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Case presentation: A 32-year-old man with a history of hemophilia A presented to the emergency department with right shoulder pain, swelling, and decreased range of motion.Discussion: Emergency physicians can use ultrasound to quickly and accurately identify hemarthrosis at the bedside.

Venous malformations (VMs) are the most common vascular anomalies and have been associated with somatic variants in TEK. Current treatment of VM joint component might be challenging due to the size or location of some lesions or ineffective with recurrence of malformed veins. Targeted molecular therapies after identification of genetic defects might be an alternative. We report a case with intraarticular bleeding due to VM with a TEK pathogenic somatic variant treated with rapamycin. A 26-year-old female patient was evaluated for right calf pain secondary to venous malformation of the right inferior limb with an intraarticular component in the right knee. Hemarthrosis and degenerative chondropathy of the knee were evidenced at MRA. Molecular diagnosis evidenced a pathogenic somatic TEK variant. Rapamycin was introduced to stop bleeding, with good tolerance and efficacy. The TEK receptor signals through the PI3K/AKT/mTOR pathway and TEK mutations have been linked to AKT activation. As rapamycin acts against angiogenesis and reduces phosphorylated-AKT levels, targeted molecular therapy should be discussed as first-line therapy in patients with proven molecular diagnosis and diffuse VM inaccessible to conventional treatment.

Case presentation: A 32-year-old man with a history of hemophilia A presented to the emergency department with right shoulder pain, swelling, and decreased range of motion.Discussion: Emergency physicians can use ultrasound to quickly and accurately identify hemarthrosis at the bedside.

Background: Haemophilia is a hereditary coagulopathy disease affecting males. It is characterized by musculoskeletal bleeding, leading to chronic synovitis and severe joint hemarthrosis. Objective: To determine the impact of pulsed electro- magnetic field on swelling, range of motion and muscle strength of hemarthrotic knee joints of haemophilic adolescents. Participants and Methodology: Thirty haemophilic adolescent males ranging in age between thirteen and sixteen years who fulfilled the inclusion criteria participated in this study. They were assigned randomly into two groups of equal numbers A (control) and B (study). Groups A and B received a specific program of physical therapy for sixty minutes, in addition, group A received a placebo pulsed electromagnetic field for twenty minutes, while group B received pulsed electromagnetic field for twenty minutes. The treatment program was applied three days/week for three successive months. Evaluation of knee swelling using tape measurement, range of motion using electronic goniometer and muscle strength using isokinetic dynamometer was conducted for each patient of groups A and B before and after treatment. Results: Significant improvement was observed in the post-treatment mean values of the measuring variables of groups A and B when compared with their pre-treatment results (p < .05). High significant improvement was observed in group B when comparing the post-treatment results of groups, A and B (p < .05). Conclusions: Pulsed electromagnetic field is an effective modality which can be used with the traditional methods for treatment of knee hemarthrosis in haemophilic adolescents.

IntroductionJoint iron accumulation is the incendiary factor triggering osteochondral destruction, synovial hypertrophy, inflammation, and vascular remodelling in haemophilic arthropathy (HA). Hemosiderin depositions have been described in synovium and, more recently, in cartilage. Clinical observations also suggest hemosiderin accumulation in subchondral cysts, implying cyst bleeding.AimWe explored associations between cystic iron accumulation, vascular remodelling and HA status to determine if cystic bleeding may contribute to HA progression.MethodsThirty-six haemophilic joints (16 knees, 10 ankles, and 10 elbows; 31 adult patients with haemophilia A/B) were evaluated by magnetic resonance imaging (MRI) for subchondral cysts and hemosiderin. Cyst score (WORMS) and hemosiderin presence were compared between haemophilic and osteoarthritic knees, matched for the degree of arthritis (Kellgren-Lawrence score). Cystic iron accumulation, vascular remodelling and macrophage cell counts were also compared by immunohistochemistry in explanted joint tissues. In haemophilic knees, cyst number and extent of hemosiderin deposition were correlated with haemophilia joint health scores (HJHS).ResultsCystic hemosiderin was detected in 78% of haemophilic joints. Cyst score and presence of hemosiderin were significantly higher in haemophilic compared to osteoarthritic knees. Cyst score and presence of hemosiderin strongly correlated with HJHS. Moreover, iron deposition and vascular remodelling were significantly more pronounced within cysts in haemophilic compared to osteoarthritic knees, with similar total cell and macrophage count.ConclusionThese findings suggest the presence of subchondral bleeding in haemophilia, contributing to poor joint health outcomes. Observations of bleeding into osseous structures are novel and should inform investigations of new therapies.

Background: Haemophilia is a hereditary coagulopathy disease affecting males. It is characterized by musculoskeletal bleeding, leading to chronic synovitis and severe joint hemarthrosis. Objective: To determine the impact of pulsed electro- magnetic field on swelling, range of motion and muscle strength of hemarthrotic knee joints of haemophilic adolescents. Participants and Methodology: Thirty haemophilic adolescent males ranging in age between thirteen and sixteen years who fulfilled the inclusion criteria participated in this study. They were assigned randomly into two groups of equal numbers A (control) and B (study). Groups A and B received a specific program of physical therapy for sixty minutes, in addition, group A received a placebo pulsed electromagnetic field for twenty minutes, while group B received pulsed electromagnetic field for twenty minutes. The treatment program was applied three days/week for three successive months. Evaluation of knee swelling using tape measurement, range of motion using electronic goniometer and muscle strength using isokinetic dynamometer was conducted for each patient of groups A and B before and after treatment. Results: Significant improvement was observed in the post-treatment mean values of the measuring variables of groups A and B when compared with their pre-treatment results (p < .05). High significant improvement was observed in group B when comparing the post-treatment results of groups, A and B (p < .05). Conclusions: Pulsed electromagnetic field is an effective modality which can be used with the traditional methods for treatment of knee hemarthrosis in haemophilic adolescents.

INTRODUCTION: Hemophilic arthropathy can affect multiple joints including ankle. However, only one report has been published regarding both arthroscopic ankle arthrodesis with hemophilic arthropathy. PRESENTATION OF CASE: The patient was a 23-year-old man with hemophilia A and a 3-year history of recurrent hemarthrosis in both ankles. We undertook surgery to treat arthropathy. His left ankle was treated first and the right ankle 6 months later. In both ankles, the cartilage was worn and eburnated. The remaining cartilage was removed and more dimples were created to fuse the tibia and talus. The ankle was fixed using 3 cannulated screws. Postoperatively, the patient wore an immobilization cast with no weight-bearing for 2 weeks. Thereafter, weight-bearing was allowed and the cast was removed 4 weeks after surgery. DISCUSSION: At the 1-year follow-up, bony union was satisfactory, functional outcome was acceptable, and pain relief was good. The Japanese Society for Surgery of the Foot ankle-hindfoot scale score increased from 24 preoperatively to 87 postoperatively. CONCLUSION: We report successful treatment with arthroscopic arthrodesis in a case of hemophilic arthropathy in both ankles.

Essentials The best imaging modality for joint blood detection in hemophilia is unknown. Blood appearance and detection thresholds were studied with ultrasound and conventional MRI. Ultrasound is sensitive to low volume and concentration of blood, whereas conventional MRI is not. The findings establish the validity of ultrasound for rapid bleed detection in hemophilia care. SUMMARY:Background There is increasing demand for musculoskeletal ultrasound (MSKUS) to detect hemophilic joint bleeding, but there is uncertainty regarding blood detection concentration thresholds or if magnetic resonance imaging (MRI) is more accurate. Aims Compare the sensitivity of blood detection by MSKUS and MRI. Methods Increasing blood concentrations in plasma were imaged with MSKUS and MRI 1-2 h, 3-4 days and 7 days after blood withdrawal in vitro, and after injection into cadaveric pig joints. Additionally, effusions in the joints of two patients with hemophilia joints were imaged, followed by aspiration. MSKUS was performed using an 8-18-MHz linear transducer; MRI was performed at 3T using T1-weighted and T2-weighted fat-suppressed sequences. Images were reviewed by a hematologist certified in MSKUS and a musculoskeletal radiologist. Results MSKUS permitted the detection of blood in vitro and in pig joint spaces at concentrations as low as 5%, demonstrated by the presence of echogenic signals that were absent with plasma alone. In contrast, no differences between fluids were discernible on the T1-weighted or T2-weighted MRI images. Results were confirmed in the two patients with hemophilia. Blood clots demonstrated varying and dynamic echogenicity patterns over time and, using MRI, were visualized best with T2 sequences. Conclusion MSKUS is extremely sensitive in detecting low concentrations of intra-articular blood and in discriminating between bloody and non-bloody fluid, whereas conventional MRI is not. These observations demonstrate the advantages of MSKUS over MRI in detecting int

The lateral collateral ligament (LCL) complex of the elbow plays a crucial role in the stability of the elbow joint, especially to varus loads. Deficiency of particularly the lateral ulnar collateral component of the LCL can lead to chronic posterolateral rotatory instability, which can be functionally debilitating and can lead to a rapid onset of early degenerative arthritis. Commonly, in the setting of acute rupture of the LCL, the ligament is repaired using an open technique with suture anchor fixation to the lateral epicondyle insertion point. However, with advancing arthroscopic techniques, it has become possible to repair the LCL arthroscopically. We present a relatively simple method for an all-arthroscopic repair of the LCL to the humerus using a knotless suture anchor technique.Copyright © 2017 Arthroscopy Association of North America

The lateral collateral ligament (LCL) complex of the elbow plays a crucial role in the stability of the elbow joint, especially to varus loads. Deficiency of particularly the lateral ulnar collateral component of the LCL can lead to chronic posterolateral rotatory instability, which can be functionally debilitating and can lead to a rapid onset of early degenerative arthritis. Commonly, in the setting of acute rupture of the LCL, the ligament is repaired using an open technique with suture anchor fixation to the lateral epicondyle insertion point. However, with advancing arthroscopic techniques, it has become possible to repair the LCL arthroscopically. We present a relatively simple method for an all-arthroscopic repair of the LCL to the humerus using a knotless suture anchor technique.Copyright © 2017 Arthroscopy Association of North America

Essentials The best imaging modality for joint blood detection in hemophilia is unknown. Blood appearance and detection thresholds were studied with ultrasound and conventional MRI. Ultrasound is sensitive to low volume and concentration of blood, whereas conventional MRI is not. The findings establish the validity of ultrasound for rapid bleed detection in hemophilia care. SUMMARY:Background There is increasing demand for musculoskeletal ultrasound (MSKUS) to detect hemophilic joint bleeding, but there is uncertainty regarding blood detection concentration thresholds or if magnetic resonance imaging (MRI) is more accurate. Aims Compare the sensitivity of blood detection by MSKUS and MRI. Methods Increasing blood concentrations in plasma were imaged with MSKUS and MRI 1-2 h, 3-4 days and 7 days after blood withdrawal in vitro, and after injection into cadaveric pig joints. Additionally, effusions in the joints of two patients with hemophilia joints were imaged, followed by aspiration. MSKUS was performed using an 8-18-MHz linear transducer; MRI was performed at 3T using T1-weighted and T2-weighted fat-suppressed sequences. Images were reviewed by a hematologist certified in MSKUS and a musculoskeletal radiologist. Results MSKUS permitted the detection of blood in vitro and in pig joint spaces at concentrations as low as 5%, demonstrated by the presence of echogenic signals that were absent with plasma alone. In contrast, no differences between fluids were discernible on the T1-weighted or T2-weighted MRI images. Results were confirmed in the two patients with hemophilia. Blood clots demonstrated varying and dynamic echogenicity patterns over time and, using MRI, were visualized best with T2 sequences. Conclusion MSKUS is extremely sensitive in detecting low concentrations of intra-articular blood and in discriminating between bloody and non-bloody fluid, whereas conventional MRI is not. These observations demonstrate the advantages of MSKUS

The purpose was to examine the test-retest reliability of the Rolimeter measurement procedure in the acute time phase, following a substantial knee trauma. In total, 15 participants with acute knee trauma were examined by one single observer at three different time-points with the Rolimeter using a maximum force. The selected time-points were: baseline (0–7 days after the trauma), midpoint (3–4 weeks after the trauma), and endpoint (3–4 weeks after the trauma). The anterior-posterior displacement was recorded where the endpoint evaluation was used as the reference value. The mean anterior laxity scores remained constant over the measurement time-points for both knees, with an anterior laxity that was 2.7 mm higher (on average) in the injured than the noninjured knee (9.5 mm vs. 6.8 mm). The mean difference (i.e., bias) between laxity scores, for the injured knee, measured at endpoint versus baseline was 0.2±1.0 mm and −0.2±1.1 mm when measured at endpoint versus midpoint, with average typical errors of 0.7 and 0.8 mm and intra-class correlations that were very strong (both r=~0.93). For the same comparisons on the noninjured knee, systematic bias was close to zero (0.1±0.3 and −0.1±0.3 mm, respectively), and both the intra-class correlations were almost perfect (r=~0.99). The current study implicates that repeated Rolimeter measurements are relatively reliable for quantifying anterior knee laxity during the acute time-phases following knee trauma. Hence, the Rolimeter, in combination with manual tests, seems to be a valuable tool for identifying anterior cruciate ligament injuries.

The purpose was to examine the test-retest reliability of the Rolimeter measurement procedure in the acute time phase, following a substantial knee trauma. In total, 15 participants with acute knee trauma were examined by one single observer at three different time-points with the Rolimeter using a maximum force. The selected time-points were: baseline (0–7 days after the trauma), midpoint (3–4 weeks after the trauma), and endpoint (3–4 weeks after the trauma). The anterior-posterior displacement was recorded where the endpoint evaluation was used as the reference value. The mean anterior laxity scores remained constant over the measurement time-points for both knees, with an anterior laxity that was 2.7 mm higher (on average) in the injured than the noninjured knee (9.5 mm vs. 6.8 mm). The mean difference (i.e., bias) between laxity scores, for the injured knee, measured at endpoint versus baseline was 0.2±1.0 mm and −0.2±1.1 mm when measured at endpoint versus midpoint, with average typical errors of 0.7 and 0.8 mm and intra-class correlations that were very strong (both r=~0.93). For the same comparisons on the noninjured knee, systematic bias was close to zero (0.1±0.3 and −0.1±0.3 mm, respectively), and both the intra-class correlations were almost perfect (r=~0.99). The current study implicates that repeated Rolimeter measurements are relatively reliable for quantifying anterior knee laxity during the acute time-phases following knee trauma. Hence, the Rolimeter, in combination with manual tests, seems to be a valuable tool for identifying anterior cruciate ligament injuries.

The purpose was to examine the test-retest reliability of the Rolimeter measurement procedure in the acute time phase, following a substantial knee trauma. In total, 15 participants with acute knee trauma were examined by one single observer at three different time-points with the Rolimeter using a maximum force. The selected time-points were: baseline (0–7 days after the trauma), midpoint (3–4 weeks after the trauma), and endpoint (3–4 weeks after the trauma). The anterior-posterior displacement was recorded where the endpoint evaluation was used as the reference value. The mean anterior laxity scores remained constant over the measurement time-points for both knees, with an anterior laxity that was 2.7 mm higher (on average) in the injured than the noninjured knee (9.5 mm vs. 6.8 mm). The mean difference (i.e., bias) between laxity scores, for the injured knee, measured at endpoint versus baseline was 0.2±1.0 mm and −0.2±1.1 mm when measured at endpoint versus midpoint, with average typical errors of 0.7 and 0.8 mm and intra-class correlations that were very strong (both r=~0.93). For the same comparisons on the noninjured knee, systematic bias was close to zero (0.1±0.3 and −0.1±0.3 mm, respectively), and both the intra-class correlations were almost perfect (r=~0.99). The current study implicates that repeated Rolimeter measurements are relatively reliable for quantifying anterior knee laxity during the acute time-phases following knee trauma. Hence, the Rolimeter, in combination with manual tests, seems to be a valuable tool for identifying anterior cruciate ligament injuries.

The purpose was to examine the test-retest reliability of the Rolimeter measurement procedure in the acute time phase, following a substantial knee trauma. In total, 15 participants with acute knee trauma were examined by one single observer at three different time-points with the Rolimeter using a maximum force. The selected time-points were: baseline (0–7 days after the trauma), midpoint (3–4 weeks after the trauma), and endpoint (3–4 weeks after the trauma). The anterior-posterior displacement was recorded where the endpoint evaluation was used as the reference value. The mean anterior laxity scores remained constant over the measurement time-points for both knees, with an anterior laxity that was 2.7 mm higher (on average) in the injured than the noninjured knee (9.5 mm vs. 6.8 mm). The mean difference (i.e., bias) between laxity scores, for the injured knee, measured at endpoint versus baseline was 0.2±1.0 mm and −0.2±1.1 mm when measured at endpoint versus midpoint, with average typical errors of 0.7 and 0.8 mm and intra-class correlations that were very strong (both r=~0.93). For the same comparisons on the noninjured knee, systematic bias was close to zero (0.1±0.3 and −0.1±0.3 mm, respectively), and both the intra-class correlations were almost perfect (r=~0.99). The current study implicates that repeated Rolimeter measurements are relatively reliable for quantifying anterior knee laxity during the acute time-phases following knee trauma. Hence, the Rolimeter, in combination with manual tests, seems to be a valuable tool for identifying anterior cruciate ligament injuries.

The purpose was to examine the test-retest reliability of the Rolimeter measurement procedure in the acute time phase, following a substantial knee trauma. In total, 15 participants with acute knee trauma were examined by one single observer at three different time-points with the Rolimeter using a maximum force. The selected time-points were: baseline (0–7 days after the trauma), midpoint (3–4 weeks after the trauma), and endpoint (3–4 weeks after the trauma). The anterior-posterior displacement was recorded where the endpoint evaluation was used as the reference value. The mean anterior laxity scores remained constant over the measurement time-points for both knees, with an anterior laxity that was 2.7 mm higher (on average) in the injured than the noninjured knee (9.5 mm vs. 6.8 mm). The mean difference (i.e., bias) between laxity scores, for the injured knee, measured at endpoint versus baseline was 0.2±1.0 mm and −0.2±1.1 mm when measured at endpoint versus midpoint, with average typical errors of 0.7 and 0.8 mm and intra-class correlations that were very strong (both r=~0.93). For the same comparisons on the noninjured knee, systematic bias was close to zero (0.1±0.3 and −0.1±0.3 mm, respectively), and both the intra-class correlations were almost perfect (r=~0.99). The current study implicates that repeated Rolimeter measurements are relatively reliable for quantifying anterior knee laxity during the acute time-phases following knee trauma. Hence, the Rolimeter, in combination with manual tests, seems to be a valuable tool for identifying anterior cruciate ligament injuries.

The purpose was to examine the test-retest reliability of the Rolimeter measurement procedure in the acute time phase, following a substantial knee trauma. In total, 15 participants with acute knee trauma were examined by one single observer at three different time-points with the Rolimeter using a maximum force. The selected time-points were: baseline (0–7 days after the trauma), midpoint (3–4 weeks after the trauma), and endpoint (3–4 weeks after the trauma). The anterior-posterior displacement was recorded where the endpoint evaluation was used as the reference value. The mean anterior laxity scores remained constant over the measurement time-points for both knees, with an anterior laxity that was 2.7 mm higher (on average) in the injured than the noninjured knee (9.5 mm vs. 6.8 mm). The mean difference (i.e., bias) between laxity scores, for the injured knee, measured at endpoint versus baseline was 0.2±1.0 mm and −0.2±1.1 mm when measured at endpoint versus midpoint, with average typical errors of 0.7 and 0.8 mm and intra-class correlations that were very strong (both r=~0.93). For the same comparisons on the noninjured knee, systematic bias was close to zero (0.1±0.3 and −0.1±0.3 mm, respectively), and both the intra-class correlations were almost perfect (r=~0.99). The current study implicates that repeated Rolimeter measurements are relatively reliable for quantifying anterior knee laxity during the acute time-phases following knee trauma. Hence, the Rolimeter, in combination with manual tests, seems to be a valuable tool for identifying anterior cruciate ligament injuries.

IntroductionJoint haemorrhage is the principal clinical manifestation of haemophilia frequently leading to advanced arthropathy and arthrofibrosis, resulting in severe disability. The degree and prevalence of arthrofibrosis in hemophilic arthropathy is more severe than in other forms of arthropathy. Expression of connective tissue growth factor (CTGF) has been linked to many fibrotic diseases, but has not been studied in the context of haemophilic arthropathy.AimWe aim to compare synovial tissues histologically from haemophilia and osteoarthritis patients with advanced arthropathy in order to compare expression of proteins that are possibly aetiologic in the development of arthrofibrosis.MethodsHuman synovial tissues were obtained from 10 haemophilia and 10 osteoarthritis patients undergoing joint surgery and processed for histology and immunohistochemistry.ResultsAll samples from haemophilia patients had synovitis with hypertrophy and hyperplasia of synovial villi. Histologically, synovial tissues contained hyperplastic villi with increased cellularity and abundant haemosiderin- and ferritin-pigmented macrophage-like cells (HMCs), with a perivascular localization in the sub-surface layer. CTGF staining was observed in the surface layer and sub-surface layer in all haemophilia patients, exclusively co-localizing with HMCs. Quantification showed that the extent of CTGF-positive areas was correlated with the degree of detection of HMCs. CTGF was not observed in any of the samples from osteoarthritis patients.ConclusionUsing histological analysis, we showed that CTGF expression is elevated in haemophilia patients with arthrofibrosis and absent in patients with osteoarthritis. Additionally, we found that CTGF is always associated with haemosiderin-pigmented macrophage-like cells, which suggests that CTGF is produced by synovial A cells following the uptake of blood breakdown products.

IntroductionJoint haemorrhage is the principal clinical manifestation of haemophilia frequently leading to advanced arthropathy and arthrofibrosis, resulting in severe disability. The degree and prevalence of arthrofibrosis in hemophilic arthropathy is more severe than in other forms of arthropathy. Expression of connective tissue growth factor (CTGF) has been linked to many fibrotic diseases, but has not been studied in the context of haemophilic arthropathy.AimWe aim to compare synovial tissues histologically from haemophilia and osteoarthritis patients with advanced arthropathy in order to compare expression of proteins that are possibly aetiologic in the development of arthrofibrosis.MethodsHuman synovial tissues were obtained from 10 haemophilia and 10 osteoarthritis patients undergoing joint surgery and processed for histology and immunohistochemistry.ResultsAll samples from haemophilia patients had synovitis with hypertrophy and hyperplasia of synovial villi. Histologically, synovial tissues contained hyperplastic villi with increased cellularity and abundant haemosiderin- and ferritin-pigmented macrophage-like cells (HMCs), with a perivascular localization in the sub-surface layer. CTGF staining was observed in the surface layer and sub-surface layer in all haemophilia patients, exclusively co-localizing with HMCs. Quantification showed that the extent of CTGF-positive areas was correlated with the degree of detection of HMCs. CTGF was not observed in any of the samples from osteoarthritis patients.ConclusionUsing histological analysis, we showed that CTGF expression is elevated in haemophilia patients with arthrofibrosis and absent in patients with osteoarthritis. Additionally, we found that CTGF is always associated with haemosiderin-pigmented macrophage-like cells, which suggests that CTGF is produced by synovial A cells following the uptake of blood breakdown products.

Essentials Joint bleeding in hemophilia may induce significant remodeling of the extracellular matrix. Biomarkers of collagen turnover were investigated in a F8−/− rat model of hemophilic arthropathy. Biomarkers of cartilage degradation increased significantly during development of arthropathy. Basement membrane and interstitial matrix turnover changed significantly following hemarthrosis. Summary: Background Hemophilic arthropathy is a severe complication of hemophilia. It is caused by recurrent bleeding into joint cavities, which leads to synovial inflammation, fibrosis, cartilage degradation and bone remodeling. Extracellular matrix remodeling of affected tissues is a hallmark of these pathological processes. Objectives The aim of this study was to use serological biomarkers of collagen turnover to evaluate extracellular matrix remodeling in a factor VIII-deficient rat model of hemophilic arthropathy. Methods F8−/− rats and wild-type littermate controls were subjected to repeated knee bleeds induced by needle puncture on days 0 and 14. Development of arthropathy was confirmed by histology after termination on day 28. Serum samples were collected at baseline and throughout the study and analyzed for biomarkers of collagen turnover, including collagens of the basement membrane (type IV collagen), the interstitial matrix (collagen types III, V and VI) and cartilage (type II collagen). Results In F8−/− rats, induced knee bleeding and subsequent development of arthropathy caused significant alterations in collagen turnover, measured as changes in serological biomarkers of basement membrane turnover, interstitial matrix turnover and cartilage degradation. Biomarkers of type II collagen degradation correlated significantly with cartilage degradation and degree of arthropathy. Hemophilic rats had a 50% higher turnover of the basement membrane than wild-type littermates at baseline. Conclusions Joint bleeding and hemophilic arthropathy

Background Translational animal models of hemophilia are valuable for determining the pathobiology of the disease and its co-morbidities (e.g. hemophilic arthropathy, HA). The biologic mechanisms behind the development of HA, a painful and debilitating condition, are not completely understood. We recently characterized a F8(-/-) rat, which could be a new preclinical model of HA. Objectives To establish the F8(-/-) rat as a model of HA by determining if the F8(-/-) rat develops HA resembling human HA after an induced joint bleed and whether a second joint bleed causes further disease progression. Methods Wild-type and F8(-/-) rats were treated with vehicle or recombinant human factor VIII (rhFVIII) prior to a needle-induced joint bleed. Joint swelling was measured prior to injury, the following 7 days and upon euthanasia. Histologic sections of the joint were stained, and athropathic changes identified and scored with regard to synovitis, bone remodelling, cartilage degradation and hemosiderin deposition. Results Vehicle-treated F8(-/-) rats experienced marked joint swelling and developed chronic degenerative joint changes (i.e. fibrosis of the subsynovial membrane, chondrocyte loss and excessive bone remodeling). Treatment with rhFVIII reduced or prevented swelling and degenerative joint changes, returning the F8(-/-) animals to a wild-type phenotype. Conclusion The hemophilic phenotype of the F8(-/-) rat resulted in a persistent hemarthrosis following an induced joint bleed. This caused development of HA resembling human HA, which was prevented by rhFVIII treatment, confirming the potential of the F8(-/-) rat as a model of HA., Background Translational animal models of hemophilia are valuable for determining the pathobiology of the disease and its co-morbidities (e.g. hemophilic arthropathy, HA). The biologic mechanisms behind the development of HA, a painful and debilitating condition, are not completely understood. We recently characterized a F8(-/-) rat, which could be a new preclinical model of HA. Objectives To establish the F8(-/-) rat as a model of HA by determining if the F8(-/-) rat develops HA resembling human HA after an induced joint bleed and whether a second joint bleed causes further disease progression. Methods Wild-type and F8(-/-) rats were treated with vehicle or recombinant human factor VIII (rhFVIII) prior to a needle-induced joint bleed. Joint swelling was measured prior to injury, the following 7 days and upon euthanasia. Histologic sections of the joint were stained, and athropathic changes identified and scored with regard to synovitis, bone remodelling, cartilage degradation and hemosiderin deposition. Results Vehicle-treated F8(-/-) rats experienced marked joint swelling and developed chronic degenerative joint changes (i.e. fibrosis of the subsynovial membrane, chondrocyte loss and excessive bone remodeling). Treatment with rhFVIII reduced or prevented swelling and degenerative joint changes, returning the F8(-/-) animals to a wild-type phenotype. Conclusion The hemophilic phenotype of the F8(-/-) rat resulted in a persistent hemarthrosis following an induced joint bleed. This caused development of HA resembling human HA, which was prevented by rhFVIII treatment, confirming the potential of the F8(-/-) rat as a model of HA.

Background: Treatment of mucosal bleeding (epistaxis, gastrointestinal bleeding, and menorrhagia) and joint bleeding remains problematic in clinically severe von Willebrand disease (VWD). Patients are often unresponsive to treatment (e.g. desmopressin or antifibrinolytic therapy) and may require von Willebrand factor (VWF) replacement therapy. There are little data on the use of prophylaxis in VWD, and none have been applied in a prospective, treatment escalation design. Objective: Evaluate the effect of escalating dose prophylaxis in severe VWD. Methods: Patients eligible for enrollment in this prospective study included those with type 1 VWD with VW factor activity-ristocetin cofactor ratio ≤ 20% and unresponsive to desmopressin, patients with type 2 VWD not responsive to desmopressin and all subjects with type 2B and type 3 VWD. Entry criteria were strictly defined, as were therapy escalation parameters and clinical data collection. Results: Eleven subjects completed the study. Six had type 2A, and five had type 3 VWD. Six patients presented with epistaxis, three with GI bleeding, and two with joint bleeding. Seven had dose escalation above the first level. Among the 10 subjects with evaluable bleeding log data, use of prophylaxis decreased the median annualized bleeding rate from 25 to 6.1 (95% confidence interval of the rate difference: -51.6 to -1.7), and the median annualized bleeding rate was even lower (4.0; 95% confidence interval: -57.5 to -5.3) when the subjects reached their final dosing level. Conclusion: This is the first prospective study to demonstrate that prophylaxis with VW factor concentrates is highly effective in reducing mucosal and joint bleeding rates in clinically severe VWD.

PurposeTo correlate ankle and foot fracture patterns with the presence of tenosynovial fat on computed tomography (CT).Materials and methodsIn this retrospective, cross-sectional, observation study, two blinded musculoskeletal radiologists independently reviewed 89 CT scans of patients with ankle or foot fractures and recorded the presence of fat about Henry's knot, tibialis posterior tendon, and peroneus longus tendon.ResultsThe agreement between the two readers ranged from excellent to substantial. Sixteen to 23 percent of fractures were associated with tenosynovial fat.ConclusionsThe finding of tenosynovial fat following ankle or foot trauma warrants a closer search for a fracture.

The paper discuss approaches to improving methods of medical diagnosis of acute injuries of the knee joint, the use of magnetic resonance imaging (MRI) and arthroscopy., Розглянуто підходи до покращення методики медичної діагностики при гострих ушкодженнях колінного суглоба, використання магнітнорезонансної томографії (МРТ) та артроскопії.

The World Federation of Hemophilia (WFH) 2010 World Congress held in Buenos Aires, Argentina, in July 2010, attracted more than 4,300 participants from 106 countries. This report summarizes two symposia held during the congress. The first, titled "Emerging Co-Morbidities in the Aging Hemophilia Population: Healthcare Challenges and Treatment Opportunities," chaired by Gerry Dolan, MD, and Jussara Almeida Cruz, MD, examined the co-morbidities experienced by the aging hemophilic patient population, such as cardiovascular disease, cancer, arthritis, osteoporosis, hypertension, and obesity. In addition, Bayer's products in preclinical and clinical development were reviewed, including a novel factor VIIa variant and a long-acting factor VIII molecule, i.e., one that has undergone site-specific PEGylation (attachment of polyethylene glycol [PEG] polymer chains to another molecule). The other symposium, titled "Practical Steps to Making Better Care for Hemophilia Patients a Reality," chaired by Carmen Altisent, MD, and Cesar Guerrero, RN, reviewed the steps that hemophilia caregivers can take to improve the care of their patients. Issues such as the treatment of hemarthroses, the role of the research nurse, and the management of pediatric patients transitioning to adulthood were discussed.

Acute haemarthrosis is a frequent type of bleeding in individuals with haemophilia. Delayed and/or inadequate treatment can trigger a series of pathological changes within the joint, leading to a painful and disabling arthropathy. The early management of intra-articular bleeding has the potential to prevent chronic joint disease and may include a combination of factor replacement, rest, ice, rehabilitation and, in certain cases, joint aspiration. Little data are, however, available regarding the optimal management of acute haemarthrosis, especially with respect to replacement therapy and the use of adjunctive therapies (aspiration, avoidance of weight bearing and immobilization, as well as the use of anti-inflammatory medication and embolization). To provide more insight into the management of acute haemarthrosis in patients with haemophilia, a literature review was conducted. Concomitantly, current management was surveyed in 26 European haemophilia comprehensive care centres representing 15 different countries. The review highlights the need for future robust studies to better define the appropriate replacement therapy and the role of adjunctive therapies such as aspiration. The survey reveals much heterogeneity in the management of acute haemarthrosis across the EU. Within the constraints discussed, treatment recommendations are presented that reflect the literature, current practice and the clinical experience of the European Haemophilia Therapy Standardisation Board (EHTSB).

With the availability of clotting factor concentrates, advances in surgical techniques, better implant design, and improvements in postoperative management, total knee arthroplasty has become the treatment of choice for haemophilia patients suffering from end-stage haemophilic knee arthropathy. The success of this surgery is also dependent on close collaborations among the orthopaedic surgeon, the haematologist and the physiotherapist. Although haemophilic patients undergoing this surgery would likely benefit from a targeted rehabilitation programme, its specificities, modalities and limitations have thus far not been extensively studied. Employing the published data of rehabilitation after knee prosthesis in patients with osteoarthritis and haemophilic arthropathy along with clinical experience, the authors present a comprehensive and original review of the role of physiotherapy for patients with haemophilia undergoing knee arthroplasty.

We report the case of a 3-year-old boy with severe haemophilia A presenting with recurrent haemarthroses despite daily infusions of factor VIII delivered through a central venous access device (CVAD). Regular rinsing of the CVAD with heparin, according to a standard protocol, resulted in systemic anticoagulation, as demonstrated by prolonged thrombin time and therapeutic anti-Xa levels. The bleeding symptoms resolved after replacing heparin with a normal saline solution. This case illustrates that heparin administered to maintain CVAD patency should be used with caution in young haemophiliacs. Prolonged thrombin time should alert the physician to this possible CVAD complication.