Association between serum iron status and the risk of five bone and joint-related diseases: a Mendelian randomization analysis.

Background: According to reports, iron status has been associated with the risk of bone and joint-related diseases. However, the exact role of iron status in the development of these conditions remains uncertain. Method: We obtained genetic data on iron status, specifically serum iron, ferritin, transferrin saturation (TSAT), and transferrin, as well as data on five common bone and joint-related diseases (osteoarthritis, osteoporosis, rheumatoid arthritis [RA], ankylosing spondylitis [AS], and gout) from independent genome-wide association studies involving individuals of European ancestry. Our primary approach for causal estimation utilized the inverse variance weighted (IVW) method. To ensure the reliability of our findings, we applied complementary sensitivity analysis and conducted reverse causal analysis. Result: Using the IVW method, we revealed a positive causal relationship between ferritin levels and the risk of osteoarthritis (OR [95% CI], 1.0114 [1.0021-1.0207]). Besides, we identified a protective causal relationship between serum iron levels and TSAT levels in the risk of RA (OR [95% CI] values of serum iron and TSAT were 0.9987 [0.9973-0.9999] and 0.9977 [0.9966-0.9987], respectively). Furthermore, we found a positive causal relationship between serum iron levels and the risk of AS (OR [95% CI], 1.0015 [1.0005-1.0026]). Regarding gout, both serum iron and TSAT showed a positive causal relationship (OR [95% CI] values of 1.3357 [1.0915-1.6345] and 1.2316 [1.0666-1.4221] for serum iron and TSAT, respectively), while transferrin exhibited a protective causal relationship (OR [95% CI], 0.8563 [0.7802-0.9399]). Additionally, our reverse causal analysis revealed a negative correlation between RA and ferritin and TSAT levels (OR [95% CI] values of serum iron and TSAT were 0.0407 [0.0034-0.4814] and 0.0049 [0.0002-0.1454], respectively), along with a positive correlation with transferrin (OR [95% CI], 853.7592 [20.7108-35194.4325]). To ensure the validity of our findings, we replicated the results through sensitivity analysis during the validation process. Conclusion: Our study demonstrated a significant correlation between iron status and bone and joint-related diseases.

Deciphering the circulating microRNA signature of hemophilic arthropathy.

BACKGROUND: Haemophilic arthropathy (HArt) is a serious complication in patients with hemophilia. Early diagnosis and treatment are essential to minimise the development of HArt. The use of biomarkers may improve early diagnosis of HArt. Circulating microRNAs (miRNAs) are small, non-coding RNAsthat regulate gene expression, and are being investigated as promising biomarkers due to their role in joint and bone metabolism. AIMS: To investigate differential expression of miRNAs and their relationship to arthropathy in patients with hemophilia A. METHODS: miRNA expression was examined in a pilot study followed by a validation study (100 hemophilia A patients with [n = 83] and without HArt [n = 17], 14 controls). Differential miRNA expression was investigated using real-time quantitative PCR. RESULTS: The pilot study identified 2 miRNAs differentially expressed in patients with Hart (Pettersson score ≥ 1), after adjusting for the false discovery rate (FDR). The validation study evaluated these 2 miRNAs. The results demonstrated that two miRNAs (miR- 208a-3p and 524-3p) were significantly underexpressed in plasma of patients with HArt compared to patients without arthropathy, with FDR <0.05 (Fig. 1). In addition, 3 miRNAs (130a-3p, miR- and 506-3p) were significantly underexpressed in patients with moderate HArt (Pettersson score 4 to 7). CONCLUSIONS: In this proof of concept study we identified a signature of 5 circulating miRNAs associated with Hart with potential as diagnosis tools for HArt. These miRNAs are potential negative regulators of gene expression, suggesting their activity in HArt by interfering with osteoblastic (miR- 208a-3p) and osteoclastic (miR-506-3p) differentiation to impair bone mineralization and remodeling processes, or regulating chondrogenesis (miR-335-5p). miRNAs associated with earlier stages of HArt will be further investigated in a sub-study of the prospective clinical trial PROVE, which will investigate the effects of long-term prophylaxis with simoctocog alfa versus emicizumab in adults with hemophilia A.

Hematologic Expression After Shoulder Surgery: Normalization Curve of Serum Inflammatory Markers.

PURPOSE: To determine the normalization curves of the serologic markers including white blood cell (WBC) count, WBC differential for segmented neutrophil (WBC seg.), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) after elective shoulder surgery and to investigate the hematologic differences among different shoulder surgeries. METHODS: Seventy-seven patients underwent arthroscopic rotator cuff repair (RCR, group A), 44 patients had open rotator cuff repair (group B), and 84 patients had shoulder arthroplasty (group C). Peak and normalization times of markers were determined at preoperatively, postoperative day (POD) 1 and 2 days, 1 and 2 weeks, 1, 2, 3, 6 months, and 1 year after surgery. The normal ranges of serologic markers were set to WBC 4000 to10,000/µL, WBC seg. 40% to 60%, ESR 0 to 20 mm/h, and CRP 0 to 0.8 mg/dL. RESULTS: Groups reached peak mean WBC count and WBC seg. on POD 1; mean WBC count started decreasing on POD 2 but was within normal value afterwards. Mean WBC seg. decreased to normal value at 1 month postoperatively in group A and B and at 2 months postoperatively in group C. Mean ESR peaked at 2 weeks postoperatively and normalized after 1 month in groups A and B and 3 months in group C. Mean CRP levels peaked on POD 2 in all groups and normalized within 2 weeks postoperatively in groups A and B and 1 month postoperatively in Group C. Normalized values of WBC count, WBC seg., and ESR varied widely. In contrast, CRP showed a consistent undetectable median, upper and lower quartile values less than 0.5 after normalization. Mean serum ESR and CRP values at peak time were significantly greater in group C than in the other groups (P = .001). CONCLUSIONS: The mean CRP levels were normalized at 2 weeks after rotator cuff repair and at 1 month after arthroplasties. Unlike the other serologic markers, CRP had consistent normalized values of median, upper and lower quartile afterwards. The peak levels of the inflammatory markers were greater and therefore normalized slower following more invasive surgery. LEVEL OF EVIDENCE: Level III, case control study.

Association of serum CXCL12 levels with arthropathy in patients with systemic sclerosis.

AIM: Systemic sclerosis (SSc) is an autoimmune connective tissue disease, in which extensive fibrotic change and vasculopathy affect the skin and various internal organs. It also involves the joints, causing stiffness, arthralgia, and arthritis. Although arthropathy is commonly observed in SSc, its underlying mechanism remains unknown. CXCL12, also known as stromal cell derived factor 1, is associated with inflammation, mesenchymal cell recruitment, angiogenesis, and collagen production, and is implicated in the development of various joint diseases. To assess the potential contribution of CXCL12 to SSc development, we investigated the clinical association of serum CXCL12 levels in patients with SSc. METHOD: We conducted a cross-sectional analysis of 68 patients with SSc and 20 healthy controls recruited in a single center over 9 years. Serum CXCL12 levels were measured by enzyme-linked immunosorbent assay. RESULTS: Serum CXCL12 levels were significantly higher in patients with SSc than in healthy controls (median 1554.0 pg/mL, 25th-75th centiles 1313.0-1914.0 pg/mL vs 967.4 pg/mL, 608.8-1271.0 pg/mL, P < 0.001). Patients with SSc with elevated CXCL12 levels had significantly more cases of arthropathy than those with normal CXCL12 levels (85.7% vs 25.0%, P = 0.01). Furthermore, patients with SSc with elevated CXCL12 levels showed an increased trend in the prevalence of limited range of motion of the finger joints compared with those with normal CXCL12 levels (60.0% vs 18.6%, P =0 .07). Moreover, serum CXCL12 levels were significantly correlated with the titers of rheumatoid factor in patients with SSc (r = .41, P = 0.001). CONCLUSION: Elevated serum CXCL12 levels may be related to the development of SSc arthropathy.

Rapid direct detection of pathogens for diagnosis of joint infections by MALDI-TOF MS after liquid enrichment in the BacT/Alert blood culture system.

Pathogen identification is a critical step during diagnosis of infectious diseases. Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight mass spectrometry (MALDI-TOF-MS) has become the gold standard for identification of microorganisms cultured on solid media in microbiology laboratories. Direct identification of microbes from liquid specimen, circumventing the need for the additional overnight cultivation step, has been successfully established for blood culture, urine and liquor. Here, we evaluate the ability of MALDI-TOF MS for direct identification of pathogens in synovial fluid after liquid enrichment in BacT/Alert blood culture bottles. Influence of synovial specimen quality on direct species identification with the MALDI BioTyper/Sepsityper was tested with samples inoculated from pretested native synovia with concomitant inoculation of blood or pus, or highly viscous fluid. Here, we achieved >90% concordance with culture on solid medium, and only mixed-species samples posed significant problems. Performance in routine diagnostics was tested prospectively on bottles inoculated by treating physicians on ward. There, we achieved >70% concordance with culture on solid media. The major contributors to test failure were the absence of a measurable mass signal and mixed-specimen samples. The Sepsityper workflow worked well on samples derived from BacT/Alert blood culture bottles inoculated with synovial fluid, giving concordant results to identification from solid media. Host remnant material in the inoculum, such as blood or pus, had no detrimental effect on identification score values of the BioTyper system after processing with the Sepsityper workflow, and neither had the initial viscosity of the synovial sample.

The Progression of Hemophilic Arthropathy: The Role of Biomarkers.

BACKGROUND: Hemophilia A and B are X-linked congenital bleeding disorders characterized by recurrent hemarthroses leading to specific changes in the synovium and cartilage, which finally result in the destruction of the joint: this process is called hemophilic arthropathy (HA). This review highlights the most prominent molecular biomarkers found in the literature to discuss their potential use in the clinical practice to monitor bleeding, to assess the progression of the HA and the effectiveness of treatments. METHODS: A review of the literature was performed on PubMed and Embase, from 3 to 7 August 2020. Study selection and data extraction were achieved independently by two authors and the following inclusion criteria were determined a priori: English language, available full text and articles published in peer-reviewed journal. In addition, further articles were identified by checking the bibliography of relevant articles and searching for the studies cited in all the articles examined. RESULTS: Eligible studies obtained at the end of the search and screen process were seventy-three (73). CONCLUSIONS: Despite the surge of interest in the clinical use of biomarkers, current literature underlines the lack of their standardization and their potential use in the clinical practice preserving the role of physical examination and imaging in early diagnosis.

Understanding minimum and ideal factor levels for participation in physical activities by people with haemophilia: An expert elicitation exercise.

INTRODUCTION: The benefits of physical activity (PA) for people with haemophilia (PWH) may include improvements in joint, bone and muscle health. However, the factor VIII activity level required to avoid a bleeding episode associated with PA is unknown. AIM: To elicit the opinion of clinical experts on the minimum level and ideal factor VIII activity ('level') required to avoid a bleeding episode during participation in different types of PA for PWH. METHODS: Based on the 2017 National Hemophilia Foundation PA descriptions, clinical experts estimated a minimally acceptable and an ideal factor level at which a bleed could be avoided. The uncertainty around estimates was quantified using an approach to construct a probability distribution to represent expert opinion. RESULTS: Minimum and ideal factor level increased with higher risk PA, whether or not joint morbidity was present, as did the experts' uncertainty in their estimates (ie the range between lowest and highest estimates for minimum and ideal levels). Mean minimum levels ranged from 4% to 48% for low to high risk for people without joint morbidity, and from 7% to 47% for those with joint morbidity. For ideal factor levels, corresponding figures were 9%-52% and 12%-64%, respectively. CONCLUSION: To support a patient-centric outcome, expert opinion indicates that the clinical norm of 0.01 IU/mL (1%) trough level is insufficient. It is anticipated that introducing a more targeted approach to meet the needs of patients who are increasingly physically active will benefit patients further in addition to recent treatment advances.

[Mid-term and long-term results of metal-on-metal total hip arthroplasty]. / Srednesrochnye i otdalennye rezul'taty éndoprotezirovaniia tazobedrennogo sustava s ispol'zovaniem pary treniia metall-metall.

OBJECTIVE: To assess mid-term and long-term results of metal-on-metal total hip arthroplasty. MATERIAL AND METHODS: There were 349 operations for the period 2006-2012 in our clinic. Sixty-four patients underwent a full examination. All patients underwent X-ray examination of the pelvis, MRI of hip joint with metal artifact reduction sequence (MARS). The concentration of cobalt and chromium metal ions was determined in blood serum. Each patient completed a questionnaire (Harris, Oxford, Womac, SF-36). 'Survival' of endoprostheses was calculated using the Kaplan-Meier method. RESULTS: According to the Oxford scale, 76.6% of patients had excellent clinical and functional outcomes, 10.9% - good, 9.4% - satisfactory, 3.1% - unsatisfactory. According to the Harris scale, 57.9% of patients had excellent results, 15.6% - good, 7.8% - satisfactory, 18.7% - unsatisfactory. Inclination less than 45 degrees was noted in 77.2% of acetabular components. It is optimal installation angle. According to MRI data, effusion was the main type of periprosthetic changes (16 cases). There were no periprosthetic changes in 33 cases. Pseudotumor was diagnosed in 5 cases. Mean concentrations of cobalt and chromium ions were 1.27 (13.57-0.12) and 0.59 (0.4-0.87) µg/l, respectively. Normal concentration of chromium ions was observed in all cases. Kaplan-Meier survival rate of endoprostheses was 89% (80-97%). CONCLUSION: There was no correlation between female sex, young age of patients and incidence of complications. It is necessary to exclude pseudotumor in case of pain syndrome and no signs of aseptic loosening of the components of the endoprosthesis.

Postoperative creatine kinase elevation following hip arthroscopy and associated risk factors.

OBJECTIVE: The aim of this study was to investigate postoperative CK and risk factors for CK elevation after hip arthroscopy. METHODS: This retrospective study reviewed 122 patients (50 males, 72 females; mean age, 44.1 years) who underwent hip arthroscopy from September 2012 to March 2018. For all patients, CK was investigated preoperatively, on postoperative days 1 and 3, and at postoperative weeks 1 and 2. Univariate and multivariate analysis was performed for parameters including sex, age, body mass index, preoperative glomerular filtration rate, diagnosis, duration of surgery, and duration of traction to determine the risk factors for CK > 10 upper limit of normal (CK > 10 ULN; 1900 IU/L for males and 1500 IU/L for females) after surgery. RESULTS: Mean CK was 104.7 ± 68.7 IU/L preoperatively and 839.2 ± 2214.0, 523.9 ± 1449.4, 186.0 ± 690.7, and 122.0 ± 307.1 IU/L on postoperative days 1 and 3 and at postoperative weeks 1 and 2, respectively. CK was significantly higher on postoperative days 1 and 3 than before surgery. In total, 11 patients (9.0%), including 8 males (16.0%) and 3 females (4.2%), had CK > 10 ULN. Younger age and longer duration of traction are independent risk factors for CK > 10 ULN. CONCLUSION: After hip arthroscopy, CK levels should be monitored, especially in young patients and cases of prolonged duration of traction during surgery. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Evaluación de fugas extrarticulares del Fosfato crómico marcado con Fósforo-32 de producción nacional en pacientes hemofílicos / Evaluation of joint leakage of national Chromic Phosphate labeled with Phosphorus-32 in hemophilic patients

La radiosinoviortesis como tratamiento de la artropatía hemofílica, frecuentemente, ofrece excelentes resultados, al reducir grandemente el número de episodios de sangramiento y evitar daños ulteriores a las articulaciones. El Centro de Isótopos desarrolló el fosfato crómico coloidal marcado con Fósforo-32, producto listo para su empleo en pacientes hemofílicos. El objetivo de este trabajo fue evaluar la fuga extrarticular de este radiofármaco utilizado en la radiosinoviortesis en pacientes hemofílicos. Se determinó el porcentaje de fuga extrarticular del radiofármaco en 9 pacientes hemofílicos con sinovitis crónica, a los que se les realizó la radiosinoviortesis en la articulación de la rodilla. La radiactividad se midió, con un contador Geiger-Muller, sobre la rodilla tratada, en sus aspectos lateral, encima y medial; la rodilla contralateral; las cadenas linfáticas inguinales, de ambos lados, y el hígado. Los valores de fuga encontrados posteriormente a la inyección fueron 0,0046 por ciento a los 10 min; 0,0023 por ciento a las 24 horas; 0,1332 por ciento el día 7 y 4,0213 por ciento el día 30. Estos resultados coinciden con los valores comunicados por otros autores y con lo esperado de acuerdo a las características del producto, indican que se ejecutó el proceder adecuadamente y que los pacientes fueron seleccionados correctamente(AU)

Radiosynoviorthesis as a treatment for hemophilic arthropathy often offers excellent results, greatly reducing the number of bleeding episodes and avoiding further damage to the joints. The Isotope Center developed a product, Colloidal Chromic Phosphate labeled with Phosphorus-32, ready for use in hemophiliac patients. Our objective was to evaluate the joint leakage of this radiopharmaceutical use in radiosynoviorthesis in hemophilic patients. The percentage of radiopharmaceutical joint leakage was evaluated in 9 hemophilic patients with chronic synovitis, who underwent radiosynoviorthesis in the knee joint. The radioactivity was measured on the treated knee, in its lateral, above and medial aspects, the contralateral knee, the inguinal lymphatic chains of both sides and the liver, with a Geiger-Muller detector. The leakage values 8203;​found after the injection were 0.0046 percent at 10 minutes, 0.0023 percent at 24 hours, 0.1332 percent on day 7 and 4.0213 percent on day 30. These results are agreed with the values reported by other authors and with was expected according to the characteristics of the product, indicatate that the procedure was executed properly and that the patients were correctly selected(AU)

Prevalence and natural course of pseudotumours after small-head metal-on-metal total hip arthroplasty: a minimum 18-year follow-up study of a previous report.

AIMS: The present study investigated the five-year interval changes in pseudotumours and measured serum metal ions at long-term follow-up of a previous report of 28 mm diameter metal-on-metal (MoM) total hip arthroplasty (THA). PATIENTS AND METHODS: A total of 72 patients (mean age 46.6 years (37 to 55); 43 men, 29 women; 91 hips) who underwent cementless primary MoM THA with a 28 mm modular head were included. The mean follow-up duration was 20.3 years (18 to 24). All patients had CT scans at a mean 15.1 years (13 to 19) after the index operation and subsequent follow-up at a mean of 20.2 years (18 to 24). Pseudotumour volume, type of mass, and new-onset pseudotumours were evaluated using CT scanning. Clinical outcomes were assessed by Harris Hip Score (HHS) and the presence of groin pain. Serum metal ion (cobalt (Co) and chromium (Cr)) levels were measured at the latest follow-up. RESULTS: At final follow-up, pseudotumours were observed in 26/91 hips (28.6%). There was an increase in volume of the pseudotumour in four hips (15.4%), no change in volume in 21 hips (80.8%), and a decrease in volume in one hip (3.8%). There were no new-onset pseudotumours. There was no significant difference in HHS between patients with and without pseudotumours. At final follow-up, mean serum Co ion levels and median Co:Cr ratios were significantly greater in patients with pseudotumours, but the serum Cr ion levels were not significantly different. CONCLUSION: At a mean 20 years of follow-up, pseudotumours were observed in 26/91 hips (28.6%) with no new-onset pseudotumours during subsequent follow-up. Most pseudotumours in small-head MoM THA were static in volume and asymptomatic with normal serum metal ion levels. Cite this article: Bone Joint J 2019;101-B:317-324.

BONE MARKERS IN ARTHROPATHIES.

Bone endures a lifelong course of construction and destruction, with bone marker (BM) molecules released during this cycle. The field of measuring BM levels in synovial fluid and peripheral blood is a cardinal part of bone research within modern clinical medicine and has developed extensively in the last years. The purpose of our work was to convey an up-to-date overview on synovial fluid and serum BMs in the most common arthropathies.

[Osteoarthropathies and Myopathies associated with Disorders of the Thyroid Endocrine System]. / Osteoarthropathien und Myopathien bei Schilddrüsenerkrankungen.

Triiodothyronine (T3) is a key regulator of bone, muscle and articular cartilage. Musculoskeletal symptoms of hyperthyroidism include loss of bone mass finally leading to osteoporosis and weakness of the skeletal musculature. Hypothyroidism on the other side frequently leads to muscle stiffness and cramping and, occasionally, results in rhabdomyolysis. To prevent terminal differentiation of chondrocytes with consecutive cartilage degeneration, cartilage probably depends on exact regulation of local T3 availability by the intracellular deiodinase system. Recent findings underline the importance of local T3 generation by deiodinase type 2 and support the existence of local hypo- or hyperthyroidism.In the review, the implications of the recent literature for current understanding of osteoarthritis, myopathies and diabetic osteoarthropathy will be discussed. Further emphasis will be placed on the association of autoimmune thyroiditis with musculoskeletal diseases and fibromyalgia.

Immunoglobulin G4-Related Disease of the Hip.

The authors report a case of immunoglobulin G4-related disease (IgG4-RD) of the hip. A 60-year-old man diagnosed with osteoarthritis of the right hip was referred to the authors' outpatient clinic for surgical intervention. Laboratory test results revealed elevated C-reactive protein and serum IgG levels. A subsequent laboratory test revealed an IgG4 level of 318 mg/dL. Magnetic resonance imaging revealed an abnormal mass in the right hip joint. The authors suspected IgG4-RD of the hip. The mass was resected during total hip arthroplasty. Immunohistochemical analysis for IgG revealed positive staining of many plasma cells. Most of the IgG-positive plasma cells were positive for IgG4, and the ratio of IgG4/IgG-positive cells was 51%. This case met all criteria for IgG4-RD; thus, the authors made a definitive diagnosis of IgG4-RD of the hip. The C-reactive protein level decreased to a negative value, and the IgG level decreased to a normal range at 3 weeks postoperatively. The IgG4 level gradually decreased to 152 mg/dL at 5 months postoperatively. This is the first reported case of IgG4-RD of the hip joint. [Orthopedics. 2018; 41(6):e876-e879.].

Significance of combined anti-CCP antibodies and rheumatoid factor in a New Zealand cohort of patients with systemic sclerosis.

BACKGROUND: Systemic sclerosis (SSc) can present as an overlap syndrome with rheumatoid arthritis (SSc-RA overlap). OBJECTIVE: To evaluate the frequency of rheumatoid factor (RF) and anticyclic citrullinated peptide antibodies (anti-CCP) in our SSc cohort and their association with clinical features. METHODS: Data were gathered prospectively from the Waikato Hospital Systemic Sclerosis Clinics. Patients with SSc and SOS (systemic sclerosis overlap syndrome) underwent baseline auto-antibody profiling including RF and anti-CCP along with annual clinical review. RESULTS: Our cohort comprised of 132 patients (two had incomplete data); 115 (87.1%) were female. Out of 89 limited cutaneous SSc (lcSSc) patients, arthralgia, synovitis, contractures, tendon crepitus and erosions on imaging were found in three, 10, 31, five and nine patients, respectively. Within the 33 diffuse cutaneous SSc (dcSSc) patients, arthralgia, synovitis, contractures, tendon crepitus and erosion were found in 15, five, 27, five and one patient, respectively. In the 10 SOS patients, arthralgia, synovitis and contractures were found in six, three and two patients; none had tendon crepitus or erosions. RF positivity was found in 15.7%, 9% and 20% of patients with lcSSc, dcSSc and SOS, and anti-CCP positivity was found in 13.5%, 6.1% and 0% in lcSSc, dcSSc and SOS patients. A statistically significant relationship of double antibody positivity with arthralgia (P = 0.03) and erosions (P < 0.001) was found. Anti-CCP positivity association with erosions was significant at P = 0.007. CONCLUSION: Our study confirms that articular manifestations are common in SSc. Statistically significant associations of double antibody positivity with arthralgia and erosions were demonstrated. Significant association between anti-CCP antibody and erosions was also confirmed.

Prophylactic versus on-demand treatments for hemophilia: advantages and drawbacks.

INTRODUCTION: Early long-term prophylaxis is the standard of care to prevent joint bleeding and chronic arthropathy in patients with severe hemophilia. Areas covered: Despite the obvious prophylaxis advantages upon the clinical outcomes, there are still several drawbacks to be addressed for the optimal patients' compliance. Frequency of treatment due to short half-life of conventional FVIII and FIX concentrates, difficult venous access, adherence to the prescribed therapy and costs may represent significant critical issues. The development of inhibitors also makes replacement therapy ineffective, preventing patients from receiving long-term prophylaxis. This paper will review these drawbacks and the tools to overcome these limitations, mainly thanks to the use of extended half-life products and the development of novel non-conventional therapeutic approaches. Expert commentary: The use of extended half-life products may help in reducing the burden of the frequent intravenous administration and in better tailoring an individualized prophylaxis. The development of novel therapeutic approaches, like the bi-specific antibody mimicking the coagulation function of FVIII or inhibition of anticoagulant proteins may facilitate prophylaxis treatment not only in patients with inhibitors, but also in severe hemophilia patients without inhibitors. Exciting opportunities are emerging for improving prophylaxis in hemophilia.

Contribution of a multiplex serological test for the preoperative diagnosis of prosthetic joint infection: a prospective study.

BACKGROUND: Prosthetic joint infection (PJI) is a severe complication of orthopaedic surgery. Preoperative diagnosis, although sometimes difficult, is key to choose the relevant treatment. METHODS: We conducted a prospective study aimed at evaluating the diagnostic performance of a multiplex serological test for the pre-operative diagnosis of PJI. Blood samples were collected between 1 July 2016 and 31 July 2017 among patients referred for suspected PJI that occurred at least six weeks prior. Infection diagnosis was confirmed using intraoperative bacteriological cultures during prosthetic exchange. RESULTS: Seventy-one patients were included, with a median age of 73 years (interquartile range [IQR]: 66-81) and 40 (56%) were male. Twenty-six patients had aseptic loosening and 45 patients had PJI. Among the latter, median time since the last surgery was 96 weeks (IQR: 20-324). Intraoperative cultures found Staphylococcus spp, Streptococcus spp or both in 39, 5 and 1 patients, respectively. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 81.8, 95.4, 97.3 and 72.4%, respectively, for all patients and 87.5, 93.5, 94.6 and 85.3%, respectively, for staphylococcal infections. Patients with false negative (FN) results had a significantly lower blood lymphocyte count (p = .045). CONCLUSIONS: Multiplex serological test performed well among patients with chronic staphylococcal prosthetic infection. This approach could contribute to PJI diagnosis especially in patients for whom the pre-operative analysis of joint fluid is not informative.

Anti-alpha-enolase antibodies in Behçet's disease: a marker of mucocutaneous and articular disease activity?

OBJECTIVES: To assess IgM anti-alpha-enolase antibodies (AAEA) in systemic Behçet's disease (BD) and its possible association with clinical manifestations and disease activity. METHODS: Ninety-seven consecutively selected BD patients were compared to 36 enteropathic spondyloarthritis (ESpA) [24 Crohn's disease (CD) and 12 ulcerative colitis (UC)] patients and 87 healthy controls. IgM AAEA was detected by immunoblotting. Disease activity was assessed by standardised indexes, Brazilian BD Current Activity Form (BR-BDCAF) for BD and Harvey-Bradshaw Index (HBI) for CD and UC patients. A second evaluation was performed in BD patients (n=56), regarding IgM AAEA presence, disease activity scores and C-reactive protein (CRP). RESULTS: Higher IgM AAEA prevalence was found in 97 BD (17.7%) compared to ESpA (2.8%) and healthy controls (2.3%), p<0.001. IgM AAEA frequency was higher in active BD compared to inactive BD (30.2% vs. 7.4%, p=0.006), a finding confirmed in the second cross-sectional evaluation of 56 of these BD patients (45.5% vs. 13.3%, p=0.02). Mean BR-BDCAF scores were higher in IgM AAEA positive group on both evaluations (9.1 ± 5.4 vs. 4.9 ± 4.9, p=0.002; 5.0 ± 4.9 vs. 2.2 ± 2.9, p=0.01, respectively). BD patients with mucocutaneous and articular symptoms presented higher IgM AAEA positivity in the first and second evaluations (64.7% vs. 27.5%, p=0.005; 36.4% vs. 7.1%, p=0.039 respectively). CONCLUSIONS: Our data support the notion that alpha-enolase is a target antigen in BD, particularly associated with disease activity, mucocutaneous and articular involvement. In addition, IgM AAEA may distinguish BD from ESpA, especially in patients with high disease activity.

Association of CXCL13 serum level and ultrasonographic findings of joints in patients with systemic lupus erythematosus and Jaccoud's arthropathy.

Objectives The objective of this paper is to perform an ultrasonography (US) analysis of hands and wrists in two groups of patients with systemic lupus erythematosus (SLE), with and without Jaccoud's arthropathy, matched by age and disease duration and to correlate them with levels of CXCL13 clinical features, laboratory tests and disease activity score. Methods Sixty-four patients with SLE were enrolled, 32 with and 32 without Jaccoud's arthropathy. Each patient underwent physical examination, laboratory tests (including CXCL13 by ELISA) and bilateral US. Synovial hypertrophy, tenosynovitis and erosions were evaluated according to a semiquantitative grading system with a 0-3 rating. US findings were correlated with serum levels of CXCL13, other serological parameters and disease activity index. Results Synovitis was found in 25/64 patients (39%) and tenosynovitis in 14/64 (22%). These findings were more frequent in SLE patients with Jaccoud's arthropathy, particularly tenosynovitis ( p = 0.002) and synovitis ( p = 0.01). Median serum level of CXCL13 was 20.16 pg/ml in the whole population (23.21 pg/ml in the Jaccoud's arthropathy group and 11.48 pg/ml in the group without). There was an association between the presence of disease activity and high level of CXCL13 ( p = 0.004). However, no association was found between high levels of CXCL13 and "arthritis" in SLEDAI, swollen joints on physical examination or synovitis on US. Conclusions US findings in joints of SLE patients with Jaccoud's arthropathy confirm that synovitis and tenosynovitis are common in these patients. In addition, serum level of CXCL13 is associated with disease activity in SLE but does not seem to be a biomarker for arthritis in these patients.