Impact of intraoperative imaging on decision-making during spine surgery: a survey among spine surgeons using simulated intraoperative images.

PURPOSE: To assess whether the intention to intraoperatively reposition pedicle screws differs when spine surgeons evaluate the same screws with 2D imaging or 3D imaging. METHODS: In this online survey study, 21 spine surgeons evaluated eight pedicle screws from patients who had undergone posterior spinal fixation. In a simulated intraoperative setting, surgeons had to decide if they would reposition a marked pedicle screw based on its position in the provided radiologic imaging. The eight assessed pedicle screws varied in radiologic position, including two screws positioned within the pedicle, two breaching the pedicle cortex < 2 mm, two breaching the pedicle cortex 2-4 mm, and two positioned completely outside the pedicle. Surgeons assessed each pedicle screw twice without knowing and in random order: once with a scrollable three-dimensional (3D) image and once with two oblique fluoroscopic two-dimensional (2D) images. RESULTS: Almost all surgeons (19/21) intended to reposition more pedicle screws based on 3D imaging than on 2D imaging, with a mean number of pedicle screws to be repositioned of, respectively, 4.1 (± 1.3) and 2.0 (± 1.3; p < 0.001). Surgeons intended to reposition two screws placed completely outside the pedicle, one breaching 2-4mm, and one breaching < 2 mm more often based on 3D imaging. CONCLUSION: When provided with 3D imaging, spine surgeons not only intend to intraoperatively reposition pedicle screws at risk of causing postoperative complications more often but also screws with acceptable positions. This study highlights the potential of intraoperative 3D imaging as well as the need for consensus on how to act on intraoperative 3D information.

In Vitro and In Vivo Degradation of Photo-Crosslinked Poly(Trimethylene Carbonate-co-ε-Caprolactone) Networks.

Three-armed poly(trimethylene carbonate) (PTMC) and poly(trimethylene carbonate-co-Ɛ-caprolactone) (P(TMC-co-ε-CL)) macromers with molecular weights of approximately 30 kg mol-1 are synthesized by ring-opening polymerization and subsequent functionalization with methacrylic anhydride. Networks are then prepared by photo-crosslinking. To investigate the in vitro and in vivo degradation properties of these photo-crosslinked networks and assess the effect of ε-caprolactone content on the degradation properties, PTMC networks, and copolymer networks with two different TMC:ε-CL ratios are prepared. PTMC networks degraded slowly, via an enzymatic surface erosion process, both in vitro and in vivo. Networks prepared from P(TMC-co-ε-CL) macromers with a 74:26 ratio are found to degrade slowly as well, via a surface erosion process, albeit at a higher rate compared to PTMC networks. Increasing the ε-CL content to a ratio of 52:48, resulted in a faster degradation. These networks lost their mechanical properties much sooner than the other networks. Thus, PTMC and P(TMC-co-ε-CL) networks are interesting networks for tissue engineering purposes and the exact degradation properties can be tuned by varying the TMC:ε-CL ratio, providing researchers with a tool to obtain copolymer networks with the desired degradation rate depending on the intended application.

Assessing the accuracy of a new 3D2D registration algorithm based on a non-invasive skin marker model for navigated spine surgery.

PURPOSE: We assessed the accuracy of a new 3D2D registration algorithm to be used for navigated spine surgery and explored anatomical and radiologic parameters affecting the registration accuracy. Compared to existing 3D2D registration algorithms, the algorithm does not need bone-mounted or table-mounted instruments for registration. Neither does the intraoperative imaging device have to be tracked or calibrated. METHODS: The rigid registration algorithm required imaging data (a pre-existing CT scan (3D) and two angulated fluoroscopic images (2D)) to register positions of vertebrae in 3D and is based on non-invasive skin markers. The algorithm registered five adjacent vertebrae and was tested in the thoracic and lumbar spine from three human cadaveric specimens. The registration accuracy was calculated for each registered vertebra and measured with the target registration error (TRE) in millimeters. We used multivariable analysis to identify parameters independently affecting the algorithm's accuracy such as the angulation between the two fluoroscopic images (between 40° and 90°), the detector-skin distance, the number of skin markers applied, and waist circumference. RESULTS: The algorithm registered 780 vertebrae with a median TRE of 0.51 mm [interquartile range 0.32-0.73 mm] and a maximum TRE of 2.06 mm. The TRE was most affected by the angulation between the two fluoroscopic images obtained (p < 0.001): larger angulations resulted in higher accuracy. The algorithm was more accurate in thoracic vertebrae (p = 0.004) and in the specimen with the smallest waist circumference (p = 0.003). The algorithm registered all five adjacent vertebrae with similar accuracy. CONCLUSION: We studied the accuracy of a new 3D2D registration algorithm based on non-invasive skin markers. The algorithm registered five adjacent vertebrae with similar accuracy in the thoracic and lumbar spine and showed a maximum target registration error of approximately 2 mm. To further evaluate its potential for navigated spine surgery, the algorithm may now be integrated into a complete navigation system.

Arthroscopic meniscectomy versus non-surgical or sham treatment in patients with MRI confirmed degenerative meniscus lesions: a protocol for an individual participant data meta-analysis.

INTRODUCTION: Arthroscopic partial meniscectomy (APM) after degenerative meniscus tears is one of the most frequently performed surgeries in orthopaedics. Although several randomised controlled trials (RCTs) have been published that showed no clear benefit compared with sham treatment or non-surgical treatment, the incidence of APM remains high. The common perception by most orthopaedic surgeons is that there are subgroups of patients that do need APM to improve, and they argue that each study sample of the existing trials is not representative for the day-to-day patients in the clinic. Therefore, the objective of this individual participant data meta-analysis (IPDMA) is to assess whether there are subgroups of patients with degenerative meniscus lesions who benefit from APM in comparison with non-surgical or sham treatment. METHODS AND ANALYSIS: An existing systematic review will be updated to identify all RCTs worldwide that evaluated APM compared with sham treatment or non-surgical treatment in patients with knee symptoms and degenerative meniscus tears. Time and effort will be spent in contacting principal investigators of the original trials and encourage them to collaborate in this project by sharing their trial data. All individual participant data will be validated for missing data, internal data consistency, randomisation integrity and censoring patterns. After validation, all datasets will be combined and analysed using a one-staged and two-staged approach. The RCTs' characteristics will be used for the assessment of clinical homogeneity and generalisability of the findings. The most important outcome will be the difference between APM and control groups in knee pain, function and quality of life 2 years after the intervention. Other outcomes of interest will include the difference in adverse events and mental health. ETHICS AND DISSEMINATION: All trial data will be anonymised before it is shared with the authors. The data will be encrypted and stored on a secure server located in the Netherlands. No major ethical concerns remain. This IPDMA will provide the evidence base to update and tailor diagnostic and treatment protocols as well as (international) guidelines for patients for whom orthopaedic surgeons consider APM. The results will be submitted for publication in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42017067240.

Septoplasty versus non-surgical management for nasal obstruction due to a deviated nasal septum in adults: A modelling study of cost-effectiveness.

OBJECTIVE: The objective of this study was to demonstrate how decision-analytic modelling can help to determine circumstances under which surgery may become cost-effective, using septoplasty as an example. DESIGN: We developed a decision-analytic model comparing septoplasty to non-surgical management for nasal obstruction in adults with a deviated septum. Based on the estimated cost difference between both treatments, we calculated the minimal (a) gain in quality-adjusted life-years, or (b) reduction in productivity losses needed for septoplasty to be cost-effective. Input was derived from literature and publicly available data sources. The time horizon of our model was one year, and the willingness-to-pay per quality-adjusted life-year was €20 000, in accordance with current guidelines. RESULTS: The cost difference between septoplasty and non-surgical management for nasal obstruction due to a deviated nasal septum was €2227 per patient from a healthcare perspective (including direct healthcare costs) and €3288 per patient from an extended perspective (additionally including travel expenses and productivity losses due to poor health). In comparison with non-surgical management, septoplasty needed to gain 0.11 to 0.16 QALYs or save 13 sick days for nasal obstruction. The longer septoplasty's effect lasts, the more time it will have to compensate its extra costs. CONCLUSION: This study shows that the known cost difference between treatments can be used as the starting point to determine beneficial effects needed for cost-effectiveness of surgical interventions. The effect required by septoplasty from a healthcare perspective seems potentially achievable, meaning that it would be useful to perform an RCT assessing the actual benefits of septoplasty.

The Role of Multiparametric Magnetic Resonance Imaging in Active Surveillance for Men with Low-risk Prostate Cancer: A Cost-effectiveness Modeling Study.

BACKGROUND: Active surveillance (AS) has limitations that include missing high-risk tumors and performing unnecessary biopsies. The use of multiparametric magnetic resonance imaging (mpMRI) in AS may overcome these limitations, but its cost-effectiveness remains uncertain. OBJECTIVE: To determine the cost-effectiveness of three AS strategies: AS with transrectal ultrasound-guided biopsy (TRUSGB), AS with mpMRI and MRI ultrasound-guided biopsy (MR-TRUSGB), and AS with mpMRI without biopsies. DESIGN, SETTING, AND PARTICIPANTS: A Markov cohort model for men with low-risk prostate cancer was developed to assess the three strategies. Input data were derived from meta-analysis, other published literature, and national cost reports. A health care perspective was used for a European setting. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Health care costs and quality-adjusted life years (QALYs) were modeled over a lifetime horizon. Deterministic and probabilistic sensitivity analyses were performed to address uncertainty in model parameters. RESULTS AND LIMITATIONS: In the base case analysis, expected mean costs per man screened were €5150 for TRUSGB, €5994 for mpMRI without biopsy, and €4848 for mpMRI with biopsy. Corresponding QALYs were higher for mpMRI with biopsy compared to TRUSGB (18.67 vs 18.66) and lower for mpMRI without biopsy compared to TRUSGB (18.27 vs 18.66). Owing to lower costs and higher effects, the mpMRI with biopsy strategy was cost-effective compared to the TRUSGB strategy. CONCLUSIONS: mpMRI with MR-TRUSGB appears to be the most cost-effective AS strategy for men with low-risk prostate cancer. PATIENT SUMMARY: We compared costs and quality of life for the standard active surveillance (AS) program for men diagnosed with low-risk prostate cancer to a monitoring program comprising multiparametric magnetic resonance imaging (mpMRI) with and without biopsies. Our results suggest that an AS strategy using mpMRI with biopsy improves quality of life and costs decrease. An AS strategy using mpMRI without biopsy was not beneficial compared to the standard program.

Meniscus surgery is still widely performed in the treatment of degenerative meniscus tears in The Netherlands.

PURPOSE: Studies have demonstrated rising incidences of meniscus procedures for degenerative meniscus tears in several countries, despite accumulating evidence that questions the efficacy of the treatment. It is not clear if this rise in incidences also applies to the practice of arthroscopic surgery in the Netherlands. The objective of this study was, therefore, to evaluate the number of meniscal surgeries performed in the Netherlands between 2005 and 2014. METHODS: We used registry-based data on meniscal surgeries that originated from Dutch national hospital basic care registrations from 2005 to 2014. Poisson regression models were used to test differences in incidences of meniscus surgeries performed in the Netherlands between 2005 and 2014, and to find out if changes in incidences over this period differed for younger and older patients. RESULTS: The number of meniscus surgeries was highest in patients aged 40-65 years, who accounted for half of the total number of meniscal surgeries. The incidences of meniscus surgeries decreased from 2005 to 2014 (p < 0.001); this decrease was observed in all age groups, although the decrease in incidences was more pronounced for younger patients (aged less than 40 years) compared to middle-aged and older patients (aged 40 years and older) (p < 0.001). CONCLUSIONS: The implementation of a nationwide guideline for arthroscopic procedures for meniscus tears may have contributed to a decrease in incidences of meniscus procedures. Despite accumulating evidence that questions the rationalisation and effectiveness of the treatment, meniscus surgery is still widely performed in the treatment of degenerative meniscus tears in the Netherlands, demonstrating a delay in the dissemination, acceptance, and implementation of clinical evidence in the practice of arthroscopic surgery in the Netherlands. LEVEL OF EVIDENCE: II.

In Vitro and In Vivo Characterization of Biodegradable Reactive Isocyanate-Terminated Three-Armed- and Hyperbranched Block Copolymeric Tissue Adhesives.

Tissue adhesives are an attractive class of biomaterials, which can serve as a treatment for meniscus tears. In this study, physicochemical and adhesive properties of novel biodegradable three-armed- and hyperbranched block copolymeric adhesives are evaluated. Additionally, their degradation in vitro and in vivo, and the tissue reaction after subcutaneous injection in rats are assessed. The developed adhesives have sufficient adhesive strength to meniscus tissue after curing (66-88 kPa). Networks based on the three-armed adhesive have tensile properties that are in the same range as human meniscus. After 26 weeks, networks based on the hyperbranched adhesive show a faster mass loss (25.4%) compared to networks prepared from the three-armed ones (5.5%). Both adhesives induce an inflammatory reaction, however, no necrosis and only initial toxic effects on peripheral tissues are observed. The proposed materials are suitable candidates for the use as resorbable tissue adhesives for meniscus repair.

Degradation behavior of, and tissue response to photo-crosslinked poly(trimethylene carbonate) networks.

Photo-crosslinked networks prepared from three-armed methacrylate functionalized PTMC oligomers (PTMC-tMA macromers) are attractive materials for developing an anatomically correct meniscus scaffold. In this study, we evaluated cell specific biocompatibility, in vitro and in vivo degradation behavior of, and tissue response to, such PTMC networks. By evaluating PTMC networks prepared from PTMC-tMA macromers of different molecular weights, we were able to assess the effect of macromer molecular weight on the degradation rate of the PTMC network obtained after photo-crosslinking. Three photo-crosslinked networks with different crosslinking densities were prepared using PTMC-tMA macromers with molecular weights 13.3, 17.8, and 26.7 kg/mol. Good cell biocompatibility was demonstrated in a proliferation assay with synovium derived cells. PTMC networks degraded slowly, but statistically significant, both in vitro as well as subcutaneously in rats. Networks prepared from macromers with higher molecular weights demonstrated increased degradation rates compared to networks prepared from initial macromers of lowest molecular weight. The degradation process took place via surface erosion. The PTMC networks showed good tissue tolerance during subcutaneous implantation, to which the tissue response was characterized by the presence of fibrous tissue and encapsulation of the implants. Concluding, we developed cell and tissue biocompatible, photo-crosslinked PTMC networks using PTMC-tMA macromers with relatively high molecular weights. These photo-crosslinked PTMC networks slowly degrade by a surface erosion process. Increasing the crosslinking density of these networks decreases the rate of surface degradation. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2823-2832, 2016.

Societal and Economic Effect of Meniscus Scaffold Procedures for Irreparable Meniscus Injuries.

BACKGROUND: Meniscus scaffolds are currently evaluated clinically for their efficacy in preventing the development of osteoarthritis as well as for their efficacy in treating patients with chronic symptoms. Procedural costs, therapeutic consequences, clinical efficacy, and future events should all be considered to maximize the monetary value of this intervention. PURPOSE: To examine the socioeconomic effect of treating patients with irreparable medial meniscus injuries with a meniscus scaffold. STUDY DESIGN: Economic and decision analysis; Level of evidence, 2. METHODS: Two Markov simulation models for patients with an irreparable medial meniscus injury were developed. Model 1 was used to investigate the lifetime cost-effectiveness of a meniscus scaffold compared with standard partial meniscectomy by the possibility of preventing the development of osteoarthritis. Model 2 was used to investigate the short-term (5-year) cost-effectiveness of a meniscus scaffold compared with standard partial meniscectomy by alleviating clinical symptoms, specifically in chronic patients with previous meniscus surgery. For both models, probabilistic Monte Carlo simulations were applied. Treatment effectiveness was expressed as quality-adjusted life-years (QALYs), while costs (estimated in euros) were assessed from a societal perspective. We assumed €20,000 as a reference value for the willingness to pay per QALY. Next, comprehensive sensitivity analyses were performed to identify the most influential variables on the cost-effectiveness of meniscus scaffolds. RESULTS: Model 1 demonstrated an incremental cost-effectiveness ratio of a meniscus scaffold treatment of €54,463 per QALY (€5991/0.112). A threshold analysis demonstrated that a meniscus scaffold should offer a relative risk reduction of at least 0.34 to become cost-effective, assuming a willingness to pay of €20,000. Decreasing the costs of the meniscus scaffold procedure by 33% (€10,160 instead of €15,233; an absolute change of €5073) resulted in an incremental cost-effectiveness ratio of €7876 per QALY. Model 2 demonstrated an incremental cost-effectiveness ratio of a meniscus scaffold treatment of €297,727 per QALY (€9825/0.033). On the basis of the current efficacy data, a meniscus scaffold provides a relative risk reduction of "limited benefit" postoperatively of 0.37 compared with standard treatment. A threshold analysis revealed that assuming a willingness to pay of €20,000, a meniscus scaffold would not be cost-effective within a period of 5 years. Most influential variables on the cost-effectiveness of meniscus scaffolds were the cost of the scaffold procedure, cost associated with osteoarthritis, and quality of life before and after the scaffold procedure. CONCLUSION: Results of the current health technology assessment emphasize that the monetary value of meniscus scaffold procedures is very much dependent on a number of influential variables. Therefore, before implementing the technology in the health care system, it is important to critically assess these variables in a relevant context. The models can be improved as additional clinical data regarding the efficacy of the meniscus scaffold become available.

Comparison of Registered and Published Primary Outcomes in Randomized Controlled Trials of Orthopaedic Surgical Interventions.

BACKGROUND: The selective reporting of a subset of the outcomes that had been originally reported to a registry is a potential threat to the validity of evidence-based medicine. The extent of selective reporting has not been described for randomized controlled trials (RCTs) assessing the effectiveness of orthopaedic surgical interventions. The objective of this study was (1) to determine the percentage of orthopaedic surgical RCTs published in high-impact orthopaedic journals that were reported to have been registered, (2) to evaluate the consistency between the primary outcome measures recorded in the registry and those reported in the article, and (3) to evaluate whether selective reporting favored statistically significant outcomes. METHODS: We searched PubMed for articles on RCTs assessing orthopaedic surgical interventions indexed from January 2010 through December 2014 and published in the ten orthopaedic journals with the highest impact factors. For every article in which the authors reported registration of the RCT, we extracted the number and nature of the outcome measures from the article and the corresponding information from the registry. We then evaluated the consistency between the primary outcome measures reported in the registry and those reported in the published article. Moreover, we evaluated whether selective reporting favored statistically significant outcomes. RESULTS: Of the 362 articles on orthopaedic surgical RCTs, ninety (24.9%) reported that the RCT had been registered and thirty-four (37.8%) of the ninety had been registered adequately (registered before the study end with a clear description of the primary outcome measure and its time frame, with no substantial change after the study end). Twenty-six reports were eligible for our evaluation of the consistency between the registered primary outcome measures and those reported in the published article. This analysis identified one or multiple major discrepancies for fourteen articles, eight of which favored statistically significant results. CONCLUSIONS: Few articles on orthopaedic surgical RCTs reported registration of the trial, and even fewer of these trials were registered adequately. Inconsistencies between registered primary outcome measures and those reported in the published articles, as well as selective outcome reporting favoring statistically significant outcomes, were prevalent. CLINICAL RELEVANCE: Although trial registration is now the rule, it is currently far from optimal for orthopaedic surgical RCTs, and selective outcome reporting is prevalent. Full involvement of authors, editors, and reviewers is necessary to ensure publication of quality, unbiased results.

Biomaterials in search of a meniscus substitute.

The menisci fulfill key biomechanical functions in the tibiofemoral (knee) joint. Unfortunately meniscal injuries are quite common and most often treated by (partial) meniscectomy. However, some patients experience enduring symptoms, and, more importantly, it leads to an increased risk for symptomatic osteoarthritis. Over the past decades, researchers have put effort in developing a meniscal substitute able to prevent osteoarthritis and treat enduring clinical symptoms. Grossly, two categories of substitutes are observed: First, a resorbable scaffold mimicking biomechanical function which slowly degrades while tissue regeneration and organization is promoted. Second, a non resorbable, permanent implant which mimics the biomechanical function of the native meniscus. Numerous biomaterials with different (material) properties have been used in order to provide such a substitute. Nevertheless, a clinically applicable cartilage protecting material is not yet emerged. In the current review we provide an overview, and discuss, these different materials and extract recommendations regarding material properties for future developmental research.

Cumulative effect of 5 daily sessions of θ burst stimulation on corticospinal excitability in amyotrophic lateral sclerosis.

INTRODUCTION: Excitotoxicity plays an important role in the pathogenesis of the preferential motor neuron death observed in amyotrophic lateral sclerosis (ALS). Continuous theta burst stimulation (cTBS) by transcranial magnetic stimulation has an inhibitory effect on corticospinal excitability (CSE). We characterized the neurophysiological changes induced by cTBS in ALS. METHODS: The patients received 5 daily sessions of cTBS. CSE was assessed at baseline and after each session of cTBS. RESULTS: The amplitude of a single pulse motor evoked potential was significantly decreased (34%) over the days. The amplitude returned to baseline a week after the last session. The resting motor threshold increased significantly, whereas intracortical inhibition and facilitation did not change over the sessions. CONCLUSIONS: Daily cTBS has a cumulative depressing effect on CSE in patients with ALS. These results suggest that modulation of CSE in ALS is possible, but repetitive sessions are needed to maintain the effect.

Transcranial direct current stimulation does not modulate motor cortex excitability in patients with amyotrophic lateral sclerosis.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a progressive disease caused by the degeneration of upper and lower motor neurons. The etiology of ALS is unclear, but there is evidence that loss of cortical inhibition could be related to motor neuron degeneration. We sought to determine whether cathodal transcranial direct current stimulation (tDCS) can reduce cortical excitability in patients with ALS. METHODS: Three sessions of cathodal tDCS, lasting 7, 11, or 15 minutes, were performed in 10 patients and 10 healthy controls. Corticospinal excitability was measured before and after the tDCS. RESULTS: Cathodal tDCS induced a consistent decrease in corticospinal excitability in healthy controls, but not in ALS patients. CONCLUSIONS: The failure of tDCS to produce an excitability shift in the patients supports the potential diagnostic value of tDCS as a marker of upper motor neuron involvement. However, variation in corticospinal excitability measurements both inter- and intraindividually will limit its usefulness.