The Utility of Flexion-Extension Radiographs in Degenerative Cervical Spondylolisthesis.

STUDY DESIGN: Retrospective radiologic analysis. OBJECTIVE: The aim was to investigate if lateral flexion-extension radiographs identify additional cases of degenerative cervical spondylolisthesis (DCS) that would be missed by obtaining solely neutral upright radiographs, and determine the reliability of magnetic resonance imaging (MRI) in diagnosis. SUMMARY OF BACKGROUND DATA: DCS and instability can be a cause of neck pain, radiculopathy, and even myelopathy. Standard anteroposterior and lateral radiographs and MRI of the cervical spine will identify most cervical spine pathology, but spondylolisthesis and instability are dynamic issues. Standard imaging may also miss DCS in some cases. METHODS: We compared the number of patients who demonstrated cervical spondylolisthesis on lateral neutral and flexion-extension radiographs in addition to MRI. We used established criteria to define instability as ≥2 mm of listhesis on neutral imaging, and ≥1 mm of motion between flexion-extension radiographs. RESULTS: A total of 111 patients (555 cervical levels) were analyzed. In all, 41 patients (36.9%) demonstrated cervical spondylolisthesis on neutral and/or flexion-extension radiographs. Of the 77 levels of spondylolisthesis, 17 (22.1%) were missed on neutral radiographs ( P ,0.05). Twenty levels (26.0%) were missed when flexion-extension radiographs were used alone ( P =0.02). Twenty-nine levels (37.7%) of DCS identified on radiograph were missed by MRI ( P =0.004). CONCLUSIONS: Lateral flexion-extension views can be useful in the diagnosis of DCS. These views provide value by identifying a significant cohort of patients that would be undiagnosed based on neutral radiographs alone. Moreover, MRI missed 38% of DCS cases identified by radiographs. Therefore, lateral radiographs can be a useful adjunct to neutral radiographs and MRI when instability is suspected or if these imaging modalities are unable to identify the source of a patient's neck or arm pain.

Biomechanical Comparison of Capsular Repair, Capsular Shift, and Capsular Plication for Hip Capsular Closure: Is a Single Repair Technique Best for All?

BACKGROUND: In hip arthroscopy, the best capsular closure technique to prevent microinstability in some patients while preventing overconstraints in other patients has yet to be determined. PURPOSE: To evaluate the biomechanical effects of capsular repair, capsular shift, and combination capsular shift and capsular plication for closure of the hip capsule. STUDY DESIGN: Controlled laboratory study. METHODS: Eight cadaveric hips (4 male and 4 female hips; mean age, 55.7 years) were evaluated in 7 conditions: intact, vented, capsulotomy, side-to-side repair, side-to-side repair with capsular plication (interval closure between iliofemoral and ischiofemoral ligaments), capsular shift repair, and capsular shift repair with plication. Measurements, via a 360° goniometer, included internal and external rotation with 1.5 N·m of torque at 5° of extension and 0°, 30°, 60°, and 90° of flexion. In addition, the degree of maximum extension with 5 N·m of torque and the amount of femoral distraction with 40 N and 80 N of force were obtained. Repeated-measures analysis of variance and Tukey post hoc analyses were used to analyze differences between capsular conditions. RESULTS: At lower hip positions (5° of extension, 0° and 30° of flexion), there was a significant increase in external rotation and total rotation after capsulotomy versus the intact state (P < .05). At all hip flexion angles, there was a significant increase in external rotation, internal rotation, and total rotation as well as a significant increase in maximum extension after capsulotomy versus capsular shift with plication (P < .05 for all). At all flexion angles, both capsular closure with side-to-side repair (with or without plication) and capsular shift without capsular plication were able to restore rotation, with no significant differences compared with the intact capsule (P > .05). Among repair constructs, there were significant differences in range of motion between side-to-side repair and combined capsular shift with plication (P < .05). CONCLUSION: At all positions, significantly increased rotational motion was seen after capsulotomy. Capsular closure was able to restore rotation similar to an intact capsule. Combined capsular shift and plication may provide more restrained rotation for conditions of hip microinstability but may overconstrain hips without laxity. CLINICAL RELEVANCE: More advanced closure techniques or a combination of techniques may be needed for patients with hip laxity and microinstability. At the same time, simple repair may suffice for patients without these conditions.

Impact of Cirrhosis on Morbidity and Mortality After Spinal Fusion.

STUDY DESIGN: Retrospective large database study. OBJECTIVE: To determine the impact of cirrhosis on perioperative outcomes and resource utilization in elective spinal fusion surgery. METHODS: Elective spinal fusion hospitalizations in patients with and without cirrhosis were identified using ICD-9-CM codes between the years of 2009 and 2011 using the Nationwide Inpatient Sample database. Main outcome measures were in-hospital neurologic, respiratory, cardiac, gastrointestinal, renal and urinary, pulmonary embolism, wound-related complications, and mortality. Length of stay and inpatient costs were also collected. Multivariable logistic regressions were conducted to compare the in-hospital outcomes of patients with and without cirrhosis undergoing spinal fusion. RESULTS: A total of 1 214 694 patients underwent elective spinal fusions from 2009 to 2011. Oh these, 6739 were cirrhotic. Cirrhosis was a significant independent predictor for respiratory (odds ratio [OR] = 1.43, confidence interval [CI] 1.29-1.58; P < .001), gastrointestinal (OR = 1.72, CI 1.48-2.00; P < .001), urinary and renal (OR = 1.90, CI 1.70-2.12; P < 0.001), wound (OR = 1.36, CI 1.17-1.58; P < 0.001), and overall inpatient postoperative complications (OR = 1.43, CI 1.33-1.53; P < .001). Cirrhosis was also independently associated with significantly greater inpatient mortality (OR = 2.32, CI 1.72-3.14; P < .001). Cirrhotic patients also had significantly longer lengths of stay (5.35 vs 3.35 days; P < .001) and inpatient costs ($36 738 vs $29 068; P < .001). CONCLUSIONS: Cirrhosis is associated with increased risk of perioperative complications, mortality and greater resource utilization. Cirrhotic patients undergoing spinal fusion surgeries should be counseled on these increased risks. Current strategies for perioperative management of cirrhotic patients undergoing spinal fusion surgery need improvement.

Hip Fractures: Relevant Anatomy, Classification, and Biomechanics of Fracture and Fixation.

INTRODUCTION: Hip fractures represent an important health-care dilemma, costing the US$ billions annually. Hip fractures can diminish quality of life and significantly increase morbidity and mortality if not properly treated. Recent research has brought forth new information regarding treatment as well as information on emerging complications seen within the fixation constructs themselves. SIGNIFICANCE: Understanding the pathoanatomy of hip fractures and the biomechanics of surgical fixation constructs is critical for successful treatment. In this article, we review the relevant anatomy and classification of femoral neck and intertrochanteric fractures. Furthermore, the biomechanics of hip fracture fixation strategies as well as implant-related complications are addressed. RESULTS: Even though laboratory testing demonstrated that intramedullary nails have greater biomechanical stability, the clinical results between fixation constructs have been similar when the chosen implant (ie, sliding hip screw vs cephalomedullary nail) has been correctly applied to the specific fracture pattern. Recently, data have shown that when using cephalomedullary nails, there is potential for increased failure with cutout when using the helical blade versus the lag screw, with majority being the atypical "medial cutout." CONCLUSION: The goal of surgical treatment of hip fractures is surgical treatment that allows for early mobilization and weight bearing. A full understanding of the anatomy and fracture characteristics will allow the surgeon to correctly apply the right implant to allow for uneventful healing. Surgeons need to be aware, however, of complications that can arise when using specific implants. Further research is ongoing to further determine the treatments that will allow optimal cost-effective care for the geriatric patient with hip fracture.

Outcomes and Complications After Spinal Fusion in Patients With Obstructive Sleep Apnea.

STUDY DESIGN: Retrospective database study. OBJECTIVE: To investigate the impact obstructive sleep apnea (OSA) has on perioperative complications, inpatient mortality, and costs in patients undergoing spinal fusions. METHODS: Hospitalizations for spinal fusion surgery between the years 2009 and 2011 were identified using the Nationwide Inpatient Sample and grouped into patients with and without OSA. Patient demographic data, comorbidities, hospital characteristics, hospitalization outcomes, and costs were extracted and compared. Multivariable logistic regressions were conducted to compare the in-hospital outcomes of patients undergoing spinal fusion with and without OSA. RESULTS: A total of 107 451 (7.7%) OSA patients who underwent spinal fusions were identified from 2009 to 2011. Compared with patients without OSA, OSA patients were significantly older, more likely to be male, and have significantly greater comorbidity burden. Multivariable regression analysis demonstrated that OSA had a significant independent association with slightly increased respiratory (odds ratio [OR] = 1.13, confidence interval [CI] = 1.09-1.16; P < .001), urinary and renal (OR = 1.11, CI = 1.07-1.16; P < .001) or overall inpatient complications (OR = 1.05, CI = 1.02-1.05; P < .001). OSA was also independently associated with significantly lower inpatient mortality (OR = 0.39, CI = 0.33-0.45; P < .001). CONCLUSIONS: While OSA confers greater comorbidity burden and is associated with slightly higher inpatient complication rates following spinal fusions, diagnosed OSA was not an independent predictor of inpatient mortality. A cautious interpretation of this finding is that on a national level, the current methods of preoperative medical optimization and inpatient management of OSA are satisfactory.

Impact of Sickle Cell Anemia on Inpatient Morbidity After Spinal Fusion.

STUDY DESIGN: A retrospective study. OBJECTIVE: To determine the impact of sickle cell anemia on perioperative outcomes and resource utilization in elective spinal fusion surgery. SUMMARY OF BACKGROUND DATA: Sickle cell anemia has been identified as an important surgical risk factor in otolaryngology, cardiothoracic surgery, general surgery, and total joint arthroplasty. However, the impact of sickle cell anemia on elective spine surgery is unknown. METHODS: Hospitalizations for elective spinal fusion surgery between the years of 2001-2014 from the US National Inpatient Sample were identified using ICD-9-CM codes and patients were grouped into those with and without sickle cell anemia. The main outcome measures were in-hospital neurological, respiratory, cardiac, gastrointestinal, renal and urinary, pulmonary embolism, and wound-related complications and mortality. Length of stay and inpatient costs were also collected. Multivariable logistic regressions were conducted to compare the in-hospital outcomes of patients undergoing elective spinal fusion with or without sickle cell anemia. RESULTS: From a total of 4,542,719 patients undergoing elective spinal fusions from 2001 to 2014, 456 sickle cell disease patients were identified. Sickle cell anemia is a significant independent predictor for pulmonary embolism [odds ratio (OR)=7.37; confidence interval (CI), 4.27-12.71; P<0.001], respiratory complications (OR=2.36; CI, 1.63-3.42; P<0.001), wound complications (OR=3.84; CI, 2.72-5.44; P<0.001), and overall inpatient complications (OR=2.58; CI, 2.05-3.25; P<0.001). Sickle cell anemia patients also have significantly longer length of stay (7.0 vs. 3.8 d; P<0.001) and higher inpatient costs ($20,794 vs. $17,608 P<0.05). CONCLUSIONS: Sickle cell anemia is associated with increased risk of perioperative complications and greater health care resource utilization. Sickle cell anemia patients undergoing spinal fusion surgeries should be counseled on these increased risks. Moreover, current strategies for perioperative management of sickle cell anemia patients undergoing spinal fusion surgery need to be improved.

Biomechanical Comparison of C1 Lateral Mass-C2 Short Pedicle Screw-C3 Lateral Mass Screw-Rod Construct Versus Goel-Harms Fixation for Atlantoaxial Instability.

STUDY DESIGN: A biomechanical in vitro study using human cadaveric spines. OBJECTIVE: The aim of this study was to compare atlantoaxial stability and stiffness of a C1 lateral mass - C2 short pedicle - C3 lateral mass screw-rod construct versus C1 lateral mass - C2 pedicle screw-rod construct. SUMMARY OF BACKGROUND DATA: The C1 lateral mass - C2 pedicle screw-rod construct provides excellent atlantoaxial fixation, but C2 pedicle screw placement is associated with risk of vertebral artery injury. The use of shorter C2 pedicle screws may mitigate the risk of vascular injury but may result in reduced C1-C2 stabilization. Extending C1 lateral mass - C2 short pedicle screw-rod construct with C3 lateral mass screws may mitigate the risk of vascular injury without compromising C1-C2 fixation. METHODS: Seven cervical spines were tested with internal control experimental design in the following sequence: intact state, and following creation of type II odontoid fracture, the specimen was instrumented with C1 lateral mass - C2 pedicle screw fixation (C2PED), C1 lateral mass - C2 short pedicle screw fixation (C2SPED), and C1 lateral mass - C2 short pedicle - C3 lateral mass screw fixation (C2SPED-C3LM). For each condition, the angular stiffness and range of motion (ROM) with 1.5-Nm load in flexion/extension (FE), lateral bending (LB), and right/left axial rotation (RAR/LAR) were quantified. RESULTS: Instrumented conditions demonstrated significantly lower C1-C2 angular ROM and greater stiffness than the intact state. Compared with C2PED, C2SPED-C3LM demonstrated significantly lower C1-C2 ROM during FE and LB, significantly greater C1-C2 stiffness in flexion and right/left LB, similar C1-C2 ROM and stiffness in RAR/LAR, and similar stiffness in extension. C2SPED-C3LM demonstrated significantly greater atlantoaxial stabilization in the sagittal and coronal planes than C2PED construct. CONCLUSION: Compared with C2PED, C2SPED-C3LM may be a suitable alternative surgical strategy for atlantoaxial instability that provides superior atlantoaxial fixation. LEVEL OF EVIDENCE: N/A.

The Burden of Clostridium difficile after Cervical Spine Surgery.

Study Design Retrospective database analysis. Objective The purpose of this study is to investigate incidence, comorbidities, and impact on health care resources of Clostridium difficile infection after cervical spine surgery. Methods A total of 1,602,130 cervical spine surgeries from the Nationwide Inpatient Sample database from 2002 to 2011 were included. Patients were included for study based on International Classification of Diseases Ninth Revision, Clinical Modification procedural codes for cervical spine surgery for degenerative spine diagnoses. Baseline patient characteristics were determined. Multivariable analyses assessed factors associated with increased incidence of C. difficile and risk of mortality. Results Incidence of C. difficile infection in postoperative cervical spine surgery hospitalizations is 0.08%, significantly increased since 2002 (p < 0.0001). The odds of postoperative C. difficile infection were significantly increased in patients with comorbidities such as congestive heart failure, renal failure, and perivascular disease. Circumferential cervical fusion (odds ratio [OR] = 2.93, p < 0.0001) increased the likelihood of developing C. difficile infection after degenerative cervical spine surgery. C. difficile infection after cervical spine surgery results in extended length of stay (p < 0.0001) and increased hospital costs (p < 0.0001). Mortality rate in patients who develop C. difficile after cervical spine surgery is nearly 8% versus 0.19% otherwise (p < 0.0001). Moreover, multivariate analysis revealed C. difficile to be a significant predictor of inpatient mortality (OR = 3.99, p < 0.0001). Conclusions C. difficile increases the risk of in-hospital mortality and costs approximately $6,830,695 per year to manage in patients undergoing elective cervical spine surgery. Patients with comorbidities such as renal failure or congestive heart failure have increased probability of developing infection after surgery. Accepted antibiotic guidelines in this population must be followed to decrease the risk of developing postoperative C. difficile colitis.

Chronic ingestion of advanced glycation end products induces degenerative spinal changes and hypertrophy in aging pre-diabetic mice.

Intervertebral disc (IVD) degeneration and pathological spinal changes are major causes of back pain, which is the top cause of global disability. Obese and diabetic individuals are at increased risk for back pain and musculoskeletal complications. Modern diets contain high levels of advanced glycation end products (AGEs), cyto-toxic components which are known contributors to obesity, diabetes and accelerated aging pathologies. There is little information about potential effects of AGE rich diet on spinal pathology, which may be a contributing cause for back pain which is common in obese and diabetic individuals. This study investigated the role of specific AGE precursors (e.g. methylglyoxal-derivatives (MG)) on IVD and vertebral pathologies in aging C57BL6 mice that were fed isocaloric diets with standard (dMG+) or reduced amounts of MG derivatives (dMG-; containing 60-70% less dMG). dMG+ mice exhibited a pre-diabetic phenotype, as they were insulin resistant but not hyperglycemic. Vertebrae of dMG+ mice displayed increased cortical-thickness and cortical-area, greater MG-AGE accumulation and ectopic calcification in vertebral endplates. IVD morphology of dMG+ mice exhibited ectopic calcification, hypertrophic differentiation and glycosaminoglycan loss relative to dMG- mice. Overall, chronic exposure to dietary AGEs promoted age-accelerated IVD degeneration and vertebral alterations involving ectopic calcification which occurred in parallel with insulin resistance, and which were prevented with dMG- diet. This study described a new mouse model for diet-induced spinal degeneration, and results were in support of the hypothesis that chronic AGE ingestion could be a factor contributing to a pre-diabetic state, ectopic calcifications in spinal tissues, and musculoskeletal complications that are more generally known to occur with chronic diabetic conditions.

Three-dimensional Intraoperative Imaging Modalities in Orthopaedic Surgery: A Narrative Review.

Intraoperative imaging and navigation systems have revolutionized orthopaedic surgery for the spine, joints, and orthopaedic trauma. Imaging modalities such as the isocentric C-arm, O-arm imaging, and intraoperative MRI or navigation systems allow the visualization of surgical instruments and implants relative to a three-dimensional CT image or MRI. Studies show that these technologies lower the rates of implant misplacement and inadequate fracture reduction, thereby improving surgical outcomes and reducing reoperation rates. An additional benefit is reduced radiation exposure compared with that for conventional fluoroscopy. Concerns surrounding adoption of these technologies include cost and increased operating times, but improvements in design and protocol may improve the integration of these imaging modalities into the operating room.

The effect of increasing pedicle screw size on thoracic spinal canal dimensions: an anatomic study.

STUDY DESIGN: Anatomic study. OBJECTIVE: To determine whether the thoracic spinal canal diameter decreases when the pedicle is allowed to expand with increasing screw diameter. To observe whether osseous breach occurs medially or laterally. SUMMARY OF BACKGROUND DATA: Insertion of a pedicle screw that is larger in diameter than that of the native pedicle has been shown to expand the pedicle and increase biomechanical fixation strength. With this technique, there is concern for medial expansion of the pedicle causing decrease in spinal canal diameter, especially in the concavity of scoliosis, resulting in spinal cord compression. Also, large pedicle screws that are inserted correctly may still cause undetected medial bony breach during surgery. METHODS: A total of 162 pedicles from 81 thoracic vertebrae (T1-T12) of 7 fresh-frozen adult cadavers were analyzed. After undertapping the pedicle by 1 mm, pedicle screws were inserted in increasing diameter (range, 4.0-9.5 mm) bilaterally until there was an osseous breach in the pedicle. A total of 938 screws were used. Transverse spinal canal diameter and pedicle circumference were measured (in millimeters) before and after each pedicle screw placement. Photographs and fluoroscopic images of representative specimens were obtained for visual assessment. RESULTS: The average transverse spinal canal diameter was 17.7 mm. The average transverse canal diameter with the largest screw inserted before bony breach was detected was 17.6 mm (P = 0.92). The average diameter of the largest screw inserted before breach was 6.9 mm. Pedicle circumference increased from 41.8 mm before screw placement to 43.4 mm at maximal expansion before bony breach with the next sized screw. Twenty-eight pedicles did not break with 9.5-mm-diameter screws. There were 133 lateral and 1 medial breaches. CONCLUSION: Increasing pedicle screw size caused pedicle expansion laterally but did not significantly alter transverse spinal canal dimensions. When there was an osseous breach, most were lateral (99.3%). LEVEL OF EVIDENCE: N/A.

Nonoperative management of discogenic back pain: a systematic review.

STUDY DESIGN: Systematic review of the literature. OBJECTIVE: A systematic evaluation of the literature was performed to investigate current nonoperative management of the treatment of discogenic low back pain. SUMMARY OF BACKGROUND DATA: Back pain is a major health care concern with up to 39% being discogenic in origin according to one study. Nonoperative therapy is likely to be the initial treatment strategy for discogenic low back pain. METHODS: PubMed, EMBASE, and Cochrane Central Register of Controlled Trials were searched for clinical studies evaluating nonoperative methods of treating discogenic back pain that were published between 2000 and 2012. Only prospective randomized controlled studies that compared a nonsurgical intervention with sham or placebo therapy were included. After removal of duplicate citations, a total of 226 articles were initially identified from the search terms. From these, we identified 11 randomized controlled trials (RCTs) from which data analysis was performed. RESULTS: The 11 RCTs investigated traction therapy, injections, and ablative techniques. Results from 5 RCTs investigating methylene blue injection, steroid injection, ramus communicans ablation, intradiscal electrothermal therapy, and biacuplasty favored intervention over sham therapy. However, results from the study on methylene blue injections have not been replicated in other RCTs. Evaluation of the selection criteria used in the studies on ramus communicans ablation and intradiscal biacuplasty and a stratified analysis of results from the RCTs on intradiscal electrothermal therapy casts doubt on whether the conclusions from these RCTs can be applied to the general patient population with discogenic pain. CONCLUSION: There are few high-quality studies evaluating nonoperative treatments for reducing discogenic low back pain. Although conclusions from several studies favor intervention over sham, it is unclear whether these interventions confer stable long-term benefit. There is some promise in newer modalities such as biacuplasty; however, more inclusive studies need to be performed.

Cost-effective studies in spine surgeries: a narrative review.

BACKGROUND CONTEXT: Although the pathologic processes that affect the spine remain largely unchanged, our techniques to correct them continue to evolve with the development of novel medical and surgical interventions. Although the primary purpose of new technologies is to improve patients' quality of life, the economic impact of such therapies must be considered. PURPOSE: To review the available peer-reviewed literature on spine surgery that addresses the cost-effectiveness of various treatments and technologies. STUDY DESIGN: A narrative literature review. METHODS: Articles published between January 1, 2000 and December 31, 2012 were selected from two Pubmed searches using keywords cost-effectiveness AND spine (216 articles) and cost analysis AND spine (358 articles). Relevant articles on cost analyses and cost-effectiveness were selected by the authors and reviewed. RESULTS: Cervical and lumbar surgeries (anterior cervical discectomy and fusion, standard open lumbar discectomy, and standard posterior lumbar laminectomy) are reasonably cost effective at 2 years after the procedure (<100,000 US dollars per quality-adjusted life years gained) and become more cost effective with time because of sustained clinical improvements with relatively low additional incurred costs. The usage of transfusion avoidance technology is not cost effective because of the low risk of complications associated with allogenic transfusions. Although intraoperative neuromonitoring and imaging modalities are both cost saving and cost-effective, their cost-effectiveness is largely dependent on the baseline rate of neurologic complications and implant misplacement, respectively. More rigorous studies are needed to evaluate the cost-effectiveness of recombinant bone morphogenetic protein. CONCLUSIONS: An ideal new technology should be able to achieve maximal improvement in patient health at a cost that society is willing to pay. The cost-effectiveness of technologies and treatments in spine care is dependent on their durability and the rate and severity of the baseline clinical problem that the treatment was designed to address.

Detrimental effects of discectomy on intervertebral disc biology can be decelerated by growth factor treatment during surgery: a large animal organ culture model.

BACKGROUND CONTEXT: Lumbar discectomies are common surgical interventions that treat radiculopathy by removing herniated and loose intervertebral disc (IVD) tissues. However, remaining IVD tissue can continue to degenerate resulting in long-term clinical problems. Little information is available on the effects of discectomy on IVD biology. Currently, no treatments exist that can suspend or reverse the degeneration of the remaining IVD. PURPOSE: To improve the knowledge on how discectomy procedures influence IVD physiology and to assess the potential of growth factor treatment as an augmentation during surgery. STUDY DESIGN: To determine effects of discectomy on IVDs with and without transforming growth factor beta 3 (TGFß3) augmentation using bovine IVD organ culture. METHODS: This study determined effects of discectomy with and without TGFß3 injection using 1-, 6-, and 19-day organ culture experiments. Treated IVDs were injected with 0.2 µg TGFß3 in 20 µL phosphate-buffered saline+bovine serum albumin into several locations of the discectomy site. Cell viability, gene expression, nitric oxide (NO) release, IVD height, aggrecan degradation, and proteoglycan content were determined. RESULTS: Discectomy significantly increased cell death, aggrecan degradation, and NO release in healthy IVDs. Transforming growth factor beta 3 injection treatment prevented or mitigated these effects for the 19-day culture period. CONCLUSIONS: Discectomy procedures induced cell death, catabolism, and NO production in healthy IVDs, and we conclude that post-discectomy degeneration is likely to be associated with cell death and matrix degradation. Transforming growth factor beta 3 injection augmented discectomy procedures by acting to protect IVD tissues by maintaining cell viability, limiting matrix degradation, and suppressing NO. We conclude that discectomy procedures can be improved with injectable therapies at the time of surgery although further in vivo and human studies are required.

Utilization trends of cervical artificial disc replacement after FDA approval compared with anterior cervical fusion: adoption of new technology.

STUDY DESIGN: Epidemiologic study. OBJECTIVE: To compare the utilization of anterior cervical discectomy and fusion (ACDF) versus cervical disc arthroplasty (CDA) in terms of patient and hospital characteristics during the 3 years after Food and Drug Administration (FDA) approval of CDA devices in 2007. SUMMARY OF BACKGROUND DATA: There was a surge in CDA adoption in the 3 years prior to FDA approval of CDA devices in 2007. However, utilization trends of CDA versus ACDF since the FDA approval are unknown. METHODS: The Nationwide Inpatient Sample database was used to identify CDA and ACDF procedures performed in the United States in the 3 years after FDA approval of CDA devices (2008-2010). The frequencies of CDA and ACDF were estimated, stratified by patient and hospital characteristics. Average length of hospital stay and total charges and costs were estimated. Multivariable analysis was performed to identify patient and hospital characteristics associated with CDA utilization. RESULTS: In the 3 years after FDA approval of cervical disc devices, population-adjusted growth rates for CDA and ACDF were 4.9% and 11.8%, respectively (P = 0.6977). Female, African American and Medicaid patients were less likely to receive CDA. CDA was less likely to be performed in patients with cervical spondylotic changes and more likely to be performed in younger and healthier patients. CDA was less likely to be performed in the Midwestern United States or in public hospitals. CONCLUSION: The prevalence of CDA increased in the 3 years after FDA approval with a growth rate that is approximately twice than that for ACDF. Although there seems to be CDA adoption, CDA growth seemed to have reached a plateau and ACDF still remained the dominant surgical strategy for cervical disc disease. Possible regional, racial, and sex disparities in CDA utilization and a more strict approach in the selection of CDA over traditional ACDF may have impeded rapid adoption of CDA. LEVEL OF EVIDENCE: 3.

Utilization trends of cervical artificial disc replacement during the FDA investigational device exemption clinical trials compared to anterior cervical fusion.

While anterior cervical discectomy and fusion (ACDF) is the gold standard surgical treatment for cervical disc disease, concerns regarding adjacent segment degeneration lead to the development of cervical disc arthroplasty (CDA). This study compares the utilization trends of CDA versus ACDF during the period of the Food and Drug Administration Investigational Device Exemption clinical trials from 2004 to 2007. The Healthcare Cost and Utilization Project Nationwide Inpatient Sample database was used to identify CDA and ACDF procedures performed in the USA between 2004 and 2007. The prevalence of CDA and ACDF procedures was estimated and stratified by age, sex, diagnosis, census region, payor class, and hospital characteristics. The average length of hospital stay, total charges, and costs were also estimated. The number of CDA surgeries significantly increased annually from 2004 to 2007 and mostly took place at urban non-teaching hospitals. There were no regional differences between CDA and ACDF utilization. There was no difference between sex or admission type between CDA and ACDF patients. ACDF patients were older and had more diabetes, hypertension, and chronic obstructive pulmonary disease. CDA patients were more likely to be discharged home and had shorter hospital stays but had a higher rate of deep venous thrombosis than ACDF patients. Significantly more CDA patients had private insurance while more ACDF patients had Medicare. The average cost was higher for ACDF than CDA. While ACDF dominated surgical intervention for cervical disc disease during the trial period, CDA utilization increased at a significantly greater rate suggesting rapid early adoption.

Broad overexpression of ribonucleotide reductase genes in mice specifically induces lung neoplasms.

Ribonucleotide reductase (RNR) catalyzes the rate-limiting step in nucleotide biosynthesis and plays a central role in genome maintenance. Although a number of regulatory mechanisms govern RNR activity, the physiologic effect of RNR deregulation had not previously been examined in an animal model. We show here that overexpression of the small RNR subunit potently and selectively induces lung neoplasms in transgenic mice and is mutagenic in cultured cells. Combining RNR deregulation with defects in DNA mismatch repair, the cellular mutation correction system, synergistically increased RNR-induced mutagenesis and carcinogenesis. Moreover, the proto-oncogene K-ras was identified as a frequent mutational target in RNR-induced lung neoplasms. Together, these results show that RNR deregulation promotes lung carcinogenesis through a mutagenic mechanism and establish a new oncogenic activity for a key regulator of nucleotide metabolism. Importantly, RNR-induced lung neoplasms histopathologically resemble human papillary adenocarcinomas and arise stochastically via a mutagenic mechanism, making RNR transgenic mice a valuable model for lung cancer.