Comparison of Different Osteobiologics in Terms of Imaging Modalities and Time Frames for Fusion Assessment in Anterior Cervical Discectomy and Fusion: A Systematic Review.

STUDY DESIGN: Systematic review. OBJECTIVES: The study's primary objective was to determine how osteobiologic choice affects fusion rates in patients undergoing anterior cervical discectomy and fusion (ACDF). The study's secondary objectives were to 1) determine the optimal timing of fusion assessment following ACDF and 2) determine if osteobiologic type affects the timing and optimal modality of fusion assessment. METHODS: A systematic search of PubMed/MEDLINE was conducted for literature published from 2000 through October 2020 comparing anterior fusion in the cervical spine with various osteobiologics. Both comparative studies and case series of ≥10 patients were included. RESULTS: A total of 74 studies met the inclusion criteria. Seventeen studies evaluated the efficacy of autograft on fusion outcomes, and 23 studies assessed the efficacy of allograft on fusion outcomes. 3 studies evaluated the efficacy of demineralized bone matrix, and seven assessed the efficacy of rhBMP-2 on fusion outcomes. Other limited studies evaluated the efficacy of ceramics and bioactive glasses on fusion outcomes, and 4 assessed the efficacy of stem cell products. Most studies utilized dynamic radiographs for the assessment of fusion. Overall, there was a general lack of supportive data to determine the optimal timing of fusion assessment meaningfully or if osteobiologic type influenced fusion timing. CONCLUSIONS: Achieving fusion following ACDF appears to remain an intricate interplay between host biology and various surgical factors, including the selection of osteobiologics. While alternative osteobiologics to autograft exist and may produce acceptable fusion rates, limitations in study methodology prevent any definitive conclusions from existing literature.

The economic and societal burden associated with adolescent idiopathic scoliosis: A burden-of-disease study protocol.

Background: Adolescent idiopathic scoliosis (AIS) has an estimated general population prevalence of 2% to 3%. The impact of adolescent idiopathic scoliosis (AIS) on the patients' experienced quality of life and psychological well-being and the resulting societal burden are increasingly recognized. However, there is limited knowledge on the economic burden of AIS. This cross-sectional, prevalence-based, bottom-up approach burden of disease study aims to determine the impact associated with adolescent idiopathic scoliosis in terms of the cost-of-illness and health-related quality of life from a societal perspective in the Netherlands. Methods: Persons diagnosed with AIS or parents of a child with AIS that are willing and able to answer the questionnaires will be eligible to participate. Patients will be included consecutively between June until January 2023. Costs and self-perceived health-related quality of life will be estimated using 3 steps: identification, measurement and valuation. To assess the costs associated with AIS the institute for Medical Technology Assessment - Medical Consumption Questionnaire and the institute for Medical Technology Assessment - Productivity Cost Questionnaire will be used. To assess the HRQoL of adult AIS patients the EuroQol 5-dimensions or EuroQol 5-dimensions Youth questionnaire for children under the age of 12 and the Scoliosis Research Society-22 revised questionnaire will be considered. Discussion: This is the first study in this field. It will help raise awareness for AIS and wider support for both the patient community and informal care takers among healthcare professionals and policymakers. Major strengths of this study will be the use of mostly validated, standardized questionnaires. Limitations include the cross-sectional and retrospective nature of the study design.

Cost-Effectiveness Study of One-Stage Treatment of Chronic Osteomyelitis with Bioactive Glass S53P4.

This study was set up to evaluate the costs of a one-stage treatment of chronic osteomyelitis using bioactive glass S53P4 versus a two-stage treatment using gentamicin-loaded PMMA beads. Furthermore, a cost-effectiveness analysis was performed from a hospital's perspective together with the evaluation of clinical outcome. A treatment group (n = 25) receiving one-stage surgery with bioactive glass was retrospectively compared with a two-stage control group (n = 25). An assessment was made of all costs included from first outpatient visit until one year after treatment. Bootstrap simulation and sensitivity analyses were performed. The primary endpoint was cost-effectiveness with clinical outcome as the secondary endpoint. The base case analyses shows dominance of the one-stage treatment with bioactive glass S53P4 due to lower costs and a better clinical outcome. Sensitivity analyses confirm these findings. This study is the first in its kind to show one-stage treatment of chronic osteomyelitis with bioactive glass S53P4 to be cost-effective.

Radiopaque UHMWPE sublaminar cables for spinal deformity correction: Preclinical mechanical and radiopacifier leaching assessment.

Polymeric sublaminar cables have a number of advantages over metal cables in the field of spinal deformity surgery, with decreased risk of neurological injury and potential for higher correction forces as the two most predominant. However, currently available polymer cables are radiolucent, precluding postoperative radiological assessment of instrumentation stability and integrity. This study provides a preclinical assessment of a woven UHMWPE cable made with radiopaque UHMWPE fibers. Our primary goal was to determine if the addition of a radiopacifier negatively affects the mechanical properties of UHMWPE woven cables. Tensile mechanical properties were determined and compared to suitable controls. Radiopacity was evaluated and radiopacifier leaching was assessed in vitro and in vivo. Finally, in vivo bismuth organ content was quantified after a 24-week implantation period in sheep. Results show that the mechanical properties of woven UHMWPE cables were not deleteriously affected by the addition of homogenously dispersed bismuth oxide particles within each fiber. Limited amounts of bismuth oxide were released in vitro, well below the toxicological threshold. Tissue concentrations lower than generally accepted therapeutic dosages for use against gastrointestinal disorders, well below toxic levels, were discovered in vivo. These results substantiate controlled clinical introduction of these radiopaque UHMWPE cables. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 771-779, 2018.

Development and assessment of a digital X-ray software tool to determine vertebral rotation in adolescent idiopathic scoliosis.

BACKGROUND CONTEXT: The amount of vertebral rotation in the axial plane is of key importance in the prognosis and treatment of adolescent idiopathic scoliosis (AIS). Current methods to determine vertebral rotation are either designed for use in analogue plain radiographs and not useful in digital images, or lack measurement precision and are therefore less suitable for the follow-up of rotation in AIS patients. PURPOSE: This study aimed to develop a digital X-ray software tool with high measurement precision to determine vertebral rotation in AIS, and to assess its (concurrent) validity and reliability. STUDY DESIGN/SETTING: In this study a combination of basic science and reliability methodology applied in both laboratory and clinical settings was used. METHODS: Software was developed using the algorithm of the Perdriolle torsion meter for analogue AP plain radiographs of the spine. Software was then assessed for (1) concurrent validity and (2) intra- and interobserver reliability. Plain radiographs of both human cadaver vertebrae and outpatient AIS patients were used. Concurrent validity was measured by two independent observers, both experienced in the assessment of plain radiographs. Reliability-measurements were performed by three independent spine surgeons. RESULTS: Pearson correlation of the software compared with the analogue Perdriolle torsion meter for mid-thoracic vertebrae was 0.98, for low-thoracic vertebrae 0.97 and for lumbar vertebrae 0.97. Measurement exactness of the software was within 5° in 62% of cases and within 10° in 97% of cases. Intraclass correlation coefficient (ICC) for inter-observer reliability was 0.92 (0.91-0.95), ICC for intra-observer reliability was 0.96 (0.94-0.97). CONCLUSIONS: We developed a digital X-ray software tool to determine vertebral rotation in AIS with a substantial concurrent validity and reliability, which may be useful for the follow-up of vertebral rotation in AIS patients.

UHMWPE Sublaminar Wires in Posterior Spinal Instrumentation: Stability and Biocompatibility Assessment in an Ovine Pilot Study.

STUDY DESIGN: An animal study. OBJECTIVE: To explore ultra-high molecular weight polyethylene (UHMWPE) sublaminar wires in spinal surgery and to assess stability and biocompatibility of the UHMWPE instrumentation in an ovine model. SUMMARY OF BACKGROUND DATA: Sublaminar wiring is a well-established technique in segmental scoliosis surgery. However, during introduction and/or removal of the metal sublaminar wires, neurological problems can occur. Abrasion after cutting metal wires for removal can lead to damage to the dural sac. Sublaminar wires have to withhold large forces and breakage of the wires can occur. Different types of sublaminar wires have been developed to address these problems. UHMWPE sublaminar wires can potentially substitute currently used metal sublaminar metal wires. In vivo testing and biocompatibility analysis of UHMWPE wires are recommended before clinical use in spinal surgery. MATERIALS AND METHODS: In 6 immature sheep, pedicle screws were instrumented at lumbar level L4 and attached with titanium rods to 4 thoracolumbar vertebrae using 3- and 5-mm-wide UHMWPE sublaminar wiring constructions in 5 animals. Titanium sublaminar wires were applied in 1 animal to function as a control subject. After a follow-up period of 16 weeks, the animals were sacrificed and the spines were isolated. Radiographs and computed tomography (CT) scans were made to assess stability of the instrumentation. The vertebrae were dissected for macroscopic and histologic evaluation. RESULTS: None of the wires had loosened and the instrumentation remained stable. CT scans and radiographs showed no signs of failure of the instrumentation and no neurological complications occurred. Although several bony bridges were seen on CT, growth was observed at the operated levels. Biocompatibility was assessed by macroscopical and histologic analysis, showing no signs of dural or epidural inflammation. CONCLUSIONS: This pilot animal study shows that UHMWPE sublaminar wiring is a safe technique. The UHMWPE wires are biocompatible and provide sufficient stability in spinal instrumentation. Heterotopic ossification because of periost reactions in the ovine spine led to some restrictions in this study.

How to prepare a systematic review of economic evaluations for informing evidence-based healthcare decisions: a five-step approach (part 1/3).

INTRODUCTION: Systematic reviews of economic evaluations are useful for synthesizing economic evidence about health interventions and for informing evidence-based decisions. Areas covered: As there is no detailed description of the methods for performing a systematic review of economic evidence, this paper aims to provide an overview of state-of-the-art methodology. This is laid out in a 5-step approach, as follows: step 1) initiating a systematic review; step 2) identifying (full) economic evaluations; step 3) data extraction, risk of bias and transferability assessment; step 4) reporting results; step 5) discussion and interpretation of findings. Expert commentary: The paper aims to help inexperienced reviewers and clinical practice guideline developers, but also to be a resource for experts in the field who want to check on current methodological developments.

The longitudinal assessment of osteomyelitis development by molecular imaging in a rabbit model.

INTRODUCTION: Osteomyelitis is a severe orthopaedic complication which is difficult to diagnose and treat. Previous experimental studies mainly focussed on evaluating osteomyelitis in the presence of an implant or used a sclerosing agent to promote infection onset. In contrast, we focused on the longitudinal assessment of a nonimplant related osteomyelitis. METHODS: An intramedullary tibial infection with S. aureus was established in NZW rabbits. Clinical and haematological infection status was evaluated weekly, combined with X-ray radiographs, biweekly injections of calcium binding fluorophores, and postmortem micro-CT. The development of the infection was assessed by micro-PET at consecutive time points using 18F-FDG as an infection tracer. RESULTS: The intramedullary contamination of the rabbit tibia resulted in an osteomyelitis. Haematological parameters confirmed infection in mainly the first postoperative weeks (CRP at the first 5 postoperative weeks, leucocyte differentiation at the second and sixth postoperative weeks, and ESR on the second postoperative week only), while micro-PET was able to detect the infection from the first post-operative week onward until the end of the study. CONCLUSIONS: This study shows that osteomyelitis in the rabbit can be induced without use of an implant or sclerosing agent. The sequential follow-up indicates that the diagnostic value of each infection parameter is time point dependant. Furthermore, from all parameters used, the diagnostic value of 18F-FDG micro-PET is the most versatile to assess the presence of an orthopaedic infection in this model.

Assessment of the healing process in distal radius fractures by high resolution peripheral quantitative computed tomography.

In clinical practice, fracture healing is evaluated by clinical judgment in combination with conventional radiography. Due to limited resolution, radiographs don't provide detailed information regarding the bone micro-architecture and bone strength. Recently, assessment of in vivo bone density, architectural and mechanical properties at the microscale became possible using high resolution peripheral quantitative computed tomography (HR-pQCT) in combination with micro finite element analysis (µFEA). So far, such techniques have been used mainly to study intact bone. The aim of this study was to explore whether these techniques can also be used to assess changes in bone density, micro-architecture and bone stiffness during fracture healing. Therefore, the fracture region in eighteen women, aged 50 years or older with a stable distal radius fracture, was scanned using HR-pQCT at 1-2 (baseline), 3-4, 6-8 and 12weeks post-fracture. At 1-2 and 12 weeks post-fracture the distal radius at the contra-lateral side was also scanned as control. Standard bone density, micro-architectural and geometric parameters were calculated and bone stiffness in compression, torsion and bending was assessed using µFEA. A linear mixed effect model with time post-fracture as fixed effect was used to detect significant (p-value ≤0.05) changes from baseline. Wrist pain and function were scored using the patient-rated wrist evaluation (PRWE) questionnaire. Correlations between the bone parameters and the PRWE score were calculated by Spearman's correlation coefficient. At the fracture site, total and trabecular bone density increased by 11% and 20%, respectively, at 6-8 weeks, whereas cortical density was decreased by 4%. Trabecular thickness increased by 23-31% at 6-8 and 12 weeks and the intertrabecular area became blurred, indicating intertrabecular bone formation. Compared to baseline, calculated bone stiffness in compression, torsion and bending was increased by 31% after 12 weeks. A moderate negative correlation was found between the stiffness and the PRWE score. No changes were observed at the contra-lateral side. The results demonstrate that it is feasible to assess clinically relevant and significant longitudinal changes in bone density, micro-architecture and mechanical properties at the fracture region during the healing process of stable distal radius fractures using HR-pQCT.

A rabbit osteomyelitis model for the longitudinal assessment of early post-operative implant infections.

BACKGROUND: Implant infection is one of the most severe complications within the field of orthopaedic surgery, associated with an enormous burden for the healthcare system. During the last decades, attempts have been made to lower the incidence of implant-related infections. In the case of cemented prostheses, the use of antibiotic-containing bone cement can be effective. However, in the case of non-cemented prostheses, osteosynthesis and spinal surgery, local antibacterial prophylaxis is not a standard procedure. For the development of implant coatings with antibacterial properties, there is a need for a reliable animal model to evaluate the preventive capacity of such coatings during a specific period of time. Existing animal models generally present a limited follow-up, with a limited number of outcome parameters and relatively large animal numbers in multiple groups. METHODS: To represent an early post-operative implant infection, we established an acute tibial intramedullary nail infection model in rabbits by contamination of the tibial nail with 3.8 × 105 colony forming units of Staphylococcus aureus. Clinical, haematological and radiological parameters for infection were weekly assessed during a 6-week follow-up with post-mortem bacteriological and histological analyses. RESULTS: S. aureus implant infection was confirmed by the above parameters. A saline control group did not develop osteomyelitis. By combining the clinical, haematological, radiological, bacteriological and histological data collected during the experimental follow-up, we were able to differentiate between the control and the infected condition and assess the severity of the infection at sequential timepoints in a parameter-dependent fashion. CONCLUSION: We herein present an acute early post-operative rabbit implant infection model which, in contrast to previously published models, combines improved in-time insight into the development of an implant osteomyelitis with a relatively low amount of animals.