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Objectives: To compare inflammatory and structural differences in active Psoriatic Arthritis (PsA) between disease-modifying antirheumatic drug (DMARD)-naive and DMARD-failure patients using diverse imaging approaches for future analyses. Additionally, to explore the influence of patient characteristics (clinical and demographic variables) on imaging findings., Methods: Of the 80 patients included from the first cohort of the ongoing multicentre TOFA-PREDICT trial, 40 were DMARD-naive and 40 were DMARD-failure (csDMARD failure; 1 prior bDMARD excluding etanercept was allowed), all meeting classification criteria for PsA with a minimum disease duration of eight weeks. Baseline conventional radiographs of hands and feet, MRIs of both ankles, and whole-body 18F-FDG PET/CT were evaluated for inflammatory and structural imaging parameters, including Sharp-van der Heijde (SHS), Heel Enthesitis Magnetic Resonance Imaging Scoring System (HEMRIS) and Deauville synovitis scoring. Differences between groups and the influence of patient characteristics were examined with multiple linear regression., Results: At baseline, patient characteristics were similar between groups. Imaging parameters showed limited inflammation and structural damage. Inflammatory imaging parameters were not significantly different (p> 0.200). Among structural parameters, only HEMRIS Achilles tendon structural damage was significantly different (p= 0.024, R2=0.071) and, SHS Joint Space Narrowing was not statistically significant (p= 0.050, R2=0.048) with higher values for both in DMARD-failures. After correction of patient characteristics, these differences in imaging disappeared (both p> 0.600)., Conclusion: At baseline, PsA patient groups were comparable concerning structural and inflammatory imaging parameters, especially after correcting for patient characteristics. Thus, DMARD-naive and DMARD-failure patient groups may be combined in future PsA progression and treatment decision studies., Clinical Trial Registration Number: EudraCT: 2017-003900-28., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Introduction: Visualization of scoliosis typically requires ionizing radiation (radiography and CT) to visualize bony anatomy. MRI is often additionally performed to screen for neural axis abnormalities. We propose a 14-minutes radiation-free scoliosis-specific MRI protocol, which combines MRI and MRI-based synthetic CT images to visualize soft and osseous structures in one examination. We assess the ability of the protocol to visualize landmarks needed to detect 3D patho-anatomical changes, screen for neural axis abnormalities, and perform surgical planning and navigation., Methods: 18 adult volunteers were scanned on 1.5 T MR-scanner using 3D T2-weighted and synthetic CT sequences. A predefined checklist of relevant landmarks was used for the parameter assessment by three readers. Parameters included Cobb angles, rotation, torsion, segmental height, area and centroids of Nucleus Pulposus and Intervertebral Disc. Precision, reliability and agreement between the readers measurements were evaluated., Results: 91 % of Likert-based questions scored ≥ 4, indicating moderate to high confidence. Precision of 3D dot positioning was 1.0 mm. Precision of angle measurement was 0.6° (ICC 0.98). Precision of vertebral and IVD height measurements was 0.4 mm (ICC 0.99). Precision of area measurement for NP was 8 mm 2 (ICC 0.55) and for IVD 18 mm 2 (ICC 0.62) for IVD. Precision of centroid measurement for NP was 1.3 mm (ICC 0.88-0.92) and for IVD 1.1 mm (ICC 0.88-91)., Conclusions: The proposed MRI protocol with synthetic CT reconstructions, has high precision, reliability and agreement between the readers for multiple scoliosis-specific measurements. It can be used to study scoliosis etiopathogenesis and to assess 3D spinal morphology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: To assess the diagnostic contribution of different imaging studies to diagnose necrotizing soft tissue infections (NSTIs) and the time to surgery in relation to imaging with the hypothesis that imaging studies may lead to significant delays without being able to sufficiently dismiss or confirm the diagnosis since a NSTI is a surgical diagnosis., Methods: A retrospective multicenter cohort study of all NSTI patients between 2010 and 2020 was conducted. The primary outcome was the number of cases in which imaging contributed to or led to change in treatment. The secondary outcomes were time to treatment determined by the time from presentation to surgery and patient outcomes (amputation, intensive care unit (ICU) admission, length of ICU stay, hospital stay, and mortality)., Results: A total of 181 eligible NSTI patients were included. The overall mortality was 21% (n = 38). Ninety-eight patients (53%) received imaging in the diagnostic workup. In patients with a clinical suspicion of a NSTI, 81% (n = 85) went directly to the operating room and 19% (n = 20) underwent imaging before surgery; imaging was contributing in only 15% (n = 3) by ruling out or determining underlying causes. In patients without a clinical suspicion of a NSTI, the diagnosis of NSTI was considered in 35% and only after imaging was obtained., Conclusion: In patients with clinically evident NSTIs, there is no role for standard imaging workup unless it is used to examine underlying diseases (e.g., diverticulitis, pancreatitis). In atypical presenting NSTIs, CT or MRI scans provided the most useful information. To prevent unnecessary imaging and radiation and not delay treatment, the decision to perform imaging studies in patients with a clinical suspicion of a NSTI must be made extremely careful., (© 2024. The Author(s).)

Objectives: Ectopic bone deposition plays an important role in osteoarthritis (OA) and in arterial wall disease. We aimed to investigate the prevalence and progression of arterial calcifications on whole-body computed tomography (CT) in persons with knee OA., Methods: We included 118 (36 male) participants who satisfied the clinical American College of Rheumatology classification criteria for knee OA. Baseline investigations included Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Kellgren-Lawrence grading. At baseline and after two years, a whole-body CT was performed using the same scanner and protocol. Calcifications were quantified in the carotid, brachiocephalic, coronary, thoracic aortic, abdominal aortic, iliac, femoropopliteal and crural arteries. Multivariable linear and logistic regression modeling was used for analyses., Results: At baseline males were 66.9 ± 7.7 and females were 68.0 ± 5.6 years old. Calcifications were common, all participants except two females had some calcification, and prevalence ranged between 41.8% and 94.4% for various arterial beds. Baseline femoropopliteal calcifications were associated with a higher Kellgren-Lawrence grade (more severe knee OA). Median annual progression rate was 13.1% in males and 15.7% in females. Structural OA severity was not associated with progression, but a five points lower (worse) WOMAC was associated with 1% faster progression of arterial calcifications (p= 0.008)., Conclusion: Around age 70 nearly all persons with knee OA have arterial calcifications, which progress substantially. For further investigation into shared causality intervention studies are needed., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: T2-relaxometry could differentiate between physiological and haemorrhagic joint effusion (≥ 5% blood) in vitro. Are quantitative T2-relaxation time measurements of synovial fluid feasible and reproducible in vivo in clinically bleed-free joints of men with haemophilia?, Materials and Methods: In this cross-sectional study, we measured T2-relaxation times of synovial fluid in clinically bleed-free ankles, knees or elbows of men with severe haemophilia A using a T2-mapping sequence (duration ≤ 7 min) at 3 Tesla MRI. Manual and circular regions of interest (ROI) were drawn in the synovial fluid of each joint by two independent observers to measure T2-relaxation times. Measurement feasibility was expressed as the success rate of the measurements by both observers. The interobserver and intraobserver reproducibility of the measurements were evaluated by the intraclass correlation coefficient of absolute agreement (ICC) and the limits of agreement (LoA) from Bland Altman analysis., Results: We evaluated 39 clinically bleed-free joints (11 ankles, 12 knees, 16 elbows) of 39 men (median age, 24 years; range 17-33) with severe haemophilia A. The success rate of the T2-measurements was ≥ 90%. Interobserver reliability was good to excellent (manual ROI: ICC = 0.92, 95% CI 0.76-0.97; circular ROI: ICC = 0.82, 95% CI 0.66-0.91) and interobserver agreement was adequate (manual ROI: LoA = 71 ms; circular ROI: LoA = 146 ms). Intraobserver reliability was good to excellent (manual ROI: ICC = 0.78, 95% CI - 0.06-0.94; circular RO: ICC = 0.99, 95% CI 0.98-0.99) and intraobserver agreement was good (manual ROI: LoA = 63 ms; circular ROI: LoA = 41 ms)., Conclusion: T2-relaxometry of synovial fluid in haemophilia patients is feasible with good interobserver and intraobserver reproducibility., (© 2024. The Author(s).)

Background: Arthropathy following repeated bleeding is common in persons with hemophilia. Since the introduction of prophylaxis, treatment has intensified and joint health has improved. However, data on the long-term development of arthropathy are still scant., Objectives: To evaluate long-term arthropathy development since the introduction of prophylaxis according to birth cohort, hemophilia severity, and inhibitor status., Methods: This single-center historic cohort study included persons with severe and moderate hemophilia A and hemophilia B born between 1935 and 2005. Arthropathy on X-rays was evaluated using the Pettersson score. Patient and joint characteristics were studied per birth cohort (<1970, 1970-1980, 1981-1990, and >1990) and compared according to hemophilia severity. The distribution of affected joints and cumulative incidence of arthropathy were analyzed. The association of Pettersson score with birth cohort and inhibitor characteristics was explored using multivariable regression analyses adjusted for age at evaluation., Results: In total, 1064 X-rays of 363 patients were analyzed. Of persons with severe hemophilia ( n  = 317, 87.3%), 244 (77.0%) developed arthropathy. Prophylaxis was started at younger ages over time, from a median of 18 to 2.1 years, and concomitantly, arthropathy decreased in consecutive birth cohorts. Ankles were most commonly affected in 188 of 258 (72.9%) patients. Persons with moderate hemophilia ( n  = 46, 12.7%) had a lower risk of arthropathy (27/46 [58.7%]), but a reduction over time was less pronounced. In the multivariable analyses, birth cohort and age at evaluation were predictors for the development of arthropathy, while inhibitor status showed no association., Conclusion: The development and severity of arthropathy have decreased over the past decades. However, patients have remained at risk for developing arthropathy, especially in their ankles., (© 2024 The Authors.)

Background: Patients with psoriatic arthritis (PsA) have an increased risk of cardiovascular disease, possibly due to a chronic inflammatory state., Objectives: The main objective of this study was to investigate the difference in vascular inflammation, measured with 18-fluorodeoxyglucose positron emission tomography/CT (PET/CT), in PsA patients and controls. We conducted a secondary analysis to assess the association between clinical parameters of disease activity with vascular inflammation in PsA., Methods: We included a total of 75 PsA patients with active peripheral arthritis (defined as ≥2 tender and swollen joints) from an ongoing clinical trial (EudraCT 2017-003900-28) and a retrospective group of 40 controls diagnosed with melanoma, without distant metastases and not receiving immunotherapy. The main outcome measure was aortic vascular inflammation which was measured on PET/CT scans using target-to-background ratios. Clinical disease activity in PsA was assessed with joint counts, body surface area and the Disease Activity index for PsA. Laboratory assessments included C reactive protein and erythrocyte sedimentation rate., Results: Vascular inflammation was increased in patients with PsA in comparison with controls (mean target-to-background ratio for entire aorta, respectively, 1.63±0.17 vs 1.49±0.16; p=<0.001). This association remained significant after correction for gender, age, body mass index, mean arterial pressure and aortic calcification (p=0.002). Vascular inflammation was not associated with disease-related parameters., Conclusions: Aortic vascular inflammation was significantly increased in patients with active PsA compared with controls. This evidence supports the theory that inflammation in PsA is not limited to the skin and joints but also involves the vascular system., Competing Interests: Competing interests: KPMS: consulting/advisory relationship: Bristol-Myers Squibb, Merck Sharp and Dome, Abbvie, Pierre Fabre, Novartis, Sairopa. Honoraria received: Novartis, Roche, Merck Sharp and Dome. Research funding: TigaTx, Bristol Myers Squibb, Philips. All paid to the institution and outside the submitted work. PAdJ has a research collaboration with Vifor Pharma and Philips Healthcare. WF received research grants unrelated to the topic of the present study from Novo Nordisk and Pfizer, which were paid to the institution. HEV reports having received grants, consulting fees or honorarium from AbbVie, Boehringer Ingelheim, Novartis, Pfizer, UCB, Janssen and Galapagos; all outside the submitted work., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The treatment landscape for haemophilia is changing rapidly, creating opportunities for personalized treatment. As major morbidity is still caused by haemophilic arthropathy, understanding the factors affecting joint damage and joint damage progression might lead to more individualized treatment regimens. We investigated the association of HFE mutations or HMOX1 polymorphisms affecting iron/heme handling with radiographic joint damage in 252 haemophilia patients (severe and moderate). Although iron levels and transferrin saturation were significantly increased in the 95 patients with an HFE mutation, neither carrying this mutation nor the HMOX1 polymorphism was associated with radiographic joint damage, and the same was true after adjustment for well-known factors associated with arthropathy. In conclusion, this study does not support the hypothesis that HFE mutations or HMOX1 polymorphisms can be used to predict the development of haemophilic arthropathy.

Background: Subjects with ankylosing spinal disorders, including diffuse idiopathic skeletal hyperostosis (DISH) and ankylosing spondylitis (AS) are more prone to vertebral fractures and frequently present with neurological deficit compared to the patients without an ankylosed spine. Moreover, prevalent vertebral fractures are an important predictor for subsequent fracture risk. However, the pooled fracture prevalence for DISH is unknown and less recent for AS. We aimed to systematically investigate the prevalence and risk of vertebral fractures in DISH and AS populations., Methods: Publications in Medline and EMBASE were searched from January 1980 until July 2023 for cohort studies reporting vertebral fractures in AS and DISH. Data on prevalence were pooled with random effects modeling after double arcsine transformation. Heterogeneity was assessed with I 2 statistics and we performed subgroup analysis and meta-regression to explore sources of heterogeneity., Results: We included 7 studies on DISH (n = 1,193, total fractures = 231) with a pooled vertebral fracture prevalence of 22.6% (95%CI: 13.4%-33.4%). For AS, 26 studies were included (n = 2,875, total fractures = 460) with a pooled vertebral fracture prevalence of 15.2% (95%CI: 11.6%-19.1%). In general, fracture prevalence for AS remained similar for several study-level and clinically relevant characteristics, including study design, diagnostic criteria, spine level, and patient characteristics in subgroup analysis. AS publications from 2010 to 2020 showed higher fracture prevalence compared to 1990 to 2010 (18.6% vs. 11.6%). Fractures in DISH were most common at the thoracolumbar junction, whereas for AS, the most common location was the mid-thoracic spine., Conclusions: Vertebral fractures are prevalent in AS and DISH populations. Differences in fracture distribution along the spinal axis exist between the 2 disorders. Additional longitudinal studies are needed for incident fracture assessment in patients with ankylosing spinal disorders., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Background: Lumbar interbody fusion (IF) is a common procedure to fuse the anterior spine. However, a lack of consensus on image-based fusion assessment limits the validity and comparison of IF studies. This systematic review aims to (1) report on IF assessment strategies and definitions and (2) summarize available literature on the diagnostic reliability and accuracy of these assessments., Methods: Two searches were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Search 1 identified studies on adult lumbar IF that provided a detailed description of image-based fusion assessment. Search 2 analyzed studies on the reliability of specific fusion criteria/classifications and the accuracy assessed with surgical exploration., Results: A total of 442 studies were included for search 1 and 8 studies for search 2. Fusion assessment throughout the literature was highly variable. Eighteen definitions and more than 250 unique fusion assessment methods were identified. The criteria that showed most consistent use were continuity of bony bridging, radiolucency around the cage, and angular motion <5°. However, reliability and accuracy studies were scarce., Conclusion: This review highlights the challenges in reaching consensus on IF assessment. The variability in IF assessment is very high, which limits the translatability of studies. Accuracy studies are needed to guide innovations of assessment. Future IF assessment strategies should focus on the standardization of computed tomography-based continuity of bony bridging. Knowledge from preclinical and imaging studies can add valuable information to this ongoing discussion., Level of Evidence: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSREV/B53)., (Copyright © 2024 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated. All rights reserved.)

Background: Pseudoxanthoma elasticum (PXE) is an autosomal recessive disease characterized by diminished inorganic plasma pyrophosphate (PPi), a strong calcification inhibitor. In addition to more typical calcification of skin, retina and arterial wall a diminished plasma PPi could lead to other ectopic calcification, such as formation of kidney stones., Objective: To compare the prevalence of kidney stones between PXE patients and hospital controls on computed tomography (CT)., Method: Low-dose CT images of PXE patients and controls were assessed by one radiologist, who was blinded for the diagnosis PXE. The number of kidney stones, and the size of the largest stone was recorded. Odds ratios (ORs) for having kidney stone were calculated using multivariable adjusted logistic regression., Results: Our study comprised 273 PXE patients and 125 controls. The mean age of PXE patients was 51.5 ± 15.9 years compared to 54.9 ± 14.2 in the control group (p = 0.04) and PXE patients more often were women (63 vs. 50%, p = 0.013). The prevalence of kidney stones on CT was similar: 6.9% in PXE patients, compared to 5.6% in controls (p = 0.6). In the multivariate analysis adjusting for age and sex, there was no significantly higher odds for PXE patients on having stones, compared to controls: OR 1.48 (95% CI 0.62-3.96)., Conclusion: There is no significant difference in the prevalence of incidental kidney stones on CT in PXE patients versus controls., (© 2023. The Author(s).)

Magnetic resonance Imaging is the gold standard for assessment of soft tissues; however, X-ray-based techniques are required for evaluating bone-related pathologies. This study evaluated the performance of synthetic computed tomography (sCT), a novel MRI-based bone visualization technique, compared with CT, for the scoring of knee osteoarthritis. sCT images were generated from the 3T T1-weighted gradient-echo MR images using a trained machine learning algorithm. Two readers scored the severity of osteoarthritis in tibiofemoral and patellofemoral joints according to OACT, which enables the evaluation of osteoarthritis, from its characteristics of joint space narrowing, osteophytes, cysts and sclerosis in CT (and sCT) images. Cohen's κ was used to assess the interreader agreement for each modality, and intermodality agreement of CT- and sCT-based scores for each reader. We also compared the confidence level of readers for grading CT and sCT images using confidence scores collected during grading. Inter-reader agreement for tibiofemoral and patellofemoral joints were almost-perfect for both modalities (κ = 0.83-0.88). The intermodality agreement of osteoarthritis scores between CT and sCT was substantial to almost-perfect for tibiofemoral (κ = 0.63 and 0.84 for the two readers) and patellofemoral joints (κ = 0.78 and 0.81 for the two readers). The analysis of diagnosis confidence scores showed comparable visual quality of the two modalities, where both are showing acceptable confidence levels for scoring OA. In conclusion, in this single-center study, sCT and CT were comparable for the scoring of knee OA., (© 2023 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

Aim: Subclinical bleeding and inflammation play a role in progression of haemophilic arthropathy. Synovial proliferation is predictive of joint bleeding and its early detection may guide treatment changes and prevent arthropathy progression. This study evaluated the prevalence of active and inactive subclinical synovial proliferation and investigated potential biochemical blood/urine markers to identify patients with active subclinical synovial proliferation., Methods: This cross-sectional study included patients with severe haemophilia A born 1970-2006 who were evaluated during routine clinic visits. Patients with (a history of) inhibitors or recent joint bleeding were excluded. Elbows, knees and ankles were examined for subclinical synovial proliferation by ultrasound and physical examination. Active synovial proliferation was distinguished from inactive synovial proliferation using predefined criteria. Blood/urine biochemical markers (serum osteopontin, sVCAM-1, Coll2-1, COMP, CS846, TIMP, and urinary CTX-II) were compared individually and as combined indexes between patients with and without active synovial proliferation., Results: This cohort consisted of 79 patients with a median age of 31 years (range 16.5-50.8 years) with 62/79 (78%) of the patients using continuous prophylaxis. The annualized joint bleeding rate over the last 5 years was .6 (.2-1.1). Active (17/79, 22%) and inactive subclinical synovial proliferation (17/79, 22%) were both prevalent in this cohort. Biochemical markers were not correlated with active subclinical synovial proliferation., Conclusion: Subclinical synovial proliferation, both active and inactive, was prevalent in patients with severe haemophilia A with access to prophylaxis and would be overlooked without routinely performed ultrasounds. Biochemical markers were unable to identify patients with active subclinical synovial proliferation., (© 2023 The Authors. Haemophilia published by John Wiley & Sons Ltd.)

Aim: Haemophilia is characterized by recurrent joint bleeding caused by a lack of clotting factor VIII or IX. Due to repeated joint bleeding, end-stage arthropathy occurs in relatively young patients. A total knee replacement (TKR) can be a solution. However, TKR may be complicated by perioperative and postoperative bleeds despite clotting factor therapy. The aim of this study was to evaluate the prevalence of pre-operative synovial hyperaemia and the effects of Genicular Artery Embolization on synovial hyperaemia and 3-month postoperative joint bleeding., Methods: In this retrospective cohort study, all patients with haemophilia who underwent periarticular catheter angiography between 2009 and 2020 were evaluated after written informed consent. Synovial hyperaemia on angiography was scored by an interventional radiologist., Results: Thirty-three angiography procedures in 24 patients were evaluated. Median age was 54.4 years (IQR 48.4-65.9). Preoperative synovial hyperaemia was observed in 21/33 joints (64%). Moderate and severe synovial hyperaemia was observed in 10/33 joints (30%). Synovial hyperaemia decreased in 13/15 (87%) joints after embolization. Three-month postoperative joint bleeding occurred in 5/32 joints: in 2/18 joints (11%) without synovial hyperaemia and in 3/14 joints (21%) with mild synovial hypertrophy. Non-embolized and embolized joints did not differ regarding 3-month postoperative bleeding (P = .425). No complications were observed after embolization., Conclusion: One-third of patients with haemophilia requiring a TKR had moderate or severe synovial hyperaemia which can be reduced safely by Genicular Artery Embolization prior to TKR. Three-month postoperative bleeding appears to occur independently of the presence of residual mild synovial hyperaemia., (© 2023 The Authors. Haemophilia published by John Wiley & Sons Ltd.)

Background: Healthcare stakeholders in the Netherlands came to an agreement in 2022 to deal with present and future challenges in healthcare. Among others, this agreement contains clear statements regarding the concentration of trauma patients, including the minimal required number of annual severe trauma patients for Major Trauma Centers. This review investigates the effects of trauma patient volumes on several domains of the quality of healthcare., Methods: PubMed was searched; studies published during the last 10 years reporting quantitative data on trauma patient volume and quality of healthcare were included. Results were summarized and categorized into the quality domains of healthcare., Results: Seventeen studies were included with a total of 1,517,848 patients. A positive association between trauma patient volume and survival was observed in 11/13 studies with adjusted analyses. Few studies addressed other quality domains: efficiency ( n = 5), safety ( n = 2), and time aspects of care ( n = 4). None covered people-centeredness, equitability, or integrated care., Conclusions: Most studies showed a better survival of trauma patients when treated in high-volume hospitals compared to lower volume hospitals. However, the ideal threshold could not be determined. The association between trauma volume and other domains of the quality of healthcare remains unclear.

Background: Previous studies suggest that subclinical bleeding occurs in persons with hemophilia., Objectives: The aim of this study was to investigate whether patients with lifelong access to prophylaxis showed signs of previous subclinical bleeding on magnetic resonance imaging (MRI) in joints without a history of joint bleeding., Methods: This single-center cross-sectional study included persons with severe hemophilia A on prophylaxis, aged 16 to 33 years, with lifetime bleeding records available. Per participant, 1 index joint without a history of joint bleeding was evaluated with 3-Tesla MRI, including hemosiderin sensitive sequences. MRI scans were reviewed according to the International Prophylaxis Study Group (IPSG) additive MRI scale (range, 0-17/joint). Hemosiderin deposits with/without synovial hypertrophy were considered signs of previous subclinical bleeding. Additionally, physical examination was performed, followed by ultrasound examination according to the Hemophilia Early Arthropathy Detection with Ultrasound protocol., Results: In 43 patients with a median age of 23.5 years, 43 joints (16 elbows, 13 knees, 14 ankles) without reported bleeds were evaluated with MRI. The median IPSG MRI score was 1 (range, 0-9). Signs of previous subclinical bleeding were observed in 7 of 43 joints (16%; 95% CI, 7-30): 7 of 7 joints showed hemosiderin deposits, with concomitant synovial hypertrophy in 2 of 7 joints. MRI changes were accompanied by swelling and ultrasound-detected synovial hypertrophy in 1 ankle only. None of the other joints showed abnormalities at physical examination and ultrasound., Conclusion: In this study, 16% of the joints without reported bleeds showed signs of previous subclinical bleeding, providing evidence for subclinical bleeding in people with severe hemophilia with lifelong access to prophylaxis., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Ankle joint distraction (AJD) is a promising treatment for patients with severe haemophilic ankle arthropathy (HAA). However, some patients showed no clinical improvement after AJD and these differences may be related to structural differences., Aim: Primarily to quantify the structural changes after AJD in patients with HAA by the use of 3D joint space width (JSW) measurements and biochemical markers and secondarily to correlate these findings with clinical pain/function., Methods: Patients with haemophilia A/B who underwent AJD were included for this study. Bone contours on MRI (performed before and 12 and 36 months after AJD) were drawn manually and percentage change in JSW was calculated. Blood/urine (before and 6, 12, 24 and 36 months after AJD) was collected for biomarker measurement (COMP, CS846, C10C, CALC2, PRO-C2, CTX-II) and combined indexes of markers were calculated. Mixed effects models were used for analyses on group level. Structural changes were compared with clinical parameters., Results: Eight patients were evaluated. On group level, percentage changes in JSW showed a slight decrease after 12 months followed by a non-statistically significant increase in JSW after 36 months compared to baseline. Biochemical marker collagen/cartilage formation also showed an initial decrease, followed by a trend towards net formation 12, 24 and 36 months after AJD. On individual patient level, no clear correlations between structural changes and clinical parameters were observed., Conclusion: Cartilage restoration activity on group level in patients with HAA after AJD was in concordance with clinical improvements. Correlating structural modifications with clinical parameters in the individual patient remains difficult., (© 2023 The Authors. Haemophilia published by John Wiley & Sons Ltd.)