Intervertebral disc human nucleus pulposus cells associated with back pain trigger neurite outgrowth in vitro and pain behaviors in rats.

Low back pain (LBP) is often associated with the degeneration of human intervertebral discs (IVDs). However, the pain-inducing mechanism in degenerating discs remains to be elucidated. Here, we identified a subtype of locally residing human nucleus pulposus cells (NPCs), generated by certain conditions in degenerating discs, that was associated with the onset of discogenic back pain. Single-cell transcriptomic analysis of human tissues showed a strong correlation between a specific cell subtype and the pain condition associated with the human degenerated disc, suggesting that they are pain-triggering. The application of IVD degeneration-associated exogenous stimuli to healthy NPCs in vitro recreated a pain-associated phenotype. These stimulated NPCs activated functional human iPSC-derived sensory neuron responses in an in vitro organ-chip model. Injection of stimulated NPCs into the healthy rat IVD induced local inflammatory responses and increased cold sensitivity and mechanical hypersensitivity. Our findings reveal a previously uncharacterized pain-inducing mechanism mediated by NPCs in degenerating IVDs. These findings could aid in the development of NPC-targeted therapeutic strategies for the clinically unmet need to attenuate discogenic LBP.

An Atypical Presentation of Early Periprosthetic Infection After Cervical Disc Arthroplasty: A Case Report.

CASE: A 22-year-old woman with Klippel-Feil syndrome who underwent cervical disc arthroplasty (CDA) presented 3 months postoperatively with worsening neck pain and radiculopathy. Work-up was negative for infection, but single-photon emission computed tomography revealed increased metabolic activity in the vertebral body below the implant. During revision, the implant was grossly loose and multiple cultures grew Cutibacterium acnes. She was treated with an antibiotic course and conversion to anterior fusion without recurrence. CONCLUSION: This report highlights the rare presentation of an early periprosthetic infection after CDA caused by C. acnes.

Range of motion after 1, 2, and 3 level cervical disc arthroplasty.

Background: Motion of a solid body involves translation and rotation. Few investigations examine the isolated translational and rotational components associated with disc arthroplasty devices. This study investigates single- and multi-level cervical disc arthroplasty with respect to index and adjacent level range of motion. The investigators hypothesized that single- and multilevel cervical disc replacement will lead to comparable or improved motion at implanted and adjacent levels. Methods: Seven human cervical spines from C2 to C7 were subjected to displacement-controlled loading in flexion, extension, and lateral bending under intact, 1-Level (C5-C6), 2-Level (C5-C6, C6-C7) and 3-Level (C5-C6, C6-C7, C4-C5) conditions. 3D motions sensors were mounted at C4, C5, and C6. Motion data for translations and rotations at each level for each surgical condition and loading mode were compared to intact conditions. Results: 1-Level: The index surgery resulted in statistically increased translations in extension and lateral bending at all levels with statistically increased translation observed in flexion in the superior and inferior levels. In rotation, the index surgeries decreased rotation under flexion, with remaining levels not statistically different to intact conditions. 2-Level: A device placed inferiorly resulted in statistically increased translations at all levels in extension with statistically increased translations superior and inferior to the index level in flexion. Lateral bending resulted in increased nonsignificant translations. Rotations were elevated or comparable to the intact level for all loading. 3-Level: Translations were statistically increased for all levels in all loading modes while rotations were elevated or were comparable to the intact level for all loading modes and levels. Conclusions: Micromotion sensors permitted monitoring and recording of small magnitude angulations and translations using a loading mechanism that did not over constrain cervical segmental motion. Multilevel cervical disc arthroplasty yielded comparable or increased overall motion at the index and adjacent levels compared to intact conditions.

Anterior Cervical Foraminotomy for Radiculopathy After Cervical Artificial Disc Replacement: Technique Description and Case Report.

BACKGROUND: Patients may occasionally have persistent or recurrent radicular symptoms after cervical artificial disc replacement (ADR) for cervical spondylotic radiculopathy. We describe our approach using anterior cervical foraminotomy (ACF) to provide symptom relief in such patients without the need to convert to a fusion or remove the ADR implant. METHODS: Our operative technique for ACF after cervical ADR begins by starting at the lateral edge of the ADR at the superior end plate of the inferior vertebral body. The ipsilateral uncovertebral joint is drilled with a combination of a high-speed burr and diamond-coated burr to minimize the risk of injury to the vertebral artery. The neuroforamen is entered after drilling through the posterior aspect of the uncinate process. The exiting cervical nerve root should be directly visualized, and a Kerrison rongeur may be used to trace along the nerve root laterally to remove any remaining uncinate osteophyte or process. We queried our internal database for patients with recurrent or new radicular pain following cervical ADR who underwent ACF. Clinical characteristics and outcomes were reported. RESULTS: Five patients with recurrent radicular symptoms after ADR were reviewed. Two ACFs were performed at C5-6, and 2 were performed at C6-7. Four patients developed ipsilateral recurrent radicular symptoms, and only 1 patient developed contralateral new radicular symptoms. Three patients reported complete resolution of their new or recurrent radicular symptoms following ACF, and 2 patients reported only partial resolution. No patients required conversion to a fusion. CONCLUSIONS: In patients with recurrent symptoms of cervical spondylotic radiculopathy following ADR, ACF with uncovertebral joint resection can be used to provide direct foraminal decompression without the need for implant removal. This approach also preserves motion at the affected level, preserves cervical spinal stability, and prevents the need for spinal fusion. CLINICAL RELEVANCE: Patients with persistent or recurrent radicular symptoms after cervical ADR may achieve resolution of symptoms through a modified ACF technique.

Single and Multilevel Lumbar Total Disc Replacement Adjacent to L5-S1 ALIF (Lumbar Hybrid): 6 Years of Follow-up.

BACKGROUND: Single and multilevel lumbar arthroplasty has had excellent results, but the L5-S1 level frequently has pathology that precludes arthroplasty. This study evaluated clinical outcomes and sagittal range of motion (ROM) of operated levels and adjacent motion segments in single- and multiple-level ProDisc-L above a simultaneous L5-S1 fusion (hybrid) after a 2- to 6-year follow-up. METHODS: In this prospective cohort study, 46 patients underwent simultaneous lumbar total disc replacement (TDR) at one to three levels and anterior lumbar interbody fusion (ALIF) at L5-S1. Twenty-three patients had L5-S1 ALIF + L4-5 TDR, 19 patients had L5-S1 ALIF + two-level TDR, and 4 patients had L5-S1 ALIF + three-level TDR. Oswestry disability index (ODI) and visual analog scores (VAS) of patient satisfaction (VAS-S) and pain (VAS-P) were recorded. Sagittal motion on pre- and postoperative lumbar radiographs at each operative segment and adjacent segment was acquired. Patients were evaluated preoperatively and at 6 weeks, 3 months, 6 months, and annually for 24 to 72 months postoperatively. RESULTS: For clinical results, there were no differences among the groups for age, gender, body mass index, tobacco use, or worker's compensation status. At 2-6 years postoperation, all patients had significant reductions in ODI and VAS scores. For radiographic results, at the nonsurgical level adjacent to the TDR + ALIF constructs, the mean preoperative ROM was 9.40 ± 1.80° compared with 10.50 ± 2.25° postoperatively. The mean preoperative ROM at levels undergoing TDR was 10.4 ± 2.71° versus 12.6 ± 2.25° postoperatively. There was no statistically significant difference in ROM at each prosthetic motion segment between patients receiving one-, two-, or three-level TDR. The mean preoperative ROM at the L5-S1 segment to undergo fusion was 2.4 ± 2.44°, with all patients having a postoperative ROM of 0.00°. CONCLUSIONS: Multilevel TDR above an L5-S1 ALIF (hybrid procedure) preserves ROM at the individual TDR levels and does not reduce the fusion rate of the L5-S1 fused level. Most significantly, the nonoperative adjacent level maintains its preoperative ROM at 2-6 years postoperatively.

Outpatient Versus Inpatient Anterior Lumbar Spine Surgery: A Multisite, Comparative Analysis of Patient Safety Measures.

BACKGROUND: The frequency and complexity of spinal surgery performed in an ambulatory surgery center (ASC) is increasing. However, safety and efficacy data of most spinal procedures adapted to the ASC are sparse and have focused on anterior cervical surgery. The purpose of this study was to compare the 90-day complication and readmission rates of anterior lumbar spine surgery performed in an ASC or inpatient setting. METHODS: We performed a retrospective comparative analysis of 226 consecutive anterior lumbar surgeries (283 levels treated) completed in an ASC (n = 124) or in an inpatient tertiary care hospital (n = 102) over a 3-year period. These included anterior lumbar interbody fusion (ALIF), artificial disc replacement (ADR), and hybrids. Patients undergoing simultaneous or staged posterior procedures within 3 months were excluded. Patient demographics and surgical parameters between the two surgical settings were compared. Ninety-day medical complications and readmission rates were assessed. One-way analysis of variance and Chi-square analysis were used. A P value of less than .05 was considered statistically significant. RESULTS: The two study groups had similar baseline characteristics. While there was a trend toward fewer complications, reoperations, and readmissions for the ASC cohort, the differences were not statistically significant. There were 7 intraoperative complications (5.6% minor vascular injury) in the inpatient cohort and 0 in the ASC cohort. The overall 90-day postoperative complication rate was 5.6% for the inpatient cohort and 0.9% for the ASC cohort. The 90-day readmission rate was 1.9% in the ASC cohort and 1.6% in the inpatient cohort. The 90-day reoperation rate was 0.8% for the inpatient cohort and 0% in the ASC cohort. The average hospital stay was 2.3 ± 1.5 days for the inpatient cohort. CONCLUSION: The 90-day readmission rates were lower for outpatients than for inpatients, while the complication and reoperation rates were similar. Our results demonstrate that anterior lumbar procedures, including single-level and multilevel ALIF, ADR, and hybrid procedures, can be performed safely in an ASC. This has significant cost savings implications for the ASC setting.

Low Complication Rate of Anterior Lumbar Spine Surgery in an Ambulatory Surgery Center.

BACKGROUND: As healthcare costs rise, attempts are being made to perform an increasing proportion of spine surgery in ambulatory surgery centers (ASCs). ASCs are more efficient, both economically and functionally. There remains uncertainty regarding the safety of performing anterior lumbar procedures requiring vascular access, as little has been published on this subset of patients. METHODS: This is a consecutive case series analysis of anterior lumbar spine surgeries that were performed in a free-standing ASC in a private-practice setting over a 1-year period, including anterior lumbar interbody fusion, artificial disc replacement, and hybrid procedures. The preoperative, intraoperative, and postoperative data recorded included age, gender, body mass index, tobacco use, and the presence of diabetes; level and procedure, operating room time, estimated blood loss, complications; discharge site, occurrence of reoperation, hospital admission, or any medical complication or infection over a 90-day period. RESULTS: Fifty-one patients underwent 63 treated levels (34 artificial disc replacement, 29 anterior lumbar interbody fusion): 40 single-level, 10 two-level, one three-level. Average age was 45 years; 27 female, 24 males. None of the patients were diabetics, three were current smokers, seven were former smokers. Average body mass index was 27 ± 4 (range 16-36). Average total anesthesia time was 100 minutes (range 57-187 minutes). Average estimated blood loss was 23 mL (range 5-250 mL). Seventy-one percent of patients were discharged directly home, 29% to an aftercare facility. In the 30-day postoperative period there were no deaths, one hospital admission for pain, and no significant medical complications or surgical site infections. CONCLUSION: In this consecutive case series artificial disc replacement or anterior lumbar interbody fusion was performed at 63 levels in 51 patients in the ASC setting with an observed major complication rate of zero and hospital unplanned admission rate of 2% (1/51). This provides some evidence that these procedures are safe to perform in the ASC setting. However, a highly experienced vascular surgeon and efficient surgical team, and strict patient selection criteria are all critical in making this possible.

Restoration of Spinal Motion: Conversion of Anterior Cervical Fusion With Pseudarthrosis to Artificial Disc Replacement.

BACKGROUND: Describe the technique and outcomes of the conversion of prior anterior cervical discectomy and fusion (ACDF) with pseudarthrosis to an artificial disc replacement (ADR). METHODS: Case report. Five patients completed the following pain and function questionnaires at baseline and postoperatively: visual analog pain scale (VAS), Neck Disability Index (NDI), PROMIS Emotional Distress-Depression Short Form-4a (P-EDD), PROMIS Pain Interference Short Form 6b (P-PI), and PROMIS Physical Function Short Form-10a (P-SF). Pseudarthrosis was diagnosed using computed tomography imaging of the cervical spine. The level of prior fusion with pseudarthrosis was remobilized after a standard anterior approach was made, and an artificial disc replacement was performed after revision discectomy. RESULTS: The conversion of fusion to ADR was successful in all 5 patients without intraoperative or postoperative complication or the need to perform revision fusion. The average follow-up duration was 12.4 months (range 6-24months). VAS improved on average (median) from 6 (6.0) to 2 (2.2), NDI improved from 23 (21) to 15 (17), P-EDD 4a improved from 11 (11) to 4 (4), and P-PI and P-SF improved from 23 (22) to 16 (19) and from 37 (35) to 41 (39.5), respectively. Radiographic range of motion increased at the fusion conversion level from an average of 1° ± 1.2° to 8.1° ± 4.6° after the insertion of the artificial disc replacement. CONCLUSIONS: The reversal of ACDF and conversion to an artificial disc replacement is feasible and achieves postoperative range of motion that is similar to that achieved when performed in a segment not previously fused.

NF-κB inhibitor, NEMO-binding domain peptide attenuates intervertebral disc degeneration.

BACKGROUND CONTEXT: Nonphysiological mechanical loading and inflammation are both critically involved in intervertebral disc (IVD) degeneration, which is characterized by an increase in cytokines and matrix metalloproteases (MMPs) in the nucleus pulposus (NP). This process is known to be mediated by the NF-κB pathway. CLINICAL SIGNIFICANCE: Current clinical treatments for IVD degeneration focus on the alleviation of symptoms rather than targeting the underlying mechanism. Injection of an NF-κB inhibitor may attenuate the progression of IVD degeneration. PURPOSE: To investigate the ability of the NF-κB inhibitor, NEMO binding domain peptide (NBD), to alter IVD degeneration processes by reducing IL-1ß- and mechanically-induced cytokine and MMP levels in human nucleus pulposus cells in vitro, and by attenuating IVD degeneration in an in vivo rat model for disc degeneration. STUDY DESIGN: Experimental in vitro and animal model. PATIENT SAMPLE: Discarded specimens of lumbar disc from 21 patients, and 12 Sprague Dawley rats. OUTCOME MEASURES: Gene and protein expression, cell viability, µMRI and histology. METHODS: IL-1ß-prestimulated human nucleus pulposus cells embedded into fibrin constructs were loaded in the Flexcell FX-5000 compression system at 5 kPa and 1 Hz for 48 hours in the presence and absence of NBD. Unloaded hNPC/fibrin constructs served as controls. Cell viability in loaded and unloaded constructs was quantified, and gene and protein expression levels determined. For in vivo testing, a rat needle disc puncture model was employed. Experimental groups included injured discs with and without NBD injection and uninjured controls. Levels of disc degeneration were determined via µMRI, qPCR and histology. Funding sources include $48,874 NASS Young Investigator Research Grant and $119,174 NIH 5K01AR071512-02. There were no applicable financial relationships or conflicts of interest. RESULTS: Mechanical compression of hNPC/fibrin constructs resulted in upregulation of MMP-3 and IL-8. Supplementation of media with 10 µM NBD during loading increased cell viability, and decreased MMP-3 gene and protein levels. IVD injury in rat resulted in an increase in MMP-3, IL-1ß and IL-6 gene expression. Injections of 250 µg of NBD during disc injury resulted in decreased IL-6 gene expression. µMRI analysis demonstrated a reduction of disc hydration in response to disc needle injury, which was attenuated in NBD-treated IVDs. Histological evaluation showed NP and AF lesion in injured discs, which was attenuated by NBD injection. CONCLUSIONS: The results of this study show NBD peptide's capacity to reduce IL-1ß- and loading-induced MMP-3 levels in hNPC/fibrin constructs while increasing the cells' viability, and to attenuate IVD degeneration in rat, involving downregulation of IL-6. Therefore, NBD may be a potential therapeutic agent to treat IVD degeneration.

The Safety of Single and Multilevel Cervical Total Disc Replacement in Ambulatory Surgery Centers.

STUDY DESIGN: Retrospective cohort. OBJECTIVE: Evaluate the safety profile of single- and multilevel cervical artificial disc replacement (ADR) performed in an outpatient setting. SUMMARY OF BACKGROUND DATA: As healthcare costs rise, attempts are made to perform an increasing proportion of spine surgery in ambulatory surgery centers (ASCs). ASCs are more efficient, economically and functionally. Few studies have published on the safety profile of multilevel cervical ADR. METHODS: We have performed an analysis of all consecutive cervical ADR surgeries that we performed in an ASC over a 9-month period, including multilevel and revision surgery. The pre-, intra-, and postoperative data recorded included age, sex, body mass index, tobacco use, and diabetes; level and procedure, operating room time, estimated blood loss (EBL), and complications; and discharge site, occurrence of reoperation, hospital admission, or any medical complication or infection over a 90-day period. RESULTS: A total of 147 patients underwent 231 treated levels: 71 single-level, 76 multilevel: 69 two-level, 6 three-level, and 1 four-level. Average age was 50 ±â€Š10 years; 71 women, 76 men. None of the patients had insulin-dependent diabetes, 4 were current smokers, and 16 were former smokers. Average body mass index was 26.8 ±â€Š4.6 (range 18-40). Average total anesthesia time was 88 minutes (range 39-168 min). Average EBL was 15 mL (range 5-100 mL). Approximately 90.3% of patients were discharged directly home, 9.7% to an aftercare facility. In the 90-day postoperative period there were zero deaths and two hospital admissions (1.4%)-one for medical complication (0.7%) and one for a surgical site infection (0.7%). CONCLUSION: In this consecutive case series we performed 231 ADRs in 147 patients in the outpatient setting, including multilevel and revision procedures, with 2 minor postoperative complications resulting in hospital unplanned admissions within 90 days. We believe that these procedures are safe to perform in an ASC. An efficient surgical team and careful patient selection criteria are critical in making this possible. LEVEL OF EVIDENCE: 3.

Multiple-Level Lumbar Total Disk Replacement: A Prospective Clinical and Radiographic Analysis of Motion Preservation at 24-72 Months.

BACKGROUND: Recent studies demonstrate the efficacy of lumbar arthroplasty using the ProDisc-L. Patients frequently present with multilevel pathology and may be candidates for multilevel disk replacement. PURPOSE: To evaluate clinical outcomes and sagittal range of motion of operated levels and adjacent lumbar motion segments in multiple-level ProDisc-L constructs after 2-6 years follow-up. PATIENT SAMPLE: A total of 159 patients underwent adjacent 2-level (n=114), 3-level (n=41), or 4-level (n=4) lumbar total disk replacement (TDR). STUDY-DESIGN: This is a prospective cohort. OUTCOME MEASURES: Clinical measures: Oswestry Disability Index and Visual Analog Score of patient satisfaction (VAS-S) and pain (VAS-P) data were collected. Radiographic measures: sagittal motion on preoperative and postoperative lumbar radiographs at each operative segment and adjacent segment. METHODS: Patients were evaluated with radiographic and clinical outcomes measures preoperatively, at 6 weeks, 3 months, 6 months, and annually for 24-72 months postoperatively. RESULTS: Radiographic: at the motion segment adjacent to the TDR, mean preoperative range of motion (ROM) was 8.20±2.88 degrees, compared with 8.40±2.4 degrees postoperatively at last follow-up (P>0.05). Between the 3 TDR groups, there were no significant differences in ROM at any time point except at L5-S1. Across both groups for TDR motion segments, the mean preoperative ROM was 10.15±2.71 versus 12.30±2.25 degrees postoperatively (P=0.011) at last follow-up. At L5-S1 mean preoperative motion was 7.60±3.90 versus 5.81±3.1 degrees postoperatively (P=0.60). Clinical: at 24-72 months postoperatively, all patients had significant reductions in Oswestry Disability Index, VAS-P, and VAS-S scores (P<0.05). At up to 72 months of follow-up, no patient underwent adjacent-level surgery but there were 3 cases of index-level revision surgery. CONCLUSIONS: Multilevel TDR preserves ROM at the individual TDR levels. Most significantly, the nonoperative adjacent level maintains its preoperative ROM at 2-6 years postoperatively. At up to 6 years of follow-up, there has been no need for revision or adjacent-segment surgery. Patients also demonstrate significant improvement in pain and disability at latest follow-up.

Anti-Inflammatory Peptide Attenuates Edema and Promotes BMP-2-Induced Bone Formation in Spine Fusion.

Recombinant human bone morphogenic protein-2 (BMP-2)-loaded absorbable collagen sponges (ACS) have been successfully used to enhance bone formation and to induce spinal fusion in humans. However, side effects, such as soft tissue edema and inflammation, have been reported. NEMO binding domain peptide (NBD) inhibits activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), a central regulator of immune response. In this study, we investigated NBD's potential to reduce BMP-2-induced soft tissue inflammation without affecting BMP-2-mediated spinal fusion in rat. For evaluation of soft tissue inflammation, ACS containing BMP-2, BMP-2+NBD, NBD, or ACS only were implanted into intramuscular paraspinal sites of 32 rats. At day 2 postsurgery, edema formation at the implant sites was assessed using magnetic resonance imaging. T2-weighted relaxation time (T2-RT) values were increased in the BMP-2 group compared with BMP-2+NBD, NBD, and ACS groups. No difference in T2-RT values was detected between BMP-2+NBD versus NBD and ACS controls. Postsacrifice, histological analysis of the implant-surrounding zones showed increased mononuclear cell infiltration in the BMP-2 group compared with BMP-2+NBD and controls. The presence of BMP-2 increased relative NF-κB binding and gene expression of inflammatory markers, interleukin (IL)1ß, IL6, IL18, and chemokine ligand (CCL)2 and CCL3 compared with controls. In the BMP-2+NBD group, cytokine expression was blocked. No differences were found between BMP-2+NBD and control groups. For evaluation of spinal fusion, posterolateral intertransverse lumbar fusion procedures were performed on 16 rats. ACS were loaded with BMP-2 or BMP-2+NBD. After sacrifice at week 12, microcomputed tomographic assessment of the fusion site detected a higher bone volume and reduced trabecular spacing in the BMP-2+NBD group compared with BMP-2. Histological analysis did not show any differences in newly formed bone microarchitecture. In summary, addition of NBD to BMP-2-loaded ACS reduces BMP-2-induced soft tissue edema formation and mononuclear cell infiltration, diminishes NF-κB binding, and thus blocks transcription of NF-κB-regulated cytokines in rat. Furthermore, NBD stimulates bone formation in BMP-2-mediated spinal fusion, possibly through crosstalk of the NF-κB pathway with other pathways. The results of this study might provide the basis to develop new therapeutic bone grafting approaches with combinatory administration of BMP-2 and NBD for spinal fusion.

α2-Macroglobulin: Autologous Protease Inhibition Technology.

α2-Macroglobulin (A2M) is a plasma glycoprotein best known for its ability to inhibit a broad spectrum of serine, threonine, and metalloproteases as well as inflammatory cytokines by a unique bait-and-trap method. A2M has emerged as a unique potential treatment of cartilage-based pathology and inflammatory arthritides. This article describes the unique method by which A2M not only inhibits the associated inflammatory cascade but also disrupts the catabolic process of cartilage degeneration. Autologous concentrated A2M from plasma is currently in use to successfully treat various painful arthritides. Future directions will focus on recombinant variants that enhance its anti-inflammatory and disease-modifying potential.

Distraction Laminoplasty With Interlaminar Lumbar Instrumented Fusion (ILIF) for Lumbar Stenosis With or Without Grade 1 Spondylolisthesis: Technique and 2-Year Outcomes.

STUDY DESIGN: Prospective, nonrandomized cohort. OBJECTIVE: Describe the surgical technique and clinical outcome of distraction lumbar laminoplasty with allograft bone block augmentation and interlaminar lumbar instrumented fusion (ILIF) SUMMARY OF BACKGROUND DATA.: ILIF is a recently described technique that may offer a less invasive alternative to traditional posterior pedicle screw fixation for stabilization during posterior or posterolateral lumbar fusion after decompression for lumbar spinal stenosis. METHODS: Data from two sites of a prospective, multicenter clinical study is described in this report and includes 37 patients over age 40 with single-level degenerative disc disease between L1-2 and L4-5 with neurogenic claudication. Subjects were treated with lumbar decompression using a distraction laminoplasty procedure followed by insertion of a preshaped allograft bone block and interspinous stabilization with a fixation device. BMP-2 was not used. Follow-up clinical evaluation was performed at baseline and at 6 weeks, 3, 6, 12, and 24 months, including perioperative complications, visual analog pain score, Oswestry Disability Index, Zurich Claudication Questionnaire scores and return to activity and work. Radiographic evaluation of fusion and segmental and regional lumbar lordosis were performed to 2 years. RESULTS: Thirty-three patients (89%) of mean age 71 years (17% woman) met all follow-up criteria at 2 years. Levels treated were L4-5 (78.4%), L3-4 (16.2%), or L2-3 (5.4%). Thirty-two of 37 (86%) of patients had a grade-1 spondylolisthesis. Mean hospital length of stay (LOS) was 2 days. Complications included one dural tear, one new neuro deficit that resolved by 6 weeks, one implant failure, one seroma, and one case of cancer diagnosis. At 2 years, 67% had >2 cm improvement on visual analog pain score and 73% had >12.4% Oswestry Disability Index improvement. Symptom severity and physical function subset scores of Zurich Claudication Questionnaire improved by >0.5 cm in 76 and 73% of patients, respectively. At 2 years 94% of patients were off all narcotics and NSAIDS and 94% reported satisfaction with the procedure. Mean lumbar lordosis at baseline and 2 years was 53 ±â€Š14° and 53 ±â€Š13°, respectively. Seventy-two percent of subjects met strict fusion criterion of <3° motion on flexion/extension XRAY and bridging bone; 97% met criteria for stability by independent surgeon evaluation. CONCLUSION: Distraction laminoplasty with allograft bone block augmentation and ILIF may provide a less-invasive alternative to traditional pedicle screw fixation after decompression and posterolateral fusion. The present study describes this technique, and demonstrates excellent clinical outcomes and an acceptable rate of radiographic fusion success. LEVEL OF EVIDENCE: NA.

Does provocative discography cause clinically important injury to the lumbar intervertebral disc? A 10-year matched cohort study.

BACKGROUND CONTEXT: Provocative discography, an invasive diagnostic procedure involving disc puncture with pressurization, is a test for presumptive discogenic pain in the lumbar spine. The clinical validity of this test is unproven. Data from multiple animal studies confirm that disc puncture causes early disc degeneration. A recent study identified radiographic disc degeneration on magnetic resonance imaging (MRI) performed 10 years later in human subjects exposed to provocative discography. The clinical effect of this disc degeneration after provocative discography is unknown. PURPOSE: The aim of this study was to investigate the clinical effects of lumbar provocative discography on patients subjected to this evaluation method. STUDY DESIGN/SETTING: A prospective, 10-year matched cohort study. PATIENT SAMPLE: Subjects (n=75) without current low back pain (LBP) problems were recruited to participate in a study of provocative discography at the L3-S1 discs. A closely matched control cohort was simultaneously recruited to undergo a similar evaluation except for discography injections. OUTCOME MEASURES: The primary outcome variables were diagnostic imaging events and lumbar disc surgery events. The secondary outcome variables were serious LBP events, disability events, and medical visits. METHODS: The discography subjects and control subjects were followed by serial protocol evaluations at 1, 2, 5, and 10 years after enrollment. The lumbar disc surgery events and diagnostic imaging (computed tomography (CT) or MRI) events were recorded. In addition, the interval and cumulative lumbar spine events were recorded. RESULTS: Of the 150 subjects enrolled, 71 discography subjects and 72 control subjects completed the baseline evaluation. At 10-year follow-up, 57 discography and 53 control subjects completed all interval surveillance evaluations. There were 16 lumbar surgeries in the discography group, compared with four in the control group. Medical visits, CT/MRI examinations, work loss, and prolonged back pain episodes were all more frequent in the discography group compared with control subjects. CONCLUSION: The disc puncture and pressurized injection performed during provocative discography can increase the risk of clinical disc problems in exposed patients.

Correlation of Synovial Fluid Biomarkers With Cartilage Pathology and Associated Outcomes in Knee Arthroscopy.

PURPOSE: To correlate the intraoperative concentrations of 20 synovial fluid biomarkers with preoperative symptoms, intraoperative findings, and postoperative outcomes in patients undergoing knee arthroscopy, with comparisons made to samples obtained from asymptomatic knees. METHODS: Synovial fluid samples were obtained from 81 patients undergoing knee arthroscopy meeting the inclusion criteria, which included 70 samples from operative knees and 32 samples from contralateral knees. Preoperatively, baseline data obtained from clinical questionnaires including a visual analog scale (VAS) score, the Lysholm score, and the Knee Injury and Osteoarthritis Outcome Score-Physical Function Short Form were recorded. Synovial fluid was collected from both the operative knee and asymptomatic contralateral knee. Synovial fluid was stored with a protease inhibitor at -80°C until analysis. Intraoperative findings, procedures performed, and International Cartilage Repair Society (ICRS) cartilage status scores in all operative knees were documented. The concentrations of the following 20 biomarkers were measured using a multiplex magnetic bead immunoassay: matrix metalloproteinase (MMP) 3; MMP-13; tissue inhibitor of metalloproteinase (TIMP) 1; TIMP-2; TIMP-3; TIMP-4; fibroblast growth factor 2; eotaxin; interferon γ; interleukin (IL) 10; platelet-derived growth factor BB; IL-1 receptor antagonist; IL-1ß; IL-6; monocyte chemotactic protein 1 (MCP-1); macrophage inflammatory protein 1α; macrophage inflammatory protein 1ß; RANTES (regulated upon activation, normal T cell expressed and secreted); tumor necrosis factor α; and vascular endothelial growth factor. Clinical outcome scores were obtained in 83% of patients at a mean of 17 months' follow-up postoperatively. Analysis of variance and Pearson correlation analysis were performed to determine statistical significance between preoperative data, intraoperative findings, postoperative outcomes, and synovial fluid biomarker concentrations compared with asymptomatic contralateral knees. RESULTS: Analysis was performed on 70 operative and 32 contralateral samples. There were strong positive correlations between ICRS score and age, symptom duration, VAS score, and Knee Injury and Osteoarthritis Outcome Score-Physical Function Short Form. A strong positive correlation was found between MCP-1 and IL-6 concentrations, intraoperative ICRS score, and continued pain at the time of final follow-up. MCP-1 and IL-6 were the strongest predictors of severe cartilage lesions, whereas IL-1 receptor antagonist was inversely related. MMP-3 levels were consistently elevated in all operative samples and directly correlated to increased preoperative VAS scores. RANTES, vascular endothelial growth factor, and platelet-derived growth factor BB were the strongest predictors of postoperative improvement at final follow-up regardless of injury and cartilage status. CONCLUSIONS: Synovial fluid biomarkers have the capacity to reflect the intra-articular environment before surgery and potentially predict postoperative clinical outcomes. Recognition of key molecular players may yield future therapeutic targets, and large clinical trials exploring these discoveries are anticipated. LEVEL OF EVIDENCE: Level III, therapeutic case-control study.

Does aspirin administration increase perioperative morbidity in patients with cardiac stents undergoing spinal surgery?

STUDY DESIGN: Cohort. OBJECTIVE: To compare the perioperative morbidity of patients with cardiac stents after spine surgery who continue to take aspirin before and after the operation with a similar group of patients who preoperatively discontinued aspirin. SUMMARY OF BACKGROUND DATA: The preoperative discontinuation of anticoagulant therapy has been the standard of care for orthopedic surgical procedures. However, recent literature has demonstrated significant cardiac risk associated with aspirin withdrawal in patients with cardiac stents. Although it has recently been demonstrated that performing orthopedic surgery while continuing low-dose aspirin therapy seems to be safe, studies focused on spinal surgery have not yet been performed. Because of the risk of intraspinal bleeding and the serious consequences of subsequent epidural hematoma with associated spinal cord compression, spinal surgeons have been reluctant to operate on patients taking aspirin. METHODS: This institutional review board-approved study included 200 patients. Preoperative parameters and postoperative outcome measures were analyzed for 100 patients who underwent spinal surgery after the discontinuation of anticoagulation therapy and 100 patients who continued to take daily aspirin through the perioperative period. The primary outcome measure was serious bleeding-related postoperative complications such as spinal epidural hematoma. The operative time, intraoperative estimated blood loss, hospital length of stay, transfusion of blood products, and 30-day hospital readmission rates were also recorded and compared. RESULTS: The patients who continued taking aspirin in the perioperative period had a shorter hospital length of stay on average (4.1 ± 2.7 vs. 6.2 ± 5.8; P < 0.005), as well as a reduced operative time (210 ± 136 vs. 266 ± 143; P < 0.01), whereas there was no significant difference in the estimated blood loss (642 ± 905 vs. 697 ± 1187), the amount of blood products transfused, overall intra- and postoperative complication rate (8% vs. 11%), or 30-day hospital readmission rate (5% vs. 5%). No clinically significant spinal epidural hematomas were observed in either of the study groups. CONCLUSION: The current study has observed no appreciable increase in bleeding-related complication rates in patients with cardiac stents undergoing spine surgery while continuing to take aspirin compared with patients who discontinued aspirin prior to surgery. Although very large studies will be needed to determine whether aspirin administration results in a small complication rate increase, the current study provides evidence that perioperative aspirin therapy is relatively safe in patients undergoing spinal surgery. LEVEL OF EVIDENCE: 2.

The effects of Amicar and TXA on lumbar spine fusion in an animal model.

STUDY DESIGN: Animal model. OBJECTIVE: To determine whether aminocaproic acid (Amicar) and tranexamic acid (TXA) inhibit spine fusion volume. SUMMARY OF BACKGROUND DATA: Amicar and TXA are antifibrinolytics used to reduce perioperative bleeding. Prior in vitro data showed that antifibrinolytics reduce osteoblast bone mineralization. This study tested whether antifibrinolytics Amicar and TXA inhibit spine fusion. METHODS: Posterolateral L4-L6 fusion was performed in 50 mice, randomized into groups of 10, which received the following treatment before and after surgery: (1) saline; (2) TXA 100 mg/kg; (3) TXA 1000 mg/kg; (4) Amicar 100 mg/kg; and (5) Amicar 1000 mg/kg. High-resolution plane radiography was performed after 5 weeks and micro-CT (computed tomography) was performed at the end of the 12-week study. Radiographs were graded using the Lenke scale. Micro-CT was used to quantify fusion mass bone volume. One-way analysis of variance by ranks with Kruskal-Wallis testing was used to compare the radiographical scores. One-way analysis of variance with least significant difference post hoc testing was used to compare the micro-CT bone volume. RESULTS: The average±standard deviation bone volume/total volume (%) measured in the saline, TXA 100 mg/kg, TXA 1000 mg/kg, Amicar 100 mg/kg, and Amicar 1000 mg/kg groups were 10.8±2.3%, 9.7±2.2%, 13.4±3.2%, 15.5±5.2%, and 17.9±3.5%, respectively. There was a significant difference in the Amicar 100 mg/kg (P<0.05) and Amicar 1000 mg/kg (P<0.001) groups compared with the saline group. There was greater bone volume in the Amicar groups compared with the TXA group (P<0.001). There was more bone volume in the TXA 1000 mg/kg group compared with TXA 100 mg/kg (P<0.05) but the bone volume in neither of the TXA groups was different to saline (P=0.49). There were no between-group differences observed using plane radiographical scoring. CONCLUSION: Amicar significantly "enhanced" the fusion bone mass in a dose-dependent manner, whereas TXA did not have a significant effect on fusion compared with saline control.These data are in contrast to prior in vitro data that antifibrinolytics inhibit osteoblast bone mineralization. LEVEL OF EVIDENCE: N/A.

Does a fibronectin and aggrecan complex play a role in painful vertebral disks?

OBJECTIVE: To determine the presence of a fibronectin-aggrecan complex (FAC) in the disk space of persons with chronic low back pain as relates to provocative diskography. DESIGN: A single-center prospective consecutive case series. SETTING: A single private practice setting. PATIENTS: Thirty-seven patients with symptomatic degenerative disk disease of the cervical, thoracic, or lumbar spine undergoing provocative diskography to identify a source of pain. METHODS: Diskographic lavage for analysis was simultaneously performed at each disk level injected during diskography. MAIN OUTCOME MEASURES: Visual analog scale (VAS) pain scores, Pfirrmann magnetic resonance imaging grade, and biochemical analysis of disk material were statistically analyzed. RESULTS: A total of 105 levels in 37 patients had a complete set of data (mean age 43.2 ± 11.9 years; 15 male/22 female). The FAC was present in 43 of 108 levels and in at least one level in 25 of 37 patients. The Pfirrmann magnetic resonance imaging grade did not differ between complex-positive and negative levels (P = .125), nor did the intraoperative VAS (IO-VAS) score for pain by level (P = .206). A significant but loose correlation was found between Pfirrmann grade and IO-VAS (R(2) = 0.4, P < .001), but no significant correlation was found between VAS or IO-VAS and complex concentration (R(2) = 0.08, P = .11 and R(2) = 0.003, P = .5). CONCLUSIONS: The FAC was identified in some painful disks by diskography. There was no significant correlation between the Pfirrmann grade or pre/intraoperative pain scores during diskography and complex concentrations within the disk measured by disk lavage.