Ephrin B2 (EFNB2) potentially protects against intervertebral disc degeneration through inhibiting nucleus pulposus cell apoptosis.

Nucleus pulposus (NP) cell apoptosis is a significant indication of accelerated intervertebral disc degeneration; however, the precise mechanism is unelucidated as of yet. Ephrin B2 (EFNB2), the only gene down-regulated in the three degraded intervertebral disc tissue microarray groups (GSE70362, GSE147383 and GSE56081), was screened for examination in this study. Subsequently, EFNB2 was verified to be down-regulated in degraded NP tissue samples. Interleukin-1 (IL-1ß) treatment of NP cells to simulate the IDD environment indicated that IL-1ß treatment decreased EFNB2 expression. In degenerative NP cells stimulated by IL-1ß, EFNB2 knockdown significantly increased the rate of apoptosis as well as the apoptosis-related molecules cleaved-caspase-3 and the Bax to Bcl-2 ratio. EFNB2 was found to promote AKT, PI3K, and mTOR phosphorylation; the PI3K/AKT signaling role was investigated using the PI3K inhibitor LY294002. EFNB2 overexpression significantly increased PI3K/AKT pathway activity in IL-1ß-stimulated NP cells than the normal control. Moreover, EFNB2 partially alleviated NP cell apoptosis induced by IL-1ß, reduced the cleaved-cas3 level, and decreased the Bax/Bcl-2 ratio after the addition of the inhibitor LY294002. Additionally, EFNB2 overexpression inhibited the ERK1/2 phosphorylation; the effects of EFNB2 overexpression on ERK1/2 phosphorylation, degenerative NP cell viability, and cell apoptosis were partially reversed by ERK signaling activator Ceramide C6. EFNB2 comprehensively inhibited the apoptosis of NP cells by activating the PI3K/AKT signaling and inhibiting the ERK signaling, obviating the exacerbation of IDD. EFNB2 could be a potential target to protect against degenerative disc changes.

Predicting the ideal apex of lumbar lordosis based on individual pelvic incidence and inflection point in asymptomatic adults.

Objective: The main aim of this study was to comprehensively explore the relationship among pelvic incidence (PI), inflection point (IP), and apex of lumbar lordosis (LLA), and establish a predictive formula for LLA based on individual PI and IP in asymptomatic Chinese adults. Methods: A total of 385 asymptomatic adults with average age 38.3 ± 11.9 years (range 20-73 years) were recruited between November 2020 and October 2021. Full-spine, standing x-rays were then obtained from each participant. Next, the following sagittal parameters were measured: PI, IP, LLA, the horizontal offset between the plumb line of the lumbar apex and that of the posterosuperior corner of S1 (LASO), the upper lumbar lordosis (ULL) and lower lumbar lordosis (LLL), lumbar lordosis (LL), and thoracic kyphosis (TK). Moreover, the association among PI, IP, and the other sagittal parameters was evaluated, followed by linear regression analyses. A P-value of <0.05 was considered statistically significant. Results: PI showed statistically significant correlations with LLA (rs = -0.629; P < 0.01), LASO (rs = 0.537; P < 0.01), LLL (rs = 0.788; P < 0.01), and LL (rs = 0.663; P < 0.01). On the other hand, IP also showed statistically significant correlations with LLA (rs = 0.671; P < 0.01), LASO (rs = -0.493; P < 0.01), LLL (rs = -0.402; P < 0.01), and LL (rs = -0.283; P < 0.01). The corresponding predictive formulae were displayed as follows: LLA = -0.03 * PI + 0.23 * IP + 14.45 (R 2 = 0.669); LASO = 0.38 * PI-2.09 * IP + 53.62 (R 2 = 0.460); and LLL = 0.58 * PI-0.88 * IP + 18.86 (R 2 = 0.659). Conclusion: The specific lumbar shape should be modulated by pelvic morphology and IP level. In addition, we established predictive formulae for ideal sagittal lumbar profile based on individual PI and IP, with the overarching goal of helping surgeons to better comprehend the regulatory mechanisms of the individual sagittal lumbar alignment, and design a precise and personalized corrective plan.

Restoring Theoretically Optimal Lumbar Lordosis Deduced from Pelvic Incidence and Thoracic Kyphosis has Advantages to Decrease the Risk of Postoperative Mechanical Complications in Adult Spinal Deformity.

Objective: To establish a regression formula for LL based on individual PI and TK in asymptomatic population aged over 50 years and evaluate its predictive power for the occurrence of postoperative mechanical complications in patients with adult spinal deformity (ASD). Methods: A total of 178 asymptomatic adults were recruited for the study. The association between LL and PI, LL and TK, was investigated to establish a predictive formula for ideal LL based on PI and TK. Additionally, 93 ASD patients undergoing posterior correction surgery were retrospectively analyzed. The absolute value of the gap between postoperative actual LL and theoretical LL was defined as ΔLL. Patients were classified into two groups depending on the presence or absence of mechanical complications. The demographic and radiological data of patients were compared between the two groups. Results: A significant association was found between LL and PI (r = 0.599, P < 0.001), LL and TK (r = 0.523, P < 0.001). A novel formula was developed as follows: LL = 0.7*PI + 0.4*TK + 1 (R 2 = 0.524). In the validation cohort, 29 patients developed mechanical complications. Postoperative ΔLL (12.5 ± 7.6° vs. 7.0 ± 5.4°, P = 0.001) significantly increased the incidence of mechanical complications. The most appropriate threshold of ΔLL for predicting mechanical complications was 9.8°. For patients whose ΔLL were <9.8° and >9.8°, the incidence of mechanical complications was 19.4% and 54.8%, respectively. Conclusion: Ideal lumbar lordosis should be matched for PI and TK. The developed prediction formula for LL based on PI and TK in asymptomatic adults may help surgeons to understand the mechanisms of lumbar alignment generation and predict occurrence of mechanical complications after ASD surgery.

The top 100 most-cited articles on adult spinal deformity: The most popular topics are still sagittal plane parameters and complications.

Purpose: This study aimed to summarize the characteristics of the 100 most-cited articles on adult spinal deformity (ASD) and to analyze past and current research hotspots and trends. Methods: Literature searches (from inception to 28 April 2022) using Web of Science databases were conducted to identify ASD-related articles. The top 100 most-cited articles were collected for further analysis. Meanwhile, author keywords from articles published in the last 5 years were selected for further analysis. Results: The top 100 most-cited articles on ASD were selected from 3,354 papers. The publication year ranged from 1979 to 2017, and all papers were written in English. The citation count among them ranged from 100 to 1,145, and the mean citation number was 215.2. The foremost productive first author was Schwab F. University of Washington had the largest number of publications. The United States of America had the largest number of published articles (n = 84) in this field. Spine was the most popular journal. Complications were the most studied themes. The visualization analysis of author keywords from the literature in the recent 5 years showed that complications, sagittal plane parameters, and surgical techniques are still the research hotspots, and minimally invasive surgery will continue to develop rapidly. Conclusion: Based on a comparative analysis of the results of bibliometric and visualization, complications and sagittal plane parameters are still the major topics of research at present and even later, and minimally invasive surgery has a growth trend in this field of ASD.

Activation of TREM-1 induces endoplasmic reticulum stress through IRE-1α/XBP-1s pathway in murine macrophages.

Increasing evidence suggests that endoplasmic reticulum (ER) stress activates several pro-inflammatory signaling pathways in many diseases, including acute lung injury (ALI). We have reported that blocking triggering receptor expressed on myeloid cells 1 (TREM-1) protects against ALI by suppressing pulmonary inflammation in mice with ALI induced by lipopolysaccharides (LPS). However, the molecular mechanism underlying the TREM-1-induced pro-inflammatory microenvironment in macrophages remains unclearly. Herein, we aimed to determine whether TREM-1 regulates the inflammatory responses induced by LPS associated with ER stress activation. We found that the activation of TREM-1 by a monoclonal agonist antibody (anti-TREM-1) increased the mRNA and protein levels of IL-1ß, TNF-α, and IL-6 in primary macrophages. Treatment of the anti-TREM-1 antibody increased the expression of ER stress markers (ATF6, PERK, IRE-1α, and XBP-1s) in primary macrophages. While pretreatment with 4-PBA, an inhibitor of ER stress, significantly inhibited the expression of ER stress markers and pro-inflammatory cytokines and reduced LDH release. Furthermore, inhibiting the activity of the IRE-1α/XBP-1s pathway by STF-083010 significantly mitigated the increased levels of IL-1ß, TNF-α, and IL-6 in macrophages treated by the anti-TREM-1 antibody. XBP-1 silencing attenuated pro-inflammatory microenvironment evoked by activation of TREM-1. Besides, we found that blockade of TREM-1 with LR12 ameliorated ER stress induced by LPS in vitro and in vivo. In conclusion, we conclude that TREM-1 activation induces ER stress through the IRE-1α/XBP-1s pathway in macrophages, contributing to the pro-inflammatory microenvironment.

The Relationship Between Tumor-Stroma Ratio, the Immune Microenvironment, and Survival in Patients With Spinal Chordoma.

BACKGROUND: Currently, little is known about the clinical relevance of tumor-stroma ratio (TSR) in chordoma and data discussing the relationship between TSR and immune status of chordoma are lacking. OBJECTIVE: To characterize TSR distribution in spinal chordoma, and investigated its correlation with clinicopathologic or immunological features of patients and outcome. METHODS: TSR was assessed visually on hematoxylin and eosin-stained sections from 54 tumor specimens by 2 independent pathologists. Multiplex immunofluorescence was used to quantify the expression levels of microvessel density, Ki-67, Brachyury, and tumor as well as stromal PD-L1. Tumor immunity status including the Immunoscore and densities of tumor-infiltrating lymphocytes (TILs) subtypes were obtained from our published data and reanalyzed. RESULTS: Bland-Altman plot showed no difference between mean TSR derived from the two observers. TSR was positively associated with stromal PD-L1 expression, the Immunoscore and CD3+ as well as CD4+ TILs density, but negatively correlated with tumor microvessel density, Ki-67 index, surrounding muscle invasion by tumor and number of Foxp3+ and PD-1+ TILs. Low TSR independently predicted poor local recurrence-free survival and overall survival. Moreover, patients with low TSR and low Immunoscore chordoma phenotype were associated with the worst survival. More importantly, combined TSR and Immunoscore accurately reflected prognosis and enhanced the ability of TSR or Immunoscore alone for outcome prediction. CONCLUSION: These data reveal the significant impact of TSR on tumor progression and immunological response of patients. Subsequent use of agents targeting the stroma compartment may be an effective strategy to treat chordoma especially in combination with immune-based drugs.

Unilateral Versus Bilateral Pedicle Screw Fixation in Transforaminal Lumbar Interbody Fusion: A Monocentric Study of 215 Patients With a Minimum of 4-Year Follow-up.

STUDY DESIGN: A retrospective clinical study. OBJECTIVE: This study sought to retrospectively compare the mid-term to long-term outcomes between unilateral pedicle screw (UPS) and bilateral pedicle screw (BPS) augmented transforaminal lumbar interbody fusion (TLIF) in lumbar degenerative diseases. SUMMARY OF BACKGROUND DATA: Recently, UPS fixation has been applied in TLIF, for its satisfactory clinical outcome, less implants and less invasiveness. However, only short-term outcome has been reported, the mid-term to long-term outcome has not been well characterized. MATERIALS AND METHODS: From June 2007 to February 2011, 215 of 348 consecutive patients suffering from lumbar degenerative diseases were operated in our hospital and accomplished a minimum of 4-year follow-up. These patients were divided into 2 groups according to the operative techniques: UPS group (n=109), and bilateral pedicle screw group (n=106). Operative time, blood loss, length of hospital stay, hospital bill, fusion status, and complications were recorded and analyzed statistically. Visual analog scale, Oswestry disability index, and Japanese Orthopaedic Association scores were used to assess the preoperative and postoperative pain and functional outcome. RESULTS: The mean follow-up duration was 52.2 months. A significant decrease occurred in operative time, blood loss, and hospital bill in unilateral group, compared with bilateral group (P<0.05). The average postoperative visual analog scale, Oswestry disability index, and Japanese Orthopaedic Association scores improved significantly in each group than the preoperative counterparts (P<0.05); however, there were no significant difference between groups at any follow-up time point (P>0.05). No statistically difference was detected regarding fusion rate and complication rate between the 2 groups (P>0.05), except the cage migration rate (P<0.05). CONCLUSIONS: UPS fixation could achieve satisfactory clinical outcome similar to bilateral fixation in TLIF at a mid-term to long-term follow-up. To avoid cage migration, bullet-shaped cages should not be used in the unilateral group.

Miniopen Transforaminal Lumbar Interbody Fusion with Unilateral Fixation: A Comparison between Ipsilateral and Contralateral Reherniation.

The aim of this study was to evaluate the risk factors between ipsilateral and contralateral reherniation and to compare the effectiveness of miniopen transforaminal lumbar interbody fusion (TLIF) with unilateral fixation for each group. From November 2007 to December 2014, clinical and radiographic data of each group (ipsilateral or contralateral reherniation) were collected and compared. Functional assessment (Visual Analog Scale (VAS) score and Japanese Orthopaedic Association (JOA)) and radiographic evaluation (fusion status, disc height, lumbar lordosis (LL), and functional spine unit (FSU) angle) were applied to compare surgical effect for each group preoperatively and at final followup. MacNab questionnaire was applied to further evaluate the satisfactory rate after the discectomy and fusion. No difference except pain-free interval was found between ipsilateral and contralateral groups. There was a significant difference in operative time between two groups. No differences were found in clinical and radiographic data for assessment of surgical effect between two groups. The satisfactory rate was decreasing in both groups with time passing after discectomy. Difference in pain-free interval may be a distinction for ipsilateral and contralateral reherniation. Miniopen TLIF with unilateral pedicle screw fixation can be a recommendable way for single level reherniation regardless of ipsilateral or contralateral reherniation.

Clinical outcomes and sagittal alignment of single-level unilateral instrumented transforaminal lumbar interbody fusion with a 4 to 5-year follow-up.

PURPOSE: A retrospective study was designed to evaluate clinical outcomes and sagittal alignment following single-level unilateral instrumented transforaminal lumbar interbody fusion (TLIF). METHODS: From November 2008 to December 2010, a total of 139 patients, who suffered from single-level lumbar degenerative disease, were included in this study. Forty-seven males and seventy-two females with a mean age of 57.3 years were enrolled. The average follow-up period was 51.7 months with a range of 41-66 months. The follow-up rate was 85.6 %. Thirty-one patients had diagnosis of discogenic low back pain, ten had recurrent disk herniation, thirty-four had spinal stenosis, and fourty-four had spondylolisthesis. Clinical outcomes were evaluated using the Oswestry disability index (ODI), visual analog scale (VAS) and Japanese Orthopedic Association. Operating time, blood loss, length of stay, and complications were also evaluated. The sagittal alignment and fusion status were assessed by X-ray and three-dimensional computed tomography. RESULTS: The average operating time was 92.1 ± 27.5 min, the average blood loss was 135.1 ± 113.5 ml, and the average length of stay was 12.0 ± 2.9 days. The overall complication rate was 13.4 %, and the fusion rate was 82.4 %. The postoperative clinical outcomes and sagittal alignment were significantly different from the preoperative values. The final lumbar lordosis angle and segment lordosis angle were associated with back pain VAS and ODI scores, respectively. CONCLUSION: Unilateral instrumented TLIF is a safe and effective treatment option for single-level lumbar degenerative disease, and is less invasive, yields good outcomes and has a low complication rate. In addition, the procedure has the potential to partly restore sagittal alignment.