Background and Purpose We have previously demonstrated that the local delivery of monocyte chemotactic protein-1 (MCP-1) via a MCP-1-releasing poly(lactic-co-glycolic acid) (PLGA) -coated coil promotes intra-aneurysmal tissue healing. In this study, we demonstrate that interleukin-6 (IL-6) and osteopontin (OPN) are downstream mediators in the MCP-1-mediated aneurysm healing pathway. Methods Murine carotid aneurysms were created in C57BL/6 mice. Drug-releasing coils (MCP-1, IL-6 and OPN) and control PLGA coils were created and then implanted into the aneurysms in order to evaluate their intra-aneurysmal healing capacity. In order to investigate the downstream mediators for aneurysm healing, blocking antibodies for IL-6 receptor and OPN were given to the mice implanted with the MCP-1-releasing coils. A histological analysis of both murine and human aneurysms was utilized to cross-validate the data. Results We observed increased expression of IL-6 in MCP-1-coil treated aneurysms and not in control-PLGA-only treated aneurysms. MCP-1-mediated intra-aneurysmal healing is inhibited in mice given blocking antibody to IL-6 receptor. MCP-1-mediated intra-aneurysmal healing is also inhibited by blocking antibody to OPN. The role of IL-6 in intra-aneurysmal healing is in recruiting of endothelial cells and fibroblasts. Local delivery of OPN to murine carotid aneurysms via OPN-releasing coil significantly promotes intra-aneurysmal healing, but IL-6-releasing coil does not, suggesting that IL-6 cannot promote aneurysm healing independent of MCP-1. In the MCP-1-mediated aneurysm healing, OPN expression is dependent on IL-6; inhibition of IL-6 receptor significantly inhibits OPN expression in MCP-1-mediated aneurysm healing. Conclusions Our findings suggest that IL-6 and OPN are key downstream mediators of MCP-1-mediated intra-aneurysmal healing.

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OBJECTIVE As an alternative procedure to anterior cervical discectomy and fusion, total disc arthroplasty (TDA) facilitates direct neural decompression and disc height restoration while also preserving cervical spine kinematics. To date, few studies have reported long-term functional outcomes after TDA. This paper reports the results of a systematic review and meta-analysis that investigated how segmental range of motion (ROM) at the operative level is maintained with long-term follow-up. METHODS PubMed and MEDLINE were queried for all published studies pertaining to cervical TDA. The methodology for screening adhered strictly to the PRISMA guidelines. All English-language prospective studies that reported ROM preoperatively, 1 year postoperatively, and/or at long-term follow-up of 5 years or more were included. A meta-analysis was performed using Cochran’s Q and I2 to test data for statistical heterogeneity, in which case a random-effects model was used. The mean differences (MDs) and associated 95% confidence intervals (CIs) were reported. RESULTS Of the 12 studies that met the inclusion criteria, 8 reported the long-term outcomes of 944 patients with an average (range) follow-up of 99.86 (60–142) months and were included in the meta-analysis. There was no difference between preoperative segmental ROM and segmental ROM at 1-year follow-up (MD 0.91°, 95% CI −1.25° to 3.07°, p = 0.410). After the exclusion of 1 study from the comparison between preoperative and 1-year ROM owing to significant statistical heterogeneity according to the sensitivity analysis, ROM significantly improved at 1 year postoperatively (MD 1.92°, 95% CI 1.04°–2.79°, p < 0.001). However, at longer-term follow-up, the authors again found no difference with preoperative segmental ROM, and no study was excluded on the basis of the results of further sensitivity analysis (MD −0.22°, 95% CI −1.69° to −1.23°, p = 0.760). In contrast, there was a significant decrease in ROM from 1 year postoperatively to final long-term follow-up (MD −0.77°, 95% CI −1.29° to −0.24°, p = 0.004). CONCLUSIONS Segmental ROM was found to initially improve beyond preoperative values for as long as 1 year postoperatively, but then ROM deteriorated back to values consistent with preoperative motion at long-term follow-up. Although additional studies with further longitudinal follow-up are needed, these findings further support the notion that cervical TDA may successfully maintain physiological spinal kinematics over the long term.

Study Design Retrospective cohort Objective Anterior lumbar interbody fusion (ALIF) may be complicated by subsidence, which can lead to significant morbidity including pain, disc space collapse, neural compression, segmental kyphosis, instability, and vertebral body fracture. This study sought to identify patient and procedural risk factors for subsidence in patients undergoing ALIF. Methods This study analyzed consecutive patients who underwent ALIF at a single institution with a minimum of 2 years follow-up. Patients were grouped as either Non-Subsidence (NS-ALIF) or Cage Subsidence (CS-ALIF) based on the final postoperative radiograph. Demographic variables, operative characteristics, and radiographic outcomes were evaluated to identify significant predictors on univariate and multivariate statistics. Results 144 patients (170 levels) were included with an average follow-up of 50.70 ± 28.44 months (4.23 years). The incidence of subsidence was 22.94% (39/170 levels). On univariate statistics, the CS-ALIF group was significantly older (P = .020), had higher BMI (P = .048), worse ASA (P = .001), higher prevalence of comorbid osteoporosis (P < .001), and a more anteriorly placed interbody device (P = .005). On multivariate analysis, anterior cage placement remained the only significant predictor (OR: 1.08, 95% CI: 1.03–1.14; P = .003). There was a significantly higher rate of subsequent adjacent segment surgery among the CS-ALIF group (P = .035). Conclusion Factors contributing to subsidence in ALIF included older age, higher BMI, severe ASA, and osteoporosis, while anterior cage placement remained the only independent predictor on multivariate analysis. Subsidence was associated with a higher rate of subsequent adjacent segment surgery. Surgical technique should optimize placement of the interbody cage and avoid overstuffing the disc space.

Study Design Retrospective cohort Objective Lateral lumbar interbody fusion (LLIF) commonly involves a transpsoas approach. Despite the association between LLIF, postoperative iliopsoas weakness, and iatrogenic neuropraxia, no study has yet examined the effect of psoas or multifidus muscle quality on patient-reported outcomes (PROs). Methods This study retrospectively reviewed patients who underwent LLIF with 1-year minimum follow-up. Psoas and multifidus muscle qualities were graded on preoperative magnetic resonance imaging using two validated classification systems for muscle atrophy. Average muscle quality was calculated as the mean score from all levels (L1-2 through L5-S1). Univariate and multivariate statistics were utilized to investigate the relationship between psoas/multifidus muscle quality and preoperative, 6-weeks postoperative, and final postoperative PROs. Results 74 patients (110 levels) with a mean follow-up of 18.71 ± 8.02 months were included for analysis. Greater multifidus atrophy was associated with less improvement on ODI, SF12, and VR12 ( P < .05) on univariate analysis. On multivariate analysis, worse multifidus atrophy predicted less improvement on SF12 and VR12 ( P < .05). Conclusion Despite the direct manipulation of the psoas muscle inherent to LLIF, preoperative psoas muscle quality did not affect postoperative outcomes. Rather, the extent of preoperative multifidus fatty infiltration and atrophy was more likely to predict postoperative pain and disability. These findings suggest that multifidus atrophy may be more pertinent than psoas atrophy in its association with patient-reported outcome measures after LLIF.