WTAP contributes to the tumorigenesis of osteosarcoma via modulating ALB in an m6A-dependent manner.

PURPOSE: Osteosarcoma (OS) is a prevalent bone malignancy mainly occurred in adolescents. WTAP/N6-methyladenosine (m6A) modification is confirmed to be involved in OS progression. This study is conducted to bring some novel insights to the action mechanism of WTAP/m6A under the hidden pathogenesis of OS. METHODS: qRT-PCR was executed to evaluate the expression levels of WTAP and ALB. ALB protein level in OS cells was measured by western blotting. The content of m6A in total RNA was assessed by m6A quantification assay. Me-RIP, dual luciferase reporter, and mRNA stability assays confirmed the target relationship of WTAP with ALB. With the use of the wound healing, CCK-8, and transwell invasion assays, the functional relationship between WTAP and ALB in OS cells was confirmed. The influences of WTAP on tumor growth in vivo were performed in the xenograft model of mouse. RESULTS: WTAP was increased but ALB was diminished in OS tissues and/or cell lines. WTAP modulated ALB expression in an m6A-dependent manner. Silencing of WTAP retarded the development of OS via inhibiting cell viability, migration, invasion, and tumor growth. Knockdown of ALB exerted the opposite effects on OS progression. Additionally, ALB deficiency partially eliminated the inhibiting effects of WTAP silencing on cellular processes in OS. CONCLUSIONS: This is the first report to clarify the interaction of WTAP/m6A with ALB in OS progression. These experimental data to some extent broadened the horizons of WTAP/m6A in the development of OS.

Impact of bone-implant gap size on the interfacial osseointegration: an in vivo study.

BACKGROUND: The bone-implant gap resulted from morphological mismatch between cervical bony endplates and implant footprint may have adverse impact on bone-implant interfacial osseointegration of cervical disc arthroplasty (CDA). The purpose of the study was to evaluate the impact of bone-implant gap size on the interfacial osseointegration in a rabbit animal model. METHODS: A series of round-plate implants with different teeth depth (0.5 mm, 1.0 mm, 1.5 mm and 2.0 mm) was specifically designed. A total of 48 New Zealand white rabbits were randomly categorized into four groups by the implants they received (0.5 mm: group A, 1.0 mm: group B, 1.5 mm: group C, 2.0 mm: group D). At 4th and 12th week after surgery, animals were sacrificed. Micro-CT, acid fuchsin and methylene blue staining and hematoxylin and eosin (HE) staining were conducted. RESULTS: At 4th week and 12th week after surgery, both micro-CT and HE staining showed more new bone formation and larger bone coverage in group A and group B than that in group C and group D. At 12th week, the bone biometric parameters were significantly superior in group C when compared with group D (p < 0.05). At 12th week, hard tissue slicing demonstrated larger portion of direct contact of new bone to the HA coating in group A and group B. CONCLUSIONS: Bone-implant gap size larger than 1.0 mm negatively affected bone-implant osseointegration between compact bone and HA coated implant surface.

WTAP contributes to the tumorigenesis of osteosarcoma via modulating ALB in an m6A-dependent manner.

PURPOSE: Osteosarcoma (OS) is a prevalent bone malignancy mainly occurred in adolescents. WTAP/N6-methyladenosine (m6A) modification is confirmed to be involved in OS progression. This study is conducted to bring some novel insights to the action mechanism of WTAP/m6A under the hidden pathogenesis of OS. METHODS: qRT-PCR was executed to evaluate the expression levels of WTAP and ALB. ALB protein level in OS cells was measured by western blotting. The content of m6A in total RNA was assessed by m6A quantification assay. Me-RIP and dual luciferase reporter assays confirmed the target relationship of WTAP with ALB. With the use of the wound healing, CCK-8, and transwell invasion assays, the functional relationship between WTAP and ALB in OS cells was confirmed. The influences of WTAP on tumor growth in vivo were performed in the xenograft model of mouse. RESULTS: WTAP was increased but ALB was diminished in OS tissues and/or cell lines. WTAP modulated ALB expression in an m6A-dependent manner. Silencing of WTAP retarded the development of OS via inhibiting cell viability, migration, invasion, and tumor growth. Knockdown of ALB exerted the opposite effects on OS progression. Additionally, ALB deficiency partially eliminated the inhibiting effects of WTAP silencing on cellular processes in OS. CONCLUSIONS: This is the first report to clarify the interaction of WTAP/m6A with ALB in OS progression. These experimental data to some extent broadened the horizons of WTAP/m6A in the development of OS.

Biomechanical evaluation of cervical disc replacement with a novel prosthesis based on the physiological curvature of endplate.

BACKGROUND: Most of the current available cervical disc prostheses present a flat surface instead of an arcuate surface which is most similar to the morphology of cervical endplate. Therefore, we designed a novel prosthesis (Pretic-I, Trauson) based on the physiological curvature of the cervical endplate. Biomechanical evaluation of cervical disc replacement (CDR) with this novel prosthesis was performed and compared with the Prestige LP prosthesis. METHODS: Three motion segments of 18 cadaveric cervical specimens (C2-C7) were evaluated with a 75 N follower load. Overall, the biomechanics of three models, intact specimen, CDR with the novel prosthesis and CDR with the Prestige LP prosthesis, were studied to gain insight into the effective function of the novel prosthesis. The range of motion (ROM) of all three segments and intradiscal pressure (IDP) on adjacent levels were measured and analysed. RESULTS: Compared to the intact condition, the ROM of all three segments showed no significant difference in the replacement group. Moreover, there was also no significant difference in the ROM between the two prostheses. Besides, the IDP on the cranial adjacent level showed no obvious difference between the two prostheses; nevertheless, the IDP on the caudal adjacent level of the novel prosthesis was significantly less than the Prestige LP prosthesis. CONCLUSIONS: In summary, the novel disc prosthesis was effective to maintain the ROM at the target segment and adjacent segments. Besides, CDR with the novel prosthesis could reduce the IDP on the caudal adjacent level to a certain extent, compared with the Prestige LP prosthesis.

Anterior corpectomy and reconstruction using dynamic cervical plate and titanium mesh cage for cervical spondylotic myelopathy: A minimum 5-year follow-up study.

Anterior cervical corpectomy and fusion (ACCF) is an effective surgical technique for cervical spondylotic myelopathy (CSM). However, no data exist regarding long-term outcomes after ACCF with the dynamic cervical plate for CSM. This study aimed to provide minimum 5-year clinical and radiographic outcomes of anterior corpectomy and reconstruction using dynamic cervical plate and titanium mesh cage (TMC) for CSM.Thirty-five patients who underwent single- or 2-level ACCF with dynamic cervical plate and TMC for the treatment of CSM were retrospectively investigated. The Japanese Orthopedic Association (JOA) score was used to assess the clinical outcome. Radiographic evaluations included TMC subsidence, fusion status, cervical lordosis, segmental angle, and segmental height.Twenty-eight patients underwent single-level and 7 patients underwent 2-level corpectomy with a mean follow-up period of 69.5 months. The average preoperative JOA score was 11.3 ±â€Š3.0 and improved significantly to 14.2 ±â€Š2.0 at the last follow-up (P < .001). Both cervical lordosis (P = .013) and segmental angle (P = .001) were significantly increased toward lordosis at the last follow-up. The TMC subsidence rate was 31.4% (n = 11) at the last follow-up. There was no significant difference in JOA recovery rate between subsidence and no subsidence group (P = .43). All patients obtained solid fusion at 1-year follow-up.Anterior corpectomy and reconstruction with dynamic cervical plate and TMC might be an effective method for the treatment of CSM at a minimum 5-year follow-up. It can maintain or restore cervical sagittal alignment. Subsidence of the TMC did not influence the clinical outcome.

The impact of the difference in O-C2 angle in the development of dysphagia after occipitocervical fusion: a simulation study in normal volunteers combined with a case-control study.

BACKGROUND CONTEXT: Dysphagia has been recognized as one of the most serious complications after occipitocervical fusion (OCF), and the difference between postoperative and preoperative O-C2 angle (dO-C2A) was proposed to be an indicator in predicting and preventing dysphagia. Therefore, to prevent postoperative dysphagia, previous studies recommend that surgeons should correct the O-C2 angle (O-C2A) during surgery if the occipitocervical alignment was in an excessively flexed position. However, until now, there was no explicit indicator of the condition in which surgeons should adjust the patient's O-C2A during surgery. PURPOSE: One of the purposes of this study was to explore the threshold of dO-C2A between dysphagia and normal swallowing by a simulation study. The other aim was to evaluate the validity of the threshold of dO-C2A in predicting dysphagia after OCF via a case-control study. STUDY DESIGN: This is a simulation study combined with a retrospective case-control study. PATIENT SAMPLE: Thirty volunteers were enrolled in the simulation study. Thirty-four consecutive patients who underwent OCF between September 2011 and September 2016 were included in the case-control study. OUTCOME MEASURES: The outcome measures included O-C2A, C2-7 angle (C2-7A), atlantodental interval (ADI), the narrowest oropharyngeal airway space (nPAS), the rate of change in dnPAS (%dnPAS), and the prevalence of postoperative dysphagia. MATERIALS AND METHODS: In the simulation study, each volunteer received two lateral x-rays of their cervical spine in neutral position and dysphagia position, respectively. We compared the radiographic parameters in neutral and dysphagia positions. The cumulative frequency diagram of dO-C2A in the dysphagia position was analyzed to identify the threshold of dO-C2A in the development of dysphagia. In the case-control study, these 34 patients were divided into two groups according to the threshold of dO-C2A identified in the simulation study. The impact of radiographic parameters on nPAS was analyzed. The prevalence of postoperative dysphagia between the two groups was compared to evaluate the validity of the threshold of dO-C2A in predicting dysphagia after OCF. RESULTS: In the simulation study, the mean O-C2A and nPAS in the dysphagia position were significantly smaller than in the neutral position (p<.05). There was no significant difference between the mean C2-7A in the neutral and dysphagia positions (p>.05). There was a significant positive correlation between dO-C2A and dnPAS (p<.05). A dO-C2A of -5° delineated the threshold between normal swallowing and dysphagia. In the case-control study, multiple regression analysis showed that dO-C2A was the only significant variable correlated with dnPAS (ß=0.769, p<.001). Among the reviewed 34 patients, the incidence of dysphagia was 17.6% (6/34) at 2 weeks after surgery and decreased over time to 11.8% (4 of 34) at the last follow-up. There was also a significant positive correlation between the dO-C2A and dnPAS (p<.05). The prevalence of dysphagia after OCF in patients with dO-C2A<-5° was as high as 66.7% (6/9). However, there was no patient suffering from dysphagia in patients with dO-C2A≥-5°. CONCLUSION: The present study showed that the dO-C2A should be a key factor in the development of postoperative dysphagia after OCF. A dO-C2A of -5° could be the threshold between dysphagia and normal swallowing. Furthermore, to avoid dysphagia, surgeons should correct the O-C2A just before the final occipitocervical fixation if the checked dO-C2A during surgery is less than -5°.

In-vivo study of osseointegration in Prestige LP cervical disc prosthesis.

BACKGROUND: A study was designed to quantify the extent of porous osseointegration at the prosthesis-bone interface in the Prestige LP prosthesis containing a plasma-sprayed titanium coating. METHODS: Using an anterior surgical approach, cervical disc arthroplasty was performed in 8 mature male goats at the C3-C4 segment, followed by implantation of the Prestige LP prosthesis. The vertebral specimens were examined using microcomputed tomograph for histomorphometric quantification, and proceeded by routine paraffin processing for histological observation. Hence, the porous osseointegration at the prosthesis-bone interface was evaluated based on histologic and histomorphometric analyses. RESULTS: At 6 months after surgery, there was no evidence of prosthesis migration, loosening, subsidence, or neurologic or vascular complications. Based on gross histologic analysis, there was excellent porous ingrowth at the prosthesis-bone interface, without significant histopathologic changes. Histomorphometric analysis at the prosthesis-bone interface indicated the mean porous ingrowth of 48.5% ± 10.4% and the total ingrowth range of 36.6 to 59.8%. CONCLUSIONS: As the first comprehensive in vivo investigation into the Prestige LP prosthesis, this project established a successful animal model in the evaluation of cervical disc arthroplasty. Moreover, histomorphometric analysis of porous ingrowth at the prosthesis-bone interface was more favorable for cervical disc arthroplasty with the Prestige LP prosthesis compared to historical reports of appendicular total joint arthroplasty.

In vitro biomechanical comparison after fixed- and mobile-core artificial cervical disc replacement versus fusion.

In vitro biomechanical analysis after cervical disc replacement (CDR) with a novel artificial disc prosthesis (mobile core) was conducted and compared with the intact model, simulated fusion, and CDR with a fixed-core prosthesis. The purpose of this experimental study was to analyze the biomechanical changes after CDR with a novel prosthesis and the differences between fixed- and mobile-core prostheses.Six human cadaveric C2-C7 specimens were biomechanically tested sequentially in 4 different spinal models: intact specimens, simulated fusion, CDR with a fixed-core prosthesis (Discover, DePuy), and CDR with a mobile-core prosthesis (Pretic-I, Trauson). Moments up to 2 Nm with a 75 N follower load were applied in flexion-extension, left and right lateral bending, and left and right axial rotation. The total range of motion (ROM), segmental ROM, and adjacent intradiscal pressure (IDP) were calculated and analyzed in 4 different spinal models, as well as the differences between 2 disc prostheses.Compared with the intact specimens, the total ROM, segmental ROM, and IDP at the adjacent segments showed no significant difference after arthroplasty. Moreover, CDR with a mobile-core prosthesis presented a little higher values of target segment (C5/6) and total ROM than CDR with a fixed-core prosthesis (P > .05). Besides, the difference in IDP at C4/5 after CDR with 2 prostheses was without statistical significance in all the directions of motion. However, the IDP at C6/7 after CDR with a mobile-core prosthesis was lower than CDR with a fixed-core prosthesis in flexion, extension, and lateral bending, with significant difference (P < .05), but not under axial rotation.CDR with a novel prosthesis was effective to maintain the ROM at the target segment and did not affect the ROM and IDP at the adjacent segments. Moreover, CDR with a mobile-core prosthesis presented a little higher values of target segment and total ROM, but lower IDP at the inferior adjacent segment than CDR with a fixed-core prosthesis.

How to choose when implants of adjacent height both fit the disc space properly in single-level cervical artificial disc replacement.

In cervical artificial disc replacement (C-ADR), sometimes we encountered with such cases that implants of adjacent height both fit the target disc space properly. No study was available discussing the choice of implant height and the clinical outcomes under such circumstance. The purpose of this study was to evaluate the impact of different implant heights on the clinical outcomes and radiographic results when the implants of adjacent height both fit the disc space properly. This retrospective study included 34 patients underwent single-level C-ADR at the C5-C6 level at our institution. In these 34 patients, implant with either 5 mm height or 6 mm height fit the surgical level properly without overstretching the disc space or the facet joint space. Clinical outcomes were evaluated using the Japanese Orthopedic Association score, visual analog scale (VAS), and Neck Disability Index. Radiographic assessments were conducted on static and dynamic radiographs for the determination of the disc space height, intersegmental range of motion (ROM), and the ROM of the functional spinal unit (FSU) at the surgical level. The baseline information of the patients, such as age, gender, weight, follow-up time, and diagnosis, was similar between the 2 groups (P > .05). Postoperative mean VAS in group B was significantly lower than that in group A (2.1 ±â€Š0.7 vs. 2.7 ±â€Š1.0, P < .05). The mean VAS decrease in group B was significantly larger than that in group A (5.3 ±â€Š0.8 vs. 4.6 ±â€Š1.1, P < .05). Significant difference was found in the postoperative disc height of the surgical segment between the 2 groups (6.4 ±â€Š0.4 mm vs. 7.5 ±â€Š0.5 mm, P < .05). No significant differences were noted in the intersegmental ROM and ROM of the FSU between the 2 groups both before the surgery and at the last follow-up (P > .05). No hypermobility or instability was observed in these patients. Our results suggested that when implants of adjacent height both fit the disc space properly, using the larger implant could result in better pain relief without the risk of segmental hypermobility in patients underwent single-level C-ADR at the C5-C6 level.

Multilevel cervical disc replacement versus multilevel anterior discectomy and fusion: A meta-analysis.

BACKGROUND: Cervical disc replacement (CDR) has been developed as an alternative surgical procedure to anterior cervical discectomy and fusion (ACDF) for the treatment of single-level cervical degenerative disc disease. However, patients with multilevel cervical degenerative disc disease (MCDDD) are common in our clinic. Multilevel CDR is less established compared with multilevel ACDF. This study aims to compare the outcomes and evaluate safety and efficacy of CDR versus ACDF for the treatment of MCDDD. METHODS: A meta-analysis was performed for articles published up until August 2016. Randomized controlled trials (RCTs) and prospective comparative studies associated with the use of CDR versus ACDF for the treatment of MCDDD were included in the current study. Two reviewers independently screened the articles and data following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. RESULTS: Seven studies with 702 enrolled patients suffering from MCDDD were retrieved. Patients who underwent CDR had similar operative times, blood loss, Neck Disability Index (NDI) scores, and Visual Analog Scale (VAS) scores compared to patients who underwent ACDF. Patients who underwent CDR had greater overall motion of the cervical spine and the operated levels than patients who underwent ACDF. Patients who underwent CDR also had lower rates of adjacent segment degeneration (ASD). The rate of adverse events was significantly lower in the CDR group. CONCLUSION: CDR may be a safe and effective surgical strategy for the treatment of MCDDD. However, there is insufficient evidence to draw a strong conclusion due to relatively low-quality evidence. Future long-term, multicenter, randomized, and controlled studies are needed to validate the safety and efficacy of multilevel CDR.

Clinical and radiographic features of hybrid surgery for the treatment of skip-level cervical degenerative disc disease: A minimum 24-month follow-up.

We describe the radiographic changes of IS and investigate the safety and feasibility of hybrid surgery (HS) coupling cervical disc arthroplasty (CDA) and anterior cervical discectomy and fusion (ACDF) for the treatment of skip-level cervical degenerative disc disease (CDDD). Twenty-seven patients who received HS were retrospectively reviewed. Clinical evaluation based on the Japanese Orthopedic Association (JOA) and Neck Disability Index (NDI) and Visual Analog Scale (VAS) scores. Radiographic parameters included cervical alignment (CA), functional spine unite (FSU) angle of intermediated segment (IS), range of motion (ROM) and intervertebral disc height (IDH). Data regarding radiographic changes at IS were collected. The mean follow-up duration of 30.10months. Compared with preoperative value, JOA, NDI and VAS scores significantly improved after surgery (p<0.05). The CA was recovered significantly after surgery (p<0.05). There was no significant difference in the FSU angle and the IDH of IS between before and at 24months postoperatively (p>0.05). The ROM of IS significantly decreased at the first week after surgery (p<0.05), was similar to preoperative value at 3months postoperatively and significantly increased after 6months (p<0.05). Radiographic changes at IS were observed in 2 patients and Class II Heterotopic ossification (HO) was detected in 2 patients. HS is a safe and feasible alternative procedure for the treatment of skip-level CDDD. It preserved the IS intact and achieved satisfactory clinical and radiographic outcomes over a 24-month follow-up.

[Domestic artificial cervical disc interface pressure distribution and effect of bone-implant interface pressure on osseointegration].

Objective: To analyze the distribution of stress in the upper and lower plates of the prosthesis-bone interface, and the effect of interface pressure on osseointegration. Methods: CT scanning was performed on goats at 1 week after artificial cervical disc replacement to establish the finite element model of C 3, 4. The stress distribution of the upper and lower plates of the interface was observed. At 6 and 12 months after replacement, Micro-CT scan and three dimensional reconstruction were performed to measure the bone volume fraction (BVF), trabecular number (Tb. N), trabecular thickness (Tb. Th), trabecular separation (Tb. Sp), bone mineral density (BMD), bone surface/bone volume (BS/BV), and trabecular pattern factor (Tb. Pf). The C 3 lower plate and C 4 upper plate of 4 normal goat were chosen to made the cylinder of the diameter of 2 mm. The gene expressions of receptor activator for nuclear factor κB ligand (RANKL), osteoprotegerin (OPG), transforming growth factor ß (TGF-ß), and macrophage colony-stimulating factor (M-CSF) were detected by real time fluorescent quantitative PCR at immediate after cutting and at 24 and 48 hours after culture. The samples of appropriate culture time were selected to made mechanical loading, and the gene expressions of RANKL, OPG, M-CSF, and TGF-ß were detected by real time fluorescent quantitative PCR; no mechanical loading samples were used as normal controls. Results: Under 25 N axial loading, the stress of the upper plate of C 3, 4 was concentrated to post median region, and the stress of the lower plate to middle-front region and two orbits. According to stress, the plate was divided into 5 regions. The Micro-CT scan showed that BMD, Tb.Th, BVF, and Tb.N significantly increased, and BS/BV, Tb.Sp, and Tb.Pf significantly decreased at 12 months after replacement when compared with ones at 6 months ( P<0.05). At 24 and 48 hours after culture, the gene expressions of RANKL, OPG, and TGF-ß were signifi-cantly higher than those at immediate ( P<0.05), but no significant difference was found between at 24 and 48 hours after culture ( P>0.05). The mechanical loading test results at 24 hours after culture showed that the RANKL and OPG gene expressions and OPG/RANKL ratio in C 3 lower plate and C 4 upper plate were significantly up-regulated when compared with controls ( P<0.05), but no significant difference was shown in TGF-ß and M-CSF gene expressions ( P>0.05). Conclusion: Domestic artificial cervical disc endplate has different pressure distribution, the stress of lower plate is higher than that of upper plate. Pressure has important effect on local osseointegration; the higher pressure area is, the osseointegration is better. Under the maximum pressure in interface, the osteoblast proliferation will increase, which is advantageous to the local osseointegration.

[Clinical outcome of ISOBAR TTL dynamic stabilization with pars bone grafting for treatment of lumbar spondylolysis].

Objective: To evaluate the effectiveness of ISOBAR TTL dynamic stabilization with pars bone grafting for the treatment of lumbar spondylolysis. Methods: A retrospective analysis was made the clinical data of 26 patients with lumbar spondylolysis who received ISOBAR TTL dynamic stabilization with pars bone grafting between September 2009 and March 2014. There were 14 males and 12 females, with a mean age of 31 years (range, 19-47 years). The disease duration ranged from 9 to 60 months (mean, 16 months). Preoperative lumbar anteroposterior and lateral X-ray films, CT three-dimensional reconstruction, and MRI scans were performed to identify the location of pars defect. The involved levels were L 4 in 9 cases and L 5 in 17 cases. There were 10 cases of pure spondylolysis and 16 cases of spondylolysis accompanied with I degree slipping. The clinical outcome was assessed by visual analogue scale (VAS) and Oswestry disability index (ODI) scores at preoperation and 1 week, 3 months, 6 months after operation, and at last follow-up. The lumbar CT three-dimensional reconstruction was obtained at 6 months after operation to evaluate bone fusion of the pars. The adjacent segment degeneration was assessed by the University of California at Los Angeles (UCLA) grading scale at preoperation and last follow-up. Results: All incisions healed by first intention; no infection, cerebrospinal fluid leakage, or pain at iliac crest donor site occurred. Twenty-six patients were followed up 2-5 years (mean, 36.5 months). No secondary spondylolisthesis, internal fixation loosening and breakage were found during follow-up. The postoperative VAS and ODI scores showed significant differences ( P<0.05) when compared with preoperative scores, and the scores at 3 months, 6 months, and last follow-up were significantly better than that at 1 week ( P<0.05), but no significant difference was shown between the other time points after operation ( P>0.05). The CT three-dimensional reconstruction indicated satisfactory union at the pars in 23 cases (88.5%) at 6 months after operation. Of the 3 nonunion patients, good union was obtained in 1 patient at 1 year after operation; nonunion was observed in 2 patients at last follow-up, but low back pain was obviously alleviated. According to the UCLA grading scale, 20 cases were rated as grade I and 6 cases as grade II at last follow-up, which was the same as preoperative grade and indicated no adjacent segment degeneration. Conclusion: It is safe and effective to use the ISOBAR TTL dynamic stabilization with pars bone grafting technique to treat lumbar spondylolysis with or without degree I slipping. The fusion rate is satisfactory, and adjacent segment degeneration can be slowed down after lumbar fusion surgery.

Artificial cervical disc replacement with the Prestige-LP prosthesis for the treatment of non-contiguous 2-level cervical degenerative disc disease: A minimum 24-month follow-up.

OBJECTIVE: We describe the features of non-contiguous 2-level cervical degenerative disc disease (NCDDD), investigate the safety and feasibility of artificial cervical disc replacement (ACDR) for the treatment of NCDDD, and expect that our study will provide spine surgeons with an alternative procedure for NCDDD. METHODS: Twenty-five patients with NCDDD received ACDR with a Prestige-LP prosthesis. Clinical outcomes were evaluated using the 36-Short Form (SF-36, Mental Component Summary [MCS] and Physical Component Summary [PCS]), Visual Analog Scale (VAS), Japanese Orthopedic Association (JOA), and Neck Disability Index (NDI) scores. Radiographic evaluations included cervical lordosis (CL), range of motion (ROM), and disc height (DH). Data regarding complications were collected as well. RESULTS: The mean follow-up period was 32.24 months. Clinical outcomes, including SF-36 MCS and PCS, VAS, JOA, and NDI scores significantly improved at the 24-month follow-up (p<0.05). There were no significant differences in CL and ROM at the 24-month follow-up (p>0.05). Although there was a significant difference between the before and 3-month follow-up (p<0.05), the ROM of the intermediate segment (IS) showed a tendency of returning to the preoperative state. The DH of the IS was maintained at each measurement while the DH of the upper and lower operated segments significantly increased at the 24-month follow-up (p<0.05). One patient, whose prosthesis remained mobile at the last follow-up, showed evidence of heterotopic ossification (HO). CONCLUSION: ACDR with the Prestige-LP prosthesis is a safe and feasible alternative procedure for treatment of NCDDD. In the future, a large-sample, prospective randomized controlled study with long-term follow-up will be needed to further demonstrate noncontiguous ACDR as an optimal surgical option for NCDDD.

Migration of titanium cable into spinal cord and spontaneous C2 and C3 fusion: Case report of possible causes of fatigue failure after posterior atlantoaxial fixation.

INTRODUCTION: Atlantoaxial instability is a common and serious injury of the upper cervical spine. Brooks' procedure is widely used to reconstruct the unstable atlantoaxial joint. The migration into spinal cord of titanium cable and spontaneous fusion between C2 and C3 has been little reported and the management of such a patient is difficult. We describe an unusual case of fatigue failure of posterior titanium atlantoaxial cable fixation with migration into the spinal cord and spontaneous fusion between C2 and C3. CASE REPORT: A 16-year-old girl complained of cervico-occipital pain with numbness and weakness of extremities 3 months ago. The girl underwent posterior C1-C2 arthrodesis with titanium cables and autogenous iliac crest bone grafting when she was 6 years old. When presented to our emergency department, imaging revealed the cracked titanium atlantoaxial cable and the spontaneous fusion between C2 and C3. Computed tomography demonstrated a broken wire with anterior migration of the cable into the spinal cord. The patient underwent posterior approach cervical spinal surgery to remove the broken cables. She remains neurologically intact a year following the posterior approach cervical spine surgery. CONCLUSIONS: Brooks' posterior stabilization could not effectively control rotation at the atlantoaxial articulation, so surgeons must be aware of the potential of fatigue failure of cables as well as the possibility of its migration into the spinal cord when using Brooks' posterior stabilization. Bilateral C1 lateral mass and C2 pedicle screw fixation or transarticular screw fixation are recommended by the authors in the event of rotatory instability.

Use of a biological reactor and platelet-rich plasma for the construction of tissue-engineered bone to repair articular cartilage defects.

Articular cartilage defects are a major clinical burden worldwide. Current methods to repair bone defects include bone autografts, allografts and external fixation. In recent years, the repair of bone defects by tissue engineering has emerged as a promising approach. The present study aimed to assess a novel method using a biological reactor with platelet-rich plasma to construct tissue-engineered bone. Beagle bone marrow mesenchymal stem cells (BMSCs) were isolated and differentiated into osteoblasts and chondroblasts using platelet-rich plasma and tricalcium phosphate scaffolds cultured in a bioreactor for 3 weeks. The cell scaffold composites were examined by scanning electron microscopy (SEM) and implanted into beagles with articular cartilage defects. The expression of osteogenic markers, alkaline phosphatase and bone γ-carboxyglutamate protein (BGLAP) were assessed using polymerase chain reaction after 3 months. Articular cartilage specimens were observed histologically. Adhesion and distribution of BMSCs on the ß-tricalcium phosphate (ß-TCP) scaffold were confirmed by SEM. Histological examination revealed that in vivo bone defects were largely repaired 12 weeks following implantation. The expression levels of alkaline phosphatase (ALP) and BGLAP in the experimental groups were significantly elevated compared with the negative controls. BMSCs may be optimum seed cells for tissue engineering in bone repair. Platelet-rich plasma (PRP) provides a rich source of cytokines to promote BMSC function. The ß-TCP scaffold is advantageous for tissue engineering due to its biocompatibility and 3D structure that promotes cell adhesion, growth and differentiation. The tissue-engineered bone was constructed in a bioreactor using BMSCs, ß-TCP scaffolds and PRP and displayed appropriate morphology and biological function. The present study provides an efficient method for the generation of tissue-engineered bone for cartilage repair, compared with previously used methods.

Effect of intervertebral disc height on the range of motion and clinical outcomes after single-level implantation of Prestige LP cervical disc prosthesis.

OBJECTIVES: Cervical total disc replacement (TDR) is an emerging technology. Cervical arthroplasty theoretically reduces the risk of adjacent level disc degeneration and segmental instability. However, the factors that influence postoperative range of motion (ROM) and clinical outcomes are not fully understood. The aim of our study was to evaluate the effect of intervertebral disc height on the range of motion and clinical outcomes after single-level implantation of Prestige LP cervical disc prosthesis METHODS: A total of 160 patients with single-level Prestige LP cervical disc prosthesis were evaluated. Preoperative and postoperative disc height and ROM were measured from lateral and flexion-extension radiographs by the CANVAS, and the clinical outcomes were evaluated by Japanese Orthopaedic Association (JOA) and Neck Disability Index (NDI). RESULTS: Patients with less than 4mm of preoperative disc height had a mean 1.4° increase in flexion-extension ROM after cervical arthroplasty, whereas patients with greater than 4mm of preoperative disc height had no change in flexion-extension ROM. Patients with a 6-8mm of postoperative disc height had significantly higher postoperative flexion-extension ROM (11.0°±2.9) than those with less than 6mm of postoperative disc height (8.7°±3.1, p=0.01). Patients with greater than 8mm of postoperative disc height have significantly lower postoperative flexion-extension ROM (mean, 8.9°±3.2) than those with 6-8mm of postoperative disc height (p=0.03). No significant difference was found between patients with <6mm of postoperative disc height and patients with >8mm of postoperative disc height (p=0.12). The postoperative JOA and NDI both have significant difference compared with preoperation(p<0.05). No correlation could be found between disc height and the postoperative ROM, JOA or NDI. CONCLUSION: Patients with less than 4mm of preoperative intervertebral disc height have a larger ROM after cervical arthroplasty. A 6-8mm of postoperative intervertebral disc height is the optimum range to maximize ROM. However, the optimal range did not translate into better clinical outcomes.

Location change of center of rotation after single-level cervical total disc replacement with ProDisc-C.

OBJECTIVE: Previous studies reported that the location of the center of rotation (COR) at instrumented level after cervical total disc replacement (TDR) deviated from its preoperative location. However, currently, it is unknown whether the deviated COR is linked to the range of motion (ROM) at instrumented level. The purpose of this study was to evaluate the clinical outcomes after cervical TDR with ProDisc-C (Synthes, West Chester, PA, USA), as well as investigate the location change of COR at instrumented level and its clinical significance. METHODS: A total of 23 patients who underwent single-level cervical TDR with ProDisc-C were included. Japanese Orthopaedic Association (JOA) score and Neck Disability Index (NDI) were used to assess clinical outcomes. Radiographic parameters such as cervical ROM, instrumented segmental ROM, adjacent segmental ROM, and intervertebral height were analyzed. Additionally, the location change of COR at instrumented level and its clinical significance were further analyzed by the alteration of its coordinates (COR-X, COR-Y). RESULTS: JOA scores increased significantly, while NDI scores decreased at final follow-up. No differences were found in cervical global ROM, instrumented segmental ROM, adjacent segmental ROM, and COR-Y at instrumented level between preoperative and final follow-up measurements (p>0.05); however, intervertebral height and COR-X increased significantly (p<0.05). CONCLUSION: Cervical global ROM, instrumented segmental ROM, and adjacent segmental ROM could be effectively maintained, and intervertebral height was increased after TDR with ProDisc-C. The location of COR at instrumented level shifted forward after cervical TDR.

Geometry of inferior endplates of the cervical spine.

OBJECTIVES: Device subsidence is a well-known complication following cervical disc arthroplasty. Its occurrence has been closely tied with the endplate-implant contact interface. But current literature on the geometry of cervical endplate is very scarce. The aim of this anatomical investigation was to analyze geometry of inferior endplates of the cervical vertebrae, thereby identifying the common endplate shape patterns and providing morphological reference values consummating the design of the implant. PATIENTS AND METHODS: Reformatted CT scans of 85 individuals were analyzed and endplate concave depth, endplate concave apex location, sagittal diameter of endplate, coronal concave angle, as well as transverse diameter of endplate were measured in mid-sagittal plane and specified coronal plane. According to the endplate concave apex location, the inferior endplates in mid-sagittal plane were classified into 3 types: type I with posteriorly positioned apex, type II with middle situated concave apex and type III with anteriorly positioned apex. Moreover, the inferior endplates in specified coronal plane were also classified into three types: concave, flat and irregular. RESULTS: Based on visual assessment, for the mid-sagittal plane, type I endplate accounted for 26.9% of all the 510 endplates of 85 individuals, while the proportion of type II and type III endplates were 53.9 and 19.2% respectively. For the specified coronal plane, 68.6% of all the 510 endplates were evaluated as concave, 26.9% as flat and the remaining 4.5% as irregular. Among all measured segments, C3 had the largest endplate concave depth values in mid-sagittal plane, while C7 the least; C5 and C6 had the largest sagittal endplate diameter values, while C2 the least. For each level, the sagittal endplate concave depth and endplate diameter of females were significantly smaller than those of males (P<0.05). Among all measured segments, C7 had the least coronal concave angle. Gender did not influence coronal concave angle significantly (P>0.05). Increasing from C2 to C7, the endplate transverse diameters of females were significantly smaller than those of males (P<0.05). CONCLUSION: The exact shape and geometry of cervical endplate are crucial for the design and improvement of cervical disc prosthesis. Gender difference of sagittal and transverse diameters of cervical endplate should be given more attention when implanting a disc prosthesis. These endplate geometrical parameters should be taken into consideration when calculating most suitable geometric parameters of new disc prosthesis.

Posterior distraction reduction and occipitocervical fixation for the treatment of basilar invagination and atlantoaxial dislocation.

OBJECT: To introduce a novel distraction technique for the treatment of basilar invagination (BI) and atlantoaxial dislocation (AAD) via a posterior-only approach. METHODS: Twenty-one consecutive patients with BI and AAD who underwent posterior distraction reduction and occipitocervical fixation between January 2009 and June 2013 were enrolled in the present study. This novel distraction technique included two steps. First, the distraction between the occipitocervical junction of the rod (OCJR) and the occipital screws was performed to achieve horizontal and partial vertical reduction. Secondly, the distraction was performed between the C2 screws and OCJR to achieve complete vertical reduction. The pre- and postoperative JOA score, the extent of reduction, the fusion status, and the complications were recorded and analyzed. RESULTS: The mean follow-up was 18.3 months with a range of 10-32 months. No patient incurred neurovascular injury during surgery. The mean JOA score at the last follow-up (15.4) showed significant improvement (P<0.01) compared with the pre-operative parameters (11.2). Complete horizontal reduction was achieved in 18 patients (85.7%), and complete vertical reduction was achieved in 17 patients (80.9%). The rest patients are all received greater than 50% horizontal and vertical reduction. Solid fusion was achieved in 20 patients (95.2%). Mild dysphagia was observed in two patients. One patient suffered from postoperative fever and pulmonary infection. CONCLUSION: This novel distraction technique may provide satisfactory reduction via a posterior-only approach without exposure of the C1/2 facet joint. Therefore, it is a safe and effective method for the treatment of BI with AAD.