Faculty Bibliography

This article is temporarily under embargo.

Study design: This study constitutes a systematic review of the literature. Objective: The aim of this study was to identify and present all available studies that report on the costs of osteobiologics used in anterior cervical discectomy and fusion (ACDF). Methods: The literature was systematically reviewed to identify studies with specific inclusion criteria: (1) randomized controlled trials and observational studies, (2) in adult patients, (3) with herniated disc(s) or degenerative cervical spine disease, (4) reporting on either direct or indirect costs of using specific osteobiologics in an ACDF operation. (5) Only studies in English were included. The quality of the included studies was assessed using the MINORS and RoB 2.0 tools. Results: Overall, 14 articles were included; one randomized controlled trial and 13 observational studies. The most commonly used osteobiologics other than autograft/iliac crest bone graft (ICBG) were allograft and bone morphogenetic protein (BMP). None of the studies was reported to be industry-supported. There was considerable heterogeneity on the reported costs. Overall, most studies reported on surgery-related costs, such as anesthesia, operating room, surgical materials and surgeon"™s fee. Only two studies, both using allograft, reported the exact cost of the osteobiologic used (450 GBP, $700). Some of the studies reported on the cost of care during hospitalization for the surgical operation, such as radiology studies, emergency room costs, cardiologic evaluation, laboratory studies, pharmacy costs, and room costs. Only a few studies reported on the cost of follow-up, reoperation, and physical therapy and rehabilitation. Conclusion: Based on the data of this current systematic review, no recommendations can be made regarding the cost-effectiveness of using osteobiologics in ACDF. Given the high costs of osteobiologics, this remains a topic of importance. The design of future studies on the subject should include cost effectiveness.

BACKGROUND CONTEXT/BACKGROUND:Cervical fusion for degenerative disorders carries a known risk of adjacent segment disease (ASD), a complication that often requires surgical intervention to relieve symptoms. Proposed risk factors for development of ASD include both clinical and radiographic patient characteristics. However, the true impact of these risk factors is less understood due to limitations in sample sizes and loss to follow-up in individual studies. PURPOSE/OBJECTIVE:To review and critically examine current literature on the clinical risk factors associated with development of ASD in the cervical spine following ACDF. STUDY DESIGN/METHODS:Systematic Review and Meta-Analysis. METHODS:We systematically reviewed the literature in December 2019 according to the PRISMA guidelines. Methodological quality of included papers and quality of evidence were evaluated according to MINORS and GRADE framework. Meta-analysis was performed to compute the odds ratio(OR)with corresponding 95% confidence interval(CI)for dichotomous data, and mean difference(MD) with 95% CI for continuous variables. RESULTS:6,850 records were obtained using database query. Title/abstract screening resulted in 19 articles for full review, from which 10 papers met the criteria for analysis. There were no significant differences in gender (OR 0.99, 95% CI 0.75-1.30), BMI (MD -0.09, 95% CI -0.46 to 0.29), smoking (OR 1.13, 95% CI 0.80-1.59), alcohol (OR 1.07, 95% CI 0.70-1.64), diabetes (OR 0.85, 95% CI 0.56-1.31), number of segments fused (OR 0.86, 95% CI 0.64-1.16), and preoperative JOA (MD -0.50, 95% CI -1.04 to 0.04). Age (MD 3.21, 95% CI 2.00-4.42), congenital/developmental stenosis (OR 1.94, 95% CI 1.06-3.56), preoperative NDI (MD 4.18, 95% CI 2.11 to 6.26), preoperative VAS (neck) (MD 0.54 95% CI 0.09-0.99), and preoperative VAS (arm) (MD 0.98, 95% CI 0.43-1.34) were found to be statistically significant risk factors. CONCLUSION/CONCLUSIONS:Patients with congenital stenosis, advanced age, and high preoperative NDI are at increased risk of developing ASD.

PURPOSE/OBJECTIVE:Lumbar fusion is widely used to treat degenerative and traumatic conditions of the spine, with various perioperative complications. This study compared lumbar fusion complications in patients with and without chronic hyperlipidemia. METHODS:Using the MSpine division of the PearlDiver database, patients with or without chronic hyperlipidemia who underwent lumbar fusions were identified. The appropriate Current Procedural Terminology (CPT) codes identified patients with single- or multi-level lumbar spinal fusion surgeries. International Classification of Diseases (ICD-9 and ICD-10) codes identified patients with chronic hyperlipidemia. The surgical and medical complications were obtained utilizing the appropriate ICD-9, ICD-10, and CPT codes. Propensity score matching analysis was used to control for confounding factors. Chi-square test was applied to compare the incidence of complications among different groups. RESULTS:In single-level fusion group, patients with hyperlipidemia had a higher incidence of wound complications (P < 0.001), surgical site infection (P < 0.001), failed back syndrome (P < 0.001), hardware removal (P < 0.001), deep venous thrombosis/pulmonary embolism (P = 0.031), myocardial infarction (P < 0.001) cerebrovascular accident (P < 0.001), renal failure (P < 0.001), sepsis (P < 0.001), and urinary tract infection/incontinence (P < 0.001). In multi-level fusion group, patients with hyperlipidemia had a higher incidence of nerve root injury (P = 0.034), wound complications (P < 0.001), surgical site infection (P < 0.001), failed back syndrome (P < 0.001), hardware removal (P < 0.001), revision (P = 0.002), myocardial infarction (P < 0.001), renal failure (P < 0.001), and urinary tract infection/incontinence (P < 0.001). CONCLUSION/CONCLUSIONS:Following lumbar fusion, patients with chronic hyperlipidemia have an increased risk of perioperative complications, including wound complications, surgical site infection, failed back surgery syndrome, hardware removal, myocardial infarction, renal failure, and urinary tract infection/incontinence.

PURPOSE/OBJECTIVE:Failed back surgery syndrome (FBSS) is a complex and multifaceted condition associated with significant disability and morbidity. The purpose of this study was to investigate the association between FBSS with new incidences of mental health disorders. METHODS:Our cohort included patients diagnosed with FBSS within 12 months of a posterior fusion, laminectomy, or discectomy, identified using The International Classification of Disease, both Ninth and Tenth Revisions (ICD-9 and ICD-10). In the next step, both non-FBSS and FBSS-diagnosed patients were queried for the diagnosis of first-time occurrence of mental health disorders. The incidence of new mental health disorders was determined within 12-months following FBSS diagnosis. RESULTS:FBSS patients were significantly at greater risk than non-FBSS patients of developing all included mental health pathologies: Depression: OR 1.9, 95% CI 1.8-2.0, p < 0.0001); Anxiety: OR 1.5, 95% CI 1.4-1.6, p < 0.0001; Sleep Disorder: OR 1.9, 95% CI 1.7-2.0, p < 0.0001; Bipolar Disorder: OR 1.7, 95% CI 1.5-2.0 p < 0.0001; PTSD: OR 1.5, 95% CI 1.3-1.8, p < 0.0001; Panic Disorder: OR 1.8, 95% CI 1.5-2.1, p < 0.0001; Suicidal Disorder: OR 1.7 95% CI 1.4-2.0, p < 0.0001, ADHD: OR 1.3, 95% CI 1.0-1.5, p = 0.0367. CONCLUSIONS:In the current study, patients diagnosed with FBSS were at a significantly greater risk of developing mental health pathologies. While other studies have suggested pre-surgical psychological support and treatment, the current results suggest that a post-operative psychologic care may also be warranted. By identifying potential psychosocial unforeseen obstacles that occur in patients diagnosed with FBSS, more precise treatment pathways can be developed leading to improved patient outcomes.

PURPOSE/OBJECTIVE:To evaluate the trends and patterns of cervical degenerative disc disease in the cervical spine in different age groups of symptomatic patients. METHODS:Overall, 1300 symptomatic patients who had undergone cervical spine MRI from February 2019 to November 2021 were included. Pfirrmann grading was used to evaluate the IVD degeneration. Patients were divided into five groups based on age: group 1 from 20 to 29 years, group 2 from 30 to 39 years, group 3 from 40 to 49 years, group 4 from 50 to 59 years, and group 5 from 60 years and above. The patterns, severity, and the number of degenerated levels in each age group were analysed. RESULTS:The total number of degenerated IVDs (grades IV and V) increased significantly with age, ranging from 76 (4.9%) in group 1 to 677 (43.4%) in group 5. The most common degenerated levels were C2/3 (25% of the total degenerated levels) in group 1, C5/6 (29.0%) in group 2, C5/6 (33.1%) in group 3, C5/6 (31.3%) in group 4, C5/6 (24.8%), in group 5. The number of degenerated IVDs increased significantly with age (P < 0.001). In patients with two or more degenerated levels, contiguous-level disc degeneration was more common than skip lesions. CONCLUSION/CONCLUSIONS:This study evaluated the severity and pattern of cervical disc degeneration at each level in different age groups. The severity and number of degenerated levels increased significantly with increased age. Adjacent-level degeneration is more common than skip lesions in patients with more than one-level degeneration.

BACKGROUND:Failed back surgery syndrome (FBSS) is a significant cause of lumbar disability and is associated with severe patient morbidity. As the etiology of FBSS is not completely elucidated, the risk factors and evaluation of patients with FBSS remains challenging. Our analysis of a wide variety of operation types, clinical setting, and their correlation to FBSS seeks to allow fellow clinicians to be aware of the potential risk factors that leads to this devastating diagnosis. METHODS:Data were obtained for patients undergoing anterior lumbar fusion, posterior lumbar fusion, or decompression procedures from January 2010 to December 2017 from the Mariner insurance database. Rates of FBSS at six- and twelve-months post-surgery were determined for patients undergoing single/multilevel procedures according to place of service, and approach/procedure type. RESULTS:From 2010 to 2017, 102,047 patients underwent lumbar fusion or decompression surgery (54% decompression procedures, 36% posterior fusions, and 8.9% anterior fusions).5.4% of patients were diagnosed with FBSS within six months of the index procedure, and 8.4% were diagnosed with FBSS within twelve months. FBSS was higher in the inpatient (6.0%) vs. outpatient (4.3%) cohort. Among the surgical techniques, multi-level procedures had significantly higher rates of FBSS than single-level procedures, the highest being 10% in multi-level inpatient decompression procedures (p < 0.05). CONCLUSION/CONCLUSIONS:The highest rates of FBSS occurred in in the elderly (age group 70-74), for those patients whose index procedure was received in an inpatient setting, as well as for those receiving a multi-level surgery.

STUDY DESIGN/METHODS:Retrospective Cohort Study. PURPOSE/OBJECTIVE:This study evaluates the impact of patient frailty status on postoperative complications in those undergoing multi-level lumbar fusion surgery. METHODS:The Nationwide Readmission Database (NRD) was retrospectively queried between 2016 and 2017 for patients receiving multi-level lumbar fusion surgery. Demographics, frailty status, and relevant complications were queried at index admission and readmission intervals. Primary outcome measures included perioperative complications and 30-, 90-, and 180-day complication and readmission rates. Perioperative complications of interest were infection, urinary tract infection (UTI), and posthemorrhagic anemia. Secondary outcome measures included inpatient length of stay (LOS), adjusted all-payer costs, and discharge disposition. Nearest-neighbor propensity score matching for demographics was implemented to identify non-frail patients with similar diagnoses and procedures. Subgroup analysis of minimally invasive surgery (MIS) versus open surgery within frail and non-frail cohorts was conducted to evaluate differences in surgical and medical complication rates. The analysis used nonparametric Mann-Whitney U testing and odds ratios. RESULTS:Frail patients encountered higher rates perioperative complications including posthemorrhagic anemia (OR: 1.73, 95%CI 1.50-2.00, p < 0.0001), infection (OR: 2.94, 95%CI 2.04-4.36, p < 0.0001), UTI (OR: 2.57, 95%CI 2.04-3.26, p < 0.0001), and higher rates of non-routine discharge (OR: 2.07, 95%CI 1.80-2.38, p < 0.0001). Frail patients had significantly greater LOS and total all-payer inpatient costs compared to non-frail patients (p < 0.0001). Frailty was associated with significantly higher rates of 90- (OR: 1.43, 95%CI 1.18-1.74, p = 0.0003) and 180-day (OR: 1.28, 95%CI 1.03-1.60, p = 0.02) readmissions along with higher rates of wound dehiscence (OR: 2.21, 95%CI 1.17-4.44, p = 0.02) at 90 days. Subgroup analysis revealed that frail patients were at significantly higher risk for surgical complications with open surgery (16%) compared to MIS (0%, p < 0.0001). No significant differences were found between surgical approaches with respect to medical complications in both cohorts, nor surgical complications in non-frail patients. CONCLUSIONS:Frailty was associated with higher odds of all perioperative complications, LOS, and all-payer costs following multi-level lumbar fusion. Frail patients had significantly higher rates of 90 and 180-day readmission and higher rates of wound disruption at 90-days. On subgroup analysis, MIS was associated with significantly reduced rates of surgical complications specifically in frail patients. Our results suggest frailty status to be an important predictor of perioperative complications and long-term readmissions in geriatric patients receiving multi-level lumbar fusions. Frail patients should undergo surgery utilizing minimally invasive techniques to minimize risk of surgical complications. Future studies should explore the utility of implementing frailty in risk stratification assessments for patients undergoing spine surgery.

BACKGROUND CONTEXT:The concept of frailty has become increasingly recognized, and while patients with cancer are at increased risk for frailty, its influence on perioperative outcomes in metastatic spine tumors is uncertain. Furthermore, the impact of frailty can be confounded by comorbidities or metastatic disease burden. PURPOSE:The purpose of this study was to evaluate the influence of frailty and comorbidities on adverse outcomes in the surgical management of metastatic spine disease. STUDY DESIGN/SETTING:Retrospective analysis of a nationwide database to include patients undergoing spinal fusion for metastatic spine disease. PATIENT SAMPLE:A total of 1,974 frail patients who received spinal fusion with spinal metastasis, and 1,975 propensity score matched non-frail patients. OUTCOME MEASURES:Outcomes analyzed included mortality, complications, length of stay (LOS), nonroutine discharges and costs. METHODS:A validated binary frailty index (Johns Hopkins Adjusted Clinical Groups) was used to identify frail and non-frail groups, and propensity score-matched analysis (including demographics, comorbidities, surgical and tumor characteristics) was performed. Sub-group analysis of levels involved was performed for cervical, thoracic, lumbar and junctional spine. Multivariable-regression techniques were used to develop predictive models for outcomes using frailty and the Elixhauser Comorbidity Index (ECI). RESULTS:7,772 patients underwent spinal fusion with spinal metastasis, of which 1,974 (25.4%) patients were identified as frail. Following propensity score matching for frail (n=1,974) and not-frail (n=1,975) groups, frailty demonstrated significantly greater medical complications (OR=1.58; 95% CI 1.33-1.86), surgical complications (OR=1.46; 95% CI 1.15-1.85), LOS (OR=2.65; 95% CI 2.09-3.37), nonroutine discharges (OR=1.79; 95% CI 1.46-2.20) and costs (OR=1.68; 95% CI 1.32-2.14). Differences in mortality were only observed in subgroup analysis and were greater in frail junctional and lumbar spine subgroups. Models using ECI alone (AUC=0.636-0.788) demonstrated greater predictive ability compared to those using frailty alone (AUC=0.633-0.752). However, frailty combined with ECI improved the prediction of increased LOS (AUC=0.811), cost (AUC=0.768), medical complications (AUC=0.723) and nonroutine discharges (AUC=0.718). Predictive modeling of frailty in subgroups demonstrated the greatest performance for mortality (AUC=0.750) in the lumbar spine, otherwise performed similarly for LOS, costs, complications, and discharge across subgroups. CONCLUSIONS:A high prevalence of frailty existed in the current patient cohort. Frailty contributed to worse short-term adverse outcomes and could be more influential in the lumbar and junctional spine due to higher risk of deconditioning in the postoperative period. Predictions for short term outcomes can be improved by adding frailty to comorbidity indices, suggesting a more comprehensive preoperative risk stratification should include frailty.

Growth of long bones and vertebrae is maintained postnatally by a long-lasting pool of progenitor cells. Little is known about the molecular mechanisms that regulate the output and maintenance of the cells that give rise to mature cartilage. Here we demonstrate that postnatal chondrocyte-specific deletion of a transcription factor Stat3 results in severely reduced proliferation coupled with increased hypertrophy, growth plate fusion, stunting and signs of progressive dysfunction of the articular cartilage. This effect is dimorphic, with females more strongly affected than males. Chondrocyte-specific deletion of the IL-6 family cytokine receptor gp130, which activates Stat3, phenocopied Stat3-deletion; deletion of Lifr, one of many co-receptors that signals through gp130, resulted in a milder phenotype. These data define a molecular circuit that regulates chondrogenic cell maintenance and output and reveals a pivotal positive function of IL-6 family cytokines in the skeletal system with direct implications for skeletal development and regeneration.