Impact of Cervical Disc Arthroplasty vs Anterior Cervical Discectomy and Fusion on Driving Disability: Post Hoc Analysis of a Randomized Controlled Trial With 10-Year Follow-Up.

BACKGROUND: Driving an automobile requires the ability to turn the neck laterally. Anecdotally, patients with multilevel fusions often complain about restricted turning motion. The purpose of this study was to compare the effectiveness of cervical disc arthroplasty (CDA) with anterior cervical discectomy and fusion (ACDF) on driving disability improvement at 10-year follow-up after a 2-level procedure. METHODS: In the original randomized controlled trial, patients with cervical radiculopathy or myelopathy at 2 levels underwent CDA or ACDF. The driving disability question from the Neck Disability Index was rated from 0 to 5 years preoperatively and up to 10 years postoperatively. Severity of driving disability was categorized into "none" (score 0), "mild" (1 or 2), and "severe" (3, 4, or 5). Score and severity were compared between groups. RESULTS: Out of 397 patients, 148 CDA and 118 ACDF patients had 10-year follow-up. Driving disability scores were not different between the groups preoperatively (CDA: 2.65; ACDF: 2.71, P = 0.699). Postoperatively, the scores in the CDA group were significantly lower than those in the ACDF group at 5 (0.60 vs 1.08, P ≤ 0.001) and 10 years (0.66 vs 1.07, P = 0.001). Mean score improvement in the CDA group was significantly greater than the ACDF group at 10-year follow-up (-1.94 vs -1.63, P = 0.003). The majority of patients reported severe driving disability (CDA: 56.9%, ACDF: 58.0%, P = 0.968) before surgery. After surgery, a greater proportion of patients in the CDA group had neck pain-free driving compared with the ACDF group at 5 (63.3% vs 41.8%, P < 0.001) and 10 years (61.8% vs 41.2%, P = 0.003). CONCLUSION: In patients with cervical radiculopathy/myelopathy and 2-level disease, CDA provided greater improvements in driving disability as compared with ACDF at 10-year follow-up. This is the first report of its kind. This finding may be attributable to preservation of motion associated with CDA. CLINICAL RELEVENCE: This study provides valuable information regarding the improvement of driving disability after both CDA and ACDF. It demonstrates that both procedures result in significant improvements, with CDA resulting in even better improvements than ACDF, up to 10 year follow-up.

Lateral lumbar interbody fusion using a cellular allogeneic bone matrix in the treatment of symptomatic degenerative lumbar disc disease and lumbar spinal instability.

BACKGROUND: Cellular allogeneic bone grafts are used as a biologic adjuvant in lumbar spinal fusions. The clinical use of a minimally invasive extreme lateral approach to the lumbar spine has been widely adopted; however, there are few clinical studies that have documented the clinical and radiographic outcomes associated with the use of cellular allografts as an adjunct to fusion in this advanced surgical approach. METHODS: A consecutive series of 67 patients (34 males and 33 females) with a mean age of 66.8 years (26-85 years) who underwent single- or multilevel lateral lumbar interbody fusion (LLIF) with supplemental posterior segmental spinal fixation using a cellular allogeneic bone matrix as the only bone graft material was retrospectively reviewed by a single surgeon. Patients' preoperative and 3- and 12-month postoperative data were studied. All patients were followed for a minimum of 12 months. Standardized clinical outcome measures-36-Item Short Form Surgery (SF-36), Oswestry Disability Index (ODI), and visual analog scale (VAS) back and leg pain scores-were used to evaluate the clinical outcomes. An average of 2.25 levels was treated per patient (151 total levels). Fusion status was assessed by dynamic radiographs and computed tomography (CT) scans. The statistical method used to identify the significance of the observed changes in clinical outcomes was the paired 2-sided t-tests. Significance was ascribed to P values <0.05. RESULTS: Fusion was achieved at 142 levels (142/151; 94%). Eight levels (8/151; 5.3%) showed partial fusions and one patient (single level) had no fusion. In the group of patients with fusions, the mean back and leg pain scores showed improvement from preoperative scores at both 3 and 12 months (P<0.001). Functional outcomes showed similar clinical success in both in SF-36 and ODI scores. CONCLUSIONS: The use of a cellular allogeneic bone matrix provided osteoconductive and osteoinductive components for successful spine fusions and was associated with statistically significant improvement in SF-36, VAS, and ODI scores.

The Effect of ACDF or Arthroplasty on Cervicogenic Headaches: A Post Hoc Analysis of a Prospective, Multicenter Study With 10-Year Follow-up.

STUDY DESIGN: This was a post hoc analysis of a prospective FDA-IDE study. OBJECTIVE: The purpose of this study is to determine the effectiveness of a 2-level anterior cervical discectomy and fusion (ACDF) or cervical disk arthroplasty (CDA) at relieving headaches associated with cervical radiculopathy or myelopathy at 10 years postoperative. BACKGROUND: To our knowledge, there is no large, prospective study that has examined the efficacy of cervical spine surgery for relieving headaches associated with radiculopathy or myelopathy at 10 years postoperative. MATERIALS AND METHODS: This was a post hoc analysis of a prospective FDA-IDE study for the Prestige LP versus ACDF for radiculopathy or myelopathy due to 2 levels. Preoperatively and out to 10 years, their Neck Disability Index documented if they had headaches (0: no headaches; 1: infrequent slight; 2: infrequent moderate; 3: frequent moderate; 4: frequent severe; 5: nearly constant). RESULTS: Three hundred ninety-seven patients were randomized to CDA (209) or ACDF (188). Preoperatively 86% had headaches and 55.9% (52.2% of CDA, 60.1% of ACDFs) had frequent moderate, severe, or nearly constant headache (grades 3-5). By 6 weeks postoperative, 64.4% had headaches and only 12.5% had grades 3-5 headaches (9.3% of CDA and 16% of ACDFs). The benefit lasted to the 10-year follow-up such that 60.3% had any headaches and 16.8% had grades 3-5 headaches (10.9% CDA; 24.3% ACDF). CONCLUSIONS: These results suggest that 86% of patients with radiculopathy or myelopathy complain of headaches preoperatively, with 55.9% having frequent or constant, moderate to severe headaches (grades 3-5). By 6 weeks postoperative, only 12.5% had grades 3-5 headaches. At 10-year follow-up, 16.8% had grades 3-5 headaches. Both arthroplasty and ACDF are often effective at alleviating headaches associated with radiculopathy or myelopathy.

Occurrence and clinical implications of heterotopic ossification after cervical disc arthroplasty with the Prestige LP Cervical Disc at 2 contiguous levels.

OBJECTIVE: The authors sought to assess the impact of heterotopic ossification (HO) on clinical outcomes and angular range of motion (ROM) after cervical disc arthroplasty (CDA) performed with the Prestige LP Cervical Disc (Prestige LP disc) at 2 levels. METHODS: HO was assessed and graded from 0 to IV for increasing severity on lateral neutral radiographs at each visit in 209 patients who underwent implantation of Prestige LP discs at 2 cervical levels in a clinical trial with extended 10-year follow-up. ROM was compared by using HO grade, and clinical outcomes were compared between HO subgroups (grade 0-II vs III/IV) based on HO severity at 2 and 10 years after surgery. RESULTS: The grade III/IV HO incidence at either or both index levels was 24.2% (48/198) at 2 years and 39.0% (57/146) at 10 years. No statistical difference was found in overall success; neurological success; or Neck Disability Index (NDI), neck pain, arm pain, or SF-36 Physical Component Summary (PCS) scores between the HO subgroups (grade 0-II vs III/IV) at either 2 or 10 years. The cumulative rate of possible implant-related adverse events (AEs) was higher in patients having grade III/IV HO at 2 years (56.3%) and 10 years (47.8%) compared with those having grade 0-II HO at 2 years (24.4%) and 10 years (17.9%), specifically in 2 subcategories: spinal events and HOs reported by the investigators. No statistical difference was found between the HO subgroups in possible implant-related serious AEs or secondary surgeries at the index or adjacent levels. The average angular ROMs at index levels were lower in subjects with higher-grade HO at 2 and 10 years. The average ROMs at the superior level were 8.8°, 6.6°, 3.2°, and 0.3°, respectively, for the HO grade 0/I, II, III, and IV groups at 10 years, and 7.9°, 6.2°, 3.7°, and 0.6°, respectively, at the inferior level. CONCLUSIONS: Radiographically severe (grade III or IV) HO after CDA with the Prestige LP disc at 2 levels did not significantly affect efficacy or safety outcomes (severe AEs or secondary surgeries). However, severe HO, particularly grade IV HO, significantly limited ROM, as expected.

Adiponectin stimulates glucose uptake in mouse blastocysts and embryonic carcinoma cells.

Preimplantation embryos are sensitive to maternal hormones affecting embryonic signal transduction and metabolic functions. We examined whether adiponectin, the most abundantly secreted adipokine, can influence glucose transport in mouse embryonic cells. In mouse blastocysts full-length adiponectin stimulated glucose uptake, while no effect of globular adiponectin was found. Full-length adiponectin stimulated translocation of GLUT8 glucose transporter to the cell membrane; we did not detect significant changes in the intracellular localization of GLUT4 glucose transporter in adiponectin-treated blastocysts. To study adiponectin signaling in detail, we used embryoid bodies formed from mouse embryonic carcinoma cell (ECC) line P19. We confirmed the expression of adiponectin receptors in these cells. Similar to mouse blastocysts, full-length adiponectin, but not globular adiponectin, stimulated glucose uptake in ECC P19 embryoid bodies. Moreover, full-length adiponectin stimulated AMPK and p38 MAPK phosphorylation. These results indicate that besides AMPK, p38 MAPK is a potential target of adiponectin in mouse embryonic cells. AMPK inhibitor did not influence the adiponectin-stimulated p38 MAPK phosphorylation, indicating independent action of these two signaling pathways. In mouse embryos adiponectin acts as a hormonal regulator of glucose uptake, which becomes especially important in phases with reduced levels of circulating insulin. Our results suggest that adiponectin maintains the glucose supply for early embryos under hypoinsulinaemic conditions, for example, in mothers suffering from type 1 diabetes mellitus.

Two-level cervical disc arthroplasty versus anterior cervical discectomy and fusion: 10-year outcomes of a prospective, randomized investigational device exemption clinical trial.

OBJECTIVE: The authors assessed the 10-year clinical safety and effectiveness of cervical disc arthroplasty (CDA) to treat degenerative cervical spine disease at 2 adjacent levels compared to anterior cervical discectomy and fusion (ACDF). METHODS: A prospective, randomized, controlled, multicenter FDA-approved clinical trial was conducted comparing the low-profile titanium ceramic composite-based Prestige LP Cervical Disc (n = 209) at two levels with ACDF (n = 188). Ten-year follow-up data from a postapproval study were available on 148 CDA and 118 ACDF patients and are reported here. Clinical and radiographic evaluations were completed preoperatively, intraoperatively, and at regular postoperative follow-up intervals for up to 10 years. The primary endpoint was overall success, a composite variable that included key safety and efficacy considerations. Ten-year follow-up rates were 86.0% for CDA and 84.9% for ACDF. RESULTS: From 2 to 10 years, CDA demonstrated statistical superiority over ACDF for overall success, with rates at 10 years of 80.4% versus 62.2%, respectively (posterior probability of superiority [PPS] = 99.9%). Neck Disability Index (NDI) success was also superior, with rates at 10 years of 88.4% versus 76.5% (PPS = 99.5%), as was neurological success (92.6% vs 86.1%; PPS = 95.6%). Improvements from preoperative results in NDI and neck pain scores were consistently statistically superior for CDA compared to ACDF. All other study effectiveness measures were at least noninferior for CDA compared to ACDF through the 10-year follow-up period, including disc height. Mean angular ranges of motion at treated levels were maintained in the CDA group for up to 10 years. The rates of grade IV heterotopic ossification (HO) at the superior and inferior levels were 8.2% and 10.3%, respectively. The rate of severe HO (grade III or IV) did not increase significantly from 7 years (42.4%) to 10 years (39.0%). The CDA group had fewer serious (grade 3-4) implant-related or implant/surgical procedure-related adverse events (3.8% vs 8.1%; posterior mean 95% Bayesian credible interval [BCI] of the log hazard ratio [LHR] -0.92 [-1.88, -0.01]). The CDA group also had statistically fewer secondary surgical procedures at the index levels (4.7%) than the ACDF group (17.6%) (LHR [95% BCI] -1.39 [-2.15, -0.61]) as well as at adjacent levels (9.0% vs 17.9%). CONCLUSIONS: The Prestige LP Cervical Disc, implanted at two adjacent levels, maintains improved clinical outcomes and segmental motion 10 years after surgery and is a safe and effective alternative to fusion.Clinical trial registration no.: NCT00637156 (clinicaltrials.gov).

Lumbar disc arthroplasty versus anterior lumbar interbody fusion: 5-year outcomes for patients in the Maverick disc investigational device exemption study.

OBJECTIVE: Despite evidence of its safety and effectiveness, the use of lumbar disc arthroplasty has been slow to expand due in part to concerns about late complications and the risks of revision surgery associated with early devices. More recently, FDA approval of newer devices and improving reimbursements have reversed this trend in the United States. Additional long-term data on lumbar disc arthroplasty are still needed. This study reports the 5-year results of the FDA investigational device exemption clinical trial of the Medtronic Spinal and Biologics' Maverick total disc replacement. METHODS: Patients with single-level degenerative disc disease from L4 to S1 were randomized 2:1 at 31 investigational sites. In the period from April 2003 to August 2004, 405 patients received the investigational device and 172 patients underwent the control procedure of anterior lumbar interbody fusion. Outcome measures included the Oswestry Disability Index (ODI), numeric rating scales (NRSs) for back and leg pain, the SF-36, disc height, interbody motion, heterotopic ossification (investigational device), adverse events (AEs), additional surgeries, and neurological status. Treatment was considered an overall success when all of the following criteria were met: 1) ODI score improvement ≥ 15 points over the preoperative score; 2) maintenance or improvement in neurological status compared with preoperatively; 3) disc height success, that is, no more than a 2-mm reduction in anterior or posterior height; 4) no serious AEs caused by the implant or by the implant and the surgical procedure; and 5) no additional surgery classified as a failure. RESULTS: Compared to that in the control group, improvement in the investigational group was statistically greater according to the ODI and SF-36 Physical Component Summary (PCS) at 1, 2, and 5 years; the NRS for back pain at 1 and 2 years; and the NRS for leg pain at 1 year. The rates of heterotopic ossification increased over time: 1.0% (4/382) at 1 year, 2.6% (9/345) at 2 years, and 5.9% (11/187) at 5 years. Investigational patients had fewer device-related AEs and serious device-related AEs than the control patients at both 2 and 5 years postoperatively. Noninferiority of the composite measure overall success was demonstrated at all follow-up intervals; superiority was demonstrated at 1 and 2 years. CONCLUSIONS: Lumbar disc arthroplasty is a safe and effective treatment for single-level lumbar degenerative disc disease, resulting in improved physical function and reduced pain up to 5 years after surgery.Clinical trial registration no.: NCT00635843 (clinicaltrials.gov).

Cervical disc arthroplasty: 10-year outcomes of the Prestige LP cervical disc at a single level.

OBJECTIVE: Food and Drug Administration-approved investigational device exemption (IDE) studies have provided level I evidence supporting cervical disc arthroplasty (CDA) as a safe and effective alternative to anterior cervical discectomy and fusion (ACDF). Long-term CDA outcomes continue to be evaluated. Here, the authors present outcomes at 10 years postoperatively for the single-level CDA arm of an IDE study (postapproval study). METHODS: The primary endpoint was overall success, a composite variable composed of five criteria: 1) Neck Disability Index score improvement ≥ 15 points; 2) maintenance or improvement in neurological status; 3) no decline in anterior or posterior functional spinal unit (FSU) height of more than 2 mm compared to 6 weeks postoperatively; 4) no serious adverse event (AE) caused by the implant or the implant and the surgical procedure; and 5) no additional surgery classified as a failure. Additional safety and effectiveness measures included numeric rating scales for neck pain and arm pain, SF-36 quality-of-life physical and mental components, patient satisfaction, range of motion, and AEs. RESULTS: From the reported assessments at 7 years postoperatively to the 10-year postoperative follow-up, the scores for all patient-reported outcomes, rate of overall success (without FSU), and proportion of patients at least maintaining their neurological function remained stable for the CDA group. Nine patients had secondary surgery at the index level, increasing the secondary surgery cumulative rate from 6.6% to 10.3%. In that same time frame, four patients experienced a serious implant or implant/surgical procedure-related AE, for a 10-year cumulative rate of 7.8%. Seven patients had any second surgery at adjacent levels, for a 10-year cumulative rate of 13.8%. Average angular motion at both the index and adjacent levels was well maintained without creating hypermobility. Class IV heterotopic ossification increased from 1.2% at 2 years to 4.6% at 7 years and 9.0% at 10 years. Patient satisfaction was > 90% at 10 years. CONCLUSIONS: CDA remained safe and effective out to 10 years postoperatively, with results comparable to 7-year outcomes and with high patient satisfaction.Clinical trial registration no.: NCT00667459 (clinicaltrials.gov).

One-Level Versus 2-Level Treatment With Cervical Disc Arthroplasty or Fusion: Outcomes Up to 7 Years.

BACKGROUND: Anterior cervical discectomy and fusion (ACDF) and cervical disc arthroplasty (CDA) have been used to treat degenerative disc disease at single as well as multiple cervical levels. This study compares the safety and efficacy of 1-level versus 2-level CDA and ACDF. METHODS: In total, 545 and 397 patients with degenerative disc disease were studied in 1-level and 2-level Food and Drug Administration (FDA)-approved clinical trials, respectively: CDA (n = 280 and 209), ACDF (n = 265 and 188). Data from these studies were used to compare 1- versus 2-level procedures: the propensity score method was used to adjust for potential confounding effects, and adjusted mean outcome safety and efficacy scores at 2 and 7 years postsurgery were compared between 1-level and 2-level procedures within treatment type. RESULTS: One-level and 2-level procedures had similar rates of improvement in overall success and patient-reported outcomes scores for both CDA and ACDF. There were no statistical differences in rates of implant-related adverse events (AEs) or serious implant-related AEs between 1-level and 2-level CDA. The 7-year rate of implant-related AEs was higher for 2-level than 1-level ACDF (27.7% vs 18.9%, P ≤ .036), though the rates of serious implant-related AEs between ACDF groups did not differ significantly. Secondary surgery rates were not statistically different between 1-level and 2-level procedures (CDA or ACDF) at the index or adjacent levels at 2 or 7 years. Grade IV heterotopic ossification at 7 years was reported in 4.6% of 1-level CDA patients and 8.6%/7.3% at the superior/inferior levels, respectively, of 2-level CDA patients. CONCLUSIONS: One- and 2-level CDA appear equally safe and effective in the treatment of cervical degenerative disc disease. Two-level ACDF appears to be as effective as 1-level ACDF but with a higher rate of some AEs at long-term follow-up. LEVEL OF EVIDENCE: 2. CLINICAL TRIALS: clinicaltrials.gov: NCT00667459, NCT00642876, and NCT00637156.

Treatment of Cervical Myelopathy: Long-term Outcomes of Arthroplasty for Myelopathy Versus Radiculopathy, And Arthroplasty Versus Arthrodesis for Myelopathy.

STUDY DESIGN: Analysis of 2- and 7-year outcomes from a clinical trial comparing 2-level cervical disk arthroplasty (CDA) to anterior cervical discectomy and fusion (ACDF) in 287 patients with radiculopathy alone, and 110 patients with myelopathy alone or myelopathy with radiculopathy. OBJECTIVE: To compare the long-term safety and effectiveness of CDA for myelopathy versus radiculopathy. SUMMARY OF BACKGROUND DATA: CDA for myelopathy is safe and effective in short term. MATERIALS AND METHODS: We analyzed Neck Disability Index (NDI), neck/arm pain, SF-36, neurological status, adverse events (AEs), and secondary surgeries at index and adjacent levels. RESULTS: All groups improved significantly for NDI, neck/arm pain, and physical component summary (PCS) scores from preoperative to postoperative. CDA Myelopathy versus CDA Radiculopathy: 2- and 7-year improvements were not significantly different. The 7-year score improvements for CDA Myelopathy and CDA Radiculopathy were: NDI (37.8 vs. 35.8, P=0.352), neck pain (12.0 vs. 12.1, P=0.477), arm pain (11.6 vs. 9.6, P=0.480), and PCS (14.1 vs. 13.7, P=0.863). The 2 groups had similar proportions of patients who maintained or improved their neurological status (87.2% vs. 93.5%, P=0.218), similar rates of serious AEs (54.5% vs. 57.5%, P=0.291) and similar rates of secondary surgeries at index (3.7% vs. 4.4%, P=0.839) and adjacent levels (3.7% vs. 7.6%, P=0.367). CDA Myelopathy versus ACDF myelopathy: 2 and 7-year improvements were not significantly different. The 7-year CDA and ACDF score improvements were: NDI (37.8 vs. 31.1, P=0.147), neck pain (12.0 vs. 10.4, P=0.337), arm pain (11.6 vs. 11.4, P=0.791), and PCS (14.1 vs. 11.2, P=0.363). The 2 groups had statistically similar proportions who maintained or improved their neurological status (87.2% vs. 96.2%, P=0.409), statistically similar overall rates of secondary surgeries at the index levels (3.7% vs. 9.4%, P=0.374), and statistically similar rates of secondary surgeries at adjacent levels (3.7% vs. 15.4%, P=0.088). CDA group demonstrated lower rates of serious AEs than ACDF (54.5% vs. 65.9%, P=0.019). CONCLUSIONS: CDA for myelopathy is a safe and effective long-term treatment.

Effect of porous orthopaedic implant material and structure on load sharing with simulated bone ingrowth: A finite element analysis comparing titanium and PEEK.

Osseointegration of load-bearing orthopaedic implants, including interbody fusion devices, is critical to long-term biomechanical functionality. Mechanical loads are a key regulator of bone tissue remodeling and maintenance, and stress-shielding due to metal orthopaedic implants being much stiffer than bone has been implicated in clinical observations of long-term bone loss in tissue adjacent to implants. Porous features that accommodate bone ingrowth have improved implant fixation in the short term, but long-term retrieval studies have sometimes demonstrated limited, superficial ingrowth into the pore layer of metal implants and aseptic loosening remains a problem for a subset of patients. Polyether-ether-ketone (PEEK) is a widely used orthopaedic material with an elastic modulus more similar to bone than metals, and a manufacturing process to form porous PEEK was recently developed to allow bone ingrowth while preserving strength for load-bearing applications. To investigate the biomechanical implications of porous PEEK compared to porous metals, we analyzed finite element (FE) models of the pore structure-bone interface using two clinically available implants with high (> 60%) porosity, one being constructed from PEEK and the other from electron beam 3D-printed titanium (Ti). The objective of this study was to investigate how porous PEEK and porous Ti mechanical properties affect load sharing with bone within the porous architectures over time. Porous PEEK substantially increased the load share transferred to ingrown bone compared to porous Ti under compression (i.e. at 4 weeks: PEEK = 66%; Ti = 13%), tension (PEEK = 71%; Ti = 12%), and shear (PEEK = 68%; Ti = 9%) at all time points of simulated bone ingrowth. Applying PEEK mechanical properties to the Ti implant geometry and vice versa demonstrated that the observed increases in load sharing with PEEK were primarily due to differences in intrinsic elastic modulus and not pore architecture (i.e. 4 weeks, compression: PEEK material/Ti geometry = 53%; Ti material/PEEK geometry = 12%). Additionally, local tissue energy effective strains on bone tissue adjacent to the implant under spinal load magnitudes were over two-fold higher with porous PEEK than porous Ti (i.e. 4 weeks, compression: PEEK = 784 ± 351 microstrain; Ti = 180 ± 300 microstrain; and 12 weeks, compression: PEEK = 298 ± 88 microstrain; Ti = 121 ± 49 microstrain). The higher local strains on bone tissue in the PEEK pore structure were below previously established thresholds for bone damage but in the range necessary for physiological bone maintenance and adaptation. Placing these strain magnitudes in the context of literature on bone adaptation to mechanical loads, this study suggests that porous PEEK structures may provide a more favorable mechanical environment for bone formation and maintenance under spinal load magnitudes than currently available porous 3D-printed Ti, regardless of the level of bone ingrowth.

Getting PEEK to Stick to Bone: The Development of Porous PEEK for Interbody Fusion Devices.

Interbody fusion cages are routinely implanted during spinal fusion procedures to facilitate arthrodesis of a degenerated or unstable vertebral segment. Current cages are most commonly made from polyether-ether-ketone (PEEK) due to its favorable mechanical properties and imaging characteristics. However, the smooth surface of current PEEK cages may limit implant osseointegration and may inhibit successful fusion. We present the development and clinical application of the first commercially available porous PEEK fusion cage (COHERE®, Vertera, Inc., Atlanta, GA) that aims to enhance PEEK osseointegration and spinal fusion outcomes. The porous PEEK structure is extruded directly from the underlying solid and mimics the structural and mechanical properties of trabecular bone to support bone ingrowth and implant fixation. Biomechanical testing of the COHERE® device has demonstrated greater expulsion resistance versus smooth PEEK cages with ridges and greater adhesion strength of porous PEEK versus plasma-sprayed titanium coated PEEK surfaces. In vitro experiments have shown favorable cell attachment to porous PEEK and greater proliferation and mineralization of cell cultures grown on porous PEEK versus smooth PEEK and smooth titanium surfaces, suggesting that the porous structure enhances bone formation at the cellular level. At the implant level, preclinical animal studies have found comparable bone ingrowth into porous PEEK as those previously reported for porous titanium, leading to twice the fixation strength of smooth PEEK implants. Finally, two clinical case studies are presented demonstrating the effectiveness of the COHERE® device in cervical spinal fusion.

Long-term clinical and radiographic outcomes of the Prestige LP artificial cervical disc replacement at 2 levels: results from a prospective randomized controlled clinical trial.

OBJECTIVE The aim of this study was to assess long-term clinical safety and effectiveness in patients undergoing anterior cervical surgery using the Prestige LP artificial disc replacement (ADR) prosthesis to treat degenerative cervical spine disease at 2 adjacent levels compared with anterior cervical discectomy and fusion (ACDF). METHODS A prospective, randomized, controlled, multicenter FDA-approved clinical trial was conducted at 30 US centers, comparing the low-profile titanium ceramic composite-based Prestige LP ADR (n = 209) at 2 levels with ACDF (n = 188). Clinical and radiographic evaluations were completed preoperatively, intraoperatively, and at regular postoperative intervals to 84 months. The primary end point was overall success, a composite variable that included key safety and efficacy considerations. RESULTS At 84 months, the Prestige LP ADR demonstrated statistical superiority over fusion for overall success (observed rate 78.6% vs 62.7%; posterior probability of superiority [PPS] = 99.8%), Neck Disability Index success (87.0% vs 75.6%; PPS = 99.3%), and neurological success (91.6% vs 82.1%; PPS = 99.0%). All other study effectiveness measures were at least noninferior for ADR compared with ACDF. There was no statistically significant difference in the overall rate of implant-related or implant/surgical procedure-related adverse events up to 84 months (26.6% and 27.7%, respectively). However, the Prestige LP group had fewer serious (Grade 3 or 4) implant- or implant/surgical procedure-related adverse events (3.2% vs 7.2%, log hazard ratio [LHR] and 95% Bayesian credible interval [95% BCI] -1.19 [-2.29 to -0.15]). Patients in the Prestige LP group also underwent statistically significantly fewer second surgical procedures at the index levels (4.2%) than the fusion group (14.7%) (LHR -1.29 [95% BCI -2.12 to -0.46]). Angular range of motion at superior- and inferior-treated levels on average was maintained in the Prestige LP ADR group to 84 months. CONCLUSIONS The low-profile artificial cervical disc in this study, Prestige LP, implanted at 2 adjacent levels, maintains improved clinical outcomes and segmental motion 84 months after surgery and is a safe and effective alternative to fusion. Clinical trial registration no.: NCT00637156 (clinicaltrials.gov).

Cervical disc arthroplasty with the Prestige LP disc versus anterior cervical discectomy and fusion, at 2 levels: results of a prospective, multicenter randomized controlled clinical trial at 24 months.

OBJECTIVE The authors compared the efficacy and safety of arthroplasty using the Prestige LP cervical disc with those of anterior cervical discectomy and fusion (ACDF) for the treatment of degenerative disc disease (DDD) at 2 adjacent levels. METHODS Patients from 30 investigational sites were randomized to 1 of 2 groups: investigational patients (209) underwent arthroplasty using a Prestige LP artificial disc, and control patients (188) underwent ACDF with a cortical ring allograft and anterior cervical plate. Patients were evaluated preoperatively, intraoperatively, and at 1.5, 3, 6, 12, and 24 months postoperatively. Efficacy and safety outcomes were measured according to the Neck Disability Index (NDI), Numeric Rating Scales for neck and arm pain, 36-Item Short-Form Health Survey (SF-36), gait abnormality, disc height, range of motion (investigational) or fusion (control), adverse events (AEs), additional surgeries, and neurological status. Treatment was considered an overall success when all 4 of the following criteria were met: 1) NDI score improvement of ≥ 15 points over the preoperative score, 2) maintenance or improvement in neurological status compared with preoperatively, 3) no serious AE caused by the implant or by the implant and surgical procedure, and 4) no additional surgery (supplemental fixation, revision, or nonelective implant removal). Independent statisticians performed Bayesian statistical analyses. RESULTS The 24-month rates of overall success were 81.4% for the investigational group and 69.4% for the control group. The posterior mean for overall success in the investigational group exceeded that in the control group by 0.112 (95% highest posterior density interval = 0.023 to 0.201) with a posterior probability of 1 for noninferiority and 0.993 for superiority, demonstrating the superiority of the investigational group for overall success. Noninferiority of the investigational group was demonstrated for all individual components of overall success and individual effectiveness end points, except for the SF-36 Mental Component Summary. The investigational group was superior to the control group for NDI success. The proportion of patients experiencing any AE was 93.3% (195/209) in the investigational group and 92.0% (173/188) in the control group, which were not statistically different. The rate of patients who reported any serious AE (Grade 3 or 4) was significantly higher in the control group (90 [47.9%] of 188) than in the investigational group (72 [34.4%] of 209) with a posterior probability of superiority of 0.996. Radiographic success was achieved in 51.0% (100/196) of the investigational patients (maintenance of motion without evidence of bridging bone) and 82.1% (119/145) of the control patients (fusion). At 24 months, heterotopic ossification was identified in 27.8% (55/198) of the superior levels and 36.4% (72/198) of the inferior levels of investigational patients. CONCLUSIONS Arthroplasty with the Prestige LP cervical disc is as effective and safe as ACDF for the treatment of cervical DDD at 2 contiguous levels and is an alternative treatment for intractable radiculopathy or myelopathy at 2 adjacent levels. Clinical trial registration no.: NCT00637156 ( clinicaltrials.gov ).

Cervical Disc Arthroplasty with Prestige LP Disc Versus Anterior Cervical Discectomy and Fusion: Seven-Year Outcomes.

BACKGROUND: Cervical disc arthroplasty (CDA) has emerged as an alternative to anterior cervical discectomy and fusion (ACDF) for the treatment of cervical pathologies. Studies are on-going to assess the long term outcomes of CDA. This study assessed the safety and efficacy of the Prestige(®) LP Disc at 84-months follow up. METHODS: Prospective data from 280 CDA patients with single-level cervical disc disease with radiculopathy or myelopathy were compared with 265 historical control ACDF patients. Clinical and radiographic follow up was completed pre-operatively, intraoperatively, and at intervals up to 84 months. RESULTS: Follow-up rate was 75.9% for CDA and 70.0% for ACDF patients. Statistical improvements (p < 0.001) in Neck Disability Index (NDI), neck/arm pain, and SF-36 were achieved by 1.5 months in both groups and maintained through 84 months. At 84 months, 86.1% of CDA versus 80.1% of ACDF patients achieved NDI success, (≥15-point improvement over baseline). Mean NDI score improvements exceeded 30 points in both groups. SF-36 PCS/MCS mean improvements were 13.1±11.9/8.2±12.3 points for CDA and 10.7±11.8/8.3±13.6 points for ACDF. Neurological success was 92.8% for CDA and 79.7% for ACDF patients. The rate of Overall Success was 74.9% for CDA and 63.2% for ACDF. At 84 months, 17.5% of CDA and 16.6% of ACDF patients had a possibly implant- or implant-surgical procedure-related adverse event. Eighteen (6.4%) CDA and 29 (10.9%) ACDF patients had a second surgery at the index level. In CDA patients, mean angular motion at the target level was maintained at 24 (7.5°) and 84 (6.9°) months. Bridging bone was reported in 5.9%/9.5%/10.2%/13.0% of CDA patients at 24/36/60/84 months. Change in mean preoperative angulation of the adjacent segment above/below the index level was1.06±4.39/1.25±4.06 for CDA and (-0.23)±5.37/1.25±5.07 for ACDF patients. At 84 months, 90.9% of CDA and 85.6% of ACDF patients were satisfied with the results of their treatment. CONCLUSIONS: Prestige LP maintained significantly improved clinical outcomes and segmental motion; statistical superiority of CDA was concluded for overall success. This investigational device exemption study was sponsored by Medtronic Spinal and Biologics, Memphis, TN. Study approved by the Hughston Sports Medicine Center Institutional Review Board on January 7, 2005. Clinical trial registered at clinicaltrials.gov: NCT00667459. All participants signed an informed consent.

Heterotopic ossification following single-level anterior cervical discectomy and fusion: results from the prospective, multicenter, historically controlled trial comparing allograft to an optimized dose of rhBMP-2.

OBJECTIVE Heterotopic ossification (HO) has been reported following total hip, knee, cervical, and lumbar arthroplasty, as well as following posterolateral lumbar fusion using recombinant human bone morphogenetic protein-2 (rhBMP-2). Data regarding HO following anterior cervical discectomy and fusion (ACDF) with rhBMP-2 are sparse. A subanalysis was done of the prospective, multicenter, investigational device exemption trial that compared rhBMP-2 on an absorbable collagen sponge (ACS) versus allograft in ACDF for patients with symptomatic single-level cervical degenerative disc disease. METHODS To assess differences in types of HO observed in the treatment groups and effects of HO on functional and efficacy outcomes, clinical outcomes from previous disc replacement studies were compared between patients who received rhBMP-2/ACS versus allograft. Rate, location, grade, and size of ossifications were assessed preoperatively and at 24 months, and correlated with clinical outcomes. RESULTS Heterotopic ossification was primarily anterior in both groups. Preoperatively in both groups, and including osteophytes in the target regions, HO rates were high at 40.9% and 36.9% for the rhBMP-2/ACS and allograft groups, respectively (p = 0.350). At 24 months, the rate of HO in the rhBMP-2/ACS group was higher than in the allograft group (78.6% vs 59.2%, respectively; p < 0.001). At 24 months, the rate of superior-anterior adjacent-level Park Grade 3 HO was 4.2% in both groups, whereas the rate of Park Grade 2 HO was 19.0% in the rhBMP-2/ACS group compared with 9.8% in the allograft group. At 24 months, the rate of inferior-anterior adjacent-level Park Grade 2/3 HO was 11.9% in the rhBMP-2/ACS group compared with 5.9% in the allograft group. At 24 months, HO rates at the target implant level were similar (p = 0.963). At 24 months, the mean length and anteroposterior diameter of HO were significantly greater in the rhBMP-2/ACS group compared with the allograft group (p = 0.033 and 0.012, respectively). Regarding clinical correlation, at 24 months in both groups, Park Grade 3 HO at superior adjacent-level disc spaces significantly reduced range of motion, more so in the rhBMP-2/ACS group. At 24 months, HO negatively affected Neck Disability Index scores (excluding neck/arm pain scores), neurological status, and overall success in patients in the rhBMP-2/ACS group, but not in patients in the allograft group. CONCLUSIONS Implantation of rhBMP-2/ACS at 1.5 mg/ml with polyetheretherketone spacer and titanium plate is effective in inducing fusion and improving pain and function in patients undergoing ACDF for symptomatic single-level cervical degenerative disc disease. At 24 months, the rate and dimensions (length and anteroposterior diameter) of HO were higher in the rhBMP-2/ACS group. At 24 months, range of motion was reduced, with Park Grade 3 HO in both treatment groups. The impact of Park Grades 2 and 3 HO on Neck Disability Index success, neurological status, and overall success was not consistent among the treatment groups. The study data may offer a deeper understanding of HO after ACDF and may pave the way for improved device designs. Clinical trial registration no.: IDE# G060021; data compared with pooled data from control arms of IDE# G010188/NCT00642876 and IDE# G000123/NCT00437190 ( www.clinicaltrials.gov ).

Cervical disc arthroplasty with PRESTIGE LP disc versus anterior cervical discectomy and fusion: a prospective, multicenter investigational device exemption study.

OBJECT This study compared the safety and efficacy of treatment with the PRESTIGE LP cervical disc versus a historical control anterior cervical discectomy and fusion (ACDF). METHODS Prospectively collected PRESTIGE LP data from 20 investigational sites were compared with data from 265 historical control ACDF patients in the initial PRESTIGE Cervical Disc IDE study. The 280 investigational patients with single-level cervical disc disease with radiculopathy and/or myelopathy underwent arthroplasty with a low-profile artificial disc. Key safety/efficacy outcomes included Neck Disability Index (NDI), Neck and Arm Pain Numerical Rating Scale scores, 36-Item Short Form Health Survey (SF-36) score, work status, disc height, range of motion, adverse events (AEs), additional surgeries, and neurological status. Clinical and radiographic evaluations were completed preoperatively, intraoperatively, and at 1.5, 3, 6, 12, and 24 months postoperatively. Predefined Bayesian statistical methods with noninformative priors were used, along with the propensity score technique for controlling confounding factors. Analysis by independent statisticians confirmed initial statistical findings. RESULTS The investigational and control groups were mostly similar demographically. There was no significant difference in blood loss (51.0 ml [investigational] vs 57.1 ml [control]) or hospital stay (0.98 days [investigational] vs 0.95 days [control]). The investigational group had a significantly longer operative time (1.49 hours vs 1.38 hours); 95% Bayesian credible interval of the difference was 0.01-0.21 hours. Significant improvements versus preoperative in NDI, neck/arm pain, SF-36, and neurological status were achieved by 1.5 months in both groups and were sustained at 24 months. Patient follow-up at 24 months was 97.1% for the investigational group and 84.0% for the control group. The mean NDI score improvements versus preoperative exceeded 30 points in both groups at 12 and 24 months. SF-36 Mental Component Summary superiority was established (Bayesian probability 0.993). The mean SF-36 PCS scores improved by 14.3 points in the investigational group and by 11.9 points in the control group from baseline to 24 months postoperatively. Neurological success at 24 months was 93.5% in the investigational group and 83.5% in the control group (probability of superiority ~ 1.00). At 24 months, 12.1% of investigational and 15.5% of control patients had an AE classified as device or device/surgical procedure related; 14 (5.0%) investigational and 21 (7.9%) control patients had a second surgery at the index level. The median return-to-work time for the investigational group was 40 days compared with 60 days for the control group (p = 0.020 after adjusting for preoperative work status and propensity score). Following implantation of the PRESTIGE LP device, the mean angular motion was maintained at 12 months (7.9°) and 24 months (7.5°). At 24 months, 90.0% of investigational and 87.7% of control patients were satisfied with the results of surgery. PRESTIGE LP superiority on overall success (without disc height success), a composite safety/efficacy end point, was strongly supported with 0.994 Bayesian probability. CONCLUSIONS This device maintains mean postoperative segmental motion while providing the potential for biomechanical stability. Investigational patients reported significantly improved clinical outcomes compared with baseline, at least noninferior to ACDF, up to 24 months after surgery.

Clinical and radiographic analysis of an artificial cervical disc: 7-year follow-up from the Prestige prospective randomized controlled clinical trial: Clinical article.

OBJECT: The authors assess the long-term safety and efficacy of cervical disc replacement with the Prestige Cervical Disc in a prospective, randomized, multicenter trial at 7 years of follow-up. METHODS: At 31 investigational sites, 541 patients with single-level cervical disc disease with radiculopathy were randomized to 1 of 2 treatment groups: 276 investigational group patients underwent anterior cervical discectomy and arthroplasty with the Prestige disc, and 265 control group patients underwent anterior cervical discectomy and fusion. Clinical outcomes included Neck Disability Index, the 36-Item Short-Form Health Survey, and neck and arm pain scores. Radiographs were assessed for angle of motion and fusion. Clinical and radiographic outcomes were evaluated preoperatively, intraoperatively, and at 1.5, 3, 6, 12, 24, 36, 60, and 84 months. RESULTS: Of the 541 patients treated, 395 patients (73%; 212 investigational and 183 control patients) completed 7 years of clinical follow-up. Significant improvements achieved by 1.5 months in both groups were sustained at 7 years. In the investigational group, mean Neck Disability Index improvements from preoperative scores were 38.2 and 37.5 at 60 and 84 months, respectively. In the control group, the corresponding means were 33.8 and 31.9. The differences between the investigational and control groups at the 60-month and 84-month periods were significant (p = 0.014 and 0.002, respectively). The overall rates of maintenance or improvement in neurological status in the investigational group were significantly higher: 92.2% and 88.2% at 60 months and 84 months, respectively, compared with 85.7% and 79.7% in the control group (p = 0.017 and 0.011, respectively). At 84 months, the percentage of working patients in the investigational group was 73.9%, and in the control group, 73.1%. Postoperatively, the implant effectively maintained average angular motion of 6.67° at 60 months and 6.75° at 84 months. Cumulative rates for surgery at the index level were lower (p < 0.001) in the investigational group (11 [4.8%] of 276) when compared with the control group (29 [13.7%] of 265) (based on life-table method), and there were statistical differences between the investigational and control groups with specific regard to the rate of subsequent revision and supplemental fixation surgical procedures. Rates for additional surgical procedures that involved adjacent levels were lower in the investigational group than in the control group (11 [4.6%] of 276 vs. 24 [11.9%] of 265, respectively). CONCLUSIONS: Cervical disc arthroplasty has the potential for preserving motion at the operated level while providing biomechanical stability and global neck mobility and may result in a reduction in adjacent-segment degeneration. The Prestige Cervical Disc maintains improved clinical outcomes and segmental motion after implantation at 7-year follow-up. Clinical trial registration no. NCT00642876 ( ClinicalTrials.gov ).

Two-generation diet-induced obesity model producing mice with increased amount of body fat in early adulthood.

The aim of our study was to develop a model producing obese mice in early adulthood (4-6 weeks) based on their over-nutrition during fetal and early postnatal development. The fertilized dams of the parental generation were fed the standard diet supplemented with high-energy nutritional product Ensure Plus during gestation and lactation. Delivered weanlings were then fed with standard or supplemented diet and assessed for body fat deposits using EchoMRI at the time of early and late adulthood. Maternal over-feeding during the period before weaning had the most significant effect on obesity development in the filial generation. In weanlings, significantly higher body fat deposits and average body weight were recorded. Later, further significant increase in percentage of body fat in both male and female mice was observed. Withdrawal of the Ensure Plus supplement caused a decrease in the percentage of body fat in part of the filial generation. In offspring fed the standard diet, higher fat deposits persisted till the time of late adulthood. We conclude that this diet-induced obesity model might be used in exploration of the effects of elevated body fat on physiological functions of various organ systems during juvenile and early adulthood periods of life of a human being.

Expression of adrenergic receptors in bovine and rabbit oocytes and preimplantation embryos.

Catecholamines play an important role in embryogenesis, and data obtained in the rodent model indicate that they can act even during the preimplantation period of development. Using RT-PCR with specific oligonucleotide primers distinguishing among all members of the adrenergic receptor family, we examined expression of adrenergic receptors in bovine and rabbit oocytes, morulas and blastocysts. We found several profiles of adrenoceptor mRNA expression. Transcripts for some receptor subtypes (bovine alpha 2 receptors, rabbit α2A, α2C, ß1 and ß2 receptors) were detected at all examined stages, which suggests receptor expression throughout (or at most stages) the preimplantation developmental period. Expression in oocytes but not at later stages was found in only one adrenoceptor subtype (rabbit α1B). In contrast, mRNA for several adrenoceptors was found in embryos but not in oocytes (bovine beta adrenoceptors and rabbit α1A). Nucleotide sequences of our PCR products amplified in rabbit oocytes, and preimplantation embryos represent the first published mRNA sequences (partial sequences coding at least one transmembrane region) of rabbit α2C, ß1 and ß2 adrenoceptors. Our results suggest that the expression of adrenergic receptors can be a general feature of mammalian oocytes and preimplantation embryos. On the other hand, comparison of three mammalian species (cattle, rabbit and mouse) revealed possible interspecies differences in the expression of particular adrenoceptor subtypes. Our results support the opinion that stress mediators can act directly in cells of preimplantation embryos.