Structural equation models for slaughtering weight prediction for broilers.

The aim of this research was to determine the effect of gut health parameters on the flock's final weight of broilers and to calculate an accurate equation to estimate this weight with information available at 7, 14, and 21 days, in field conditions. Gut health parameters (gizzard erosion, coccidiosis, feed passage, and redness, gut tone, consistency of content, and presence of mucus for each part of the small intestine [duodenum, jejunum, and ileum], and color, consistency, and presence of gas for caeca content) were evaluated at 7 and 14 days. Other parameters evaluated for impact on flock final weight were body weight and mortality, both at 7, 14, and 21 days; stocking density; litter reuse; and downtime period. Structural equation model evaluation of the data showed that stocking density and litter reuse did not affect (P > 0.05) flock final weight, while downtime period, body weight (14 and 21 days), and mortality (14 and 21 days) directly affected (P ≤ 0.05) the flock final weight. Gut health parameters did not directly affect the flock's final weight; however, they affected body weight and mortality at 14 days, thus showing an indirect effect on the flock's final weight. It was also possible to determine two accurate equations to estimate the flock's final weight using information available at both 14 (R2 = 0.56) and 21 (R2 = 0.77) days.

Genome Association Study for Visual Scores in Nellore Cattle Measured at Weaning.

BACKGROUND: Genome-wide association studies (GWAS) are utilized in cattle to identify regions or genetic variants associated with phenotypes of interest, and thus, to identify design strategies that allow for the increase of the frequency of favorable alleles. Visual scores are important traits of cattle production in Brazil because they are utilized as selection criteria, helping to choose more harmonious animals. Despite its importance, there are still no studies on the genome association for these traits. This study aimed to identify genome regions associated with the traits of conformation, precocity and muscling, based on a visual score measured at weaning. RESULTS: Bayesian approaches with BayesC and Bayesian LASSO were utilized with 2873 phenotypes of Nellore cattle for a GWAS. The animals were genotyped with Illumina BovineHD BeadChip, and a total of 309,865 SNPs were utilized after quality control. In the analyses, phenotype and deregressed breeding values were utilized as dependent variables; a threshold model was utilized for the former and a linear model for the latter. The association criterion was the percentage of genetic variance explained by SNPs found in 1 Mb-long windows. The Bayesian approach BayesC was better adjusted to the data because it could explain a larger phenotypic variance for both dependent variables. CONCLUSIONS: There were no large effects for the visual scores, indicating that they have a polygenic nature; however, regions in chromosomes 1, 3, 5, 7, 14, 15, 16, 19, 20 and 23 were identified and explained a large part of the genetic variance.

Agreement between semiquantitative and quantitative Doppler scoring systems for the assessment of synovial pathological vascularisation in rheumatoid arthritis.

OBJECTIVES: To compare colour Doppler (CD) versus power Doppler (PD) semiquantitative and quantitative scoring of synovial vascularisation and to evaluate the relationship between semiquantitative and quantitative scores in patients with rheumatoid arthritis (RA). METHODS: One hundred RA patients underwent B-mode, PD, and CD assessments of 12 joints at two European centres. Each joint with synovial hypertrophy (SH) detected on B-mode was semiquantitatively scored (0-3) for PD (SPD score) and CD (SCD score) synovial signal. PD and CD synovial signal were also quantitatively scored (0-100%) (QPD and QCD scores, respectively) using a software integrated in the US equipment for counting the colour fraction. RESULTS: We found SH in 184 joints. SPD and SCD agreed in 92.3% (95%CI: 88.4; 96.2%) of paired scores, with Kendall rank correlation coefficient tau-b=0.95. QPD and QCD scores were highly correlated (Pearson's coefficient=0.70) but Blamd-Altman plot showed insufficient agreement, being the QCD scores systematically slightly higher than the QPD scores. The comparison of mean values of QPD and QCD between scores of SPD and SCD, respectively, showed significant differences between grade 0 and grade 1 (p<0.001), and grade 2 and grade 3 (p=0.042 and p=0.007, respectively) but not between grade 1 and 2 (p=0.154 and p=0.150, respectively). CONCLUSIONS: The SPD and SCD scores were concordant and the QPD and QCD scores highly correlated but were not concordant. There was an overlap between SPD and SCD mild and moderate scores regarding QPD and QCD scores.

Intravenous administration of expanded allogeneic adipose-derived mesenchymal stem cells in refractory rheumatoid arthritis (Cx611): results of a multicentre, dose escalation, randomised, single-blind, placebo-controlled phase Ib/IIa clinical trial.

OBJECTIVES: To evaluate the safety and tolerability of the intravenous administration of Cx611, a preparation of allogeneic expanded adipose-derived stem cells (eASCs), in patients with refractory rheumatoid arthritis (RA), as well as to obtain preliminary clinical efficacy data in this population. METHODS: It is a multicentre, dose escalation, randomised, single-blind (double-blind for efficacy), placebo-controlled, phase Ib/IIa clinical trial. Patients with active refractory RA (failure to at least two biologicals) were randomised to receive three intravenous infusions of Cx611: 1 million/kg (cohort A), 2 million/kg (cohort B), 4 million/kg (cohort C) or placebo, on days 1, 8 and 15, and they were followed for therapy assessment for 24 weeks. RESULTS: Fifty-three patients were treated (20 in cohort A, 20 in cohort B, 6 in cohort C and 7 in placebo group). A total of 141 adverse events (AEs) were reported. Seventeen patients from the group A (85%), 15 from the group B (75%), 6 from the group C (100%) and 4 from the placebo group (57%) experienced at least one AE.Eight AEs from 6 patients were grade 3 in intensity (severe), 5 in cohort A (lacunar infarction, diarrhoea, tendon rupture, rheumatoid nodule and arthritis), 2 in cohort B (sciatica and RA) and 1 in the placebo group (asthenia). Only one of the grade 3 AEs was serious (the lacunar infarction). American College of Rheumatology 20 responses for cohorts A, B, C and placebo were 45%, 20%, 33% and 29%, respectively, at month 1, and 25%, 15%, 17% and 0%, respectively, at month 3. CONCLUSIONS: The intravenous infusion of Cx611 was in general well tolerated, without evidence of dose-related toxicity at the dose range and time period studied. In addition, a trend for clinical efficacy was observed. These data, in our opinion, justify further investigation of this innovative therapy in patients with RA. TRIAL REGISTRATION NUMBERS: EudraCT: 2010-021602-37; NCT01663116; Results.

Structural damage in rheumatoid arthritis: comparison between tendon damage evaluated by ultrasound and radiographic damage.

OBJECTIVE: To compare structural damage assessed by conventional radiography and tendon damage assessed by musculoskeletal US (MSUS) at wrist and ankle in RA patients. METHODS: We evaluated 72 consecutive patients [56 (77.8%) females] with RA. The MSUS evaluation consisted in a B-mode examination of bilateral extensor carpi ulnaris and tibialis posterior tendons. Tendon damage was defined and scored according to OMERACT. A total score for the tendon damage score (TDS) was calculated by summing the grades for each tendon. For the radiographic evaluations we used the van der Heijde score; a total radiographic score (RTS) was calculated by summing a bone erosion score (ERS) and a joint space narrowing score (JSNS). RESULTS: We evaluated 288 tendons. The mean (s.d.) of TDS was 2.3 (1.8). Fifty-four (75%) patients presented tendon damage of at least one tendon. From all evaluated tendons, 134 (46.5%) had no tendon damage, 146 (50.7%) had grade 1 and 8 (2.8%) had grade 2 tendon damage. The mean (s.d.) for RTS was 91.4 (97), for ERS was 47.3 (61.9) and for JSNS was 44.1 (37.2). We found a significant correlation between disease duration and both TDS and RTS (r = 0.413 and r = 0.560, respectively; P < 0.0001). We found a good significant correlation between TDS and all variables of radiographic structural damage (RTS, r = 0.65; ERS, r = 0.637; JSNS, r = 0.618; P < 0.001). CONCLUSION: The MSUS assessment of only four tendons can be an additional feasible method to assess structural damage in RA patients.

The feet in systemic lupus erythematosus; are we underestimating their involvement and functional impact?

OBJECTIVES: To evaluate biomechanical and ultrasound (US) abnormalities in SLE patients as compared with controls and to assess the relationship between these abnormalities and SLE activity. METHODS: Fifty-four consecutive female patients with SLE with and without foot pain and 60 female controls (30 with foot pain and 30 without foot pain) were recruited. SLE activity was assessed by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). SLE patients and controls blindly underwent a comprehensive podiatric, biomechanical and US evaluation of the feet. US assessment included detection of B-mode synovitis, tenosynovitis, enthesopathy, bone changes and synovial, tenosynovial and entheseal power Doppler (PD) signal. RESULTS: Thirty-one (57.4%) SLE patients had bilateral foot pain and 5 (9.3%) had unilateral foot pain. Metatarsalgia was the most common location for pain but without significant difference between groups (p=0.284). Toe joint deformities were significantly more common in SLE feet as compared with control feet (p<0.0005). SLE feet showed significantly more biomechanical abnormalities than control feet (p<0.05). B-mode synovitis in the tibiotalar joint was strongly associated with having SLE (p<0.0005) and the presence of synovial PD signal in the MTP joints was found only in painful feet of SLE patients. SLEDAI was significantly higher in patients with foot pain than in those with painless feet (p=0.008). However, SLEDAI did not discriminate between patients with and without biomechanical or US abnormalities. CONCLUSIONS: SLE patients showed more biomechanical and US abnormalities in the feet than controls, which were not captured by standardised assessment of the disease activity.

How does a cadaver model work for testing ultrasound diagnostic capability for rheumatic-like tendon damage?

To establish whether a cadaver model can serve as an effective surrogate for the detection of tendon damage characteristic of rheumatoid arthritis (RA). In addition, we evaluated intraobserver and interobserver agreement in the grading of RA-like tendon tears shown by US, as well as the concordance between the US findings and the surgically induced lesions in the cadaver model. RA-like tendon damage was surgically induced in the tibialis anterior tendon (TAT) and tibialis posterior tendon (TPT) of ten ankle/foot fresh-frozen cadaveric specimens. Of the 20 tendons examined, six were randomly assigned a surgically induced partial tear; six a complete tear; and eight left undamaged. Three rheumatologists, experts in musculoskeletal US, assessed from 1 to 5 the quality of US imaging of the cadaveric models on a Likert scale. Tendons were then categorized as having either no damage, (0); partial tear, (1); or complete tear (2). All 20 tendons were blindly and independently evaluated twice, over two rounds, by each of the three observers. Overall, technical performance was satisfactory for all items in the two rounds (all values over 2.9 in a Likert scale 1-5). Intraobserver and interobserver agreement for US grading of tendon damage was good (mean κ values 0.62 and 0.71, respectively), with greater reliability found in the TAT than the TPT. Concordance between US findings and experimental tendon lesions was acceptable (70-100 %), again greater for the TAT than for the TPT. A cadaver model with surgically created tendon damage can be useful in evaluating US metric properties of RA tendon lesions.

Ultrasound-detected activity in rheumatoid arthritis on methotrexate therapy: Which joints and tendons should be assessed to predict unstable remission?

The aim of the study was to investigate the predictive value of different reduced joint ultrasound (US) assessments of synovitis and tenosynovitis in relation to unstable remission in a cohort of rheumatoid arthritis (RA) patients on methotrexate therapy. Forty-seven RA patients (38 women, 9 men), being treated with methotrexate (MTX), in clinical remission as judged by their consultant rheumatologist were evaluated for disease activity according to the Disease Activity Score (DAS) 28 at baseline and 6 months. Sustained remission and unstable remission were defined according to the baseline and 6-month DAS28 and changes in RA therapy during the follow-up. Each patient underwent at baseline a B-mode and power Doppler (PD) assessment of 44 joints and 20 tendons/tendon compartments by a rheumatologist blinded to the clinical and laboratory data. B-mode synovial hypertrophy (SH), synovial PD signal, B-mode tenosynovitis, and Doppler tenosynovitis were scored 0-3. The presence and index of synovial PD signal in 44 joints [odds ratio (OR) 8.21 (p = 0.016) and OR 2.20 (p = 0.049), respectively] and in 12 joints [OR 5.82 (p = 0.041) and OR 4.19 (p = 0.020), respectively], the presence of SH in wrist and MCP joints [OR 4.79 (p = 0.045)], and the presence of synovial PD signal in wrist-MCP-ankle-MTP joints [OR 4.62 (p = 0.046)] were predictors of unstable remission. The 12-joint or wrist-hand-ankle-MTP US assessments can predict unstable remission in RA patients in apparent clinical remission being treated with MTX.

Predictive value of Doppler ultrasound-detected synovitis in relation to failed tapering of biologic therapy in patients with rheumatoid arthritis.

OBJECTIVE: To investigate the predictive value of synovitis detected by Doppler US in relation to failed tapering of biologic therapy (BT) in RA patients in sustained clinical remission. METHODS: A total of 77 RA patients (52 women, 25 men) in sustained clinical remission, treated with a stable dosage of BT were prospectively recruited. BT was tapered according to an agreed strategy implemented in clinical practice (i.e. increasing the interval between doses for s.c. BT and reducing the dose for i.v. BT). BT tapering failure was assessed at 6 and 12 months. Doppler US investigation of 42 joints for the presence and grade (0-3) of B-mode synovial hypertrophy and synovial power Doppler signal (i.e. Doppler synovitis) was performed at baseline by a rheumatologist blinded to clinical and laboratory data. Hand and foot radiographs were obtained at baseline and at 12-month follow-up. RESULTS: Of the 77 patients, 46 (59.7%) were on s.c. BT and 31 (40.3%) on i.v. BT. At 12 months, 35 patients (45.5%) presented BT tapering failure, 23 of them (29.9% of all patients) in the first 6 months of BT tapering. In logistic regression analysis, the baseline DAS28 and the global score of Doppler synovitis were identified as independent predictors of BT tapering failure at 12 and 6 months. The presence of Doppler synovitis was the strongest predictor for BT tapering failure. No patient showed radiographic progression. CONCLUSION: Our results suggest that the presence of Doppler-detected synovitis may predict BT tapering failure in RA patients in sustained clinical remission.

Impact of musculoskeletal ultrasound on clinical practice in paediatric rheumatology.

OBJECTIVES: Musculoskeletal ultrasound (MSUS) is an imaging technique increasingly used in paediatric rheumatology. The aim of our study was to evaluate the extent to which MSUS may influence the diagnosis and management decisions in daily clinical practice in paediatric rheumatology. METHODS: All child patients attending our PR unit over a 3-month period were included. A consultant rheumatologist assessed juvenile patients and weighted the need for MSUS assessment under a Likert scale from 0 (not necessary) to 5 (very necessary) with scanning performed when the Likert score was greater than 0. The rheumatologist completed a questionnaire used to report previous and current diagnosis, therapeutic decisions and disease activity. An assistant rheumatologist who was blinded to the questionnaire carried out the MSUS scanning of selected joints. After MSUS examination, a second questionnaire was completed by the consultant rheumatologist reporting changes in diagnosis and systemic and local treatment, if applicable. RESULTS: We included 111 patients [73 (65.8%) female]. Fifteen (13.5%) were new patients and 96 (86.5%) follow-up patients. Fifty-one (45.9%) patients were diagnosed with JIA. 65 (58.6%) patients qualified for MSUS. A total of 108 joints from 65 patients were clinically assessed with 93 (86.1%) joints deemed to require complementary MSUS assessment (mean assessed joints 1.4 per patient). Of the 65 patients undergoing MSUS, 38 (58.5%) patients there was a change in diagnosis, therapeutic decisions or both following the MSUS information. CONCLUSIONS: MSUS may play a significant role in local diagnosis and therapeutic decisions among follow-up JIA patients and could help in the management of rheumatic diseases in children. Further longitudinal studies are needed to confirm the impact of MSUS in paediatric rheumatology.

Investigating the link between disease activity and infliximab serum levels in rheumatoid arthritis patients.

OBJECTIVES: The aim of this study was to examine the extent to which infliximab (IFX) serum levels impact disease activity in rheumatoid arthritis (RA) patients. METHODS: In this cross sectional study, serum samples were taken prior to drug infusion from 60 RA patients who had been undergoing IFX therapy > 12 months as a first line of biological treatment. Patient IFX levels were tested and then associated with clinical disease activity. Three DAS28 cut-off points, <2.6, <3.2 and <5.1 were used to determine whether detectable IFX levels were any predictor of clinical disease activity. Logistic regression analysis was run to check other possible factors associated with RA clinical outcomes such as MTX concomitant use, CRP and ESR. RESULTS: Sixteen (27%) out of the 60 patients tested negative; 28 (46%) presented subtherapeutic and 16 (27%) therapeutic IFX levels. Median IFX levels were higher in patients either in remission or showing low disease activity than in those with moderate and high disease activity (p=0.014). Significant association was found between IFX levels and clinical disease activity (p=0.001). Detectable levels of IFX shows better sensitivity and specificity to identify patients with DAS28<3.2 than to identify patients with DAS28<2.6 or DAS28<5.1. Conversely, the best DAS28 cut-off to identify detectable/undetectable IFX was 3.19, with AUC under ROC curve 0.804 (Sd.E 0.070), 76% specificity and 83% sensitivity (p<0.001). MTX use, CRP and ESR did not interfere with this association. Seven out of the 8 patients with anti-IFX antibodies presented DAS28>3.2 (p=0.005). CONCLUSIONS: DAS28 and IFX serum levels were shown to have an inverse correlation. Undetectable IFX serum levels were associated to RA patients presenting DAS28>3.2 meaning that DAS28 <3.2 may be useful to clinicians to evaluate patient response to drug therapy.

Relation of Doppler ultrasound synovitis versus clinical synovitis with changes in native complement component levels in rheumatoid arthritis patients treated with biologic disease-modifying anti-rheumatic drugs.

OBJECTIVES: The complement system plays a fundamental role in mediating the activity of rheumatoid arthritis (RA). Biologic therapy can reduce native complement component levels and its activation. We aimed to study the relation of Doppler ultrasound (US) synovitis versus clinical synovitis with changes in native complement component levels in RA patients on biologic therapy. METHODS: This was a cross-sectional study. Ninety-seven consecutive patients with RA on biologic therapy for at least 3 months were recruited. Clinical, laboratory and Doppler US assessments were performed. The Disease Activity Score in 28 joints (DAS28), Simplified Disease Activity Index (SDAI) and a 12-joint US assessment were carried out. Synovitis was semiquantitatively scored in B-mode and power Doppler (PD) mode. RESULTS: A significant decrease in native complement (i.e. C3 and C4) and C-reactive protein (CRP) levels was observed. This was highly significant for C3 decrease (p<0.0005), and C4 decrease (p<0.0005). Synovitis detected by PD US showed significant negative association with C3 change (p<0.008), where patients with higher C3 change were more likely to have PD US inactive status on assessment. CONCLUSIONS: Our results suggested that disease inactive status determined by PD US but not by clinical assessment can be related with decrease in complement in RA patients treated with biologic therapy.

Comparison of two ELISA versions for infliximab serum levels in patients diagnosed with ankylosing spondylitis.

There are various immunosorbent assays which can be used to determine infliximab (IFX) levels. Results vary between assays complicating reliability in everyday clinical practice. The aim of this study was to determine whether quantitative or qualitative assay data prove more accurate in the assessment of infliximab levels in AS patients. We analyzed 40 serum samples, taken prior to infusion, from AS patients who had been undergoing IFX therapy as a first-line of biological treatment for more than a year. IFX levels and IFX-anti-drug antibodies (ADA) were measured using two different ELISA assays [Promonitor IFX R1 and R2 (version 1), Promonitor IFX and anti-IFX (version 2) (Progenika Biopharma, Spain)] strictly following the manufacturer's guidelines. Cohen's unweighted kappa and the intraclass correlation coefficient determined qualitative and quantitative agreement for serum levels in version 1 and version 2. Bland-Altman plots were drawn to compare both assays. The comparison of data measuring IFX levels for version 1 and version 2 resulted in questionable quantitative agreement (ICC 0.659; 95% CI 0.317-0.830) and moderate qualitative agreement (κ 0.607; 95% CI 0.387-0.879) owing to systematically higher values in version 2 than version 1. Version 2 consistently detected higher levels of infliximab, particularly when analyzed in a quantitative context. Further research is needed to synchronize cutoff levels between essays and diseases so therapeutic drug ranges can be established.

Does ultrasound-scored synovitis depend on the pharmacokinetics of subcutaneous anti-TNF agents in patients with rheumatoid arthritis?

OBJECTIVE: The aim of this study was to investigate the influence of the pharmacokinetics of s.c. anti-TNF agents on the grade of US-detected synovitis in RA patients. METHODS: Fifty RA patients were prospectively recruited from the Biologic Therapy Unit of our hospital. Inclusion criteria were being in treatment with s.c. anti-TNF agents and having had neither changes in therapy nor local corticosteroid injections in the previous 3 months. Patients underwent clinical, laboratory [28-joint DAS (DAS28) and Simplified Disease Activity Index (SDAI)] and US assessment at two time points, i.e. at peak plasma drug concentration and at trough plasma drug concentration. US assessments were performed blindly to the anti-TNF agent, the administration time and the clinical and laboratory data. Twenty-eight joints were investigated for the presence and grade (0-3) of B-mode synovitis and synovial power Doppler signal. Global indices for B-mode synovitis (BSI) and Doppler synovitis (DSI) were calculated for 12 joints and for wrist-hand-ankle-foot joints. B-mode US remission was defined as a BSI <1 and Doppler US remission as a DSI <1. RESULTS: There were no significant differences between the clinical, laboratory and B-mode and Doppler US parameters at peak time and trough time (P = 0.132-0.986). There were no significant differences between the proportion of patients with active disease and those in remission according to DAS28, SDAI, B-mode US and Doppler US at peak time and trough time assessments (P = 0.070-1). CONCLUSION: Our results suggested that s.c. anti-TNF pharmacokinetics do not significantly influence US-scored synovitis in RA patients.

Salivary gland ultrasound in children: a useful tool in the diagnosis of juvenile Sjögren's syndrome.

Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease uncommon in children, clinically characterized by recurrent parotitis at the onset, which is a common disorder in childhood, most of them of infectious origin. Juvenile pSS diagnosis is based on clinical symptoms and presence of autoantibodies, after exclusion of infectious or lymphoproliferative diseases. However, salivary gland ultrasound (SGU) shows typical features of pSS that can add useful information for the diagnosis of this disorder. We describe three patients who presented with recurrent parotitis in which characteristic autoantibodies and typical SGU pattern allow us to make the diagnosis of juvenile pSS. We suggest that in children with recurrent parotitis SGU and autoantibodies should be routinely performed.

Clinical relevance of monitoring serum levels of adalimumab in patients with rheumatoid arthritis in daily practice.

OBJECTIVES: The aim of this paper is to assess the usefulness of measuring serum levels of adalimumab (ADL) and anti-ADL antibodies in 57 patients with rheumatoid arthritis (RA) treated with ADL for at least 3 months in daily practice. METHODS: All patients received concomitant disease-modifying anti-rheumatic drug (DMARD). Receiver-operator characteristics (ROC) analysis was used to obtain the cut-off value of ADL for low disease activity (DAS28-ESR ≤3.2). RESULTS: Anti-ADL antibodies were detected in 4 (7%) patients with a mean (SD) DAS28 score of 4.6 (0.9). Patients with positive anti-ADL antibodies had significantly lower levels of ADL and higher DAS28 scores than those with negative antibodies. Patients with DAS28 ≤3.2 as compared with patients with DAS28 >3.2 showed significantly better SDAI score, higher serum concentrations of ADL and none of them showed anti-ADL antibodies. The cut-off of serum level of ADL for DAS28 <3.2 was 4.3 mg/L. According to serum levels of ADL, patients were grouped into group 1 (low level) <5.5 mg/L, group 2 (medium level) 5.5-11.3 mg/L and group 3 (high level) >11.3 mg/L. Patients in the medium group were closed to clinical remission (median DAS28 2.7) and patients in the high group were on clinical remission (DAS28 2.1). CONCLUSIONS: Serum levels of ADL should be maintained >4.3 mg/L. In patients with ADL levels >11.3 mg/L, a decrease of the dose of ADL or an increase in the interval between doses may be planned. The presence of anti-ADL antibodies was associated with a loss of clinical efficacy of ADL.

Young male patient diagnosed with cutaneous polyarteritis nodosa successfully treated with etanercept.

Cutaneous polyarteritis nodosa (CPAN) is a form of necrotizing vasculitis of small and medium-sized arteries. It is limited to the skin and has a recurrent and chronic course, possibly associated with fever, arthralgia, myalgia and neuropathy, but without visceral involvement. We report the clinical case of a 7-year-old male patient with CPAN refractory to treatment with high doses of corticoids and cyclophosphamide, who was successfully treated with the TNF-α (tumor necrosis factor-alpha) inhibitor, etanercept, in monotherapy.

Changes in the pattern of DNA methylation associate with twin discordance in systemic lupus erythematosus.

Monozygotic (MZ) twins are partially concordant for most complex diseases, including autoimmune disorders. Whereas phenotypic concordance can be used to study heritability, discordance suggests the role of non-genetic factors. In autoimmune diseases, environmentally driven epigenetic changes are thought to contribute to their etiology. Here we report the first high-throughput and candidate sequence analyses of DNA methylation to investigate discordance for autoimmune disease in twins. We used a cohort of MZ twins discordant for three diseases whose clinical signs often overlap: systemic lupus erythematosus (SLE), rheumatoid arthritis, and dermatomyositis. Only MZ twins discordant for SLE featured widespread changes in the DNA methylation status of a significant number of genes. Gene ontology analysis revealed enrichment in categories associated with immune function. Individual analysis confirmed the existence of DNA methylation and expression changes in genes relevant to SLE pathogenesis. These changes occurred in parallel with a global decrease in the 5-methylcytosine content that was concomitantly accompanied with changes in DNA methylation and expression levels of ribosomal RNA genes, although no changes in repetitive sequences were found. Our findings not only identify potentially relevant DNA methylation markers for the clinical characterization of SLE patients but also support the notion that epigenetic changes may be critical in the clinical manifestations of autoimmune disease.

Patient self-assessment and physician's assessment of rheumatoid arthritis activity: which is more realistic in remission status? A comparison with ultrasonography.

OBJECTIVE: The objective of this study was to compare disease activity assessed by the patient, the physician and musculoskeletal US in patients with RA in clinical remission. METHODS: We evaluated 69 patients with RA in clinical remission according to their attending rheumatologist. Tenderness and swelling in 28 joints were blindly assessed by patients and physicians. The presence of B-mode and Doppler synovitis was blindly investigated in the above joints. The DAS28 and Simplified Disease Activity Index (SDAI) were calculated. RESULTS: The percentage of patients in remission according to the self-derived DAS28 (26.1%) was significantly less than that according to the physician-derived DAS28 (52.2%) (P < 0.0005). There was no significant difference in the percentage of patients in remission according to the self-derived SDAI (14.5%) and the physician-derived SDAI (11.6%) (P = 0.172). We found moderate agreement between the patient-derived and physician-derived DAS28 and SDAI [intraclass correlation coefficient (ICC) = 0.620 and ICC = 0.678, respectively]. Agreement between patient and physician was better for the tender joint count (TJC; ICC = 0.509) than for the swollen joint count (SJC; ICC = 0.279). The mean (S.D.) count for B-mode synovitis [4.09 (3.25)] was significantly greater than the SJC assessed by both the patient and physician [2 (3.71) and 1.42 (2.03), respectively] (P < 0.0005 and P = 0.033, respectively). We found moderate agreement between the physician-assessed SJC and the joint count for Doppler synovitis (ICC = 0.528). CONCLUSION: Patient-assessed and physician-assessed overall RA activity showed acceptable agreement. Patient self-assessment overestimated disease activity determined by the DAS28. At the patient level, physician-assessed joint swelling showed an acceptable concordance with Doppler US synovitis.

Young male patient diagnosed with cutaneous polyarteritis nodosa successfully treated with etanercept.

Cutaneous polyarteritis nodosa (CPAN) is a form of necrotizing vasculitis of small and medium-sized arteries. It is limited to the skin and has a recurrent and chronic course, possibly associated with fever, arthralgia, myalgia and neuropathy, but without visceral involvement. We report the clinical case of a 7-year-old male patient with CPAN refractory to treatment with high doses of corticoids and cyclophosphamide, who was successfully treated with the TNF-α (tumor necrosis factor-alpha) inhibitor, etanercept, in monotherapy.