Effect of Postoperative Analgesic Exposure to the Cannabinoid Receptor Agonist WIN55 on Osteogenic Differentiation and Spinal Fusion in Rats.

BACKGROUND: After spinal surgery and other orthopaedic procedures, most patients receive opioids for pain, leading to potential complications such as pseudarthrosis and opioid abuse associated with long-term use. As an alternative, the endocannabinoid system has been shown to have antinociceptive activity, while contributing to bone homeostasis via the CB1 and CB2 cannabinoid receptors. This study evaluates the impact of the cannabinoid receptor agonist WIN55,212-2 (WIN55) on osteogenic differentiation in vitro as well as bone regeneration and spinal fusion in a preclinical rat model. METHODS: Primary rat bone marrow stromal cells were cultured in standard or osteogenic media and exposed to vehicle alone or WIN55. Runx2 and Alkaline phosphatase (Alpl) were quantified via qPCR (quantitative real-time polymerase chain reaction), followed by assessment of ALP activity and matrix mineralization. For in vivo evaluation, 45 female Sprague Dawley rats (n = 15 per group) underwent L4-L5 posterolateral spinal fusion with bilateral placement of collagen scaffolds preloaded with low-dose rhBMP-2 (recombinant human bone morphogenetic protein-2; 0.5 µg/implant). Postoperatively, rats received the vehicle alone or 0.5 or 2.5 mg/kg WIN55 via daily intraperitoneal injections for 5 days. Bone regeneration and spinal fusion were assessed using radiography, manual palpation-based fusion scoring, microcomputed tomography imaging, and histology. RESULTS: mRNA expression levels of Runx2 and Alp were similar among cells treated with vehicle alone and WIN55. Likewise, exposure to WIN55 did not inhibit ALP activity or bone matrix mineralization. In this animal model, no significant differences were found among groups with regard to mean fusion score, fusion rate, or new bone volume. CONCLUSIONS: WIN55 showed no adverse impact on osteogenic differentiation, bone regeneration, and spinal fusion. This supports that cannabinoid receptor agonists should be further investigated as a potential alternative approach for postoperative analgesia following spinal fusion and other orthopaedic procedures requiring bone-healing. CLINICAL RELEVANCE: The identification of alternative treatments for postoperative pain following orthopaedic surgical procedures is crucial in combating the ongoing opioid abuse crisis. The endocannabinoid system may represent a viable alternative target for addressing orthopaedic postoperative pain.

Thoracic Endovascular Aortic Repair Adverse Events Reported In The Food And Drug Administration Manufacturer And User Facility Device Experience Database.

PURPOSE: The purpose of this study is to identify adverse events (device- and patient-related) associated with thoracic aortic stent graft systems and their timing post-procedure. MATERIALS AND METHODS: The Food and Drug Administration's Manufacturer and User Facility Device Experience (FDA-MAUDE) voluntary database was searched for Thoracic Aortic Endovascular Repair (TEVAR) devices reported over the course of 1 year (January 1, 2014 to December 31, 2014). The data abstracted included the indication for treatment, device used, and adverse events. RESULTS: During 2014, there were 334 original submissions to the FDA-MAUDE database describing 371 adverse events regarding TEVAR devices that met inclusion criteria for this study. All submissions were from manufacturers, and none were from physicians. The most common pathologies treated were thoracic aortic aneurysm (67.6%) and type B aortic dissection (25.1%). The most frequently reported intraoperative, early postoperative (<30 days), and late postoperative (>30 days) events overall were technical device failure, neurologic complications (stroke, paraplegia), and endoleak, respectively. Of note, there were descriptions of retained deployment materials, late graft infections, and aorto-visceral fistula formation up to 3 years postoperatively. CONCLUSION: The MAUDE database is a valuable repository for complications and device failures that are not otherwise in the published literature and submitted by manufacturers relating to this relatively new technology.

3D Printing Applications in Minimally Invasive Spine Surgery.

3D printing (3DP) technology continues to gain popularity among medical specialties as a useful tool to improve patient care. The field of spine surgery is one discipline that has utilized this; however, information regarding the use of 3DP in minimally invasive spine surgery (MISS) is limited. 3D printing is currently being utilized in spine surgery to create biomodels, hardware templates and guides, and implants. Minimally invasive spine surgeons have begun to adopt 3DP technology, specifically with the use of biomodeling to optimize preoperative planning. Factors limiting widespread adoption of 3DP include increased time, cost, and the limited range of diagnoses in which 3DP has thus far been utilized. 3DP technology has become a valuable tool utilized by spine surgeons, and there are limitless directions in which this technology can be applied to minimally invasive spine surgery.

Economics of Malignant Gliomas: A Critical Review.

PURPOSE: Approximately 18,500 persons are diagnosed with malignant glioma in the United States annually. Few studies have investigated the comprehensive economic costs. We reviewed the literature to examine costs to patients with malignant glioma and their families, payers, and society. METHODS: A total of 18 fully extracted studies were included. Data were collected on direct and indirect costs, and cost estimates were converted to US dollars using the conversion rate calculated from the study's publication date, and updated to 2011 values after adjustment for inflation. A standardized data abstraction form was used. Data were extracted by one reviewer and checked by another. RESULTS: Before approval of effective chemotherapeutic agents for malignant gliomas, estimated total direct medical costs in the United States for surgery and radiation therapy per patient ranged from $50,600 to $92,700. The addition of temozolomide (TMZ) and bevacizumab to glioblastoma treatment regimens has resulted in increased overall costs for glioma care. Although health care costs are now less front-loaded, they have increased over the course of illness. Analysis using a willingness-to-pay threshold of $50,000 per quality-adjusted life-year suggests that the benefits of TMZ fall on the edge of acceptable therapies. Furthermore, indirect medical costs, such as productivity losses, are not trivial. CONCLUSION: With increased chemotherapy use for malignant glioma, the paradigm for treatment and associated out-of-pocket and total medical costs continue to evolve. Larger out-of-pocket costs may influence the choice of chemotherapeutic agents, the economic implications of which should be evaluated prospectively.