Publications by authors named "Jorrit-Jan Verlaan"

86 Publications

Sensory innervation of human bone: an immunohistochemical study to further understand bone pain.

J Pain 2021 May 5. Epub 2021 May 5.

Department of Orthopedic Surgery, University Medical Center Utrecht, the Netherlands; SentryX B.V., Woudenbergseweg 41, Austerlitz, the Netherlands.

Skeletal diseases and their surgical treatment induce severe pain. The innervation density of bone potentially explains the severe pain reported. Animal studies concluded that sensory myelinated A∂-fibers and unmyelinated C-fibers are mainly responsible for conducting bone pain, and that the innervation density of these nerve fibers was highest in periosteum. However, literature regarding sensory innervation of human bone is scarce. This observational study aimed to quantify sensory nerve fiber density in periosteum, cortical bone, and bone marrow of axial and appendicular human bones using immunohistochemistry and confocal microscopy. Multivariate Poisson regression analysis demonstrated that the total number of sensory and sympathetic nerve fibers was highest in periosteum, followed by bone marrow, and cortical bone for all bones studied. Bone from thoracic vertebral bodies contained most sensory nerve fibers, followed by the upper extremity, lower extremity, and parietal neurocranium. The number of nerve fibers declined with age and did not differ between male and female specimens. Sensory nerve fibers were organized as a branched network throughout the periosteum. The current results provide an explanation for the severe pain accompanying skeletal disease, fracture, or surgery. Further, the results could provide more insight into mechanisms that generate and maintain skeletal pain and might aid in developing new treatment strategies. PERSPECTIVE: This article presents the innervation of human bone and assesses the effect of age, gender, bone compartment and type of bone on innervation density. The presented data provide an explanation for the severity of bone pain arising from skeletal diseases and their surgical treatment.
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http://dx.doi.org/10.1016/j.jpain.2021.04.006DOI Listing
May 2021

Availability and reporting quality of external validations of machine-learning prediction models with orthopedic surgical outcomes: a systematic review.

Acta Orthop 2021 Apr 18:1-9. Epub 2021 Apr 18.

Orthopedic Oncology Service, Massachusetts General Hospital, Harvard Medical School, Boston, USA;

Background and purpose - External validation of machine learning (ML) prediction models is an essential step before clinical application. We assessed the proportion, performance, and transparent reporting of externally validated ML prediction models in orthopedic surgery, using the Transparent Reporting for Individual Prognosis or Diagnosis (TRIPOD) guidelines.Material and methods - We performed a systematic search using synonyms for every orthopedic specialty, ML, and external validation. The proportion was determined by using 59 ML prediction models with only internal validation in orthopedic surgical outcome published up until June 18, 2020, previously identified by our group. Model performance was evaluated using discrimination, calibration, and decision-curve analysis. The TRIPOD guidelines assessed transparent reporting.Results - We included 18 studies externally validating 10 different ML prediction models of the 59 available ML models after screening 4,682 studies. All external validations identified in this review retained good discrimination. Other key performance measures were provided in only 3 studies, rendering overall performance evaluation difficult. The overall median TRIPOD completeness was 61% (IQR 43-89), with 6 items being reported in less than 4/18 of the studies.Interpretation - Most current predictive ML models are not externally validated. The 18 available external validation studies were characterized by incomplete reporting of performance measures, limiting a transparent examination of model performance. Further prospective studies are needed to validate or refute the myriad of predictive ML models in orthopedics while adhering to existing guidelines. This ensures clinicians can take full advantage of validated and clinically implementable ML decision tools.
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http://dx.doi.org/10.1080/17453674.2021.1910448DOI Listing
April 2021

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

J Orthop Res 2021 Mar 18. Epub 2021 Mar 18.

Orthopedic Oncology Service, Department of Orthopedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.

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.
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http://dx.doi.org/10.1002/jor.25036DOI Listing
March 2021

Costs Associated With Timely and Delayed Surgical Treatment of Spinal Metastases.

Global Spine J 2021 Jan 29:2192568220984789. Epub 2021 Jan 29.

Department of Orthopedics, 569621University Medical Center Utrecht, the Netherlands.

Study Design: Retrospective cohort study.

Objectives: Symptoms caused by spinal metastases are often difficult to distinguish from symptoms caused by non-malignant spinal disease, complicating timely diagnosis, referral and treatment. The ensuing delays may promote the risk of neurological deficits or severe mechanical instability and consequent emergency surgery, leading to poorer prognosis. Presumably, treatment delay may subsequently lead to more health-care consumption and therefore increased average costs of treatment.

Methods: All patients surgically treated for spinal metastases were included in the current study. Based on the presence of alarming symptoms and urgency of the required intervention, patients were categorized as having received timely or delayed treatment. Pre-surgical, in-hospital, aftercare and total costs were analyzed and compared between the 2 groups.

Results: In total, 299 patients were included, of which 205 underwent timely and 94 delayed treatment. There was no significant difference in pre-surigcal costs (€3.229,13 in the timely treated group €2.528,70 in the delayed treatment group, p = 0.849). The in-hospital costs (€16.738,49 €13.108,81, p < 0.001) and the aftercare costs (€13.950,37 . 3.981,93, p < 0.001) were significantly higher for delayed treatment timely treatment, respectively. The total costs were €33.741,71 for delayed treatment and €20.318,52 for timely treatment (p < 0.001).

Conclusions: The total costs for timely treated patients with spinal metastases are significantly lower compared with patients receiving delayed treatment. Investing in the optimization of referral patterns may therefore reduce the overall pretreatment delay and subsequently increase patient outcome, leading to better clinical outcomes at lower costs.
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http://dx.doi.org/10.1177/2192568220984789DOI Listing
January 2021

Diffuse Idiopathic Skeletal Hyperostosis (DISH) and a Possible Inflammatory Component.

Curr Rheumatol Rep 2021 Jan 26;23(1). Epub 2021 Jan 26.

Case Western Reserve University, Cleveland, OH, USA.

Purpose Of Review: Diffuse Idiopathic Skeletal Hyperostosis (DISH) is considered a metabolic condition, characterized by new bone formation affecting mainly at entheseal sites. Enthesitis and enthesopathies occur not only in the axial skeleton but also at some peripheral sites, and they resemble to some extent the enthesitis that is a cardinal feature in spondyloarthritis (SpA), which is an inflammatory disease.

Recent Findings: We review the possible non-metabolic mechanism such as inflammation that may also be involved at some stage and help promote new bone formation in DISH. We discuss supporting pathogenic mechanisms for a local inflammation at sites typically affected by this disease, and that is also supported by imaging studies that report some similarities between DISH and SpA. Local inflammation, either primary or secondary to metabolic derangements, may contribute to new bone formation in DISH. This new hypothesis is expected to stimulate further research in both the metabolic and inflammatory pathways in order to better understand the mechanisms that lead to new bone formation. This may lead to development of measures that will help in earlier detection and effective management before damage occurs.
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http://dx.doi.org/10.1007/s11926-020-00972-xDOI Listing
January 2021

Do Cohabitants Reliably Complete Questionnaires for Patients in a Terminal Cancer Stage when Assessing Quality of Life, Pain, Depression, and Anxiety?

Clin Orthop Relat Res 2021 04;479(4):792-801

O. Q. Groot, N. R. P. Pereira, M. E. R. Bongers, P. T. Ogink, E. T. Newman, K. A. Raskin, S. A. Lozano-Calderon, J. H. Schwab, Department of Orthopaedic Surgery, Orthopaedic Oncology Service, Massachusetts General Hospital - Harvard Medical School, Boston, MA, USA.

Background: Patients with bone metastases often are unable to complete quality of life (QoL) questionnaires, and cohabitants (such as spouses, domestic partners, offspring older than 18 years, or other people who live with the patient) could be a reliable alternative. However, the extent of reliability in this complicated patient population remains undefined, and the influence of the cohabitant's condition on their assessment of the patient's QoL is unknown.

Questions/purposes: (1) Do QoL scores, measured by the 5-level EuroQol-5D (EQ-5D-5L) version and the Patient-reported Outcomes Measurement Information System (PROMIS) version 1.0 in three domains (anxiety, pain interference, and depression), reported by patients differ markedly from scores as assessed by their cohabitants? (2) Do cohabitants' PROMIS-Depression scores correlate with differences in measured QoL results?

Methods: This cross-sectional study included patients and cohabitants older than 18 years of age. Patients included those with presence of histologically confirmed bone metastases (including lymphoma and multiple myeloma), and cohabitants must have been present at the clinic visit. Patients were eligible for inclusion in the study regardless of comorbidities, prognosis, prior surgery, or current treatment. Between June 1, 2016 and March 1, 2017 and between October 1, 2017 and February 26, 2018, all 96 eligible patients were approached, of whom 49% (47) met the selection criteria and were willing to participate. The included 47 patient-cohabitant pairs independently completed the EQ-5D-5L and the eight-item PROMIS for three domains (anxiety, pain, and depression) with respect to the patients' symptoms. The cohabitants also completed the four-item PROMIS-Depression survey with respect to their own symptoms.

Results: There were no clinically important differences between the scores of patients and their cohabitants for all questionnaires, and the agreement between patient and cohabitant scores was moderate to strong (Spearman correlation coefficients ranging from 0.52 to 0.72 on the four questionnaires; all p values < 0.05). However, despite the good agreement in QoL scores, an increased cohabitant's depression score was correlated with an overestimation of the patient's symptom burden for the anxiety and depression domains (weak Spearman correlation coefficient of 0.33 [95% confidence interval 0.08 to 0.58]; p = 0.01 and moderate Spearman correlation coefficient of 0.52 [95% CI 0.29 to 0.74]; p < 0.01, respectively).

Conclusion: The present findings support that cohabitants might be reliable raters of the QoL of patients with bone metastases. However, if a patient's cohabitant has depression, the cohabitant may overestimate a patient's symptoms in emotional domains such as anxiety and depression, warranting further research that includes cohabitants with and without depression to elucidate the effect of depression on the level of agreement. For now, clinicians may want to reconsider using the cohabitant's judgement if depression is suspected.

Clinical Relevance: These findings suggest that a cohabitant's impressions of a patient's quality of life are, in most instances, accurate; this is potentially helpful in situations where the patient cannot weigh in. Future studies should employ longitudinal designs to see how or whether our findings change over time and with disease progression, and how specific interventions-like different chemotherapeutic regimens or surgery-may factor in.
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http://dx.doi.org/10.1097/CORR.0000000000001525DOI Listing
April 2021

Postoperative adverse events secondary to iatrogenic vascular injury during anterior lumbar spinal surgery.

Spine J 2020 Nov 3. Epub 2020 Nov 3.

Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA.

Background: Anterior lumbar spine surgery (ALSS) requires mobilization of the great vessels, resulting in a high risk of iatrogenic vascular injury (VI). It remains unclear whether VI is associated with increased risk of postoperative complications and other related adverse outcomes.

Purpose: The purpose of this study was to (1) assess the incidence of postoperative complications attributable to VI during ALSS, and (2) outcomes secondary to VI such as procedural blood loss, transfusion of blood products, length of stay (LOS), and in hospital mortality.

Study Design: Retrospective propensity-score matched, case-control study at 2 academic and 3 community medical centers, PATIENT SAMPLE: Patients 18 years of age or older, undergoing ALSS between January 1st, 2000 and July 31st, 2019 were included in this analysis.

Outcome Measures: The primary outcome was the incidence of postoperative complications attributable to VI, such as venous thromboembolism, compartment syndrome, transfusion reaction, limb ischemia, and reoperations. The secondary outcomes included estimated operative blood loss (milliliter), transfused blood products, LOS (days), and in-hospital mortality.

Methods: In total, 1,035 patients were identified, of which 75 (7.2%) had a VI. For comparative analyses, the 75 VI patients were paired with 75 comparable non-VI patients by propensity-score matching. The adequacy of the matching was assessed by testing the standardized mean differences (SMD) between VI and non-VI group (>0.25 SMD).

Results: Two patients (2.7%) had VI-related postoperative complications in the studied period, which consisted of two deep venous thromboembolisms (DVTs) occurring on day 3 and 7 postoperatively. Both DVTs were located in the distal left common iliac vein (CIV). The VI these patients suffered were to the distal inferior vena cava and the left CIV, respectively. Both patients did not develop additional complications in consequence of their DVTs, however, did require systemic anticoagulation and placement of an inferior vena cava filter. There was no statistical difference with the non-VI group where no instances (0%) of postoperative complications were reported (p=.157). No differences were found in LOS or in hospital mortality between the two groups (p=.157 and p=.999, respectively). Intraoperative blood loss and blood transfusion were both found to be higher in the VI group in comparison to the non-VI group (650 mL, interquartile range [IQR] 300-1400 vs. 150 mL, IQR 50-425, p≤.001; 0 units, IQR 0-3 vs. 0 units, IQR 0-1, p=.012, respectively).

Conclusion: This study found a low number of serious postoperative complications related to VI in ALSS. In addition, these complications were not significantly different between the VI and matched non-VI ALSS cohort. Although not significant, the found DVT incidence of 2.7% after VI in ALSS warrants vigilance and preventive measures during the postoperative course of these patients.
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http://dx.doi.org/10.1016/j.spinee.2020.10.031DOI Listing
November 2020

The importance of timely treatment for quality of life and survival in patients with symptomatic spinal metastases.

Eur Spine J 2020 12 18;29(12):3170-3178. Epub 2020 Sep 18.

Department of Orthopedic Surgery, University Medical Center Utrecht, P.O. Box 85500 (G05.228), 3508 GA, Utrecht, The Netherlands.

Purpose: A major challenge in metastatic spinal disease is timely identification of patients. Left untreated, spinal metastases may lead to gross mechanical instability and/or neurological deficits, often requiring extensive invasive surgical treatment. The aim of this cohort study was to assess the correlation between delayed treatment of patients with spinal metastases and functional performance, quality of life and survival.

Methods: All patients surgically treated for metastatic spinal disease at a tertiary care facility were included for analysis. Patients who underwent elective surgery were considered as timely treated, whereas patients requiring emergency surgery were considered to be treated in a delayed fashion. EQ-5D scores, KPS scores and mortality rates were compared between the two groups.

Results: A total of 317 patients (215 timely treated, 102 delayed) had survivorship data available and 202 patients (147 timely treated, 55 delayed) had clinical data available. Multivariate analyses showed delayed treatment was associated with lower EQ-5D and KPS scores and higher mortality rates, independent of confounders such as baseline EQ-5D/KPS scores, neurological status, tumor prognosis and patient age.

Conclusions: The results from the present study show delayed treatment of patients with symptomatic spinal metastases has both direct and indirect adverse consequences for functional performance status, quality of life and survival. Optimization of referral pattern may accelerate the time to surgical treatment, potentially leading to better quality of life and survival.
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http://dx.doi.org/10.1007/s00586-020-06599-xDOI Listing
December 2020

Does Artificial Intelligence Outperform Natural Intelligence in Interpreting Musculoskeletal Radiological Studies? A Systematic Review.

Clin Orthop Relat Res 2020 12;478(12):2751-2764

O. Q. Groot, M. E. R. Bongers, A. V. Karhade, J. H. Schwab, Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Background: Machine learning (ML) is a subdomain of artificial intelligence that enables computers to abstract patterns from data without explicit programming. A myriad of impactful ML applications already exists in orthopaedics ranging from predicting infections after surgery to diagnostic imaging. However, no systematic reviews that we know of have compared, in particular, the performance of ML models with that of clinicians in musculoskeletal imaging to provide an up-to-date summary regarding the extent of applying ML to imaging diagnoses. By doing so, this review delves into where current ML developments stand in aiding orthopaedists in assessing musculoskeletal images.

Questions/purposes: This systematic review aimed (1) to compare performance of ML models versus clinicians in detecting, differentiating, or classifying orthopaedic abnormalities on imaging by (A) accuracy, sensitivity, and specificity, (B) input features (for example, plain radiographs, MRI scans, ultrasound), (C) clinician specialties, and (2) to compare the performance of clinician-aided versus unaided ML models.

Methods: A systematic review was performed in PubMed, Embase, and the Cochrane Library for studies published up to October 1, 2019, using synonyms for machine learning and all potential orthopaedic specialties. We included all studies that compared ML models head-to-head against clinicians in the binary detection of abnormalities in musculoskeletal images. After screening 6531 studies, we ultimately included 12 studies. We conducted quality assessment using the Methodological Index for Non-randomized Studies (MINORS) checklist. All 12 studies were of comparable quality, and they all clearly included six of the eight critical appraisal items (study aim, input feature, ground truth, ML versus human comparison, performance metric, and ML model description). This justified summarizing the findings in a quantitative form by calculating the median absolute improvement of the ML models compared with clinicians for the following metrics of performance: accuracy, sensitivity, and specificity.

Results: ML models provided, in aggregate, only very slight improvements in diagnostic accuracy and sensitivity compared with clinicians working alone and were on par in specificity (3% (interquartile range [IQR] -2.0% to 7.5%), 0.06% (IQR -0.03 to 0.14), and 0.00 (IQR -0.048 to 0.048), respectively). Inputs used by the ML models were plain radiographs (n = 8), MRI scans (n = 3), and ultrasound examinations (n = 1). Overall, ML models outperformed clinicians more when interpreting plain radiographs than when interpreting MRIs (17 of 34 and 3 of 16 performance comparisons, respectively). Orthopaedists and radiologists performed similarly to ML models, while ML models mostly outperformed other clinicians (outperformance in 7 of 19, 7 of 23, and 6 of 10 performance comparisons, respectively). Two studies evaluated the performance of clinicians aided and unaided by ML models; both demonstrated considerable improvements in ML-aided clinician performance by reporting a 47% decrease of misinterpretation rate (95% confidence interval [CI] 37 to 54; p < 0.001) and a mean increase in specificity of 0.048 (95% CI 0.029 to 0.068; p < 0.001) in detecting abnormalities on musculoskeletal images.

Conclusions: At present, ML models have comparable performance to clinicians in assessing musculoskeletal images. ML models may enhance the performance of clinicians as a technical supplement rather than as a replacement for clinical intelligence. Future ML-related studies should emphasize how ML models can complement clinicians, instead of determining the overall superiority of one versus the other. This can be accomplished by improving transparent reporting, diminishing bias, determining the feasibility of implantation in the clinical setting, and appropriately tempering conclusions.

Level Of Evidence: Level III, diagnostic study.
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http://dx.doi.org/10.1097/CORR.0000000000001360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899420PMC
December 2020

Diffuse idiopathic skeletal hyperostosis: Etiology and clinical relevance.

Best Pract Res Clin Rheumatol 2020 06 23;34(3):101527. Epub 2020 May 23.

Department of Orthopedics, University Medical Center Utrecht, Postbus 85500, 3508 GA, Utrecht, the Netherlands.

Diffuse idiopathic skeletal hyperostosis (DISH) is a systemic bone-forming condition characterized by the presence of at least three bony bridges at the anterolateral spine. The aim of this review was to address the present state of pathophysiological knowledge, the clinical relevance, and diagnosis of DISH. The pathogenesis of DISH is currently unknown. The presence of DISH has been associated with older age, male sex, obesity, hypertension, atherosclerosis, and diabetes mellitus. Because the new bone forms mainly at entheseal sites, local fibroblasts, chondrocytes, collagen fibers, and calcified matrix are probably influenced by genetic, vascular, metabolic, and mechanical factors. Diagnosing the presence of DISH is of clinical importance, because the risk of a spinal fracture increases and associations with the metabolic syndrome, coronary and aortic disease, and respiratory effects are strong. Unravelling the pathogenesis of DISH can impact the field of regenerative medicine and bone tissue regeneration.
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http://dx.doi.org/10.1016/j.berh.2020.101527DOI Listing
June 2020

Imaging of diffuse idiopathic skeletal hyperostosis (DISH).

RMD Open 2020 02;6(1)

Rheumatology Unit, Department of Internal and Experimental Medicine, University of Messina, Messina, Italy.

Diffuse idiopathic skeletal hyperostosis (DISH) is a condition characterised by calcification and ossification of ligaments and entheses. The condition usually affects the axial skeleton, in particular, at the thoracic segment, though also other portions of the spine are often involved. DISH often involves also peripheral tendinous and/or entheseal sites either alone, or in association with the involvement of peripheral joints. At times, new bone formation involves the bone itself, but sometimes it involves joints not usually affected by osteoarthritis (OA) which result in bony enlargement of the epiphysis, joints space narrowing and a reduced range of motion. Because of the entheseal involvement, DISH can be mistaken for seronegative spondyloarthropathies or for a "simple" OA. Furthermore, other implications for the recognition of DISH include spinal fractures, difficult intubation and upper endoscopies, decreased response rates in DISH with concomitant spondyloarthritides, and increased likelihood to be affected by metabolic syndrome and cardiovascular diseases. This Atlas is intended to show the imaging finding in DISH in patients diagnosed with the condition by the Resnick classification criteria.
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http://dx.doi.org/10.1136/rmdopen-2019-001151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7046956PMC
February 2020

An understanding of bone pain: A narrative review.

Bone 2020 05 13;134:115272. Epub 2020 Feb 13.

Department of Orthopedics, University Medical Centre Utrecht, Heidelberglaan 100, 3508 GA Utrecht, the Netherlands. Electronic address:

Skeletal pathologies are often accompanied by bone pain, which has negative effects on the quality of life and functional status of patients. Bone pain can be caused by a wide variety of injuries and diseases including (poorly healed) fractures, bone cancer, osteoarthritis and also iatrogenic by skeletal interventions. Orthopedic interventions are considered to be the most painful surgical procedures overall. Two major groups of medication currently used to attenuate bone pain are NSAIDs and opioids. However, these systemic drugs frequently introduce adverse events, emphasizing the need for alternative therapies that are directed at the pathophysiological mechanisms underlying bone pain. The periosteum, cortical bone and bone marrow are mainly innervated by sensory A-delta fibers and C-fibers. These fibers are mostly present in the periosteum rendering this structure most sensitive to nociceptive stimuli. A-delta fibers and C-fibers can be activated upon mechanical distortion, acidic environment and increased intramedullary pressure. After activation, these fibers can be sensitized by inflammatory mediators, phosphorylation of acid-sensing ion channels and cytokine receptors, or by upregulation of transcription factors. This can result in a change of pain perception such that normally non-noxious stimuli are now perceived as noxious. Pathological conditions in the bone can produce neurotrophic factors that bind to receptors on A-delta fibers and C-fibers. These fibers then start to sprout and increase the innervation density of the bone, making it more sensitive to nociceptive stimuli. In addition, repetitive painful stimuli cause neurochemical and electrophysiological alterations in afferent sensory neurons in the spinal cord, which leads to central sensitization, and can contribute to chronic bone pain. Understanding the pathophysiological mechanisms underlying bone pain in different skeletal injuries and diseases is important for the development of alternative, targeted pain treatments. These pain mechanism-based alternatives have the potential to improve the quality of life of patients suffering from bone pain without introducing undesirable systemic effects.
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http://dx.doi.org/10.1016/j.bone.2020.115272DOI Listing
May 2020

Clinical, radiological, and patient-reported outcomes 13 years after pedicle screw fixation with balloon-assisted endplate reduction and cement injection.

Eur Spine J 2020 04 8;29(4):914-921. Epub 2020 Feb 8.

Department of Orthopedics, University Medical Center Utrecht, Postbus 85500, 3508 GA, Utrecht, The Netherlands.

Purpose: In management of traumatic thoracolumbar burst fractures, short-segment pedicle screw fixation with balloon-assisted endplate reduction (BAER) and cement injection is a safe, feasible, and effective technique to maintain radiological alignment with minimum spinal segments involved. However, 20% of patients report daily discomfort despite good spinal alignment and fusion after this technique. This study provides clinical, radiological, and patient-reported outcomes after a minimum 13 years of follow-up.

Methods: Eighteen patients were invited at the outpatient clinic for clinical/radiological examinations. The cohort (originally 20 patients) was treated 13-14 years earlier with pedicle screw fixation, BAER, and cement injection for traumatic thoracolumbar burst fractures. Patient-reported outcome measures were obtained at time of examinations. Current data were compared with data obtained at 6 years of follow-up.

Results: Seventeen patients (median age 50; range 32-80) cooperated. No/minimal back pain was reported by 15 patients, and 12 patients returned to their previous heavy labor work. Median visual analog score of health (80%; 50-100%) was similar to results at 6 years (80%; 60-100% p = 0.259). An Oswestry Disability Index score of less than 20% (reflecting minimal disability) was reported by 14 patients, compared with 15 patients at 6 years of follow-up. No significant differences were found in wedge or Cobb angle between the time points. Intravertebral cement resorption was not observed.

Conclusion: Results from this study suggest that, 13 years after pedicle screw fixation with BAER and cement injection for traumatic thoracolumbar burst fractures, functional performance, pain and radiological outcomes of the current cohort were stable or had slightly improved. These slides can be retrieved under Electronic Supplementary Material.
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http://dx.doi.org/10.1007/s00586-020-06321-xDOI Listing
April 2020

How good are the outcomes of instrumented debulking operations for symptomatic spinal metastases and how long do they stand? A subgroup analysis in the global spine tumor study group database.

Acta Neurochir (Wien) 2020 04 17;162(4):943-950. Epub 2020 Jan 17.

Department of Neurosurgery, National Hospital for Neurology and Neurosurgery, University College London, London, UK.

Background: The benefits of surgery for symptomatic spinal metastases have been demonstrated, largely based on series of patients undergoing debulking and instrumentation operations. However, as cancer treatments improve and overall survival lengths increase, the incidence of recurrent spinal cord compression after debulking may increase. The aim of the current paper is to document the postoperative evolution of neurological function, pain, and quality of life following debulking and instrumentation in the Global Spine Tumor Study Group (GSTSG) database.

Methods: The GSTSG database is a prospective multicenter data repository of consecutive patients that underwent surgery for a symptomatic spinal metastasis. For the present analysis, patients were selected from the database that underwent decompressive debulking surgery with instrumentation. Preoperative tumor type, Tomita and Tokuhashi scores, EQ-5D, Frankel, Karnofsky, and postoperative complications, survival, EQ-5D, Frankel, Karnofsky, and pain numeric rating scores (NRS) at 3, 6, 12, and 24 months were analyzed.

Results: A total of 914 patients underwent decompressive debulking surgery with instrumentation and had documented follow-up until death or until 2 years post surgery. Median preoperative Karnofsky performance index was 70. A total of 656 patients (71.8%) had visceral metastases and 490 (53.6%) had extraspinal bone metastases. Tomita scores were evenly distributed above (49.1%) and below or equal to 5 (50.9%), and Tokuhashi scores almost evenly distributed below or equal to 8 (46.3%) and above 8 (53.7%). Overall, 12-month survival after surgery was 56.3%. The surgery resulted in EQ-5D health status improvement and NRS pain reduction that was maintained throughout follow-up. Frankel scores improved at first follow-up in 25.0% of patients, but by 12 months neurological deterioration was observed in 18.8%.

Conclusion: We found that palliative debulking and instrumentation surgeries were performed throughout all Tomita and Tokuhashi categories. These surgeries reduced pain scores and improved quality of life up to 2 years after surgery. After initial improvement, a proportion of patients experienced neurological deterioration by 1 year, but the majority of patients remained stable.
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http://dx.doi.org/10.1007/s00701-019-04197-5DOI Listing
April 2020

Metastatic Spine Disease: Should Patients With Short Life Expectancy Be Denied Surgical Care? An International Retrospective Cohort Study.

Neurosurgery 2020 08;87(2):303-311

Division of Spine Surgery, Department of Orthopaedics, Vancouver General Hospital, University of British Columbia, Vancouver, Canada.

Background: Despite our inability to accurately predict survival in many cancer patients, a life expectancy of at least 3 mo is historically necessary to be considered for surgical treatment of spinal metastases.

Objective: To compare health-related quality of life (HRQOL) in patients surviving <3 mo after surgical treatment to patients surviving >3 mo to assess the validity of this inclusion criteria.

Methods: Patients who underwent surgery for spinal metastases between August 2013 and May 2017 were retrospectively identified from an international cohort study. HRQOL was evaluated using generic and disease-specific outcome tools at baseline and at 6 and 12 wk postsurgery. The primary outcome was the HRQOL at 6 wk post-treatment measured by the Spine Oncology Study Group Outcomes Questionnaire (SOSGOQ).

Results: A total of 253 patients were included: 40 patients died within the first 3 mo after surgery and 213 patients survived more than 3 mo. Patients surviving <3 mo after surgery presented with lower baseline performance status. Adjusted analyses for baseline performance status did not reveal a significant difference in HRQOL between both groups at 6 wk post-treatment. No significant difference in patient satisfaction at 6 wk with regard to their treatment could be detected between both groups.

Conclusion: When controlled for baseline performance status, quality of life 6 wk after surgery for spinal metastasis is independent of survival. To optimize improvement in HRQOL for this patient population, baseline performance status should take priority over expected survival in the surgical decision-making process.
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http://dx.doi.org/10.1093/neuros/nyz472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360875PMC
August 2020

[Spinal metastases: early recognition and a multidisciplinary approach].

Ned Tijdschr Geneeskd 2019 07 12;163. Epub 2019 Jul 12.

UMC Utrecht Hersencentrum, afd. Neurologie en Neurochirurgie, Utrecht.

Early diagnosis of spinal metastases is essential. The neurological condition at the time of diagnosis determines functional outcome. Optimal treatment planning requires a multidisciplinary approach by the general practitioner, internist/oncologist/haematologist, radiotherapist, radiologist, neurologist and the spinal surgeon. Radiation therapy is the most common treatment for patients with spinal metastases. However, in specific cases, surgery or chemotherapy should be the primary treatment. We present three patients with spinal metastases: a 55-year-old woman with back pain and a history of breast cancer, a 71-year-old woman with instability of the spine requiring surgical stabilisation and a 68-year-old man with spinal localisation of multiple myeloma treated with systemic therapy. Their cases illustrate the early symptoms of spinal metastases, the role of spinal stability in treatment decisions and the role of systemic therapy in patients with spinal metastases or haematological tumours located in the spine. Recognising early symptoms and appropriate multidisciplinary treatment planning are essential in improving the functional outcome in patients with spinal metastases.
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July 2019

Malnutrition in patients who underwent surgery for spinal metastases.

Ann Transl Med 2019 May;7(10):213

Department of Orthopaedic Surgery, University Medical Center Utrecht, Utrecht, The Netherlands.

Background: Malnutrition is common among cancer patients and has been associated with increased morbidity and mortality. The primary objective of this study was to evaluate the nutritional status of patients who underwent surgical treatment for spinal metastases. In addition, the association between nutritional status and length of stay, health related quality of life (HRQOL), the occurrence of adverse events and survival was investigated.

Methods: A single center prospective observational cohort study including patients with spinal metastases who underwent surgical treatment was performed. Demographic, diagnostic, treatment, and HRQOL (SOSGOQ2.0 and EQ-5D-3L) data were prospectively collected at baseline and 12 weeks post-treatment. Nutritional status was evaluated with the Patient-Generated Subjective Global Assessment (PG-SGA).

Results: A total of 39 patients were included. Malnutrition as determined by the PG-SGA was present in 36 (92%) of the patients, of whom 32 (82%) were moderately malnourished and 4 (10%) were severely malnourished. Malnourishment was associated with lower baseline SOSGOQ2.0 total scores, SOSGOQ2.0 physical function, mental health and social functioning scores, EQ-5D total scores and EQ-5D mobility scores. No association between malnutrition and survival could be determined.

Conclusions: The prevalence of malnutrition among surgically treated patients with spinal metastases is high. Malnutrition demonstrated to be associated with lower baseline HRQOL scores. Future larger studies are needed to further investigate the prognostic significance of malnutrition.
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http://dx.doi.org/10.21037/atm.2019.04.53DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6595204PMC
May 2019

Subjects with diffuse idiopathic skeletal hyperostosis have an increased burden of coronary artery disease: An evaluation in the COPDGene cohort.

Atherosclerosis 2019 08 30;287:24-29. Epub 2019 May 30.

National Jewish Health, Denver CO, Division of Rheumatology, USA.

Background And Aims: Diffuse idiopathic skeletal hyperostosis (DISH) is a common incidental finding on medical imaging and often thought to be benign. Our objective was to investigate whether DISH is associated with coronary artery disease as measured with the coronary artery calcification (CAC) score in a large cohort of current and former smokers.

Methods: In a subset of subjects from the COPDGene study, DISH was scored by a minimum of two independent readers if there were four adjacent levels of flowing osteophytes and a third reader adjudicated discrepancies. CAC was calculated using a modified Agatston method. Associations of DISH with the presence and extent of CAC were analyzed with and without adjustment for COPD and known atherosclerotic risk factors, including age, sex, race, diabetes, hypertension, high cholesterol, body mass index and smoking.

Results: DISH was present in 361 subjects (13.2%) from a total group of 2728. Median (interquartile range) Agatston was 81 (0-329) in DISH subjects compared to 0 (0-94 in subjects without DISH (p < 0.001). DISH prevalence was 8.8% in CAC = 0, 12.8% in CAC1-100, 20.0% in CAC100-400 and 24.7% in CAC.400. Subjects with DISH had a significantly higher risk of having coronary artery calcifications; OR [CI95%] 1.37[1.05-1.78] (p=0.019) after correction for age, gender, race, COPD and atherosclerotic risk factors.

Conclusions: Subjects with DISH, a common musculoskeletal disorder involving bone formation anterior to the spine, have an increased burden of coronary artery disease, and therefore DISH may be a more relevant incidental finding than commonly thought.
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http://dx.doi.org/10.1016/j.atherosclerosis.2019.05.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041152PMC
August 2019

Essential Concepts for the Management of Metastatic Spine Disease: What the Surgeon Should Know and Practice.

Global Spine J 2019 May 8;9(1 Suppl):98S-107S. Epub 2019 May 8.

Memorial Sloan-Kettering Cancer Center, New York, NY.

Study Design: Literature review.

Objective: To provide an overview of the recent advances in spinal oncology, emphasizing the key role of the surgeon in the treatment of patients with spinal metastatic tumors.

Methods: Literature review.

Results: Therapeutic advances led to longer survival times among cancer patients, placing significant emphasis on durable local control, optimization of quality of life, and daily function for patients with spinal metastatic tumors. Recent integration of modern diagnostic tools, precision oncologic treatment, and widespread use of new technologies has transformed the treatment of spinal metastases. Currently, multidisciplinary spinal oncology teams include spinal surgeons, radiation and medical oncologists, pain and rehabilitation specialists, and interventional radiologists. Consistent use of common language facilitates communication, definition of treatment indications and outcomes, alongside comparative clinical research. The main parameters used to characterize patients with spinal metastases include functional status and health-related quality of life, the spinal instability neoplastic score, the epidural spinal cord compression scale, tumor histology, and genomic profile.

Conclusions: Stereotactic body radiotherapy revolutionized spinal oncology through delivery of durable local tumor control regardless of tumor histology. Currently, the major surgical indications include mechanical instability and high-grade spinal cord compression, when applicable, with surgery providing notable improvement in the quality of life and functional status for appropriately selected patients. Surgical trends include less invasive surgery with emphasis on durable local control and spinal stabilization.
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http://dx.doi.org/10.1177/2192568219830323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512191PMC
May 2019

Systematic Review of the Role of Stereotactic Radiotherapy for Bone Metastases.

J Natl Cancer Inst 2019 10;111(10):1023-1032

Background: Stereotactic radiotherapy (SBRT) might improve pain and local control in patients with bone metastases compared to conventional radiotherapy, although an overall estimate of these outcomes is currently unknown.

Methods: A systematic review was carried out following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Pubmed, Embase, and Cochrane databases were systematically searched to identify studies reporting pain response and local control among patients with bone metastases from solid-organ tumors who underwent SBRT in 1-6 fractions. All studies prior to April 15, 2017, were included. Study quality was assessed by predefined criteria, and pain response and local control rates were extracted.

Results: A total of 2619 studies were screened; 57 were included (reporting outcomes for 3995 patients) of which 38 reported pain response and 45 local control rates. Local control rates were high with pain response rates above those previously reported for conventional radiotherapy. Marked heterogeneity in study populations and delivered treatments were identified such that quantitative synthesis was not appropriate. Reported toxicity was limited. Of the pain response studies, 73.7% used a retrospective cohort design and only 10.5% used the international consensus endpoint definitions of pain response. The median survival within the included studies ranged from 8 to 30.4 months, suggesting a high risk of selection bias in the included observational studies.

Conclusions: This review demonstrates the potential benefit of SBRT over conventional palliative radiotherapy in improving pain due to bone metastases. Given the methodological limitations of the published literature, however, large randomized trials are now urgently required to better quantify this benefit.
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http://dx.doi.org/10.1093/jnci/djz101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6792073PMC
October 2019

Diffuse Idiopathic Skeletal Hyperostosis in Smokers and Restrictive Spirometry Pattern: An Analysis of the COPDGene Cohort.

J Rheumatol 2020 04 1;47(4):531-538. Epub 2019 May 1.

From the University Medical Center Utrecht and Utrecht University, Department of Radiology and Nuclear Medicine, and Department of Orthopedics, Utrecht, the Netherlands; National Jewish Health, Department of Radiology, and divisions of Oncology, Pulmonary, Critical Care, Sleep Medicine, and Rheumatology, Denver, Colorado; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts; Division of Pulmonary, Allergy, and Critical Care Medicine, and Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA; London School of Hygiene and Tropical Medicine, London, UK.

Objective: Diffuse idiopathic skeletal hyperostosis (DISH) is a condition characterized by bony proliferation at sites of tendinous and ligamentous insertions in the spine. Spinal mobility is reduced in DISH and may affect movement in the thorax, potentially leading to restrictive pulmonary function. This study investigated whether DISH is associated with restrictive spirometric pattern (RSP) in former and current smokers.

Methods: Participants (n = 1784) with complete postbronchodilator spirometry who did not meet spirometric criteria for chronic obstructive pulmonary disease (COPD) at time of enrollment in the COPDGene study were included in this study. Subjects were classified as RSP if they had forced expiratory volume in 1 s(FEV1) to forced vital capacity (FVC) ratio > 0.7 with an FVC < 80%. Computed tomography (CT) scans were scored for the presence of DISH in accordance with the Resnick criteria. Chest CT measures of interstitial and alveolar lung disease, clinical symptoms, health surveys, and 6-min walking distance were recorded. Uni- and multivariable analyses were performed to test the association of DISH with RSP.

Results: DISH was present in 236 subjects (13.2%). RSP was twice as common in participants with DISH (n = 90/236, 38.1%) compared to those without DISH (n = 301/1548, 19.4%; p < 0.001). In multivariable analysis, DISH was significantly associated with RSP (OR 1.78; 95% CI 1.22-2.60; p = 0.003) after adjusting for potential confounders. The RSP group with and without DISH had significantly worse spirometry, dyspnea, St. George's Respiratory Questionnaire score, BODE index (Body mass index, airflow Obstruction, Dyspnea and Exercise capacity), and Medical Outcomes Study Short Form-36 questionnaire score.

Conclusion: In heavy smokers with an FEV1/FVC ratio > 0.70, DISH is associated with RSP after adjustment for intrinsic and extrinsic causes of restrictive lung function. (Clinical trial registration number: NCT00608764.).
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http://dx.doi.org/10.3899/jrheum.181357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083968PMC
April 2020

Delayed presentation to a spine surgeon is the strongest predictor of poor postoperative outcome in patients surgically treated for symptomatic spinal metastases.

Spine J 2019 09 18;19(9):1540-1547. Epub 2019 Apr 18.

Department of Orthopedic Surgery, University Medical Center Utrecht, the Netherlands.

Background Context: Symptoms associated with spinal metastases are often nonspecific and resemble noncancer-related symptoms. Therefore, patients with spinal metastases are at risk for delayed referral and treatment. Delayed presentation of symptomatic spinal metastases may lead to the development of neurological deficits, often followed by emergency surgery.

Purpose: The aim of this cohort study was to analyze the effect of delayed referral and treatment of spinal metastases on clinical outcome.

Methods: We included all patients surgically treated for spinal metastases at our tertiary care center. Based on the (in)ability to undergo elective surgery, patients were identified as timely treated or delayed. Patient- and tumor-characteristics, surgical variables, and postoperative variables such as complication rate, the ability to return home and length of hospital stay were recorded and compared between the two groups.

Results: Based on the urgency of treatment at admission, 206 patients were identified as timely treated and 98 as delayed. At baseline, the two groups did not differ significantly except for the extent of neurological symptoms. Timely treated patients underwent less invasive procedures (52.9% vs 13.3% percutaneous pedicle screw fixations), had less median blood loss (200cc vs 450cc), shorter median admission time (7 vs 13 days), lower complication rate (26.2% vs 48.0%) and higher chances of being discharged home immediately (82.6% vs 41.1%) compared with delayed patients. Using multivariate regression models these correlations remained present independent of tumor prognosis, preoperative mobility, and American Society of Anesthesiologists-score.

Conclusions: The delayed presentation of patients with spinal metastases to a spinal surgeon is strongly and independently associated with worse surgical and postoperative outcome parameters. Improvements in referral patterns could potentially lead to more scheduled care, negating the detrimental effects of delay.
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http://dx.doi.org/10.1016/j.spinee.2019.04.011DOI Listing
September 2019

Local and Distant Recurrence in Resected Sacral Chordomas: A Systematic Review and Pooled Cohort Analysis.

Global Spine J 2019 Apr 30;9(2):191-201. Epub 2018 May 30.

The Johns Hopkins University, Baltimore, MD, USA.

Study Design: Systematic review.

Objectives: Sacral chordomas are rare, primary tumors of the spine, best treated with en bloc resection. The purpose of this study was to assess the literature for resected sacral chordoma and to quantify the prevalence of, risk factors for, and treatment outcomes of local and distant recurrence therein.

Methods: We searched 5 online databases from January 1980 to May 2016 to find articles that report survival, recurrence outcomes, and/or prognostic factors for the resected sacral chordoma patient population. Characteristics and clinical outcomes of the pooled cohort are reported. Fisher exact tests, unpaired tests, and one-way analysis of variance were used to investigate patient- and treatment-associated prognostic factors for local and distant recurrence. Survival analyses were performed for time to local recurrence and death. The protocol's PROSPERO ID is CRD42015024384.

Results: Fifty-seven studies, with 1235 unique sacral chordoma patients, were included in this review. Local and distant recurrence occurred in 42.6% and 22.4% of patients with adequate follow-up, respectively. Kaplan-Meier overall median survival for patients with and without recurrence were 98 and 209 months after surgery, respectively. Wide surgical margin was associated with a lower rate of local recurrence; and wide surgical margin, female sex, and patient age ≥65 years were associated with lower rates of distant recurrence.

Conclusions: While surgical margin remains the most significant prognostic factor for local and distant recurrence, combined surgical approach may be associated with local recurrence. Male sex and age <65 years may be associated with distant recurrence. Patients with risk factors for recurrence should undergo close monitoring to maximize survival.
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http://dx.doi.org/10.1177/2192568217741114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6448196PMC
April 2019

Criteria for Early-Phase Diffuse Idiopathic Skeletal Hyperostosis: Development and Validation.

Radiology 2019 05 2;291(2):420-426. Epub 2019 Apr 2.

From the Departments of Orthopedic Surgery (J.S.K., W.P.G., J.W., F.C.O., J.J.V.) and Radiology (S.F.O., W.F., F.A.M.H., P.A.d.J.), University Medical Center Utrecht, Box 85500, 3508 GA, Utrecht, the Netherlands; and Department of Radiology, National Jewish Health, Denver, Colo (E.A.R., D.A.L.).

Background Diffuse idiopathic skeletal hyperostosis (DISH) is a condition characterized by the formation of new bone along the anterolateral spinal column at four adjacent vertebral bodies. Purpose To propose and validate criteria for the early phase of DISH by using CT data from two large-scale retrospective cohorts, each with 5-year follow-up. Materials and Methods For this retrospective study, CT data at baseline and follow-up in 1367 patients (cohort I) from 2004 to 2011 were evaluated by two observers to define no DISH, early-stage DISH, and definite DISH on the basis of interval development of consecutive complete or incomplete bone bridges. An independent group of 2267 participants from the COPDGene cohort from 2008 to 2016 was used to validate the early DISH criteria (cohort II). The sensitivity and specificity of early DISH criteria were based on findings in the last CT study as the reference standard by using a nested case-control design. κ Values were calculated between seven readers and with a 3-month interval for one reader. Results Cohort I consisted of 100% men, with a mean age of 60.0 years ± 5.6 (standard deviation) and a mean time between baseline and follow-up CT of 5.0 years ± 1.1. Cohort II consisted of 51% men, with a mean age of 59.9 years ± 8.6 and a mean time between baseline and follow-up CT of 5.4 years ± 0.5. In the derivation cohort, 55 patients comprised the early DISH group. Early DISH was defined as the presence of a spinal segment with a complete bone bridge with an adjacent segment of at least a near-complete bone bridge and another adjacent segment with at least the presence of newly formed bone or when three or more adjacent segments were recorded as showing a near-complete bone bridge. In the validation cohort, sensitivity for early DISH (vs no DISH) was 96% (99 of 103 participants; 95% confidence interval [CI]: 90%, 99%). The corresponding specificity was 83% (1695 of 2034 participants; 95% CI: 82%, 85%). The Fleiss κ for interrater reliability was 0.78 (95% CI: 0.77, 0.78), and the κ for intrarater reliability was 0.89 (95% CI: 0.82, 0.96). Conclusion Early diffuse idiopathic skeletal hyperostosis (DISH) criteria had high sensitivity and specificity for predicting the development of DISH. © RSNA, 2019 See also the editorial by Block in this issue.
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http://dx.doi.org/10.1148/radiol.2019181695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6493062PMC
May 2019

Visceral Fat Volume From Standard Preoperative CT is an Independent Predictor of Short-term Survival in Patients Undergoing Surgery for Metastatic Spine Disease.

Clin Spine Surg 2019 07;32(6):E303-E310

Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD.

Study Design: This is a retrospective cohort.

Objective: Determine the relationship of body morphometry to postoperative survival in patients with vertebral metastases.

Summary Of Background Data: Most operations for vertebral metastases aim for palliation not cure, yet expected patient survival heavily influences treatment plans. We seek to demonstrate that preoperative fat and muscle volumes on standard-of-care computed tomography (CT) are independent predictors of survival after surgery for vertebral metastases.

Materials And Methods: Included data were preoperative neurological status, adjuvant treatments, CT-assessed body composition, health comorbidities, details of oncologic disease, and Tomita and Tokuhashi scores. Body composition-visceral fat area, subcutaneous fat area, and total muscle area-were assessed on preoperative L3/4 CT slice with Image J software. Multivariable logistic regressions were used to determine independent predictors of 3-, 6-, and 12-month survival.

Results: We included 75 patients (median age, 57, 57.3% male, 66.7% white) with the most common primary lesions being lung (17.3%), prostate (14.7%), colorectal (12.0%), breast (10.7%), and kidney (9.3%). The only independent predictor of 3-month survival was visceral fat area [95% confidence interval (CI): 1.02-1.23 per 1000 mm; P=0.02]. Independent predictors of survival at 6 months were body mass index (95% CI: 1.04-1.35 per kg/m; P=0.009), Karnofsky performance status (95% CI: 1.00-1.15; P<0.05), modified Charlson Comorbidity Index (95% CI: 1.11-7.91; P=0.03), and postoperative chemotherapy use (95% CI: 1.13-4.71; P=0.02). Independent predictors of 12-month survival were kidney primary pathology (95% CI: 0.00-0.00; P<0.01), body mass index (95% CI: 1.03-1.39 per kg/m; P=0.02), and being ambulatory preoperatively (95% CI: 1.28-17.06; P=0.02).

Conclusions: Visceral fat mass was an independent, positive predictor of short-term postoperative survival in patients treated for vertebral metastases. As a result, we believe that the prognostic accuracy of current predictors may be improved by the addition of visceral fat volume as a risk factor.
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http://dx.doi.org/10.1097/BSD.0000000000000784DOI Listing
July 2019

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

Front Oncol 2018 20;8:626. Epub 2018 Dec 20.

Department of Orthopedics, University Medical Center Utrecht, Utrecht, Netherlands.

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. 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. 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. 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.
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http://dx.doi.org/10.3389/fonc.2018.00626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6306560PMC
December 2018

Evaluation of effectiveness of palliative radiotherapy for bone metastases: a prospective cohort study.

J Radiat Oncol 2018 10;7(4):325-333. Epub 2018 Nov 10.

1Department of Radiation Oncology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.

Objective: Radiotherapy is the standard local treatment for patients with painful bone metastases, but effectiveness has primarily been evaluated in trial populations. The aim of this study was to study pain response to palliative radiotherapy in a prospective cohort of unselected patients with bone metastases.

Methods: Patients with painful bone metastases referred to the UMC Utrecht for radiotherapy and enrolled in the PRESENT cohort were included in this study. For all patients, pain response to radiotherapy was assessed, and responders were defined as patients with a complete or partial pain response. Patients with stable pain scores, pain increase, or undetermined response were regarded non-responders. Pain scores obtained at baseline and after 2, 4, 6, 8, and 12 weeks following radiotherapy were obtained. Pain response rates of the total treated population, as well as response rates of the assessable patients, were calculated. To measure the percentage of the remaining time spent with pain relief, the net pain relief (NPR) was calculated by dividing the period of pain relief by the period of survival.

Results: Of the 432 patients enrolled in this study, 262 patients (61%) experienced a complete or partial response. In the 390 assessable patients, this percentage was 67%. Median time to response was 4 weeks (range 1-15 weeks), and the NPR was 64%.

Conclusion: Compared to randomized trial populations, palliative radiotherapy in our unselected patients with bone metastases showed similar pain response rates (61%), with a reasonable duration of this effect.
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http://dx.doi.org/10.1007/s13566-018-0363-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6290653PMC
November 2018

A novel risk calculator to predict outcome after surgery for symptomatic spinal metastases; use of a large prospective patient database to personalise surgical management.

Eur J Cancer 2019 01 7;107:28-36. Epub 2018 Dec 7.

Department of Neurosurgery, The National Hospital for Neurology and Neurosurgery, University College London, London, UK.

Aim: Surgery for spinal metastases can improve symptoms, but sometimes complications can negate the benefits. Operations may have different indications, complexities and risks, and the choice for an individual is a tailor-made personalised decision. Previous prognostic scoring systems are becoming out of date and inaccurate. We designed a risk calculator to estimate survival after surgery, to inform clinicians and patients when making management decisions.

Methods: A prospective cohort study was performed, including 1430 patients with spinal metastases who underwent surgery. Of them, 1264 patients from 20 centres were used for model development using a Cox frailty model. Calibration slope, D-statistic and C-index were used for model validation based on 166 patients. Follow-up was to death or minimum of 2 years after surgery. Pre-operative indices (examination findings, pain, Karnofsky physical functioning score, and radiology) were assessed.

Results: An algorithm to predict survival was constructed including the tumour type, ambulatory status, analgesic use, American Society of Anesthesiologists score, number of spinal metastases, previous radiotherapy or chemotherapy, presence of visceral metastases, cervical or thoracic spine involvement, as predictors. An Internet-based risk calculator was developed based on this algorithm, with similar or improved accuracy compared to other validated prognostic scoring systems (C-index, 0.68; 95% confidence interval, 0.63--0.73, and calibration slope, 1.00; 95% confidence interval, 0.68--1.32).

Conclusion: A large, prospective, surgical series of patients with symptomatic spinal metastases was used to create a validated risk calculator that can help clinicians to inform patients about the most appropriate treatment plan. The calculator is available at www.spinemet.com.
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http://dx.doi.org/10.1016/j.ejca.2018.11.011DOI Listing
January 2019

Prediction Accuracy of Common Prognostic Scoring Systems for Metastatic Spine Disease: Results of a Prospective International Multicentre Study of 1469 Patients.

Spine (Phila Pa 1976) 2018 12;43(23):1678-1684

Department of Neurosurgery, National Hospital for Neurology and Neurosurgery, University College London, London, United Kingdom.

Study Design: A prospective multicenter cohort study.

Objective: To assess the clinical accuracy of six commonly cited prognostic scoring systems for patients with spinal metastases.

Summary Of Background Data: There are presently several available methods for the estimation of prognosis in metastatic spinal disease, but none are universally accepted by surgeons for clinical use. These scoring systems have not been rigorously tested and validated in large datasets to see if they are reliable enough to inform day-to-day patient management decisions. We tested these scoring systems in a large cohort of patients. A total of 1469 patients were recruited into a secure internet database, and prospectively collected data were analyzed to assess the accuracy of published prognostic scoring systems.

Methods: We assessed six prognostic scoring systems, described by the first authors Tomita, Tokuhashi, Bauer, van der Linden, Rades, and Bollen. Kaplan-Meier survival estimates were created for different patient subgroups as described in the original publications. Harrell's C-statistic was calculated for the survival estimates, to assess the concordance between estimated and actual survival.

Results: All the prognostic scoring systems tested were able to categorize patients into separate prognostic groups with different overall survivals. However none of the scores were able to achieve "good concordance" as assessed by Harrell's C-statistic. The score of Bollen and colleagues was found to be the most accurate, with a Harrell's C-statistic of 0.66.

Conclusion: No prognostic scoring system was found to have a good predictive value. The scores of Bollen and Tomita were the most effective with Harrell's C-statistic of 0.66 and 0.65, respectively. Prognostic scoring systems are calculated using data from previous years, and are subject to inaccuracies as treatments advance in the interim. We suggest that other methods of assessing prognosis should be explored, such as prognostic risk calculation.

Level Of Evidence: 3.
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http://dx.doi.org/10.1097/BRS.0000000000002576DOI Listing
December 2018

Simultaneous occurrence of ankylosing spondylitis and diffuse idiopathic skeletal hyperostosis: a systematic review.

Rheumatology (Oxford) 2018 12;57(12):2120-2128

Department of Orthopaedics, University Medical Center Utrecht, Utrecht, The Netherlands.

Objectives: AS and DISH are both spinal ankylosing conditions with a 4-fold increased risk of spinal fractures. The most commonly used criteria for DISH were designed to exclude radiographic signs of spondyloarthritis. However, case reports describing the presence of both conditions exist. In this study, the co-occurrence of AS and DISH were reviewed in the literature to explore the potential need to revise the criteria for DISH.

Methods: A search was conducted in Pubmed, Embase, Web of Science and the Cochrane library using the terms 'spondyloarthritis' and 'DISH' and their matching synonyms. Full-text articles describing the coexistence of both conditions in the same patient were included. A quality assessment was performed, and the case descriptions were extracted.

Results: Twenty articles describing simultaneous occurrence of AS and DISH in 39 cases were retrieved. All articles were case reports or series of moderate quality. Back or neck pain was present in 97% of the patients (mean age 61.2 years, 90% male) and HLA-B27 was positive in 9/27 documented measurements. Radiographic abnormalities were described in the SI joint (82% AS, 13% DISH) and in the spine (49% AS, 100% DISH).

Conclusion: Simultaneous occurrence of AS and DISH has been reported in the literature in at least 39 cases. AS and DISH should not be seen as mutually exclusive. If the results of the current study are confirmed in a large observational study, revision of the current criteria to include the co-existence of both conditions should be considered.
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http://dx.doi.org/10.1093/rheumatology/key211DOI Listing
December 2018