POEMS syndrome is a rare paraneoplastic disorder caused by an underlying plasma cell dyscrasia, characterized by a constellation of clinical features including polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and sclerotic bone lesions. Due to its rarity and variable presentation, diagnosis is often delayed. We present a case of POEMS syndrome in which the patient was initially ineligible for autologous stem cell transplantation (ASCT) due to poor performance status. Front-line treatment with daratumumab, lenalidomide, and dexamethasone (DRd) resulted in a rapid and durable clinical and biochemical response, including normalization of vascular endothelial growth factor levels. This improvement ultimately enabled the patient to successfully undergo ASCT.This case highlights the potential role of DRd as an effective induction strategy in functionally impaired patients with POEMS syndrome.

OBJECTIVE:To identify aggressive regions in high-grade and dedifferentiated chondrosarcomas on MRI by obtaining an exact correlation between radiology and histopathology. MATERIALS AND METHODS:One chondrosarcoma grade II (CSII), chondrosarcoma grade III (CSIII) and dedifferentiated chondrosarcoma (DDCS) were segmented on (DCE-)MRI images. Around the segmentations, a patient specific mold was constructed and 3D-printed with cutting grooves perfectly aligned with selected MRI slices. In this way, resection specimens could be cut at the same locations as the MRI slices. Histopathology slides were stained with hematoxylin-eosin and CD31 (vascularization) and correlated with the (DCE-)MRI. Histopathologically, atypical cartilaginous tumor (ACT), CSII, CSIII and DDCS regions were delineated and vascular hotspots were selected by an experienced pathologist. Exact point-to-point correlation was performed. RESULTS:ACT, CSII, CSIII and DDCS regions all had similar mean signal intensity on T1-weighted images. On fat-saturated T2-weigthed images, CSII and CSIII regions had a higher mean signal intensity. On fat-saturated T1-weighted images after gadolinium contrast injection and on wash-in parametric maps DDCS regions had the highest mean signal intensity and highest wash-in values. There was a higher microvessel density in CSII and CSIII regions. This corresponded with a thick enhancing rim on fat-saturated T1-weighted images after gadolinium contrast injection and with a higher wash-in. CONCLUSION:This new 3D mold helps to identify high-grade chondrosarcoma regions with myxoid. This may be useful for targeted biopsy and histopathological investigation.

Teaching point: T2 Dixon imaging is valuable in assessing soft tissue lesions. Water-only images highlight fluid or edema, while fat-only images identify macroscopic fat and help delineate fat-devoid regions, which often indicate suspicious areas-or confirm their absence in benign lesions.

Objectives: To evaluate the value of (dynamic) contrast-enhanced MRI for the diagnosis and follow-up of central cartilage tumors (CCT) of the proximal humerus, distal femur and proximal tibia. Materials & methods: 97 patients (44 +/- 11 years, 31men) with a CCT (histopathologically proven and/or > 2 years follow-up (5 +/- 3 years)) were retrospectively/consecutively included at the Ghent University Hospital (Belgium, 2003-2021). Thickness of the enhancing rim and dynamic contrast-enhanced MRI parameters of the entire tumor were calculated. Tumor volumes were calculated to assess tumor growth. Significant differences between enchondromas, atypical cartilaginous tumors, high-grade chondrosarcomas, tumors with and without growth at follow-up were evaluated and ROC-curves were analyzed. Results: A significant difference (p = 0.015) existed in enhancing rim thickness between high-grade chondrosarcomas and other groups. A ROC-curve with an AUC of 0.89 and cut-off value of 1.2 mm had a sensitivity of 100 % and a specificity of 64 % to identify high-grade chondrosarcomas. A significant correlation was found between the relative maximal enhancement (Rel-Emax) of the whole tumor compared to muscle and the absolute growth rate (rho = 0.75, p < 0.001). Lesions with a Rel-Emax < 1 remained stable or showed regression during follow-up (mean-0.1 +/- 0.3 ml/year). Lesions with a Rel-Emax between 1 and 2 showed little growth (mean + 0.2 +/- 0.2 ml/year), and lesions with a Rel-Emax > 2 had the highest growth rate (mean 0.4 +/- 0.2 ml/year). Conclusion: A thick enhancing rim > 1.2 mm has a high sensitivity to detect high-grade chondrosarcomas. The higher the Rel-Emax of the whole tumor compared to muscle, the higher the growth rate of a CCT.

Objective This randomized controlled trial (RCT) investigated whether adding daily use of flat flexible footwear (FFF) to a strengthening and aerobic exercise program improved short- and longer-term outcomes compared with adding stable supportive shoes (SSS) in people with medial tibiofemoral OA.Methods Participants (n = 97) with medial tibiofemoral OA were randomly assigned (1:1) to the FFF (n = 50) or SSS (n = 47) group. Participants in both groups received a 9-month intervention (3 months supervised followed by 6 months unsupervised exercise). The primary outcome was the change in knee pain on walking at 3 months measured using an 11-point numeric rating scale (NRS). Secondary outcomes included the change from baseline to 3 and 9 months in the severity of knee pain overall (NRS), physical function (WOMAC subscale), habitual physical activity level (Physical Activity Scale for the Elderly), quality of life (QoL) (European Quality of Life 5-Dimensions 5-Levels questionnaire) and markers of inflammation (effusion and Hoffa synovitis) and structural disease progression (bone marrow lesions).Results There were no significant differences between the groups in the change in pain on walking [between-group difference -0.67 (95% CI -1.62, 0.29)] at 3 months. Knee pain on walking and overall knee pain significantly decreased in both groups at 3 and 9 months. Physical function and QoL improved in both groups at 3 and 9 months. We found no between-group differences in any secondary outcome at any time.Conclusions FFF added to exercise therapy did not provide additional better symptom nor structure-modification benefit compared with conventional SSS and exercise in people with medial tibiofemoral OA.Trial registration ClinicalTrials.gov (http://clinicaltrials.gov), NCT03796832. What does this mean for patients?This study aimed to see if wearing flexible flat footwear (FFF) alongside a 9-month exercise program could provide more pain relief and functional improvement for people with knee osteoarthritis (OA) than wearing stable supportive shoes (SSS) with the same exercise program. We randomly assigned 97 participants with (medial tibiofemoral) knee OA into two groups: one wore FFF and the other wore SSS, with both groups doing exercises (strength and endurance) for 3 months supervised by physiotherapists followed by exercising 6 months at home. After 3 months, the main outcome was knee pain during walking, rated on a scale of 0 to 10. Both groups showed similar improvements in pain and overall knee function, and these improvements continued after 9 months. There was no significant difference between the FFF and SSS groups for knee pain, physical functioning, quality of life and physical activity. In summary, exercise benefits knee pain during walking in people with knee OA. Adding FFF to this program did not provide extra benefits over wearing SSS.

To determine the value of CT and dynamic contrast-enhanced (DCE-)MRI for monitoring denosumab therapy of giant cell tumors of bone (GCTB) by correlating it to histopathology. Patients with GCTB under denosumab treatment and monitored with CT and (DCE-)MRI (2012-2021) were retrospectively included. Imaging and (semi-)quantitative measurements were used to assess response/relapse. Tissue samples were analyzed using computerized segmentation for vascularization and number of neoplastic and giant cells. Pearson’s correlation/Spearman’s rank coefficient and Kruskal-Wallis tests were used to assess correlations between histopathology and radiology. Six patients (28 ± 8years; five men) were evaluated. On CT, good responders showed progressive re-ossification (+7.8HU/month) and cortical remodeling (woven bone). MRI showed an SI decrease relative to muscle on T1-weighted (−0.01 A.U./month) and on fat-saturated T2-weighted sequences (−0.03 A.U./month). Time-intensity-curves evolved from a type IV with high first pass, high amplitude, and steep wash-out to a slow type II. An increase in time-to-peak (+100

This study aimed to externally validate the Birmingham Atypical Cartilage Tumour Imaging Protocol (BACTIP) recommendations for differentiation/follow-up of central cartilage tumours (CCTs) of the proximal humerus, distal femur, and proximal tibia and to propose BACTIP adaptations if the results provide new insights. MRIs of 123 patients (45 ± 11 years, 37 men) with an untreated CCT with MRI follow-up (n = 62) or histopathological confirmation (n = 61) were retrospectively/consecutively included and categorised following the BACTIP (2003–2020 / Ghent University Hospital/Belgium). Tumour length and endosteal scalloping differences between enchondroma, atypical cartilaginous tumour (ACT), and high-grade chondrosarcoma (CS II/III/dedifferentiated) were evaluated. ROC-curve analysis for differentiating benign from malignant CCTs and for evaluating the BACTIP was performed. For lesion length and endosteal scalloping, ROC-AUCs were poor and fair-excellent, respectively, for differentiating different CCT groups (0.59–0.69 versus 0.73–0.91). The diagnostic performance of endosteal scalloping and the BACTIP was higher than that of lesion length. A 1° endosteal scalloping cut-off differentiated enchondroma from ACT + high-grade chondrosarcoma with a sensitivity of 90

Importance Ligamentous ankle lesions are among the most frequent sport injuries. One of the key intrinsic stabilizers of the ankle joint is the incisura fibularis (IF), as it interlocks the distal tibia and fibula. Despite an abundant amount of studies related to ligamentous ankle injuries, scant attention has been given to the specific role of the IF morphology. Objective We systematically reviewed all literature focused on the relation between ligamentous ankle lesions and IF morphology. Evidence Review A systematic literature search was conducted on PubMed, Embase and Web of Science according to the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) guidelines and registered on the International prospective register of systematic reviews (PROSPERO) database (CRD42021282862). In general, search terms were related to ankle and syndesmosis trauma/instability in combination with morphology parameters of the incisura fibularis. Studies categorizable as original research (randomized controlled trial or observational) were included. Studies concerning degenerative ankle disease and cadavers were excluded. Findings Thirteen studies were confirmed eligible and consisted of a prospective cohort (n=1), retrospective comparative (n=10), and observational (n=2) study design. Several studies have found an increased number of ankle ligament injuries and a higher incidence of chronic ankle instability in association with a shallow IF depth. In addition, statistically significant differences in incisura height and angle were also noted: a shorter incisura and more obtuse angle were more present in patients with ankle ligament injuries. Conclusion and Relevance The majority of studies found distinct characteristics of the IF morphology associated with ligamentous ankle lesions, potentially due to lower osseous resistance against tibiofibular displacement. However, not all studies could identify this association and presented a heterogeneous methodological quality. Therefore, further prospective studies are warranted to clarify the relation between the IF morphology and ligamentous ankle injuries. Lever of evidence Level III, systematic review.

BACKGROUND:A subgroup of patients with knee osteoarthritis (OA) reports symptoms attributable to a neuropathic cause. Little to no attention has been invested on investigating differences in knee loading and inflammation in these patients.AIM:To explore differences in inflammation and knee loading in patients with knee OA categorized based on the presence of neuropathic-like pain.DESIGN:Cross-sectional study.SETTING:Ghent University Hospital, Ghent, Belgium.POPULATION:Knee OA patients.METHODS:cross-sectional analysis of data from 96 patients (mean age 64.18±7.11 years) with primary knee OA participating in a randomized controlled trial. Participants were divided into three groups (unlikely, possible and indication of neuropathic-like pain) according to the modified painDETECT questionnaire (mPDQ). Data on demographics, symptoms and physical function were obtained by questionnaires. Effusion/synovitis and bone marrow lesions (BMLs) were measured using magnetic resonance imaging. Knee loading variables (knee adduction moment [KAM], KAM impulse, and knee flexion moment [KFM]) were assessed by 3D-motion analysis. One-way analysis of covariance (ANCOVA), Chi-square test and curve analyses were used to analyze continuous, categorical and loading variables respectively. Multinomial logistic regression was used to identify predictors for neuropathic-like pain.RESULTS:Patients with indication of neuropathic-like pain exhibited higher KAM impulse compared to those with no indication of neuropathic-like pain (standard mean difference (SMD): -0.036 Nm normalized to body weight and height per second, 95% CI: -0.071, -0.001) along with greater pain intensity (SMD: 3.87 units, 95% CI: 1.90, 5.84), stiffness (SMD: 1.34 units, 95% CI: 0.19, 2.48) and worse physical function (SMD: 13.98 units 95% CI: 7.52, 20.44). Curve analysis showed no significant differences in KFM and KAM between groups. Effusion/synovitis and BMLs did not differ significantly between groups. The best predictors for indication of neuropathic-like pain were KAM impulse, Hoffa and sex.CONCLUSIONS:Knee OA patients with indication of neuropathic-like pain exhibited higher dynamic medial loading, greater pain severity and worse physical function, while inflammatory markers were not significantly different across mPDQ groups. Future longitudinal studies are warranted to strengthen the evidence and establish mechanisms to explain associations between neuropathic-like pain and knee loading.CLINICAL REHABILITATION IMPACT:Knee loading is a modifiable factor and patients with neuropathic-like pain may benefit from offloading interventions.

OBJECTIVE:To identify which dynamic contrast-enhanced (DCE-)MRI features best predict histological response to neoadjuvant chemotherapy in patients with an osteosarcoma.METHODS:Patients with osteosarcoma who underwent DCE-MRI before and after neoadjuvant chemotherapy prior to resection were retrospectively included at two different centers. Data from the center with the larger cohort (training cohort) was used to identify which method for region-of-interest selection (whole slab or focal area method) and which change in DCE-MRI features (time to enhancement, wash-in rate, maximum relative enhancement and area under the curve) gave the most accurate prediction of histological response. Models were created using logistic regression and cross-validated. The most accurate model was then externally validated using data from the other center (test cohort).RESULTS:Fifty-five (27 poor response) and 30 (19 poor response) patients were included in training and test cohorts, respectively. Intraclass correlation coefficient of relative DCE-MRI features ranged 0.81-0.97 with the whole slab and 0.57-0.85 with the focal area segmentation method. Poor histological response was best predicted with the whole slab segmentation method using a single feature threshold, relative wash-in rate <2.3. Mean accuracy was 0.85 (95%CI: 0.75-0.95), and area under the receiver operating characteristic curve (AUC-index) was 0.93 (95%CI: 0.86-1.00). In external validation, accuracy and AUC-index were 0.80 and 0.80.CONCLUSION:In this study, a relative wash-in rate of <2.3 determined with the whole slab segmentation method predicted histological response to neoadjuvant chemotherapy in osteosarcoma. Consistent performance was observed in an external test cohort.

Purpose or Learning Objective: To evaluate the feasibility and diagnostic accuracy of deep learning for automated detection of structural lesions of sacroiliitis on multicenter pelvic computed tomography (CT).

The incisura fibularis (IF) provides intrinsic stability to the ankle joint complex by interlocking the distal tibia and fibula. Despite a high frequency of ligamentous ankle injuries, scant attention has been given to the morphology of the IF morphology incisura fibularis in the onset and development of these lesions. Therefore, we systematically reviewed the relation between ligamentous ankle disorders and the morphometrics of the IF. A systematic literature search was conducted on following databases: PubMed, Embase and Web of Science. Search terms consisted of ‘ankle trauma’, ‘ankle injury’, ‘ankle sprain’, ‘ankle fracture’, ‘tibiofibular’, ‘fibular notch’, ‘fibular incisura’, ‘incisura fibularis’, ‘morphometric analysis’, ‘ankle syndesmosis’, ‘syndesmotic stability’. The evaluation instrument developed by Hawker et al. was used to assess the quality of the selected studies. This protocol was performed according to the PRISMA guidelines and is registered on PROSPERO (CRD42021282862). Nineteen studies were included and consisted of prospective cohort (n=1), retrospective comparative (n=10), and observational (n=8) study design. Comparative studies have found certain morphological characteristics in patients with ankle instability. Several studies (n=5) have correlated a shallow IF depth with a higher incidence of ankle injury. A significant difference has also been found concerning the incisura height and angle (n=3): a shorter incisura and more obtuse angle have been noted in patients with ankle sprains. The mean Hawker score was 28 out of 36 (range=24-31). A shallower IF is associated with ligamentous ankle lesions and might be due to a lower osseous resistance against tibiofibular displacement. However, these results should be interpreted in light of moderate methodological quality and should always be correlated with clinical findings. Further prospective studies are needed to further assess the relation between the incisura morphometrics and ligamentous disorders of the ankle joint. Keywords: ankle instability, ankle injury, incisura fibularis, fibular notch, tibiofibular morphometrics, ankle syndesmosis

Teaching point: Cortical metastasis has to be considered in older patients with a cortical osteolytic lesion.

To evaluate the feasibility and diagnostic accuracy of a deep learning network for detection of structural lesions of sacroiliitis on multicentre pelvic CT scans. Pelvic CT scans of 145 patients (81 female, 121 Ghent University/24 Alberta University, 18–87 years old, mean 40 ± 13 years, 2005–2021) with a clinical suspicion of sacroiliitis were retrospectively included. After manual sacroiliac joint (SIJ) segmentation and structural lesion annotation, a U-Net for SIJ segmentation and two separate convolutional neural networks (CNN) for erosion and ankylosis detection were trained. In-training validation and tenfold validation testing (U-Net—n = 10 × 58; CNN—n = 10 × 29) on a test dataset were performed to assess performance on a slice-by-slice and patient level (dice coefficient/accuracy/sensitivity/specificity/positive and negative predictive value/ROC AUC). Patient-level optimisation was applied to increase the performance regarding predefined statistical metrics. Gradient-weighted class activation mapping (Grad-CAM++) heatmap explainability analysis highlighted image parts with statistically important regions for algorithmic decisions. Regarding SIJ segmentation, a dice coefficient of 0.75 was obtained in the test dataset. For slice-by-slice structural lesion detection, a sensitivity/specificity/ROC AUC of 95 • Structural lesions of sacroiliitis can be detected automatically in pelvic CT scans. • Both automatic segmentation and disease detection yield excellent statistical outcome metrics. • The algorithm takes decisions based on cortical edges, rendering an explainable solution.

Purpose or Learning Objective: (1) To determine the value of computed tomography (CT) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for monitoring denosumab therapy of giant cell tumors of bone (GCTB) by correlating imaging with pathology; and (2) to optimize denosumab therapy dosage, duration, and interval.

Purpose or Learning Objective: Our aim was (1) to evaluate the value of computed tomography (CT) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for monitoring denosumab therapy of giant cell tumor of bone (GCTB); (2) to describe imaging findings at diagnosis and during treatment; and (3) to offer an overview of good and poor response, relapse, and therapeutic complications.

Diagnosing complicating osteomyelitis (COM) is clinically challenging. Laboratory tests are of limited utility, and other than isolation of the offending organism, diagnostic imaging tests are of paramount importance. Nuclear Medicine techniques play an important role in noninvasive evaluation of osteomyelitis, using both single-photon emission tomography (SPECT) and positron emission tomography (PET) radiopharmaceuticals. It is well-known that those conventional imaging modalities are not performing well in the distinction between soft-tissue and deep bone infection due to the lack of anatomical information. These difficulties have been overcome, to a great extent, with the introduction of in-line SPECT-CT and PET-CT systems which have revolutionized the field of diagnostic medical imaging. Hybrid imaging is especially useful in sites of suspected COM with underlying structural bone alterations. The first clinical studies with these integrated hybrid machines in the field of COM, including metallic implants imaging, are highly promising. In summary, WBC/AGA SPECT-CT and FDG-PET-CT seem to be the most accurate hybrid imaging modality for COM of the peripheral bone. However, there are still false positives, especially in aseptic tibial nonunions and/or metallic implants, as well as in the immediate postoperative setting. Furthermore, there is a lack of well-designed large multicentre prospective studies. Hopefully, in the future, the complementary use of morphological and functional hybrid imaging modalities may overcome some of the challenges faced in the assessment of COM.