Interleukin-1ß and cathepsin D modulate formation of the terminal complement complex in cultured human disc tissue.

PURPOSE: Formation of terminal complement complex (TCC), a downstream complement system activation product inducing inflammatory processes and cell lysis, has been identified in degenerated discs. However, it remains unclear which molecular factors regulate complement activation during disc degeneration (DD). This study investigated a possible involvement of the pro-inflammatory cytokine interleukin-1ß (IL-1ß) and the lysosomal protease cathepsin D (CTSD). METHODS: Disc biopsies were collected from patients suffering from DD (n = 43) and adolescent idiopathic scoliosis (AIS, n = 13). Standardized tissue punches and isolated cells from nucleus pulposus (NP), annulus fibrosus (AF) and endplate (EP) were stimulated with 5% human serum (HS) alone or in combination with IL-1ß, CTSD or zymosan. TCC formation and modulation by the complement regulatory proteins CD46, CD55 and CD59 were analysed. RESULTS: In DD tissue cultures, IL-1ß stimulation decreased the percentage of TCC + cells in AF and EP (P < 0.05), whereas CTSD stimulation significantly increased TCC deposition in NP (P < 0.01) and zymosan in EP (P < 0.05). Overall, the expression of CD46, CD55 and CD59 significantly increased in all isolated cells during culture (P < 0.05). Moreover, cellular TCC deposition was HS concentration dependent but unaffected by IL-1ß, CTSD or zymosan. CONCLUSION: These results suggest a functional relevance of IL-1ß and CTSD in modulating TCC formation in DD, with differences between tissue regions. Although strong TCC deposition may represent a degeneration-associated event, IL-1ß may inhibit it. In contrast, TCC formation was shown to be triggered by CTSD, indicating a multifunctional involvement in disc pathophysiology.

Terminal complement complex formation is associated with intervertebral disc degeneration.

PURPOSE: The complement system is a crucial part of innate immunity. Recent work demonstrated an unexpected contribution to tissue homeostasis and degeneration. This study investigated for the first time, in human disc tissues, the deposition profile of the complement activation product terminal complement complex (TCC), an inflammatory trigger and inducer of cell lysis, and its inhibitor CD59, and their correlation with the degree of disc degeneration (DD). METHODS: Disc biopsies were collected from patients diagnosed with DD (n = 39, age 63 ± 12) and adolescent idiopathic scoliosis (AIS, n = 10, age 17 ± 4) and compared with discs from healthy Young (n = 11, age 7 ± 7) and Elder (n = 10, age 65 ± 15) donors. Immunohistochemical detection of TCC and CD59 in nucleus pulposus (NP), annulus fibrosus (AF) and endplate (EP) was correlated with age, Pfirrmann grade and Modic changes. RESULTS: Higher percentage of TCC+ cells was detected in the NP and EP of DD compared to Elder (P < 0.05), and in the EP of Young versus Elder (P < 0.001). In DD, TCC deposition was positively correlated with Pfirrmann grade, but not with Modic changes, whereas for Young donors, a negative correlation was found with age, indicating TCC's involvement not only in DD, but also in early stages of skeletal development. Higher CD59 positivity was found in AIS and DD groups compared to Young (P < 0.05), and it was negatively correlated with the age of the patients. CONCLUSION: TCC deposition positively correlated with the degree of disc degeneration. A functional relevance of TCC may exist in DD, representing a potential target for new therapeutics.

Interleukin-1ß More Than Mechanical Loading Induces a Degenerative Phenotype in Human Annulus Fibrosus Cells, Partially Impaired by Anti-Proteolytic Activity of Mesenchymal Stem Cell Secretome.

Mesenchymal stem/stromal cell (MSC)-based therapies for low back pain and intervertebral disc (IVD) degeneration have been emerging, despite the poor knowledge of their full mechanism of action. As failure of the annulus fibrosus (AF) is often associated with IVD herniation and inflammation, the objective of the present study was to investigate the impact of the MSC secretome on human AF cells exposed to mechanical loading and a pro-inflammatory environment. Human AF cells isolated from IVD biopsies from patients with adolescent idiopathic scoliosis (AIS) or disc degeneration (DD) were exposed to physiological cyclic tensile strain (CTS) for 72 h in a custom-made device, with or without interleukin (IL)-1ß medium supplementation. AF cells stimulated with CTS + IL-1ß were then treated with secretome from IL-1ß-preconditioned MSCs for 48 h. AF cell metabolic activity, gene expression, protein secretion, matrix metalloproteinase (MMP) activity, and tissue inhibitor of MMPs (TIMP) concentration were evaluated. Expanded AF cells from AIS and DD patients revealed similar metabolic activity and gene expression profiles. CTS stimulation upregulated collagen type I (COL1A1) expression, while IL-1ß significantly stimulated IL-6, IL-8, MMP-1, and MMP-3 gene expression and prostaglandin E2 production by AF cells but downregulated COL1A1. The combination of CTS + IL-1ß had a similar outcome as IL-1ß alone, accompanied by a significant upregulation of elastin. The MSC secretome did not show any immunomodulatory effect on CTS + IL-1ß-stimulated AF cells but significantly decreased MMP-1, MMP-2, MMP-3, and MMP-9, while increasing the production of TIMP-1. The obtained results demonstrate a stronger impact of the inflammatory milieu on human AF cells than upper physiologic mechanical stress. In addition, a new MSC mechanism of action in degenerated IVD consisting of the modulation of AF MMP activity was also evidenced, contributing to the advancement of knowledge in AF tissue metabolism.

Anterior cervical distraction and screw elevating-pulling reduction for traumatic cervical spine fractures and dislocations: A retrospective analysis of 86 cases.

Treatment of cervical fracture and dislocation by improving the anterior cervical technique.Anterior cervical approach has been extensively used in treating cervical spine fractures and dislocations. However, when this approach is used in the treatment of locked facet joints, an unsatisfactory intraoperative reduction and prying reduction increases the risk of secondary spinal cord injury. Thus, herein, the cervical anterior approach was improved. With distractor and screw elevation therapy during surgery, the restoration rate is increased, and secondary injury to the spinal cord is avoided.To discuss the feasibility of the surgical method of treating traumatic cervical spine fractures and dislocations and the clinical application.This retrospective study included the duration of patients' hospitalization from January 2005 to June 2015. The potential risks of surgery (including death and other surgical complications) were explained clearly, and written consents were obtained from all patients before surgery.The study was conducted on 86 patients (54 males and 32 females, average age of 40.1 ±â€Š5.6 years) with traumatic cervical spine fractures and dislocations, who underwent one-stage anterior approach treatment. The effective methods were evaluated by postoperative follow-up.The healing of the surgical incision was monitored in 86 patients. The follow-up duration was 18 to 36 (average 26.4 ±â€Š7.1) months. The patients achieved bones grafted fusion and restored spine stability in 3 to 9 (average 6) months after the surgery. Statistically, significant improvement was observed by Frankel score, visual analog scale score, Japanese Orthopedic Association score, and correction rate of the cervical spine dislocation pre- and postoperative (P < .01).The modified anterior cervical approach is simple with a low risk but a good effect in reduction. In addition, it can reduce the risk of iatrogenic secondary spinal cord injury and maintain optimal cervical spine stability as observed during follow-ups. Therefore, it is suitable for clinical promotion and application.

Emergency 1-stage anterior approach for cervical spine infection complicated by epidural abscess.

It was a retrospective analysis.The aim of the study was to explore the safety and reliability of emergency 1-stage radical debridement and reconstruction using titanium mesh filled with autologous bone for patients with cervical spine infection complicated by epidural abscess.At present, cervical spine infection complicated by epidural abscess is known as a severe spine disease. Recently, case report of this disease is showing quite an increasing tendency, particularly in economically undeveloped areas and countries. Regarding the treatment of this disease, 1-stage radical debridement and reconstruction has been widely adopted; however, emergency 1-stage anterior approach surgery without medication is considered as a relatively taboo, since it is generally acknowledged that such operation would possibly cause unexpected infection. Nevertheless, regular elective surgery may require longer time for preparation. In addition, long hour compression and stimulation of the abscess may leave the patients with irreversible spinal neural impairment. However, our department has finished 14 cases of cervical spine infection complicated with epidural abscess without 1 single case of postoperative infection.A retrospective study was conducted on 14 patients (9 males and 5 females; average age 57.4 years) who were diagnosed with cervical spine infection complicated by epidural abscess from January 2005 to December 2014. All the patients were admitted to hospital with varying degrees of neurological function losses, and then underwent 1-stage anterior focal debridement and reconstruction using titanium mesh within 24 hours after admission. They received postoperative standard antibiotic chemotherapy for 10 to 12 weeks. They were followed up for 18 to 36 months, an average of 27.4 months. X-ray, computed tomography (CT), and MRI (magnetic resonance imaging (MRI) were used to determine the fusion state and vertebral stability. American Spinal Injury Association (ASIA) international standards for neurological classification were adopted, white blood cell count (WBC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were evaluated to infection activity, and Japanese Orthopaedic Association (JOA) and visual analog scale (VAS) criteria were used to judge clinical efficacy.All the 14 patients had no postoperative spread of infection. No recurrence of infection was found during the last follow-up. ASIA grade, VAS score, and JOA score were significantly improved (P < .05) after the operation. WBC, ESR, and CRP became normal after the operation (P < .05). Postoperative follow-up imaging results showed no significant loss of cervical curvature, collapse of the grafted bone or implant displacement but good spinal canal volume.Emergency 1-stage radical debridement and reconstruction using titanium mesh filled with autologous bone, combined with antibiotic chemotherapy, is a safe and effective surgical therapy for cervical infection complicated by epidural abscess.

Does the longus colli have an effect on cervical vertigo?: A retrospective study of 116 patients.

The aim of the study was to evaluate the role of the longus colli muscles in cervical vertigo.We retrospectively analyzed 116 adult patients who underwent anterior cervical discectomy and fusion (ACDF) during 2014 in our department. Patients were assigned to the vertigo group or the nonvertigo group. Demographic data were recorded. Inner distance and cross-sectional area (CSA) of longus colli were measured using coronal magnetic resonance imaging (MRI).The vertigo group (n = 44) and the nonvertigo group (n = 72) were similar in demographic data. Mean preoperative Japanese Orthopaedic Association (JOA) score was higher in the vertigo group than in the nonvertigo group (P = 0.037), but no difference postoperatively. Mean JOA scores increased significantly postoperatively in both groups (P = 0.002 and P = 0.001). The mean vertigo score decreased significantly from pre- to postoperatively in the vertigo group (P = 0.023). The mean preoperative Cobb angle was significantly smaller in the vertigo group than in the nonvertigo group (P <0.001), but no significant difference postoperatively. After ACDF, the mean Cobb angle increased significantly in the vertigo group (P <0.001). The instability rates of C3/4 and C4/5 were significantly higher in the vertigo group (P <0.001 and P <0.001). The inner distance of longus colli was significantly shorter (P = 0.032 and P = 0.026) and CSA significantly smaller (P = 0.041 and P = 0.035), at C3/4 and C4/5 in the vertigo group than in the nonvertigo group. Mean Miyazaki scores were significantly higher in the vertigo group at C3/4 and C4/5 (P = 0.044 and P = 0.037). Moreover, a shorter inner distance and smaller CSA were related to a higher Miyazaki score.Inner distance and cross-sectional area (CSA) of longus colli are associated closely with cervical vertigo. Shorter inner distance and smaller CSA of the longus colli muscles might be risk factors for cervical vertigo. ACDF provided a good resolution of cervical vertigo.

Transforaminal endoscopic system technique for discogenic low back pain: A prospective Cohort study.

OBJECTIVE: To investigate the clinical outcomes of transforaminal endoscopic system(TESSYS) for discogenic low back pain(DLBP). METHODS: 62 consecutive patients with one-level DLBP applying to the including criteria underwent TESSYS from January 2010 to December 2013. These patients included 38 males and 24 females with a mean age of 42.7 ± 5.4 years (range, 18-73 yr) and a mean follow-up of 26.8 ± 4.2 months (range, 12-48 months). The visual analog scale (VAS) were used for back pain, the Oswestry Disability Index (ODI) for lumbar function, and the modified MacNab criteria for clinical global outcomes. RESULTS: 24 patients showed only inflammatory granuloma on annulus tear tissues(Group A), 16 patients showed no annulus tear but adhesion and inflammatory granuloma among the intracanal annulus fibrous(AF), posterior longitudinal ligament(PLL) and the abdomen side of the dura sac(Group B) and 22 patients showed both(Group C). Concordant pain could be triggered by touching the inflammation with the bipolar radiofrequency probe. The success rate (excellent and good) of group C was much higher than A and B(P < 0.05). The whole success rate was 75.8%. Of the 4 patients with poor result, 2 refused further surgical treatment and showed either no improvement or worsening. The remaining 2 patients had spinal fusion surgery and achieved better results. VAS and ODI had significantly improved after surgery (P < 0.01). No unexpected complications were seen. CONCLUSION: TEEYS is an effective method in treating DLBP and the complete management of the inflammatory granuloma was the key point in achieving better results.

Risk factors for cage retropulsion after lumbar interbody fusion surgery: Series of cases and literature review.

OBJECTIVE: To identify the risk factors for cage retropulsion after lumbar interbody fusion surgery. METHODS: 667 patients underwent lumbar interbody fusion surgery between November 2011 to December 2014 were retrospectively reviewed by the medical recording system in our institute. 8 patients experiencing cage retropulsion were included and 2 underwent the initial surgery in other hospitals. The clinical outcomes were evaluated by visual analog scores (VAS) and Oswestry Disability Index (ODI). Plain radiographs and three-dimensional computed tomography scans were used to analyze the incidence of cage retropulsion. Data were analyzed by SPSS 19.0. RESULTS: The incidence of cage retropulsion was 0.90%(6 out of 665) in our institution. There were 6 male and 2 female with an average age of 45.63 ± 15.48(range, 21-60). The average follow-up time was 23.88 ± 12.69 months(range, 6-43 months) and average retropulsion onset time was 2.75 months(range,1-6 months). 6 patients experienced cage retropulsion at L5/S1 and 2 at L4/5. 6 used bullet-shaped cages and two had kidney-shaped cages. Average bed rest time after the initial surgery was 5.75 ± 1.67 days. 6 patients had neurological deficits and underwent revision surgery. Average operation time and blood loss for revision surgery were much higher than those of the initial surgery (P < 0.05). All the patients got a good result in VAS and ODI both from initial surgery and revision surgery (P < 0.05). CONCLUSIONS: There were multiple risk factors for cage retropulsion after lumbar interbody fusion surgery, including patient factors, radiological characteristics, surgical techniques and postoperative reasons. In case of retropulsion, revision surgery was essential for the patients who presented neurological deficits and conservative treatment was recommended for asymptomatic patients.

Lumbar Spinal Tuberculosis Presenting as Abdominal Pain: Case Report.

More than 230 years after the characteristic clinical features of tuberculosis spondylitis were first described, this serious infection can still present diagnostic dilemmas in clinical practice. Atypical presentations of spinal tuberculosis mimicking malignancy have been described. We report a 50-year-old woman with abdominal pain as a presenting symptom of lumbar spinal tuberculosis. She presented with chronic intermittent abdominal pain of 6 months' duration, without low-grade fever and weight loss. There were no bowel/bladder complaints, vomiting, or worm infestation. Magnetic resonance imaging of the lumbar spine showed the L3, L4, and L5 vertebrae bodies had been destroyed and disease had invaded the lumbar spinal canal. There was a giant abscess in the right musculus psoas major. The C-reactive protein level was 130 g/L, and the erythrocyte sedimentation rate was 165 mm/h. A diagnosis of lumbar spinal tuberculosis with abdominal pain was made. After 3 weeks of antituberculosis treatment, an operation was performed to debride the necrotic tissues and reconstruct the L3 vertebrae through an anterior approach combined with a posterior approach to establish the spine stability. On 6-month follow-up, the patient had recovered from the operation and had no focal neurologic deficit.