmonary function and prevalence of complications were the main measurements. RESULTS: Sixteen studies, a total of 351 patients, were included in this review. Generally, the initial Cobb angle was 101.1° in the coronal plane and 80.5° in the sagittal plane, and it was corrected to 49.4° and 56.0° after final spinal fusion. The preoperative correction due to traction alone was 24.1 and 19.3%, respectively. With traction, the flexibility improved 6.1% but postoperatively the patients did not have better correction. Less aggressive procedures and improved pulmonary function were observed in patients with traction. The prevalence of traction-related complications was 22% and three cases of neurologic complication related to traction were noted. The prevalence of total complications related to surgery was 32% and that of neurologic complications was 1%. CONCLUSION: Partial correction could be achieved preoperatively with halo-gravity traction, and it may help decrease aggressive procedures, improve preoperative pulmonary function, and reduce neurologic complications. However, traction could not increase preoperative flexibility or final correction. Traction-related complications, although usually not severe, were not rare.

Posterior vertebral column resection in spinal deformity: a systematic review.

PURPOSE: This study aimed to assess the amount of correction and risk of complications of posterior vertebral column resection (PVCR) in the treatment of spinal deformity. METHODS: A comprehensive research was conducted in MEDLINE, EMBASE and Cochrane Database of Systematic Reviews for published articles about PVCR in spinal deformity. Data from these included studies were pooled with the help of the Review Manager software from the Cochrane Collaboration and the R software. The amount of correction of PVCR was indicated with change of coronal and sagittal Cobb angle after operation. Risk of complications was demonstrated with prevalence. RESULTS: 7 studies, a total of 390 patients, were included for analysis. The average operative time for PVCR was 430 min and the estimated blood loss was 2,639 ml. The mean amount of correction by PVCR was 64.1° in scoliosis and 58.9° in kyphosis, accounting a correction rate of 61.2 and 63.1 %, respectively. As to coronal and sagittal imbalance, data were limited. The overall prevalence of complications of PVCR was 32 % (95 % CI 12-54 %). The most common was neurologic complications, estimated to be 8 % (95 % CI 2-16 %). And risk of spinal cord injury was 2 % (95 % CI 0-3 %). The revision rate was 6 % (95 % CI 1-13 %). Incidence of infection was pooled to be 2 % (95 % CI 1-4 %). Complication rate related with implant was 2 % (95 % CI 0-6 %). CONCLUSION: PVCR is a powerful surgical procedure for severe spinal deformity. However, it has the risk of excessive blood loss and major complications. Decision of PVCR should be prudent and the procedure should be performed by an experienced surgical team.

TGF-ß1 antagonizes TNF-α induced up-regulation of matrix metalloproteinase 3 in nucleus pulposus cells: role of the ERK1/2 pathway.

Tumor necrosis factor-α (TNF-α) has been shown to have a catabolic effect on intervertebral disc degeneration (IVDD), including increasing MMP3 expression and subsequent extracellular matrix (ECM) degradation. In contrast, transforming growth factor-ß1 (TGF-ß1) has an anabolic effect on nucleus pulposus (NP) cells. However, the anti-catabolic effect of TGF-ß1 under inflammatory condition is unknown. The aim of this study was to demonstrate whether TGF-ß1 can reverse TNF-α-induced MMP3 increase in NP cells and to further investigate the underlying mechanisms. The transcriptional activity, gene expression, and protein levels of MMP3 were measured by luciferase reporter assay, qRT-PCR and western blot, respectively. TNF-α increased MMP3 expression in rat NP cells time and dose dependently. TGF-ß1 could abolish TNF-α-mediated up-regulation of collagen I and MMP3 expression, and down-regulate aggrecan and collagen II expression. The ERK1/2 signaling pathway was activated after exposure to TGF-ß1. Treatment with ERK1/2 inhibitors (PD98059 and U0126) abolished the antagonistic effect of TGF-ß1 on TNF-α mediated catabolic responses. These findings provide novel evidence supporting the anti-catabolic role of TGF-ß1 in IVDD, which is important for the potential clinical application of TGF-ß1 in disc degenerative disorders.

TNF-α and TGF-ß1 regulate Syndecan-4 expression in nucleus pulposus cells: role of the mitogen-activated protein kinase and NF-κB pathways.

Syndecan-4 is emerging as an important player in cell interaction with the extracellular environment and has been shown to be involved in the progression of intervertebral disc degeneration. However, the mechanism of syndecan-4 regulation by TNF-α and the role of TGF-ß1 in regulating syndecan-4 expression remain poorly understood in nucleus pulposus (NP) cells. The aim of this study was to investigate these mechanisms. We exposed NP cells to TNF-α and the gene, protein expression, and promoter activity levels of syndecan-4 were measured by qPCR, western blotting, and the luciferase reporter assay, respectively. The activation of the MAPK and NF-κB pathways was detected using western blot analysis. Syndecan-4 expression in rat NP cells was increased by TNF-α, but this was neither time nor dose dependent in response to TNF-α. ERK1/2, JNK, and NF-κB pathways were activated following TNF-α treatment. Treatment with ERK1/2 and NF-κB inhibitors decreased the up-regulation of syndecan-4 by TNF-α. However, JNK inhibition showed no effect on syndecan-4 expression induced by TNF-α. TNF-α mediated up-regulation of syndecan-4 was antagonized by TGF-ß1. This study provided evidence for the differential regulation by MAPK and NF-κB pathways in the over-expression of syndecan-4 promoted by TNF-α in NP cells. Our results demonstrate that TGF-ß1 exerts anabolic effects on intervertebral discs by inhibiting the expression of syndecan-4.

Pelvic retroversion is the key protective mechanism of L4-5 degenerative spondylolisthesis.

PURPOSE: To explore the role of spinopelvic sagittal alignment in the pathological mechanism of degenerative spondlylolisthesis (DS) development. METHOD: A total of 52 asymptomatic volunteers, 32 single segment L4-5 DS and 29 lumbar spinal stenosis (LSS) without spondylolisthesis patients were enrolled. All subjects had standard lumbar spine X-ray films with standard position along with lumbar spine magnetic resonance image. Comparative analysis of sagittal parameters and disc degeneration grades among asymptomatic volunteers and patients with the two disorders were performed. RESULTS: Compared to normal population (NP) and LSS, DS showed significantly greater pelvic incidence (PI), sacral slope (SS) and lumbar lordosis (LL), while LSS showed significantly smaller PT and PT/SS. DS showed significantly greater L5 slope than NP and LSS. In both Great-PI group and Small-PI group, all above differences between DS and LSS remained. LSS showed significantly higher degenerative grade of each adjacent disc than DS. Population with adjacent segment degeneration showed higher incidence of pelvic retroversion (PT/SS ≥1), and LSS showed greater proportion of adjacent segment degeneration than DS. CONCLUSIONS: Lumbar spine morphology of great LL determined by great PI is a risk factor of L4-5 DS. L5 slope is a parameter that can be used to predict the risk of L4-5 DS. Pelvic retroversion is the key protective mechanism from DS. Adjacent segment degeneration is a driving factor of pelvic retroversion for compensation of lumbar sagittal malalignment.

Comparison of the Wake-up Test and Combined TES-MEP and CSEP Monitoring in Spinal Surgery.

STUDY DESIGN: A retrospective clinical analysis. OBJECTIVE: The aim of this study was to compare the effectiveness of the wake-up test with that of combined monitoring of transcranial electrical stimulation motor evoked potentials (TES-MEP) and cortical somatosensory evoked potentials (CSEP) in spinal surgery. SUMMARY OF BACKGROUND DATA: TES-MEP/CSEP combined monitoring is being increasingly recognized as the ideal approach to detect spinal neurophysiological compromise during spinal surgery; however, as a result the merit of the wake-up test is now in doubt. MATERIALS AND METHODS: TES-MEP/CSEP combined monitoring was performed simultaneously in 426 patients who underwent spinal surgery at our department, and wake-up tests were conducted on 23 patients because of positive neurophysiological monitoring results with uncertain causes or persistent positive monitoring findings after all potential causes had been resolved. Preoperative and postoperative neurological examinations were performed as the gold standard to detect irreversible spinal function compromise. All data were collected to compare the efficiency of TES-MEP/CSEP combined monitoring with that of the wake-up test. RESULTS: Positive results of TES-MEP/CSEP combined monitoring were recorded in 64 cases. Among them, the positive monitoring findings agreed with the results of the neurological examination in 51 cases, and the monitoring results did not match that of neurological examination in 13 cases. No false-negative result was observed. The sensitivity of TES-MEP/CSEP monitoring was 100%, the specificity was 96.5%, and the Youden index was 0.965. Wake-up tests were conducted in 23 cases. In 8 patients the positive monitoring findings completely matched the postoperative neurological examination results. In contrast, in the other 15 cases with negative neurophysiological monitoring results, only 9 patients retained intact neurological function and 6 patients suffered compromised neurological function. The sensitivity of the wake-up test was 57.1%, the specificity was 100%, and the Youden index was 0.571. CONCLUSIONS: Combined TES-MEP and CSEP monitoring, with its high sensitivity and specificity, is an effective method for monitoring spinal function during surgery and should be the preferred choice. The wake-up test is a useful complementary method for monitoring because of its high specificity.

[Radiological factors influencing pulmonary function test in severe spinal deformity].

OBJECTIVE: To investigate the pulmonary dysfunction patterns in severe spinal deformity and to identify radiological factors affecting the pulmonary function. METHODS: From September 2009 to December 2014, a total of 66 patients were involved in this Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen University. Preoperative pulmonary function testing (PFTs) and radiographic examination were performed on all of the involved patients. Correlation analysis and subsequent stepwise multiple regression analysis were carried out to assess the associations between radiographic measurements of deformity and the results of pulmonary function testing. RESULTS: Fifty-seven out of 66 patients had impaired pulmonary dysfunction, and more than half of were ≤59% predicted forced expiratory volume in 1 second (FEV1). Most of the patients with severe spinal deformity demonstrated a restrictive pattern of pulmonary function. The magnitude of the major curve, the number of involved thoracic vertebrae had significant effect on pulmonary function. While these 2 factors were associated with an increased risk of pulmonary impairment, they explained only 46.2%-55.1% of the observed variability in vital capacity, forced vital capacity, and forced expiratory volume in one second. CONCLUSIONS: Preoperative PFTs are clinically impaired in 86% of patients with severe spinal deformity, and more than half of that were moderate and severe pulmonary dysfunction. The magnitude of the major curve and the number of involved thoracic vertebrae are the main risk factors influencing the pulmonary dysfunction.

Inflammatory cytokines induce NOTCH signaling in nucleus pulposus cells: implications in intervertebral disc degeneration.

The objective of the study was to investigate how inflammatory cytokines, IL-1ß, and TNF-α control NOTCH signaling activity in nucleus pulposus (NP) cells. An increase in expression of selective NOTCH receptors (NOTCH1 and -2), ligand (JAGGED2), and target genes (HES1, HEY1, and HEY2) was observed in NP cells following cytokine treatment. A concomitant increase in NOTCH signaling as evidenced by induction in activity of target gene HES1 and HEY1 promoters and reporter 12xCSL was seen. Moreover, treatment increased activity of a 2-kb NOTCH2 promoter. Treatment of cells with NF-κB and MAPK inhibitors abolished the inductive effect of cytokines on NOTCH2 promoter and its expression. Gain and loss-of-function studies confirmed the inductive effect of p65 on NOTCH2 promoter activity. In contrast, p50 blocked the cytokine induction of promoter activity. Supporting promoter studies, lentiviral delivery of sh-p65, and sh-IKKß significantly decreased cytokine dependent change in NOTCH2 expression. Interestingly, MAPK signaling showed an isoform-specific control of NOTCH2 promoter; p38α/ß2/δ, ERK1, and ERK2 contributed to cytokine dependent induction, whereas p38γ played no role. Analysis of human NP tissues showed that NOTCH1 and -2 and HEY2 expression correlated with each other. Moreover, expression of NOTCH2 and IL-1ß as well as the number of cells immunopositive for NOTCH2 significantly increased in histologically degenerate discs compared with non-degenerate discs. Taken together, these results explain the observed dysregulated expression of NOTCH genes in degenerative disc disease. Thus, controlling IL-1ß and TNF-α activities during disc disease may restore NOTCH signaling and nucleus pulposus cell function.

Comparison of unilateral versus bilateral pedicle screw fixation in lumbar interbody fusion: a meta-analysis.

PURPOSE: This is a meta-analysis to compare the clinical results between unilateral and bilateral pedicle screw (PS) fixation in lumbar interbody fusion. METHODS: We included published studies with no language and year restrictions. The criteria which Koes et al. designed in 1995 were used to evaluate the risk of bias of the included studies. All data were analyzed by Review Manager 5.1. The primary outcomes included fusion rate and screw complications, and the secondary outcomes were operative time, blood loss, and hospital time. RESULTS: A total of five prospective studies with 407 patients were included in the current meta-analysis, and four of them were randomized controlled trials. There was no significant difference between unilateral PS fixation and bilateral PS fixation group in fusion rate and screw complications (fusion rate: OR 0.54, Z = 1.33, P = 0.18, I (2) = 0 %; screw complications: OR 1.45, Z = 0.71, P = 0.48; I (2) = 44 %). In the secondary outcomes, the operative time (Z = 3.35, P = 0.0008; I (2) = 95 %) and blood loss (Z = 4.35, P < 0.0001; I (2) = 98 %) was significantly higher in bilateral PS fixation group than in unilateral PS fixation group. Besides, no significant difference was found in hospital time (Z = 1.19, P = 0.24; I (2) = 99 %). CONCLUSIONS: In our meta-analysis, we found that unilateral PS fixation in lumbar fusion was as effective as bilateral PS fixation for lumbar degenerative diseases without major instability, no significant difference was found in hospital time, fusion rate and screw complications. In terms of operative time and blood loss, unilateral PS fixation even produced better results.