Reginald J. Davis

Cervical total disc replacement with the mobi-C cervical artificial disc compared with anterior discectomy and fusion for treatment of 2-level symptomatic degenerative disc disease: A prospective, randomized, controlled multicenter clinical trial: Clinical article

OBJECT Cervical total disc replacement (TDR) is intended to treat neurological symptoms and neck pain associated with degeneration of intervertebral discs in the cervical spine. Anterior cervical discectomy and fusion (ACDF) has been the standard treatment for these indications since the procedure was first developed in the 1950s. While TDR has been shown to be a safe and effective alternative to ACDF for treatment of patients with degenerative disc disease (DDD) at a single level of the cervical spine, few studies have focused on the safety and efficacy of TDR for treatment of 2 levels of the cervical spine. The primary objective of this study was to rigorously compare the Mobi-C cervical artificial disc to ACDF for treatment of cervical DDD at 2 contiguous levels of the cervical spine. METHODS This study was a prospective, randomized, US FDA investigational device exemption pivotal trial of the Mobi-C cervical artificial disc conducted at 24 centers in the US. The primary clinical outcome was a composite measure of study success at 24 months. The comparative control treatment was ACDF using allograft bone and an anterior plate. A total of 330 patients were enrolled, randomized, and received study surgery. All patients were diagnosed with intractable symptomatic cervical DDD at 2 contiguous levels of the cervical spine between C-3 and C-7. Patients were randomized in a 2:1 ratio (TDR patients to ACDF patients). RESULTS A total of 225 patients received the Mobi-C TDR device and 105 patients received ACDF. At 24 months only 3.0% of patients were lost to follow-up. On average, patients in both groups showed significant improvements in Neck Disability Index (NDI) score, visual analog scale (VAS) neck pain score, and VAS arm pain score from preoperative baseline to each time point. However, the TDR patients experienced significantly greater improvement than ACDF patients in NDI score at all time points and significantly greater improvement in VAS neck pain score at 6 weeks, and at 3, 6, and 12 months postoperatively. On average, patients in the TDR group also maintained preoperative segmental range of motion at both treated segments immediately postoperatively and throughout the study period of 24 months. The reoperation rate was significantly higher in the ACDF group at 11.4% compared with 3.1% for the TDR group. Furthermore, at 24 months TDR demonstrated statistical superiority over ACDF based on overall study success rates. CONCLUSIONS The results of this study represent the first available Level I clinical evidence in support of cervical arthroplasty at 2 contiguous levels of the cervical spine using the Mobi-C cervical artificial disc. These results continue to support the use of cervical arthroplasty in general, but specifically demonstrate the advantages of 2-level arthroplasty over 2-level ACDF. Clinical trial registration no.: NCT00389597 (ClinicalTrials.gov).

Prospective, Randomized Comparison of Cervical Total Disk Replacement Versus Anterior Cervical Fusion: Results at 48 Months Follow-up

Study Design: This was a prospective, randomized, controlled multicenter trial. Objective: The purpose of this study was to compare clinical outcomes at 4-year follow-up of patients receiving cervical total disk replacement (TDR) with those receiving anterior cervical discectomy and fusion (ACDF). Summary of Background Data: ACDF has been the traditional treatment for symptomatic disk degeneration. Several studies found single-level TDR to be as safe and effective as ACDF at ≥2 years follow-up. Methods: Patients from 23 centers were randomized in a 2:1 ratio with 164 receiving the investigational device (Mobi-C Cervical Disc Prosthesis) and 81 receiving ACDF using an anterior plate and allograft. Patients were evaluated preoperatively and 6 weeks, 3, 6, 12, 18, 24, 36, and 48 months postoperatively. Outcome assessments included a composite success score, Neck Disability Index, visual analog scales assessing neck and arm pain, patient satisfaction, major complications, subsequent surgery, segmental range of motion, and adjacent-segment degeneration. Results: The composite success rate was similar in the 2 groups at 48-month follow-up. Mean Neck Disability Index, visual analog scale, and SF-12 scores were significantly improved in early follow-up in both groups with improvements maintained throughout 48 months. On some measures, TDR had significantly greater improvement during early follow-up. At no follow-up were TDR scores significantly worse than ACDF scores. Subsequent surgery rate was significantly higher for ACDF compared with TDR (9.9% vs. 3.0%, P<0.05). Range of motion was maintained with TDR having a mean baseline value of 8 degrees compared with 10 degrees at 48 months. The incidence of adjacent-segment degeneration was significantly higher with ACDF at inferior and superior segments compared with TDR (inferior: 50% vs. 30%, P<0.025; superior: 53% vs. 34%, P<0.025). Conclusions: Significant improvements were observed in pain and function. TDR patients maintained motion and had significantly lower rates of reoperation and adjacent-segment degeneration compared with ACDF. This study supports the safety and efficacy of TDR in appropriately selected patients.

Role of Oxygen Free Radicals in Focal Brain Ischemia

Oxygen-derived free radicals have been implicated in a wide variety of disease states [1,2] and have been postulated to mediate an element of cerebral ischemic injury. We tested the hypothesis that neutralization of oxygen free radicals using superoxide dismutase (SOD) ameliorates the cerebral ischemic injury produced by temporary occlusion of the middle cerebral artery.

Can low-grade spondylolisthesis be effectively treated by either coflex interlaminar stabilization or laminectomy and posterior spinal fusion? Two-year clinical and radiographic results from the randomized, prospective, multicenter US investigational device exemption trial: clinical article.

OBJECT Posterolateral spinal fusion (PSF) has long been the standard of care for degenerative spondylolisthesis, but less invasive, motion-preserving alternatives have been proposed to reduce the complications associated with fusion while still providing neural decompression and stabilization. The object of the current study is to evaluate the safety and efficacy of coflex Interlaminar Stabilization compared with PSF to treat low-grade spondylolisthesis with spinal stenosis. METHODS This is a prospective, randomized, multicenter FDA investigational device exemption (IDE) trial comparing coflex Interlaminar Stabilization with laminectomy and PSF. A total of 322 patients from 21 sites in the US were enrolled between 2006 and 2008 for the IDE trial. The current study evaluated only the subset of patients from this overall cohort with Grade 1 spondylolisthesis (99 in the coflex group and 51 in the fusion group). Subjects were randomized 2:1 to receive decompression and coflex interlaminar stabilization or decompression and posterolateral spinal fusion with spinal instrumentation. Data collected included perioperative outcomes, Oswestry Disability Index (ODI), back and worse leg visual analog scale (VAS) scores, 12-Item Short Form Health Survey, Zurich Claudication Questionnaire (ZCQ), and radiographic outcomes at a minimum of 2 years. The FDA criteria for overall device success required the following to be met: 15-point reduction in ODI, no reoperations, no major device-related complications, and no postoperative epidural injections. RESULTS At a minimum of 2 years, patient follow-up was 94.9% and 94.1% in the coflex and fusion control groups, respectively. There were no group differences at baseline for any demographic, clinical, or radiographic parameter. The average age was 63 years in the coflex cohort and 65 years in the fusion cohort. Coflex subjects experienced significantly shorter operative times (p < 0.0001), less estimated blood loss (p < 0.0001), and shorter length of stay (p < 0.0001) than fusion controls. Both groups experienced significant improvements from baseline at 2 years in ODI, VAS back, VAS leg, and ZCQ, with no significant group differences, with the exception of significantly greater ZCQ satisfaction with coflex at 2 years. FDA overall success was achieved in 62.8% of coflex subjects (59 of 94) and 62.5% of fusion controls (30 of 48) (p = 1.000). The reoperation rate was higher in the coflex cohort (14 [14.1%] of 99) compared with fusion (3 [5.9%] of 51, p = 0.18), although this difference was not statistically significant. Fusion was associated with significantly greater angulation and translation at the superior and inferior adjacent levels compared with baseline, while coflex showed no significant radiographic changes at the operative or index levels. CONCLUSIONS Low-grade spondylolisthesis was effectively stabilized by coflex and led to similar clinical outcomes, with improved perioperative outcomes, compared with PSF at 2 years. Reoperation rates, however, were higher in the coflex cohort. Patients in the fusion cohort experienced significantly increased superior and inferior level angulation and translation, while those in the coflex cohort experienced no significant adjacent or index level radiographic changes from baseline. Coflex Interlaminar Stabilization is a less invasive, safe, and equally efficacious clinical solution to PSF to treat low-grade spondylolisthesis, and it appears to reduce stresses at the adjacent levels. Clinical trial registration no.: NCT00534235 (ClinicalTrials.gov).

Subsequent surgery rates after cervical total disc replacement using a Mobi-C Cervical Disc Prosthesis versus anterior cervical discectomy and fusion: a prospective randomized clinical trial with 5-year follow-up.

OBJECTIVE Cervical total disc replacement (TDR) has been shown in a number of prospective clinical studies to be a viable treatment alternative to anterior cervical discectomy and fusion (ACDF) for the treatment of symptomatic degenerative disc disease. In addition to preserving motion, evidence suggests that cervical TDR may result in a lower incidence of subsequent surgical intervention than treatment with fusion. The goal of this study was to evaluate subsequent surgery rates up to 5 years in patients treated with TDR or ACDF at 1 or 2 contiguous levels between C-3 and C-7. METHODS This was a prospective, multicenter, randomized, unblinded clinical trial. Patients with symptomatic degenerative disc disease were enrolled to receive 1- or 2-level treatment with either TDR as the investigational device or ACDF as the control treatment. There were 260 patients in the 1-level study (179 TDR and 81 ACDF patients) and 339 patients in the 2-level study (234 TDR and 105 ACDF patients). RESULTS At 5 years, the occurrence of subsequent surgical intervention was significantly higher among ACDF patients for 1-level (TDR, 4.5% [8/179]; ACDF, 17.3% [14/81]; p = 0.0012) and 2-level (TDR, 7.3% [17/234]; ACDF, 21.0% [22/105], p = 0.0007) treatment. The TDR group demonstrated significantly fewer index- and adjacent-level subsequent surgeries in both the 1- and 2-level cohorts. CONCLUSIONS Five-year results showed treatment with cervical TDR to result in a significantly lower rate of subsequent surgical intervention than treatment with ACDF for both 1 and 2 levels of treatment. Clinical trial registration no.: NCT00389597 ( clinicaltrials.gov ).

Evaluation of Decompression and Interlaminar Stabilization Compared with Decompression and Fusion for the Treatment of Lumbar Spinal Stenosis: 5-year Follow-up of a Prospective, Randomized, Controlled Trial

Introduction If nonoperative treatment for lumbar stenosis fails, surgery may be considered. This traditionally includes decompression often combined with fusion. Desire for less extensive surgery led to developing new techniques and implants, including an interlaminar device designed with the goal of providing segmental stability without fusion, following decompression. The purpose of this study was to investigate 5-year outcomes associated with an interlaminar device. Methods This prospective, randomized, controlled trial was conducted at 21 centers. Patients with moderate to severe lumbar stenosis at one or two contiguous levels and up to Grade I spondylolisthesis were randomized (2:1 ratio) to decompression and interlaminar stabilization (D+ILS; n=215) using the coflex® Interlaminar Stabilization® device (Paradigm Spine, LLC) or decompression and fusion with pedicle screws (D+PS; n=107). Clinical evaluations were made preoperatively and at 6 weeks and 3, 6, 12, 18, 24, 36, 48, and 60 months postoperatively. Overall Food and Drug Administration success criteria required that a patient meet 4 criteria: 1) >15 point improvement in Oswestry Disability Index (ODI) score; 2) no reoperation, revision, removal, or supplemental fixation; 3) no major device-related complication; and 4) no epidural steroid injection after surgery. Results At 5 years, 50.3% of D+ILS vs. 44% of D+PS patients (p>0.35) met the composite success criteria. Reoperation/revision rates were similar in the two groups (16.3% vs. 17.8%; p >0.90). Both groups had statistically significant improvement through 60 months in ODI scores with 80.6% of D+ILS patients and 73.2% of D+PS patients demonstrating >15 point improvement (p>0.30). VAS, SF-12, and ZCQ scores followed a similar pattern of maintained significant improvement throughout follow-up. On the SF-12 and ZCQ, D+ILS group scores were statistically significantly better during early follow-up compared to D+PS. In the D+ILS group, foraminal height, disc space height, and range of motion at the index level were maintained through 5 years. Conclusion Both treatment groups achieved and maintained statistically significant improvements on multiple outcome assessments throughout 5-year follow-up. On some clinical measures, there were statistically significant differences during early follow-up favoring D+ILS. At no point were there significant differences favoring D+PS. Results of this 5-year follow-up study demonstrate that decompression and interlaminar stabilization with coflex is a viable alternative to traditional decompression and fusion in the treatment of patients with moderate to severe stenosis at one or two lumbar levels. Level of Evidence and Ethical Statements This is a Level I study. Institutional approval was received at each of the sites participating in the trial. Each patient gave informed consent to participate in the trial.

Three-Year Follow-up of the Prospective, Randomized, Controlled Trial of Coflex Interlaminar Stabilization vs Instrumented Fusion in Patients With Lumbar Stenosis.

BACKGROUND Traditional surgical options for the treatment of symptomatic lumbar spinal stenosis include decompression alone vs decompression and fusion; both options have potential limitations. OBJECTIVE To report the 36-month follow-up analysis of the coflex Interlaminar Stabilization (Paradigm Spine, LLC, New York, New York) after decompression, examined under a Food and Drug Administration investigational device exemption clinical trial, which is intended to provide stabilization after decompression while preserving normal segmental motion at the treated level. METHODS The coflex trial was a prospective, randomized investigational device exemption study conducted at 21 clinical sites in the United States. Baseline and follow-up visits collected demographics, clinical, and radiographic status. The primary endpoint was a measure of composite clinical success 24 months postoperatively. For this current 36-month analysis, composite clinical success was calculated using analogous methods. RESULTS Composite clinical success at 36 months was achieved by 62.2% among 196 coflex Interlaminar Stabilization patients and 48.9% among 94 fusion patients (difference = 13.3%, 95% confidence interval, 1.1%-25.5%, P = .03). Bayesian posterior probabilities for noninferiority (margin = -10%) and superiority of cofle Interlaminar Stabilization vs fusion were >0.999 and 0.984, respectively. Substantial and comparable improvements were observed in both groups for patient-reported outcomes, although the percentage with a clinically significant improvement (≥15) in the Oswestry Disability Index seemed larger for the coflex Interlaminar Stabilization group relative to the fusion group (P = .008). Radiographic measurements maintained index level and adjacent level range of motion in coflex Interlaminar Stabilization patients, although range of motion at the level superior to fusion was significantly increased (P = .005). CONCLUSION Coflex Interlaminar Stabilization for stenosis is proven to be effective and durable at improving overall composite clinical success without altering normal spinal kinematic motion at the index level of decompression or adjacent levels. ABBREVIATIONS CCS, composite clinical successCEC, clinical events committeeFDA, Food and Drug AdministrationIDE, investigational device exemptionILS, Coflex Interlaminar StabilizationODI, Oswestry Disability IndexSF-12, Short-Form 12VAS, visual analogue scalesZCQ, Zurich Claudication Questionnaire.

Long-term Evaluation of Cervical Disc Arthroplasty with the Mobi-C© Cervical Disc: A Randomized, Prospective, Multicenter Clinical Trial with Seven-Year Follow-up

Background Cervical total disc replacement (TDR) is an increasingly accepted procedure for the treatment of symptomatic cervical degenerative disc disease. Multiple Level I evidence clinical trials have established cervical TDR to be a safe and effective procedure in the short-term. The objective of this study is to provide a long-term assessment of TDR versus anterior discectomy and fusion for the treatment of one- and two-level disc disease. Methods This study was a continuation of a prospective, multicenter, randomized, US FDA IDE clinical trial comparing cervical TDR with the Mobi-C© Cervical Disc versus ACDF through 7 years follow-up. Inclusion criteria included a diagnosis of symptomatic cervical degenerative disc disease at one or two cervical levels. TDR patients were treated using a Mobi-C© artificial disc (Zimmer Biomet, Austin TX, USA). ACDF with allograft and anterior plate was used as a control treatment. Outcome measures were collected preoperatively and postoperatively at 6 weeks, at 3, 6, 12, 18 months, annually through 60 months, and at 84 months. Measured outcomes included Overall success, Neck Disability Index (NDI), VAS neck and arm pain, segmental range of motion (ROM), patient satisfaction, SF-12 MCS/PCS, major complications, and subsequent surgery rate. The primary endpoint was an FDA composite definition of success comprising clinical improvement and an absence of major complications and secondary surgery events. Results A total of 599 patients were enrolled and treated, with 164 treated with one-level TDR, 225 treated with two-level TDR, 81 treated with one-level ACDF, and 105 treated with two-level ACDF. At seven years, follow-up rates ranged from 73.5% to 84.4% (overall 80.2%). The overall success rates of two level TDR and ACDF patients were 60.8% and 34.2%, respectively (p<0.0001). The overall success rates of one level TDR and ACDF patients were 55.2% and 50%, respectively (p>0.05). Both the single and two level TDR and ACDF groups showed significant improvement from baseline NDI scores, VAS neck and arm pain scores, and SF-12 MCS/PCS scores (p<0.0001). In the single level cohort, there was an increased percentage of TDR patients who reported themselves as “very satisfied” (TDR 90.9% vs ACDF 77.8%; p= 0.028). There was a lower rate of adjacent level secondary surgery in the single level TDR patients (3.7%) versus the ACDF patients (13.6%; p = 0.007). In the two level TDR group, the NDI success rate was significantly greater in the TDR group (TDR: 79.0% vs. ACDF: 58.0%; p=0.001). There was significantly more improvement in NDI change score at 7 years in the TDR patients versus ACDF. The TDR group had a significantly higher rate of patients who were “very satisfied” with their treatment compared to the ACDF group (TDR: 85.9% vs. ACDF: 73.9%). The rate of subsequent surgery at the index level was significantly lower in the TDR group compared to the ACDF group (TDR: 4.4% vs. ACDF: 16.2%; p=0.001). The rate of adjacent level secondary surgery was significantly lower in the two level TDR (4.4%) patients compared to the ACDF (11.3%; p=0.03) patients. In both single and two level cohorts, the percentage of patients with worse NDI (2.5%-3.8% of two level surgeries and 1.2%-2.5% of single level surgeries) or worse neck pain (5%-6.8% of the two level surgeries and 1.3% - 3.8% of the single level surgeries) was strikingly low in both groups but trended lower in the TDR patients. Conclusions At seven years, the composite success analysis demonstrated clinical superiority of two level TDR over ACDF and non-inferiority of single level TDR versus ACDF. There were lower rates of secondary surgery and higher adjacent level disc survivorship in both groups. Both surgeries were remarkably effective in alleviating pain relative to baseline and the rate of patients with worse disability or neck pain was surprisingly low. Overall, greater than 95% of patients (from both groups) who underwent TDR and 88% of patients who underwent ACDF were “very satisfied” at seven years. The differences in clinical effectiveness of TDR versus ACDF becomes more apparent as treatment increases from one to two levels, indicating a significant benefit for TDR over ACDF for two-level procedures. Ethical Standards The Mobi-C Clinical Trial (ClinicalTrials.gov registration number: NCT00389597) was conducted at 24 sites in the US and was approved by the Institutional Review Board, Research Ethics Committee, or local equivalent of each participating site. Level of Evidence 1.

Two-level total disc replacement with mobi-c® over 3-years

Objective: To evaluate the safety and effectiveness of two-level total disc replacement (TDR) using a Mobi-C(r) Cervical Artificial Disc at the 36 month follow-up. Methods: a Prospective, randomized, controlled, multicenter clinical trial of an artificial cervical disc (Mobi-C(r) Cervical Artificial Disc) was conducted under the Investigational Device Exemptions (IDE) and the U.S. Food & Drug Administration (FDA) regulations. A total of 339 patients with degenerative disc disease were enrolled to receive either two-level treatment with TDR, or a two-level anterior cervical discectomy and fusion (ACDF) as control. The 234 TDR patients and 105 ACDF patients were followed up at regular time points for three years after surgery. Results: At 36 months, both groups demonstrated an improvement in clinical outcome measures and a comparable safety profile. NDI scores, SF-12 PCS scores, patient satisfaction, and overall success indicated greater statistically significant improvement from baseline for the TDR group, in comparison to the ACDF group. The TDR patients experienced lower subsequent surgery rates and a lower rate of adjacent segment degeneration. On average, the TDR patients maintained segmental range of motion through 36 months with no device failure. Conclusion: Results at three-years support TDR as a safe, effective and statistically superior alternative to ACDF for the treatment of degenerative disc disease at two contiguous cervical levels.

The ROI-C zero-profile anchored spacer for anterior cervical discectomy and fusion: biomechanical profile and clinical outcomes

Introduction Anterior cervical discectomy and fusion (ACDF) has been the gold standard for treating cervical degenerative disc disease (cDDD). The use of anterior plates in ACDF poses an increased risk of complications such as screw or plate dislodgement, soft tissue injury, esophagus perforation, and dysphagia. The ROI-C™ implant system consists of a zero-profile interbody fusion cage with self-locking plates designed for stand-alone fusion without external plates or screws. Objective The purpose of this report is to describe the ROI-C™ implant system with VerteBRIDGE™ anchor plates, including indications for use, surgical technique, preclinical testing, and clinical study results. The objectives of the clinical study were to assess fusion status, incidence of dysphagia and other device-related complications, and patient reported outcomes. Methods This was a retrospective, multicenter cohort study of 110 patients who underwent ACDF with ROI-C at seven study centers. Patient charts and radiographs were reviewed for any complications or device malfunction. The final follow-up was conducted prospectively and included collection of neck disability index, and visual analog scale (VAS) neck and arm pain scores. Results The mean operation time was 73 minutes, and mean blood loss was 25 mL (range 0–75 mL). Mean follow-up was 20.7 months (range 9.5–42.2). Dysphagia was reported in two patients (1.8%), and 99.1% of patients achieved fusion. One patient had radiographically confirmed pseudarthrosis at 12 months that was asymptomatic and did not require surgery. One patient had subsequent surgery owing to adjacent level degeneration. The mean neck disability index, VAS neck pain, and VAS right and left arm pain scores at final follow-up were 19, 26.5, 12.5, and 15.3, respectively. Conclusion The ROI-C interbody cage with VerteBRIDGE anchor plates achieved a high rate of fusion, with a low incidence of dysphagia. These patients had similar or better outcomes compared to ACDF with anterior plating reported in peer-reviewed literature.