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Study Design: A post-test design biological experiment., Objective: The aim of this study was to evaluate the osteogenic effects of riluzole on human mesenchymal stromal cells and osteoblasts., Summary of Background Data: Riluzole may benefit patients with spinal cord injury (SCI) from a neurologic perspective, but little is known about riluzole's effect on bone formation, fracture healing, or osteogenesis., Methods: Human mesenchymal stromal cells (hMSCs) and human osteoblasts (hOB) were obtained and isolated from healthy donors and cultured. The cells were treated with riluzole of different concentrations (50, 150, 450 ng/mL) for 1, 2, 3, and 4 weeks. Cytotoxicity was evaluated as was the induction of osteogenic differentiation of hMSCs. Differentiation was evaluated by measuring alkaline phosphatase (ALP) activity and with Alizarin red staining. Osteogenic gene expression of type I collagen (Col1), ALP, osteocalcin (Ocn), Runx2, Sox9, Runx2/Sox9 ratio were measured by qRT-PCR., Results: No cytotoxicity or increased proliferation was observed in bone marrow derived hMSCs and primary hOBs cultured with riluzole over 7 days. ALP activity was slightly increased in hMSCs after treatment for 2 weeks with riluzole 150 ng/mL and slightly upregulated by 150% (150 ng/mL) and 90% (450 ng/mL) in hMSCs at 3 weeks. In hOBs, ALP activity almost doubled after 2 weeks of culture with riluzole 150 ng/mL (P < 0.05). More pronounced 2.6-fold upregulation was noticed after 3 weeks of culture with riluzole at both 150 ng/mL (P = 0.05) and 450 ng/mL (P = 0.05). No significant influence of riluzole on the mRNA expression of osteocalcin (OCN) was observed., Conclusion: The effect of riluzole on bone formation is mixed; low-dose riluzole has no effect on the viability or function of either hMSCs or hOBs. The activity of ALP in both cell types is upregulated by high-dose riluzole, which may indicate that high-dose riluzole can increase osteogenic metabolism and subsequently accelerate bone healing process. However, at high concentrations, riluzole leads to a decrease in osteogenic gene expression, including Runx2 and type 1 collagen., Level of Evidence: N/A.

Study Design: Laboratory study., Objective: Evaluate the effect of substance P (SP) on an intervertebral disc rat organ culture model., Summary of Background Data: Monolayer cell experiments have demonstrated that exposure intervertebral disc tissue cells to SP leads to upregulation in inflammatory cytokine expression; however, this has not been evaluated in a more complex organ culture model., Methods: Forty-eight intervertebral discs from eight rats were used in an organ culture model. Intervertebral discs were divided into three groups: control, SP-treated group, and a group treated with an SP antagonist followed by SP. Cytokine antibody array was used to quantify expression patterns, which were confirmed using ELISA and real-time polymerase chain reaction., Results: The cytokine array demonstrated a 3.40 ±  0.59-fold increase in interleukin 6 (IL-6) expression in the SP group (P = 0.004), and the effect of SP was mitigated by the SP antagonist (P = 0.03). These results were verified as ELISA demonstrated a significant difference in the IL-6 level between the control group and SP group (0.73 vs. 5.80 ng/mL, P < 0.001), and there was a significant difference in the IL-6 level between the SP and the SP antagonist group (5.80 vs. 4.02 ng/mL, P = 0.01). Similarly, the real-time polymerase chain reaction demonstrated that the discs treated with SP had a 4.77-fold increase in IL-6 levels (P = 0.01) compared to controls, and a significantly greater increase in IL-6 levels between the intervertebral discs in the SP group and those in the SP antagonist group versus control (4.77 vs. 1.57, P = 0.02)., Conclusion: SP lead to the activation of an inflammatory pathway by increasing expression of IL-6 in an intervertebral disc organ culture model. These results provide evidence that SP may be an important factor in the link between intervertebral disc degeneration and low back pain., Level of Evidence: N/A.

Insertion of locking screws through the proximal thigh while locking retrograde femoral nails is arguably more difficult and traumatic to local tissues than locking at other intramedullary nail sites. The purpose of this study was to evaluate whether a "standard" screw length for proximal interlocking of retrograde nails is possible, therefore assessing whether the act of measuring for these screws can be omitted. This article retrospective evaluates screw position and estimated proximal locking screw length in patients undergoing retrograde nailing using a large radiographically measured computed tomography cohort, with validation through a smaller clinical cohort. According to these data, it seems reasonable to skip depth gauge measurement during anteroposterior interlocking of retrograde femoral nails and insert a standard length screw based on location relative to the lesser trochanter. This should decrease the amount of local trauma to the patient at the locking screw site while increasing operating room efficiency by avoiding what can often become a difficult step during the procedure.

Study Design: Laboratory study., Objective: To evaluate whether blockade of the Substance P (SP) NK1R attenuates its proinflammatory effect on human intervertebral disc cells (IVD), and to evaluate the signaling pathways associated with SP., Summary of Background Data: SP and its receptors are expressed in human IVD cells, and cause upregulation of inflammatory mediators; however, the effects of blocking these receptors have not been studied in human IVD cells., Methods: Human annulus fibrosus (AF) and nucleus pulposus (NP) cells were expanded in monolayer, and then suspended in alginate beads. The alginate beads were treated with culture medium first containing a high affinity NK1R antagonist (L-760735) at different concentrations, and then with medium containing both NK1R antagonist and SP at 2 concentrations. Ribonucleic acid was isolated and transcribed into cDNA. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to evaluate expression of interleukin (IL)-1β, IL-6, and IL-8. Western blot analysis was performed to examine levels of the phosphorylated p38 mitogen-activated protein kinase (MAPK), extracellular signal regulated kinase 1/2 (ERK1/2) and nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB p65). The cells were pretreated with specific inhibitors of p38 (SB203580), ERK1/2 (PD98059), and p65 (SM7368) and then stimulated with SP., Results: We detected expression of NK1R, neurokinin receptor 2 (NK2R), and neurokinin receptor 3 (NK3R) in AF and NP cells. Treatment of disc cells with the NK1R antagonist was able to suppress expression of IL-1β, IL-6, and IL-8 in a dose-dependent manner. SP stimulation increased phosphorylation of p38-MAPK and ERK1/2, but not of NFκB p65. This indicates that p38-MAPK and ERK1/2 control SP-induced cytokine expression independently from NF-kB p65. Inhibition of p38 and ERK1/2 activation reduced SP-induced IL-6 production in human disc cells., Conclusion: NK1R is responsible for the proinflammatory effect of SP on IVD cells and this effect can be blocked by preventing binding of SP to NK1R. This study shows for the first time that SP mediates signaling in disc cells through NK1R and that SP activates the proinflammatory p38-MAPK and ERK1/2 pathways., Level of Evidence: 4.

Study Design: Multinational survey of spine trauma surgeons., Objectives: To survey spine trauma surgeons, examine the variety of management practices for thoracolumbar fractures, and investigate the need for future areas of study., Background: Attempts to develop a universal thoracolumbar classification system represent the first step in standardizing treatment of thoracolumbar injuries, but there is little consensus regarding diagnosis and management of these injuries., Methods: A survey questionnaire regarding a fictional neurologically intact patient with a burst fracture was administered to 46 spine surgeons. The questionnaire consisted of 2 domains: management of thoracolumbar fractures and management of postoperative infection. Survey results were compiled and evaluated and consensus arbitrarily assumed when the majority of surgeons agreed on a single question answer., Results: Although majority consensus was reached on most questions, the interobserver reliability was poor. Consensus was achieved that magnetic resonance imaging should be performed during initial imaging. The majority would also operate regardless of magnetic resonance imaging findings, and would not operate at night. The favored technique was a posterior approach with decompression. Percutaneous fusion was considered a viable option by the majority of surgeons. No consensus was reached regarding instrumentation levels or construct length. The majority would use posterolateral bone grafting, and would not remove instrumentation nor perform an anterior reconstruction. Consensus was reached that postoperative bracing is unnecessary. Regarding management of infection, consensus was reached to use intraoperative vancomycin powder but not culture the nares before surgery. The majority used a set time period for antibiotic treatment when a drain was required, and would not apply supplementary bone graft at the time of final debridement and closure., Conclusions: There is lack of consensus regarding the appropriate management of thoracolumbar fractures. In the future, multicenter prospective studies are necessary to establish guidelines for the management of thoracolumbar fractures.

Study Design: Survey of spine surgeons., Objective: To develop a validated regional and global injury severity scoring system for thoracolumbar trauma., Summary of Background Data: The AOSpine Thoracolumbar Spine Injury Classification System was recently published and combines elements of both the Magerl system and the Thoracolumbar Injury Classification System; however, the injury severity of each fracture has yet to be established., Methods: A survey was sent to 100 AOSpine members from all 6 AO regions of the world (North America, South America, Europe, Africa, Asia, and the Middle East). Each respondent was asked to numerically grade the severity of each variable of the AOSpine Thoracolumbar Spine Injury Classification System including the morphology, neurological grade, and patient specific modifiers. A grade of zero was considered to be not severe at all, and a grade of 100 was the most severe injury possible., Results: Seventy-four AOSpine surgeons from all 6 AO regions of the world numerically graded the severity of each variable of the AOSpine Thoracolumbar Spine Injury Classification System to establish the injury severity score. The reported fracture severity increased significantly (P < 0.0001) as the subtypes of fracture type A and type B increased, and a significant difference (P < 0.0001) in severity was established for burst fractures with involvement of 2 versus 1 endplates. Finally, no regional or experiential difference in severity or classification was identified., Conclusion: Development of a globally applicable injury severity scoring system for thoracolumbar trauma is possible. This study demonstrates no regional or experiential difference in perceived severity or thoracolumbar spine trauma. The AOSpine Thoracolumbar Spine Injury Classification System provides a logical approach to assessing these injuries and enables rational strategies for treatment., Level of Evidence: 4.

Objectives: The purpose of this study was to determine significant factors that may impact the postoperative differences in femoral version (DFV) and differences in femoral length (DFL) between the fixed and uninjured sides after intramedullary nailing (IMN) secondary to gunshot wounds., Design: Retrospective data registry study., Setting: Academic level I trauma center., Patients: Over a 10-year period, 417 patients underwent IMN of a diaphyseal femur fracture (OTA/AO 32A-C). Of these, 57 patients sustained fractures caused by gunshots and had a postoperative computed tomographic scanogram., Main Outcome Measures: DFV and DFL. The effect of the following variables on DFV and DFL were determined through univariate and stepwise multivariate regression analyses: age, sex, body mass index, trauma fellowship-trained versus nontrauma surgeon, daytime versus nighttime surgery, antegrade versus retrograde nail insertion, use of traction, type of operating table, and AO and Winquist classifications., Results: The mean postoperative DFV for all patients was 8.62 degrees (±6.67 degrees). Postoperative DFV greater than 15 degrees was found in 12.3% of all patients. After IMN, no significant differences in DFV were found with increasing complexity of AO/OTA or Winquist fracture classification. None of the aforementioned independent variables were significantly predictive of postoperative DFV in univariate or multivariate analyses. The mean postoperative DFL for all patients was 5.25 mm (±4.36 mm). In a multivariate model, classification as Winquist type 3 or 4 was weakly (adjusted R = 0.075) but significantly predictive of less DFL than categorization as type 1 or 2 (P = 0.027)., Conclusions: Although gunshot-associated femur fractures may present surgical challenges for treatment through IMN, acceptable femoral rotation and length are obtainable regardless of the fracture complexity or a variety of demographic and surgically-related variables., Level of Evidence: Prognostic level II.

Study Design: Laboratory study., Objective: To evaluate the differential gene expression of cytokines and growth factors in anterior versus posterior annulus fibrosus (AF) intervertebral disc (IVD) specimens., Summary of Background Data: Histological analysis has demonstrated regional differences in vascular and neural ingrowth in the IVD, and similar differences may exist for cytokine and growth factor expression in patients with degenerative disc disease (DDD). Regional expression of these cytokines may also be related to the pain experienced in DDD., Methods: IVD tissue was obtained from patients undergoing anterior lumbar interbody fusion surgery for back pain with radiological evidence of disc degeneration. For a control group, the discs of patients undergoing anterior lumbar discectomy for degenerative scoliosis were obtained as well. The tissue was carefully removed and separated into anterior and posterior AF. After tissue processing, an antibody array was completed to determine expression levels of 42 cytokines and growth factors., Results: Nine discs from 7 patients with DDD and 5 discs from 2 patients with scoliosis were analyzed. In the DDD group, there were 10 cytokines and growth factors with significantly increased expression in the posterior AF versus the anterior AF ([interleukin] IL-4, IL-5, IL-6, M-CSF, MDC, tumor necrosis factor β, EGF, IGF-1, angiogenin, leptin). In the scoliosis group, only angiogenin and PDGF-BB demonstrated increased expression in the posterior AF. No cytokines or growth factors had increased expression in the anterior AF compared with posterior AF., Conclusion: The posterior AF expresses increased levels of cytokines and growth factors compared with the anterior AF in patients with DDD. This differential expression may be important for targeting treatment of painful IVDs., Level of Evidence: N/A.

Study Design: Retrospective uncontrolled case series., Objective: The purpose of this study was to determine the association, if any, between intraoperative blood loss and need for transfusion with the use of periapical (Ponte) osteotomies, as well as other patient and surgical variables among patients with adolescent idiopathic scoliosis (AIS) undergoing posterior spinal instrumentation and fusion., Summary of Background Data: Blood loss during posterior spinal fusion for AIS can be substantial. Numerous techniques are used to minimize intraoperative blood loss and the need for allogeneic transfusion. However, it is unclear which patient and surgeon variables affect blood loss most significantly., Methods: A review was conducted on consecutive patients with AIS who had undergone posterior spinal fusion from July 1997 to February 2013 by a single primary surgeon at 1 institution. The relationship of estimated blood loss, normalized blood loss (normalized blood loss = estimated blood loss/number of levels fused/patient's weight in kilograms), autologous blood retrieved, and allogeneic transfusion received with various patient- and procedure-related variables were analyzed., Results: Estimated blood loss, normalized blood loss, and autologous blood retrieved were higher in patients who underwent periapical Ponte osteotomies (n = 38) (P < 0.0001, P < 0.001, P < 0.01, respectively). The mean major curve correction was 64% in patients without osteotomies, and 65% in patients with osteotomies (P = 0.81). All patients who underwent osteotomies (38/38) received allogeneic transfusion versus 26% (19/73) of those without osteotomies (P < 0.001). The likelihood of transfusion correlated with increasing number of osteotomies and a lower preoperative hemoglobin level (odds ratio, 3.34; P = 0.003; and odds ratio, 0.51; P = 0.02, respectively)., Conclusion: In patients with AIS undergoing posterior spinal fusion with instrumentation, performing periapical osteotomies increased all measures of intraoperative blood loss and need for transfusion without substantially improving major curve correction. As expected, a lower preoperative hemoglobin level was observed in patients who received a blood transfusion after posterior instrumentation and fusion., Level of Evidence: 4.

Objective: The purpose of this study was to compare various gender and ethnic groups to characterize differences in baseline version and rates of retroversion., Design: Retrospective., Setting: Level 1 trauma center., Patients/participants: Between 2000 and 2009, 417 consecutive patients with femur fractures were treated with an intramedullary nail at level I trauma and tertiary referral center. Of these, 328 with computed tomography scanogram of the normal, uninjured contralateral femur were included in this study., Main Outcome Measurements: Femoral version., Results: The mean alignment for the all patients was 8.84 ± 9.66° of anteversion. There were no statistically significant differences in mean version between African American, white, and Hispanic patients for males or females. Although there were also no significant differences in rates between ethnicities, retroversion was found to be common in white males (21.4%), African American males (15.1%), and all groups of females (>14.3%). Furthermore, nearly 6% of both African American males and females exhibited >10° retroversion., Conclusions: Although there may not be a significant difference in average femoral version between ethnic and gender groups, retroversion is relatively common, and retroversion >10° was observed in nearly 6% of the African American population. This may have important implications in proper alignment restoration and successful clinical outcomes after intramedullary nailing of femur fractures.