Under pressure - A historical vignette on surgical timing in traumatic spinal cord injury.

Introduction: It was not even a century ago when a spinal cord injury (SCI) would inevitably result in a fatal outcome, particularly for those with complete SCI. Throughout history, there have been extensive endeavours to change the prospects for SCI patients by performing surgery, even though many believed that there was no way to alter the catastrophic course of SCI. To this day, the debate regarding the efficacy of surgery in improving the neurological outcome for SCI patients persists, along with discussions about the timing of surgical intervention. Research question: How have the historical surgical results shaped our perspective on the surgical treatment of SCI? Material and methods: Narrative literature review. Results: Throughout history there have been multiple surgical attempts to alter the course of SCI, with conflicting results. While studies suggest a potential link between timing of surgery and neurological recovery, the exact impact of immediate surgery on individual cases remains ambiguous. It is becoming more evident that, alongside surgical intervention, factors specific to both the patient and their surgical treatment will significantly influence neurological recovery. Conclusion: Although a growing number of studies indicates a potential correlation of surgical timing and neurological outcome, the precise influence of urgent surgery on an individual basis remains uncertain. It is increasingly apparent that, despite surgery, patient- and treatment-specific factors will also play a role in determining the neurological outcome. Notably, these very factors have influenced the results in previous studies and our views concerning surgical timing.

Understanding Decision Making as It Influences Treatment in Thoracolumbar Burst Fractures Without Neurological Deficit: Conceptual Framework and Methodology.

STUDY DESIGN: This paper presents a description of a conceptual framework and methodology that is applicable to the manuscripts that comprise this focus issue. OBJECTIVES: Our goal is to present a conceptual framework which is relied upon to better understand the processes through which surgeons make therapeutic decisions around how to treat thoracolumbar burst fractures (TL) fractures. METHODS: We will describe the methodology used in the AO Spine TL A3/4 Study prospective observational study and how the radiographs collected for this study were utilized to study the relationships between various variables that factor into surgeon decision making. RESULTS: With 22 expert spine trauma surgeons analyzing the acute CT scans of 183 patients with TL fractures we were able to perform pairwise analyses, look at reliability and correlations between responses and develop frequency tables, and regression models to assess the relationships and interactions between variables. We also used machine learning to develop decision trees. CONCLUSIONS: This paper outlines the overall methodological elements that are common to the subsequent papers in this focus issue.

Using Equipoise to Determine the Radiographic Characteristics Leading to Agreement on Best Treatment for Thoracolumbar Burst Fractures Without Neurologic Deficits.

STUDY DESIGN: Retrospective analysis of prospectively collected data. OBJECTIVES: Our goal was to assess radiographic characteristics associated with agreement and disagreement in treatment recommendation in thoracolumbar (TL) burst fractures. METHODS: A panel of 22 AO Spine Knowledge Forum Trauma experts reviewed 183 cases and were asked to: (1) classify the fracture; (2) assess degree of certainty of PLC disruption; (3) assess degree of comminution; and (4) make a treatment recommendation. Equipoise threshold used was 77% (77:23 distribution of uncertainty or 17 vs 5 experts). Two groups were created: consensus vs equipoise. RESULTS: Of the 183 cases reviewed, the experts reached full consensus in only 8 cases (4.4%). Eighty-one cases (44.3%) were included in the agreement group and 102 cases (55.7%) in the equipoise group. A3/A4 fractures were more common in the equipoise group (92.0% vs 83.7%, P < .001). The agreement group had higher degree of certainty of PLC disruption [35.8% (SD 34.2) vs 27.6 (SD 27.3), P < .001] and more common use of the M1 modifier (44.3% vs 38.3%, P < .001). Overall, the degree of comminution was slightly higher in the equipoise group [47.8 (SD 20.5) vs 45.7 (SD 23.4), P < .001]. CONCLUSIONS: The agreement group had a higher degree of certainty of PLC injury and more common use of M1 modifier (more type B fractures). The equipoise group had more A3/A4 type fractures. Future studies are required to identify the role of comminution in decision making as degree of comminution was slightly higher in the equipoise group.

What Factors Influence Surgeons in Decision-Making in Thoracolumbar Burst Fractures? A Survey-Based Investigation of a Panel of Spine Surgery Experts.

STUDY DESIGN: Cross-sectional survey study. OBJECTIVE: To investigate factors affecting decision-making in thoracolumbar burst-fractures without neurologic deficit. METHODS: A 40-question survey addressing expert-related, economic, and radiological factors was distributed to 30 international trauma experts. Descriptive statistics were used to assess the impact of these factors on operative or non-operative management preferences. RESULTS: Out of 30 experts, 27 completed the survey. The majority of respondents worked at level 1 trauma centers (81.5%) within university settings (77.8%). They were primarily orthopedic surgeons (66.7%) and had over 10 years of experience (70.4%). About 81% found distinguishing between A3 and A4 fractures relevant for decision-making. Most experts (59%) treated A3 fractures non-surgically, while only 30% treated A4 fractures conservatively. Compensation systems did not influence treatment recommendations, and hospital measures promoting surgeries did not significantly affect distribution. Radiological factors, such as local kyphosis (25/27), fracture comminution (23/27), overall sagittal balance (21/27), and spinal canal narrowing (20/27), influenced decisions. CONCLUSION: Incomplete burst fractures (A3) are predominantly treated non-surgically, while complete burst fractures (A4) are primarily treated surgically. Compensation, third-party incentives, and outpatient care did not significantly impact decision-making. Radiological factors beyond the AO Spine thoracolumbar classification system seem to be essential and warrant further evaluation.

Predictive Algorithm for Surgery Recommendation in Thoracolumbar Burst Fractures Without Neurological Deficits.

STUDY DESIGN: Predictive algorithm via decision tree. OBJECTIVES: Artificial intelligence (AI) remain an emerging field and have not previously been used to guide therapeutic decision making in thoracolumbar burst fractures. Building such models may reduce the variability in treatment recommendations. The goal of this study was to build a mathematical prediction rule based upon radiographic variables to guide treatment decisions. METHODS: Twenty-two surgeons from the AO Knowledge Forum Trauma reviewed 183 cases from the Spine TL A3/A4 prospective study (classification, degree of certainty of posterior ligamentous complex (PLC) injury, use of M1 modifier, degree of comminution, treatment recommendation). Reviewers' regions were classified as Europe, North/South America and Asia. Classification and regression trees were used to create models that would predict the treatment recommendation based upon radiographic variables. We applied the decision tree model which accounts for the possibility of non-normal distributions of data. Cross-validation technique as used to validate the multivariable analyses. RESULTS: The accuracy of the model was excellent at 82.4%. Variables included in the algorithm were certainty of PLC injury (%), degree of comminution (%), the use of M1 modifier and geographical regions. The algorithm showed that if a patient has a certainty of PLC injury over 57.5%, then there is a 97.0% chance of receiving surgery. If certainty of PLC injury was low and comminution was above 37.5%, a patient had 74.2% chance of receiving surgery in Europe and Asia vs 22.7% chance in North/South America. Throughout the algorithm, the use of the M1 modifier increased the probability of receiving surgery by 21.4% on average. CONCLUSION: This study presents a predictive analytic algorithm to guide decision-making in the treatment of thoracolumbar burst fractures without neurological deficits. PLC injury assessment over 57.5% was highly predictive of receiving surgery (97.0%). A high degree of comminution resulted in a higher chance of receiving surgery in Europe or Asia vs North/South America. Future studies could include clinical and other variables to enhance predictive ability or use machine learning for outcomes prediction in thoracolumbar burst fractures.

Interobserver Reliability in the Classification of Thoracolumbar Fractures Using the AO Spine TL Injury Classification System Among 22 Clinical Experts in Spine Trauma Care.

STUDY DESIGN: Reliability study utilizing 183 injury CT scans by 22 spine trauma experts with assessment of radiographic features, classification of injuries and treatment recommendations. OBJECTIVES: To assess the reliability of the AOSpine TL Injury Classification System (TLICS) including the categories within the classification and the M1 modifier. METHODS: Kappa and Intraclass correlation coefficients were produced. Associations of various imaging characteristics (comminution, PLC status) and treatment recommendations were analyzed through regression analysis. Multivariable logistic regression modeling was used for making predictive algorithms. RESULTS: Reliability of the AO Spine TLICS at differentiating A3 and A4 injuries (N = 71) (K = .466; 95% CI .458 - .474; P < .001) demonstrated moderate agreement. Similarly, the average intraclass correlation coefficient (ICC) amongst A3 and A4 injuries was excellent (ICC = .934; 95% CI .919 - .947; P < .001) and the ICC between individual measures was moderate (ICC = .403; 95% CI .351 - .461; P < .001). The overall agreement on the utilization of the M1 modifier amongst A3 and A4 injuries was fair (K = .161; 95% CI .151 - .171; P < .001). The ICC for PLC status in A3 and A4 injuries averaged across all measures was excellent (ICC = .936; 95% CI .922 - .949; P < .001). The M1 modifier suggests respondents are nearly 40% more confident that the PLC is injured amongst all injuries. The M1 modifier was employed at a higher frequency as injuries were classified higher in the classification system. CONCLUSIONS: The reliability of surgeons differentiating between A3 and A4 injuries in the AOSpine TLICS is substantial and the utilization of the M1 modifier occurs more frequently with higher grades in the system.

Expert Opinion, Real-World Classification, and Decision-Making in Thoracolumbar Burst Fractures Without Neurologic Deficits?

STUDY DESIGN: Retrospective analysis of prospectively collected data. OBJECTIVES: To compare decision-making between an expert panel and real-world spine surgeons in thoracolumbar burst fractures (TLBFs) without neurological deficits and analyze which factors influence surgical decision-making. METHODS: This study is a sub-analysis of a prospective observational study in TL fractures. Twenty two experts were asked to review 183 CT scans and recommend treatment for each fracture. The expert recommendation was based on radiographic review. RESULTS: Overall agreement between the expert panel and real-world surgeons regarding surgery was 63.2%. In 36.8% of cases, the expert panel recommended surgery that was not performed in real-world scenarios. Conversely, in cases where the expert panel recommended non-surgical treatment, only 38.6% received non-surgical treatment, while 61.4% underwent surgery. A separate analysis of A3 and A4 fractures revealed that expert panel recommended surgery for 30% of A3 injuries and 68% of A4 injuries. However, 61% of patients with both A3 and A4 fractures received surgery in the real world. Multivariate analysis demonstrated that a 1% increase in certainty of PLC injury led to a 4% increase in surgery recommendation among the expert panel, while a .2% increase in the likelihood of receiving surgery in the real world. CONCLUSION: Surgical decision-making varied between the expert panel and real-world treating surgeons. Differences appear to be less evident in A3/A4 burst fractures making this specific group of fractures a real challenge independent of the level of expertise.

The Influence of Comminution and Posterior Ligamentous Complex Integrity on Treatment Decision Making in Thoracolumbar Burst Fractures Without Neurologic Deficit?

STUDY DESIGN: A prospective study. OBJECTIVE: to evaluate the impact of vertebral body comminution and Posterior Ligamentous Complex (PLC) integrity on the treatment recommendations of thoracolumbar fractures among an expert panel of 22 spine surgeons. METHODS: A review of 183 prospectively collected thoracolumbar burst fracture computed tomography (CT) scans by an expert panel of 22 trauma spine surgeons to assess vertebral body comminution and PLC integrity. This study is a sub-study of a prospective observational study of thoracolumbar burst fractures (Spine TL A3/A4). Each expert was asked to grade the degree of comminution and certainty about the PLC disruption from 0 to 100, with 0 representing the intact vertebral body or intact PLC and 100 representing complete comminution or complete PLC disruption, respectively. RESULTS: ≥45% comminution had a 74% chance of having surgery recommended, while <25% comminution had an 86.3% chance of non-surgical treatment. A comminution from 25 to 45% had a 57% chance of non-surgical management. ≥55% PLC injury certainity had a 97% chance of having surgery, and ≥45-55% PLC injury certainty had a 65%. <20% PLC injury had a 64% chance of having non-operative treatment. A 20 to 45% PLC injury certainity had a 56% chance of non-surgical management. There was fair inter-rater agreement on the degree of comminution (ICC .57 [95% CI 0.52-.63]) and the PLC integrity (ICC .42 [95% CI 0.37-.48]). CONCLUSION: The study concludes that vetebral comminution and PLC integrity are major dterminant in decision making of thoracolumbar fractures without neurological deficit. However, more objective, reliable, and accurate methods of assessment of these variables are warranted.

The AO Spine Thoracolumbar Injury Classification System and Treatment Algorithm in Decision Making for Thoracolumbar Burst Fractures Without Neurologic Deficit.

STUDY DESIGN: Prospective Observational Study. OBJECTIVE: To determine the alignment of the AO Spine Thoracolumbar Injury Classification system and treatment algorithm with contemporary surgical decision making. METHODS: 183 cases of thoracolumbar burst fractures were reviewed by 22 AO Spine Knowledge Forum Trauma experts. These experienced clinicians classified the fracture morphology, integrity of the posterior ligamentous complex and degree of comminution. Management recommendations were collected. RESULTS: There was a statistically significant stepwise increase in rates of operative management with escalating category of injury (P < .001). An excellent correlation existed between recommended expert management and the actual treatment of each injury category: A0/A1/A2 (OR 1.09, 95% CI 0.70-1.69, P = .71), A3/4 (OR 1.62, 95% CI 0.98-2.66, P = .58) and B1/B2/C (1.00, 95% CI 0.87-1.14, P = .99). Thoracolumbar A4 fractures were more likely to be surgically stabilized than A3 fractures (68.2% vs 30.9%, P < .001). A modifier indicating indeterminate ligamentous injury increased the rate of operative management when comparing type B and C injuries to type A3/A4 injuries (OR 39.19, 95% CI 20.84-73.69, P < .01 vs OR 27.72, 95% CI 14.68-52.33, P < .01). CONCLUSIONS: The AO Spine Thoracolumbar Injury Classification system introduces fracture morphology in a rational and hierarchical manner of escalating severity. Thoracolumbar A4 complete burst fractures were more likely to be operatively managed than A3 fractures. Flexion-distraction type B injuries and translational type C injuries were much more likely to have surgery recommended than type A fractures regardless of the M1 modifier. A suspected posterior ligamentous injury increased the likelihood of surgeons favoring surgical stabilization.

From Radiographic Evaluation to Treatment Decisions in Neurologically Intact Patients With Thoraco-lumbar Burst Fractures.

We propose that the key to improving care for these patients is to truly understand the processes that take place from the interpretation of radiographic findings, through the assessment of the severity of various injuries, to inclusion within a classification category and finally to selecting a specific treatment.

Lumbo-sacral Junction Instability by Traumatic Sacral Fractures: Isler's Classification Revisited - A Narrative Review.

STUDY DESIGN: Narrative review. OBJECTIVES: Multiple classifications have been proposed for sacral fractures since the last century. While initial classifications focussed on vertical and transverse fractures, the recent fracture classifications encompass all injury patterns. In 1990, Isler classified unilateral vertical sacral fractures based on its potential influence on lumbo-sacral joint (LSJ) stability. METHODS: We re-visited the original description of Isler's classification of sacral fractures and subsequent studies that have cited it. We will further describe basic LSJ anatomy, evolution of sacral classification systems and the use of Isler's classification system as it relates to LSJ instability and chronic low back pain. RESULTS: Isler described a subset of unilateral vertical sacral fractures where the fracture line exited medial or through the L5-S1 facet joint, based on radiographic review of 193 sacral fractures (incidence -3.5%). He stated that such a fracture should be recognised as it can impede hemi-pelvis reduction and can result in late LSJ instability. The article has been cited in 106 studies and only a few studies have described the incidence of this variant. Nevertheless, the injury is considered as an indication for surgical fixation. CONCLUSION: A review of various classifications indicates that sacral fractures have three important bio-mechanical implications, namely, pelvic ring continuity (vertical fractures), spino-pelvic alignment (high transverse fractures) and lumbo-sacral joint integrity (Isler's fractures). Though there is a universal recognition of Isler's fractures and its impact on LSJ integrity, there is a lack of clinical and bio-mechanical evidence regarding the concept of instability caused by a unilateral Isler fracture.

Injuries related to bicycle accidents: an epidemiological study in The Netherlands.

BACKGROUND: This study aims to analyze the incidence and outcomes of bicycle-related injuries in hospitalized patients in The Netherlands. METHODS: Bicycle accidents resulting in hospitalization in a level-I trauma center in The Netherlands between 2007 and 2017 were retrospectively identified. We subcategorized data of patients involved in a regular bicycle, race bike, off-road bike or e-bike accident. The primary outcomes were mortality rate and incidence of multitrauma. Secondary outcomes were differences between bicycle subcategories. Independent risk factors were identified using multivariable logistic regression. All variables with a p value < 0.20 in univariable analysis were entered in multivariable analysis. RESULTS: We identified 1986 patients. The mortality rate after emergency room admission was 5.7%, and 41.0% were multitraumas. A higher age, multitrauma and cerebral haemorrhages were independent risk factors for in hospital mortality. Independent risk factors found for multitrauma were a higher age, two-sided trauma, e-bike accidents and cerebral haemorrhage. CONCLUSION: Bicycle accidents resulting in hospitalization have a high mortality rate. Furthermore, a high incidence of multitrauma, fractures and cerebral haemorrhages were found. Considering the increasing incidence of bicycle accident victims needing hospital admission, new and more efficient prevention strategies are essential.

BMP-2 gene delivery in cell-loaded and cell-free constructs for bone regeneration.

To induce osteogenicity in bone graft substitutes, plasmid-based expression of BMP-2 (pBMP-2) has been successfully applied in gene activated matrices based on alginate polymer constructs. Here, we investigated whether cell seeding is necessary for non-viral BMP-2 gene expression in vivo. Furthermore, to gain insight in the role of BMP-producing cells, we compared inclusion of bone progenitor cells with non-osteogenic target cells in gene delivery constructs. Plasmid DNA encoding GFP (pGFP) was used to trace transfection of host tissue cells and seeded cells in a rat model. Transgene expression was followed in both cell-free alginate-ceramic constructs as well as constructs seeded with syngeneic fibroblasts or multipotent mesenchymal stromal cells (MSCs). Titration of pGFP revealed that the highest pGFP dose resulted in frequent presence of positive host cells in the constructs. Both cell-loaded groups were associated with transgene expression, most effectively in the MSC-loaded constructs. Subsequently, we investigated effectiveness of cell-free and cell-loaded alginate-ceramic constructs with pBMP-2 to induce bone formation. Local BMP-2 production was found in all groups containing BMP-2 plasmid DNA, and was most pronounced in the groups with MSCs transfected with high concentration pBMP-2. Bone formation was only apparent in the recombinant protein BMP-2 group. In conclusion, we show that non-viral gene delivery of BMP-2 is a potentially effective way to induce transgene expression in vivo, both in cell-seeded as well as cell-free conditions. However, alginate-based gene delivery of BMP-2 to host cells or seeded cells did not result in protein levels adequate for bone formation in this setting, calling for more reliable scaffold compatible transfection methods.

Fixation of flail chest or multiple rib fractures: current evidence and how to proceed. A systematic review and meta-analysis.

PURPOSE: The aim of this systematic review and meta-analysis was to present current evidence on rib fixation and to compare effect estimates obtained from randomized controlled trials (RCTs) and observational studies. METHODS: MEDLINE, Embase, CENTRAL, and CINAHL were searched on June 16th 2017 for both RCTs and observational studies comparing rib fixation versus nonoperative treatment. The MINORS criteria were used to assess study quality. Where possible, data were pooled using random effects meta-analysis. The primary outcome measure was mortality. Secondary outcome measures were hospital length of stay (HLOS), intensive care unit length of stay (ILOS), duration of mechanical ventilation (DMV), pneumonia, and tracheostomy. RESULTS: Thirty-three studies were included resulting in 5874 patients with flail chest or multiple rib fractures: 1255 received rib fixation and 4619 nonoperative treatment. Rib fixation for flail chest reduced mortality compared to nonoperative treatment with a risk ratio of 0.41 (95% CI 0.27, 0.61, p < 0.001, I2 = 0%). Furthermore, rib fixation resulted in a shorter ILOS, DMV, lower pneumonia rate, and need for tracheostomy. Results from recent studies showed lower mortality and shorter DMV after rib fixation, but there were no significant differences for the other outcome measures. There was insufficient data to perform meta-analyses on rib fixation for multiple rib fractures. Pooled results from RCTs and observational studies were similar for all outcome measures, although results from RCTs showed a larger treatment effect for HLOS, ILOS, and DMV compared to observational studies. CONCLUSIONS: Rib fixation for flail chest improves short-term outcome, although the indication and patient subgroup who would benefit most remain unclear. There is insufficient data regarding treatment for multiple rib fractures. Observational studies show similar results compared with RCTs.

The evidence on surgical interventions for low back disorders, an overview of systematic reviews.

PURPOSE: Many systematic reviews have been published on surgical interventions for low back disorders. The objective of this overview was to evaluate the available evidence from systematic reviews on the effectiveness of surgical interventions for disc herniation, spondylolisthesis, stenosis, and degenerative disc disease (DDD). An earlier version of this review was published in 2006 and since then, many new, better quality reviews have been published. METHODS: A comprehensive search was performed in the Cochrane database of systematic reviews (CDSR), database of reviews of effectiveness (DARE) and Pubmed. Two reviewers independently performed the selection of studies, risk of bias assessment, and data extraction. Included are Cochrane reviews and non-Cochrane systematic reviews published in peer-reviewed journals. The following conditions were included: disc herniation, spondylolisthesis, and DDD with or without spinal stenosis. The following comparisons were evaluated: (1) surgery vs. conservative care, and (2) different surgical techniques compared to one another. The methodological quality of the systematic reviews was evaluated using AMSTAR. We report (pooled) analyses from the individual reviews. RESULTS: Thirteen systematic reviews on surgical interventions for low back disorders were included for disc herniation (n = 6), spondylolisthesis (n = 2), spinal stenosis (n = 4), and DDD (n = 4). Nine (69 %) were of high quality. Five reviews provided a meta-analysis of which two showed a significant difference. For the treatment of spinal stenosis, intervertebral process devices showed more favorable results compared to conservative treatment on the Zurich Claudication Questionnaire [mean difference (MD) 23.2 95 % CI 18.5-27.8]. For degenerative spondylolisthesis, fusion showed more favorable results compared to decompression for a mixed aggregation of clinical outcome measures (RR 1.40 95 % CI 1.04-1.89) and fusion rate favored instrumented fusion over non-instrumented fusion (RR 1.37 95 % CI 1.07-1.75). CONCLUSIONS: For most of the comparisons, the included reviews were not significant and/or clinically relevant differences between interventions were identified. Although the quality of the reviews was quite acceptable, the quality of the included studies was poor. Future studies are likely to influence our assessment of these interventions.

The effect of cell-based bone tissue engineering in a goat transverse process model.

A disadvantage of traditional posterolateral spinal fusion models is that they are highly inefficient for screening multiple conditions. We developed a multiple-condition model that concentrates on the initial process of bone formation from the transverse process and not on a functional fusion. The effect of bone marrow stromal cells (BMSCs) in four different porous ceramic scaffolds was investigated in this setting. Polyacetal cassettes were designed to fit on the goat transverse process and house four different ceramic blocks, i.e: hydroxyapatite (HA) sintered at 1,150 degrees and 1,250 degrees; biphasic calcium phosphate (BCP) and tricalcium phosphate (TCP). Goat BMSCs (n=10) were cultured and per-operatively seeded autologeously on one of two cassettes implanted per animal. The cassettes were bilaterally mounted on the dorsum of decorticated L2-processes for 9 weeks. To asses the dynamics of bone formation, fluorochrome labels were administered and histomorphometry focused on the distribution of bone in the scaffolds. A clear difference in the extent of bone ingrowth was determined for the different scaffold types. An obvious effect of BMSC seeding was observed in three of four scaffold types, especially in scaffold regions adjacent to the overlying muscle. Generally, the BCP and TCP scaffolds showed better osteoconduction and an increased response to BMSCs administration. In conclusion the model provides a reliable and highly efficient method to study bone formation in cell-based tissue engineering. An effect of cell administration was obvious in three of the four scaffold materials.