Outcome of traumatic thoracolumbar spine fractures in elderly: A systematic review.

Introduction: Adequate guidelines for treatment of people over 65 years, suffering traumatic thoracolumbar spine fractures without neurologic deficit, are currently lacking. Research question: The aim of this study was to systematically review the available literature regarding the outcome of conservative and surgical treatment of thoracolumbar spinal trauma in elderly patients. Material and methods: A systematic review according the PRISMA guidelines was performed. Pubmed, Web of Science, EMBASE and the Cochrane Central register were searched until June 2021. Risk of bias of the included studies was evaluated. Clinical and radiological results, as well as complications of conservative or surgical treatment were reviewed. Results: Six articles were included (one prospective randomized trial, two prospective and three retrospective cohort studies). In these studies conflicting results were observed with regard to pain, radiological results and complications following both conservative and surgical treatment strategies for thoracolumbar spine fractures in elderly. Discussion and conclusion: Treatment of thoracolumbar fractures in elderly should focus on early mobilization to reduce complications and hospital stay. This may improve functional outcome and prevent worsening of frailty in this vulnerable group of patients. To elucidate the optimal treatment for elderly patient with thoracolumbar fractures, future research should focus on patient specific treatment rather than the mere difference between outcome of surgical and conservative treatment.

Term and definition of a deformity after a spine trauma: Results of an international Delphi study.

Introduction: Deformity of the spinal column after trauma could lead to pain, impaired function, and may sometimes necessitate extensive and high-risk surgery. This 'condition' has multiple terms and definitions that are used in research and clinics. A specific term and definition of this condition however is still lacking. A uniform and internationally accepted term and definition are necessary to compare cases and treatments in the future. Research question: Reach consensus on the term and definition of this deformity after spine trauma using a Delphi approach. Material and methods: An 'all-rounds invitation' Delphi process was used in this study among a group of international experts. The first round consisted of an online survey using input from preparatory studies, a typical clinical case and ICD-11 codes. The second round showed the results in-person and discussion was encouraged. Participants voted for rejection of certain terms. In the third round the final vote took place. When >80 % of the votes was for or against a term the term was rejected or accepted. Results: Response rate was high (≥84 %). The 3 Delphi rounds were completed. Unanimous voting led to the acceptance of the term and abbreviation as PSD. Deformity in any plane, pain, impaired function, and neurological deficit, were deemed important to include in the definition of PSD. Discussion and conclusion: Unanimous consensus was reached on 'Posttraumatic spinal deformity: Condition where a trauma to the spine results in a deformity in any plane and results in pain and an impaired function with or without a neurological deficit.'

Surgeon reported treatment choices for AO type B and C thoracolumbar fractures without neurological deficits: An expert survey.

INTRODUCTION: Less invasive spine surgery (LISS) has become well-established for thoracolumbar burst fractures without neurological deficits. However, notable controversy persists regarding the adequacy of LISS for more unstable AO type B and C injuries, as it does not allow for formal open fusion. MATERIALS AND METHODS: In this cross-sectional survey experienced spine surgeons of the Dutch Spine Society were invited to participate (56 participants). They were asked to indicate the most appropriate treatment for AO type B1, B2 (L1: A1 and L1: A3), B3 and C (L1: A4) injuries at level Th12-L1. Taking into account: age, AO N0-N1, or polytrauma. Specific agreement between participants was obtained applying Variation Ratio (VR). RESULTS: A significant level of overall agreement was observed for AO type-B1 injuries with 73.8% of participants opting for percutaneous short-segment fixation (VR 0.775). For AO type-B3 injuries, 79.4% of participants favored percutaneous long-segment fixation (VR 0.794). for AO type-B2 injuries, there was less overall agreement (VR 0.571-0.657). Nonetheless, when considering all AO type-B injuries combined, percutaneous fixation emerged as the most preferred treatment option with substantial agreement (VR 0.871-0.923). Conversely, for AO type-C injuries, there was less agreement among the participants (VI 0.411), 26.5% of them chose additional open spinal fusion. CONCLUSION: For all AO type-B injuries there was substantial agreement to treat these fractures with percutaneous techniques. For AO type-C injuries, the survey results do not support a consensus. Nevertheless, the responses raise important questions about the necessity of spinal fusion for such injuries.

Natural Experiments as a Study Method in Spinal Trauma Surgery: A Systematic Review.

STUDY DESIGN: Systematic review. OBJECTIVES: To determine if the natural experiment design is a useful research methodology concept in spinal trauma care, and to determine if this methodology can be a viable alternative when randomized controlled trials are either infeasible or unethical. METHODS: A Medline, Embase and Cochrane database search was performed between 2004 and 2023 for studies comparing different treatment modalities of spinal trauma. All observational studies with a natural experiment design comparing different treatment modalities of spinal trauma were included. Data extraction and quality assessment with the MINORS criteria was performed. RESULTS: Four studies with a natural experiment design regarding patients with traumatic spinal fractures were included. All studies were retrospective, one study collected follow-up data prospectively. Three studies compared different operative treatment modalities, whereas one study compared different antibiotic treatment strategies. Two studies compared preferred treatment modalities between expertise centers, one study between departments (neuro- and orthopedic surgery) and one amongst surgeons. For the included retrospective studies, MINORS scores (maximum score 18) were high ranging from 12-17 and with a mean (SD) of 14.6 (1.63). CONCLUSIONS: Since 2004 only four studies using a natural experiment design have been conducted in spinal trauma. In the included studies, comparability of patient groups was high emphasizing the potential of natural experiments in spinal trauma research. Natural experiments design should be considered more frequently in future research in spinal trauma as they may help to address difficult clinical problems when RCT's are infeasible or unethical.

Surgical techniques in restoration lumbar lordosis: a biomechanical human cadaveric study.

PURPOSE: Degenerative changes of the lumbar spine lead in general to decrease of lumbar lordosis (LL). This change affects the overall balance of the spine, and when surgery is deemed, necessary restoration of the LL is considered. How this restoration can be achieved is a matter of controversy. The main purpose of this cadaveric study was to investigate the different steps of common posterior surgical techniques to understand the contribution of each successive step in restoring LL. METHODS: Ten fresh-frozen human lumbar spine specimens were used to perform a sequential correction and instrumentation with a pedicle screw construct. RESULTS: The mean LL angle measured at L3-L4 in intact condition was 12.9°; after screw insertion and compression, this increased to 13.8° (+ 7%, p = 0.04), after bilateral facetectomy to 16.3° (+ 20%, p = 0.005), after discectomy and insertion of interbody cage to 18.0º (+ 9%, p = 0.012), after resection of the lamina and the processes spinosus to 19.8° (+ 10%, p = 0.017), and after resection of the anterior longitudinal ligament to 25.4° (+ 22%, p = 0.005). CONCLUSIONS: Each step contributed statistically significant to restoration of segmental lordosis with bilateral facetectomy contributing the most in terms of percentage. LEVEL OF EVIDENCE: IV.

Correction of the pelvic incidence using a bilateral extending pelvic osteotomy: a proof of concept study.

INTRODUCTION: The aim of this proof of concept human cadaver study was to quantify the effect of a bilateral extending pelvic osteotomy (BEPO) on pelvic incidence (PI) as a potential alternative for a pedicle subtraction osteotomy (PSO) in patients with severe spinal sagittal malalignment. MATERIALS AND METHODS: 10 fresh frozen human cadavers were treated with the BEPO technique. CT images were made before and after the osteotomy and pure sagittal images were created on which PI was measured. RESULTS: The mean pre-osteotomy PI was 47.9° (range 36.4-63.9) and the mean post-osteotomy PI was 36.5° (range 22.1-54.4). The mean correction was - 10.4° with a range of - 8.4° to - 17.3° (p = 0.03), which resulted in a mean decrease of 23% in the PI (range 16-42). CONCLUSIONS: There was a feasible and effective correction of PI using the BEPO technique on the os ilium. This was a preliminary cadaveric study. No conclusions could be made on global sagittal alignment. We postulate that an extending osteotomy of the ilium could be a potential alternative for a PSO reducing the complexity of spine surgery in patients with severe spinal sagittal malalignment.

N(6)-methyladenosine RNA methyltransferase like 3 inhibits extracellular matrix synthesis of endplate chondrocytes by downregulating sex-determining region Y-Box transcription factor 9 expression under tension.

OBJECTIVE: Tension stimulation is an important inducer of endplate cartilage degeneration, but the specific regulatory mechanism remains unclear. This study was the first to reveal the mechanism by which methyltransferase-like 3 (METTL3)-mediated N(6)-methyladenosine (m6A) modification affected the extracellular matrix anabolism by tension-induced endplate chondrocytes. METHOD: We examined the differences in METTL3 expression and m6A methylation levels in human endplate chondrocytes and human cartilage endplate tissues under in vitro tension. The effect on endplate cartilage degeneration was evaluated by manipulating m6A methylation mediated by METTL3 in vivo and in vitro. The effect of METTL3-mediated m6A methylation on the stability of sex-determining region Y-box transcription factor 9 (SOX9) gene expression was determined experimentally. RESULTS: METTL3 expression and m6A methylation levels were significantly increased in degenerative human endplate cartilage tissue. Similarly, tension stimulation inhibited the ability of human endplate chondrocytes to synthesize extracellular matrix, which was accompanied by an increase in METTL3-mediated m6A methylation. The ability of endplate chondrocytes to resist tension was significantly enhanced by inhibiting METTL3 expression and subsequently downregulating m6A methylation in vitro and in vivo, thereby reducing intervertebral disc degeneration. Furthermore, METTL3 mediated SOX9 RNA methylation and disrupted SOX9 mRNA stability, thereby inhibiting the gene expression of the downstream collagen type II alpha 1 chain. CONCLUSION: Tension stimulation downregulated SOX9 expression through METTL3-mediated m6A methylation, thereby inhibiting the synthesis of extracellular matrix in endplate chondrocytes.

Machine learning prediction models in orthopedic surgery: A systematic review in transparent reporting.

Machine learning (ML) studies are becoming increasingly popular in orthopedics but lack a critically appraisal of their adherence to peer-reviewed guidelines. The objective of this review was to (1) evaluate quality and transparent reporting of ML prediction models in orthopedic surgery based on the transparent reporting of multivariable prediction models for individual prognosis or diagnosis (TRIPOD), and (2) assess risk of bias with the Prediction model Risk Of Bias ASsessment Tool. A systematic review was performed to identify all ML prediction studies published in orthopedic surgery through June 18th, 2020. After screening 7138 studies, 59 studies met the study criteria and were included. Two reviewers independently extracted data and discrepancies were resolved by discussion with at least two additional reviewers present. Across all studies, the overall median completeness for the TRIPOD checklist was 53% (interquartile range 47%-60%). The overall risk of bias was low in 44% (n = 26), high in 41% (n = 24), and unclear in 15% (n = 9). High overall risk of bias was driven by incomplete reporting of performance measures, inadequate handling of missing data, and use of small datasets with inadequate outcome numbers. Although the number of ML studies in orthopedic surgery is increasing rapidly, over 40% of the existing models are at high risk of bias. Furthermore, over half incompletely reported their methods and/or performance measures. Until these issues are adequately addressed to give patients and providers trust in ML models, a considerable gap remains between the development of ML prediction models and their implementation in orthopedic practice.

The SNAP Trial: 2-Year Results of a Double-Blind Multicenter Randomized Controlled Trial of a Silicon Nitride Versus a PEEK Cage in Patients After Lumbar Fusion Surgery.

STUDY DESIGN: Randomized controlled trial. OBJECTIVES: Lumbar interbody fusion with cages is performed to provide vertebral stability, restore alignment, and maintain disc and foraminal height. Polyetheretherketone (PEEK) is commonly used. Silicon nitride (Si3N4) is an alternative material with good osteointegrative properties. This study was designed to assess if Si3N4 cages perform similar to PEEK. METHODS: A non-inferiority double-blind multicenter RCT was designed. Patients presenting with chronic low-back pain with or without leg pain were included. Single- or double-level instrumented transforaminal lumbar interbody fusion (TLIF) using an oblique PEEK or Si3N4 cage was performed. The primary outcome was the Roland-Morris Disability Questionnaire (RMDQ). The non-inferiority margin for the RMDQ was 2.6 points on a scale of 24. Secondary outcomes included the Oswestry Disability Questionnaire (ODI), Visual Analogue Scales (VAS), SF-36 Physical Function, patient and surgeon Likert scores, radiographic evaluations for subsidence, segmental motion, and fusion. Follow-up was planned at 3, 6, 12, and 24-months. RESULTS: Ninety-two patients were randomized (i.e. 48 to PEEK and 44 to Si3N4). Both groups showed good clinical improvements on the RMDQ scores of up to 5-8 points during follow-up. No statistically significant differences were observed in clinical and radiographic outcomes. Mean operative time and blood loss were statistically significantly higher for the Si3N4 cohort. Although not statistically significant, there was a higher incidence of complications and revisions associated with the Si3N4 cage. CONCLUSIONS: There was insufficient evidence to conclude that Si3N4 was non-inferior to PEEK.

Are the Roland Morris Disability Questionnaire and Oswestry Disability Index interchangeable in patients after lumbar spinal fusion?

BACKGROUND: Low back pain is a common health problem for which there are several treatment options. For optimizing clinical decision making, evaluation of treatments and research purposes it is important that health care professionals are able to evaluate the functional status of patients. Patient reported outcome measures (PROMs) are widely accepted and recommended. The Roland Morris Disability Questionnaire (RMDQ) and the Oswestry Disability Index (ODI) are the two mainly used condition-specific patient reported outcomes. Concerns regarding the content and structural validity and also the different scoring systems of these outcome measures makes comparison of treatment results difficult. OBJECTIVE: Aim of this study was to determine if the RMDQ and ODI could be used exchangeable by assessing the correlation and comparing different measurement properties between the questionnaires. METHODS: Clinical data from patients who participated in a multicenter RCT with 2 year follow-up after lumbar spinal fusion were used. Outcome measures were the RMDQ, ODI, Short Form 36 - Health Survey (SF-36), leg pain and back pain measured on a 0-100 mm visual analogue scale (VAS). Cronbach's alpha coefficients, Spearman correlation coefficients, multiple regression analysis and Bland-Altman plots were calculated. RESULTS: three hundred and seventy-six completed questionnaires filled out by 87 patients were used. The ODI and RMDQ had both a good level of internal consistency. There was a very strong correlation between the RMDQ and the ODI (r= 0.87; p< 0.001), and between the VAS and both the ODI and RMDQ. However, the Bland-Altman plot indicated bad agreement between the ODI and RMDQ. CONCLUSIONS: The RMDQ and ODI cannot be used interchangeably, nor is there a possibility of converting the score from one questionnaire to the other. However, leg pain and back pain seemed to be predictors for both the ODI and the RMDQ.

Long-term (> 10 years) clinical outcomes of instrumented posterolateral fusion for spondylolisthesis.

PURPOSE: Despite the rapid increase in instrumented spinal fusions for a variety of indications, most studies focus on short-term fusion rates. Long-term clinical outcomes are still scarce and inconclusive. This study investigated clinical outcomes > 10 years after single-level instrumented posterolateral spinal fusion for lumbar degenerative or isthmic spondylolisthesis with neurological symptoms. METHODS: Cross-sectional long-term follow-up among the Dutch participants of an international multicenter randomized controlled trial comparing osteogenic protein-1 with autograft. Clinical outcomes were assessed using the Oswestry Disability Index (ODI), EQ-5D-3L and visual analogue scale (VAS) for leg and back pain, as well as questions on satisfaction with treatment and additional surgery. RESULTS: The follow-up rate was 73% (41 patients). At mean 11.8 (range 10.1-13.7) years after surgery, a non-significant deterioration of clinical outcomes compared to 1-year follow-up was observed. The mean ODI was 20 ± 19, mean EQ-5D-3L index score 0.784 ± 0.251 and mean VAS for leg and back pain, respectively, 34 ± 33 and 31 ± 28. Multiple regression showed that diagnosis (degenerative vs. isthmic spondylolisthesis), graft type (OP-1 vs. autograft) and 1-year fusion status (fusion vs. no fusion) were not predictive for the ODI at long-term follow-up (p = 0.389). Satisfaction with treatment was excellent and over 70% of the patients reported lasting improvement in back and/or leg pain. No revision surgeries for non-union were reported. CONCLUSION: This study showed favourable clinical outcomes > 10 years after instrumented posterolateral spinal fusion and supports spondylolisthesis with neurological symptoms as indication for fusion surgery.

Surgical Restoration of Sagittal Alignment of the Spine: Correlation with Improved Patient-Reported Outcomes: A Systematic Review and Meta-Analysis.

BACKGROUND: The sagittal-plane curvatures of the human spine are the consequence of evolution from quadrupedalism to bipedalism and are needed to maintain the center of mass of the body within the base of support in the bipedal position. Lumbar degenerative disorders can lead to a decrease in lumbar lordosis and thereby affect overall alignment of the spine. However, there is not yet enough direct evidence that surgical restoration of spinal malalignment would lead to a better clinical outcome. Therefore, the aim of this study was to assess the correlation between patient-reported outcomes and actual obtained spinal sagittal alignment in adult patients with lumbar degenerative disorders who underwent surgical treatment. METHODS: A comprehensive literature search was conducted through databases (PubMed, Cochrane, Web of Science, and Embase). The last search was in November 2018. Risk of bias was assessed with the Newcastle-Ottawa quality assessment scale. A meta-regression analysis was performed. RESULTS: Of 2,024 unique articles in the original search, 34 articles with 973 patients were included. All studies were either retrospective or prospective cohort studies; no randomized controlled trials were available. A total of 54 relations between preoperative-to-postoperative improvement in patient-reported outcome measures (PROMs) and radiographic spinopelvic parameters were found, of which 20 were eligible for meta-regression analysis. Of these, 2 correlations were significant: pelvic tilt (PT) versus Oswestry Disability Index (ODI) (p = 0.009) and PT versus visual analog scale (VAS) pain (p = 0.008). CONCLUSIONS: On the basis of the current literature, lower PT was significantly correlated with improved ODI and VAS pain in patients with sagittal malalignment caused by lumbar degenerative disorders that were treated with surgical correction of the sagittal balance. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

The role of bacterial stimuli in inflammation-driven bone formation.

Immune cells and their soluble factors regulate skeletal cells during normal bone regeneration and pathological bone formation. Bacterial infections can trigger immune responses that activate pro-osteogenic pathways, but these are usually overshadowed by osteolysis and concerns of systemic inflammation. The aim of this study was to determine whether the transient local inflammatory reaction to non-viable bacterial immune agonists could lead to favourable new bone formation. In a series of rabbit studies, as proof-of-concept, how tibial intramedullary injection of viable or killed bacterial species affected bone remodelling and new bone formation was determined. Application of killed bacteria led to considerable new bone formation after 4 weeks, without the prolonged systemic inflammation and exaggerated bone lysis seen with active infection. The osteo-immunomodulatory effects of various species of killed bacteria and the dose response relationship were subsequently screened in ectopically-implanted ceramic scaffolds. Histomorphometry after 8 weeks showed that a relatively low dose of killed bacteria enhanced ectopic bone induction. Moreover, lipoteichoic acid - the bacterial cell-wall derived toll-like-receptor (TLR)-2 activator - was identified as an osteo-stimulatory factor. Collectively, the data indicated that bacterial stimuli could be harnessed to stimulate osteogenesis, which occurs through a synergy with osteoinductive signals. This finding holds promise for the use of non-viable bacteria, bacterial antigens, or their simplified analogues as immuno-modulatory bone regenerating tools in bone biomaterials.

Sparing the surgical area with stereotactic body radiotherapy for combined treatment of spinal metastases: a treatment planning study.

INTRODUCTION: Decreasing the radiation dose in the surgical area is important to lower the risk of wound complications when surgery and radiotherapy are combined for the treatment of spinal metastases. The purpose of this study was to compare the radiation dose in the surgical area for spinal metastases between single fraction external beam radiotherapy (EBRT), single fraction stereotactic body radiotherapy (SBRT) and single fraction SBRT with active sparing (SBRT-AS) of the posterior surgical area. METHODS: Radiotherapy treatment plans for EBRT, SBRT and SBRT-AS of the posterior surgical area were created for 13 patients with spinal metastases. A single fraction of 8Gy was prescribed to the spinal metastasis in the EBRT plan. For the SBRT treatment plans, a single fraction of 18Gy was prescribed to the metastasis and 8Gy to the rest of the vertebral body. For the SBRT plan with active sparing the dose in the designated surgical area was minimized without compromising the dose to the organs at risk. RESULTS: The median dose in the surgical area was 2.6Gy (1.6-5.3Gy) in the SBRT plan with active sparing of the surgical area compared to a median dose of 3.7Gy (1.6-6.3Gy) in the SBRT plan without sparing and 6.5Gy (3.5-9.1Gy) in the EBRT plans (p < .001). The radiation doses to the spinal metastases and organs at risk were not significantly different between the SBRT plan with and without sparing the surgical area. CONCLUSIONS: The radiation dose to the surgical area is significantly decreased with the use of SBRT compared to EBRT. Active sparing of the surgical area further decreased the mean radiation dose in the surgical area without compromising the dose to the spinal metastasis and the organs at risk.

Less Invasive Surgery is Feasible in the Management of Traumatic Thoracolumbar Fractures in Isolated and Polytrauma Injury.

BACKGROUND: Less invasive stabilization systems (LISSs) have gained popularity. However, limited quality of life (QOL) and clinical outcome data exist for trauma patients treated with LISSs. The objective of this study is to describe QOL and outcome for posterior percutaneous pedicle screw fixation in the management of traumatic thoracolumbar fractures. METHODS: Between January 2006 and December 2011, data from all patients treated with a posterior percutaneous pedicle screw fixation technique for thoracolumbar fractures were collected and analyzed. Sixty-nine patients met the inclusion criteria. Additional vertebral reduction and cement augmentation was used in 25 patients, when there was more than 50% of vertebral body comminution. RESULTS: Mean follow up of 19 months (range = 6-49 months). Fifty-one percent of the study population consisted of polytrauma patients, with 22% having injury severity score ≥ 15. In 6 cases (8.7%) there were perioperative complications. Response rate for the follow-up health survey was 78%, with a satisfactory overall median EuroQuol score of 0.811 (Q1-Q3 95% confidence interval = 0.709-0.897). CONCLUSIONS: Posterior percutaneous pedicle screw fixation proves to be effective in the management of traumatic thoracolumbar fractures, with a good overall functional outcome. Percutaneous techniques that reduce perioperative morbidity are an alternative approach well suited for damage control orthopaedics, as long as there are no neurological deficits. Especially in polytrauma patients with spine fractures, the spinal column can be stabilized in an emergency setting, while limiting the risks of "a second hit" at the patients' already frail condition. LEVEL OF EVIDENCE: 3.

Neurological Outcome After Traumatic Transverse Sacral Fractures: A Systematic Review of 521 Patients Reported in the Literature.

BACKGROUND: The purpose of this study was to determine the neurological outcome after transverse sacral fractures in patients with neurological impairment. METHODS: A systematic review of the English, French, German, and Dutch literature was conducted. All study designs, including retrospective cohort studies and case reports, describing transverse sacral fractures were included. Two authors independently extracted the predefined data and scored the neurological impairment according to the Gibbons classification after the trauma and at the time of follow-up. The neurological outcomes were pooled according to the Gibbons classification. RESULTS: No randomized controlled trials or prospective case series were found. A total of 139 articles were included, consisting of 81 case reports and 58 retrospective case series involving 521 patients. Regardless of the type of management, neurological recovery of at least 1 Gibbons category was reported in 62% of these patients. A comparison of the neurological outcome of nonoperatively treated patients and surgically treated patients showed similar neurological recovery rates. For the surgically treated patients, fixation of the fracture resulted in a better neurological improvement compared with an isolated decompression. CONCLUSIONS: This review could not provide evidence of improved neurological recovery after surgical treatment compared with nonoperative treatment. When surgical treatment was considered, there was a low level of evidence that fixation of the fracture results in better neurological improvement compared with isolated decompression. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Interleukin 17 enhances bone morphogenetic protein-2-induced ectopic bone formation.

Interleukin 17 (IL-17) stimulates the osteogenic differentiation of progenitor cells in vitro through a synergy with bone morphogenetic protein (BMP)-2. This study investigates whether the diverse responses mediated by IL-17 in vivo also lead to enhanced BMP-2-induced bone formation. Since IL-17 is known to induce osteoclastogenesis, we studied the interactions between IL-17 and BMP-2 in ceramic scaffolds either or not carrying a coating with the bisphosphonate zoledronic acid (ZOL). Histological evaluation revealed that IL-17 alone did not induce any osteoclasts at day 10. On the other hand, BMP-2 clearly stimulated early tissue ingrowth and osteoclastogenesis. Both of these processes were blocked in presence of ZOL. IL-17 signaling restored early vascularized connective tissue formation and osteoclastogenesis induced by BMP-2 in ZOL-coated scaffolds. After 12 weeks, the bone volume induced by co-delivery of BMP-2 and IL-17 was doubled as compared to that induced by BMP-2 alone. We conclude that IL-17 has osteo-stimulatory effects through a synergy with bone-inductive BMP-2. Although local and single application of IL-17 does not mediate osteoclast formation, it could promote other processes involved in bone formation such as connective tissue ingrowth. The use of IL-17 may contribute to the development of improved bone graft substitutes.

Bone formation by heterodimers through non-viral gene delivery of BMP-2/6 and BMP-2/7.

Non-viral gene delivery is a safe technique to release sustained physiologic dosages of bone morphogenetic protein (BMP). Co-delivery of multiple BMPs can result in the formation of more potent BMP heterodimers. In this study, non-viral co-delivery of BMP-2/6 and BMP-2/7, as a mean to produce heterodimers, was assessed. Goat MSCs were non-virally transfected with plasmid DNA encoding BMP isoforms (pBMP) known to be relevant for osteogenesis: BMP-2, -6 or -7. As a result, BMP-2, -6 and -7 were produced and detectable for up to 14 d and their combined delivery (pBMP-2 with pBMP-6 or pBMP-7) was used to create BMP-2/6 and BM-2/7 heterodimers. Formation and secretion of the heterodimer proteins was validated by sandwich enzyme-linked immunosorbent assay (ELISA). Produced BMPs and heterodimers were biologically active, as confirmed by differentiation of reporter cells and MSCs. To assess bone formation, transfected MSCs were seeded on to ceramic scaffolds and implanted subcutaneously into nude mice. Bone formation was significantly enhanced in the pBMP-2/6 condition and a trend for more bone formation was observed in the pBMP-2/7 and pBMP-6 homodimer condition. No bone was found in the pBMP-2, pBMP-7 or control condition. In conclusion, simultaneous delivery of pBMP-2 with pBMP-6 or -7 resulted in the production of heterodimers that were beneficial for bone formation as compared to BMP homodimers. Combination of BMP sequences could reduce the need for high BMP protein dosages and might enhance prolonged availability of the growth factors.

Timing of surgery in traumatic spinal cord injury: a national, multidisciplinary survey.

PURPOSE: The optimal surgical timeframe for neurological recovery in traumatic spinal cord injury (tSCI) still remains unknown. Recent guidelines have recommended performing surgery within 24 h for all patients with tSCI regardless of initial neurological deficit. It remains unclear whether patients with complete, incomplete tSCI, or traumatic central cord injury (TCCI) will experience the same degree of improvement after urgent surgical intervention. We investigated if the severity of initial neurological injury influenced surgeons on their decision-making of surgical timing in tSCI. METHODS: With a web-based survey, we investigated the current opinion in The Netherlands on timing of surgical decompression and stabilization, depending on the initial degree of neurological injury. RESULTS: Surgeons prefer to perform more urgent surgery for incomplete tSCI compared to complete tSCI. In addition, 43% of patients with complete tSCI are not preferably operated within the recommended 24 h. Even though TCCI is the most common form of incomplete tSCI, these patients are preferably managed less urgently than patients with other types of incomplete tSCI. CONCLUSION: The severity of initial neurological injury seems to play an important role in the urgency of surgical timing for tSCI. A substantial number of patients with complete tSCI are not preferably treated within the recommended surgical timeframe, while patients with incomplete tSCI are preferably operated far more urgent than recommended in the current guidelines. These slides can be retrieved under Electronic Supplementary Material.

Stereotactic Radiotherapy Followed by Surgical Stabilization Within 24 h for Unstable Spinal Metastases; A Stage I/IIa Study According to the IDEAL Framework.

Background: Routine treatment for unstable spinal metastases consists of surgical stabilization followed by external beam radiotherapy (EBRT) or stereotactic body radiotherapy (SBRT) after a minimum of 1-2 weeks to allow for initial wound healing. Although routine treatment, there are several downsides. First, radiotherapy induced pain relief is delayed by the time interval required for wound healing. Second, EBRT often requires multiple hospital visits and only 60% of the patients experience pain relief. Third, spinal implants cause imaging artifacts hindering SBRT treatment planning and delivery. Reversing the order of surgery and radiotherapy, with dose sparing of the surgical area by SBRT, could overcome these disadvantages and by eliminating the interval between the two treatments, recovery, and palliation may occur earlier. Design: The safety of SBRT followed by surgical stabilization within 24 h for the treatment of unstable spinal metastases was investigated. Safety was evaluated using the Common-Toxicity-Criteria-Adverse-Events-4.0, with the occurrence of wound complications within 90-days being the primary concern. Results: Between June-2015 and January-2017, 13 patients underwent SBRT followed by surgical stabilization for unstable spinal metastases. The median time between SBRT and surgery was 17-h (IQR 5-19). None of the patients experienced wound complications. Improvements in pain and quality of life were observed over time for all patients. Conclusion: SBRT followed by surgical stabilization within 24 h for the treatment of unstable spinal metastases is safe. Palliation may be experienced earlier and with both treatments being performed in one hospital admission the treatment burden decreases.