Faculty Bibliography

Animal and human studies demonstrate the anabolic properties of low-magnitude mechanical stimulation (LMMS) in its ability to improve bone formation by enhancing the proliferation of mesenchymal stem cells and their subsequent commitment down an osteoblastic lineage. Response to mechanical strains as low as 10μɛ have been seen, illustrating the sensitivity of mechanosensory cells to mechanotransduction pathways. Applications to the spine include treatment of osteoporosis in preparation for instrumented fusion, fracture reduction in spinal cord injury patients to slow bone mineral density loss, and bone tissue engineering and enhancement of bone-implant osseointegration for pseudarthrosis and hardware failure. This review provides an overview of the fundamentals of LMMS, highlights the cellular basis and biomechanics of how mechanical strain is translated into bone formation, and then discusses current and potential applications of these concepts to spinal disorders. Mechanical signals represent a key regulatory mechanism in the maintenance and formation of bone. Developing practical clinical applications of these mechanotransduction pathways continues to be an important area of investigation in its relation to spinal pathology.

OBJECT:To investigate the efficacy of debridement, open drainage, and early feeding to treat early esophageal fistula complicated with anterior cervical surgery. METHODS:Retrospective analysis was conducted on data from 3154 patients who had undergone anterior cervical surgeries for cervical vertebra diseases between January 2006 and January 2013, in which eight patients had esophageal fistula with five males and three females. Four patients had cervical spinal injuries and four patients had cervical spondylosis. All of whom had postoperative esophageal fistulas and underwent debridement and drainage. The wounds were left open for natural drainage. No drainage devices were placed in surgical sites, and no gastric tubes were placed after surgeries. Such normal food as rice balls but not liquid or semiliquid diet was recommended. Local pressurization was conducted with fists during feeding to prevent food overflowing from orificium fistulae. RESULTS:Healed esophageal fistulas were achieved in all of the patients after 1-2 weeks treatment. There weren't recurrent esophageal fistulas and delayed infection found during 2-5 years follow-up. Good swallowing functions and stable cervical vertebrae were achieved in all of the patients. The satisfactory therapeutic effects were achieved in patients with previous neck diseases. Frankel classifications were increased by 1-2 grades in patients with cervical spinal injuries. JOA scores were increased from 9.5 before surgery to 15.5 after surgery in patients with cervical vertebra diseases. CONCLUSIONS:Early postoperative esophageal fistula complication after anterior cervical surgery can successfully be treated by debridement, drainage without gastric tube, and with early oral postoperative feeding but without fluids.

STUDY DESIGN/METHODS:This study was a retrospective, multicenter cohort study. OBJECTIVES/OBJECTIVE:Rare complications of cervical spine surgery are inherently difficult to investigate. Pseudomeningocoele (PMC), an abnormal collection of cerebrospinal fluid that communicates with the subarachnoid space, is one such complication. In order to evaluate and better understand the incidence, presentation, treatment, and outcome of PMC following cervical spine surgery, we conducted a multicenter study to pool our collective experience. METHODS:This study was a retrospective, multicenter cohort study of patients who underwent cervical spine surgery at any level(s) from C2 to C7, inclusive; were over 18 years of age; and experienced a postoperative PMC. RESULTS:Thirteen patients (0.08%) developed a postoperative PMC, 6 (46.2%) of whom were female. They had an average age of 48.2 years and stayed in hospital a mean of 11.2 days. Three patients were current smokers, 3 previous smokers, 5 had never smoked, and 2 had unknown smoking status. The majority, 10 (76.9%), were associated with posterior surgery, whereas 3 (23.1%) occurred after an anterior procedure. Myelopathy was the most common indication for operations that were complicated by PMC (46%). Seven patients (53%) required a surgical procedure to address the PMC, whereas the remaining 6 were treated conservatively. All PMCs ultimately resolved or were successfully treated with no residual effects. CONCLUSIONS:PMC is a rare complication of cervical surgery with an incidence of less than 0.1%. They prolong hospital stay. PMCs occurred more frequently in association with posterior approaches. Approximately half of PMCs required surgery and all ultimately resolved without residual neurologic or other long-term effects.

STUDY DESIGN/METHODS:A multicenter retrospective case series was compiled involving 21 medical institutions. Inclusion criteria included patients who underwent cervical spine surgery between 2005 and 2011 and who sustained a vertebral artery injury (VAI). OBJECTIVE:To report the frequency, risk factors, outcomes, and management goals of VAI in patients who have undergone cervical spine surgery. METHODS:Patients were evaluated on the basis of condition-specific functional status using the Neck Disability Index (NDI), modified Japanese Orthopaedic Association (mJOA) score, the Nurick scale, and the 36-Item Short-Form Health Survey (SF-36). RESULTS:= .20-.94). CONCLUSIONS:Vertebral artery injuries are potentially catastrophic complications that can be sustained from anterior or posterior cervical spine approaches. The data from this study suggest that with proper steps to ensure hemostasis, patients recover function at a high rate and do not exhibit residual deficits.

STUDY DESIGN/METHODS:Retrospective analysis of a nationwide private insurance database. Chi-square analysis and linear regression models were utilized for outcome measures. PURPOSE/OBJECTIVE:The purpose of this study was to investigate any relationship between lumbar degenerative disc disease, diabetes, obesity and smoking tobacco. OVERVIEW OF LITERATURE/BACKGROUND:Diabetes, obesity, and smoking tobacco are comorbid conditions known to individually have effect on degenerative disc disease. Most studies have only been on a small populous scale. No study has yet to investigate the combination of these conditions within a large patient cohort nor have they reviewed the combination of these conditions on degenerative disc disease. METHODS:A retrospective analysis of insurance billing codes within the nationwide Humana insurance database was performed, using PearlDiver software (PearlDiver, Inc., Fort Wayne, IN, USA), to identify trends among patients diagnosed with lumbar disc degenerative disease with and without the associated comorbidities of obesity, diabetes, and/or smoking tobacco. Patients billed for a comorbidity diagnosis on the same patient record as the lumbar disc degenerative disease diagnosis were compared over time to patients billed for lumbar disc degenerative disease without a comorbidity. There were no sources of funding for this manuscript and no conflicts of interest. RESULTS:<0.05). CONCLUSIONS:Diabetes, obesity and cigarette smoking each are significantly associated with an increased diagnosis of lumbar degenerative disc disease. The combination of smoking and obesity had a synergistic effect on increased rates of lumbar degenerative disc disease. Patient education and preventative care is a vital goal in prevention of degenerative disc disease within the general population.

STUDY DESIGN/METHODS:Retrospective review. OBJECTIVE:The aim of our study was to quantify the frequency of complications associated with recombinant human bone morphogenetic protein 2 (rhBMP-2) use in anterior lumbar interbody fusion (ALIF). METHODS:The orthopedic subset of the Medicare database (PearlDiver) was queried for this retrospective cohort study using International Statistical Classification of Diseases 9 (ICD-9) and Current Procedure Terminology (CPT) codes for ALIF procedures with and without rhBMP-2 between 2005 and 2010. Frequencies of complications and reoperations were then identified within 1 year from the index procedure. Complications included reoperations, pulmonary embolus, deep vein thrombosis, myocardial infarction, nerve-related complications, incision and drainage procedures, wound, sepsis, pneumonia, urinary tract infections, respiratory, heterotopic ossification, retrograde ejaculation, radiculopathy, and other medical complications. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the statistical significance. RESULTS:We identified a total of 41 865 patients who had an ALIF procedure. A total of 14 384 patients received rhBMP-2 while 27 481 did not. Overall, 6016 (41.8%) complications within 1 year from surgery were noted within the group who received rhBMP-2 and 12 950 (47.1%) complications within 1 year from surgery were recorded in those who did not receive rhBMP-2 (OR = 0.81, CI = 0.77-0.84). Overall, exposure to rhBMP-2 was associated with significantly decreased odds of complications with exception to reoperation rates (0.9% rhBMP-2 vs 1.0% no rhBMP-2; OR = 0.88, CI = 0.71-1.09) and radiculopathy (4.4% rhBMP-2 vs 4.3% no rhBMP-2; OR = 1.02, CI = 0.93-1.13). CONCLUSIONS:The use of rhBMP-2 in patients undergoing ALIF procedure was associated with a significantly decreased rate of complications. Further studies are needed to elucidate a true incidence of complication.

STUDY DESIGN/METHODS:Retrospective database review. OBJECTIVE:To analyze and report the trends and cost of posterior cervical fusions (PCFs) with and without off-label recombinant human bone morphogenetic protein-2 (rhBMP-2) in the Medicare population. METHODS:Patient records from the PearlDiver database were retrospectively reviewed from January 1, 2005, to December 31, 2012, to distinguish individuals who underwent a PCF with or without rhBMP-2. Total numbers, incidence, age, gender, geographic region, reimbursement, and length of stay were analyzed and summarized. RESULTS:The combined total of non-rhBMP-2 (n = 39 479; 85.51%) and rhBMP-2 PCF (n = 6692; 14.49%) procedures performed between 2005 and 2012 was 46 171. In general, the number of PCFs without rhBMP-2 consistently increased over time, while the number of PCFs with rhBMP-2 had only a slight increase from 2005 to 2012. On average, PCFs without rhBMP-2 were associated with $1197 higher cost than those with rhBMP-2, but the average length of stay was similar (6 days). From 2005 to 2012, the average cost for procedures with and without rhBMP-2 increased by $12 605 and $7291, respectively. The percentage of rhBMP-2 use peaked in 2007 and dwindled until 2010, and declined an additional 2.84% from 2011 to 2012. Multiple age, region, and gender tendencies were observed. CONCLUSIONS:To our knowledge, this was the first study to use the PearlDiver database to report incidence and cost trends of PCF procedures. This article provides meaningful trend data on PCFs to surgeons and clinicians, researchers, and patients, as well as functions as a beacon for future research questions.

PURPOSE:This study defined the incidence and trends of surgeries performed for patients with cervical disc degeneration with and without tobacco use disorder (TUD). METHODS:This study utilized the Humana Inc. database between 2007 and 2013 to identify patients with cervical disc degeneration with or without myelopathy. International Classification of Diseases, ninth revision (ICD-9) and Current Procedural Terminology (CPT) codes determined the initial diagnosis of disc degeneration, myelopathy status and TUD, whether patients received surgery, and TUD status at surgery. RESULTS:The prevalence of disc degeneration with myelopathy increased by 32.8% between 2007 and 2013, while disc disease with myelopathy and TUD increased by 91.6%. For patients without myelopathy, the prevalence of disc degeneration alone increased by 65.4%, and disc degeneration with myelopathy increased by 148.7%. Of myelopathy patients, 1717 (6.4%) had TUD and 1024 (59.6%) received surgery, compared to 6508 patients without TUD (26.1%). For patients without myelopathy, 11,337 (3.5%) had TUD and 787 (6.9%) underwent surgery, compared to 9716 patients (3%) without TUD. Of surgical patients, 781 (76.3%) with myelopathy and TUD still had a TUD diagnosis at surgery, and 542 (68.9%) of patients without myelopathy still had a TUD diagnosis at surgery. CONCLUSIONS:The prevalence of degenerative disc disease and TUD has increased more than disc disease alone. Patients with TUD were more likely to get surgery, and to have surgeries earlier than patients without TUD. Patients with TUD at the time of the diagnosis of their disc degeneration likely still had a TUD diagnosis at the time of surgery.

The objective was to evaluate motion, disc degeneration and Space Available for Cord (SAC) at the adjacent segments of degenerative cervical spondylolisthesis (DCS) using kinematic Magnetic Resonance Imaging (kMRI). The cervical spine kMRI of sixty-one DCS spinal levels (38 anterolisthesis and 23 retrolisthesis) were analyzed at the listhesis level and its adjacent segments in three position using kMRI. MRAnalyzer3 was used to analyze translation, angular motion and SAC. The caudad level had significantly less translation motion than the listhesis level in overall DCS or grade 2 anterolisthesis group (P<0.05). The cephalad level had significant more translational motion than the caudad level in overall DCS or grade 1 retrolisthesis group (P<0.05). For disc degeneration, the cephalad level had the least disc degeneration and showed significant difference with the listhesis level in overall DCS or overall anterolisthesis or overall retrolisthesis or grade 2 anterolisthesis or grade 1 or 2 retrolisthesis (P<0.05). For SAC, the listhesis level had the narrowest space in overall DCS groups. In neutral position, grade 1 anterolisthesis had significantly larger SAC at the listhesis and the cephalad level than grade 1 retrolisthesis (P<0.05). In conclusion, DCS affected cervical spine motion and kinematics. Grade 1 retrolisthesis showed tendency of narrower SAC at the cephalad level more than the same grade anterolisthesis. The likelihood of the adjacent segment disease and spinal cord compression are higher in both grade 2 anterolisthesis and retrolisthesis.

PURPOSE:The aim of our study was to determine the effect of Oxy133 and rhBMP2 on fusion rates and new bone formation in a rat posterolateral fusion (PLF) model. Furthermore, we examined whether Oxy133 could inhibit the adipogenesis that is often present in rhBMP2-induced fusions. METHODS:Sixty-four male Lewis rats underwent two levels PLF (L3-L5). All animals were randomly divided into eight groups based on the test compound that they received: control (DMSO), low-dose rhBMP2 (0.5 µg), high-dose rhBMP2 (5 µg), low-dose Oxy133 (5 mg), high-dose Oxy133 (20 mg), low rhBMP2 + high Oxy133, high rhBMP2 + high Oxy133, and low rhBMP2 + low Oxy133. Fusion rates were assessed 8 weeks after surgery with manual palpation and plain radiographs. Bone parameters were measured using microCT. Histology was used to evaluate adipogenesis. RESULTS:No fusion was observed in the control group. Based on the manual palpation, 100% fusion was observed in all other groups except in the low-dose rhBMP2 group (69%). At 8 weeks based on X-rays, 100% fusion was observed in the following groups: high-dose rhBMP2, low-dose Oxy133, and low rhBMP2 + low Oxy133. In the other groups, the fusion rates were between 95 and 97%, except for the low rhBMP2 group (72%). We observed similar values in BV/TV ratio at L3-4 when Oxy133 groups were compared to rhBMP2 groups alone (44.62% in high-dose Oxy133 vs. 41.47% in high-dose rhBMP2 and 47.18% in low-dose Oxy133 vs. 54.98% in low-dose rhBMP2). Trabecular thickness was slightly lower in Oxy133 groups compared to rhBMP2 when comparing low- and high-dose groups from each group (118.44 µm for high-dose Oxy133 vs. 122.39 µm for high-dose rhBMP2 and 123.51 µm for low-dose Oxy133 vs. 135.74 µm for low-dose rhBMP2). At the same time, trabecular separation was lower in Oxy133 groups compared to rhBMP2 groups. Similar trends in bone parameters were observed at the L4-5 levels. Fusion masses with low- and high-dose Oxy133 had significantly less adipocytes than rhBMP2 groups that showed robust adipocyte formation. CONCLUSION:In our study, both low-dose and high-dose Oxy133 produced solid fusions with bone densities similar or higher than in the BMP2 groups. High-dose Oxy133 group had significantly less adipocytes than high- or low-dose rhBMP2 groups. Furthermore, high-dose Oxy133 was able to significantly inhibit high-dose BMP2-induced adipogenesis when combined together. Consistent with the previous reports, our preliminary findings suggest that Oxy133 has a significant potential as an alternative to rhBMP2 in spine fusion.