MR Imaging of Hemosiderin Deposition in the Ankle Joints of Patients with Haemophilia: The Contribution of a Multi-Echo Gradient-Echo Sequence-Correlation with Osteochondral Changes and the Number and Chronicity of Joint Bleeds.

We aim (a) to introduce an easy-to-perform multi-echo gradient-echo sequence (mGRE) for the detection of hemosiderin deposition in the ankle joints of boys with haemophilia (b) to explore the associations between the presence and severity of hemosiderin deposition and the other components of haemophilic arthropathy, the clinical score, and the number and chronicity of joint bleeds. An MRI of 41 ankle joints of 21 haemophilic boys was performed on a 3 T MRI system using an mGRE sequence in addition to the conventional protocol. Conventional MRI and mGRE were separately and independently assessed by three readers, namely, two musculoskeletal radiologists and a general radiologist for joint hemosiderin. We set as a reference the consensus reading of the two musculoskeletal radiologists, who also evaluated the presence of synovial thickening, effusion, and osteochondral changes. Excellent inter-reader agreement was obtained using the mGRE sequence compared to the conventional protocol (ICC: 0.95-0.97 versus 0.48-0.89), with superior sensitivity (90-95% versus 50-85%), specificity (95.2-100% versus 76.2-95.2%), and positive (95-100% versus 71-94.4%) and negative predictive value (91.3-95.5% versus 87-63%). Hemosiderin deposition was associated with osteochondral changes, synovial thickening, clinical score, and the total number of ankle bleeds, while it was inversely related with the time elapsed between the last joint bleed and MRI. (p < 0.05). The application of an mGRE sequence significantly improved hemosiderin detection, even when performed by the less experienced reader. Joint hemosiderin deposition was associated with the other components of haemophilic arthropathy and was mostly apparent in recent joint bleeds.

Clinical and Humanistic Burden of Non-inhibitor Haemophilia A in Five European Countries: Insights from the CHESS II Study.

INTRODUCTION: Haemophilia A (HA) is a congenital bleeding disorder caused by a deficiency/absence of factor VIII (FVIII) and characterised by frequent, acute and prolonged spontaneous or traumatic bleeding events, often leading to haemophilic arthropathy and progressive joint deterioration. HA severity is characterized by endogenous FVIII activity: mild (> 5-40%), moderate (1-5%), or severe (< 1%). HA poses a substantial clinical and socioeconomic burden on people with HA (PWHA), their caregivers, and society. This analysis evaluates clinical and patient-centric outcomes of a cohort of individuals with non-inhibitor HA sampled from France, Germany, Italy, Spain, and the UK in the 'Cost of Haemophilia in Europe: A Socioeconomic Survey II' (CHESS II) study. METHODS: CHESS II was a cross-sectional burden-of-illness study collecting clinical and socioeconomic data on adult (≥ 18 years) individuals with haemophilia A or B of any severity with or without inhibitors from eight European countries. Descriptive analyses were conducted examining physician-reported demographics, clinical and health resource utilisation information. PWHA-reported health-related quality of life (HRQoL) using the EQ-5D-5L and Work Productivity and Activity Impairment (WPAI) were also examined. Outcomes were stratified by HA severity and reported at country level. RESULTS: Demographics and clinical characteristics of the cohort (N = 880) were generally consistent across countries. Individuals with severe HA experienced more frequent bleeding events and joint disease despite broad use of factor replacement therapy long-term prophylaxis. A minority of those with mild or moderate HA also experienced such challenges. HRQoL and workforce participation diminished, and chronic pain increased, with increasing HA severity. CONCLUSION: This analysis provides up-to-date insights on the impact of HA across five European countries. Increasing HA severity was generally associated with worse clinical outcomes, HRQoL and workforce participation. These findings suggest a place for continued evidence-based tailored treatment and clinical management approaches in addressing the residual burden of HA.

Accuracy and clinical role of digital templating for total knee arthroplasty performed on haemophilic knees.

INTRODUCTION: In total knee arthroplasty (TKA), choosing the correct implant size is important. There is lack of data on accuracy of templating on haemophilic knees. Our aim was to test the accuracy of 2D digital templating for TKA on haemophilic arthropathy (HA) of knee. MATERIALS AND METHODS: TKAs performed on HA between January 2011 and January 2022 were screened. Osteoarthritis (OA) group was created as control group by a one-to-one matching regarding type of implant used. Intra- and interobserver correlations were measured in HA, then correlation between templated and implanted sizes was investigated in four assessments (femur AP, femur lateral, tibia AP, tibia lateral), then compared with OA group. Fifty-eight knees in each group included. RESULTS: Regarding intraobserver correlation in HA, there was excellent correlation for femur AP [.93 (.73-.98)], femur lateral [.98 (.91-.99)], and tibia AP (1.0) templating. Regarding interobserver correlation in HA, excellent correlation was observed for femur lateral [.93 (.74-.98)] and tibia AP templating [.90 (.65-.97)]. Regarding correlation of templated and applied sizes in HA; tibia AP, tibia lateral and femur lateral templating showed good correlation [.81 (.70-.89), .86 (.77-.91), .79 (.67-.87) while femur AP templating showed moderate correlation [.67 (.50-.79)]. Comparing HA and OA, there was no difference in correlation levels regarding femur AP, femur lateral, tibia AP and tibia lateral templating (p = .056, p = .781, p = .761, p = .083, respectively). CONCLUSION: Although 2D digital templating shows comparable correlation in HA and OA, clinical applicability of templating on HA appears to be limited in its current state.

AAV mediated repression of Neat1 lncRNA combined with F8 gene augmentation mitigates pathological mediators of joint disease in haemophilia.

Haemophilic arthropathy (HA), a common comorbidity in haemophilic patients leads to joint pain, deformity and reduced quality of life. We have recently demonstrated that a long non-coding RNA, Neat1 as a primary regulator of matrix metalloproteinase (MMP) 3 and MMP13 activity, and its induction in the target joint has a deteriorating effect on articular cartilage. In the present study, we administered an Adeno-associated virus (AAV) 5 vector carrying an short hairpin (sh)RNA to Neat1 via intra-articular injection alone or in conjunction with systemic administration of a capsid-modified AAV8 (K31Q) vector carrying F8 gene (F8-BDD-V3) to study its impact on HA. AAV8K31Q-F8 vector administration at low dose, led to an increase in FVIII activity (16%-28%) in treated mice. We further observed a significant knockdown of Neat1 (~40 fold vs. untreated injured joint, p = 0.005) in joint tissue of treated mice and a downregulation of chondrodegenerative enzymes, MMP3, MMP13 and the inflammatory mediator- cPLA2, in mice receiving combination therapy. These data demonstrate that AAV mediated Neat1 knockdown in combination with F8 gene augmentation can potentially impact mediators of haemophilic joint disease.

A qualitative study on the perioperative experiences and demands of haemophilic arthropathy patients undergoing total joint replacement.

INTRODUCTION: Total joint replacement is the optimal treatment option for patients with severe haemophilic arthritis. Current research emphasizes patient-reported outcomes as a vital measure for evaluating surgical outcomes and patient satisfaction. Nevertheless, very limited information about the subjective experience of perioperative haemophiliacs in the literature, highlighting the need for exploration in this area. AIM: To investigate the psychological experiences and health demands of haemophilic arthropathy patients during the perioperative period of total joint replacement. DESIGN: Qualitative descriptive research with semistructured individual interviews. METHODS: From June to September 2023, nine patients with severe haemophilic arthropathy who underwent total joint replacement at a Haemophilia Diagnosis and Treatment Centre in China were interviewed for average 37 min per person. Data were analysed using the traditional content analysis method and reported following the consolidated criteria for reporting qualitative research. The study is reported according to the COREQ checklist. RESULTS: Interviews described two main themes: (1) emotional decline which involves preoperative overoptimism, early postoperative anxiety and disease uncertainty during the early independent rehabilitation. (2) wellness aspiration which includes rehabilitation support and spiritual healing. CONCLUSION: This study reveals the patients' significant psychological changes and their well-being aspiration, particularly out-of-hospital rehabilitation needs. Strengthening communication between multidisciplinary teams and patients, enhancing the involvement of nurses, broadening the scope of functions at primary Haemophilia Treatment Centres, and developing telerehabilitation, these concerted efforts may improve the overall treatment experience for patients.

Effects of resistance training on muscle strength in adults with haemophilia: A systematic review and meta-analysis.

INTRODUCTION: Although resistance training is frequently prescribed for people with haemophilia (PWH), no previous meta-analyses have quantified the effect of this intervention on muscle strength, nor the implications of the intervention's modality and duration. AIM: (1) To determine the effects of resistance training on muscle strength in adults with haemophilia; (2) To determine the most effective duration and modality among the exercise protocols. METHODS: A systematic search from inception until 28 November 2023 was conducted in PubMed, Embase, Web of Science, CENTRAL and CINAHL databases. We included randomised controlled trials or before-after studies that involved resistance training without other physiotherapy co-interventions. Study selection, data extraction and risk of bias assessment were independently performed by two reviewers. Disagreements were resolved in consultation with a third author. The level of evidence was determined according to the GRADE methodology. RESULTS: Seven studies were included. Measurements of knee extensor strength and elbow extensor strength were included in the meta-analysis. Subgroup analysis showed significant effects for both elastic resistance protocols (SMD: 0.54; 95% CI: 0.02-1.07) and conventional training (isometric and weight-based equipment) (SMD: 0.88; 95% CI: 0.50-1.25), demonstrating small and moderate effect sizes respectively. Additionally, both protocols of duration 5-7 weeks (SMD: 1.16, 95% CI: 0.63-1.69) as well as those of duration ≥8 weeks (SMD: 0.57, 95% CI: 0.20-0.94) showed a significant difference. CONCLUSION: Resistance training is effective in improving muscle strength of the knee and elbow extensors in PWH. Both elastic resistance and conventional training show benefits.

Functional clinical motor performance tests to assess potential fall risks in patients with haemophilia: A case-control study.

INTRODUCTION: Patients with haemophilia (PwH) are at increased risk of falls due to haemophilic arthropathy. Yet, studies on clinical tests associated with the risk of falling are scarce in PwH. AIMS: (1) To evaluate the feasibility of different clinical motor performance tests associated with the risk of falling in PwH; (2) to evaluate PwH's performance of these tests compared to a control group; (3) to identify possible influencing factors that affect performance. METHODS: Twenty-nine severe and moderate PwH (57.0 years, IQR: 48.0-61.5) and 29 healthy age- and BMI-matched control participants (CG) performed 13 different clinical tests (SPPB, timed up and go, push and release, functional reach, single-leg stance, knee and grip strength). Haemophilia joint health score (HJHS), kinesiophobia (TSK-11), subjective physical performance (HEP-Test-Q), falls efficiency (FES-I) and falls were assessed. RESULTS: No adverse events occurred. PwH showed impaired performance in all clinical tests, a lower falls efficiency and a higher HJHS than CG. PwH with higher HJHS, lower HEP-Test-Q and higher TSK-11 scores showed higher deficits. Largest discrepancies were observed in the single-leg stance with eyes open and knee extensor strength, where orthopaedically majorly affected PwH showed worse performance compared to minorly affected PwH and the CG, respectively. The prevalence of ≥1 fall in the last year was 27.6% (PwH) and 10.3% (CG). CONCLUSION: These clinical tests are feasible in PwH. Impaired joint status, a high kinesiophobia and low physical performance impair performance. These tests can be used by clinicians for gaining specific information on functional motor abilities of patients.

Assessing joint health in haemophilia patients: The combined value of physical examination and ultrasound imaging.

INTRODUCTION: Early diagnosis of joint damage is pivotal in haemophilia to prevent the occurrence and progression of haemophilic arthropathy thus providing optimal personalised management. The haemophilia joint health score version 2.1 (HJHS) is based on a physical examination of the mainly affected joints. Musculoskeletal ultrasound has demonstrated the capability to detect early changes in terms of synovitis and osteochondral damage. The haemophilia early detection with ultrasound (HEAD-US) score has been proposed as a simple and reliable evaluation tool. AIM: This study aims to investigate the correlation between the HJHS and the HEAD-US scores performed by two independent operators (physical therapist and musculoskeletal ultrasound expert) for the evaluation of the joint health status of patients with haemophilia. METHODS: Consecutive adult patients independent of the severity degree were included. Elbows, knees and ankles were evaluated by a physical therapist by HJHS and by a musculoskeletal ultrasound expert following the HEAD-US protocol. RESULTS: We observed a good positive correlation between HJHS and HEAD-US (Spearman's rho 0.72). The main discrepancy in conceptually similar domains was found between the HJHS swelling and the HEAD-US synovitis (rho 0.17), as ultrasound was able to detect even mild synovitis when HJHS swelling was scored 0 in up to 40% of cases. CONCLUSIONS: The HJHS and HEAD-US correlate well even when performed by two independent operators. Musculoskeletal ultrasound is particularly useful for the early detection of synovitis. The routine assessment of both scores helps clinicians define the stage and extension of joint involvement and set up a personalised treatment.

Structural alterations and pain perception at the ankle joint in patients with haemophilia.

BACKGROUND: Patients with haemophilia (PwH) suffer from chronic pain due to joint alterations induced by recurring haemorrhage. OBJECTIVES: This study aimed to investigate the relationship between structural alterations and pain perception at the ankle joint in PwH. PATIENTS/METHODS: Ankle joints of 79 PwH and 57 healthy controls (Con) underwent ultrasound examination (US) and assessment of pain sensitivity via pressure pain thresholds (PPT). US discriminated between joint activity (synovitis) and joint damage (cartilage and/or bone degeneration) applying the HEAD-US protocol. Based on US-findings, five subgroups were built: PwH with activity/damage, PwH with activity/no damage, PwH with no activity/no damage, controls with activity/no damage and controls with no activity/no damage. RESULTS: Joint activity and joint damage were significantly increased in ankles of PwH compared to Con (p ≤.001). Subgroup analysis revealed that structural alterations negatively impact pain perception. This is particularly evident when comparing PwH with both activity/damage to PwH with no activity/no damage at the tibiotalar joint (p = .001). At the fibulotalar joint, no significant differences were observed between PwH subgroups. Further analysis showed that both joint activity and joint damage result in an increase in pain sensitivity (p ≤.001). CONCLUSION: The data suggest a relation between joint activity, joint damage and pain perception in PwH. Even minor changes due to synovitis appear to affect pain perception, with the effect not intensifying at higher levels of inflammation. In terms of joint damage, severe degeneration leads to a sensitised pain state most robustly, whereas initial changes do not seem to significantly affect pain perception.

Haemophilic arthropathy: Diagnosis, management, and aging patient considerations.

Gene therapy and universal use of safer, more effective, and personalised prophylactic regimens (factor, and nonfactor) are expected to prevent joint bleeding and promote joint health in persons with haemophilia (PwH). Growing evidence suggests that subclinical bleeding, with active and inactive synovial proliferation, continues and haemophilic arthropathy remains a major morbidity in PwH despite early institution of joint prophylaxis. Joint health assessment is evolving with physical examination scores complementing imaging scores. Point-of-care ultrasound is emerging as a safe, cost-effective, and readily available tool for acute determination of musculoskeletal abnormalities, serial evaluation of joints for sonographic markers of haemophilic arthropathy, and in providing objective insight into the efficacy of new therapies. In acute haemarthrosis, arthrocentesis expedites recovery and prevent the vicious cycle of bleed-synovitis-rebleed. When synovial proliferation develops, a multidisciplinary team approach is critical with haematology, orthopaedics, and physiotherapy involvement. Synovectomy is considered for patients with chronic synovitis that fail conservative management. Non-surgical and minimally invasive procedures should always be offered and considered first. Careful patient selection, screening and early intervention increase the success of these interventions in reducing bleeding, pain, and improving joint function and quality of life. Chemical synovectomy is practical in developing countries, but radioactive synovectomy appears to be more effective. When surgical synovectomy is considered, arthroscopic/minimally invasive approach should be attempted first. In advanced haemophilic arthropathy, joint replacement and arthrodesis can be considered. While excited about the future of haemophilia management, navigating musculoskeletal challenges in the aging haemophilia population is equally important.

The good, the bad and the ugly of pain in haemophilia: Recent evidence on the epidemiology, molecular mechanisms and knowledge gaps preventing optimal treatment.

INTRODUCTION: Haemophilia is an inherited, X-linked blood clotting disorder caused by the deficiency of coagulation factors VIII (FVIII, haemophilia A) or IX (FIX, haemophilia B). Spontaneous bleeds are common in severe forms of haemophilia and can also occur in moderate and mild haemophilia. Severe or repeated bleeding at a joint can evolve into chronic haemophilic arthropathy, with functional damage of the joint, disability, and intense chronic articular pain. Nonetheless, acute and chronic pain may emerge due to secondary conditions related to bleedings. AIM: This narrative review aims to critically discuss the most recent evidence about pain in haemophilia to give healthcare professionals a clear picture of current knowledge hence favouring the optimisation of clinical management of pain. METHODS: Extensive literature search with the terms 'hemophilia' AND 'pain', focusing on the time window 2021-2023. RESULTS: Acute and chronic pain is a critical aspect of haemophilia at all ages. It should be considered a multifaceted phenomenon, with a positive role as an early emergency signal of a clinical event (haemarthrosis), and numerous detrimental aspects linked to its burden that heavily affects the health-related quality of life, with psychological and social consequences. CONCLUSION: Despite its prevalence and frequency in people with haemophilia, pain is often underestimated by healthcare professionals, leading to insufficient and inadequate treatment, also due to uncertainty linked to the presence of the coagulation disorder or arthritic flares.

Benefits of physical activity self-monitoring in patients with haemophilia: a prospective study with one-year follow-up.

INTRODUCTION: Activity wristbands have been shown to be effective in relation to self-monitoring activity levels and increasing exercise adherence. However, previous reports have been based on short-term follow-ups in people with haemophilia (PWH). AIM: (1) To evaluate compliance with physical activity (PA) recommendations in PWH during a 1-year follow-up period using activity wristbands to record daily steps and intensity; (2) To determine the effect of PA self-monitoring on clinical outcomes. METHODS: A prospective observational study was conducted in 27 adults with severe haemophilia undergoing prophylactic treatment. The Fitbit Charge HR was used to track daily PA for an entire year. The participants were encouraged to try to reach a goal of 10,000 steps/day and to track their progress. The pre- and post-evaluation included quality of life (A36 Hemophilia-QoL Questionnaire), joint health (Haemophilia Joint Health Score), functionality (Timed Up and Go test), and muscle strength. RESULTS: A total of 323.63 (95%CI: 194-364) valid days (i.e., > 2000 steps) were recorded. The annual average number of steps per day taken by participants was 10,379. Sixteen (59%) PWH reached 10,000 steps/day at baseline and 17 (63%) at 1 year follow-up, with no significant differences (x2 = .33; p = .56). A statistically significant improvement was observed in daily moderate activity time (p = .012) and in the 'physical health' quality of life subscale (mean difference: 2.15 points; 95%CI: .64-3.65; p = .007). CONCLUSION: Our results suggest that patients with severe haemophilia who self-managed their PA can improve their long-term quality of life in the domain of physical health and also the daily time spent in moderate-intensity PA.

Single-facility study of the effectiveness of rehabilitation therapy using wearable hybrid assistive limb for patients with bleeding disorders: study protocol for a randomised controlled trial.

INTRODUCTION: Haemophilic arthropathy, a serious complication of haemophilia, results from recurrent joint bleeding, causing progressive joint damage and severely impacting patient quality of life. Rehabilitation therapy (RT) effectively addresses declining physical function due to joint degradation, but pain during RT can hinder its success. Therefore, an effective pain-alleviating treatment method is required. The single-joint hybrid assistive limb (HAL-SJ), a powered exoskeleton, measures bioelectric potential during muscle contraction and provides motorised support, potentially alleviating pain. OBJECTIVE: This study outlines our protocol for a randomised, prospective, single-blind (evaluator) trial aimed to investigate the effects of HAL-SJ on pain reduction during RT, kinesiophobia and other physical functions in patients with haemophilia. METHODS AND ANALYSIS: This two-group comparison intervention study will include 24 male patients aged 12-85 years diagnosed with a bleeding disorder necessitating RT for pain and physical function improvement. The primary outcome measures pain changes during the first and second RT session in patients receiving HAL-SJ-assisted RT compared with traditional RT without HAL-SJ. The secondary outcomes include kinesiophobia (Japanese version of the Tampa Scale for Kinesiophobia), standing position gait (zebris FDM-T treadmill), range of motion (manual goniometer) and body surface temperature (infrared thermography camera) during the study period of up to 3 months or until the end of 10 RTs. RT intensity remains below that required to move the affected joint against gravity, given HAL-SJ's muscular support. The follow-up period extends to 1 month after the last RT. Intergroup study variables are compared by an unpaired t-test or Mann-Whitney test. Intragroup comparisons of secondary outcomes are analysed by a paired t-test or Wilcoxon signed-rank test. ETHICS AND DISSEMINATION: This study was approved by the accreditation committee of Nara Medical University Hospital. The study results will disseminate through publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: jRCTs052220076.

Mobilization under anaesthesia for correction of knee flexion deformity in haemophilia.

INTRODUCTION: Haemophilia patients not treated with primary or secondary prophylaxis, often present with recurrent haemarthrosis. Knee is the most frequently involved joint leading to disabling knee flexion deformity (KFD). Here, we present a retrospective study of our experience on the role of mobilization under general anaesthesia in the correction of KFD. AIM: To study the effectiveness of mobilization under anaesthesia (MUA) for correction of knee flexion deformity (KFD) in persons with haemophilia (PWH). METHODS: Outcome of all patients managed with MUA in our multidisciplinary haemophilia clinic from 2008 to 2019 were included for analysis. PWH with KFD > 20 degree who underwent MUA were included in the study. Under general anaesthesia and cover of clotting factor replacement, gentle joint mobilization was done to achieve maximal correction in flexion deformity, followed by above knee casting in this position. The outcome measures assessed were reduction in knee flexion deformity following MUA and complications, if any. RESULTS: Thirty patients (34 knees) with knee flexion deformity were included in the study. Mean age of the study population was 14.23 years ± 8.3. Study population was analysed in two groups, Group 1 included patients who underwent single MUA and Group 2, patients who underwent two or more MUA. There was significant improvement in KFD correction in both groups. [Group 1; Mean difference: 22 ± 13.7, p value -0.01, 95% CI (16.4-27.5) and Group 2; Mean difference 48.8 ± 19.8, p value -0.00, 95% CI (34.2-64.5)]. CONCLUSION: MUA can be effective in the short-term correction of KFD in PWH particularly those below 15 years of age. It should be done judiciously when target correction is not achieved with other physical methods.

How does joint impairment affect the functional capacity of the lower limb in early haemophilia-related arthropathy?

INTRODUCTION: The impact of joint damage on functional capacity in patients with mild haemophilia (PwMH) has yet to be well studied. The primary aim of this study was to investigate the effect of joint impairment on the functional capacity of the lower limb in PwMH. The secondary aim was to identify physical predictors of lower limb functional capacity. METHOD: Forty-nine PwMH were evaluated. Dynamic balance was assessed using Time Up and Go (TUG). Thirty-second sit-to-stand (30-STS) and 60-second-STS (60-STS) were used to assess muscle power and endurance, respectively. Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) was used to assess joint damage. PwMH were divided based on HEAD-US: with joint damage (≥3 points) and without or with very low joint damage (0-2 points). Univariate ANOVA and multiple regression analyses were performed to identify differences in functional capacity and potential physical predictors. RESULTS: Only 30-STS showed significant differences between groups (p = .002). TUG and 60-STS were primarily explained by age (r2  = .21 and r2  = .44, respectively), while for 30-STS, age combined with joint damage and pain level explains 54% of the variance. CONCLUSION: Our findings indicate that the 30-STS is useful for assessing functional deterioration in people with early-stage haemophilia-related arthropathy. Our results also indicate that joint damage, combined with ageing and pain, may impact 30-STS outcomes in PwMH. Furthermore, our findings show that the loss in TUG and 60-STS performance in PwMH is related to ageing.

Barriers and facilitators of physical activity in adults with severe haemophilia: A qualitative study.

BACKGROUND: People with haemophilia (PWH) tend to be less physically active than the general population, but there is a lack of research on the specific barriers and facilitators affecting their participation in physical activities. OBJECTIVES: This study aims to explore perceived barriers and facilitators to physical activity in severe PWH. DESIGN: An explorative qualitative study based on focus groups. METHODS: Four focus groups including 16 participants (severe haemophilia A patients) were conducted to examine the factors perceived as facilitators or barriers to haemophiliacs engaging in physical activity. One researcher conducted a thematic analysis of all data. RESULTS: Three themes were identified: body function, personal factors, and environmental factors. Key facilitators identified were access to prophylaxis treatment to reduce the risk of bleeding(s), the enjoyability of physical activity, fitness and health motives, social interaction, support, and low cost. PWH faced additional barriers to being physically active including hurtful joints, mobility issues, haemophilic arthropathy, dislike or disinterest, lack of motivation, fear of injury, tiredness, lack of time, lack of guidance, negative social influence, restriction, and lack of coordination of prophylaxis treatment. CONCLUSION: This exploratory study demonstrated that participation in physical activity in PWH is influenced not only by their own abilities and attitudes, but also by external variables, including family, friends, healthcare professionals, structures, and communities. The results of this study may be used to assist caregivers and health professionals, inform programs, interventions, and policies to promote physical activity and health in severe PWH.

Structural changes after ankle joint distraction in haemophilic arthropathy: an explorative study investigating biochemical markers and 3D joint space width.

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.

Ferroptosis: a new target for iron overload-induced hemophilic arthropathy synovitis.

Iron deposition is closely related to developing haemophilic arthropathy (HA). Studying the relationship between ferroptosis signal expression and iron overload in HA synovium facilitates understanding the pathogenesis of joint synovial hyperplasia in bloodborne arthritis and the development of new protective methods. The knee synovium was collected from HA and osteoarthritis (OA) patients, and pathological changes were analysed by HE and Prussian blue staining. Ferroptosis phenotypes were examined by immunohistochemistry and western blotting. Moreover, ferric ammonium citrate (FAC)-induced was used to construct an in vitro iron overload model to investigate the relationship between iron overload and ferroptosis in synovial fibroblasts (FLS). Furthermore, the factors influencing ferroptosis in FLS were explored. Iron deposition, cell proliferation, and vascular proliferation in the synovium of HA were more obvious. Ferroptosis in HA synovium appears to inhibit. FLS ferroptosis increased with iron accumulation, malondialdehyde (MDA) in cells, and glutathione (GSH) depletion. TNF-α plays a protective role in this process. Blocking the action of TNF-α and inducing ferroptosis significantly reduced synovial proliferation. TNF-α inhibitors combined with a ferroptosis inducer may be a new therapeutic method for HA synovitis.

Mid-to long-term postoperative outcomes of ankle joint fusion in patients with haemophilia: A systematic review.

INTRODUCTION AND AIM: The ankle joint is the most common site for haemophilic arthropathy. The aim of this study was to review the outcomes of ankle joint fusion in patients with haemophilia A or B. The primary outcome measures were union rates, time to union, perioperative blood loss/transfusion, postoperative complications and length of hospital stay (LOS). Secondary outcome measures were hind foot functional outcome scores and the visual analogue pain scale (VAS). MATERIALS AND METHODS: A search of PubMed, Medline, Embase, Journals@Ovid and the Cochrane register was performed conforming to the PRISMA guidelines. Only human studies with a minimum follow-up of 1-year were included. The MINORS and ROBINS-1 tools were used for quality appraisal. RESULTS: A total of 952 articles were identified and only 17 studies met the eligibility criteria after the screening. The mean age of the patients was 37.6 (SD 10.2). A total of 271 ankle fusions were performed with the open crossed-screw fixation being the most common technique. Union rates were 71.5%-100% at 2-6 months. The pooled postoperative complication and revision rates were 13.7% and 6.5%, respectively. The range of LOS was 1.8-10.6 days. The mean preoperative American orthopedic foot and ankle society (AOFAS) ankle-hindfoot score was 35 (SD 13.1) whereas the mean postoperative AOFAS score was 79.4 (SD 5.3). The mean preoperative VAS was 6.3 (SD 1.6) while the mean postoperative VAS score was .9 (SD .4) across 38 ankle fusions. CONCLUSION: Ankle arthrodesis offers improved pain and function in haemophilic ankle arthropathy with lower revision and complication rates than that reported in the literature for total ankle replacement.

18 F-FDG PET/CT imaging for haemophilic arthropathy compared with clinical, radiological and power Doppler sonographic characteristics of 20 haemophilia patients.

INTRODUCTION AND OBJECTIVES: Repeated joint bleeding in haemophilia patients may lead to haemophilic arthropathy with marked inflammation and synovitis. This study investigated the potential of 18 F-fluorodeoxyglucose positron emission tomography-computed tomography (18 F-FDG PET/CT) as a novel diagnostic method for haemophilic arthropathy. MATERIALS AND METHODS: We recruited 20 adult haemophilia patients who reported history of hemarthroses in the shoulder, elbow, hip, knee, or ankle joints. All joints were assessed by power Doppler ultrasonography and radiography, and graded by hyperaemia score and Pettersson score, respectively. Joint pain was evaluated by visual analogue score (VAS). Range of motion (ROM), Haemophilia Joint Health Score (HJHS) and annual joint bleeding rate (AJBR) were recorded. Finally, all participants had whole-body 18 F-FDG PET/CT, and maximum standardized uptake value (SUVmax) of the joints being studied was measured. RESULTS: Thirteen patients had severe haemophilia, and seven had moderate haemophilia. The mean age was 36 years. PET SUVmax showed significant correlations with VAS, ROM, Pettersson score, hyperaemia score, HJHS score and AJBR in all large joints except hip. Joints with pain, hyperaemia and radiographic changes were found to have higher SUVmax than those without these features. Using Youden's index, the optimal cut-off value for early radiographical arthropathy was found to be between 1.9 and 2.0. CONCLUSION: Our study indicates that 18 F-FDG PET/CT imaging correlated well with various conventional diagnostic techniques. It also demonstrated high sensitivity and specificity for early radiographic arthropathy. 18 F-FDG PET/CT imaging may quantitatively evaluate disease activity of most large joints in a single examination and help detect early haemophilic arthropathy.