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.

An Assessment of the World's Contribution to Spine Trauma Care: A Bibliometric Analysis of Classifications and Surgical Management; An AO Spine Knowledge Forum Trauma Initiative.

STUDY DESIGN: Bibliometric analysis. OBJECTIVES: An analysis of the literature related to the assessment and management of spinal trauma was undertaken to allow the identification of top contributors, collaborations and research trends. METHODS: A search to identify original articles published in English between 2011 and 2020 was done using specific keywords in the Web of Science database. After screening, the top 300 most cited articles were analyzed using Biblioshiny R software. RESULTS: The highest number of contributions were from the Thomas Jefferson University, USA, University of Toronto and University of British Columbia, Canada. The top 3 most prolific authors were Vaccaro AR, Arabi B, and Oner FC. The USA and Canada were among the top contributing countries; Switzerland and Brazil had most multiple country co-authored articles. The most relevant journals were the European Spine Journal, Spine and Spine Journal. Three of the 5 most cited articles were about classification systems of fractures. The keyword analysis included clusters for different spinal regions, spinal cord injury, classification agreement and reliability studies, imaging related studies, surgical techniques and outcomes. CONCLUSIONS: The study identified the most impactful authors and affiliations, and determined the journals where most impactful research is published in the field. Study also compared the productivity and collaborations across countries. The study highlighted the impact of development of new classification systems, and identified research trends including instrumentation, fixation and decompression techniques, epidemiology and recovery after spinal trauma.

James Lind Alliance Priority Setting Partnership for Degenerative Cervical Myelopathy [AO Spine RECODE-DCM]: An Overview of the Methodology Used to Process and Short-List Research Uncertainties.

STUDY DESIGN: Overview of the methods used for a James Lind Alliance (JLA) Priority Setting Partnership (PSP). OBJECTIVES: The objectives of this article are to (i) provide a brief overview of the JLA-facilitated PSP process; (ii) outline how research uncertainties were initially processed in the AO Spine RECODE-DCM PSP; and (iii) delineate the methods for interim prioritization and the priority setting workshop. METHODS: A steering group was created to define the scope for the PSP, organize its activities, and establish protocols for decision-making. A survey was created asking what questions on the diagnosis, treatment, and long-term management of DCM should be answered by future research. Results from the survey were sorted into summary questions. Several databases were searched to identify literature that already answered these summary questions. The final list of summary questions was distributed by survey for interim prioritization. Participants were asked to select the top ten most important summary questions. The questions that were ranked the highest were discussed at an in-person consensus workshop. RESULTS: The initial survey yielded a total of 3404 potential research questions. Of the in-scope submissions, 988 were related to diagnosis, 1324 to treatment, and 615 to long-term management of DCM. A total of 76 summary questions were developed to reflect the original submissions. Following a second survey, a list of the top 26 interim priorities was generated and discussed at the in-person priority setting workshop. CONCLUSIONS: PSPs enable research priorities to be identified that consider the perspectives and interests of all relevant stakeholders.

Gathering Global Perspectives to Establish the Research Priorities and Minimum Data Sets for Degenerative Cervical Myelopathy: Sampling Strategy of the First Round Consensus Surveys of AO Spine RECODE-DCM.

STUDY DESIGN: Survey. INTRODUCTION: AO Spine Research Objectives and Common Data Elements for Degenerative Cervical Myelopathy (AO Spine RECODE-DCM) is an international initiative that aims to accelerate knowledge discovery and improve outcomes by developing a consensus framework for research. This includes defining the top research priorities, an index term and a minimum data set (core outcome set and core data elements set - core outcome set (COS)/core data elements (CDE)). OBJECTIVE: To describe how perspectives were gathered and report the detailed sampling characteristics. METHODS: A two-stage, electronic survey was used to gather and seek initial consensus. Perspectives were sought from spinal surgeons, other healthcare professionals and people with degenerative cervical myelopathy (DCM). Participants were allocated to one of two parallel streams: (1) priority setting or (2) minimum dataset. An email campaign was developed to advertise the survey to relevant global stakeholder individuals and organisations. People with DCM were recruited using the international DCM charity Myelopathy.org and its social media channels. A network of global partners was recruited to act as project ambassadors. Data from Google Analytics, MailChimp and Calibrum helped optimise survey dissemination. RESULTS: Survey engagement was high amongst the three stakeholder groups: 208 people with DCM, 389 spinal surgeons and 157 other healthcare professionals. Individuals from 76 different countries participated; the United States, United Kingdom and Canada were the most common countries of participants. CONCLUSION: AO Spine RECODE-DCM recruited a diverse and sufficient number of participants for an international PSP and COS/CDE process. Whilst PSP and COS/CDE have been undertaken in other fields, to our knowledge, this is the first time they have been combined in one process.

The development of lived experience-centered word clouds to support research uncertainty gathering in degenerative cervical myelopathy: results from an engagement process and protocol for their evaluation, via a nested randomized controlled trial.

OBJECTIVES: AO Spine REsearch objectives and Common Data Elements for Degenerative Cervical Myelopathy [RECODE-DCM] is a multi-stakeholder consensus process aiming to promote research efficiency in DCM. It aims to establish the top 10 research uncertainties, through a James Lind Alliance Priority Setting Partnership [PSP]. Through a consensus process, research questions are generated and ranked. The inclusion of people with cervical myelopathy [PwCM] is central to the process. We hypothesized that presenting PwCM experience through word cloud generation would stimulate other key stakeholders to generate research questions better aligned with PwCM needs. This protocol outlines our plans to evaluate this as a nested methodological study within our PSP. METHODS: An online poll asked PwCM to submit and vote on words associated with aspects of DCM. After review, a refined word list was re-polled for voting and word submission. Word clouds were generated and an implementation plan for AO Spine RECODE-DCM PSP surveys was subsequently developed. RESULTS: Seventy-nine terms were submitted after the first poll. Eighty-seven refined words were then re-polled (which added a further 39 words). Four word clouds were generated under the categories of diagnosis, management, long-term effects, and other. A 1:1 block randomization protocol to assess word cloud impact on the number and relevance of PSP research questions was generated. CONCLUSIONS: We have shown it is feasible to work with PwCM to generate a tool for the AO Spine RECODE-DCM nested methodological study. Once the survey stage is completed, we will be able to evaluate the impact of the word clouds. Further research will be needed to assess the value of any impact in terms of stimulating a more creative research agenda.

Communication in surgical decision-making while managing metastatic bone disease: matching patient expectations with surgical goals.

BACKGROUND: There is a paucity of research examining how surgical decision-making for metastatic bone disease (MBD) can be optimized to improve quality of life (QOL) and functional outcomes, while accurately aligning with patient goals and expectations. The objective of this study was to survey and interview patients with MBD and support persons (PS), physicians, and allied health care providers (HCP) with the goal of identifying (1) important surgical issues related to MBD management, (2) discordance in perioperative expectations, and (3) perceived measures of success in the surgical management of MBD. METHODS: Utilizing a custom survey developed by HCP and patients with MBD, participants were asked to (1) identify important issues related to MBD management, (2) rank perceived measures of success, and (3) answer open-ended questions pertaining to the management of MBD. RESULTS: From the survey, increased life expectancy, minimizing disease progression, removal of local tumour, timely surgery after diagnosis, increased length of hospitalization, and physiotherapy access were all identified as significant discordant goals between PS and physicians/HCP. Conversely, there was an agreement between physicians and HCP who considered improved QOL and functional outcomes as most important goals. Structured homogenous-group workshops identified the need for (1) improved discussions of prognosis, surgical options, expectations, timelines, and resources, (2) the use of a care team "quarterback", and (3) an increased use of multi-disciplinary treatment planning. CONCLUSIONS: We feel this data highlights the importance of improved communication and coordination in treating patients with MBD. Further research evaluating how surgical techniques influence survival and disease progression in MBD is highly relevant and important to patients.

Effect of mechanical strain on the pluripotency of murine embryonic stem cells seeded in a collagen-I scaffold.

The use of embryonic stem cells (ESC) in regenerative medicine is restricted due to the possibility of tumorigenicity after inefficient or incomplete differentiation. Studies from our group, and others, suggest that mechanical stimuli may have a suppressive effect on the pluripotency/tumorigenesis of murine ESC (mESC). Furthermore, we have demonstrated that mESC seeded in a type I collagen scaffold, and transplanted into a murine bone fracture model, demonstrated repair without tumor formation. However, it remains unknown if mechanical factors were involved in blocking tumorigenicity of the mESC. Therefore, the aims of the current study were: (i) to characterize the mechanical environment within the transplanted construct (mESC-Col I) in an in vivo murine fracture model using computational analyses; and (ii) to reproduce this mechanical environment in vitro to elucidate the role of these mechanical factors on mESC pluripotent gene expression. It was predicted that the mESC-Col I construct was subjected to an average octahedral shear strain of ∼3.8% and a compressive strain of ∼3.1% within the fracture in vivo when the murine tibia was subjected to an axial compression load of 4 N (1 Hz). When a similar strain environment was replicated experimentally in vitro, the expression patterns of marker genes for pluripotency (Oct 4, Sox 2, Nanog, Rex 1, and oncogene ERas) were significantly down-regulated. This suggests that the local micro-mechanical environment within the fracture site in vivo may be involved in regulating stem cell fate after transplantation, and that these physical factors should be considered when developing regenerative medicine strategies. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:799-807, 2018.

Reduction of pluripotent gene expression in murine embryonic stem cells exposed to mechanical loading or Cyclo RGD peptide.

BACKGROUND: Self-renewal and differentiation of embryonic stem cells (ESCs) is directed by biological and/or physical cues that regulate multiple signaling cascades. We have previously shown that mESCs seeded in a type I collagen matrix demonstrate a loss of pluripotent marker expression and differentiate towards an osteogenic lineage. In this study, we examined if this effect was mediated in part through Arginylglycylaspartic acid (RGD) dependent integrin activity and/or mechano-transduction. RESULTS: The results from this study suggest that mESC interaction with the local microenvironment through RGD dependent integrins play a role in the regulation of mESC core transcription factors (TF), Oct-4, Sox 2 and Nanog. Disruption of this interaction with a cyclic RGD peptide (cRGDfC) was sufficient to mimic the effect of a mechanical stimulus in terms of pluripotent gene expression, specifically, we observed that supplementation with cRGDfC, or mechanical stimulus, significantly influenced mESC pluripotency by down-regulating core transcription factors. Moreover, our results indicated that the presence of the cRGDfC peptide inhibited integrin expression and up-regulated early lineage markers (mesoderm and ectoderm) in a Leukemia inhibitory factor (LIF) dependent manner. When cRGDfC treated mESCs were injected in Severe combined immunodeficiency (SCID) mice, no tissue growth and/or teratoma formation was observed, suggesting that the process of mESC tumor formation in vivo is potentially dependent on integrin interaction. CONCLUSIONS: Overall, the disruption of cell-integrin interaction via cRGDfC peptide can mimic the effect of mechanical stimulation on mESC pluripotency gene expression and also inhibit the tumorigenic potential of mESCs in vivo.