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Allogenic Stem Cells in Spinal Fusion: A Systematic Review

Hsieh, Patrick C; Buser, Zorica; Skelly, Andrea C; Brodt, Erika D; Brodke, Darrel; Meisel, Hans-Joerg; Park, Jong-Beom; Yoon, S Tim; Wang, Jeffrey C
Study Design/UNASSIGNED:Systematic review. Objectives/UNASSIGNED:To review, critically appraise, and synthesize evidence on the use of allogenic stem cell products for spine fusion compared with other bone graft materials. Methods/UNASSIGNED:Systematic searches of PubMed/MEDLINE, through October 31, 2018 and of EMBASE and ClinicalTrials.gov through April 13, 2018 were conducted for literature comparing allogenic stem cell sources for fusion in the lumbar or cervical spine with other fusion methods. In the absence of comparative studies, case series of ≥10 patients were considered. Results/UNASSIGNED:From 382 potentially relevant citations identified, 6 publications on lumbar fusion and 5 on cervical fusion met the inclusion criteria. For lumbar arthrodesis, mean Oswestry Disability Index (ODI), visual analogue scale (VAS) pain score, and fusion rates were similar for anterior lumbar interbody fusion (ALIF) using allogenic multipotent adult progenitor cells (Map3) versus recombinant human bone morphogenetic protein-2 (rhBMP-2) in the one comparative lumbar study (90% vs 92%). Across case series of allogenic stem cell products, function and pain were improved relative to baseline and fusion occurred in ≥90% of patients at ≥12 months. For cervical arthrodesis across case series, stem cell products improved function and pain compared with baseline at various time frames. In a retrospective cohort study fusion rates were not statistically different for Osteocel compared with Vertigraft allograft (88% vs 95%). Fusion rates varied across time frames and intervention products in case series. Conclusions/UNASSIGNED:The overall quality (strength) of evidence of effectiveness and safety of allogenic stem cells products for lumbar and cervical arthrodesis was very low, meaning that we have very little confidence that the effects seen are reflective of the true effects.
PMCID:6512196
PMID: 31157144
ISSN: 2192-5682
CID: 5186492

Chemoprophylaxis for the Hip Fracture Patient: A Comparison of Warfarin and Low-Molecular-Weight Heparin

Trivedi, Nikunj N; Sivasundaram, Lakshmanan; Wang, Christopher; Kim, Chang Y; Buser, Zorica; Wang, Jeffrey C; Ochenjele, George
OBJECTIVE:To compare the rates of deep venous thrombosis (DVT), rates of pulmonary embolus (PE), and complication profiles of warfarin and low-molecular-weight heparin (LMWH) in patients undergoing operative fixation of hip fractures. DESIGN/METHODS:Retrospective cohort study. SETTING/METHODS:Insurance-based database of more than 22 million patient records. PATIENTS/METHODS:Adult hip fracture patients who were treated operatively and received chemoprophylaxis from 2007 to 2016. A total of 7594 patients met inclusion criteria and were available for final analysis. INTERVENTION/METHODS:Pharmacological anticoagulation with warfarin or LMWH to prevent postoperative venous thromboembolism after hip fracture surgery. MAIN OUTCOME MEASURES/METHODS:Development of DVT or PE within 30 and 90 days of surgery. RESULTS:Patients prescribed warfarin had higher rates of DVT and PE compared with those prescribed LMWH. Patients on warfarin were more likely to develop a postoperative hematoma and to be readmitted within 30 and 90 days compared with those on LMWH. Patients in both groups had similar rates of total complications. CONCLUSIONS:Patients prescribed warfarin after hip fractures had higher rates of DVT and PE compared with those prescribed LMWH, although both agents had similar complication profiles. LEVEL OF EVIDENCE/METHODS:Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
PMID: 31008818
ISSN: 1531-2291
CID: 5186462

The Impact of Cervical Spinal Muscle Degeneration on Cervical Sagittal Balance and Spinal Degenerative Disorders

Tamai, Koji; Grisdela, Phillip; Romanu, Joshua; Paholpak, Permsak; Nakamura, Hiroaki; Wang, Jeffrey C; Buser, Zorica
STUDY DESIGN:This is a retrospective analysis of kinematic magnetic resonance images (kMRI). OBJECTIVE:To assess the association of cervical paraspinal muscle with cervical sagittal balance and degenerative spinal disorders. SUMMARY OF BACKGROUND DATA:Although the effects of spinal disorders and cervical imbalance on patient's symptoms have been well described, the relationship of the cervical muscle quality and volume to cervical imbalance or spinal disorders is not well established. MATERIALS AND METHODS:In total, 100 kMRI taken in a neutral weight-bearing position were analyzed. The adjusted cross-sectional area ratio (aCSA ratio: the value of muscle CSA divided by the vertebral CSA) and fat infiltration ratio of the transversospinalis muscles at C4 and C7 vertebral levels were measured using axial slice of kMRI. The correlation with cervical balance parameters [Oc-C2 angle, C2-C7 angle, C7-T1 angle, C7 slope, T1 slope, cranial tilt, cervical tilt, thoracic inlet angle (TIA), and neck tilt] and cervical degenerative disorders (disk degeneration, Modic change, and spondylolisthesis) were evaluated. RESULTS:The aCSA ratio at C4 correlated with C2-C7 angle (r=0.267), C7 slope (r=0.207), T1 slope (r=0.221), disk degeneration at C3-4, C4-5, C5-6 (r=-0.234, -0.313, -0.262) and spondylolisthesis at C3 (anterior: r=-0.206, posterior: r=-0.249). The aCSA ratio at C7 correlated with disk degeneration at C3-4, C4-5, C5-6, C6-7 (r=-0.209, -0.294, -0.239, -0.209). The fat infiltration ratio at C4 correlated with TIA (r=0.306) and neck tilt (r=0.353), likewise the ratio at C7 correlated with TIA (r=0.270) and neck tilt (r=0.405). All correlations above were statistically significant with P<0.05. CONCLUSIONS:The paraspinal muscle volume showed significant relationship with the cervical balance parameters and disk degeneration. While, paraspinal muscle quality related to the thoracic inlet parameters. Our findings can be an important step to develop the knowledge of the association between cervical muscle and cervical degenerative disorders, as well as the sagittal balance of the cervical spine. LEVEL OF EVIDENCE:Level III.
PMID: 30762839
ISSN: 2380-0194
CID: 5186442

Kinematic characteristics of patients with cervical imbalance: a weight-bearing dynamic MRI study

Tamai, Koji; Grisdela, Phillip; Romanu, Joshua; Paholpak, Permsak; Buser, Zorica; Wang, Jeffrey C
STUDY DESIGN/METHODS:It is a retrospective analysis of 1806 consecutive cervical magnetic resonance images taken in weight-bearing flexion, neutral, and extension positions. OBJECTIVE:The aim was to identify the kinematic characteristics of patients with cervical imbalance. Additionally, factors were analysed in the neutral position that could predict the characteristics. Little is known about the kinematic characteristics during cervical flexion and extension positions of the patient with cervical imbalance (cervical sagittal vertical axis (cSVA) in neutral position ≥ 40 mm). METHODS:After evaluating the whole images, cervical imbalance group (cSVA ≥ 40 mm, n = 43) and matched control group (< 40 mm, n = 43) were created using propensity score adjusting for age, gender, and cervical alignment. They were compared for cervical motion, changes in disc bulge, and ligamentum flavum (LF) bulge from flexion to extension. Multinomial logistic regression analysis and receiver operating characteristic curve analysis were calculated to verify the predictive factors and cut-off value of the identified characteristics. RESULTS:There were no significant differences in range of motion and the change in bulged discs. There was significant difference in the presence of LF bulge from flexion to extension (p = 0.023); the incidence of LF bulge increased sharply from neutral to extension in imbalance group, while there was linear increase in control group. The canal diameter (odds ratio = 0.61, p = 0.002) and disc height (odds ratio = 1.60, p = 0.041) showed significant relationship with the segments with LF bulge observed in extension but not in neutral position in the imbalance group; the cut-off values were 10.7 mm for canal diameter (sensitivity 82.5%, specificity 66.7%) and 7.1 mm for disc height (70.8%, 58.5%). CONCLUSION/CONCLUSIONS:Patients with cervical imbalance had a stark increase in LF bulge from the neutral to extension position. Canal diameter < 10.7 mm and disc height > 7.1 mm on neutral images may predict the segments with LF bulge observed in extension, but not in the neutral position. LEVEL OF EVIDENCE/METHODS:II (Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding). These slides can be retrieved from Electronic Supplementary Material.
PMID: 30623250
ISSN: 1432-0932
CID: 5186422

Postoperative complications in adult spinal deformity patients with a mental illness undergoing reconstructive thoracic or thoracolumbar spine surgery

Shah, Ishan; Wang, Christopher; Jain, Nick; Formanek, Blake; Buser, Zorica; Wang, Jeffrey C
BACKGROUND CONTEXT:Previous studies have found an association between mental illness and poor outcomes in spine surgery, but little is known about the effects of depression and/or anxiety on the adult spinal deformity population. In addition, most relevant studies exclusively focused on the lumbar spine and had relatively small patient sizes. PURPOSE:The aim of this study was to investigate whether adult spinal deformity patients with depression and/or anxiety have an increased risk of postoperative complications and reoperation following posterior thoracolumbar spinal surgery. STUDY DESIGN/SETTING:Retrospective database study. METHODS:Adult patients (over 18 years of age) with a diagnosis of spinal deformity undergoing any reconstructive thoracic or thoracolumbar spinal procedure with a posterior approach between 2007 and 2015 Q2 were identified using Current Procedural Terminology codes to query the Pearl Diver patient record database (Pearl Diver Technologies, West Conshohocken, PA, USA). The database includes records of approximately 18 million patients across the United States having Humana insurance. Further selection of patients with depression and/or anxiety and their associated postoperative complications were identified using ICD-9 and ICD-10 diagnosis codes (International Classification of Diseases 9th-10th edition). The mental illness cohort was matched to a control group according to age, sex, and Charlson Comorbidity Index. Patient data was analyzed for reoperation rates and incidence of common postoperative complications. RESULTS:Multilevel posterolateral fusion was the most common included posterior thoracic reconstructive surgery. The mental illness cohort (n = 327) had significantly increased rates of infection (odds ratio [OR] = 1.743, p = .022) and respiratory complications (OR = 1.492, p = .02) at the 90-day postoperative period. The rates of incision and drainage (OR = 1.379, p = .475) and pneumonia (OR = 1.22, p = .573) were increased in the mental illness cohort at the 90-day postoperative period, but not significantly. There were no significant differences in complication and reoperation rates at 1-year postoperatively. CONCLUSIONS:Patients with spinal deformity and pre-existing depression and/or anxiety treated with a posterior thoracolumbar reconstructive spinal surgery had significantly elevated risk of postoperative infections and respiratory complications when compared with the control group.
PMID: 30296575
ISSN: 1878-1632
CID: 5186362

Reliability and Validity of the AOSpine Thoracolumbar Injury Classification System: A Systematic Review

Abedi, Aidin; Mokkink, Lidwine B; Zadegan, Shayan Abdollah; Paholpak, Permsak; Tamai, Koji; Wang, Jeffrey C; Buser, Zorica
Study Design/UNASSIGNED:Systematic review. Objectives/UNASSIGNED:The AOSpine thoracolumbar injury classification system (ATLICS) is a relatively simple yet comprehensive classification of spine injuries introduced in 2013. This systematic review summarizes the evidence on measurement properties of this new classification, particularly the reliability and validity of the main morphologic injury types with and without inclusion of the subtypes. Methods/UNASSIGNED:A literature search was performed using PubMed and Embase in September 2016. A revised version of the COSMIN checklist was used for evaluation of the quality of studies. Two independent reviewers performed all steps of the review. Results/UNASSIGNED:Nine articles were included in the final review, all of which evaluated the reliability of the ATLICS and had a fair methodological quality. The reliability of the modifiers was unknown. Overall, the quality of evidence for reliability of the morphologic and neurologic classification sections was low. However, there was moderate evidence for poor interobserver reliability of the morphologic classification when all subtypes were included, and moderate evidence for good intraobserver reliability with exclusion of subtypes. The reliability of the morphologic classification was independent of the observer's experience and cultural background. Conclusions/UNASSIGNED:ATLICS represents the most current system for evaluation of thoracolumbar injuries. Based on this review, further studies with robust methodological quality are needed to evaluate the measurement properties of ATLICS. Shortcomings of the reliability studies are discussed.
PMCID:6448204
PMID: 30984504
ISSN: 2192-5682
CID: 5186452

The future of disc surgery and regeneration

Buser, Zorica; Chung, Andrew S; Abedi, Aidin; Wang, Jeffrey C
Low back and neck pain are among the top contributors for years lived with disability, causing patients to seek substantial non-operative and operative care. Intervertebral disc herniation is one of the most common spinal pathologies leading to low back pain. Patient comorbidities and other risk factors contribute to the onset and magnitude of disc herniation. Spine fusions have been the treatment of choice for disc herniation, due to the conflicting evidence on conservative treatments. However, re-operation and costs have been among the main challenges. Novel technologies including cage surface modifications, biologics, and 3D printing hold a great promise. Artificial disc replacement has demonstrated reduced rates of adjacent segment degeneration, need for additional surgery, and better outcomes. Non-invasive biological approaches are focused on cell-based therapies, with data primarily from preclinical settings. High-quality comparative studies are needed to evaluate the efficacy and safety of novel technologies and biological therapies.
PMID: 30506089
ISSN: 1432-5195
CID: 5186402

Perioperative Invasive Vascular Catheterization Associated With Increased Risk of Postoperative Infection in Lumbar Spine Surgery: An Analysis of 114,259 Patient Records

Compton, Edward; Heindel, Patrick; Formanek, Blake; Schoell, Kyle; Buser, Zorica; Wang, Jeffrey C
STUDY DESIGN:This is a retrospective cohort study. OBJECTIVE:This study's objective was to determine whether perioperative invasive vascular catheter placement, independent of comorbid conditions, modified the risk of postoperative infection in lumbar spine surgery. SUMMARY OF BACKGROUND DATA:Infection is a risk inherent to lumbar spine surgery, with overall postoperative infection rates of 0.86%-8.5%. Patients experiencing postoperative infection have higher rates of mortality, revision surgeries, pseudarthrosis, and worsening pain and disability. METHODS:Data were collected for patients undergoing lumbar spine surgery between January 2007 and October 2015 with records in the nationwide Humana private insurance database. Patients receiving fusion, laminectomy, and discectomy were followed for 3 months from the date of surgery for surgical site infection (SSI), 6 months for subsequent incision and drainage (I&D), and 1 year for vertebral osteomyelitis (VO). Risk factors investigated included central venous catheter and arterial-line placement. RESULTS:Analysis of 114,259 patient records showed an overall SSI rate of 3.2% within 1 month and 4.5% within 3 months, overall vertebral osteomyelitis rate of 0.82%-0.83% within 1 year, and overall I&D rate of 2.8% within 6 months. Patients receiving a first-time invasive vascular catheter on the day of surgery were more likely to experience SSI within 1 month [risk ratios (RR), 2.5, 95% confidence interval (CI): 2.3-2.7], SSI within 3 months (RR, 2.4; 95% CI: 2.3-2.7), osteomyelitis within 1 year (RR, 4.2-4.3; 95% CI: 3.7-4.5), and undergo an I&D within 6 months (RR, 1.9; 95% CI: 1.8-2.0). These trends were consistent by procedure type and independent of the patient's weighted comorbidity index score (Charlson Comorbidity Index). CONCLUSIONS:Perioperative invasive vascular catheterization was significantly associated with an increased the risk of postoperative infections in lumbar spine surgery, independent of a patient's concomitant comorbidities. Therefore, in patients with an indication for invasive catheterization, surgeons should consider risks and benefits of surgery carefully. LEVEL OF EVIDENCE:Level III.
PMID: 30489332
ISSN: 2380-0194
CID: 5186392

Kinematic evaluation of thoracic spinal cord sagittal diameter and the space available for cord using weight-bearing kinematic magnetic resonance imaging

Paholpak, Permsak; Abedi, Aidin; Chamnan, Rattanaporn; Chantarasirirat, Kunlavit; Tamai, Koji; Buser, Zorica; Wang, Jeffrey C
STUDY DESIGN/METHODS:Retrospective kinematic MRI (kMRI) study. OBJECTIVE:To evaluate the dynamic changes of thoracic anterior and posterior space available for cord (SAC), and thoracic spinal cord in the dural sac in three positions. SETTING/METHODS:Expert MRI, Bellflower California; and University of Southern California, in Los Angeles, USA. METHODS:A total of 118 patients (66 males and 52 females, mean age ( ± SD) of 45.6 ± 10.6 years) who underwent thoracic spine kMRI were evaluated from T4-5 to T11-12 in flexion, neutral, and extension positions. The anterior SAC, posterior SAC, and mid-sagittal thoracic cord diameter were measured at each level from T4-5 to T11-12. Inter- and intraobserver agreements were analyzed. RESULTS:The anterior SAC was significantly narrower in flexion position compared with other positions at T8-9 to T11-12 levels (p < 0.01). The T8-9 level had significantly wider posterior SAC in flexion and extension positions compared with the neutral position (p < 0.005). However, the posterior SAC at T9-10 was narrower in extension than the neutral position (p = 0.002). Thoracic spinal cord diameter significantly increased in flexion position when compared with the neutral position at T8-9, T9-10, and T11-12 levels (p < 0.005). CONCLUSIONS:Thoracic spinal cord had dynamic changes with positions. In flexion position, the thoracic cord at T8-9 and below tended to move anteriorly, getting closer to the vertebral body and intervertebral disc. The mid-sagittal diameter of the thoracic cord increased in flexion position at the levels below T8-9. In the presence of lesions in anterior epidural space, the risk of spinal cord compression is higher in flexion position, especially at levels below T8-9.
PMID: 30250227
ISSN: 1476-5624
CID: 5186342

Depression Increases the Rates of Neurological Complications and Failed Back Surgery Syndrome in Patients Undergoing Lumbar Spine Surgery

Schoell, Kyle; Wang, Christopher; D'Oro, Anthony; Heindel, Patrick; Lee, Larry; Wang, Jeffrey C; Buser, Zorica
STUDY DESIGN:This was a retrospective database study. OBJECTIVE:The aim of this study was to use a large sample to accurately determine risk factors and rates of neurological complications in patients undergoing commonly performed lumbar spine surgeries. SUMMARY OF BACKGROUND DATA:Damage to neurological structures and failed back surgery syndrome (FBSS) are among the most feared complications of lumbar spine surgery. Despite the large impact on quality of life these complications have, reported rates of neurological complications vary immensely, ranging from 0.46% to 24%. MATERIALS AND METHODS:Data were obtained for patients undergoing initial posterior lumbar interbody fusion, transforaminal lumbar interbody fusion, anterior lumbar interbody fusion, posterolateral fusion, discectomy, and laminectomy procedures from January 2007 to June 2015 covered by the nationwide insurance carrier Humana. Patient records were analyzed to determine rates of dural tear, damage to nervous tissue, cauda equina syndrome, neurogenic bowel/bladder, and FBSS following each procedure. Rates were determined for patients undergoing single/multilevel procedures, by age, and for patients with a previous diagnosis of depression to determine the influence these factors had on the risk of neurologic complications. RESULTS:Analysis of 70,581 patient records revealed a dural tear rate of 2.87%, damage to the nervous tissue of 1.47%, cauda equina syndrome of 0.75%, neurogenic bowel or bladder of 0.45%, and FBSS of 15.05% following lumbar spine surgery. The incidence of complications was highest for patients undergoing multilevel procedures and posterior fusion. Depression was a significant risk factor for FBSS (risk ratio, 1.74; P<0.0001), damage to nervous tissue (1.41; P<0.0001), and dural tear (1.15; P<0.0001), but had no impact on risk of cauda equina syndrome or neurogenic bowel or bladder. Increased age was associated with higher rates of dural tear and damage to nervous tissue. CONCLUSIONS:Patients with a history of depression are at significantly increased risk for neurologic complications following lumbar spine surgery and should be managed accordingly.
PMID: 30346309
ISSN: 2380-0194
CID: 5186382