C4 constant vertebra: a novel benchmark of physiological cervical sagittal alignment.

BACKGROUND: Cervical sagittal alignment is essential, and there is considerable debate as to what constitutes physiological sagittal alignment. The purpose of this study was to identify constant parameters for characterizing cervical sagittal alignment under physiological conditions. METHODS: A cross-sectional study was conducted in which asymptomatic subjects were recruited to undergo lateral cervical spine radiographs. Each subject was classified according to three authoritative cervical sagittal morphology classifications, followed by the evaluation of variations in radiological parameters across morphotypes. Moreover, the correlations among cervical sagittal parameters, age, and cervicothoracic junction parameters were also investigated. RESULTS: A total of 183 asymptomatic Chinese subjects were enrolled with a mean age of 48.4 years. Subjects with various cervical sagittal morphologies had comparable C4 endplate slope angles under all three different typing systems. Among patients of different ages, C2-C4 endplate slope angles remained constant. Regarding the cervicothoracic junction parameters, T1 slope and thoracic inlet angle affected cervical sagittal parameters, including cervical lordosis and C2-7 sagittal vertical axis, and were correlated with the endplate slope angles of C5 and below and did not affect the endplate slope angles of C4 and above. In general, the slope of the C4 inferior endplate ranges between 13° and 15° under different physiological conditions. CONCLUSIONS: In the asymptomatic population, the C4 vertebral body maintains a constant slope angle under physiological conditions. The novel concept of C4 as a constant vertebra would provide a vital benchmark for diagnosing pathological sagittal alignment abnormalities and planning the surgical reconstruction of cervical lordosis.

Evaluation of the modified MRI vertebral bone quality score for bone quality in lumbar degenerative disorders.

OBJECTIVE: The traditional VBQ scoring method may lead to overestimation due to the concentration of intravertebral fat and vascular structures in the posterior half of vertebral bodies, potentially resulting in false-positive outcomes. This study aims to modify the measurement method of VBQ score (Modified-VBQ) and evaluate its effectiveness in evaluating bone quality of lumbar degenerative diseases. METHODS: Retrospective analysis was conducted on clinical data from patients undergoing lumbar surgery for degenerative diseases between September 2022 and September 2023. Preoperative lumbar t1-weighted Magnetic resonance imaging was used for both modified and traditional VBQ scoring. Computed tomography (CT) images and dual-energy X-ray absorptiometry (DEXA) data were collected through the picture archiving and communication system. The effectiveness of the modified VBQ score was evaluated, considering P < 0.05 as statistically significant. RESULTS: The study included 212 patients, revealing a significant difference between the modified VBQ and VBQ scores (P < 0.0001). Notably, patients with a history of hyperlipidemia exhibited a significant difference between the two scores (P = 0.0037). The area under the ROC curve (AUC) for the modified VBQ was 0.86, surpassing the VBQ score (AUC = 0.74). Linear regression analysis demonstrated a moderate to strong correlation between the modified VBQ and DEXA T-score (r = - 0.49, P < 0.0001) and a high correlation with CT Hounsfield units (HU) values (r = - 0.60, P < 0.0001). CONCLUSION: The modified VBQ score provides a simple, effective, and relatively accurate means of assessing bone quality in lumbar degenerative diseases. Preoperative implementation of the modified VBQ score facilitates rapid screening for patients with abnormal bone quality.

Use of MRI-based vertebral bone quality score (VBQ) of S1 body in bone mineral density assessment for patients with lumbar degenerative diseases.

PURPOSE: To evaluate the use of the modified and simplified vertebral bone quality (VBQ) method based on T1-weighted MRI images of S1 vertebrae in assessing bone mineral density (BMD) for patients with lumbar degenerative diseases. METHODS: We reviewed the preoperative data of patients with lumbar degenerative diseases undergoing lumbar spine surgery between January 2019 and June 2022 with available non-contrast T1-weighted magnetic resonance imaging (MRI), computed tomography (CT) images and dual-energy X-ray absorptiometry (DEXA). S1 vertebral bone quality scores (S1 VBQ) and S1 CT Hounsfield units were measured with picture archiving and communication system (PACS). One-way ANOVA was applied to present the discrepancy between the S1 VBQ of patients with normal bone density (T-score ≥ - 1.0), osteopenia (- 2.5 < T-score < - 1.0) and osteoporosis (T-score ≤ - 2.5). The receiver operating characteristic curve (ROC) was drawn to analyze the diagnostic performance of S1 VBQ in distinguishing low BMD. Statistical significance was set at p < 0.05. RESULTS: A total of 207 patients were included. The S1 VBQ were significantly different between groups (p < 0.001). Interclass correlation coefficient for inter-rater reliability was 0.86 (95% CI 0.78-0.94) and 0.94(95% CI 0.89-0.98) for intra-rater reliability. According to the linear regression analysis, the S1 VBQ has moderate-to-strong correlations with DEXA T-score (r = - 0.48, p < 0.001). The area under the ROC curve indicated a predictive accuracy of 82%. A sensitivity of 77.25% with a specificity of 70% could be achieved for distinguishing low BMD by setting the S1 VBQ cutoff as 2.93. CONCLUSIONS: The S1 VBQ was a promising tool in distinguishing poor bone quality in patients with lumbar degenerative diseases, especially in cases where the previously reported VBQ method based on L1-L4 was not available. S1 VBQ score could be useful as opportunistic assessment for screening and complementary evaluation to DEXA T-score before surgery.

A Novel Cervical Sagittal Classification for Asymptomatic Population Based on Cluster Analysis.

STUDY DESIGN: Cross-sectional study. OBJECTIVE: To propose a novel cervical sagittal classification for asymptomatic people so as to deepen the understanding of cervical sagittal alignment. SUMMARY OF BACKGROUND DATA: Cervical spine sagittal morphology varies in people. There is a lack of widely-accepted cervical sagittal classification method. METHODS: In all, 183 asymptomatic subjects were included. A series of global and segmental cervical sagittal parameters were measured. Subjects with cervical lordosis (CL)<0 degrees were incorporated directly into the kyphosis (K) group. For subjects with CL ≥0 degrees, a two-step cluster analysis was used to arrive at the optimal number of clusters. The results of the expressions for the subtypes were derived by graphing. The 60 randomly selected lateral cervical spine films were evaluated by 4 spine surgeons at 4-week intervals using our classification method, the Toyama classification method and the Donk classification method. The 3 classification methods' reliability was expressed by the intra-group correlation coefficient (ICC), and convenience was expressed by the measuring time. Finally, the distribution of 4 subtypes was depicted, and sagittal parameters were compared among subtypes. RESULTS: Four subtypes of the cervical spine were suggested: Large lordosis (LL): CL≥-1.5×T1 slope (TS)+70°; Small lordosis (SL): -1.5×TS+50°≤CL<-1.5×TS+70°; Straight (S): 0°≤CL<-1.5×TS+50°; and K: CL<0°. The measuring time for our classification method was significantly less than the Toyama classification method (P<0.001). Our classification method showed high inter-observer reliability (ICC=0.856) and high to excellent intra-observer reliability (ICC between 0.851 and 0.913). SL was the most common type (37.7%). Men had more LL type and women had more S type and K type. The proportion of S and K increased with age. Cervical sagittal parameters were significantly different among the subtypes except for C4 vertebral body (VB) angle (P=0.546), C2-C7 SVA (P=0.628) and NT (P=0.816). CONCLUSIONS: We proposed a novel cervical sagittal classification for an asymptomatic population, which proved to be simple to implement with satisfactory reliability.

HIF-1α-induced expression of the m6A reader YTHDF1 inhibits the ferroptosis of nucleus pulposus cells by promoting SLC7A11 translation.

The nucleus pulposus is in a hypoxic environment in the human body, and when intervertebral disc degeneration (IVDD) occurs, the hypoxic environment is disrupted. Nucleus pulposus cell (NPC) ferroptosis is one of the causes of IVDD. N6-methyladenosine (m6A) and its reader protein YTHDF1 regulate cellular activities by affecting RNA metabolism. However, the regulation of ferroptosis in NPCs by m6A-modified RNAs under hypoxic conditions has not been as well studied. In this study, through in vitro and in vivo experiments, we explored the underlying mechanism of HIF-1α and YTHDF1 in regulating ferroptosis in NPCs. The results indicated that the overexpression of HIF-1α or YTHDF1 suppressed NPC ferroptosis; conversely, the knockdown of HIF-1α or YTHDF1 increased ferroptosis levels in NPCs. Luciferase reporter assays and chromatin immunoprecipitation demonstrated that HIF-1α regulated YTHDF1 transcription by directly binding to its promoter region. Polysome profiling results showed that YTHDF1 promoted the translation of SLC7A11 and consequently the expression of the anti-ferroptosis protein GPX4 by binding to m6A-modified SLC7A11 mRNA. In conclusion, HIF-1α-induced YTHDF1 expression reduces NPC ferroptosis and delays IVDD by promoting SLC7A11 translation in a m6A-dependent manner.

Dihydroorotate dehydrogenase regulates ferroptosis in neurons after spinal cord injury via the P53-ALOX15 signaling pathway.

BACKGROUND: Spinal cord injury (SCI) is a highly disabling condition in spinal surgery that leads to neuronal damage and secondary inflammation. Ferroptosis is a non-apoptotic type of cell death that has only recently been identified, which is marked primarily by iron-dependent and lipid-derived reactive oxygen species accumulation, and accompanied by morphological modifications such as mitochondrial atrophy and increase in membrane density. Dihydroorotate dehydrogenase (DHODH) is a powerful inhibitor of ferroptosis and has been demonstrated to inhibit cellular ferroptosis in tumor cells, but whether it can inhibit neuronal injury following spinal cord injury remains ambiguous. METHODS: In this study, the effect of DHODH on neuronal ferroptosis was observed in vivo and in vitro using a rat spinal cord injury model and erastin-induced PC12 cells, respectively. A combination of molecular and histological approaches was performed to assess ferroptosis and explore the possible mechanisms in vivo and in vitro. RESULTS: First, we confirmed the existence of neuronal ferroptosis after spinal cord injury and that DHODH attenuates neuronal damage after spinal cord injury. Second, we showed molecular evidence that DHODH inhibits the activation of ferroptosis-related molecules and reduces lipid peroxide production and mitochondrial damage, thereby reducing neuronal ferroptosis. Further analysis suggests that P53/ALOX15 may be one of the mechanisms regulated by DHODH. Importantly, we determined that DHODH inhibits ALOX15 expression by inhibiting P53. CONCLUSIONS: Our findings reveal a novel function for DHODH in neuronal ferroptosis after spinal cord injury, suggesting a unique therapeutic target to alleviate the disease process of spinal cord injury.

Preoperative Assessment of Bone Density Using MRI-Based Vertebral Bone Quality Score Modified for Patients Undergoing Cervical Spine Surgery.

STUDY DESIGN: Diagnostic accuracy study. OBJECTIVES: Previous studies have reported the clinical application of the Vertebral Bone Quality (VBQ) scores for assessing bone density in operative lumbar spine patients. We aim to explore whether the method could be modified and applicable for patients undergoing cervical spine surgery. METHODS: Adult patients receiving cervical spine surgery for degenerative diseases between September 2020 and March 2022 with non-contrast T1-weighted MRI and DEXA were included. Correlation between cervical VBQ scores and DEXA T-scores was analyzed using Pearson's correlation. Student's t test was used to present the discrepancy between the VBQ of patients with normal bone density (T ≥ -1.0) and patients with osteopenia/osteoporosis (T < -1.0). Statistical significance was set at P < .05. RESULTS: Eighty-three patients (20 patients with T ≥ -1.0 vs 63 patients with T < -1.0 ) were included. Significant difference was found between the cervical VBQ between groups (2.99 ± .79 vs 3.80 ± .81, P < .001). Interclass correlation coefficient for inter-rater reliability was .82 (95% CI: .70-.93) and .91(95% CI: .84-.97) for intra-rater reliability. The area under the ROC curve was .78 (95% CI: .65-.90). The DEXA T-score of the femoral neck, total hip and the lowest DEXA T-score were found to be significantly correlated with the cervical VBQ score according to Pearson correlation analysis (P < .001). CONCLUSIONS: This is the first study to apply the VBQ method to assess the bone density in preoperative cervical spine patients. Cervical VBQ scores were significantly correlated with DEXA T-score. With an overall accuracy of .78, the radiation-free and cost-effective method could be a potential tool for screening patients with osteopenia and osteoporosis before surgery.

Low lumbar multifidus muscle status and bone mineral density are important risk factors for adjacent segment disease after lumbar fusion: a case-control study.

BACKGROUND: The quantity and quality of the paraspinal muscles are important factors that lead to spinal diseases. However, the role of paraspinal muscles in the pathogenesis of adjacent segment disease (ASD) after lumbar fusion surgery is rarely studied. The purpose of the research is to investigate the relationship between paraspinal muscles and ASD. METHODS: Thirty-three patients with ASD were included, and 33 controls without ASD were matched according to the basic demographic information. Cross-sectional images of the paraspinal muscles at each intervertebral disk level (L1-S1) before the first operation were analyzed, and the cross-sectional area (CSA) and degree of fat infiltration (FI) of the multifidus (MF) muscle and the erector spinae muscle were compared. RESULTS: There was no significant difference in demographic characteristics (P > 0.05) except for the bone mineral density (BMD) (P = 0.037) between the two groups. There were significant differences in the CSA and FI of the lower lumbar multifidus (P < 0.05). The CSA of the MF muscle at L3-L4, FI of the MF muscle at L4-L5 and L5-S1 and BMD were important risk factors for ASD. Among patients who received two-segment fusion for the first time, significant difference was observed in the degree of FI of the MF muscle in the lower lumbar segment (P < 0.05). CONCLUSIONS: The CSA, FI and BMD of the lower lumbar MF muscle were closely related to the occurrence of ASD. The CSA of the MF muscle at L3-L4, the degree of FI of the MF muscle at L4-L5 and L5-S1 and BMD were important risk factors for ASD. The number of fusion segments in the first operation has a certain impact on the above-mentioned conclusions.

The Short-Term to Midterm Follow-Up of Patients with Hirayama Disease After Anterior Cervical Discectomy and Fusion.

OBJECTIVE: Surgical treatment is widely used to treat patients with Hirayama disease (HD). However, postoperative follow-up with abundant samples is still scarce. This study investigated short-term to midterm clinical outcomes after anterior cervical discectomy and fusion (ACDF) among patients with HD. METHODS: We enrolled 115 patients with HD who had undergone ACDF. Radiographic parameters included cervical lordosis (CL), sagittal vertical axis, segment lordosis (SL), T1 slope (T1S), T1S minus CL, range of motion (ROM), upper/lower adjacent segment ROM, and upper adjacent SL. Electrophysiologic parameters included the maximal compound muscle action potentials (CMAPs) of abductor digit minimi and abductor pollicis brevis, the latency of the ulnar nerve F reaction, and abnormal spontaneous action potentials. Clinical assessment included the selected brief-Michigan Hand Questionnaire and Odom scale. RESULTS: The average age was 19.5 ± 4.5 years. The mean follow-up time was 16.35 ± 9.21 months. CL, SL, and T1S increased, whereas sagittal vertical axis and ROM decreased at the final follow-up (P < 0.001). Upper adjacent SL, upper adjacent ROM, and lower adjacent ROM were stable after ACDF (P > 0.05). The maximal CMAPs of abductor digit minimi and the latency of the ulnar nerve F reaction improved bilaterally (P < 0.05), whereas there was no significance in the maximal CMAPs of abductor pollicis brevis (P > 0.05). Abnormal spontaneous action potentials reduced remarkably. The selected brief-Michigan Hand Questionnaire score increased after surgery (P < 0.001). The Odom scale showed a ratio of 79.1% (excellent and good ratio). CONCLUSIONS: This study showed favorable radiologic, electrophysiologic, and clinical outcomes after ACDF among patients with HD.

Tamsulosin combined with solifenacin versus tamsulosin monotherapy for male lower urinary tract symptoms: a meta-analysis.

OBJECTIVE: To evaluate the efficacy and safety of tamsulosin and solifenacin combination therapy compared with tamsulosin monotherapy for male lower urinary tract symptoms (LUTS). METHODS: We identified all eligible studies that compared tamsulosin and solifenacin combination therapy with tamsulosin monotherapy for male LUTS (up to January 2015). The fixed- or random-effects model was selected depending on the proportion of heterogeneity. RESULTS: Seven articles were identified as eligible for this meta-analysis, with a total of 3063 participants. Synthetic data showed combination therapy had significant improvements in Storage International Prostate Symptom Score (WMD = -0.60; 95% CI: -0.81 to -0.38, P < 0.0001), quality of life (WMD = -0.23; 95% CI: -0.34 to -0.11, P < 0.0001), micturitions per 24 hours (WMD = -0.70; 95% CI: -0.86 to -0.55, P < 0.0001) and urgency episodes per 24 hours (WMD = -0.26; 95% CI: -0.48 to -0.05, P = 0.018). The incidence of adverse effects in the tamsulosin and solifenacin combined therapy group (30.82%) was similar to the tamsulosin monotherapy group (25.75%). Acute urinary retention was seldom reported in the studies and no clinically significant changes regarding Qmax were showed in our meta-analysis. CONCLUSIONS: Tamsulosin and solifenacin combination therapy may be a reasonable option for male LUTS patients, especially for those who have significant storage symptoms. However, PVR should be measured during treatment to assess the increase in PVR or the incidence of AUR.