Lionel N. Metz

Porcine Intervertebral Disc Repair Using Allogeneic Juvenile Articular Chondrocytes or Mesenchymal Stem Cells

Tissue engineering strategies for intervertebral disc repair have focused on the use of autologous disc-derived chondrocytes. Difficulties with graft procurement, harvest site morbidity, and functionality, however, may limit the utility of this cell source. We used an in vivo porcine model to investigate allogeneic non-disc-derived chondrocytes and allogeneic mesenchymal stem cells (MSCs) for disc repair. After denucleation, lumbar discs were injected with either fibrin carrier alone, allogeneic juvenile chondrocytes (JCs), or allogeneic MSCs. Discs were harvested at 3, 6, and 12 months, and cell viability and functionality were assessed qualitatively and quantitatively. JC-treated discs demonstrated abundant cartilage formation at 3 months, and to a lesser extent at 6 and 12 months. For the carrier and MSC-treated groups, however, there was little evidence of proteoglycan matrix or residual notochordal/chondrocyte cells, but rather a type I/II collagen-enriched scar tissue. By contrast, JCs produced a type II collagen-rich matrix that was largely absent of type I collagen. Viable JCs were observed at all time points, whereas no evidence of viable MSCs was found. These data support the premise that committed chondrocytes are more appropriate for use in disc repair, as they are uniquely suited for survival in the ischemic disc microenvironment.

Histomorphometric analysis of the effects of osteocyte density on osteonal morphology and remodeling

Osteocytes, the most abundant cells in the cortical bone matrix, are thought to have mechanosensory and chemosensory regulatory roles. Marotti theorized that osteocytes signal to osteoblasts to recruit them into the osteocyte lineage. Martin extended this theory, assuming that osteocytes display a general inhibitory effect on osteoblast function. The current study provides a quantitative analysis of the relationships between osteonal osteocyte density (Ot.N/BV), wall width (W.Wi), individual osteon porosity (IOP), and formation period (FP) in ulnar cortices from sheep labeled with tetracycline and calcein double labels. We postulated that osteocytes inhibit refilling so that the osteon wall width is thin enough, and the haversian canal is large enough, to allow adequate delivery of nutrients to the osteocytes throughout the forming and completed osteon. Therefore we tested the hypotheses that Ot.N/BV correlates negatively to FP and W.Wi, and positively to IOP, and that FP correlates positively with W.Wi. We found that Ot.N/BV correlated positively with IOP (P < 0.0001) and W.Wi correlated positively with FP (P < 0.0001). Significant negative correlations were observed between Ot.N/BV and both W.Wi (P < 0.0001) and FP (P = 0.006). These data support the general hypothesis that osteocytes contribute to the regulation of osteon morphology via the control of refilling rate and formation period, and the specific hypotheses that, for a given cement line diameter, high osteocyte density (1) reduces the rate of refilling and decreases the formation period and (2) decreases wall width and increases individual osteon porosity.

Complications of Morbid Obesity in Total Joint Arthroplasty: Risk Stratification Based on BMI

This study stratifies complication risk in primary total joint arthroplasty (TJA) based on body mass index (BMI). Demographics, co-morbidities, perioperative variables, and complications were reviewed for 22,808 patients. Chi-squared, one-way ANOVA, univariate and multivariable regression analysis were performed. Increasing BMI led to an increase (P<0.05) in combined complications, acute kidney injury (AKI), cardiac arrest (CA), reintubation, reoperation, and superficial infection (SI). Univariate analysis for BMI>40 revealed an increase in combined complications (15.21-vs-17.40%), AKI (1.93-vs-3.87%), CA (0.22-vs-0.57%), reintubation (0.47-vs-0.95%), reoperation (2.36-vs-3.37%), and SI (0.82-vs-1.65%). Multivariable regression showed BMI>40 as an independent predictor for combined complications (OR=1.18), AKI (OR=1.79), CA (OR=3.94), reintubation (OR=2.56), reoperation (OR=1.44), and SI (OR=2.11). Morbid obesity confers increased risk for complications in TJA.

Computer-assisted surgical planning and image-guided surgical navigation in refractory adult scoliosis surgery: case report and review of the literature.

Study Design. Case report and literature review. Objective. In this case report, we present the utility of computer-assisted surgical planning and image-guided surgical navigation in the planning and execution of a major osteotomy to correct severe kyphoscoliosis. Summary of Background Data. Computer-assisted surgical planning is useful to appreciate the three-dimensional nature of scoliotic deformities and allows for operative maneuvers to be simulated on a computer before their implementation in the operating room. Image-guided surgical navigation improves surgical accuracy and can help translate a virtual surgical plan to the operative setting. Methods. We report the case of a 38-year-old woman with severe, congenital kyphoscoliosis refractory to many previous surgeries, who presents with moderate progressive myelopathy and severe pain attributable to a sharp angular deformity at T12. Three-dimensional computed tomography reconstruction and computer-assisted surgical planning were used to determine the optimal corrective osteotomy. The surgical plan was translated to the operating room where a posterior vertebrectomy and instrumented correction were executed with the aid of image-guided surgical navigation. Results. The osteotomy was safely performed resulting in improved sagittal and coronal alignments, as well as, correction of the sharp kyphoscoliotic deformity at the thoracolumbar junction. At 6-month follow-up, the patients myelopathy and pain had largely resolved and she expressed high satisfaction with the procedure. Conclusion. We advocate this novel application of virtual surgical planning and intraoperative surgical navigation to improve the safety and efficacy of complex spinal deformity corrections.

Alterations in intervertebral disc composition, matrix homeostasis and biomechanical behavior in the UCD-T2DM rat model of type 2 diabetes.

Type 2 diabetes (T2D) adversely affects many tissues, and the greater incidence of discogenic low back pain among diabetic patients suggests that the intervertebral disc is affected too. Using a rat model of polygenic obese T2D, we demonstrate that diabetes compromises several aspects of disc composition, matrix homeostasis, and biomechanical behavior. Coccygeal motion segments were harvested from 6‐month‐old lean Sprague‐Dawley rats, obese Sprague‐Dawley rats, and diabetic obese UCD‐T2DM rats (diabetic for 69 ± 7 days). Findings indicated that diabetes but not obesity reduced disc glycosaminoglycan and water contents, and these degenerative changes correlated with increased vertebral endplate thickness and decreased endplate porosity, and with higher levels of the advanced glycation end‐product (AGE) pentosidine. Consistent with their diminished glycosaminoglycan and water contents and their higher AGE levels, discs from diabetic rats were stiffer and exhibited less creep when compressed. At the matrix level, elevated expression of hypoxia‐inducible genes and catabolic markers in the discs from diabetic rats coincided with increased oxidative stress and greater interactions between AGEs and one of their receptors (RAGE). Taken together, these findings indicate that endplate sclerosis, increased oxidative stress, and AGE/RAGE‐mediated interactions could be important factors for explaining the greater incidence of disc pathology in T2D.

Variations in Sagittal Alignment Parameters based on Age: A Prospective Study of Asymptomatic Volunteers using Full-Body Radiographs.

Study Design. Cross-sectional cohort study. Objective. Describe age-stratified normative values of traditional and novel sagittal alignment parameters. Summary of Background Data. Full-body radiographic techniques can capture coronal and sagittal standing images from the occiput to the foot without stitching or vertical distortion. This provides an ideal method to evaluate measures of global alignment. Methods. Adults with no back or neck symptoms were recruited. Age, body mass index, Neck Disability Index, and Oswestry Disability Index scores were recorded. The following parameters were measured: center sacral vertebral line, Occiput-C2 (O-C2) lordosis, cervical lordosis (C2-C7, CL), thoracic kyphosis (T2-12, TK), T2-T5 kyphosis, T5-T12 kyphosis, thoracolumbar kyphosis (T10-L2), lumbar lordosis (L1-S1, LL), sacral slope, pelvic tilt, pelvic incidence (PI), knee flexion angle, global sagittal angle, T1-pelvis angle, C2-S1 sagittal vertical axis (SVA), C7-S1 SVA, Basion-C7 SVA, B-S1 SVA and Basion to the center of the femoral head SVA and PI minus LL. Comparisons of sagittal alignment parameters between different age groups were performed. A Pearson correlation was used to determine relationships. Results. One hundred fifteen volunteers had imaging suitable for analysis; average age as 50.1 years (range 22–78), average body mass index was 28, average Neck Disability Index was 3.4 ± 4.4, and average Oswestry Disability Index was 1.7 ± 4.9. CL (r = −0.34, P = 0.001), T1-pelvis angle (r = 0.44, P < 0.001), knee flexion angle (r = 0.42, P < 0.001), global sagittal angle (r = 0.56, P < 0.001), and C7 SVA (r = 0.46, P < 0.001) all increased with age. LL decreased with age (r = 0.212, P = 0.039). We were able to establish a chain of correlation extending from the toes to the occiput and report age-based normative values for all parameters. Conclusion. We describe age-based normative sagittal alignment parameters in the adult spine with complete visualization from the occiput to the feet. We describe compensatory changes that occur to maintain sagittal balance. These values may be used as a reference for future studies. Level of Evidence: 4

Obesity Is an Independent Risk Factor of Early Complications After Revision Spine Surgery.

Study Design. Retrospective cohort analysis of risk factors in revision spine surgery using a prospectively collected database. Objective. To examine the risk of developing early (30-day) complications across obesity level after adjusting for comorbidities in patients undergoing revision spine surgery. Summary of Background Data. Prior studies suggest obesity influences early complications after primary surgery. The association between obesity and early complications after revision surgery remains to be characterized. Methods. Data were abstracted from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database from 2005 to 2012. Adult Caucasian patients undergoing removal/revision of instrumentation or exploration of fusion were included. Patients were categorized by WHO body mass index (BMI, kg/m2): Non-Obese (18.5–29.9), Obese Class I (30–34.9), and Obese Class II/III (≥35). Univariate regression was performed to assess the predictive value of obesity level and baseline risk factors in the presence of at least one early complication, and significant predictors were entered into the multivariable model. Results. Of 2538 patients, 57.6% were nonobese, 23% Obese Class I, and 19.4% Obese Class II/III. Obesity was associated with diabetes, hypertension, respiratory disease, and American Society of Anesthesiologists (ASA) score of 3–4 (all P < 0.001). BMI group (P = 0.01), older age (P = 0.008), functional dependence (P < 0.001), ASA 3–4 (P = 0.008), bleeding disorder (P = 0.04), and diabetes (P = 0.016) were identified as univariate predictors for early complications. In the multivariable model, higher BMI (P = 0.04), older age (P = 0.014), and functional dependence (P < 0.001) remained significant predictors for early complications. Notably, patients who were Obese Class II/III (OR 1.66, 95% CI [1.12–2.45]), age ≥75 (OR 1.83, [1.20–2.81]), and functionally dependent (OR 3.02 [1.85–4.94]) had significantly higher risk compared with their reference groups. Conclusion. Obesity is an independent risk factor for early complications after revision spine surgery. Although obesity may not contraindicate revision surgery, its status as a modifiable risk factor warrants disclosure and preoperative counseling to optimize outcomes. Level of Evidence: 3

Variations in Occipitocervical and Cervicothoracic Alignment Parameters based on Age: A Prospective Study of Asymptomatic Volunteers using Full-Body Radiographs.

Study Design. Cross-Sectional Cohort Study Objective. To describe age-stratified normative values of novel occipitocervical, cervical, and cervicothoracic alignment parameters. Summary of Background Data. Full-body radiographic images obtained without stitching or vertical distortion represent an ideal method to evaluate occipitocervical alignment and horizontal gaze. Methods. One hundred twenty adults with no back or neck symptoms were recruited. Age, sex, body mass index, Neck Disability Index (NDI), and Oswestry Disability Index scores were recorded. Radiographic parameters measured included: center sacral vertebral line, chin brow vertical angle (CBVA), orbital tilt (OrT), orbital slope, occipital slope (OS), occipital incidence, occiput-C2 (O-C2) lordosis, cervical lordosis (C2-C7, CL), T1 slope (TS), neck tilt, thoracic inlet angle (TIA), cervicothoracic kyphosis (C6-T4), and C2-C7 sagittal vertical axis (C2-7 SVA). Interobserver reliability was calculated for all measurements (intraclass correlation coefficient, ICC). A Pearson correlation was used to determine relationships between variables. Results. A total of 115 patients were analyzed; average age as 50.1 years (range 22–78). All measured variables had an ICC >0.6. CL (r = −0.33, P < 0.001), TS (r = 0.42, P < 0.001), TIA (r = 0.24, P = 0.010), and C7 SVA (r = 0.48, P < 0.001) all increased with age. OrT (r = −0.88, P < 0.001) and OS (r = 0.73, P < 0.001) were both strongly correlated with CBVA and each other (r = −0.83, P ⩽ 0.001). Both measures were also correlated with the C2-C7 SVA (OrT, r = 0.41, P < 0.001; OS, r = −0.29, P = 0.002) and O-C2 angle (OrT, r = 0.46, P < 0.001; OS, r = −0.28, P = 0.003). C6-T4 angulations was negatively correlated with NDI scores in this population (r = −0.25, P = 0.007). Conclusion. We present age-based normative values for occipitocervical, cervicothoracic, and cervical alignment parameters using a novel biplanar radiographic imaging technique. We introduce measures of craniocervical alignment that might provide surgeons with an intuitive way to account for the position of the orbit when planning cervical deformity correction. Level of Evidence: 4

Anterior Arthrodesis With Instrumentation for Thoracolumbar Scoliosis: Comparison of Efficacy in Adults and Adolescents

Study Design. A retrospective review was performed of adult and adolescent patients who underwent anterior spinal fusion for thoracolumbar idiopathic scoliosis; radiographic and clinical outcomes were compared. Objective. The objective of this study was to compare the efficacy of anterior instrumentation to treat thoracolumbar scoliosis in adults and adolescents by evaluating radiographic and clinical outcomes. Summary of Background Data. Anterior spinal arthrodesis is an effective treatment for idiopathic scoliosis. Deformity characteristics and clinical outcomes of adults versus adolescents have not been compared. Methods. A retrospective review of patients undergoing anterior fusion for thoracolumbar scoliosis was performed. Clinical outcomes were assessed using SRS-22. Preoperative and postoperative long films were evaluated independently. Flexibility, curve correction, and clinical outcomes were compared between adult and adolescents. Results. Fifteen adults and 15 adolescents who underwent anterior spinal fusion and instrumentation were evaluated. Mean follow-up was 47 and 46 months, respectively. Flexibility of the major curve in adults (63%) was less than in adolescents (79%) (P < 0.05). Mean preoperative, major curve Cobb angles were 51° and 49° for adults and adolescents, respectively. Mean postoperative Cobb angles improved less for adults (17°) than for adolescents (10°) (P < 0.05). The SRS-22 questionnaire revealed no statistical difference between populations. Conclusion. Anterior spinal fusion is an option for both adults and adolescents with flexible, moderate thoracolumbar/lumbar curves. Flexibility significantly decreased with increased age and curve magnitude. This significantly affected curve correction. Adult patients may develop early degeneration at primary curve and compensatory curves. Careful patient selection is critical with this technique.

Increase in spinal deformity surgery in patients age 60 and older is not associated with increased complications.

BACKGROUND CONTEXT Surgical treatment for adult spinal deformity improves patient quality of life; however, trends in surgical utilization in the elderly, who may be at higher risk for complications, remain unclear. PURPOSE To identify trends in the utilization of adult deformity and determine complication rates among older patients. STUDY DESIGN This is a retrospective database analysis. PATIENT SAMPLE The Nationwide Inpatient Sample database was queried from 2004 to 2011 to identify adult patients who underwent spinal fusion of eight or more levels using International Classification of Diseases, Ninth Revision (ICD-9) coding. OUTCOME MEASURES Incidence of surgery, complication rates, length of stay, and total hospital charges. METHODS The incidence of surgery was normalized to United States census data by age group. Trends in complications, length of stay, and inflation-adjusted hospital charges were determined using linear regression and Cochran-Armitage trend testing. RESULTS An estimated 29,237 patients underwent adult spinal deformity surgery with an increase from 2,137 to 5,030 cases per year from 2004 to 2011. Surgical incidence among patients 60 years and older increased from 1.9 to 6.5 cases per 100,000 people from 2004 to 2011 (p<.001), whereas utilization in patients younger than 60 increased from 0.59 to 0.93. Linear regression revealed that the largest increase in surgical utilization was for patients aged 65-69 years with an increase of 0.68 patients per 100,000 people per year (p<.001), followed by patients aged 70-74 years with a rate of 0.56 patients per 100,000 people per year (p=.001). Overall complication rates were 22.5% in 2004 and 26.7% in 2011. Although complication risk increased with age (≥60 vs. <60: relative risk 1.91 [1.83, 1.99], p<.001), within-age group rates were stable over time. Mean length of stay was 9.6 days in 2004 and 9.0 days in 2011. Inflation-adjusted mean hospital charges increased from