Anterior Cervical Discectomy and Fusion for Adjacent Segment Disease: Clinical Outcomes and Cost Utility of Surgical Intervention.

STUDY DESIGN: Retrospective review. OBJECTIVE: Determine clinical outcomes and cost utility of anterior cervical discectomy and fusion (ACDF) for the treatment of adjacent segment disease (ASD). SUMMARY OF BACKGROUND DATA: The incidence of symptomatic ASD after ACDF has been estimated to occur in up to 26% of patients. Commonly, these patients will undergo an additional ACDF procedure. However, there are currently no studies available that adequately describe the clinical outcomes or cost utility of performing ACDF for ASD. METHODS: A retrospective review of 40 patients undergoing ACDF for ASD was performed. Baseline and 2-year neck and arm pain (NRS-NP, NRS-AP), neck disability index (NDI), physical and mental quality of life (SF-12 PCS & MCS), and Zung depression score (ZDS) were assessed. Two-year total neck-related medical resource utilization, amount of missed work, and health-state values were determined. Quality-adjusted life years (QALYs) were calculated from EQ-5D assessments with US valuation. Comprehensive costs (indirect, direct, and total cost) and the value (cost-per-QALY gained) of performing ACDF for ASD were assessed. RESULTS: Performing ACDF to treat ASD resulted in significant improvements (P<0.05) in NRS-NP, NRS-AP, NDI, SF-12 PCS, and ZDS outcome measures. Patient-reported health states also significantly improved, with a mean cumulative 2-year gain of 0.54 QALYs. The mean 2-year cost of surgery was $32,616 (direct cost: $25,391; indirect cost: $7225). ACDF for the treatment of ASD was associated with a mean 2-year cost per QALY gained of $60,526. CONCLUSIONS: Performing ACDF for ASD resulted in significant improvements in patient pain, disability, and quality of life. Further, the mean 2-year cost-per-QALY was determined to be $60,526, which suggests surgical intervention to be cost effective. This study is the first to provide evidence that performing an ACDF for ASD is both clinically and cost effective.

Accuracy of MRI-based Diagnoses for Distal Upper Extremity Soft Tissue Masses.

UNLABELLED: To determine the accuracy of the pre-operative MRI-based diagnosis of soft tissue masses in the forearm, wrist, and hand, the records of 144 patients who underwent an MRI followed by excision of a soft tissue mass in the forearm, wrist, or hand were reviewed. The MRI-based diagnosis was compared to the histological diagnosis, which was considered the gold standard. The sensitivity, specificity, positive predictive value, and negative predictive value of the MRI-based diagnosis were calculated. A multivariate regression analysis was performed.While the accuracy of the MRI-based diagnosis varied widely, there was an overall sensitivity of 75 %. The most accurate diagnosis was an MRI-based diagnosis of ganglion cyst, which had a sensitivity of 94.7 % and a specificity of 94.4 %. Of particular concern was that the MRI-based diagnosis of a malignancy was only 66.7 % sensitive, with a positive predictive value of 44.4 %. On multivariate regression analysis, there was a trend towards improved accuracy in the wrist when compared to the finger, although this did not reach statistical significance.While pre-operative MRI remains a valuable tool for the evaluation of soft tissue masses in the distal upper extremity, caution is warranted when basing the diagnosis on MRI evidence alone. LEVEL OF EVIDENCE: Level IV/Diagnostic.

Differential regulation of embryonic and adult ß cell replication.

Diabetes results from an inadequate functional ß cell mass, either due to autoimmune destruction (Type 1 diabetes) or insulin resistance combined with ß cell failure (Type 2 diabetes). Strategies to enhance ß cell regeneration or increase cell proliferation could improve outcomes for patients with diabetes. Research conducted over the past several years has revealed that factors regulating embryonic ß cell mass expansion differ from those regulating replication of ß cells post-weaning. This article aims to compare and contrast factors known to control embryonic and postnatal ß cell replication. In addition, we explore the possibility that connective tissue growth factor (CTGF) could increase adult ß cell replication. We have already shown that CTGF is required for embryonic ß cell proliferation and is sufficient to induce replication of embryonic ß cells. Here we examine whether adult ß cell replication and expansion of ß cell mass can be enhanced by increased CTGF expression in mature ß cells.

Sensory neuron differentiation is regulated by notch signaling in the trigeminal placode.

Trigeminal sensory neurons develop from the neural crest and neurogenic placodes, and have been studied as a principal model of sensory neuron formation. While the Notch pathway has been extensively characterized in central nervous system development and other developmental processes, it has not been well characterized in sensory neurogenesis. Here we studied the functional role of Notch signaling in the trigeminal ophthalmic (opV) placode, a prime model of sensory neurogenesis. To establish a good spatiotemporal description of Notch pathway genes in the chick trigeminal placode, a stage-specific expression analysis was conducted, showing that expression of most Notch pathway genes and effectors are expressed in the placode, with expression primarily being confined to ectodermal cells. Expression was highest at stages of peak neuronal differentiation. To test the function of Notch signaling in opV placode cell differentiation, Notch receptor cleavage was blocked using the gamma-secretase inhibitor, DAPT, or signaling was activated by misexpression of the Notch intracellular domain (NICD). Notch activation resulted in a significant reduction in sensory neurogenesis. Cells remained in the ectoderm and did not differentiate. Expression of the opV specification marker Pax3 was also lost in targeted cells. DAPT exposure resulted in a dramatic increase in neurogenesis without increasing proliferation, where many differentiated cells were found in the mesenchyme and, surprisingly, within the ectoderm. This is the first result clearly showing prolific neuronal differentiation in the ectoderm of the trigeminal placodes after experimental manipulation of a molecular signaling pathway, thus identifying Notch signaling as a primary regulator of the sensory neuron fate in the opV placode.