Prospective comparison of dysphagia following anterior cervical discectomy and fusion (ACDF) with and without rhBMP-2.

BACKGROUND CONTEXT: Previous studies have called into question the safety of using rhBMP-2 in anterior cervical fusion due to the possibility of airway compromise and dysphagia. A retrospective chart review identified a significant increase in the severity of dysphagia after II-level ACDF with rhBMP-2 compared to patients who did not receive rhBMP-2. To date, this topic has not been studied prospectively. PURPOSE: Compare the incidence of dysphagia following anterior cervical discectomy and fusion (ACDF) when recombinant human bone morphogenetic protein-2 (rhBMP-2) is used with allograft compared to allograft alone. STUDY DESIGN: Prospective cohort study. PATIENT SAMPLE: A total of 114 patients completed a baseline SWAL-QOL survey and met the inclusion criteria. Thirty-nine patients underwent I- or II-level ACDF with allograft plus 0.5mg rhBMP-2/level. 44 patients underwent ACDF with allograft alone. Thirty-one patients undergoing a lumbar decompression were enrolled in a third cohort to control for dysphagia secondary to intubation. OUTCOME MEASURES: The primary outcome measure was the 14-point SWAL-QOL dysphagia questionnaire. Other patient factors obtained from anesthesia and operative records were examined to evaluate their potential relationship to postoperative dysphagia. METHODS: The 14-point SWAL-QOL questionnaire was administered at multiple time points (pre-op, post-op 7 days, 6 weeks, 6 months, and at least 1 year). Multivariable repeated-measures analysis was applied to data. RESULTS: Baseline adjusted SWAL-QOL means 7 days after surgery were significantly different between the three study groups. These differences resolved by 6 weeks postoperative, beyond which point there were no differences. At final follow-up, baseline adjusted SWAL-QOL means at 1 year were similar for the three study groups. CONCLUSIONS: This single-center study of anterior cervical surgery demonstrated that the addition of rhBMP-2 to an ACDF increased postoperative dysphagia at 7 days after surgery, but these patients recover to levels comparable to those who underwent ACDF without rhBMP-2 or lumbar surgery within 6 weeks.

Perioperative Complications of Cervical Spine Surgery: Analysis of a Prospectively Gathered Database through the Association for Collaborative Spinal Research.

Study Design Retrospective review of prospectively gathered data. Objective To report the rate and impact of perioperative complications in cervical spine surgery. To our knowledge, no prior study of the cervical spine has analyzed a large prospectively gathered data set for adverse events, based on surgical subgroup. Methods The ProSTOS database features prospectively documented perioperative adverse events for 1,269 patients who had cervical spine surgery at multiple centers in North America between 2008 and 2011. We subgrouped patients by approach, whether surgery was a primary or revision operation, and by the number of levels involved. Multivariate analysis with stepwise logistic regression was used to relate complication rates to gender, age, smoking status, body mass index, approach, revision status, and number of levels involved. Follow-up was 41%. Results Adverse events occurred significantly more frequently in posterior and combined procedures than in anterior procedures. Revision surgery had significantly more complications than primary surgery. For patients who had anterior surgery, those who had one, two, and three or more levels operated had no significant difference in complication rates. Patients who had posterior surgery had significantly more complications if they had two or more levels operated compared with one level. The lowest rates of complications were for one-level primary surgery (<5%), and multilevel posterior, revision posterior, and revision combined surgery had complication rates over 6 times higher (>28%). Patients who had complications were significantly older than patients who did not. The most common adverse events were dysphagia and cardiac complications. The most severe morbid complications, in terms of increased treatment needs and hospital stay, were paraparesis and seizure. Conclusions Perioperative complication rates in cervical spine surgery are significantly lower in younger patients, surgery performed through an anterior approach (compared with a posterior or combined approach), with fewer levels involved (particularly in posterior surgery), and in primary (compared with revision) procedures.

Posterolateral Lumbar Arthrodesis With and Without Interbody Arthrodesis for L4-L5 Degenerative Spondylolisthesis: A Comparative Value Analysis.

STUDY DESIGN: Independent retrospective review of prospectively collected data, comparative cohort study. OBJECTIVE: The objective of this study was to compare the clinical, radiographical, and cost/value of the addition of an interbody arthrodesis (IBA) to a posterolateral arthrodesis (PLA) in the surgical treatment of L4-L5 degenerative spondylolisthesis (DS). The authors hypothesized that the addition of IBA to PLA would produce added value while incurring minimal additional costs. SUMMARY OF BACKGROUND DATA: Many lumbar surgical advances have been made during the past several decades, yet there is a paucity of strong evidence-based validation, let alone comparative value analyses. The addition of an IBA to a PLA has become increasingly popular during the past 2 decades, yet the potential added value for the patient has not been carefully defined. METHODS: Patients undergoing single-level arthrodesis for L4-L5 DS performed at our institution from 2004 to 2012 were identified. Exclusion criteria included multilevel arthrodesis, spinal stenosis requiring decompression at or above L2-L3, previous L4-L5 spinal fusion, spondylolisthesis of greater than 33% of the vertebral body, and use of minimally invasive surgery. Radiographical fusion status, epidemiological, surgical, and functional outcomes, and cost/value data were recorded or calculated. RESULTS: A total of 179 patients with follow-up meeting inclusion criteria were identified: 68 with PLA alone and 111 with PLA + IBA. No statistical differences were noted in Oswestry Disability Index, 36-item Short-Form Health Survey scores, fusion rates, or cost/value at 6 months and at more than 3 years despite the PLA cohort being significantly older with more medical comorbidities. When length of stay was normalized across cohorts, the addition of an IBA increased hospital costs ranging from $577 to $5276, but this did not reach statistical significance. CONCLUSION: This single-center review of open surgical treatment of L4-L5 DS demonstrated that the addition of IBA to PLA added cost while producing equivalent results in fusion rates, Oswestry Disability Index, and 36-item Short-Form Health Survey scores when compared with PLA alone. LEVEL OF EVIDENCE: 3.

Injection of human umbilical tissue-derived cells into the nucleus pulposus alters the course of intervertebral disc degeneration in vivo.

BACKGROUND CONTEXT: Patients often present to spine clinic with evidence of intervertebral disc degeneration (IDD). If conservative management fails, a safe and effective injection directly into the disc might be preferable to the risks and morbidity of surgery. PURPOSE: To determine whether injecting human umbilical tissue-derived cells (hUTC) into the nucleus pulposus (NP) might improve the course of IDD. DESIGN: Prospective, randomized, blinded placebo-controlled in vivo study. PATIENT SAMPLE: Skeletally mature New Zealand white rabbits. OUTCOME MEASURES: Degree of IDD based on magnetic resonance imaging (MRI), biomechanics, and histology. METHODS: Thirty skeletally mature New Zealand white rabbits were used in a previously validated rabbit annulotomy model for IDD. Discs L2-L3, L3-L4, and L4-L5 were surgically exposed and punctured to induce degeneration and then 3 weeks later the same discs were injected with hUTC with or without a hydrogel carrier. Serial MRIs obtained at 0, 3, 6, and 12 weeks were analyzed for evidence of degeneration qualitatively and quantitatively via NP area and MRI Index. The rabbits were sacrificed at 12 weeks and discs L4-L5 were analyzed histologically. The L3-L4 discs were fixed to a robotic arm and subjected to uniaxial compression, and viscoelastic displacement curves were generated. RESULTS: Qualitatively, the MRIs demonstrated no evidence of degeneration in the control group over the course of 12 weeks. The punctured group yielded MRIs with the evidence of disc height loss and darkening, suggestive of degeneration. The three treatment groups (cells alone, carrier alone, or cells+carrier) generated MRIs with less qualitative evidence of degeneration than the punctured group. MRI Index and area for the cell and the cell+carrier groups were significantly distinct from the punctured group at 12 weeks. The carrier group generated MRI data that fell between control and punctured values but failed to reach a statistically significant difference from the punctured values. There were no statistically significant MRI differences among the three treatment groups. The treated groups also demonstrated viscoelastic properties that were distinct from the control and punctured values, with the cell curve more similar to the punctured curve and the carrier curve and carrier+cells curve more similar to the control curve (although no creep differences achieved statistical significance). There was some histological evidence of improved cellularity and disc architecture in the treated discs compared with the punctured discs. CONCLUSIONS: Treatment of degenerating rabbit intervertebral discs with hUTC in a hydrogel carrier solution might help restore the MRI, histological, and biomechanical properties toward those of nondegenerated controls. Treatment with cells in saline or a hydrogel carrier devoid of cells also might help restore some imaging, architectural, and physical properties to the degenerating disc. These data support the potential use of therapeutic cells in the treatment of disc degeneration.

Injection of AAV2-BMP2 and AAV2-TIMP1 into the nucleus pulposus slows the course of intervertebral disc degeneration in an in vivo rabbit model.

BACKGROUND CONTEXT: Intervertebral disc degeneration (IDD) is a common cause of back pain. Patients who fail conservative management may face the morbidity of surgery. Alternative treatment modalities could have a significant impact on disease progression and patients' quality of life. PURPOSE: To determine if the injection of a virus vector carrying a therapeutic gene directly into the nucleus pulposus improves the course of IDD. STUDY DESIGN: Prospective randomized controlled animal study. METHODS: Thirty-four skeletally mature New Zealand white rabbits were used. In the treatment group, L2-L3, L3-L4, and L4-L5 discs were punctured in accordance with a previously validated rabbit annulotomy model for IDD and then subsequently treated with adeno-associated virus serotype 2 (AAV2) vector carrying genes for either bone morphogenetic protein 2 (BMP2) or tissue inhibitor of metalloproteinase 1 (TIMP1). A nonoperative control group, nonpunctured sham surgical group, and punctured control group were also evaluated. Serial magnetic resonance imaging (MRI) studies at 0, 6, and 12 weeks were obtained, and a validated MRI analysis program was used to quantify degeneration. The rabbits were sacrificed at 12 weeks, and L4-L5 discs were analyzed histologically. Viscoelastic properties of the L3-L4 discs were analyzed using uniaxial load-normalized displacement testing. Creep curves were mathematically modeled according to a previously validated two-phase exponential model. Serum samples obtained at 0, 6, and 12 weeks were assayed for biochemical evidence of degeneration. RESULTS: The punctured group demonstrated MRI and histologic evidence of degeneration as expected. The treatment groups demonstrated less MRI and histologic evidence of degeneration than the punctured group. The serum biochemical marker C-telopeptide of collagen type II increased rapidly in the punctured group, but the treated groups returned to control values by 12 weeks. The treatment groups demonstrated several viscoelastic properties that were distinct from control and punctured values. CONCLUSIONS: Treatment of punctured rabbit intervertebral discs with AAV2-BMP2 or AAV2-TIMP1 helps delay degenerative changes, as seen on MRI, histologic sampling, serum biochemical analysis, and biomechanical testing. Although data from animal models should be extrapolated to the human condition with caution, this study supports the potential use of gene therapy for the treatment of IDD.

Emerging technologies for degenerative disk disease: potential synergy between biochemical signaling and spinal biomechanics.

Interventional spinal procedures are performed with increasing frequency, and they remain an important tool for physiatrists treating patients with spine pain. As the potential treatment options expand with novel technologies on the horizon, such as gene- and cell-based therapies, the physiatrist will be uniquely poised to deliver such treatments in conjunction with exercise-based therapies. Therefore, the development of novel technologies requires particular attention to the potential synergy between biochemical signaling and spinal biomechanics. It is hoped that such insight will result in improved treatment options for patients with pain related to degenerative disk disease, leading to improved nonoperative outcomes. This article reviews the current knowledge of precipitants of disk degeneration, the effects of beneficial and traumatic levels of disk loading, and how each of these can be impacted by novel treatment options.

Identification of candidate serum biomarkers for intervertebral disk degeneration in an animal model.

OBJECTIVE: To examine serum markers of matrix turnover in an animal model of disk degeneration. DESIGN: Randomized prospective in vivo study. SETTING: Laboratory for Orthopaedic and Spine Research and Department of Large Animal Research. PARTICIPANTS: Twenty-one New Zealand White rabbits. INTERVENTION: Rabbits were randomly grouped into control (n = 8), sham surgery (n = 5), or stab surgery (n = 8). The stab surgical group underwent annulotomy of L2-3, L3-4, and L4-5 to induce intervertebral disk degeneration. The sham surgical group underwent surgical exposure without annulotomy, and the control group received no intervention. OUTCOME MEASUREMENTS: Lumbar spine magnetic resonance imaging (MRI) and serum samples were obtained before intervention and at 0, 3, 6, and 12 weeks thereafter. MRIs were analyzed for evidence of intervertebral disk degeneration via measurement of MRI index. The serum was assayed at 0, 3, 6, and 12 weeks for the aggrecan biosynthesis marker CS846 and the C-telopeptide of collagen II (CTX-II). RESULTS: The stabbed disks demonstrate degeneration apparent by MRI criteria. CTX-II increased with time in the stabbed group compared to the control and sham surgery groups regardless of baseline levels. Aggrecan showed no statistically significant difference among groups. CONCLUSIONS: CTX-II shows promise as a useful serum biomarker for intervertebral disk degeneration.

Perioperative management of a patient with Chagas disease having mitral valve surgery.

A patient with advanced Chagas disease presented with symptoms attributable to dilated cardiomyopathy and mitral regurgitation. Although esophageal involvement is part of the constellation of findings in Chagas, transesophageal echocardiography was safely used to guide the mitral valve surgery.