Suboptimal Age-Adjusted Lumbo-Pelvic Mismatch Predicts Negative Cervical-Thoracic Compensation in Obese Patients.

BACKGROUND: Given the paucity of literature regarding compensatory mechanisms used by obese patients with sagittal malalignment, it is necessary to gain a better understanding of the effects of obesity on compensation after comparing the degree of malalignment to age-adjusted ideals. This study aims to compare baseline alignment of obese and nonobese patients using age-adjusted spino-pelvic alignment parameters, describing associated spinal changes. METHODS: Patients ≥ 18 years with full-body stereoradiographs were propensity-score matched for sex, baseline pelvic incidence (PI), and categorized as nonobese (body mass index < 30kg/m2) or obese (body mass index ≥ 30). Age-adjusted ideals were calculated for sagittal vertical axis, spino-pelvic mismatch (PI-LL), pelvic tilt, and T1 pelvic angle using established formulas. Patients were stratified as meeting alignment ideals, being above ideal, or being below. Spinal alignment parameters included C0-C2, C2-C7, C2-T3, cervical thoracic pelvic angle, cervical sagittal vertical axis SVA, thoracic kyphosis, T1 pelvic angle, T1 slope, sagittal vertical axis, lumbar lordosis (LL), PI, PI-LL, pelvic tilt. Lower-extremity parameters included sacrofemoral angle, knee flexion (KA), ankle flexion (AA), pelvic shift (PS), and global sagittal angle (GSA). Independent t tests compared parameters between cohorts. RESULTS: Included: 800 obese, 800 nonobese patients. Both groups recruited lower-extremity compensation: sacrofemoral angle (P = .004), KA, AA, PS, GSA (all P < .001). Obese patients meeting age-adjusted PI-LL had greater lower-extremity compensation than nonobese patients: lower sacrofemoral angle (P = .002), higher KA (P = .008), PS (P = .002), and GSA (P = .02). Obese patients with PI-LL mismatch higher than age-adjusted ideal recruited greater lower-extremity compensation than nonobese patients: higher KA, AA, PS, GSA (all P < .001). Obese patients showed compensation through the cervical spine: increased C0-C2, C2-C7, C2-T3, and cervical sagittal vertical axis (all P < .001), high T1 pelvic angle (P < .001), cervical thoracic pelvic angle (P = .03), and T1 slope (P < .001), with increased thoracic kyphosis (P = .015) and decreased LL (P < .001) compared to nonobese patients with PI-LL larger than age-adjusted ideal. CONCLUSIONS: Regardless of malalignment severity, obese patients recruited lower-limb compensation more than nonobese patients. Obese patients with PI-LL mismatch larger than age-adjusted ideal also develop upper-cervical and cervicothoracic compensation for malalignment. LEVEL OF EVIDENCE: III. CLINICAL RELEVANCE: Clinical evaluation should extend to the cervical spine in obese patients not meeting age-adjusted sagittal alignment ideals.

Use of Gabapentin in Posterior Spinal Fusion is Associated With Decreased Postoperative Pain and Opioid Use in Children and Adolescents.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The objective of this study was to examine associations of gabapentin use with inpatient postoperative daily pain scores and opioid use in children undergoing PSF for AIS. SUMMARY OF BACKGROUND DATA: Gabapentin use in posterior spinal fusion (PSF) postoperative pain management for adolescent idiopathic scoliosis (AIS) is increasingly common in order to decrease opioid use and improve pain control, though there is conflicting data on dosing and effectiveness to support this practice in real world settings. METHODS: Retrospective cohort study of children aged 10 to 21 years undergoing PSF for AIS between January 2013 and June 2016 at an urban academic tertiary care center. Adjuvant gabapentin exposure was defined as at least 15 mg/kg/d by postoperative day (POD) 1 with an initial loading dose of 10 mg/kg on day of surgery. Primary outcomes were daily postoperative mean pain score and opioid use [morphine milligram equivalents/kg/day(mme/kg/d)]. Secondary outcomes were short and long-term complications. RESULTS: Among 129 subjects (mean age, 14.6 y, 74% female, mean coronal cobb, 55.2 degrees), 24 (19%) received gabapentin. Unadjusted GABA exposure was associated with significantly lower opioid use on POD1 and 2 (49% and 31%mme/kg/d, respectively) and lower pain scores (14%) on POD2. Adjusting for preexisting back pain, preoperative coronal Cobb angle, and site, GABA use was associated with significantly lower mean pain scores on POD1 through POD3 (-0.68, P=0.01; -0.86, P=0.002; -0.63, P=0.04). Gabapentin use was also associated with decreased opioid use on POD1 and POD2 (-0.39mme/kg/d, P<0.001; -0.27, P=0.02). There was no difference in complications by gabapentin exposure. CONCLUSIONS: Addition of gabapentin as adjuvant therapy for adolescent PSF, beginning on day of surgery, is associated with improved pain scores and decreased opioid use in the first 48 to 72 hours postoperatively. LEVEL OF EVIDENCE: This is a retrospective cohort study, classified as Level III under "Therapeutic Studies Investigating the Results of a Treatment."

The Influence of Body Mass Index on Achieving Age-Adjusted Alignment Goals in Adult Spinal Deformity Corrective Surgery with Full-Body Analysis at 1 Year.

BACKGROUND: The impact of obesity on global spinopelvic alignment is poorly understood. This study investigated the effect of body mass index on achieving alignment targets and compensation mechanisms after corrective surgery for adult spinal deformity (ASD). METHODS: Retrospective review of a single-center database. Inclusion: patients ≥18 years with full-body stereographic images (baseline and 1 year) and who met ASD criteria (sagittal vertical axis [SVA] >5 cm, pelvic incidence minus lumbar lordosis [PI-LL] >10°, coronal curvature >20° or pelvic tilt >20°). Patients were stratified by age (<40, 40-65, and ≥65 years) and body mass index (<25, 25-30, and >30). Postoperative alignment was compared with age-adjusted ideal values. Prevalence of patients who matched ideals and unmatched (undercorrected/overcorrected) was assessed. Health-related quality of life (HRQL) scores, alignment, and compensatory mechanisms were compared across cohorts using analysis of variance and temporally with paired t tests. RESULTS: A total of 116 patients were included (average age, 62 years; 66% female). After corrective surgery, obese and overweight patients had more residual malalignment (worse PI-LL, T1 pelvic angle, pelvic tilt, and SVA) compared with normal patients (P < 0.05). In addition, obese and overweight patients recruited more pelvic shift (obese, 62.36; overweight, 49.80; normal, 31.50) and had a higher global sagittal angle (obese, 6.51; overweight, 6.35; normal, 3.40) (P < 0.05). Obese and overweight patients showed lower overcorrection rates and higher undercorrection rates (P < 0.05). Obese patients showed worse postoperative HRQL scores (Scoliosis Research Society 22 Questionnaire, Oswestry Disability Index, visual analog scale-leg) than did overweight and normal patients (P < 0.05). Obese and overweight patients who matched age-adjusted alignment targets for SVA or PI-LL showed no HRQL improvements (P > 0.05). CONCLUSIONS: After surgery, obese patients were undercorrected, showed more residual malalignment, recruited more pelvic shift, and had a greater global sagittal angle and worse HRQL scores. The benefits from age-adjusted alignment targets seem to be less substantial for obese and overweight patients.

Developments in the treatment of Chiari type 1 malformations over the past decade.

BACKGROUND: Chiari malformations type 1 (CM-1), a developmental anomaly of the posterior fossa, usually presents in adolescence or early adulthood. There are few studies on the national incidence of CM-1, taking into account outcomes based on concurrent diagnoses. To quantify trends in treatment and associated diagnoses, as retrospective review of the Kid's Inpatient Database (KID) from 2003-2012 was conducted. METHODS: Patients aged 0-20 with primary diagnosis of CM-1 in the KID database were identified. Demographics and concurrent diagnoses were analyzed using chi-squared and t-tests for categorical and numerical variables, respectively. Trends in diagnosis, treatments, and outcomes were analyzed using analysis of variance (ANOVA). RESULTS: Five thousand four hundred and thirty-eight patients were identified in the KID database with a primary diagnosis of CM-1 (10.5 years, 55% female). CM-1 primary diagnoses have increased over time (45 to 96 per 100,000). CM-1 patients had the following concurrent diagnoses: 23.8% syringomyelia/syringobulbia, 11.5% scoliosis, 5.9% hydrocephalus, 2.2% tethered cord syndrome. Eighty-three point four percent of CM-1 patients underwent surgical treatment, and rate of surgical treatment for CM-1 increased from 2003-2012 (66% to 72%, P<0.001) though complication rate decreased (7% to 3%, P<0.001) and mortality rates remained constant. Seventy percent of surgeries involved decompression-only, which increased neurologic complications compared to fusions (P=0.039). Cranial decompressions decreased from 2003-2012 (42.2-30.5%) while spinal decompressions increased (73.1-77.4%). Fusion rates have increased over time (0.45% to 1.8%) and are associated with higher complications than decompression-only (11.9% vs. 4.7%). Seven point four percent of patients experienced at least one peri-operative complication (nervous system, dysphagia, respiratory most common). Patients with concurrent hydrocephalus had increased; nervous system, respiratory and urinary complications (P<0.006) and syringomyelia increased the rate of respiratory complications (P=0.037). CONCLUSIONS: CM-1 diagnoses have increased in the last decade. Despite the decrease in overall complication rates, fusions are becoming more common and are associated with higher peri-operative complication rates. Commonly associated diagnoses including syringomyelia and hydrocephalus, can dramatically increase complication rates.

Full-Body Analysis of Adult Spinal Deformity Patients' Age-Adjusted Alignment at 1 Year.

BACKGROUND: Previous studies have built a foundation for understanding compensation in patients with adult spinal deformity (ASD) by using full-body stereographic assessments. These mechanisms, in relation to age-adjusted alignment targets, have yet to be studied fully. The aim of this study was to assess lower-limb compensatory mechanisms of patients failing to meet age-adjusted alignment goals. METHODS: Patients with ASD ≥40 years with full body baseline and follow-up radiographs were included. Patients were stratified by age (40-65 years, >65 years) and spinopelvic correction. Lower-limb compensation parameters (pelvic shift, hip extension, knee flexion [KA], ankle flexion [AA], and global sagittal angle [GSA]) for patients who matched and failed to match age-adjusted alignment targets were compared with analysis of variance and t-test analysis. RESULTS: In total, 108 patients were included. At 1 year, AA increased with age in the "match" pelvic tilt (PT) and spinopelvic mismatch (PI-LL) cohorts (PT: AA, 5.6-7.8, P = 0.041; PI-LL: 4.9-8.8, P = 0.026). KA, AA, and GSA increased with age in the "match" sagittal vertical axis (SVA) cohort (KA: 3.8-13.1, P = 0.002; AA: 5.8-10.2, P = 0.008; GSA: 3.9-7.8, P < 0.001), as did KA and GSA in the "match" T1 pelvic angle group (KA: 1.8-8.7, P = 0.020; GSA: 2.6-5.7, P = 0.004). CONCLUSIONS: Greater compensation captured by KA and GSA was associated with age progression in the "match" SVA and T1 pelvic angle cohorts. In addition, older SVA, PT, and PI-LL "match" cohorts used increased AA, suggesting that ideal postoperative alignment of aged individuals with ASD involves increased compensation.

Normal Age-Adjusted Sagittal Spinal Alignment Is Achieved with Surgical Correction in Adolescent Idiopathic Scoliosis.

STUDY DESIGN: Retrospective analysis. PURPOSE: Our hypothesis is that the surgical correction of adolescent idiopathic scoliosis (AIS) maintains normal sagittal alignment as compared to age-matched normative adolescent population. OVERVIEW OF LITERATURE: Sagittal spino-pelvic alignment in AIS has been reported, however, whether corrective spinal fusion surgery re-establishes normal alignment remains unverified. METHODS: Sagittal profiles and spino-pelvic parameters of thirty-eight postsurgical correction AIS patients ≤21 years old without prior fusion from a single institution database were compared to previously published normative age-matched data. Coronal and sagittal measurements including structural coronal Cobb angle, pelvic incidence, pelvic tilt, thoracic kyphosis, lumbar lordosis, sagittal vertical axis, C2-C7 cervical lordosis, C2-C7 sagittal vertical axis, and T1 pelvic angles were measured on standing full-body stereoradiographs using validated software to compare preoperative and 6 months postoperative changes with previously published adolescent norms. A sub-group analysis of patients with type 1 Lenke curves was performed comparing preoperative to postoperative alignment and also comparing this with previously published normative values. RESULTS: The mean coronal curve of the 38 AIS patients (mean age, 16±2.2 years; 76.3% female) was corrected from 53.6° to 9.6° (80.9%, p<0.01). None of the thoracic and spino-pelvic sagittal parameters changed significantly after surgery in previously hypo- and normo-kyphotic patients. In hyper-kyphotic patients, thoracic kyphosis decreased (p=0.003) with a reciprocal decrease in lumbar lordosis (p=0.01), thus lowering pelvic incidence-lumbar lordosis mismatch mismatch (p=0.009). Structural thoracic scoliosis patients had slightly more thoracic kyphosis than age-matched patients at baseline and surgical correction of the coronal plane of their scoliosis preserved normal sagittal alignment postoperatively. A sub-analysis of Lenke curve type 1 patients (n=24) demonstrated no statistically significant changes in the sagittal alignment postoperatively despite adequate coronal correction. CONCLUSIONS: Surgical correction of the coronal plane in AIS patients preserves sagittal and spino-pelvic alignment as compared to age-matched asymptomatic adolescents.

Radiological lumbar stenosis severity predicts worsening sagittal malalignment on full-body standing stereoradiographs.

BACKGROUND CONTEXT: Patients with degenerative lumbar stenosis (DLS) adopt a forward flexed posture in an attempt to decompress neural elements. The relationship between sagittal alignment and severity of lumbar stenosis has not previously been studied. PURPOSE: We hypothesized that patients with increasing radiological severity of lumbar stenosis will exhibit worsening sagittal alignment. STUDY DESIGN: This is a cross-sectional study. PATIENT SAMPLE: Our sample consists of patients who have DLS. OUTCOME MEASURES: Standing pelvic, regional, lower extremity and global sagittal alignment, and health-related quality of life (HRQoL) were the outcome measures. METHODS: Patients with DLS were identified from a retrospective clinical database with corresponding full-body stereoradiographs. Exclusion criteria included coronal malalignment, prior spine surgery, spondylolisthesis>Grade 1, non-degenerative spinal pathology, or skeletal immaturity. Central stenosis severity was graded on axial T2-weighted magnetic resonance imaging (MRI) from L1-S1. Foraminal stenosis and supine lordosis was graded on sagittal T1-weighted images. Standing pelvic, regional, lower extremity, and global sagittal alignment were measured using validated software. The HRQoL measures were also analyzed in relation to severity of stenosis. RESULTS: A total of 125 patients were identified with DLS on appropriate imaging. As central stenosis grade increased, patients displayed significantly increasing standing T1 pelvic angle, pelvic tilt, sagittal vertical axis, and pelvic incidence-lumbar lordosis (p<.05). No significant difference wasfound in pelvic incidence, supine lordosis, thoracic kyphosis, or T1 spinopelvic inclination between central stenosis groups. Despite similar supine lordosis between stenosis groups, patients with Grades 2 and 3 stenosis had less standing lordosis, suggesting antalgic posturing. Upper lumbar (L1-L3) stenosis predicted worse alignment than lower lumbar (L4-S1) stenosis. Increasing severity of foraminal stenosis was associated with reduced lumbar lordosis; however, no significant postural difference in lordosis, thoracolumbar, or lower extremity compensatory mechanisms were noted between foraminal stenosis groups. Stenosis grading did not predict worsening HRQoLs in central or foraminal stenosis. CONCLUSIONS: Severity of central lumbar stenosis as graded on MRI correlates with severity of sagittal malalignment. These findings support theories of sagittal malalignment as a compensatory mechanism for central lumbar stenosis.

Patient-Specific Screening Using High-Grade Glioma Explants to Determine Potential Radiosensitization by a TGF-ß Small Molecule Inhibitor.

High-grade glioma (HGG), a deadly primary brain malignancy, manifests radioresistance mediated by cell-intrinsic and microenvironmental mechanisms. High levels of the cytokine transforming growth factor-ß (TGF-ß) in HGG promote radioresistance by enforcing an effective DNA damage response and supporting glioma stem cell self-renewal. Our analysis of HGG TCGA data and immunohistochemical staining of phosphorylated Smad2, which is the main transducer of canonical TGF-ß signaling, indicated variable levels of TGF-ß pathway activation across HGG tumors. These data suggest that evaluating the putative benefit of inhibiting TGF-ß during radiotherapy requires personalized screening. Thus, we used explant cultures of seven HGG specimens as a rapid, patient-specific ex vivo platform to test the hypothesis that LY364947, a small molecule inhibitor of the TGF-ß type I receptor, acts as a radiosensitizer in HGG. Immunofluorescence detection and image analysis of γ-H2AX foci, a marker of cellular recognition of radiation-induced DNA damage, and Sox2, a stem cell marker that increases post-radiation, indicated that LY364947 blocked these radiation responses in five of seven specimens. Collectively, our findings suggest that TGF-ß signaling increases radioresistance in most, but not all, HGGs. We propose that short-term culture of HGG explants provides a flexible and rapid platform for screening context-dependent efficacy of radiosensitizing agents in patient-specific fashion. This time- and cost-effective approach could be used to personalize treatment plans in HGG patients.