The role of six biomarkers in diagnosis of hemophilic arthropathy: review of the literature.

The aim of our narrative review of the literature is to identify the role of six important biomarkers: synovial fluid thrombomodulin, fibroblast-like synoviocytes, synovial tissue growth factor , vascular endothelial growth factor in synovium and peripheral blood, urinary C-terminal telopeptide of type II collagen, and synovial fluid tumor necrosis factor alpha. These urinary, serum and synovial biomarkers illustrated should be evaluated in patients with hemophilic arthropathy for early diagnosis of hemophilic arthropathy, because they have important implications in the development of arthrofibrosis, altered inflammatory response and bleeding. Moreover, better knowledge of their biological activity is important to identify possible new biological treatment options.

Tranexamic acid is effective in decreasing postoperative intraarticular bleeding in arthroscopic knee surgery.

: Arthroscopic knee surgery to perform partial meniscectomy and anterior cruciate ligament (ACL) reconstruction is frequent and effective, although a possible complication is postoperative hemarthrosis. When intraarticular bleeding occurs, in addition to the associated pain, the patient usually requires joint aspiration (arthrocentesis) to avoid loss of range of motion (ROM). Sometimes this complication ends up associated with a poor result of surgery due to a loss of ROM. The aim of this narrative review of the literature is to attempt to clarify whether tranexamic acid (TXA) should be utilized in arthroscopic ACL reconstruction and arthroscopic meniscectomy and by what route (intraarticular or intravenous). A number of studies seem to favor the use of intravenous TXA in patients undergoing ACL reconstruction and arthroscopic synovectomy to diminish articular postoperative bleeding and its consequences (pain, swelling, loss of ROM, and the need for arthrocentesis). Regarding the use of intraarticular TXA, one in-vitro study has indicated that TXA in high concentrations is cytotoxic to chondrocytes. Common sense leads me to conclude that until better designed studies can confirm that intraarticular TXA is not cytotoxic to chondrocytes, its use should not be advised. Currently, for patients undergoing arthroscopic ACL reconstruction and arthroscopic meniscectomy, it seems safer to use intravenous TXA.

Topical therapies for knee osteoarthritis.

BACKGROUND: Symptomatic knee osteoarthritis (OA) involves millions of adults around the world. PURPOSE: To analyze the effectiveness and tolerability of topical therapies and their contemporary placement in knee OA management criteria. METHODS: A Cochrane Library and PubMed (MEDLINE) search related to the role of topical therapies in knee OA was carried out. RESULTS: Many types of local therapy have been reported, including nonsteroidal anti-inflammatory drugs (NSAIDs) like diclofenac and ketoprofen; capsaicin, cream containing glucosamine sulfate, chondroitin sulfate, and camphor; nimesulide; civamide cream 0.075%; menthol; drug-free gel containing ultra-deformable phospholipid vesicles (TDT 064); 4Jointz utilizing Acteev technology; herbal therapies; gel of medical leech (Hirudo medicinalis) saliva extract; and gel prepared using Lake Urmia mud. One systematic review showed that topical diclofenac and topical ketoprofen can alleviate pain. However, another systematic review found that topical diclofenac and ketoprofen had limited efficacy in knee OA at 6 to 12 weeks. Many studies with a low level of evidence have reported some pain mitigation using the rest of aforementioned topical therapies. CONCLUSIONS: Although some controversy exists on the role of topical NSAIDs, current management guidelines advise topical NSAIDs as an option and even first-line therapy for knee OA treatment, particularly among elderly patients. Topical NSAIDs may be contemplated as similar options to oral NSAIDs and are associated with fewer gastrointestinal complications when compared with oral NSAIDs. Caution should be taken with the use of both topical and oral NSAIDs, including close adherence to dosing regimens and monitoring, especially for patients with previous complications of NSAIDs. The role of other topical therapies needs further research.

Recommendations on multidisciplinary management of elective surgery in people with haemophilia.

Planning and undertaking elective surgery in people with haemophilia (PWH) is most effective with the involvement of a specialist and experienced multidisciplinary team (MDT) at a haemophilia treatment centre. However, despite extensive best practice guidelines for surgery in PWH, there may exist a gap between guidelines and practical application. For this consensus review, an expert multidisciplinary panel comprising surgeons, haematologists, nurses, physiotherapists and a dental expert was assembled to develop practical approaches to implement the principles of multidisciplinary management of elective surgery for PWH. Careful preoperative planning is paramount for successful elective surgery, including dental examinations, physical assessment and prehabilitation, laboratory testing and the development of haemostasis and pain management plans. A coordinator may be appointed from the MDT to ensure that critical tasks are performed and milestones met to enable surgery to proceed. At all stages, the patient and their parent/caregiver, where appropriate, should be consulted to ensure that their expectations and functional goals are realistic and can be achieved. The planning phase should ensure that surgery proceeds without incident, but the surgical team should be ready to handle unanticipated events. Similarly, the broader MDT must be made aware of events in surgery that may require postoperative plans to be changed. Postoperative rehabilitation should begin soon after surgery, with attention paid to management of haemostasis and pain. Surgery in patients with inhibitors requires even more careful preparation and should only be undertaken by an MDT experienced in this area, at a specialized haemophilia treatment centre with a comprehensive care model.

Total elbow arthroplasty in haemophilia.

INTRODUCTION: Advanced haemophilic arthropathy of the elbow can be a devastating manifestation of severe haemophilia with significant implications for activities of daily living. AIM: To summarize the currently available data on total elbow arthroplasty (TEA) for haemophilic arthropathy of the elbow, to draw comparisons to TEA for other indications, and to outline some considerations regarding TEA in this unique population. METHODS: A narrative review of the literature has been performed. RESULTS: The scant data regarding outcomes of TEA for haemophilic arthropathy are limited to small case series and case reports. A review of the available literature shows that, while pain relief and patient satisfaction are promising, variable outcomes with significant complications and infection rates may discourage routine use of TEA for haemophilic arthropathy of the elbow. CONCLUSION: While patients with severe haemophilic arthropathy of the elbow are likely to make gains in terms of pain control and range of motion following TEA, there are insufficient data to routinely recommend its use. Complication and infection rates are concerning, and the lack of survival analysis data makes it difficult to quantify the benefit to the patient in light of the risks and resources involved in the procedure.

The ICF (International Classification of Functioning, Disability and Health) developed by the WHO for measuring function in hemophilia.

INTRODUCTION: Assessment of the disease in people with hemophilia (PWH) must include an analysis of functioning. Researchers have done a lot of work over the last two decades in developing disease specific assessment tools in hemophilia - some of them based on the ICF (International Classification of Functioning, Disability and Health). AREAS COVERED: This article is a narrative review of the ICF developed by the World Health Organization (WHO) in the context of hemophilia. Expert commentary: The WFH has developed a website with a 'compendium of assessment tools' based on the ICF. The ICF developed by the WHO makes it possible to propose an approach that prioritizes capacities over difficulties. This article is intended to motivate physicians who treat PWH to incorporate the ICF into their assessments. A generalized use of the ICF will provide a common communication context. The ICF developed by the WHO should be used in hemophilia.

Radiosynovectomy in haemophilic synovitis of elbows and ankles: Is the effectiveness of yttrium-90 and rhenium-186 different?

BACKGROUND: Radiosynovectomy (RS) reduces the number of haemarthroses and the synovial size in chronic haemophilic synovitis. The purpose of this study was to quantitatively compare the effectiveness of two types of RS (yttrium-90 vs. rhenium-186) in terms of the objective improvement of haemarthroses and synovial size. METHODS: Seventy RSs were performed in 70 joints (44 elbows, 26 ankles) of 70 haemophiliacs diagnosed with chronic synovitis. Yttrium-90 was used in 21 joints and rhenium-186 was used in 49 joints. The mean patient age was 20.61 years. RESULTS: RS resulted in significant improvement in the three variables studied (six months before RS vs. six months after RS), namely in the number of episodes of haemarthrosis (67.8% improvement); the size of the synovium as measured by means of a clinical scale (43.8% improvement) and imaging techniques in millimetres (26.7% improvement). We did not find significant statistical differences between yttrium-90 and rhenium-186 regarding their efficacy. No correlation was found between the results and other variables: age, joint (ankle or elbow), presence or absence of radiological involvement, type of haemophilia (A or B), grade of haemophilia (mild, moderate or severe), previous haematological treatment (on demand or prophylaxis), and the presence or absence of inhibitor CONCLUSIONS: Yttrium-90 RS and rhenium-186 RS were equally effective in reducing the number of haemarthroses and the size of the synovium in ankles and elbows in the short-term (6 months). No correlation was found between the results and other patients' characteristics.

Hindfoot fusion in haemophilic arthropathy: 6-year mean follow-up of 41 procedures performed in 28 adult patients.

INTRODUCTION: Haemophilic arthropathy of the ankle is rare disorder caused by recurrent haemarthorses beginning in early adulthood. AIM: Our aim was to evaluate the fusion rate of various techniques of hindfoot fusion using internal fixation for the treatment of haemophilic arthropathy of the hindfoot. METHODS: We have evaluated the fusion rate of various techniques of hindfoot (tibiotalar and subtalar joints) fusion for the treatment of haemophilic arthropathy of the hindfoot. Twenty-eight patients underwent a total of 41 procedures. Thirty-four ankle (tibiotalar) fusions were performed, seven were done arthroscopically, six using a minimal access approach and 21 with an open approach. There were two isolated subtalar fusions, three combined tibiotalar and subtalar fusions, one of which included a talonavicular fusion at the second operation. There was one peritalar ankle fusion (tibiotalar, subtalar and talonavicular). The mean age at operation was 40.3 years (SD, 12.3; range, 18.7-65.7 years). The mean time to last follow-up was 77 months (SD, 50.4; range, 7-190). RESULTS: The overall non-union rate was 9.7%. All non-unions occurred in tibiotalar fusions (there were no non-unions in cases of subtalar or talonavicular fusion). A single deep infection (2.4%) occurred in an arthroscopically fused ankle. The revision rate was 4.8% (2 cases) and was carried out for non-unions. Both revisions were successful. CONCLUSION: Hindfoot arthrodesis in patients with haemophilic ankle arthropathy provides a high fusion rate with few complications. Arthroscopic tibiotalar fusion did not result in shorter hospital stays. Revision surgery for the haemophilic hindfoot is successful, and fusion of the entire hindfoot can be achieved without complications.

The current role of orthoses in treating haemophilic arthropathy.

INTRODUCTION: Haemophilic arthropathy (HA) is an inevitable consequence of repeated haemarthroses in people with haemophilia, and principally affects their ankles, knees and elbows. It is advisable that haematological treatment be complemented with rehabilitation therapy and surgery. Orthoses are devices that are used within the framework of rehabilitation, in order to change the functional or structural characteristics of the neuromusculoskeletal system. MATERIALS AND METHODS: This article reviews the design, the materials and characteristics of orthoses and the indications for the various orthoses used in HA. Ankle, knee, elbow orthoses, insoles, footwear modifications and orthopedic shoes are discussed. RESULTS: Orthoses can control or prevent joint movement, stabilise a specific joint or relieve the load or stress on it. These devices must be prescribed by a physician within the framework of rehabilitation. Recommendations for the proper selection and use of orthoses are highly complex. DISCUSSION: To maximise the benefits of this mode of therapy, a profound understanding of anatomy and biomechanics is crucial, as is an understanding of the devices available for the various joints that may be affected by HA (ankles-feet, knees, elbows). CONCLUSIONS: Orthotic devices can reduce pain and improve quality of life of people with HA, delaying surgery in many cases.

Bone health in persons with haemophilia.

INTRODUCTION: As the population of patients with haemophilia (PWH) ages, healthcare providers are required to direct greater attention to age-related co-morbidities. Low bone mineral density (BMD) is one such co-morbidity where the incidence not only increases with age, but also occurs with greater frequency in PWH. AIM: To review risk factors for low BMD, and strategies to promote bone health and identify patients who would benefit from screening for osteoporosis and subsequent treatment. METHODS: A narrative review of the literature was performed in MEDLINE with keywords haemophilia, bone density, osteoporosis and fracture. Reference lists of retrieved articles were also reviewed. RESULTS: Low BMD occurs more commonly in PWH than the general population and is most likely the result of a combination of risk factors.  Steps to promote bone health include preventing haemarthrosis, encouraging regular exercise, adequate vitamin D and calcium intake, and avoiding tobacco and excessive alcohol intake. Adults 50 years of age and older with haemophilia and those younger than 50 years with a fragility fracture or increased fracture risk based on FRAX (The Fracture Risk Assessment Tool), regardless of haemophilia severity, should be screened for low BMD using dual x-ray absorptiometry (DXA). Once osteoporosis is diagnosed based on DXA, fracture risk should guide treatment. Currently, treatment is similar to those without haemophilia and most commonly includes bisphosphonates. CONCLUSION: Haemophilia care providers should promote adequate bone formation during childhood and reduce bone loss during adulthood as well as identify patients with low BMD that would benefit from therapy.

Safety of radiation exposure after radiosynovectomy in paediatric patients with haemophilia.

Many paediatric patients with haemophilia who might benefit from radiosynovectomy (RS) for the control of synovitis do not undergo the procedure as there is controversy in the literature regarding the safety of radiation exposure after two cases of acute lymphocytic leukaemia in children with haemophilia treated with (32) P RS were reported. The purpose of this review was to analyse the safety of RS in paediatric patients with haemophilia and provide a risk-benefit assessment, which practitioners could apply to their patients. Children undergoing knee RS receive a radiation dose of approximately 0.74 mSv (90 megabecquerels-MBq) and elbow and ankle RSs a dose of approximately 0.32 mSv (30-40 MBq). The radiation dose from natural sources is approximately 2 mSv and the recommended limit for patients (apart from natural sources) is 1 mSv per year. The lifetime cancer risk increases about 0.5% per 100 mSv per year. Considering the risks and benefits of RS, the authors recommend that clinicians consider this procedure in children with inhibitors or in patients without inhibitors when bleeding is recurrent and persistent despite aggressive factor replacement.

The assessment of outcome after total knee arthroplasty: are we there yet?

The routine use of patient reported outcome measures (PROMs) in evaluating the outcome after arthroplasty by healthcare organisations reflects a growing recognition of the importance of patients' perspectives in improving treatment. Although widely embraced in the NHS, there are concerns that PROMs are being used beyond their means due to a poor understanding of their limitations. This paper reviews some of the current challenges in using PROMs to evaluate total knee arthroplasty. It highlights alternative methods that have been used to improve the assessment of outcome.

El tratamiento quirúrgico de las roturas de bíceps distal mediante técnica Endo-Button asociada a tornillo interferencial permite un programa de rehabilitación acelerado: caso clínico / Surgical treatment of distal biceps tendon rupture through the Endo-Button technique associated with interferential screw allows an accelerated rehabilitation program. A case report

Se presenta el caso de un varón de 53 años que presentó una rotura del tendón bicipital distal derecho. Se llevó a cabo la reinserción quirúrgica del tendón distal del bíceps en la tuberosidad radial, por vía anterior, mediante técnica de Endo-Button. El postoperatorio cursó sin complicaciones, inmovilizándose el codo con un vendaje durante 2 semanas. Tras ser valorado por el especialista en Rehabilitación, se estableció un programa terapéutico individualizado, de inicio precoz y de carácter acelerado. Los objetivos fueron 2: ganar la máxima amplitud articular con movilización inmediata durante la primera fase y lograr un refuerzo muscular y propioceptivo con posterioridad. El programa rehabilitador le permitió lograr la recuperación funcional completa y conseguir una musculatura bicipital competente en un periodo de 10 semanas. El paciente pudo retomar todas las actividades, cotidianas, laborales y deportivas, que realizaba antes de la lesión (AU)

We present the case of a 53-year-old man with a distal biceps tendon rupture in his right upper limb. Endo-Button repair was performed by reattaching the distal biceps tendon in the radial tuberosity through an anterior approach. There were no complications during the postoperative period. The elbow was immobilized with a bandage for 2 weeks. After the patient was assessed by the rehabilitation physician, we decided to carry out an early individualized accelerated therapeutic program. The goals of treatment were to gain the maximum range of motion by immediate mobilization in a first phase, and then to achieve adequate muscular and proprioceptive reinforcement. The rehabilitation program allowed the patient to achieve full functional recovery with a competent biceps muscle in 10 weeks. The patient was able to return to all his activities (daily living, work, sport) before the tendon rupture (AU)

Radiosynovectomy in haemophilia: long-term results of 500 procedures performed in a 38-year period.

BACKGROUND: Radiosynovectomy (RS) can reduce the number of haemarthroses in chronic haemophilic synovitis. The purpose of this study was to assess the effectiveness of RS in terms of the objective improvement of five parameters (number haemarthroses, articular pain, degree of clinical synovitis, clinical score of the World Federation of Haemophilia (WFH), and radiological score of the WFH. METHODS: In a 38-year period (1976-2013), five hundred radiosynovectomies were performed in 443 joints of 345 patients with haemophilia diagnosed with chronic synovitis. The mean patient age was 23.7 years (range, 6-53). The mean follow-up was 18.5 years (range: 6 months-38 years). The RS was carried out with either yttrium-90 or rhenium-186. We performed 1 to 3 injections (RS-1, RS-2, RS-3), with a 6-month interval between them. RESULTS: RS resulted in significant improvement in all the parameters studied, except in the WFH radiologic score that showed no improvement. On average, the number of haemarthroses decreased by 64.1% and articular pain decreased by 69.4%. The degree of synovitis showed a reduction of 31.3%. The WFH clinical score revealed an improvement of 19%. The WFH radiological score showed no improvement. There were four complications (0.9%) of RS. Twenty-eight (6.3%) joints eventually had to be subjected to arthroscopic synovectomy or total knee replacement (TKR). No cancer was observed in this group of patients during the 38-year period. CONCLUSIONS: Radiosynovectomy (RS) is an effective, safe, minimally invasive, well tolerated procedure in the long-term for the treatment of chronic haemophilic synovitis. Moreover, it is very easy to perform. The knee required more injections than the elbow or the ankle and more severe synoviums required a higher number of RS procedures.

The knee in severe haemophilia with special emphasis on surgical/invasive procedures.

Close collaboration between haematologists, orthopaedic surgeons, rehabilitation physicians, pediatricians, pharmacist, radiologist, pain specialist, psychologists, physiotherapists and nurses is essential for the proper handling of knee problems in haemophiliac patients. The ideal scenario would be for the primary prophylaxis (prevention of the disease) to prevent major degenerative changes that we still see so frequently in this type of patients. Until we achieve this we will continue having to perform multiple invasive orthopaedic procedures, such as articular punctures (joint aspiration) to drain haemarthrosis, radiosynovectomies, arthroscopic synovectomies, tendon lenghtenings, realignment osteotomies and total knee replacements (primary and revision) on the knees of people with haemophilia. As a result of this, we will improve the quality of life of haemophiliac patients with orthopaedic knee problems. The rate of potential complications following knee orthopaedic procedures, especially in patients with inhibitors, must not be underestimated.

Is radiosynovectomy (RS) effective for joints damaged by haemophilia with articular degeneration in simple radiography (ADSR)?

BACKGROUND: Radiosynovectomy (RS) is known to be effective in the treatment of chronic haemophiliac synovitis. Its effectiveness may, however, be different when the joint treated shows articular degeneration in simple radiography (ADSR). PURPOSE: The purpose of this study was to investigate the effectiveness or otherwise of RS in the presence of ADSR. To this end, the objective improvement in five joint parameters (haemarthrosis, joint pain, range of motion, muscle strength and synovial size) has been analysed with respect to the pre-existence or otherwise of ADSR in the articulation treated. MATERIALS AND METHODS: An observational retrospective cohort study was conducted. Between January 1993 and December 2006, RS was performed on 78 people with haemophilia. Their average age was 18 (range 7-51). RS procedures were performed on 104 different joints; some joints required more than one injection (a maximum of 3 were given, with a 6-month interval between them), which we refer to respectively as RS-1, RS-2, RS-3, resulting in a total of 156 procedures. The isotopes used were (90)Y on 107 occasions and (186)Re in 49 injections. RESULTS: RS treatment reduced the frequency of haemarthroses, reduced joint pain and reduced synovial size, and resulted in improved muscle strength and range of motion both in joints with ADSR (N=86) and in those without ADSR (N=18). However, no articulation without ADSR required RS-3. CONCLUSION: The five parameters studied improved to an equal degree in joints with ADSR and without ADSR. No joint without ADSR required RS-3; this was the only difference our study found between joints without ADSR and those with ADSR at the time of the RS.