Unilateral high-riding vertebral artery is associated with asymmetric morphological changes of the atlantoaxial joint: a novel risk factor for atlantoaxial osteoarthritis.

PURPOSE: This study aimed to investigate the association between unilateral high-riding vertebral artery (HRVA) and morphological changes in the atlantoaxial joint (AAJ) and to determine whether unilateral HRVA is a risk factor for atlantoaxial osteoarthritis (AAOA). METHODS: We conducted a retrospective analysis of 2496 patients admitted to our medical center between January 2020 and December 2022 who underwent CT imaging of the cervical spine. Two hundred and seventy-two patients with unilateral HRVA (HRVA group) were identified and a respective 2:1 age- and sex-matched control group without HRVA was built. Morphological parameters, including C2 lateral mass settlement (C2 LMS), C1/2 coronal inclination (C1/2 CI), lateral atlanto-dental interval (LADI), and C1/2 relative rotation angle (C1/2 RRA) were measured. The degree of AAOA was recorded. Risk factors associated with AAOA were identified using univariate and multivariable logistic regression analyses. RESULTS: The study included 61.4% women, and the overall average age of the study population was 48.7 years. The morphological parameters (C2 LMS, C1/2 CI, and LADI) in AAJ were asymmetric between the HRVA and the non-HRVA sides in the HRVA group (p < 0.001). These differences in parameters (d-C2 LMS, d-C1/2 CI, and d-LADI) between the HRVA and the non-HRVA sides, and C1/2 RRA were significantly larger than those in the control group. Eighty-three of 816 patients (10.2%) with AAOA had larger values of d-C2 LMS, d-C1/2 CI, d-LADI, and C1/2 RRA compared with the patients without AAOA (p < 0.05). The multivariable logistic regression analysis indicated that unilateral HRVA [adjusted odds ratio (OR) = 2.6, 95% CI: 1.1-6.3, p = 0.029], age in the sixth decade or older (adjusted OR = 30.2, 95% CI: 16.1-56.9, p < 0.001), women (adjusted OR = 2.1, 95% CI: 1.0-5.6, P = 0.034) were independent risk factors for AAOA. CONCLUSION: Unilateral HRVA was associated with asymmetric morphological changes of nonuniform settlement of C2 lateral mass, lateral slip of atlas, and atlantoaxial rotation displacement. Besides age ≥ 60 years and females, unilateral HRVA is an independent risk factor for AAOA.

Multisegment transforaminal lumbar interbody fusion (TLIF) combined with Ponte osteotomy in degenerative lumbar scoliosis (DLS) surgery: a minimum of five years' follow-up.

PURPOSE: To evaluate the long-term clinical outcomes of degenerative lumbar scoliosis (DLS) with the administration of multisegment transforaminal lumbar interbody fusion (TLIF) combined with Ponte osteotomy long-level fixation fusion, as well as to identify the factors affecting health-related quality of life (HRQOL). METHODS: This was a retrospective single-centre study involving comprehensive clinical data. The Oswestry Disability Index (ODI), visual analog scale (VAS) outcomes, and Scoliosis Research Society (SRS-22) questionnaire were recorded to assess HRQOL. A correlation analysis was performed to determine the association between HRQOL and radiographic parameters. RESULTS: A total of 41 consecutive patients (15 males and 26 females) met the inclusion criteria with a follow-up of 8.62 ± 1.20 years. Factors associated with HRQOL were significantly improved post-operation. Global sagittal parameters, including the sagittal vertebral axis (SVA) and T1 pelvic angle (TPA), and local parameters, including apical vertebral translation (AVT) and apical vertebral rotation (AVR), were significantly improved at the last follow-up. Significantly strong correlations between each clinical and radiographic parameter were demonstrated. Moreover, a multiple linear regression analysis demonstrated that the differences in AVT and AVR were significantly correlated with the difference in lumbar lordosis (LL), which was significantly correlated with the differences in SVA and TPA. CONCLUSION: The surgical treatment of DLS with multisegment TLIF accompanied by Ponte osteotomy and long-level fixations improved the quality of life of patients with a long-term effect. AVR correction is an important factor for LL restoration that significantly correlates with improvements in the sagittal balance parameters SVA and TPA, which are key factors for guaranteeing good HRQOL.

Up-regulation of TßRIII facilitates the osteogenesis of supraspinous ligament-derived fibroblasts from patients with ankylosing spondylitis.

Spinal supraspinous ligament (SL) osteogenesis is the key risk of ankylosing spondylitis (AS), with an unclear pathogenesis. We previously found that transforming growth factor ß1 (TGF-ß1), bone morphogenetic proteins (eg BMP2) and type III TGF-ß1 receptor (TßRIII) expression were markedly up-regulated in AS-SLs. However, the roles of these closely related molecules in AS are unknown. Here, we showed that BMP2, TGF-ß1, TßRIII and S100A4 (a fibroblast marker) were abundant in active osteogenic AS-SL tissues. In vitro, AS-SL fibroblasts (AS-SLFs) showed high BMP2, TGF-ß1 and TßRIII expression and auto-osteogenic capacity. We further evaluated the role of TßRIII in the osteogenesis of normal SLFs. BMP2 combined with TGF-ß1 induced the osteogenesis of TßRIII-overexpressing SLFs, but the activity was lost in SLFs upon TßRIII knockdown. Moreover, our data suggested that BMP2 combined with TGF-ß1 significantly activated both TGF-ß1/Smad signalling and BMP2/Smad/RUNX2 signalling to induce osteogenesis of SLFs with TßRIII up-regulation. Furthermore, our multi-strategy molecular interaction analysis approach indicated that TGF-ß1 presented BMP2 to TßRIII, sequentially facilitating BMP2 recognition by BMPR1A and promoting the osteogenesis of TßRIII-overexpressing SLFs. Collectively, our results indicate that TGF-ß1 combined with BMP2 may participate in the osteogenic differentiation of AS-SLF by acting on up-regulated TßRIII, resulting in excessive activation of both TGF-ß1/Smad and BMP2/BMPR1A/Smad/RUNX2 signalling.

Preliminary investigation of bilateral internal iliac artery ligation and anterior tumor separation through laparoscopy before posterior resection of a giant sacral tumor.

BACKGROUND: Surgical is the optimal therapeutic strategy for sacral tumors, and complete resection can effectively improve the recurrence and survival rates. However, the specialized anatomy, massive bleeding and adhesion to the anterior tissue, especially that caused by giant sacral tumors, makes complete resection difficult. The laparoscopic technique provides a new method to resect sacral tumors. METHODS: 34 patients with primary giant sacral tumors who underwent surgical resection were enrolled. After bilateral internal iliac artery ligation and anterior laparoscopic tumor separation, the sacral tumors were successfully resected posteriorly. The clinical, radiological and follow-up data were collected and analyzed. RESULTS: The average operative time was 276.47 min and that for laparoscopy was 76.24 min. The average intraoperative blood loss was 1757.64 ml. No complications associated with laparoscopic surgery, such as intestinal, urinary tract, or vascular injuries, occurred. Ten patients (29.41%) had perioperative complications, including infection, unhealed wounds, and cerebrospinal fluid leaks in 10, 5 and 2 patients, respectively. Patients with complications had significantly longer total (55.00 ± 34.53 vs 25.13 ± 14.60, P = 0.001) and postoperative (39.10 ± 30.61 vs 14.83 ± 10.00, P = 0.002) hospitalization stays than patients without complications. Postoperatively, bowel and bladder dysfunction, intestinal obstruction, pain, and perianal numbness occurred in 21, 5, 8, and 2 patients, respectively. The recurrence rate was 11.76%. CONCLUSIONS: Laparoscopically assisted sacral tumor resection is a technically feasible and effective surgical method to resect giant sacral tumors, with the advantages of reduced operative blood loss during internal iliac artery ligation and anterior tumor separation.

Single-stage posterior total en bloc spondylectomy in the treatment of lumbar spinal metastases.

OBJECTIVE: To report the clinical and radiographic outcomes of single-stage posterior total en bloc spondylectomy (TES) of lumbar spinal metastases. PATIENTS AND METHODS: From January 2012 to January 2015, 20 consecutive cases with lumbar spinal metastases who received single-stage posterior TES were retrospectively analyzed. A visual analog scale (VAS) was used to evaluate patients' pain status, American Spinal Injury Association (ASIA) classification was used to evaluate neurological status, and Eastern Cooperative Oncology Group (ECOG) score system was used to evaluate patients' performance status at pre- and post-operation and final follow-up. In addition, Intraoperative blood loss, operative time, postoperative complications, local kyphosis angle, and the postoperative duration of hospital stay were analyzed. RESULTS: The median follow-up time was 16 months (ranging from 3 to 39 months), and 4 patients were still alive at the last follow-up. The mean amount of intraoperative blood loss and operation time was 970 mL and 232.5 min, respectively. The average VAS score improved from 7.5 preoperative to 2.8 postoperative and 3.2 at the last follow-up. Postoperative complications occurred in 3 cases. Sixteen patients died within 2 years after surgery, 10 of which died within 1 year. In the remaining 4 patients, the mean follow-up period was 37.25 months. One case of local recurrence occurred but no implant failure presented during follow-up. CONCLUSIONS: Single-stage posterior TES is a challenging but rewarding procedure in the treatment of lumbar spinal metastases. Due to unique anatomy and biomechanics, surgeons should be aware of important vessels, and nerve root injury should be avoided.

Sema4D expression and secretion are increased by HIF-1α and inhibit osteogenesis in bone metastases of lung cancer.

Most lung cancer bone metastasis are characterized by osteolytic destruction and osteoblastic activity is significantly decreased, suggesting that hypoxia may play a critical role in the process, but the underlying mechanisms remain unknown. Semaphorin 4D (Sema4D) is a recently discovered osteogenic inhibitory factor that is expressed at high levels in lung cancers. Here, CoCl2-induced hypoxia significantly enhanced the inhibitory effect of lung cancer cell conditioned media on osteoblast differentiation by inducing the expression and secretion of Sema4D in a HIF-1α- but not HIF-2α-dependent manner. Moreover, HIF-1α directly regulated Sema4D expression by binding to bases 1171 to 798 in the Sema4D promoter. Furthermore, hypoxia increased Sema4D secretion by upregulating a disintegrin and metalloproteinase 17 (ADAM17) expression in lung cancer in a HIF-1α-dependent manner. In bone metastasis samples from 49 patients with lung cancer, Sema4D and ADAM17 expression significantly correlated with HIF-1α expression and strongly correlated with a poor differentiation status and osteolytic bone destruction. These results provide the first evidence that HIF-1α-induced Sema4D expression and secretion play important roles in lung cancer osteolytic bone metastasis by inhibiting osteoblast differentiation, thereby providing potential strategies for the treatment of bone metastasis via targeting osteoblasts.

Prognostic Factors and Comparison of Conservative Treatment, Percutaneous Vertebroplasty, and Open Surgery in the Treatment of Spinal Metastases from Lung Cancer.

BACKGROUND: Spinal metastases from lung cancer could result in life-threatening consequences. Few studies report the prognostic factors and compare different treatments in patients with spinal metastases from lung cancer. METHODS: From 2005 to 2014, we retrospectively reviewed and studied 140 patients with spinal metastases from lung cancer according to different treatments. To estimate overall survival and identify prognostic factors for survival, the Kaplan-Meier method and Cox regression analysis were adopted. In addition, the Kaplan-Meier method was used to compare different treatments for overall survival. RESULTS: All patients in a conservative group and a percutaneous vertebroplasty group died at a median survival time of 7 months for both groups. As for patients in the open-surgery group, 42 patients died at a median of 11 months, and 7 patients who were still alive at the time of this study were followed for a median of 29 months. Multivariate analysis suggested that better survival was significantly associated with American Spinal Injury Association grade D/E on admission, American Spinal Injury Association grade E after surgery, Eastern Cooperative Oncology Group performance status 1-2, and adjuvant radiation therapy in all 3 groups. In addition, Kaplan-Meier analysis showed that the overall survival rate of the open-surgery group (14.3%) was better than that of conservative group (0%) and the percutaneous vertebroplasty group (0%). CONCLUSIONS: A better overall survival outcome might be achieved by a series of comprehensive and individualized treatments and personalized treatment.