Objective: To assess whether the presence of bone marrow edema (BME) leads to the development of structural lesions at the same anatomical location of the sacroiliac joints (SIJ), and to... Show moreObjective: To assess whether the presence of bone marrow edema (BME) leads to the development of structural lesions at the same anatomical location of the sacroiliac joints (SIJ), and to investigate the association between BME patterns over time and structural lesions in patients with early axial spondyloarthritis (axSpA). Methods: Patients with axSpA from the DESIR cohort with & GE;2 consecutive magnetic resonance imaging (MRI)-SIJ were assessed at baseline, 2 and 5 years. MRI-SIJ images were divided into 8 quadrants. The association between BME and subsequent structural lesions (sclerosis, erosions, fatty lesions, and ankylosis) on MRI in the same quadrant was tested longitudinally. Additionally, patients were grouped according to the pattern of BME evo-lution across quadrants over time (no BME, sporadic, fluctuating, and persistent). The association between these patterns and 5-year imaging outcomes (eg: & GE;5 erosions and/or fatty lesions on MRI-SIJ) was tested. Results: In total, 196 patients were included. BME in each quadrant was associated with sclerosis (OR:1.9 (95%CI: 1.1;3.4)), erosions (1.9 (1.5;2.5)) and fatty lesions (1.9 (1.4;2.6)). Ankylosis was uncommon. There was a gradient between increased level of inflammation and subsequent damage: compared to the 'no BME' pattern, the sporadic (OR (95% CI): 2.1 (1.0;4.5)), fluctuating (OR:5.6(2.2;14.4)) and persistent (OR:7.5(2.8;19.6)) patterns were associated with higher structural damage on MRI-SIJ at 5-years. Conclusions: In early axSpA, inflammation on MRI-SIJ leads to damage at the quadrant level. The higher the exposure to inflammation across quadrants in the SIJs over time the higher the likelihood of subsequent struc-tural damage, suggesting a cumulative effect. Show less
Ankle and distal radius fractures are two of the most common musculoskeletal injuries. Over the last decades their incidences have risen due to increasing participation in athletic activities and... Show moreAnkle and distal radius fractures are two of the most common musculoskeletal injuries. Over the last decades their incidences have risen due to increasing participation in athletic activities and ageing of the population. Current national and international protocols recommend frequent outpatient clinic visits in which radiographs of the fractured extremity are obtained. The general aim of this thesis was to evaluate the added value of routine radiography in the follow-up of ankle and distal radius fractures. Specifically, we were interested in investigating whether a follow-up protocol which focuses on reducing the number of routine follow-up radiographs was able to deliver care that was comparable to the current standard of care, but without sacrificing quality nor safety, whilst increasing cost-effectiveness. Chapter 1 provides background information on the epidemiology of ankle and distal radius fractures. It also outlines the current standard of care during treatment and follow-up of the affected patients. In chapter 2 an overview of the current literature on routine radiography in extremity fractures is given. Despite the common occurrence of extremity fractures, limited data were available on the added value of routine radiography at the time that our systematic review was performed in 2018. We identified eleven studies; however, due to theirretrospective design and thus incumbent biases, the resultant quality or certainty of the evidence was considered low. Despite this, the treatment plan was modified in a very small percentage of the cases (ranging from 0 to 2.6%); therefore, the added value of routine radiography seems limited.Following our review in 2018, we conducted a retrospective analysis in four level 1 trauma centres in the Netherlands in order to determine the impact of routine radiographs on treatment strategy for patients with ankle fractures. Chapter 3 illustrates that, in accordance with studies outlined in chapter 2, the use of routine radiographs in the follow-up of ankle fracture patients in the Netherlands was common. In total, 80% of radiographs obtained after more than three weeks of follow-up were considered routine,and only 1.2% of these radiographs resulted in a change of treatment strategy. However, due to its retrospective design, the strength of the evidence was also considered low given its limitations.Chapters 4 and 5 report on the results of a multi-centre randomized controlled trial (RCT) in which participants with an ankle fracture were randomized between the current standard of care consisting of routine follow-up radiography (routine care) and a reduced imaging follow-up regimen. The clinical and functional outcomes outlined in chapter 4 suggest that routine radiographs at week 6 and 12 can be omitted without compromising treatment outcomes. Specifically, functional outcome measured with the Olerud and Molander Ankle Score was non-inferior in the reduced imaging group, while secondary outcomes, such as American Association of Orthopedic Surgeons (AAOS) foot and ankle scores, Health-Related Quality of Life (HRQoL), pain, health perception and self-perceived recovery did not differ between groups. The median number of radiographs obtained was 4 in the reduced imaging group and 5 in the routine care group (a reduction of 20%). Similar numbers and types of complications were observed in both groups; therefore, modifying the current standard of care can be implemented without sacrificing quality nor safety. In chapter 5 the results of the economic evaluation of the reduced-imaging follow-up strategy for ankle fracture patients are presented. Patients randomized to reduced imaging had a similar HRQoL in comparison with patients randomized to routine care. Costs for radiographic imaging were significantly lower in the reduced imaging group (a difference of €48 (95% CI: €-72 to €-28)). Other costs, including overall costs did not statistically differ between the groups. The probability of cost-effectiveness was 0.45 at a willingness-to-pay of €20,000 per QALY. Chapters 6 and 7 report on the outcomes from the same RCT, but which focused on patients with a fracture of the distal radius. Similar to the results of the RCT on anklefractures, functional outcome (measured with the Disabilities of Arm, Shoulder and Hand questionnaire [DASH]) was no worse than the reduced imaging group (chapter 6). Secondary outcomes such as HRQoL, pain and complications demonstrated similar outcomes between the groups. The number of radiographs obtained per patient decreased 25% to median 3 in the reduced imaging group from median 4 in the routine care group. The results of the economic evaluation described in chapter 7 demonstrated similarities to the results of the study on ankle fractures. HRQoL was similar, and costs for radiographic imaging were significantly lower in the reduced imaging group (this reduction was €48 per patient (95% CI: -68 to -27)). The probability of cost-effectiveness was 0.8 to 0.9 at willingness-to-pay of €20,000 to €80,000 per QALY.Following these analyses, we investigated which factors could encourage or discourage physicians to modify their practice behaviours, namely reduce their reliance on routine follow-up radiographs of extremities. These so-called “barriers and facilitators” were queried among orthopaedic trauma surgeons in the Netherlands (chapter 8). In total, 130 respondents (57%) completed the questionnaire, 71% indicated that they would stop ordering routine radiographs if they demonstrated no added value. In short, we identified three facilitators which were found to be independent predictors for the intention to de-implement routine radiographs: 1) ‘the reduced imaging follow-up protocol will lead to lower healthcare costs’; 2) ‘incorporation of the reduced imaging follow-up in regional protocols’; and 3) ‘reduced imaging will result in time-savings for the patient’. There was no barrier that was found to be an independent predictor for the intention to reduce the reliance on routine radiographs. With the three facilitators in mind, a proper de-implementation strategy can be drafted for the Netherlands, and other populations similar as ours. In chapter 9, I present general conclusions and discuss the clinical implications and future perspectives regarding the effectiveness and cost-effectiveness of routine radiography in ankle and distal radius fractures. This large multi-center study demonstrates that the number of routine radiographs in those with ankle and distal radius fractures can be reduced without sacrificing quality nor safety, while resulting in more cost-effective care Show less
Loef, M.; Stadt, L. van de; Bohringer, S.; Bay-Jensen, A.C.; Mobasheri, A.; Larkin, J.; ... ; Kloppenburg, M. 2022
Objective: To investigate the association of the lipidomic profile with osteoarthritis (OA) severity, considering the outcomes radiographic knee and hand OA, pain and function. Design: We used... Show moreObjective: To investigate the association of the lipidomic profile with osteoarthritis (OA) severity, considering the outcomes radiographic knee and hand OA, pain and function. Design: We used baseline data from the Applied Public-Private Research enabling OsteoArthritis Clinical Headway (APPROACH) cohort, comprising persons with knee OA fulfilling the clinical American College of Rheumatology classification criteria. Radiographic knee and hand OA severity was quantified with Kellgren-Lawrence sum scores. Knee and hand pain and function were assessed with validated questionnaires. We quantified fasted plasma higher order lipids and oxylipins with liquid chromatography with tandem mass spectrometry (LC-MS/MS)-based platforms. Using penalised linear regression, we assessed the variance in OA severity explained by lipidomics, with adjustment for clinical covariates (age, sex, body mass index (BMI) and lipid lowering medication), measurement batch and clinical centre. Results: In 216 participants (mean age 66 years, mean BMI 27.3 kg/m2, 75% women) we quantified 603 higher order lipids (triacylglycerols, diacylglycerols, cholesteryl esters, ceramides, free fatty acids, sphingomyelins, phospholipids) and 28 oxylipins. Lipidomics explained 3% and 2% of the variance in radiographic knee and hand OA severity, respectively. Lipids were not associated with knee pain or function. Lipidomics accounted for 12% and 6% of variance in hand pain and function, respectively. The investigated OA severity outcomes were associated with the lipidomic fraction of bound and free arachidonic acid, bound palmitoleic acid, oleic acid, linoleic acid and docosapentaenoic acid. Conclusions: Within the APPROACH cohort lipidomics explained a minor portion of the variation in OA severity, which was most evident for the outcome hand pain. Our results suggest that eicosanoids may be involved in OA severity. (c) 2022 Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International. Show less
Background: Investigation of polyethylene liner movement in total hip arthroplasty requires bead-marking for radiographic visibility of the liner. However, occlusion of markers poses a challenge... Show moreBackground: Investigation of polyethylene liner movement in total hip arthroplasty requires bead-marking for radiographic visibility of the liner. However, occlusion of markers poses a challenge for marker registration in radiographs.Methods: The polyethylene of a dual mobility acetabular system was marked with twelve 1-mm tantalum markers (four groups of three markers) using a custom-made drill guide. Liner motion in a phantom and a patient was investigated with dynamic radiostereometry analysis (dRSA) at 1-year follow-up and static radiostereometry analysis (sRSA) postoperatively and at 1- and 2-year follow-up. A combined marker configuration (CMC) model was calculated from the registered positions of the liner markers and the femoral head in several images. Furthermore, the CMC model and the theoretic marker positions from computer-assisted models of the drill guide were combined in a hybrid model.Results: The CMC model included eleven markers in the phantom and nine markers in the patient, which was sufficient for dRSA. Liner movement in the phantom followed liner contact with the femoral neck, while liner movement in the patient was independent. The hybrid model was necessary to determine liner orientation in sRSA recordings, which clearly changed from postoperative to 1- and 2-year follow-up even though the patient was positioned similarly.Conclusion: Polyethylene liner motion in dual mobility hip prosthesis can be assessed with CMC models in dRSA recordings. In sRSA, the liner position between follow-ups is unpredictable and analysis requires inclusion of all markers in the model, accomplished with a hybrid marker model. Show less
Gerven, P. van; Dongen, J.M. van; Rubinstein, S.M.; Termaat, M.F.; Moumni, M. el; Zuidema, W.P.; ... ; WARRIOR Study Grp 2020
Background: To evaluate the cost-effectiveness of a reduction in the number of routine radiographs in the follow-up of patients with ankle fractures.Methods: We performed an economic evaluation... Show moreBackground: To evaluate the cost-effectiveness of a reduction in the number of routine radiographs in the follow-up of patients with ankle fractures.Methods: We performed an economic evaluation alongside the multicentre, randomised WARRIOR trial. Participants were randomised to a reduced imaging follow-up protocol (i.e. radiographs at week 6 and 12 follow-up obtained on clinical indication) or usual care (i.e. routine radiography at weeks 6 and 12). The Olerud & Molander Ankle Score (OMAS) was used to assess ankle function and the EQ-5D-3L was used to estimate Quality-Adjusted Life Years (QALYs). Costs and resource use were assessed using self-reported questionnaires and medical records, and analysed from a societal perspective. Multiple imputation was used for missing data, and data were analysed using seemingly unrelated regression analysis and bootstrapping.Results: In total, 246 patients had data available for analysis (reduced imaging = 118; usual care = 128). Fewer radiographs were obtained in the reduced imaging group (median = 4) compared with the usual-care group (median = 5). Functional outcome was comparable in both groups. The difference in QALYs was - 0.008 (95% CI:-0.06 to 0.04) and the difference in OMAS was 0.73 (95% CI:-5.29 to 6.76). Imaging costs were lower in the reduced imaging group (-(sic)48; 95% CI:- (sic)72 to -(sic)25). All other cost categories did not statistically differ between the groups. The probability of the reduced imaging protocol being cost-effectiveness was 0.45 at a wiliness-to-pay of (sic)20,000 per QALY.Conclusions: Reducing the number of routine follow-up radiographs has a low probability of being cost-effective compared with usual care. Functional outcome, health-related quality of life and societal costs were comparable in both groups, whereas imaging costs were marginally lower in the reduced imaging group. Given this, adherence to a reduced imaging follow-up protocol for those with routine ankle fractures can be followed without sacrificing quality of care, and may result in reduced costs. Show less
Noortman, W.A.; Vriens, D.; Grootjans, W.; Tao, Q.; Geus-Oei, L.F. de; Velden, F.H. van 2020
In recent years, radiomics, defined as the extraction of large amounts of quantitative features from medical images, has gained emerging interest. Radiomics consists of the extraction of... Show moreIn recent years, radiomics, defined as the extraction of large amounts of quantitative features from medical images, has gained emerging interest. Radiomics consists of the extraction of handcrafted features combined with sophisticated statistical methods or machine learning algorithms for modelling, or deep learning algorithms that both learn features from raw data and perform modelling. These features have the potential to serve as non-invasive biomarkers for tumor characterization, prognostic stratification and response prediction. thereby contributing to precision medicine. However, especially in nuclear medicine, variable results are obtained when using radiomics for these purposes. Individual studies show promising results, but due to small numbers of patients per study and little standardization, it is difficult to compare and validate results on other datasets. This review describes the radiomic pipeline, its applications and the increasing role of artificial intelligence within the field. Furthermore, the challenges that need to be overcome to achieve clinical translation are discussed, so that, eventually, radiomics, combined with clinical data and other biomarkers, can contribute to precision medicine, by providing the right treatment to the right patient, with the right dose. at the right time. Show less
ObjectiveAneurysmal bone cysts (ABC) rarely present in soft tissue locations (STABC). The 30 cases of STABC reported in the English literature were reviewed. Six new cases retrieved from the files... Show moreObjectiveAneurysmal bone cysts (ABC) rarely present in soft tissue locations (STABC). The 30 cases of STABC reported in the English literature were reviewed. Six new cases retrieved from the files of the Netherlands Committee on Bone Tumors were compared to the six cases described in the radiological literature.Materials and methodsImaging studies and histopathology of six new STABC cases were reviewed. Follow-up was recorded with respect to local recurrence. FISH for USP6 rearrangement and/or anchored multiplex PCR-based targeted NGS using Archer FusionPlex Sarcoma Panel were attempted.ResultsOn imaging, the six STABC cases presented as a solid or multicystic intramuscular soft tissue mass, usually with thin peripheral mineralized bone shell. On MRI, perilesional edema was visualized in nearly all cases. Fluid-fluid levels were observed in one case. All lesions had the distinct histologic features of STABC. In three cases suitable for NGS, the diagnosis of STABC was confirmed by a COL1A1-USP6 fusion gene. In one additional case, USP6 gene rearrangement was detected by FISH. After marginal excision, none of the six STABC recurred after a mean follow-up period of 50months (range, 39-187months).ConclusionsOn imaging, it can be difficult to discriminate between STABC and myositis ossificans. The presence of a thin bony shell and fluid-fluid levels can be helpful in discriminating these two entities. STABC is readily diagnosed after histopathologic examination of the resection specimen. STABC belongs to the spectrum of tumors with USP6 rearrangements, which includes ABC, myositis ossificans, and nodular fasciitis. Show less
Studies in this thesis were performed in a secondary care cohort of patients with hand osteoarthritis. Several factors were investigated for their association with disease status and disease... Show moreStudies in this thesis were performed in a secondary care cohort of patients with hand osteoarthritis. Several factors were investigated for their association with disease status and disease progression after two years. These factors included comorbidity, illness perceptions and MRI-defined inflammatory features such as bone marrow lesions, synovitis and joint effusion. In the MRI studies we found that these MRI-features have a clinically relevant role for their association with pain (at the same moment and after two years) and progression of radiographic damage after two years. In the second part of this thesis we evaluated the clinimetric properties of two new instruments: self-reported painful joint count and semi-automatic joint space width measurements. Show less
Beest, S. van; Kroon, F.P.B.; Kroon, H.M.; Damman, W.; Liu, R.; Bloem, J.L.; ... ; Kloppenburg, M. 2019
Clavicular fractures are among the most common fractures of the shoulder. Displacement or comminution of the fracture fragments may lead to shortening of the clavicle, but could also cause mal... Show moreClavicular fractures are among the most common fractures of the shoulder. Displacement or comminution of the fracture fragments may lead to shortening of the clavicle, but could also cause mal-union or non-union of the clavicle and might lead to poor functional outcome. These fracture characteristics are therefore important in clinical decision making. The diagnostic aspects of clavicular fractures are evaluated in the first part of this thesis, whereas the second part describes studies on treatment and clinical outcomes. The third part of these thesis focuses on the complex biomechanics of the shoulder after a displaced midshaft clavicular fracture. The findings on diagnostic aspects underline the importance of fracture characteristics for classification and of two-view radiography for treatment decisions for clavicular fractures. Clavicular shortening after a midshaft clavicular fracture is deemed the most important factor in deciding whether or not to operate, but no clinically relevant changes after clavicular shortening in the scapular kinematics and functional outcome were demonstrated. Clavicular shortening should therefore not be used as the only reason to justify operative treatment. Show less
