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Background: Low-dose CT (LDCT) is underused in Arkansas for lung cancer screening, a rural state with a high incidence of lung cancer. The objective was to determine whether offering free LDCT increased the number of high-risk individuals screened in a rural catchment area., Methods: There were 5,402 patients enrolled in screening at Highlands Oncology, a community oncology clinic in Northwest Arkansas, from 2013 to 2020. Screenings were separated into time periods: period 1 (10 months for-fee), period 2 (10 months free with targeted advertisements and primary care outreach), and period 3 (62 months free with only primary care outreach). In all, 5,035 high-risk participants were eligible for analysis based on National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Enrollment rates, incidence densities (IDs), Cox proportional hazard models, and Kaplan-Meier curves were performed to investigate differences between enrollment periods and high-risk groups., Results: Patient volume increased drastically once screenings were offered free of charge (period 1 = 4.6 versus period 2 = 66.0 and period 3 = 69.8 average patients per month). Incidence density per 1,000 person-years increased through each period (ID Period 1  = 17.2; ID Period 2  = 20.8; ID Period 3  = 25.5 cases). Cox models revealed significant differences in lung cancer risk between high-risk groups (P = .012) but not enrollment periods (P = .19). Kaplan-Meier lung cancer-free probabilities differed significantly between high-risk groups (log-rank P = .00068) but not enrollment periods (log-rank P = .18)., Conclusions: This study suggests that eligible patients are more receptive to free LDCT screening, despite most insurances not having a required copay for eligible patients., (Copyright © 2023 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Background: The selection of later-line treatment for older patients with AJCC (version 7) stage IV non-small cell lung cancer (NSCLC) remains controversial. Nanoparticle albumin-bound (nab)-paclitaxel is approved with carboplatin for the first-line treatment of patients with NSCLC and subgroup analysis of phase 3 data has suggested superior survival in older patients., Methods: The authors conducted a phase 2 study of nab-paclitaxel in 42 patients aged ≥70 years who had been treated previously with a platinum doublet regimen; patients also could have received a PD-1 inhibitor. The primary endpoint of the current study was grade 3 to 5 toxicity (according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]). In addition to response rate, progression-free survival (PFS), and overall survival (OS), geriatric assessments also were performed before and during treatment, associations between baseline sarcopenia and outcomes were explored, and changes in T lymphocyte p16 before and during treatment were measured. The authors also performed a retrospective subgroup analysis of 19 older patients who were treated with nab-paclitaxel as part of a larger, randomized, phase 2 study; data were not combined., Results: The rate of grade 3 to 5 toxicities was 33.7%. The most common grade 3 to 5 toxicities were decreased white blood cell count (11.9%), neutropenia (9.5%), and fatigue (11.9%). The response rate was 34.2% (2.6% complete response rate and 31.6% partial response rate). The median PFS was 5.2 months and the median OS was 9.3 months. Adverse prognostic factors were common: 42% of patients were frail and 39% of patients were prefrail, whereas 21% had an Eastern Cooperative Oncology Group performance status of 2 and 27% were sarcopenic. Only frailty was found to be predictive of inferior survival. A subgroup analysis of 19 older patients treated with nab-paclitaxel alone in a prior trial demonstrated a response rate of 15.8%, a PFS of 4.2 months, and an OS of 13.6 months., Conclusions: Fit and prefrail older patients with stage IV NSCLC should be considered for treatment with nab-paclitaxel after disease progression with doublet chemotherapy., (© 2020 American Cancer Society.)

Objectives: This phase II, open-label study was designed to evaluate the response rate to the polo-like kinase 1 (Plk-1) inhibitor BI 2536 in patients with sensitive-relapsed small cell lung cancer (SCLC). Secondary endpoints included progression-free survival (PFS), overall survival (OS), duration of response, and safety., Materials and Methods: Patients were treated with the recommended phase II dose of 200mg of BI 2536 intravenously every 21days. This was a two-stage design with an early stopping rule in place if responses were not seen in at least 2 of the first 18 enrolled patients., Results and Conclusion: Twenty-three patients were enrolled in the study and 21 patients were evaluable for response. No responses were observed and all 23 patients have progressed. The median PFS was 1.4 months. Treatment was generally well tolerated and the most frequent adverse events were neutropenia, fatigue, nausea, vomiting, and constipation. BI 2536 is not effective in the treatment of sensitive relapsed SCLC. The criteria for expanding the trial to the second stage were not achieved, and the study was terminated for a lack of efficacy., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Single-agent gemcitabine is a standard of care for elderly patients with advanced non-small cell lung cancer, but novel therapies are needed for this patient population., Methods: We performed a noncomparative randomized phase II trial of gemcitabine, erlotinib, or the combination in elderly patients (age ≥70 years) with stage IIIB or IV non-small cell lung cancer. Patients were randomized to arms: A (gemcitabine 1200 mg/m on days 1 and 8 every 21 days), B (erlotinib 150 mg daily), or C (gemcitabine 1000 mg/m on days 1 and 8 every 21 days and erlotinib 100 mg daily). Arms B and C were considered investigational; the primary objective was 6-month progression-free survival., Results: Between March 2006 and May 2010, 146 eligible patients received protocol therapy. The majority of the patients (82%) had stage IV disease, 64% reported adenocarcinoma histology, 90% reported current or previous tobacco use, and 28% had a performance status of 2. The 6-month progression-free survival rate observed in arms A, B, and C was 22% (95% confidence interval [CI] 11-35), 24% (95% CI 13-36), and 25% (95% CI 15-38), respectively; the median overall survival observed was 6.8 months (95% CI 4.8-8.5), 5.8 months (95% CI 3.0-8.3), and 5.6 months (95% CI 3.5-8.4), respectively. The rate of grade ≥3 hematological and nonhematological toxicity observed was similar in all three arms. The best overall health-related quality of life response did not differ between treatment arms., Conclusions: Erlotinib or erlotinib and gemcitabine do not warrant further investigation in an unselected elderly patient population.

Purpose: To investigate the activity of carboplatin and cetuximab in NSCLC., Patients and Methods: This was a single arm, multicenter phase II trial, and the primary objective was response rate., Results: The overall response rate observed was 9% (95% confidence interval [CI], 3-19), the progression-free survival was 2.9 months (95% CI, 1.9-3.6), the median overall survival was 8.2 months (95% CI, 4.9-10.5), and 1-year survival rate was 33% (95% CI, 21-45)., Conclusion: The combination of carboplatin and cetuximab demonstrated lower activity than double agent platinum-based therapy and does not warrant further development.

Seven millennia of anthropological artifacts and historical tales reference human spinal deformity, its diagnosis, and treatment-many of the latter of which turned out to be worse than the deformity itself. From Hippocrates to Harrington to the 21st century, the literature base has expanded in exponential fashion to yield an imperfect but constantly improving body of evidence, experience, and understanding of this challenging disease phenomenon. This review details the pre-1990 innovations, whose failures and successes have equally contributed to the advancement and dissemination of the increasingly evidence-based field of spinal deformity.

Study Design: In vitro and in vivo biomechanical stress measurements are made of the intervertebral disc segment distraction force during anterior cervical discectomy., Objective: The purpose of this study is to determine the short-term force relaxation of the native intervertebral disc segment and to determine the short-term force relaxation of the segment after removal of the intervertebral disc, as is commonly performed in anterior cervical discectomy with fusion and arthroplasty., Summary of Background Data: No published data examine the issue of intraoperative distraction force of the cervical intervertebral disc segment. This is a novel research in this area., Methods: In vitro and in vivo studies under institutional review board approval were performed to determine the mechanical behavior of the normal and diseased cervical functional spinal unit. Seven in vitro and 11 in vivo spines were studied. Strain measurements between distracting Caspar-type pins were made before, at various points during, and after discectomy to assess how removal of the disc and other spinal components affects the force-displacement behavior of the spinal unit., Results: The in vitro data show progressive reduction in force needed for distraction after discectomy and uncovertebral joint resection. Greatest reduction is noted after discectomy. The in vivo data indicate that, on average, the cervical functional spinal unit requires 20 N less force to achieve the same degree of distraction after removal of the intervertebral disc., Conclusions: A sharp reduction in the strain across the intervertebral space occurs after distraction. The removal of the cervical intervertebral disc significantly reduces the viscoelastic response of the cervical motion segment. The long-term force used to stabilize intervertebral grafts or implants is less than what is achieved at the time of distraction. The exact magnitude of the resultant force on graft or device at a given distraction force is unknown and would depend also upon fit.

Study Design: A retrospective review was performed of adult and adolescent patients who underwent anterior spinal fusion for thoracolumbar idiopathic scoliosis; radiographic and clinical outcomes were compared., Objective: The objective of this study was to compare the efficacy of anterior instrumentation to treat thoracolumbar scoliosis in adults and adolescents by evaluating radiographic and clinical outcomes., Summary of Background Data: Anterior spinal arthrodesis is an effective treatment for idiopathic scoliosis. Deformity characteristics and clinical outcomes of adults versus adolescents have not been compared., Methods: A retrospective review of patients undergoing anterior fusion for thoracolumbar scoliosis was performed. Clinical outcomes were assessed using SRS-22. Preoperative and postoperative long films were evaluated independently. Flexibility, curve correction, and clinical outcomes were compared between adult and adolescents., Results: Fifteen adults and 15 adolescents who underwent anterior spinal fusion and instrumentation were evaluated. Mean follow-up was 47 and 46 months, respectively. Flexibility of the major curve in adults (63%) was less than in adolescents (79%) (P < 0.05). Mean preoperative, major curve Cobb angles were 51 degrees and 49 degrees for adults and adolescents, respectively. Mean postoperative Cobb angles improved less for adults (17 degrees ) than for adolescents (10 degrees ) (P < 0.05). The SRS-22 questionnaire revealed no statistical difference between populations., Conclusion: Anterior spinal fusion is an option for both adults and adolescents with flexible, moderate thoracolumbar/lumbar curves. Flexibility significantly decreased with increased age and curve magnitude. This significantly affected curve correction. Adult patients may develop early degeneration at primary curve and compensatory curves. Careful patient selection is critical with this technique.

Background Context: Percutaneous discectomy can be performed by a variety of methods. One method, electrosurgical ablation, has been shown in a chronic animal model to alter the expression of inflammatory cytokines in degenerated discs., Purpose: To determine whether electrosurgical ablation has an acute direct effect on proinflammatory mediator production by disc cells., Study Design: A short-term in vitro study using normal and interleukin (IL)-1alpha stimulated porcine disc cells cultured in alginate gel to evaluate the biochemical effects of electrosurgical ablation., Methods: Porcine annulus and nucleus cells were embedded into alginate gels and cultured using control culture media or IL-1alpha-treated media for 6 days before ablation treatment. Treated gels were ablated by using a radiofrequency-based electrosurgical device for 5 seconds and cultured an additional 3 or 6 days. IL-1beta, IL-6, IL-8, tumor necrosis factor alpha (TNF-alpha), prostaglandin E2 (PGE2), nitric oxide (NO), and heat shock protein-70 (Hsp70) levels in culture medium were measured. Levels were normalized to DNA and compared between ablated and shams., Results: For normal annulus cells, there were no significant changes in cytokine levels between ablation and sham groups. For normal nucleus cells, ablation produced significantly greater levels of IL-8 at 3 days and 6 days, Hsp70 at 3 days but not 6 days, and NO at 6 days. PGE2 was also increased at 3 days and 6 days but not significantly. For IL-1-stimulated annulus cells, IL-6 and NO in the ablation group were decreased at 3 days relative to the control group. However, IL-6, IL-8, PGE2, and Hsp70 were significantly increased in the 6-day ablation group. For degenerated nucleus cells, IL-6, IL-8, and TNF-alpha were significantly decreased in the ablation group at both 3 days and 6 days. Ablation resulted in reduced PGE2 at 3 days but not 6 and reduced Hsp70 and NO at 6 days., Conclusions: The results show that electrosurgical ablation has an acute direct effect on proinflammatory mediator production by disc cells. The effect produced depends on disc cell phenotype, the mediator, and time. These direct biologic effects may be a mechanism of pain relief after percutaneous discectomy using electrosurgical ablation. However, the measured responses are limited to the short-term (1 week), and the existence of a prolonged effect remains to be determined.

Study Design: Descriptive review., Objectives: To describe the role of pay-for-performance as a health care policy that has a significant influence on the management of spinal disorders, and to consider parameters of quality measure that are likely to optimize the efficacy of a pay-for-performance system as applied to spine care., Summary of Background Data: Pay-for-performance arrangements have been adopted in many areas of medicine with limited evidence for improvement in quality of care. There is an important role for a system that will improve quality of care in the management of spinal disorders. The absence of accepted evidence-based approaches to the management of spinal disorders makes the choice of parameters to measure for quality difficult., Results: Performance parameters to consider include a continuum of measures from process variables that focus on a discrete component of the health care experience, to outcome variables that encompass the end result of care. There are advantages and limitations to each parameter discussed., Conclusion: A pay-for-performance system in the management of spinal disorders should include both process variables that measure safety and outcome variables that reflect the end result of care.

The treatment of adult spinal deformities often involves long thoracolumbar fusions into the lower lumbar spine, raising the debate of selecting L5 or S1 as the caudal extent of the fusion. The presence of significant deformity or degenerative pathologic findings at L5-S1 mandates fusion to the sacrum. Fusion to the sacrum is of larger magnitude than fusion to L5 and introduces a higher surgical complication rate. Advantages of ending the fusion at L5 include preservation of motion, avoiding the high complication rate associated with fusion to the sacrum, and possibly avoiding a second operation. Complications with fusion to L5 include possible loss of fixation and subsequent disc degeneration at L5-S1, however, leading to possible pain and loss of sagittal balance and the need for revision surgery. To date, the functional consequences of an open disc space beneath long constructs remain poorly defined, and there is no firm evidence in the literature guiding the surgeon's choice. The issues and evidence guiding the decision to fuse to L5 or S1 are examined in this article.

In recent decades American medicine has undergone tremendous changes. Numerous reimbursement and systems approaches to controlling medical inflation and improving quality have failed to provide cost-effective, high-quality health care in most circumstances. Public and private payers are currently implementing pay for performance, a new reimbursement method linking physician pay to evidence of adherence to performance measures, to constrain costs, encourage efficiency, and maximize value for health care dollars. High-quality research regarding pay for performance and its impact is scarce, particularly in orthopaedic surgery. Although supporters argue pay for performance will remedy the fragmented, costly delivery of health services in the United States, skeptics raise concerns about disagreement over quality guidelines, financial implications for providers and hospitals, inadequate infrastructure, public reporting, system gaming, and physician support. Our survey of orthopaedic surgeons reveals limited understanding of pay for performance, marked skepticism of nonphysician stakeholders' intentions, and a strong desire for greater clinician involvement in shaping the pay for performance movement. As pay for performance will likely be a long-term change that will have an impact on every orthopaedic surgeon, clinician awareness and participation will be fundamental in creating successful pay for performance programs.

Degenerative scoliosis is a common and important cause of lumbar spine deformity in the adult. The operative management of degenerative scoliosis encompasses a spectrum of approaches, including decompression alone, or fusion that may include posterior or anterior approaches. There exists significant variability in surgical approaches to degenerative scoliosis, and evidence to support a specific approach is limited. Including the structural thoracic spine in fusions to the thoracolumbar junction has a lower rate of revision than fusions with a cephalad segment at T12 or L1. Short fusions to L5 have a low rate of revision at a minimum follow-up of 2 years. Combined anterior and posterior surgery is more effective in improving lordosis than posterior-only surgery without osteotomies. Clinical outcomes of surgery for degenerative scoliosis are variable, andwct 2 self-reported scores for pain improve more reliably than scores for function. Further investigation, including comparison of randomized or matched cohorts and measurement of outcomes related to specific preoperative complaints, will be useful in the development of an evidence-based approach to degenerative scoliosis.

Background Context: Total disc replacement is a novel approach for dynamically stabilizing a painful intervertebral segment. While this approach is gaining popularity, and several types of implants are used, the effect of disc arthroplasty on lumbar biomechanics has not been widely reported. Consequently, beneficial or adverse effects of this procedure may not be fully realized, and data for kinematic optimization are unavailable., Purpose: To characterize kinematic and load transfer modifications at L5/S1 secondary to joint replacement., Study Design: A human cadaveric biomechanical study in which the facet forces and instant axes of rotation (IAR) were measured for different spinal positions under simulated weightbearing conditions before and after total disc replacement at L5/S1 using semiconstrained (3 degrees of freedom [DOF]; Prodisc) and unconstrained (5 DOF; Charité) articulated implants., Methods: Twelve radiographically normal human cadaveric L5/S1 joints (age range 45-64 years) were tested before and after disc replacement using Prodisc II implants (Spine Solutions, Paoli, PA) in six specimens and SB Charité III (Johnson & Johnson, New Brunswick, NJ) in six other specimens. Semiconstrained fixtures in combination with a servo-hydraulic materials testing system subjected the test specimens to a physiologic combination of compression and anterior shear. Multiple intervertebral positions were studied and included up to 6 degrees of flexion, extension, and lateral bending. The IAR was calculated for every 3-degree intervals, and the force through the facet joints was simultaneously measured using flexible intra-articular sensors. Data were analyzed using repeated-measures analysis of variance., Results: During flexion/extension, the average IAR positions and directions were not significantly modified by implantation with the exception that the IAR was higher relative to S1 end plate with the Charité (p=.028). The IAR had a vertically oriented centrode throughout flexion/extension with the Prodisc (p<.001) and the Charité (p<.016). The centrode tended to be greater with the Prodisc. There was a trend that the facet force was decreased throughout flexion/extension for the Prodisc; however, this was statistically significant only at 6 degrees extension (27%, p=.013). In lateral bending, the IAR was significantly modified by Prodisc replacement, with a decreased inclination relative to S1 end plate, (ie, increased coupled axial rotation). While the IAR moved in the horizontal plane toward the side of bending, this effect was more pronounced with the Prodisc. The ipsilateral facet force was significantly increased in 6 degrees lateral bending with the Charité (85%; p=.001)., Conclusions: The degree of constraint affects post-implantation kinematics and load transfer. With the Prodisc (3 DOF), the facets were partially unloaded, though the IAR did not match the fixed geometrical center of the UHMWPE. The latter observation suggests joint surface incongruence is developed during movement. With the Charité (5 DOF), the IAR was less variable, yet the facet forces tended to increase, particularly during lateral bending. These results highlight the important role the facets play in guiding movement, and that implant constraint influences facet/implant synergy. The long-term consequences of the differing kinematics on clinically important outcomes such as wear and facet arthritis have yet to be determined.

Because the disc and facets work together to constrain spinal kinematics, changes in the instant axis of rotation associated with disc degeneration or disc replacement may adversely influence risk for facet overloading and arthritis. The relationships between L5/S1 segmental kinematics and facet forces are not well defined, since previous studies have separated investigations of spinal motion and facet force. The goal of this cadaveric biomechanical study was to report and correlate a measure of intervertebral kinematics (the centrode, or the path of the instant axis of rotation) and the facet forces at the L5/S1 motion segment while under a physiologic combination of compression and anterior shear loading. Twelve fresh-frozen human cadaveric L5/S1 joints (age range 50-64 years) were tested biomechanically under semi-constrained conditions by applying compression plus shear forces in several postures: neutral, and 3 degrees and 6 degrees of flexion, extension and lateral bending. The experimental boundary conditions imposed compression and shear representative of in vivo conditions during upright stance. The 3-D instantaneous axis of rotation (IAR) was calculated between two consecutive postures. The facet joint force was simultaneously measured using thin-film sensors placed between both facet surfaces. Variations of IAR location and facet force during motion were analyzed. During flexion and extension, the IAR was oriented laterally. The IAR intersection with the mid-sagittal plane moved cephalad relative to S1 endplate during flexion (P=0.010), and posterior during extension (P=0.001). The facet force did not correlate with posture (P=0.844). However, changes in the facet force between postures did correlate with IAR position: higher IAR's during flexion correlated with lower facet forces and vice versa (P=0.04). During lateral bending, the IAR was oblique relative to the main plane of motion and translated parallel to S1 endplate, toward the side of the bending. Overall, the facet force was increased on the ipsilateral side of bending (P=0.002). The IAR positions demonstrate that the L5 vertebral body primarily rotates forward during flexion (IAR close to vertebral body center) and rotates/translates backward during extension (IAR at or below the L5/S1 intervertebral disc). In lateral bending, the IAR obliquity demonstrated coupling with axial torsion due to resistance of the ipsilateral facet.

Study Design: A retrospective case control analysis of 48 cases of postoperative infection following spinal procedures., Objectives: Spinal procedures that became infected after surgery were analyzed to identify the significance of preoperative and intraoperative risk factors. Characterization of the nature and timing of the infections was also performed., Summary of Background Data: The rate of postoperative infection following spinal surgery varies widely depending on the nature of the procedure and the patient's diagnosis. Preoperative comorbidities and risk factors also influence the likelihood of infection., Methods: A review of 1629 procedures performed on 1095 patients revealed that a postoperative infection developed in 48 patients (4.4%). Data regarding preoperative and intraoperative risk factors were gathered from patient charts for these and a randomly selected control group of 95 uninfected patients. For analysis, these patient groups were further divided into adult and pediatric subgroups, with an age cutoff of 18 years. Preoperative risk factors reviewed included smoking, diabetes, previous surgery, previous infection, steroid use, body mass index, and alcohol abuse. Intraoperative factors reviewed included staging of procedures, estimated blood loss, operating time, and use of allograft or instrumentation., Results: The majority of infections occurred during the early postoperative period (less than 3 months). Age >60 years, smoking, diabetes, previous surgical infection, increased body mass index, and alcohol abuse were statistically significant preoperative risk factors. The most likely procedure to be complicated by an infection was a combined anterior/posterior spinal fusion performed in a staged manner under separate anesthesia. Infections were primarily monomicrobial, although 5 patients had more than 4 organisms identified. The most common organism cultured from the wounds was Staphylococcus aureus. All patients were treated with surgical irrigation and débridement, and appropriate antibiotics to treat the cultured organism., Conclusions: Aggressive treatment of patients undergoing complex or prolonged spinal procedures is essential to prevent and treat infections. Understanding a patient's preoperative risk factors may help the physician to optimize a patient's preoperative condition. Additionally, awareness of critical intraoperative parameters will help to optimize surgical treatment. It may be appropriate to increase the duration of prophylactic antibiotics or implement other measures to decrease the incidence of infection for high risk patients.

Background: Craniovertebral arthrodesis in the upper cervical spine is challenging because of the high degree of mobility afforded by this region. A novel method for achieving atlantoaxial fixation with use of polyaxial screws inserted bilaterally into the lateral masses of C1 and transpedicularly into C2 with longitudinal rod connection has recently been introduced. The question remains as to whether this technique provides adequate stability when extended cephalad to include the occiput. The purpose of this study was to determine the primary stability afforded by this novel construct and compare its stability with the current standard of bilateral longitudinal plates combined with C1-C2 transarticular screws., Methods: We used ten fresh-frozen human cadaveric cervical spines (C0-C4). Pure moment loads were applied to the occiput, and C4 was constrained during the testing protocol. We evaluated four conditions: (1) intact, (2) destabilized by means of complete odontoidectomy, (3) stabilization with longitudinal plates with C1-C2 transarticular screw fixation, and (4) stabilization with a posterior rod system with C1 lateral mass screws and C2 pedicle screws. Rigid-body three-dimensional rotations were detected by stereophotogrammetry by means of a three-camera system with use of marker triads. The range of motion data (C0-C2) for each fixation scenario was calculated, and a statistical analysis was performed., Results: Destabilization of the specimen significantly increased C0-C2 motion in both flexion-extension and lateral bending (p < 0.05). Both fixation constructs significantly reduced motion in the destabilized spine by over 90% for all motions tested (p < 0.05). No significant differences were detected between the two constructs in any of the three rotational planes., Conclusions: Both hardware systems provide equivalent construct stability in the immediate postoperative period when it is critical for the eventual success of a craniovertebral arthrodesis. On the basis of this work, we believe that the decision to use either construct should be determined by clinical rather than biomechanical concerns.

Study Design: An in vivo model was used to investigate the response of degenerated discs to various exogenous growth factors., Objectives: To study growth factor-induced alterations of the spatial and temporal patterns of disc cellularity and matrix gene expression., Summary of Background Data: Cell proliferation and proteoglycan synthesis have been stimulated by growth factors in normal disc cells, suggesting that growth factors may play a therapeutic role for degeneration. However, the response in situ in degenerated discs has not been characterized., Methods: Degeneration was induced in murine caudal discs by static compression. Degenerated discs were given single or multiple injections of growth and differentiation factor-5, transforming growth factor-beta, insulin-like growth factor-1, basic fibroblast growth factor, or saline as control. Comparisons of disc morphology, anular cell density, proliferating cells, disc height, and aggrecan and type II collagen gene expression were made either 1 week or 4 weeks after treatment., Results: In some growth and differentiation factor-5 and transforming growth factor-beta treated discs, expansion of inner anular fibrochondrocyte populations into the nucleus was observed. The cells actively expressed aggrecan and type II collagen mRNA. A lesser effect was observed for insulin-like growth factor-1 and little or no effect for basic fibroblast growth factor. Differences in cell density and proliferating cells were not significant between treatments but suggested a trend of increased cellularity and proliferation following growth factor treatment. A statistically significant increase in disc height 4 weeks after growth and differentiation factor-5 treatment was measured., Conclusions: Anular fibrochondrocytes in degenerated discs are responsive to some growth factors in vivo. The results have implications in the early intervention of disc degeneration to arrest or slow the degenerative process.

Study Design: Retrospective study of consecutive patient series., Objectives: To review the radiographic and clinical results of patients with preoperative fixed sagittal imbalance treated with combined anterior and posterior arthrodesis, and to determine factors that predict clinical outcome., Summary of Background Data: Combined anterior and posterior arthrodesis of the spine is useful in the management of fixed deformity involving the coronal and sagittal planes. The specific indications for combined surgery in the patient with regional and global imbalance have not been well defined., Methods: Retrospective review of 25 consecutive patients treated with combined anterior and posterior spinal arthrodesis. Inclusion criteria included a preoperative global sagittal imbalance of at least 5 cm. Outcome variables included radiographic measures of preoperative, postoperative, and follow-up films, and a clinical assessment using the Modified SRS Outcomes Instrument and a review of postoperative complications., Results: Twenty-five consecutive cases were reviewed. Mean age was 58 years (range 38-77), and mean follow-up was 55 months (range 24-81) for clinical and 44.5 (range 24-81) months for radiographic outcome variables. The mean preoperative sagittal imbalance was 10.5 cm (range 5.2-23.3), which improved to 2.9 cm (range 0-12.6) after surgery, and was maintained as 3.3 cm (range 0-13.5) at follow-up. Mean lumbar lordosis was -23 degrees (range +40 to -47) before surgery, and increased to -42 degrees at follow-up (range -20 degrees to -60 degrees ), an increase of 19 degrees. Patients with preoperative regional hypolordosis in the lumbar spine that was corrected surgically had the highest postoperative scores. The mean score for patient satisfaction with surgical management was 4.45 (range 2.5-5). Correlation analysis of clinical outcome domains demonstrated that patient satisfaction correlated poorly with domains of pain (r = 0.37, P = 0.1) and function (r = 0.4, P = 0.09). Within the domains, self-image showed highest correlation with patient satisfaction (r = 0.65, P = 0.006) and total score (r = 0.89, P = 0.0001)., Conclusions: Patients with global sagittal imbalance of the spine were effectively treated with a combined anterior and posterior arthrodesis as measured by radiographic parameters. Patient satisfaction with surgery, and overall clinical outcomes were best in cases that resulted in an increase in lumbar lordosis. The subset of patients with preoperative regional hypolordosis of the lumbar spine has better outcomes than those with preoperative lumbar lordosis in the physiologic range.

Study Design: Human cadaveric lumbar spines were used to assess the temperature and thermal dose distribution during intradiscal electrothermal therapy in vitro., Objectives: To determine whether intradiscal electrothermal therapy produces adequate tissue temperatures to denature annular collagen or ablate nerve cells., Summary of Background Data: Several hypothesized mechanisms for the effect of intradiscal electrothermal therapy have been suggested and include: 1) shrinkage of the nucleus and/or the annulus fibrosus by contraction of collagen fibers; and 2) thermal ablation of sensitive nerve fibers in the outer annulus., Methods: Intradiscal electrothermal therapy was performed using the standard clinical protocol on 12 lumbar specimens in a 37.0 degrees C water bath using the SpineCath by Oratec. Temperatures were recorded simultaneously at 40 different locations in the disc. Thermal dose (Equivalent Minutes 43.0 degrees C) was calculated at each temperature point., Results: The highest temperature measured (out of 520 points) was 64.0 degrees C and was within 1 mm of the heating coil. Temperatures in excess of 60 degrees C were all within 1 to 2 mm of the intradiscal electrothermal therapy catheter surface, the 50 to 60 degrees C range extended approximately 6 mm, above 48 degrees C extended approximately 7 mm, and above 45 degrees C extended to approximately 10 mm. Less than 2% of points achieved temperatures sufficient for collagen denaturation (>60 degrees C). On average, 42.5% of points accumulated >250 Equivalent Minutes 43.0 degrees C, a conservative common dose threshold for thermal necrosis of cells. The time history of thermal measurements demonstrated that the disc temperature had not reached steady state by the end of the heating protocol (16.5 minutes)., Conclusions: Except for a very limited margin (1-2 mm) around the catheter, the temperature necessary to induce collagen shrinkage was not observed within the disc. Temperatures sufficient to ablate nerves were developed in some areas but were not reliably produced in clinically relevant regions, such as the posterior annulus. These results suggest that beneficial clinical outcomes may be critically dependent on probe placement or other factors unknown.

The maintenance of mobile segments in the lumbar spine may prevent complications associated with long fusions to the sacrum and permit improved postoperative patient function and mobility. The purpose of the current study was to describe the technique of end plate osteotomy for surgical treatment of fractional curves in the lumbosacral region. This technique serves to allow the end lumbar vertebra to become horizontal, to reduce lumbosacral fractional curves, and to create a stable end vertebra above the pelvis. A review of long-term clinical and radiographic outcomes in patients treated with the technique have been satisfactory. The authors show that the techniques of end plate osteotomy with concave osteophyte excision is a clinically valuable technique for the treatment of adults with fixed lumbosacral fractional curves.

Study Design: An in vitro biomechanical study of C1-C2 posterior fusion techniques was conducted using a cadaveric model., Objective: To investigate and compare the acute stability afforded by a novel rod-based construct that uses direct polyaxial screw fixation to C1 and C2 with contemporary transarticular screw and wire techniques., Summary and Background Data: Acute stability of the atlantoaxial complex is required to achieve bony consolidation. Various forms of posterior wiring were the first standardized procedures advocated to achieve C1-C2 fixation, but because of insufficient construct stability, these techniques have been coupled with transarticular screw fixation. Significant technical difficulties, however, including the possibility of neurovascular compromise during implantation are associated with transarticular screw placement. A novel technique that uses direct polyaxial screw fixation to C1 and C2 and bilateral longitudinal rods was developed recently. However, there are no published reports detailing the biomechanical characteristics of this new construct., Methods: In this study, 10 fresh-frozen human cadaveric cervical spines with occiput (C0-C4) were used. Osteoligamentous specimens were tested in their intact condition after destabilization via odontoidectomy, and after two different Gallie wiring techniques. Each specimen was assigned to one of the two screw fixation groups. Five specimens were implanted with the polyaxial screw-rod construct and tested. The remaining five specimens were tested after application of bilateral C1-C2 transarticular screws with Gallie wiring (Magerl-Gallie technique). Pure-moment loading, up to 1.5 Nm in flexion and extension, right and left lateral bending and right and left axial rotation, was applied to the occiput, and relative intervertebral rotations were determined using stereophotogrammetry (motion analysis system). Range of motion data for all fixation scenarios were normalized to the destabilized case, and statistical analysis was performed using one-way analysis of variance with Fisher's least significant difference PLSD post hoc test for multiple comparisons., Results: The data indicate that destabilization via odontoidectomy significantly increased C1-C2 motion. Both screw techniques significantly decreased motion, as compared with both Gallie wiring methods in lateral bending and axial rotation (P < 0.02 for all) and tended toward reduced motion in flexion-extension. There was no statistically significant difference between the two screw techniques., Conclusions: The results clearly indicate the screw-rod system's equivalence in reducing relative atlantoaxial motion in a severely destabilized upper cervical spine, as compared with the transarticular screw-wiring construct. These findings mirror the previously reported clinical results attained using this new screw-rod construct. Thus, the decision to use either screw construct should be based on safety considerations rather than acute stability.

Scoliosis is commonly associated with a variety of neuromuscular disorders including conditions affecting upper and lower motor neurons as well as myopathies. Contained herein is a discussion of the spectrum of neuromuscular disorders that have been associated with scoliosis and related spinal deformities. Management, including surgical treatment in such patients, is summarized including indications, expectations, and impact on trunk balance, pulmonary function, and appearance.

Study Design: A retrospective study of adults with long fusion to the sacrum using three different fixations was performed., Objective: To compare the long-term clinical results and complications associated with three methods of lumbosacral fixation for adult spine deformities: Luque-Galveston, combined iliac and sacral screws, and sacral screws., Summary of Background Data: The preferred technique for long fusion to the sacrum is controversial, and surgery for adult deformity is fraught with significant technical difficulties and high complication rates. No clinical study compares the long-term outcome of long fusion to the sacrum using these different methods of lumbosacral fixation., Methods: This study included 54 consecutive patients who underwent elective combined anterior and posterior surgical reconstruction for adult spine deformity with a minimum follow-up period of 2 years. The patients were divided into three groups on the basis of the surgical method used for the posterior spine instrumentation. Group 1 consisted of 11 patients with smooth L-rod and segmental sublaminar wire instrumentation (Luque-Galveston technique). Group 2 consisted of 36 patients with posterior Isola segmental instrumentation and combined iliac and sacral screws. Group 3 consisted of 12 patients with Isola segmental instrumentation using bicortical sacral screws. Five patients were revised to another fixation group, giving a total of 59 cases. Radiographic, clinical results, and long-term outcome data were obtained using the modified Scoliosis Research Society (SRS) outcome instrument., Results: There were 26 late complications. Pseudarthrosis developed in 10 patients, requiring revision surgery: 4 (36%) in the Group 1, 5 (14%) in Group 2, and 1 (8.5%) in Group 3. Comparison of the modified SRS outcomes showed no difference among the groups. The average SRS grand total score was 73.4% for Group 1, 70.9% for Group 2, and 62.6% for Group 3. Overall, 76% of the patients were satisfied with their outcome. The presence of perioperative complications or pseudarthrosis significantly correlated with a lower satisfaction score (P = 0.012 and P = 0.048, respectively). Sagittal plane decompensation significantly correlated with a higher pain score (P = 0.035). Patients with prior surgeries scored lower on the self-image questions than patients with no prior surgery (P = 0.007)., Conclusions: Attention to sagittal balance is critical in these patients. Revision surgery is as safe and effective as primary surgery. According to the current findings, the Luque-Galveston fixation technique has an unacceptably high rate of pseudarthrosis, and this method is not recommended for adult deformities. Currently, the authors are using bicortical and triangulated sacral screws with an anterior interbody support in patients with good bone stock, but only when the spine balance is restored. Otherwise, they recommend using iliac fixation, although there is a higher rate of painful hardware, requiring removal.

Study Design: Retrospective review of cases in which a single solid rod was used for the anterior correction of thoracolumbar and lumbar idiopathic scoliosis in adults., Objectives: To evaluate the efficacy and outcomes in these patients., Summary of Background Data: Anterior spinal fusion with instrumentation has been found to be kyphogenic in the treatment of scoliosis. Recent reports have shown an extremely high rate of pseudarthrosis and implant failure even in adolescents who have undergone anterior spinal fusion with a single flexible or rigid rod., Methods: Fifteen consecutive adult patients with (average age, 37.5 years) had undergone anterior spinal fusion with a rigid rod were included in this study. One was lost to follow-up, leaving 14 patients with a complete radiographic follow-up of 44 months and clinical follow-up of 61 months. Patients were sent the Modified Scoliosis Research Society (SRS) Outcomes Instrument, charts were reviewed, and preoperative, postoperative, and final follow-up films of the entire spine were evaluated by independent reviewers uninvolved in the care of the patients., Results: The average preoperative major curve was 50 degrees, which improved to 16 degrees at follow-up (a 66% correction). The average correction of the upper compensatory curve and lower fractional curve were 40% and 61%, respectively. The thoracolumbar sagittal plane alignment was maintained or improved in all patients (i.e., this surgery did not induce kyphosis in any patient). On average 0.9 levels were "saved" compared with levels chosen by the authors for posterior surgery. All patients achieved a solid fusion. Follow-up Modified SRS questionnaires revealed a satisfaction score 4.5 out of a possible score of 5, a pain score of 4.1 out of 5, a self-image score of 4.1 out of 5, a function score of 4.1 out of 5, and a mental health score of 4.0 out of 5, with an overall score of 82%. All patients but one were satisfied or extremely satisfied with the results of surgery. There was no incidence of implant breakage., Conclusions: The results of anterior spinal fusion using a single solid rod in adults with idiopathic scoliosis in this series are excellent, with 100% fusion rate, no development of kyphosis, and no incidence of hardware failure.

Anterior structural support plays an important role in spinal deformity surgery. Femoral ring allografts have been widely used for this purpose despite numerous alternative implants such as cages. The literature and the authors' experience support the use of femoral ring allograft as a structural and biologic compatible implant to reconstruct anterior column defects. Pseudarthrosis rates and the rate of subsidence and loss of correction are low. No long-term studies exist that show that cages are superior in correction of deformity. Femoral ring allograft remains a viable, cost-effective, and biologic sound alternative.

Study Design: Human cadaver lumbar spines were used to assess the acute effects of intradiscal electrothermal therapy in vitro., Objective: To determine whether intradiscal electrothermal therapy produces acute changes in disc histology and motion segment stability., Summary of Background Data: Intradiscal electrothermal therapy has been introduced as an alternative for the treatment of discogenic low back pain. Several hypothesized mechanisms for the effect of intradiscal electrothermal therapy have been suggested including shrinkage of the nucleus or sealing of the anulus fibrosus by contraction of collagen fibers, and thermal ablation of sensitive nerve fibers in the outer anulus., Methods: Intradiscal electrothermal therapy was performed with the Spinecath by Oratec on 19 fresh, frozen human lumbar cadaver specimens. In a separate study, eight specimens were tested biomechanically and instrumented to map the thermal distribution, whereas five specimens were tested only biomechanically, both before and after intradiscal electrothermal therapy. Six additional specimens were heated with intradiscal electrothermal therapy, and the resulting canal was backfilled with a silicone rubber compound to allow colocalization of the catheter and anular architecture., Results: A consistent pattern of increased motion and decreased stiffness was observed. For the specimens in which only biomechanical measurements were taken, a 10% increase in the motion, on the average, at 5 Nm torque was observed after intradiscal electrothermal therapy. No apparent alteration of the anular architecture was observed around the catheter site in the intradiscal electrothermal therapy-treated discs., Conclusion: The data from this study suggest that the temperatures developed during intradiscal electrothermal therapy are insufficient to alter collagen architecture or stiffen the treated motion segment acutely.

Bone graft substitutes may be broadly classified as mineralized and demineralized preparations. This article reviews the basic science and biology underlying each preparation. A review of the clinical and experimental applications of each preparation follows. The text concludes with a review of growth factors as biological supplements.

Background Context: Intervertebral disc cell function in vitro has been linked to features of the local environment that can be related to deformation of the extracellular matrix. Epidemiologic data suggest that certain regimens of spinal loading accelerate disc degeneration in vivo. Yet, the direct association between disc cell function, spinal loading and ultimately tissue degeneration is poorly characterized., Purpose: To examine the relationships between tensile and compressive matrix strains, cell activity and annular degradation., Study Design/setting: An in vivo study of the biologic, morphologic and biomechanical consequences of static bending applied to the murine intervertebral disc. SUBJECT SAMPLE: Twenty-five skeletally mature Swiss Webster mice (12-week-old males) were used in this study., Outcome Measures: Bending neutral zone, bending stiffness, yield point in bending, number of apoptotic cells, annular matrix organization, cell shape, aggrecan gene expression, and collagen II gene expression., Methods: Mouse tail discs were loaded for 1 week in vivo with an external device that applied bending stresses. Mid-sagittal sections of the discs were analyzed for cell death, collagen II and aggrecan gene expression, and tissue organization. Biomechanical testing was also performed to measure the bending stiffness and strength., Results: Forceful disc bending induced increased cell death, decreased aggrecan gene expression and decreased tissue organization preferentially on the concave side. By contrast, collagen II gene expression was symmetrically reduced. Asymmetric loading did not alter bending mechanical behavior of the discs., Conclusions: In this model, annular cell death was related to excessive matrix compression (as opposed to tension). Collagen II gene expression was most negatively influenced by the static nature of the loading (immobilization), rather than the specific state of stress (tension or compression).

We present a study of ten consecutive patients who underwent excision of thoracic or thoracolumbar hemivertebrae for either angular deformity in the coronal plane, or both coronal and sagittal deformity. Vertebral excision was carried out anteriorly alone in two patients. Seven patients had undergone previous posterior spinal fusion. Their mean age at surgery was 13.4 years (6 to 19). The mean follow-up was 78.5 months (20 to 180). The results were evaluated by radiological review of the preoperative, postoperative and most recent follow-up films. The mean preoperative coronal curve was 78.2 degrees (30 to 115) and was corrected to 33.9 degrees (7 to 58) postoperatively, a mean correction of 59%. Preoperative coronal decompensation of 35 mm was improved to 11 mm postoperatively. Seven patients had significant coronal decompensation preoperatively, which was corrected to a physiological range postoperatively. There were no major complications and no neurological damage. We have shown that resection of thoracic and thoracolumbar hemivertebrae can be performed safely, without undue risk of neurological compromise, in experienced hands.

The radiographic and clinical results of 105 patients with symptomatic spinal deformities were categorized retrospectively based on surgical approach and type of bone autograft or allograft used for each patient's fusion surgery into seven different groups and compared with one another. The three bone autograft control groups were posterior autograft only (n = 20), anterior autograft only (n = 6), and combined anterior and posterior autograft (n = 12). The allograft groups were posterior morcellized allograft (n = 7), posterior morcellized allograft and anterior autograft (n = 11), anterior structural interbody allografts and posterior mixture of allograft and autograft (n = 37), and anterior strut allograft with posterior mixture of allograft and autograft (n = 12). Radiographs revealed high pseudoarthrosis rates for adults with a posterior-only allograft and with anterior strut allografts spanning four or more levels. Results of the self-assessment outcomes questionnaire, at a mean follow-up period of 52 months, revealed less pain and improved cosmesis for all groups, and improved function in patients who had undergone combined anteroposterior fusion. The authors conclude that posterior cancellous allograft is a poor substitute for autograft bone and that strut allografts spanning more than four levels require technique modifications to enhance their effectiveness. In general, anterior structural allografts are effective in maintaining correction, result in fusion rates comparable to those of autografts, and correlate to improved outcomes.

Although a number of studies have examined the fate of graft-derived cells during the process of fusion, there remains no consensus regarding their exact contribution to bone formation within the fusion mass. We developed two chimeric mouse isograft fusion models that allowed us to track the fate of graft cells within the host fusion bed. Cortical/cancellous bone graft (1:1 ratio of pelvic to vertebral body bone) from male mice was placed between (a) the tibia and fibula or (b) the coccygeal spine transverse processes of syngeneic female hosts. Both models were characterized histologically and histochemically. Graft-derived cells were then identified by fluorescent in situ hybridization for Y-chromosome sequences present in only the graft (male) cells. When the fusion mass was healing but not yet fused (at 1 and 2 weeks), numerous graft-derived cells were observed throughout the fusion site. The predominant graft-derived cell types included chondrocytes, osteoblasts, and fibroblasts. Chondrocytes arose from precursor cells in the graft de novo. as cartilage was not transplanted during the surgical procedure. By the time a mature fusion mass had formed (at 6 weeks), graft-derived cells persisted as osteocytes within the cortical rim surrounding the fusion mass. These osteocytes likely differentiated from graft-derived precursors that had directly formed bone, because transplanted osteocytes within cortical bone graft fragments were noted to rarely survive even at 1 and 2 weeks. Collectively, our results demonstrate for the first time that bone graft contributes cells that, in conjunction with host cells, directly form bone within the fusion mass during all phases of fusion rather than just the early phases.

Study Design: A retrospective review of a clinical series was performed., Objectives: To evaluate the incidence of adult patients who experienced spinal collapse after spinal implant removal after a long spinal arthrodesis, and to assess the various factors that may influence the likelihood of collapse after implant removal., Summary of Background Data: Published reports describing the benefits or complications of spinal implant removal do not exist. Spinal implant removal, often considered a benign procedure, is even required by the Food and Drug Administration (FDA) for certain implants., Methods: The medical records and radiographs of 116 consecutive adult patients with long posterior instrumented fusions (>5 segments) were reviewed. The information obtained included original diagnosis, patient age, number of previous surgeries before implant removal, levels of anterior and posterior fusion, time from fusion to implant removal, time from implant removal to failure, and reason for hardware removal. Radiographs also were assessed including scoliosis, lordosis, and kyphosis measurements before implant removal, after hardware removal, after failure, and after revision surgery., Results: Of 116 patients, 14 underwent spinal implant removal. Most of these patients reported prominent implants either proximally in the thoracic spine or distally in the ilium (Galveston technique). Of these 14 patients, 4 experienced increased pain and collapse after implant removal despite thorough intraoperative explorations demonstrating solid fusion., Conclusions: Spinal implant removal after long posterior fusion in adults may lead to spinal collapse and further surgery. Removal of instrumentation should be avoided or should involve partial removal of the prominent implant.