Serum interferon-alpha level in first degree relatives of systemic lupus erythematosus patients: Correlation with autoantibodies titers

Background and objectives: Interferon-a (IFN-a), a cytokine with both antiviral and immune-regulatory functions, was suggested as a useful tool which can evaluate current systemic lupus erythematosus (SLE) disease activity and identify patients whoare at risk of future disease flares. In the current study, serum IFN-a levels and associated demographic, and serological features in Egyptian SLE patients and their first degree relatives (FDRs) in comparison to unrelated healthy controls (UHCs) were examined, in order to identify individuals at the greatest risk for clinical illness.Methods: In a cross-sectional study, blood samples were drawn from 54 SLE patients, 93 of their FDRs who consented to enroll into the study and 76 UHCs. Measurement of serum IFN-a by a modified ELISA was carried out. Data were analyzed for associations of serum IFN-a levels with autoantibodies titer.Results: Meanserum IFN-a inFDRswas statistically higher than theUHCsand lower than inSLE patients (P < 0.0001) and it was correlated with ANA titer (r = 0.6, P < 0.0001) and anti ds DNA titer (r = 0.62, P < 0.0001).Conclusion: IFN-a is a crucial player in the complicated autoimmune changes that occur in SLE and serum IFN-a can be a useful marker identifying persons who are at risk of future disease development.Keywords: Interferon-a; Systemic lupus erythematosus; First degree relatives; Autoantibodie

Ultrasound measurement of joint cartilage thickness in large and small joints in healthy children: a clinical pilot study assessing observer variability

<p>Abstract</p> <p>Background</p> <p>Loss of joint cartilage is a feature of destructive disease in JIA. The cartilage of most joints can be visualized with ultrasonography (US). Our present study focuses on discriminant validity of US in children. We studied reproducibility between and within a skilled and a non-skilled investigator of US assessment of cartilage thickness in small and large joints in healthy children.</p> <p>Methods and results</p> <p>In 11 healthy children (5 girls/6 boys), aged 9.6 years (9.3–10 years), 110 joints were examined. Cartilage thickness of the right and left hip, knee, ankle, 2^ndmetacarpophalangeal (MCP), and 2^ndproximal interphalangeal (PIP) joint independently. The joints were examined twice, two days apart by a skilled and a non-skilled investigator. Mean cartilage thickness in the five joints was: hip 2.59 ± 0.41, knee 3.67 ± 0.64, ankle 1.08 ± 0.31, MCP 1.52 ± 0.27 and PIP 0.73 ± 0.15 mm. We found the same mean differences in CTh of 0.6 mm in the inter-observer part with regard of the PIP joint. Within investigators (intra-observer), the smallest mean difference of CTh was found in the MCP joint with -0.004 (skilled) and 0.013 mm (non-skilled).</p> <p>Conclusion</p> <p>We found the level of agreement between observers within a 95% Confidence Interval in assessment of cartilage thickness in hip-, knee-, ankle-, MCP-, and PIP joints in healthy children. Observer variability seems not to relate to joint size but to the positioning of the joints and the transducer. These factors seem to be of major importance for reproducible US measurements. The smallest difference in measurement of cartilage thickness <it>between observers </it>was found in the PIP joint, and <it>within observers </it>in the MCP joint and it seems that using EULAR standard US guidelines is feasible for a pediatric setting. The use of US in children is promising. Studies on larger groups of children are needed to confirm the validation and variability of US in children as well as determining the smallest detectable difference of US measures.</p

Heterochrony and Cross-Species Intersensory Matching by Infant Vervet Monkeys

Understanding the evolutionary origins of a phenotype requires understanding the relationship between ontogenetic and phylogenetic processes. Human infants have been shown to undergo a process of perceptual narrowing during their first year of life, whereby their intersensory ability to match the faces and voices of another species declines as they get older. We investigated the evolutionary origins of this behavioral phenotype by examining whether or not this developmental process occurs in non-human primates as well.We tested the ability of infant vervet monkeys (Cercopithecus aethiops), ranging in age from 23 to 65 weeks, to match the faces and voices of another non-human primate species (the rhesus monkey, Macaca mulatta). Even though the vervets had no prior exposure to rhesus monkey faces and vocalizations, our findings show that infant vervets can, in fact, recognize the correspondence between rhesus monkey faces and voices (but indicate that they do so by looking at the non-matching face for a greater proportion of overall looking time), and can do so well beyond the age of perceptual narrowing in human infants. Our results further suggest that the pattern of matching by vervet monkeys is influenced by the emotional saliency of the Face+Voice combination. That is, although they looked at the non-matching screen for Face+Voice combinations, they switched to looking at the matching screen when the Voice was replaced with a complex tone of equal duration. Furthermore, an analysis of pupillary responses revealed that their pupils showed greater dilation when looking at the matching natural face/voice combination versus the face/tone combination.Because the infant vervets in the current study exhibited cross-species intersensory matching far later in development than do human infants, our findings suggest either that intersensory perceptual narrowing does not occur in Old World monkeys or that it occurs later in development. We argue that these findings reflect the faster rate of neural development in monkeys relative to humans and the resulting differential interaction of this factor with the effects of early experience

Inter -and intraobserver variation of ultrasonographic cartilage thickness assessments in small and large joints in healthy children

<p>Abstract</p> <p>Background</p> <p>There is an increasing interest among pediatric rheumatologist for using ultrasonography (US) in the daily clinical examination of children with juvenile idiopathic arthritis (JIA). Loss of joint cartilage may be an early feature of destructive disease in JIA. However, US still needs validation before it can be used as a diagnostic bedside tool in a pediatric setting. This study aims to assess the inter- and intraobserver reliability of US measurements of cartilage thickness in the joints of healthy children.</p> <p>Methods</p> <p>740 joints of 74 healthy Caucasian children (27 girls/47 boys), aged 11.3 (7.11 – 16) years were examined with bilateral US in 5 preselected joints to assess the interobserver variability. In 17 of these children (6 girls/11 boys), aged 10.1(7.11–11.1) years, 170 joints was examined in an intraobserver sub study, with a 2 week interval between the first and second examination.</p> <p>Results</p> <p>In this study we found a good inter- and intraobserver agreement expressed as a coefficient of variation (CV) less than 10% in the knee (CV = 9.5%_{interobserver}and 5.9%_{intraobservserI}, 9.3%_{intraobserverII}respectively for the two intraobserver measurements) and fairly good for the MCP joints (CV = 11.9%_{interobserver}, 12.9%_{intraobserverI}and 11.9%_{intraobsevrerII}). In the ankle and PIP joints the inter- and intraobserver agreement was within an acceptable limit (CV<20%) but not for the wrist joint (CV>26%). We found no difference in cartilage thickness between the left and right extremity in the investigated joints.</p> <p>Conclusion</p> <p>We found a good inter -and intraobserver agreement when measuring cartilage thickness with US. The inter- and intraobserver variation seemed not to be related to joint size. These findings suggest that positioning of the joint and the transducer is of major importance for reproducible US measurements. We found no difference in joint cartilage thickness between the left and right extremity in any of the examined joint of the healthy children. This is an important finding giving the opportunity of using the non-affected extremity as a reference when assessing articular joint cartilage damage in JIA.</p

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Ultrasonography and color Doppler in juvenile idiopathic arthritis: diagnosis and follow-up of ultrasound-guided steroid injection in the wrist region. A descriptive interventional study

<p>Abstract</p> <p>Background</p> <p>The wrist region is one of the most complex joints of the human body. It is prone to deformity and functional impairment in juvenile idiopathic arthritis (JIA), and is difficult to examine clinically. The aim of this study was to evaluate the role of ultrasonography (US) with Doppler in diagnosis of synovitis, guidance of steroid injections, and follow-up examinations of the wrist in JIA.</p> <p>Methods</p> <p>In 11 patients (median age 12.5 years, range 2-16), 15 wrists with clinically active arthritis were assessed clinically by US and color Doppler (Logiq 9, GE, 16-4 MHz linear transducer) prior to and 1 and 4 weeks after US-guided steroid injection.</p> <p>Results</p> <p>US detected synovitis in the radio-carpal joints, the midcarpal joints, and the tendon sheaths in 87%, 53% and 33% of the wrists, respectively. Multiple compartments were involved in 67%. US-guidance allowed accurate placement of steroid in all 21 injected compartments, with a low rate of subcutaneous atrophy. Synovial hypertrophy was normalized in 86% of the wrists, hyperemia in 91%, and clinically active arthritis in 80%.</p> <p>Conclusions</p> <p>US enabled detection of synovial inflammation in compartments that are difficult to evaluate clinically and exact guidance of injections, and it was valuable for follow-up examinations. Normalization of synovitis was achieved in most cases, which supports the notion that US is an important tool in management of wrist involvement in JIA.</p

Elevated serum levels of soluble CD154 in children with juvenile idiopathic arthritis

<p>Abstract</p> <p>Objective</p> <p>Cytokines play important roles in mediating inflammation in autoimmunity. Several cytokines are elevated in serum and synovial fluid samples from children with Juvenile Idiopathic Arthritis (JIA). Soluble CD154 (sCD154) is elevated in other autoimmune disorders, but has not been characterized in JIA. Our objectives were to determine if sCD154 is elevated in JIA, and to examine correlations between sCD154 and other inflammatory cytokines.</p> <p>Methods</p> <p>Serum from 77 children with JIA and 81 pediatric controls was analyzed for interleukin (IL)1β, IL2, IL4, IL5, IL6, IL8, IL10, IL12, IL13, sCD154, interferon-γ (IFNγ), soluble IL2 receptor (sIL2R), and tumor necrosis factor-α (TNFα), using the Luminex Multi-Analyte Profiling system. Differences in levels of cytokines between cases and controls were analyzed. Logistic regression was also performed.</p> <p>Results</p> <p>sCD154 was significantly elevated in cases compared to controls (p < 0.0001). IL1β, IL5, IL6, IL8, IL13, IFNγ, sIL2R, and TNFα were also significantly elevated in JIA. Levels of sCD154 were highly correlated with IL1β, IL6, IL8, and TNFα (p < 0.0001). Logistic regression analysis suggested that IL6 (odds ratio (OR): 1.4, p < 0.0001), sCD154 (OR: 1.1, p < 0.0001), and TNFα (OR: 1.1, p < 0.005) were positively associated with JIA, while IL10 (OR: 0.5, p < 0.002) was protective. sCD154 was elevated in all JIA subtypes, with highest levels among more severe subtypes. IL1β, IL6, IL8, sIL2R and TNFα were also elevated in several JIA subtypes.</p> <p>Conclusion</p> <p>Serum levels of sCD154, IL1β, IL6, IL8, sIL2R and TNFα are elevated in most JIA subtypes, suggesting a major role for sCD154, and these cytokines and cytokine receptors in the pathogenesis of JIA.</p

Ultrasonography and color Doppler in juvenile idiopathic arthritis: diagnosis and follow-up of ultrasound-guided steroid injection in the ankle region. A descriptive interventional study

BACKGROUND: The ankle region is frequently involved in juvenile idiopathic arthritis (JIA) but difficult to examine clinically due to its anatomical complexity. The aim of the study was to evaluate the role of ultrasonography (US) of the ankle and midfoot (ankle region) in JIA. Doppler-US detected synovial hypertrophy, effusion and hyperemia and US was used for guidance of steroid injection and to assess treatment efficacy. METHODS: Forty swollen ankles regions were studied in 30 patients (median age 6.5 years, range 1-16 years) with JIA. All patients were assessed clinically, by US (synovial hypertrophy, effusion) and by color Doppler (synovial hyperemia) before and 4 weeks after US-guided steroid injection. RESULTS: US detected 121 compartments with active disease (joints, tendon sheaths and 1 ganglion cyst). Multiple compartments were involved in 80% of the ankle regions. The talo-crural joint, posterior subtalar joint, midfoot joints and tendon sheaths were affected in 78%, 65%, 30% and 55% respectively. Fifty active tendon sheaths were detected, and multiple tendons were involved in 12 of the ankles. US-guidance allowed accurate placement of the corticosteroid in all 85 injected compartments, with a low rate of subcutaneous atrophy (4,7%). Normalization or regression of synovial hypertrophy was obtained in 89%, and normalization of synovial hyperemia in 89%. Clinical resolution of active arthritis was noted in 72% of the ankles. CONCLUSIONS: US enabled exact anatomical location of synovial inflammation in the ankle region of JIA patients. The talo-crural joint was not always involved. Disease was frequently found in compartments difficult to evaluate clinically. US enabled exact guidance of steroid injections, gave a low rate of subcutaneous atrophy and was proved valuable for follow-up examinations. Normalization or regression of synovial hypertrophy and hyperemia was achieved in most cases, which supports the notion that US is an important tool in the management of ankle involvement in JIA