The hidden joint in children with haemophilia on prophylaxis.

Prophylaxis is the gold standard treatment for children with haemophilia (CWH). MRI studies revealed joint damage, even with this treatment; this suggests the presence of subclinical bleeding. In the case of children with haemophilia, it is relevant to detect early signs of joint damage, as this allows the medical team to provide the appropriate treatment and follow-up, in order to avoid arthropathy development and its consequences. The aim of this study is to detect the hidden joint in children with haemophilia on prophylaxis (CWHP) and analyse, by age group, which joint is the most affected. We define the hidden joint in CWH on prophylaxis as the joint that presents joint damage secondary to repetitive bleeding episodes and is detected in the joint evaluation, despite being asymptomatic or with mild symptoms. It is most commonly caused by repetitive subclinical bleeding. METHODS: This was an observational, analytical, cross-sectional study of 106 CWH on prophylaxis treated in our centre. Patients were divided according to age and type of treatment. Joint damage was defined as a HEAD-US score ≥ 1. RESULTS: Patients' median age was 12 years. All had severe haemophilia. The median age of onset of prophylaxis was 2.7. Forty-seven (44.3 %) patients received primary prophylaxis (PP) and 59 (55.7 %), secondary prophylaxis. Six hundred and thirty-six joints were analysed. Type of prophylaxis and joint involvement showed statistically significant differences (p < 0.001). However, patients on PP had a greater number of damaged joints at older ages. Twenty-two % (140) of the joints scored ≥1 on HEAD-US. Cartilage was most frequently involved, followed by synovitis, and bone damage. We observed a greater frequency and degree of arthropathy in subjects aged 11 and above. Sixty (12.7 %) joints showed a HEAD-US score ≥ 1, with no history of bleeding. The ankle was the most affected joint, representing the hidden joint according to our definition. CONCLUSION: Prophylaxis is the best treatment for CWH. However, symptomatic or subclinical joint bleeding may occur. The routine evaluation of joint health is relevant, particularly, of the ankle. In our study, early signs of arthropathy according to age and type of prophylaxis were detected by HEAD-US.

Nonsteroidal Anti-Inflammatory Drugs and Oral Corticosteroids Mitigated the Risk of Arthrofibrosis After Total Knee Arthroplasty.

BACKGROUND: The role of medications to prevent arthrofibrosis following total knee arthroplasty (TKA) remains unclear. We investigated the effect of common oral medications with reported antifibrotic properties on preventing arthrofibrosis and manipulation under anesthesia (MUA) following primary TKA. METHODS: Using our total joint registry, 9,771 patients (12,735 knees) who underwent TKA with cemented, posterior-stabilized, and metal-backed tibial components from 2000 to 2016 were identified. Arthrofibrosis, defined as range of motion (ROM) ≤90° for ≥12 weeks postoperatively or as ROM ≤90° requiring MUA, was diagnosed in 454 knees (4%) and matched 1:2 to controls. Mean age was 62 years (range, 19 to 87) and 57% were women. The majority of operative diagnoses were osteoarthritis. Perioperative use of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors (statins), angiotensin converting enzyme inhibitors (ACE inhibitors), angiotensin II receptor blockers (ARBs), oral corticosteroids, antihistamines, and nonsteroidal anti-inflammatory drugs (NSAIDs) were manually confirmed. Medication effect in preventing arthrofibrosis and MUA was assessed using adjusted multivariable analyses. Mean follow-up was 8 years (range, 2 to 20). RESULTS: Reduced risk of arthrofibrosis was associated with perioperative NSAID use (odds ratio (OR) 0.67, P = .045). A similar trend was observed with perioperative corticosteroids (OR 0.52, P = .098). Corticosteroids were associated with reduced risk of MUA (OR 0.26, P = .036), and NSAIDs trended towards reducing MUA (OR 0.69, P = .11). CONCLUSION: This investigation determined that perioperative NSAID use was associated with reduced risk of arthrofibrosis and trended towards reduced risk of subsequent MUA. Similarly, oral corticosteroids were associated with reduced risk of MUA and trended towards reduced risk of arthrofibrosis.

Avaliação do perfil clínico-terapêutico e da resposta à profilaxia dos portadores de hemofilia A e B em um centro de referência no Ceará / Evaluation of the clinical-therapeutic profile and the response to prophylaxis of patients with hemophilia A and B in a reference center in Ceará

Objetivo: Avaliar o perfil clínico-terapêutico e a resposta à profilaxia em pacientes hemofílicos A e B em um centro de referência no Ceará. Métodos: Estudo de coorte retrospectivo, com dados de 133 hemofílicos A e B, em profilaxia entre 2016 e 2021, por meio de prontuários médicos e sistema Web Coagulopatias. Resultados: Os pacientes todos do sexo masculino em sua maioria foram hemofílicos A (93,2%), na forma grave, residentes em Fortaleza, com maior prevalência do município de Guaiúba. A maioria fazia uso de Fator VIII recombinante e em profilaxia secundária, em relação ao comprometimento articular a maioria não apresentou relato de hemartroses (66,9%), articulação-alvo (87,9%) ou artropatia (54,9%), porém os hemofílicos em profilaxia terciária apresentaram um maior comprometimento articular em relação a profilaxia primária e secundária. Verificou-se uma correlação negativa entre o tempo de profilaxia e a dose de fator utilizada, demonstrando que quanto maior o tempo de profilaxia menor a dose do fator utilizada. Um total de 13 hemofílicos A grave desenvolveram inibidor de fator VIII realizando imunotolerância (ITI) com sucesso total em 84,6%. Por meio da curva ROC, foi verificado uma associação entre a necessidade de ITI e a dose de fator de coagulação, com acurácia de 67,7% de que o uso de doses maiores de fator predispõe ao desenvolvimento de inibidores. Conclusão: Os dados do estudo permitem inferir que quanto mais precoce o tratamento de profilaxia menor é comprometimento articular, dose do fator utilizada e menor predisposição de desenvolver inibidores dos fatores da coagulação.

Objective: to evaluate the clinical-therapeutic profile and response to prophylaxis in hemophiliac A and B patients at a referral center in Ceará. Methods: Retrospective cohort study, with data from 133 hemophiliacs A and B, undergoing prophylaxis between 2016 and 2021, using medical records and the Web Coagulopathies system. Results: Most of the patients were male patients with severe hemophilia A (93.2%), residing in Fortaleza, with a higher prevalence in the city of Guaiúba. Most made use of recombinant Factor VIII and in secondary prophylaxis, in relation to joint involvement, the majority did not report hemarthroses (66.9%), target joint (87.9%) or arthropathy (54.9%). however, hemophiliacs on tertiary prophylaxis showed greater joint impairment in relation to primary and secondary prophylaxis. There was a negative correlation between the prophylaxis time and the factor dose used, demonstrating that the longer the prophylaxis time, the lower the factor dose used. A total of 13 severe A hemophiliacs developed factor VIII inhibitor performing immunotolerance (ITI) with total success in 84.6%. Using the ROC curve, an association was verified between the need for ITI and the dose of coagulation factor, with an accuracy of 67.7% that the use of higher doses of factor predisposes to the development of inhibitors. Conclusion: The study data allow us to infer that the earlier the prophylaxis treatment, the less joint impairment, the dose of the factor used and the less predisposition to develop coagulation factor inhibitors.

[Prevention, physiotherapeutic preoperative and postoperative treatment and rehabilitation of arthrofibrosis]. / Prävention, physiotherapeutische prä- und postoperative Behandlung sowie Rehabilitation der Arthrofibrose.

The physiotherapeutic and rehabilitative treatment of patients suffering from primary arthrofibrosis following total joint replacement or joint reconstruction is challenging for both patients and therapists. It can be successful if basic principles are applied. The necessary treatment techniques are presented in detail immediately postoperatively and in the subsequent rehabilitation process.

Efficacy of mupirocin, neomycin and octenidine for nasal Staphylococcus aureus decolonisation: a retrospective cohort study.

BACKGROUND: Periprosthetic joint infection (PJI) causes significant morbidity. Methicillin sensitive Staphylococcus aureus (MSSA) is the most frequent organism, and the majority are endogenous. Decolonisation reduces PJIs but there is a paucity of evidence comparing treatments. Aims; compare 3 nasal decolonisation treatments at (1) achieving MSSA decolonisation, (2) preventing PJI. METHODS: Our hospital prospectively collected data on our MSSA decolonisation programme since 2013, including; all MSSA carriers, treatment received, MSSA status at time of surgery and all PJIs. Prior to 2017 MSSA carriers received nasal mupirocin or neomycin, from August 2017 until August 2019 nasal octenidine was used. RESULTS: During the study period 15,958 primary hip and knee replacements were performed. 3200 (20.1%) were MSSA positive at preoperative screening and received decolonisation treatment, 698 mupirocin, 1210 neomycin and 1221 octenidine. Mupirocin (89.1%) and neomycin (90.9%) were more effective at decolonisation than octenidine (50.0%, P < 0.0001). There was no difference in PJI rates (P = 0.452). CONCLUSIONS: Mupirocin and neomycin are more effective than octenidine at MSSA decolonisation. There was poor correlation between the MSSA status after treatment (on day of surgery) and PJI rates. Further research is needed to compare alternative MSSA decolonisation treatments.

Compliance with Early Long-Term Prophylaxis Guidelines for Severe Hemophilia A.

OBJECTIVES: To evaluate the applicability and compliance with guidelines for early initiation of long-term prophylaxis in infants with severe hemophilia A and to identify factors associated with guideline compliance. STUDY DESIGN: This real-world, prospective, multicenter, population-based FranceCoag study included almost all French boys with severe hemophilia A, born between 2000 and 2009 (ie, after guideline implementation). RESULTS: We included 333 boys in the study cohort. The cumulative incidence of long-term prophylaxis use was 61.2% at 3 years of age vs 9.5% in a historical cohort of 39 boys born in 1996 (ie, before guideline implementation). The guidelines were not applicable in 23.1% of patients due to an early intracranial bleeding or inhibitor development. Long-term prophylaxis was delayed in 10.8% of patients. In the multivariate analysis, 2 variables were significantly associated with "timely long-term prophylaxis" as compared with "delayed long-term prophylaxis": hemophilia treating center location in the southern regions of France (OR 23.6, 95% CI 1.9-286.7, P = .013 vs Paris area) and older age at long-term prophylaxis indication (OR 7.2 for each additional year, 95% CI 1.2-43.2, P = .031). Long-term prophylaxis anticipation was observed in 39.0% of patients. Earlier birth year (OR 0.5, 95% CI 0.3-0.8, P = .010 for birth years 2005-2009 vs 2000-2004) and age at first factor replacement (OR 1.9 for each additional year, 95% CI 1.2-3.0, P = .005) were significantly associated with "long-term prophylaxis guideline compliance" vs "long-term prophylaxis anticipation." CONCLUSIONS: This study suggests that long-term prophylaxis guidelines are associated with increased long-term prophylaxis use. However, early initiation of long-term prophylaxis remains a challenge.

Impact of the HEAD-US Scoring System for Observing the Protective Effect of Prophylaxis in Hemophilia Patients: A Prospective, Multicenter, Observational Study

Objective: This study aimed to observe the preventive effect of prophylactic treatment on joint health in people with hemophilia (PwH) and to investigate the importance of integration of ultrasonographic examination into clinical and radiological evaluation of the joints. Materials and Methods: This national, multicenter, prospective, observational study included male patients aged ≥6 years with the diagnosis of moderate or severe hemophilia A or B from 8 centers across Turkey between January 2017 and March 2019. Patients were followed for 1 year with 5 visits (baseline and 3th, 6th, 9th, and 12th month visits). The Hemophilia Joint Health Score (HJHS) was used for physical examination of joints, the Pettersson scoring system was used for radiological assessment, point-of-care (POC) ultrasonography was used for bilateral examinations of joints, and the Hemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) score was used for evaluation of ultrasonography results. Results: Seventy-three PwH, of whom 62 had hemophilia A and 11 had hemophilia B, were included and 24.7% had target joints at baseline. The HJHS and HEAD-US scores were significantly increased at the 12th month in all patients. These scores were also higher in the hemophilia A subgroup than the hemophilia B subgroup. However, in the childhood group, the increment of scores was not significant. The HEAD-US total score was significantly correlated with both the HJHS total score and Pettersson total score at baseline and at the 12th month. Conclusion: The HEAD-US and HJHS scoring systems are valuable tools during follow-up examinations of PwH and they complement each other. We suggest that POC ultrasonographic evaluation and the HEAD-US scoring system may be integrated into differential diagnosis of bleeding and long-term monitoring for joint health as a routine procedure.

Angiotensin Receptor Blockers Were Not Associated With Decreased Arthrofibrosis After Total Knee Arthroplasty.

Stiffness after total knee arthroplasty (TKA) remains a challenging problem. Angiotensin receptor blockers (ARBs) have been associated with decreased muscle fibrosis. The aim of this study was to evaluate whether perioperative use of ARBs was associated with a reduction in arthrofibrosis and manipulation under anesthesia (MUA) in patients undergoing primary TKA at 90 days and 1 year postoperative. In this retrospective study, the authors used a national database to evaluate patients undergoing TKA for primary osteoarthritis from 2007 to 2017. They evaluated patients with filled prescriptions for ARBs within the study time frame and the specific type of ARB and its association with arthrofibrosis and MUA. After adjusting for age, sex, a comorbidity index, and obesity, any ARB or specific ARBs were not associated with a reduction in the rate of arthrofibrosis or MUA after TKA (P≥.05). Male sex, age 55 years or older, and obesity were associated with a reduction in the rate of arthrofibrosis and MUA after TKA (P≤.05). Studies should be performed to evaluate ARBs to see whether there is a more specific role in preventing joint stiffness in certain patient subpopulations following TKA. [Orthopedics. 2021;44(2):e274-e280.].

[Prevention and treatment of bearing dislocation of mobile-bearing unicompartmental knee arthroplasty].

Bearing dislocation is a special complication of mobile-bearing unicompartmental arthroplasty, caused by many factors, such as imbalance of the flexion and extension gap, malposition of components, impingement by the remaining osteophytes and cement, damage or delayed chronic laxity of medial collateral ligament, traumatic accident and habitual high knee flexion. It can be reduced by strictly controlling the operation indications before operation, osteotomy and implanting the prosthesis accurately while protecting the medial collateral ligament during operation, actively guiding the appropriate rehabilitation actions and activity intensity of patients after operation. Treatment should be individualized according to the causes and individual conditions of patients.

Physical activity levels in men with Haemophilia-A single centre UK survey.

INTRODUCTION: Historically persons with haemophilia (PWH) were not encouraged to participate in exercise due to the risk of bleeding and the lack of factor products available. This has now changed, and the availability of safe products allows PWH to be active and participate in sports. Studies have found that exercise has a positive effect on pain, joint health and movement with PWH. AIM: To record the amount and types of physical activity undertaken by a haemophilia population at a single treatment centre. METHODS: An observational cross-sectional study to assess physical activity and quality of life of all registered patients over the age of 18 at the Oxford Haemophilia and Thrombosis Centre. Participants were posted questionnaires including the International Physical activity Questionnaire (IPAQ), Haemophilia Activity List (HAL), EQ-5D-5L and asked to list their physical activities. RESULTS: A total of 256 questionnaires were sent, with a 40% response rate for severe and 28% for mild patients. 85% met the UK physical activity guidelines. Sedentary behaviour for an average weekday was 6.4 hours, and weekends were 5.3 hours. Joint disease and severity type influenced the amount of activity undertaken, together with values for HAL and EQ-5D-5L. Twenty two types of activities were listed. CONCLUSION: It is encouraging to see the amount of physical activity PWH participate in, however, time spent in a sedentary state needs monitoring. PWH want to be active and the challenge for caregivers is to find activities they can do and strategies to maintain participation.

Tissue-inhibitors of metalloproteinase-1 and vascular-endothelial growth-factor in severe haemophilia A children on low dose prophylactic recombinant factor VIII: Relation to subclinical arthropathy.

BACKGROUND: Subclinical synovitis occur long before clinical haemophilic arthropathy (HA). New biomarkers are needed for early detection of HA. AIM: To compare the levels of tissue inhibitors of metalloproteinase-1 (TIMP-1) and vascular endothelial growth factor (VEGF)in severe haemophilia A boys on prophylaxis and on-demand therapy to healthy boys and correlate them with the haemophilia joint health score (HJHS) & the Denver magnetic resonance imaging (MRI) scale; hence, determine their values in early detection of HA. METHODS: Haemophilia joint health score, serum TIMP-1, VEGF and Denver MRI score were assessed in 50 boys with severe haemophilia A (31 on prophylactic factor VIII therapy (62%) with a dose of 15 IU/kg/twice weekly) and 50 age-matched healthy boys. RESULTS: Boys with severe haemophilia A had significantly higher TIMP-1 240 ng/mL, SD200-350 (P < .001) and VEGF 600 pg/mL, SD400-1100 (P < .001). Their mean HJHS was 4.5 ± 3.0 (0-11) and their mean Denver MRI score was 5.55 ± 1.6 (2.00-8.00). A significant positive correlation was found between TIMP-1 and VEGF (P < .001), BMI Z-score (P = .029), HJHS (P = .041)and total MRI score (<.001). Significant correlations were found between VEGF and age (P < .001), HJHS (P = .003) and total MRI score (P < .001). Boys with severe haemophilia A on prophylaxis therapy had significantly lower HJHS (P = .021), VEGF (P < .001), TIMP-1 (P = .002) and total MRI score (P = .021) than those on on-demand therapy. Receiver operating characteristic curve, defined a cut-off value of 160 ng/mL for TIMP-1 with a sensitivity of 90% and specificity of 60% and that of 350 pg/mL for VEGF with a sensitivity of 78% and specificity of 88% for discrimination between severe haemophilia A and healthy boys. CONCLUSION: Vascular endothelial growth factor and TIMP-1 can be used for early detection of HA. Further prospective studies should include larger study populations. In addition, studies should address the role of various anti-VEGFs as potential therapy for HA and their impact on prevention and treatment of HA.

Effect of triamcinolone acetonide on stiffness after surgical treatment of proximal humerus fractures: a randomized controlled study.

INTRODUCTION: The primary aim of this study was to determine the effectiveness and safety of an intraarticular triamcinolone injection for the treatment of stiffness after the operative treatment of proximal humerus fractures. MATERIALS AND METHODS: 88 patients who underwent plate fixation for proximal humerus fractures were enrolled. The patients were randomly divided into two groups, with Group I receiving a glenohumeral injection of triamcinolone 8 weeks postoperatively and Group II receiving no injection postoperatively. Outcomes were measured and compared based on the range of motion (ROM) and functional scores. Follow-up outcomes were assessed at initial, 3, 6 and 12 months postoperatively and at the last follow-up. Shoulder trauma series were taken at every visit to evaluate the fracture healing. The mean follow-up period was 25.37 (± 3.85) months Group I and 24.24 (± 6.23) months for group II. RESULTS: In both groups, the final outcome of the ROM and functional outcome was significantly better at last F/U than at postoperative 8 weeks. Group I had significantly better results than Group II at postoperative 3 and 6 month in terms of forward flexion, external rotation, and VAS for pain. Also, Group I showed better performance in terms of ASES and Constant score at postoperative 3 months. The fracture union rate did not differ between Groups I and II. CONCLUSIONS: Postoperative glenohumeral injection of triamcinolone is a safe and effective treatment modality for shoulder stiffness after internal fixation of proximal humerus fractures during the early period of rehabilitation.

Hemophilia - Impact of Recent Advances on Management.

There have been numerous advances in the field of hemophilia management in the past decade, including long acting factor products, non-factor products, and potentially curative interventions such as gene therapy. Each of these interventions introduces exciting treatment modalities to patients with both hemophilia A and B, however they also pose a daunting array of possible management options. Adverse reactions to novel agents are being reported as more patients are treated and long-term sustainability of interventions such as gene therapy is yet to be determined. The practicing hematologist should be aware of the intricacies involved in customizing care for their individual patients and be aware of the monitoring strategies for each interventional strategy to avoid adverse events. Upfront cost vs. long term benefit should be considered as choices of treatment strategies are made, especially in resource poor countries. The goal of the newer agents is to decrease annualized bleed rates and avoid debilitating arthropathy. This article looks at current treatment models for prophylaxis and management of inhibitors, reviews the recent advances in the field (with bioengineered factor products, non-factor products and gene therapy) and summarizes the incorporation of these new interventions in the treatment plan for patients with hemophilia.

Mitomycin C induces fibroblast apoptosis and reduces intra-articular scar adhesion by regulating miR-21 and its target Programmed cell death 4.

Previous studies have shown that mitomycin C (MMC) can prevent scar adhesion after joint surgery, but the specific mechanism underlying this effect remains unclear. The purpose of this study was to explore the specific mechanism by which MMC promotes fibroblast apoptosis and prevents joint adhesion. The effect of MMC on fibroblasts was assessed using cell counting kit-8 (CCK-8) assays, western blotting, and TUNEL staining. We used qRT-PCR to measure the expression of miR-21 in fibroblasts treated with MMC. Luciferase activity assays were used to determine the relationships between miR-21 and Programmed cell death 4 (PDCD4). The effects of miR-21 and PDCD4 on fibroblast apoptosis were assessed using flow cytometry and western blotting. HE staining was used to determine the role of miR-21 in scar tissue formation in a model of joint adhesion. The results showed that MMC induced apoptosis of fibroblasts and decreased the expression of miR-21. Moreover, miR-21 down-regulation also induced apoptosis of fibroblasts. PDCD4 was confirmed to be a direct target of miR-21 by luciferase activity assay. The results from the animal model indicated that miR-21 attenuated the effect of MMC on reducing the number of fibroblasts. Our study shows that MMC can induce fibroblast apoptosis and prevent joint adhesion by regulating the expression of miR-21 and its target PDCD4.

Acute ACL reconstruction shows superior clinical results and can be performed safely without an increased risk of developing arthrofibrosis.

PURPOSE: To compare acute ACL reconstruction (ACLR) within 8 days of injury with delayed reconstruction after normalized range of motion (ROM), 6-10 weeks after injury. It was hypothesized that acute ACL reconstruction with modern techniques is safe and can be beneficial in terms of patient-reported outcomes and range of motion. METHODS: The effect of acute and delayed ACLR was randomized studied on 70 patients with high recreational activity level, Tegner level 6 or more, between 2006 and 2013. Patient-reported outcomes, objective IKDC, KOOS, and manual stability measurements were documented during the 24-month follow-up period. RESULTS: The acute ACLR group did not result in increased stiffness and showed superior outcome regarding strength and how the patient felt their knee functioning at 24 months. In addition, the acute group was not inferior to the delayed group in any assessment. Regarding patient-related outcomes in KOOS, both groups showed significant improvements in all subscales, but no difference was found between the groups. Functional return (FR) rate was almost double compared to the Swedish knee ligament register and treatment failure (TF) rate was reduced by half, no significant difference between the groups. No difference regarding cyclops removal, re-injury of ACL or meniscus was found between the two surgical timing groups. CONCLUSION: Acute ACLR within 8 days of injury does not appear to adversely affect ROM or result in increased stiffness in the knee joint and was not inferior to the delayed group in any assessment when compared to delayed surgery. LEVEL OF EVIDENCE: I.

Biomechanical Considerations in Rearfoot Fusions.

This article discusses rearfoot fusions for foot and ankle surgeons. It establishes normal foot and ankle function primarily in the stance phase of gait. The foot is greatly affected by external and internal forces, which contribute to normal function or the need for compensatory mechanisms. As a result of compensation, many symptoms develop, often leading to debilitating disorders such as degenerative joint disease. The interaction of the ankle, subtalar, and midtarsal joints are outlined. Congenital deformities, trauma and abnormal compensation are reviewed along with corresponding sequelae. Surgery is often indicated to reduce symptoms, improve position, and help stabilize the foot.

Artesunate prevents knee intraarticular adhesion via PRKR-like ER kinase (PERK) signal pathway.

BACKGROUND: Intraarticular scar adhesion refers to a serious complication caused by knee surgery or trauma, leading to various sequelae (e.g., articular cartilage degeneration and knee joint stiffness). Artesunate (ART) has exhibited an effect to suppress fibroblast proliferation, whereas the exact mechanism remains unclear. This study aims to delve into the possible mechanism of ART in suppressing joint adhesion. METHODS: The effect of ART on reduced intraarticular adhesions was ascertained by histological staining and immunohistochemical analysis through vivo experiments. Cell Counting Kit-8 (CCK-8) assay, Western blot analysis, flow cytometry, and tunnel staining were used to detect the effect of ART in promoting fibroblast apoptosis and delve into its possible signaling pathway. RESULTS: The results of hematoxylin-eosin (HE) staining suggested that the number of fibroblasts decreased with the increase in ART concentration. The results of Masson staining were similar, with the increase in concentration, the collagen content decreased. Immunohistochemical results showed that the expression of endoplasmic reticulum stress (ERS) characteristic proteins 78 kDa glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) increased in a concentration-dependent manner. CCK-8 results suggested that ART could inhibit fibroblast viability in a concentration- and time-dependent manner. Results of flow cytometry, tunnel staining, and Western blot suggested the apoptosis of fibroblasts occurred after ART treatment. Cells with caspase inhibitors were treated, and apoptotic proteins cleaved-poly ADP-ribose polymerase (cleaved PARP) and cleaved-caspase 3 were detected; the results showed that the apoptotic effect of ART was reduced. The expressions of ERS-related protein CHOP and apoptosis-related protein Bax were upregulated, while the expression of Bcl-2 was downregulated, and the ratio of Bax/Bcl-2 increased in a concentration-dependent manner. Continuous detection of PRKR-like ER kinase (PERK) pathway-related proteins showed that the expression of p-PERK and phosphorylating eukaryotic initiation factor 2α (p-eIF2α) increased in a time-dependent and concentration-dependent manner. PERK pathway inhibitors could partially inhibit ART-mediated apoptosis through PERK pathway. CONCLUSIONS: ART can promote fibroblast apoptosis through PERK pathway, a classical ERS pathway, and thus prevent fibrosis in the surgical area after joint surgery.

Diabetic foot problems: prevention and management

This guideline covers preventing and managing foot problems in children, young people and adults with diabetes. It aims to reduce variation in practice, including antibiotic prescribing for diabetic foot infections.

A history of prophylaxis in haemophilia.

: Prophylaxis entails long-term continuous intravenous administration of concentrates of the deficient factor with a view to preventing spontaneous bleeds and the development of hemophilic arthropathy. Initiation of prophylaxis at an early age and continuous uninterrupted factor administration in patients with hemophilia have been hailed as essential by such organizations.The most widely used prophylaxis regimens include the Swedish (Malmö), the Dutch and the Canadian protocols. Different international groups have hailed prophylaxis as the most effective treatment in patients with hemophilia.Prophylaxis is effectiveness in preventing bleeding and arthropathy in children with (particularly early-onset) hemophilia. Although some retrospective trials confirm the benefits of prophylaxis, others point to a lack of conclusive data to support switching adult patients with established hemophilic arthropathy who always received on-demand treatment to prophylactic treatment.The potential effects of prophylaxis on the patients' sex lives, renal status, prostate involvement and cataract must be analyzed before indicating prophylactic treatment in elderly patients.The high efficacy of prophylactic treatment in patients with hemophilia and inhibitors has been widely reported in the literature.