Faculty Bibliography

STUDY DESIGN/METHODS:Consensus-building using the Delphi and nominal group technique. OBJECTIVE:To establish best practice guidelines using formal techniques of consensus building among a group of experienced spinal deformity surgeons to avert wrong-level spinal deformity surgery. SUMMARY OF BACKGROUND DATA/BACKGROUND:Numerous previous studies have demonstrated that wrong-level spinal deformity occurs at a substantial rate, with more than half of all spine surgeons reporting direct or indirect experience operating on the wrong levels. Nevertheless, currently, guidelines to avert wrong-level spinal deformity surgery have not been developed. METHODS:The Delphi process and nominal group technique were used to formally derive consensus among 16 fellowship-trained spine surgeons. Surgeons were surveyed for current practices, presented with the results of a systematic review, and asked to vote anonymously for or against item inclusion during three iterative rounds. Agreement of 80% or higher was considered consensus. Items near consensus (70% to 80% agreement) were probed in detail using the nominal group technique in a facilitated group meeting. RESULTS:Participants had a mean of 13.4 years of practice (range: 2-32 years) and 103.1 (range: 50-250) annual spinal deformity surgeries, with a combined total of 24,200 procedures. Consensus was reached for the creation of best practice guidelines (BPGs) consisting of 17 interventions to avert wrong-level surgery. A final checklist consisting of preoperative and intraoperative methods, including standardized vertebral-level counting and optimal imaging criteria, was supported by 100% of participants. CONCLUSION/CONCLUSIONS:We developed consensus-based best practice guidelines for the prevention of wrong-vertebral-level surgery. This can serve as a tool to reduce the variability in preoperative and intraoperative practices and guide research regarding the effectiveness of such interventions on the incidence of wrong-level surgery. LEVEL OF EVIDENCE/METHODS:Level V.

BACKGROUND:Spinopelvic fixation is an integral part of achieving solid fusion across the lumbosacral junction, especially in deformity procedures requiring substantial correction or long-segment constructs. Traditional S2-alar-iliac (S2AI) screw-placement techniques utilize fluoroscopy, increasing operative time and radiation exposure to the patient and surgeon. We describe a novel free-hand technique for S2AI screw placement in patients with adult spinal deformity. METHODS:We reviewed the records of 45 consecutive patients who underwent spinopelvic fixation performed with use of S2AI screws by the senior surgeon and various fellows or residents over a 12-month period (2015 to 2016). In each case, the S2AI screws were placed utilizing a free-hand technique without fluoroscopic or image guidance. Screw position and accuracy were assessed by intraoperative O-arm imaging and analyzed using 3-dimensional interactive manipulation of computed tomography images. RESULTS:A total of 100 screws were placed, 51 by the senior surgeon and 49 by trainees. The mean patient age was 57.4 ± 12.7 years at the time of surgery; 37 (82.2%) of the patients were female. Preoperative diagnoses included adult idiopathic scoliosis (n = 19), adult degenerative scoliosis (n = 15), flatback syndrome (n = 2), fixed sagittal imbalance (n = 6), and distal junctional kyphosis (n = 3). Five (5%) of the screws were placed with moderate to severe cortical breaches, all of which perforated the pelvis posteriorly, with no clinically notable neurovascular or visceral complications. The breach rate did not differ significantly between the senior surgeon and trainees. CONCLUSIONS:The free-hand technique for S2AI screw placement, when performed in a standardized manner, was demonstrated to be safe and reliable in constructs requiring spinopelvic fixation. The accuracy of screw placement relies on visible and palpable anatomic landmarks that obviate the need for intraoperative fluoroscopy or image guidance, potentially reducing operative time and radiation exposure. LEVEL OF EVIDENCE/METHODS:Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Osteoclasts play key roles in bone remodeling and pathologic osteolytic disorders such as inflammation, infection, bone implant loosening, rheumatoid arthritis, metastatic bone cancers, and pathological fractures. Osteoclasts are formed by the fusion of monocytes in response to receptor activators of NF-κB-ligand (RANKL) and macrophage colony stimulating factor 1 (M-CSF). Calreticulin (CRT), a commonly known intracellular protein as a calcium-binding chaperone, has an unexpectedly robust anti-osteoclastogenic effect when its recombinant form is applied to osteoclast precursors in vitro or at the site of bone inflammation externally in vivo. Externally applied Calreticulin was internalized inside the cells. It inhibited key pro-osteoclastogenic transcription factors such as c-Fos and nuclear factor of activated T cells, cytoplasmic 1 (NFATc1)-in osteoclast precursor cells that were treated with RANKL in vitro. Recombinant human Calreticulin (rhCRT) inhibited lipopolysaccharide (LPS)-induced inflammatory osteoclastogenesis in the mouse calvarial bone in vivo. Cathepsin K molecular imaging verified decreased Cathepsin K activity when rhCalreticulin was applied at the site of LPS application in vivo. Recombinant forms of intracellular proteins or their derivatives may act as novel extracellular therapeutic agents. We anticipate our findings to be a starting point in unraveling hidden extracellular functions of other intracellular proteins in different cell types of many organs for new therapeutic opportunities. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2658-2666, 2017.

BACKGROUND: Given the increasing societal focus on health care utilization and value-based care, it is essential to understand the demographic and economic data surrounding percutaneous vertebral augmentation procedures performed in the United States. Double-blinded prospective randomized controlled trials have shown no benefit to the use of vertebroplasty over a sham procedure in the treatment of vertebral fractures. Contrastingly, kyphoplasty may be beneficial when appropriately indicated. METHODS: The National Inpatient Sample (NIS) database was queried for patients who underwent either kyphoplasty (ICD-9-CM 81.66) or vertebroplasty (ICD-9-CM 81.65) procedures between 2006 and 2014 across 44 states. Demographic and economic data were obtained which included the annual number of surgeries, age, sex, insurance type, location, and frequency of routine discharge. The NIS database represents a 20% sample of discharges from U.S. hospitals, which is weighted to provide national estimates. RESULTS: In 2014, an estimated total number of 19,420 kyphoplasty and 6,130 vertebroplasty procedures were performed across the United States. The number of vertebroplasty procedures decreased 53% from 13,128 in 2008. Similarly, the number of kyphoplasty procedures decreased 17% from 23,320 in 2007. Based on payer, Medicare patients comprised 83% of those billed for kyphoplasty and vertebroplasty, and 75% of procedures were utilized in areas designated as "not low income". In 2014, patients in the South Atlantic region comprised 24% of vertebroplasty and 28% of kyphoplasty cases, far more than any other region. Additionally, kyphoplasty and vertebroplasty were more often performed in teaching facilities rather than community hospitals (60% and 67%, respectively). CONCLUSIONS: Since the publication of two double-blind, prospective randomized controlled trials showed no benefit of vertebroplasty over a sham procedure, there has been a significant decrease in both kyphoplasty and vertebroplasty procedures.

PURPOSE: To evaluate the current evidence in the literature on treatment strategies for degenerative lumbar spine fusion in patients with osteoporosis. METHODS: A systematic review of the literature from 1950 to 2015. RESULTS: The review of the literature yielded 15 studies on the effect of treatment options for osteoporosis on lumbar fusion rates. This study evaluated only degenerative lumbar spine conditions and excluded deformity patients. One study demonstrated an association between low bone mass as measured by Hounsfield units and lower fusion rates. Six studies evaluated perioperative medical treatment of osteoporosis and showed higher fusion rates in patients treated with alendronate and teriparatide. The strongest evidence was for perioperative teriparatide. Eight studies evaluated surgical treatment strategies in patients with osteoporosis and showed that cement augmentation of pedicle screws and expandable pedicle screws demonstrated improved fusion rates than traditional pedicle screws. The strongest evidence was for expandable pedicle screws. CONCLUSION: There are 15 articles evaluating osteoporosis in patients undergoing lumbar fusion and the highest level of evidence is for perioperative use of teriparatide.

Autograft, while currently the gold standard for bone grafting, has several significant disadvantages including limited supply, donor site pain, hematoma formation, nerve and vascular injury, and fracture. Bone allografts have their own disadvantages including reduced osteoinductive capability, lack of osteoprogenitor cells, immunogenicity and risk of disease transmission. Thus demand exists for tissue-engineered constructs that can produce viable bone while avoiding the complications associated with human tissue grafts. This review will focus on recent advancements in tissue-engineered bone graft substitutes utilizing nanoscale technology in spine surgery applications. An evaluation will be performed of bone graft substitutes, biomimetic 3D scaffolds, bone morphogenetic protein, mesenchymal stem cells and intervertebral disc regeneration strategies.

OBJECTIVES: The purpose of this study was to determine the cost/quality-adjusted life-year (QALY) of the operative treatment of lumbar spondylolisthesis and identify factors associated with cost-effectiveness at 2 years. METHODS: We evaluated patients who underwent surgery for spondylolisthesis. The QALY was determined from the EQ5D. Outcomes were also assessed using the Oswestry Disability Index (ODI). Surgical, neuromonitoring, and anesthesia Current Procedural Terminology (CPT) codes as well as hospital Diagnosis-Related Group codes were used to determine the Medicare direct care costs of surgery. Indirect costs were modeled based on existing literature. A discounting rate of 3% was applied. Analysis was performed to determine which factors were associated with a cost/QALY less than $100,000. RESULTS: There were 44 patients who underwent surgery for either degenerative (30) or isthmic spondylolisthesis (14). There were 27 women and 17 men, with an average age at surgery of 59.7 years (standard deviation [SD] = 14.69) and an average follow-up of 2 years (SD = 0.82). The average postoperative improvement in ODI was 24.77 (SD = 23.9), and change in QALY was 0.43 (SD = 0.30). The average cost/QALY at 2 years for direct care costs was $89,065. The average cost/QALY at 2 years for direct plus indirect costs was $112,588. Higher preoperative leg pain and greater leg pain change was associated with a cost/QALY <$100,000 (p < .005, p < .028). The cost-effective group had a higher proportion of patients with disease extent of two or more levels (p = .021). When comparing surgical techniques of anterior-posterior and posterior only, there was no difference in cost-effectiveness. CONCLUSIONS: Spondylolisthesis surgery is cost-effective at 2 years, with a QALY change of 0.43 and a direct cost/QALY of $89,065. Higher preoperative leg pain and larger extent of disease was associated with cost-effectiveness. LEVEL OF EVIDENCE: IV.

The osteoclast is an integral cell of bone resorption. Since osteolytic disorders hinge on the function and dysfunction of the osteoclast, understanding osteoclast biology is fundamental to designing new therapies that curb osteolytic disorders. The identification and study of lysosomal proteases, such as cathepsins, have shed light on mechanisms of bone resorption. For example, Cathepsin K has already been identified as a collagen degradation protease produced by mature osteoclasts with high activity in the acidic osteoclast resorption pits. Delving into the mechanisms of cathepsins and other osteoclast related compounds provides new targets to explore in osteoclast biology. Through our anti-osteoclastogenic compound screening experiments we encountered a modified version of the Cathepsin B inhibitor CA-074: the cell membrane-permeable CA-074Me (L-3-trans-(Propylcarbamoyl) oxirane-2-carbonyl]-L-isoleucyl-L-proline Methyl Ester). Here we confirm that CA-074Me inhibits osteoclastogenesis in vivo and in vitro in a dose-dependent manner. However, Cathepsin B knockout mice exhibited unaltered osteoclastogenesis, suggesting a more complicated mechanism of action than Cathepsin B inhibition. We found that CA-074Me exerts its osteoclastogenic effect within 24 h of osteoclastogenesis stimulation by suppression of c-FOS and NFATc1 pathways.

OBJECTIVE: To identify preoperative factors that lead to cost-effectiveness at 2 years' follow-up in the setting of surgical treatment for adult spinal deformity. METHODS: Retrospective analysis of a prospective, consecutive, multicenter database including 514 patients who underwent surgery for adult spinal deformity. The change in quality-adjusted life-years (QALY) was calculated from the 2-year change in Oswestry Disability Index (ODI). Medicare coding was used to determine the direct costs based on diagnosis-related group and Relative Value Unit reimbursement. Analysis was performed to determine which factors were associated with a cost/QALY less than $100,000, making the procedure cost-effective. RESULTS: The average QALY change for all patients in this study was 0.15 and the average cost/QALY was $243,761.97. A total of 56 patients (10.4%) had a cost/QALY of less than $100,000 at 2-year follow-up. Those patients were mostly female (89%), with a mean age of 60 years and the following diagnoses: 18 (32.1%) adult idiopathic scoliosis, 12 (35.7%) adult de novo scoliosis, 87 (14.3%) sagittal imbalance, and 10 (17.9%) other scoliosis. The Health-Related Quality of Life ODI and Scoliosis Research Society (SRS) instruments were all associated with cost-effectiveness except SRS-Mental. Factors associated with cost-effectiveness were age greater than 55 years, adult de novo scoliosis, prior surgery, higher preoperative sagittal vertical axis, lower maximum Cobb angles, 8 or fewer fusion levels, lower blood loss, worse global alignment classification, and global sagittal malalignment. Combined anterior-posterior surgeries were negatively associated with cost-effectiveness. Preoperative ODI scores between 60 and 70 and SRS Pain and Activity subscores more than 4 minimally clinically important difference points below the normative values had the highest percentage of cost-effective patients. CONCLUSIONS: The QALY change is 0.15 and the cost/QALY of adult deformity surgery is $243,761.97 at 2 years. Patients with higher preoperative morbidity are more likely to be cost-effective with a cost/QALY less than $100,000.

The choice among the many options of approach and adjunct techniques in planning a posterior lumbar fusion can be problematic. Debates remain as to whether solid fusion has an advantage over pseudarthrosis regarding long-term symptom deterioration and whether an instrumented or a noninstrumented approach will best serve clinically and/or cost effectively, particularly in elderly patients. Increased motion resulting in higher rates of nonunion and the use of nonsteroidal anti-inflammatory drugs have been studied in animal models and are presumed risk factors, despite the lack of clinical investigation. Smoking is a proven risk factor for pseudarthrosis in both animal models and level III clinical studies. Recent long-term studies and image/clinical assessment of lumbar fusions and pseudarthrosis show that, although imaging remains a key area of difficulty in assessment, including an instrumented approach and a well-selected biologic adjunct, as well as achieving a solid fusion, all carry important long-term clinical advantages in avoiding revision surgery for nonunion.