Nassr, Ahmad

ABSTRACTDegenerative disk disease of the spine is a major cause of back pain and disability. Optimization of regenerative medical therapies for degenerative disk disease requires a deep mechanistic understanding of the factors controlling the structural integrity of spinal tissues. In this investigation, we sought to identify candidate regulatory genes controlling extracellular matrix synthesis in spinal tissues. To achieve this goal we performed high throughput next generation RNA sequencing on 39 annulus fibrosus and 21 nucleus pulposus human tissue samples. Specimens were collected from patients undergoing surgical discectomy for the treatment of degenerative disk disease. Our studies identified associations between extracellular matrix genes, growth factors, and other important regulatory molecules. The fibrous matrix characteristic of annulus fibrosus was associated with expression of the growth factors platelet derived growth factor beta (PDGFB), vascular endothelial growth factor C (VEGFC), and fibroblast growth factor 9 (FGF9). Additionally we observed high expression of multiple signaling proteins involved in the NOTCH and WNT signaling cascades. Nucleus pulposus extracellular matrix related genes were associated with the expression of numerous diffusible growth factors largely associated with the transforming growth signaling cascade, including transforming factor alpha (TGFA), inhibin alpha (INHA), inhibin beta A (INHBA), bone morphogenetic proteins (BMP2, BMP6), and others. Clinical significance: this investigation provides important data on extracellular matrix gene regulatory networks in disk tissues. This information can be used to optimize pharmacologic, stem cell, and tissue engineering strategies for regeneration of the intervertebral disk and the treatment of back pain. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1356–1369, 2018.

Study Design: Retrospective review. Objectives: This study investigates the prevalence of adverse postsurgical events, or osteoporosis-related complications (ORCs), following spinal fusion. Methods: Patients undergoing primary posterior thoracolumbar or lumbar fusion by 1 of 2 surgeons practicing at a single institution were analyzed from 2007 to 2014. ORCs were defined in one of the following categories: revision surgery, compression fracture, proximal junctional kyphosis, pseudarthrosis, or failure of instrumentation. Patients with a bone mineral density of the hips and/or spine performed within 1 year of the index procedure were included. Patients were stratified into normal bone density, osteopenia, and osteoporosis using WHO guidelines. Patients were excluded if they were younger than 18 years at the time of surgery, with infection, malignancy, skeletal dysplasia, neuromuscular disorders, concomitant or staged anterior-posterior procedure, or fusion performed because of trauma. Results: Out of 140 patients included, the prevalence of normal bone density was 31.4% (44/140), osteopenia 58.6% (82/140), and osteoporosis 10.0% (14/140). There were no differences between groups for gender, age, body mass index, and interbody device rate. The overall prevalence of ORCs was 32.1% (45/140). By group, there was a prevalence of 22.7% (10/44), 32.9% (27/82), and 50.0% (7/14) for normal bone density, osteopenia, and osteoporosis, respectively. These differences were significantly higher for both the osteopenia and osteoporosis groups. Conclusions: Patients with T scores below −1.0 undergoing posterior lumbar fusion have an increased prevalence of ORCs. Consideration of bone density plays a crucial role in patient selection, medical management, and counseling patient expectations.

Study Design. Systematic review and meta-analysis. Objective. To compare postoperative surgical, radiographic, and patient-reported outcomes following anterior cervical discectomy and fusion (ACDF) with and without plate fixation. Summary of Background Data. ACDF has evolved significantly over the years, including the placement of an anterior plate construct. Although promoting bony osseo-integration at the fusion site, there are a number of plate-related complications that can arise. The non-plating approach is less invasive, however, greater rates of cage subsidence have been associated with this model. Methods. We performed an electronic literature search for human studies that directly compared ACDF with and without anterior plate fixation. Outcomes of interest comprised of postoperative dysphagia, fusion success, and cage subsidence as well as patient reported outcomes, including the Neck Disability Index (NDI) scores and Visual Analog Scale (VAS) for both neck and arm pain. Results. A total of 15 studies (12 observational and 3 randomized controlled trials) and 893 patients (57% males) were included. Overall, ACDF with plate fixation was associated with significantly higher vertebral fusion rates (odds ratio [OR] 1.98; 95% confidence interval [CI] 1.16–3.37), lower subsidence rates (odds ratio [OR] 0.31, 95% CI 0.18–0.52), and more favorable VAS-neck pain scores at last follow-up (mean difference [MD] 0.59, 95% CI −0.78 to −0.41). Conversely, ACDF procedures without plate fixation had marginally better long-term VAS-arm pain scores (mean difference [MD] 0.2, 95% CI 0.04–0.36). No difference was found with regards to dysphagia (OR 1.21, 95% CI, 0.57–2.56) and NDI (MD 0.06, 95% C.I −0.54 to 0.42). Conclusion. Available evidence, although limited, suggests superior surgical outcomes in ACDF procedures with anterior plate fixation (increased fusion, decreased subsidence) and slightly better VAS-neck pain scores at last follow-up. Future longitudinal, multicenter randomized controlled trials should be completed to validate any associations found in this study. Level of Evidence: 3

Study Design: Retrospective multicenter case series. Objective: To assess the rate of perioperative vision loss following cervical spinal surgery. Methods: Medical records for 17 625 patients from 21 high-volume surgical centers from the AOSpine North America Clinical Research Network who received cervical spine surgery (levels from C2 to C7) between January 1, 2005, and December 31, 2011, inclusive, were reviewed to identify occurrences of vision loss following surgery. Results: Of the 17 625 patients in the registry, there were 13 946 patients assessed for the complication of blindness. There were 9591 cases that involved only anterior surgical approaches; the remaining 4355 cases were posterior and/or circumferential fusions. There were no cases of blindness or vision loss in the postoperative period reported during the sampling period. Conclusions: Perioperative vision loss following cervical spinal surgery is exceedingly rare.

Study Design: Systematic review and meta-analysis. Objectives: The safety of new technology such as cervical total disc replacement (TDR) is of paramount importance and is best evaluated in randomized clinical trials (RCT). We compared complication risks of TDR to fusion using data from Investigational Device Exemptions. Methods: A systematic review of FDA Summary of Safety and Effectiveness reports of the 8 approved cervical TDRs was performed. These were all randomized controlled trials comparing anterior cervical discectomy and fusion (ACDF) to TDR. Important outcome variables were dysphagia, wound infection, neurologic injuries, heterotopic ossification, death, and secondary surgeries. A random effects model was selected a priori. Data on adverse events was abstracted and analyzed by calculating relative risk of ACDF to TDR by meta-analysis techniques. Results: The study included 3027 patients with 1377 randomized to ACDF and 1652 to TDR. No statistical differences were present between the 2 groups in dysphagia/dysphonia, hardware related, heterotopic ossification, death, and overall neurologic adverse events and incidence of neurologic deterioration. The relative risk of wound-related problems ACDF to TDR was 0.76 (95% confidence interval [CI] = 0.59, 0.98) favoring ACDF, which was statistically significant, but these were minor and never required a second surgical procedure for deep wound infection. The relative risk of ACDF to TDR in surgical-related neurologic events and secondary surgeries was 1.62 (95% CI = 1.04, 2.53) and 1.79 (95% CI = 1.17, 2.74), both favoring TDR. Conclusions: Cervical TDR appears to be as safe as or safer than ACDF at 2-year follow-up.

Study Design: A multicenter, retrospective review of C5 palsy after cervical spine surgery. Objective: Postoperative C5 palsy is a known complication of cervical decompressive spinal surgery. The goal of this study was to review the incidence, patient characteristics, and outcome of C5 palsy in patients undergoing cervical spine surgery. Methods: We conducted a multicenter, retrospective review of 13 946 patients across 21 centers who received cervical spine surgery (levels C2 to C7) between January 1, 2005, and December 31, 2011, inclusive. P values were calculated using 2-sample t test for continuous variables and χ 2 tests or Fisher exact tests for categorical variables. Results: Of the 13 946 cases reviewed, 59 patients experienced a postoperative C5 palsy. The incidence rate across the 21 sites ranged from 0% to 2.5%. At most recent follow-up, 32 patients reported complete resolution of symptoms (54.2%), 15 had symptoms resolve with residual effects (25.4%), 10 patients did not recover (17.0%), and 2 were lost to follow-up (3.4%). Conclusion: C5 palsy occurred in all surgical approaches and across a variety of diagnoses. The majority of patients had full recovery or recovery with residual effects. This study represents the largest series of North American patients reviewed to date.

Study Design: Retrospective cohort study of prospectively collected data. Objective: To examine the incidence of iatrogenic spinal cord injury following elective cervical spine surgery. Methods: A retrospective multicenter case series study involving 21 high-volume surgical centers from the AOSpine North America Clinical Research Network was conducted. Medical records for 17 625 patients who received cervical spine surgery (levels from C2 to C7) between January 1, 2005, and December 31, 2011, were reviewed to identify occurrence of iatrogenic spinal cord injury. Results: In total, 3 cases of iatrogenic spinal cord injury following cervical spine surgery were identified. Institutional incidence rates ranged from 0.0% to 0.24%. Of the 3 patients with quadriplegia, one underwent anterior-only surgery with 2-level cervical corpectomy, one underwent anterior surgery with corpectomy in addition to posterior surgery, and one underwent posterior decompression and fusion surgery alone. One patient had complete neurologic recovery, one partially recovered, and one did not recover motor function. Conclusion: Iatrogenic spinal cord injury following cervical spine surgery is a rare and devastating adverse event. No standard protocol exists that can guarantee prevention of this complication, and there is a lack of consensus regarding evaluation and treatment when it does occur. Emergent imaging with magnetic resonance imaging or computed tomography myelography to evaluate for compressive etiology or malpositioned instrumentation and avoidance of hypotension should be performed in cases of intraoperative and postoperative spinal cord injury.

Study Design: Retrospective multicenter case series study. Objective: Because cervical dural tears are rare, most surgeons have limited experience with this complication. A multicenter study was performed to better understand the presentation, treatment, and outcomes following cervical dural tears. Methods: Multiple surgeons from 23 institutions retrospectively identified 21 rare complications that occurred between 2005 and 2011, including unintentional cervical dural tears. Demographic data and surgical history were obtained. Clinical outcomes following surgery were assessed, and any reoperations were recorded. Neck Disability Index (NDI), modified Japanese Orthopaedic Association (mJOA), Nurick classification (NuC), and Short-Form 36 (SF36) scores were recorded at baseline and final follow-up at certain centers. All data were collected, collated, and analyzed by a private research organization. Results: There were 109 cases of cervical dural tears among 18 463 surgeries performed. In 101 cases (93%) there was no clinical sequelae following successful dural tear repair. There were statistical improvements ( P < .05) in mJOA and NuC scores, but not NDI or SF36 scores. No specific baseline or operative factors were found to be associated with the occurrence of dural tears. In most cases, no further postoperative treatments of the dural tear were required, while there were 13 patients (12%) that required subsequent treatment of cerebrospinal fluid drainage. Analysis of those requiring further treatments did not identify an optimum treatment strategy for cervical dural tears. Conclusions: In this multicenter study, we report our findings on the largest reported series (n = 109) of cervical dural tears. In a vast majority of cases, no subsequent interventions were required and no clinical sequelae were observed.

Study Design: This study was a retrospective, multicenter cohort study. Objectives: Rare complications of cervical spine surgery are inherently difficult to investigate. Pseudomeningocoele (PMC), an abnormal collection of cerebrospinal fluid that communicates with the subarachnoid space, is one such complication. In order to evaluate and better understand the incidence, presentation, treatment, and outcome of PMC following cervical spine surgery, we conducted a multicenter study to pool our collective experience. Methods: This study was a retrospective, multicenter cohort study of patients who underwent cervical spine surgery at any level(s) from C2 to C7, inclusive; were over 18 years of age; and experienced a postoperative PMC. Results: Thirteen patients (0.08%) developed a postoperative PMC, 6 (46.2%) of whom were female. They had an average age of 48.2 years and stayed in hospital a mean of 11.2 days. Three patients were current smokers, 3 previous smokers, 5 had never smoked, and 2 had unknown smoking status. The majority, 10 (76.9%), were associated with posterior surgery, whereas 3 (23.1%) occurred after an anterior procedure. Myelopathy was the most common indication for operations that were complicated by PMC (46%). Seven patients (53%) required a surgical procedure to address the PMC, whereas the remaining 6 were treated conservatively. All PMCs ultimately resolved or were successfully treated with no residual effects. Conclusions: PMC is a rare complication of cervical surgery with an incidence of less than 0.1%. They prolong hospital stay. PMCs occurred more frequently in association with posterior approaches. Approximately half of PMCs required surgery and all ultimately resolved without residual neurologic or other long-term effects.