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A targeted injury to the mouse intervertebral disc (IVD) is often used to recapitulate the degenerative cascade of the human pathology. Since injuries can vary in magnitude and localization, it is critical to examine the effects of different injuries on IVD degeneration. We thus evaluated the degenerative progression resulting from either a partial- or full-width injury to the mouse lumbar IVD using contrast-enhanced micro-computed tomography and histological analyses. A lateral-retroperitoneal surgical approach was used to access the lumbar IVD, and the injuries to the IVD were produced by either incising one side of the annulus fibrosus or puncturing both sides of the annulus fibrosus. Female C57BL/6J mice of 3–4 months age were used in this study. They were divided into three groups to undergo partial-width, full-width, or sham injuries. The L5/6 and L6/S1 lumbar IVDs were surgically exposed, and then the L6/S1 IVDs were injured using either a surgical scalpel (partial-width) or a 33G needle (full-width), with the L5/6 serving as an internal control. These animals recovered and then euthanized at either 2-, 4-, or 8-weeks after surgery for evaluation. The IVDs were assessed for degeneration using contrast-enhanced microCT (CEµCT) and histological analysis. The high-resolution 3D CEµCT evaluation of the IVD confirmed that the respective injuries were localized within one side of the annulus fibrosus or spanned the full width of the IVD. The full-width injury caused significant deteriorations in the nucleus pulposus, annulus fibrous and at the interfaces after 2 weeks, which was sustained through the 8 weeks, while the partial width injury caused localized disruptions that remained limited to the annulus fibrosus. The use of CEµCT revealed distinct IVD degeneration profiles resulting from partial- and full-width injuries. The partial width injury may serve as an alternative model for IVD degeneration resulting from localized annulus fibrosus injuries.

Purpose In adult spinal deformity (ASD), patients increase pelvic tilt (PT) to maintain standing alignment. Previously, ASD patients with low PT and high disability were described. This study investigates this unusual population in terms of demographic, radiographic, and clinical features after three-column osteotomy (3CO). Methods In this multicenter retrospective study, ASD patients underwent single lumbar 3CO. Since PT is proportional to pelvic incidence (PI), the low PT group (LowPT) was defined as having a baseline (BL) PT/PI <25th percentile. HRQOL and full spine x-rays were analyzed at BL and 1 year. LowPT patients were compared to those with high PT/PI (HighPT) in a matched range of T1 pelvic angle. Results LowPT group had PT/PI <0.4 ( n  = 31). High disability was reported at baseline for both groups with significant improvement postoperatively, but without difference between groups. LowPT had significantly smaller lack lumbar lordosis but larger SVA, T1 spinopelvic inclination. Postoperatively, there were improvements in all sagittal modifiers except PT in LowPT. 33 % of LowPT had an increase in PT (>5°) postoperatively. This subset had more deformity at baseline, achieving good T1SPi postoperative correction but without achieving the SRS-Schwab target SVA at 1 year. Conclusion LowPT group had high levels of disability. After 3CO surgery, low PT patients experience only partial improvements in sagittal vertical axis (SVA) and 33 % of the group increased their PT. Further work is necessary to determine optimal realignment approaches for this unusual set of patients. It is unclear if neuromuscular pathology plays a role in the setting of high SVA without pelvic retroversion.

Study Design Retrospective. Objective Severe curves >100° in adolescent idiopathic scoliosis (AIS) are rare and require careful operative planning. The aim of this study was to assess baseline, perioperative, and 2-year differences between anterior release with posterior instrumentation (AP), posterior instrumentation with posterior column osteotomies (P), and posterior instrumentation with 3-column vertebral osteotomies (VCR). Methods Two scoliosis datasets were queried for primary cases of severe thoracic AIS (≥100°) with 2-year follow-up. Pre- and 2-year postoperative radiographic measures (2D and estimated 3D kyphosis), clinical measurements, and SRS-22 outcomes were compared between three approaches. Results Sixty-one patients were included: 16 AP (26%), 38 P (62%), 7 VCR (11%). Average age was 14.4 ± 2.0 years; 75.4% were female. Preoperative thoracic curve magnitude (AP: 112°, P: 115°, VCR: 126°, P = 0.09) and T5-T12 kyphosis (AP: 38°, P: 59°, VCR: 70°, P = 0.057) were similar between groups. Estimated 3D kyphosis was less in AP vs P (−12° vs 4°, P = 0.016). Main thoracic curves corrected to 36° in AP vs 49° and 48° for P and VCR, respectively (P = 0.02). Change in estimated 3D kyphosis was greater in AP vs P and VCR (34° vs 13°, P = 0.009; 34° vs 7°, P = 0.046). One incomplete spinal cord injury had residual deficits (P; 1/61, 1.6%). All SRS-22 domains improved postoperatively. Conclusion All approaches obtained satisfactory coronal and sagittal correction, but AP had smaller residual coronal deformity and greater kyphosis restoration than the other approaches. This information may help inform the decision of whether to include an anterior release for large thoracic AIS curves.

Cells of the nucleus pulposus (NP) are essential contributors to extracellular matrix synthesis and function of the intervertebral disc. With age and degeneration, the NP becomes stiffer and more dehydrated, which is associated with a loss of phenotype and biosynthetic function for its resident NP cells. Also, with aging, the NP cell undergoes substantial morphological changes from a rounded shape with pronounced vacuoles in the neonate and juvenile, to one that is more flattened and spread with a loss of vacuoles. Here, we make use of the clinically relevant pharmacological treatment verteporfin (VP), previously identified as a disruptor of yes‐associated protein‐TEA domain family member‐binding domain (TEAD) signaling, to promote morphological changes in adult human NP cells in order to study variations in gene expression related to differences in cell shape. Treatment of adult, degenerative human NP cells with VP caused a shift in morphology from a spread, fibroblastic‐like shape to a rounded, clustered morphology with decreased transcriptional activity of TEAD and serum‐response factor. These changes were accompanied by an increased expression of vacuoles, NP‐specific gene markers, and biosynthetic activity. The contemporaneous observation of VP‐induced changes in cell shape and prominent, time‐dependent changes within the transcriptome of NP cells occurred over all timepoints in culture. Enriched gene sets with the transition to VP‐induced cell rounding suggest a major role for cell adhesion, cytoskeletal remodeling, vacuolar lumen, and MAPK activity in the NP phenotypic and functional response to changes in cell shape.

The nucleus pulposus (NP) of the intervertebral disc plays a critical role in distributing mechanical loads to the axial skeleton. Alterations in NP cells and, consequently, NP matrix are some of the earliest changes in the development of disc degeneration. Previous studies demonstrated a role for laminin-presenting biomaterials in promoting a healthy phenotype for human NP cells from degenerated tissue. Here we investigate the use of laminin-mimetic peptides presented individually or in combination on a poly(ethylene) glycol hydrogel as a platform to modulate the behaviors of degenerative human NP cells. Data confirm that NP cells attach to select laminin-mimetic peptides that results in cell signaling downstream of integrin and syndecan binding. Furthermore, the peptide-functionalized hydrogels demonstrate an ability to promote cell behaviors that mimic that of full-length laminins. These results identify a set of peptides that can be used to regulate NP cell behaviors toward a regenerative engineering strategy.

Study design Retrospective review of a prospectively-collected multicenter database. Objectives The objective of this study was to determine optimal strategies in terms of focal angular correction and length of proximal extension during revision for PJF. Methods 134 patients requiring proximal extension for PJF were analyzed in this study. The correlation between amount of proximal junctional angle (PJA) reduction and recurrence of proximal junctional kyphosis (PJK) and/or PJF was investigated. Following stratification by the degree of PJK correction and the numbers of levels extended proximally, rates of radiographic PJK (PJA >28° & ΔPJA >22°), and recurrent surgery for PJF were reported. Results Before revision, mean PJA was 27.6° ± 14.6°. Mean number of levels extended was 6.0 ± 3.3. Average PJA reduction was 18.8° ± 18.9°. A correlation between the degree of PJA reduction and rate of recurrent PJK was observed (r = −.222). Recurrent radiographic PJK (0%) and clinical PJF (4.5%) were rare in patients undergoing extension ≥8 levels, regardless of angular correction. Patients with small reductions (<5°) and small extensions (<4 levels) experienced moderate rates of recurrent PJK (19.1%) and PJF (9.5%). Patients with large reductions (>30°) and extensions <8 levels had the highest rate of recurrent PJK (31.8%) and PJF (16.0%). Conclusion While the degree of focal PJK correction must be determined by the treating surgeon based upon clinical goals, recurrent PJK may be minimized by limiting reduction to <30°. If larger PJA correction is required, more extensive proximal fusion constructs may mitigate recurrent PJK/PJF rates.

Study Design Retrospective review of prospective multicenter data. Objectives This study aimed to investigate the shape of TK before and after fusion in ASD patients treated with long fusion. Methods ASD patients undergoing posterior spinal fusions including at least T5 to L1 without prior fusion extending to the thoracic spine were included. Patients were categorized based on the preoperative T1-T12 kyphosis into: Hypo-TK (if < 30°), Normal-TK, and Hyper-TK (if > 70°). Regional kyphosis at T10-L1 (Distal), T5-T10 (Middle), and T1-T5 (Proximal) and their relative contributions to total kyphosis were compared between groups, and the pre-to postoperative changes were investigated using paired t test. Results In total, 329 patients were included in this analysis (mean age: 57 ± 16 years, 79.6% female). Preoperative T1-T12 TK for the entire cohort was 40.9 ± 2° (32% Hypo-TK, 11% Hyper-TK, 57% Normal-TK). The Hypo-TK group had the smallest distal TK (5.9 vs 17.1 & 26.0), and middle TK (8.0 vs 25.3 & 45.4), but the percentage of contribution to total kyphosis was not significantly different (Distal: 24.1% vs 34.1% vs 32.8%; Middle: 46.6% vs 53.9% vs 56.8%, all P > .1). Postoperatively, T1-12 TK increased significantly (40.9 ± 2.0° vs 57.8 ± 17.6°). Each group had a decrease in distal kyphosis (Hypo-TK 2.6 ± 10.4°; Normal-TK 8.9 ± 11.5°; Hyper-TK 14.9 ± 12°, all P < .05). The middle kyphosis significantly decreased for Hyper-TK (11.8 ± 12.4) and increased for both Normal-TK and Hypo-TK (3.8 ± 11° and 14.2 ± 11°). Proximal TK increased significantly for all groups by 14-18°. Deterioration from Normal-TK to Hyper-TK postoperatively was associated with lower rate of patient satisfaction (59.6% vs 77.3%, P = .032). Conclusions Posterior spinal fusion for ASD alters the magnitude and shape of thoracic kyphosis. While 60% of patients had a normal TK at baseline, 30% of those patients developed iatrogenic hyperkyphosis postoperatively. Patients with baseline hypokyphosis were more likely to be corrected to normal TK than hyperkyphotic patients. Future research should investigate TK restoration in ASD and its impact on clinical outcomes and complications.

Abstract BACKGROUND Novel radiographic sagittal parameters of the thoracolumbar junction orientation (TLJO, thoracolumbar slope [TLS] and thoracolumbar tilt [TLT]) have been introduced and correlated with lumbopelvic parameters and thoracic kyphosis. OBJECTIVE To determine a predictive model for reciprocal thoracic kyphosis and proximal junctional kyphosis (PJK) based on the TLJO. METHODS A total of 127 patients who had fusion from sacrum to T10-L2 from 2004 to 2014 were reviewed. TK (T5-T12), PI, SS, PT, LL, and proximal junctional angle (PJA) were measured preoperatively, 6 wk postoperatively, and at final follow-up. TLJO was measured by TLS and TLT. Changes between time points were determined (preop-6 wk = ΔParameterPre6wk and preop-final follow/up = ΔParameterPreFinal). Scoliosis Research Society (SRS) and Oswestry Disability Index (ODI) questionnaires were evaluated at final follow-up. Patients were divided into 2 groups based on the presence of PJK (ΔPJAPreFinal >15°). Independent t-tests and receiver operating characteristic (ROC) curves were used to investigate the significance of differences and cut-off values. Pearson correlations and linear regressions were used to analyze the entire cohort to determine the relationship between the changes in parameters. RESULTS Compared to patients without PJK (n = 100), those with PJK (n = 27) had significantly lower SRS scores and significantly greater ΔTKPreFinal, ΔLLPre6wk, and ΔTLSPre6wk. To maintain in the nonPJK group, ROC curves demonstrated a cut-off value of −9.4° for ΔTLSPre6wk. PJK was significantly correlated with ΔTKPreFinal and ΔTLSPre6wk. The linear correlation revealed that ΔTLSPre6wk < −25.3° is the risk factor of PJK > 15°. CONCLUSION As change of TLS reflects lumbopelvic realignment and influences reciprocal TK, reducing the change of TLS may be a sagittal realignment guideline to reduce the risk of PJK.

Low back pain is associated with degeneration of the intervertebral disc, but specific mechanisms of pain generation in this pathology remain unknown. Sensory afferent nerve fiber growth into the intervertebral disc after injury-induced inflammation may contribute to discogenic pain. We describe a clinically relevant behavioral phenotype in a rodent model of chronic intervertebral disc degeneration which provides a means to map sensory neuron changes to a single affected lumbar intervertebral disc. Unilateral disc puncture of one lumbar intervertebral disc revealed a bilateral behavioral phenotype characterized by gait changes and decreased activity. Moreover, neurons extracted from the dorsal root ganglia in animals with intervertebral disc injury demonstrated altered TRPV1 activation in vitro independent of exogenous NGF administration. Finally, neuronal nuclear hypertrophy and elevated expression of p75NTR provide evidence of active adaptation of innervating sensory neurons in chronic intervertebral disc degeneration. Therefore, this model and findings provide the template for future studies to establish specific mechanisms of nociceptive pain in chronic intervertebral disc degeneration.

Study Design: Retrospective cohort study. Objectives: Describe the rate of dural tears (DTs) in adult spinal deformity (ASD) surgery. Describe the risk factors for DT and the impact of this complication on clinical outcomes. Methods: Patients with ASD undergoing surgery between 2008 and 2014 were separated into DT and non-DT cohorts; demographics, operative details, radiographic, and clinical outcomes were compared. Statistical analysis included t tests or χ2 tests as appropriate and a multivariate analysis. Results: A total of 564 patients were identified. The rate of DT was 10.8% (n = 61). Patients with DT were older (61.1 vs 56.5 years, P = .005) and were more likely to have had prior spine surgery (odds ratio [OR] = 2.0, 95% confidence interval [CI] = 1.2-3.3, P = .007). DT patients had higher pelvic tilt, lower lumbar lordosis, and greater pelvic-incidence lumbar lordosis mismatch than non-DT patients (P < .05). DT patients had longer operative times (424 vs 375 minutes, P = .008), were more likely to undergo interbody fusions (OR = 2.0, 95% CI = 1.1-3.6, P = .021), osteotomies (OR = 2.2, 95% CI = 1.1-4.0, P = .012), and decompressions (OR = 2.3, 95% CI = 1.3-4.3, P = .003). In our multivariate analysis, only decompressions were associated with an increased risk of DT (OR = 3.2, 95% CI = 1.4-7.6, P = .006). There were no significant differences in patient outcomes at 2 years. Conclusions: The rate of DT was 10.8% in an ASD cohort. This is similar to rates of DT reported following surgery for degenerative pathology. A history of prior spine surgery, decompression, interbody fusion, and osteotomies are all associated with an increased risk of DT, but decompression is the only independent risk factor for DT.