Free-electron lasing with compact beam-driven plasma wakefield accelerator.

The possibility to accelerate electron beams to ultra-relativistic velocities over short distances by using plasma-based technology holds the potential for a revolution in the field of particle accelerators1-4. The compact nature of plasma-based accelerators would allow the realization of table-top machines capable of driving a free-electron laser (FEL)5, a formidable tool to investigate matter at the sub-atomic level by generating coherent light pulses with sub-ångström wavelengths and sub-femtosecond durations6,7. So far, however, the high-energy electron beams required to operate FELs had to be obtained through the use of conventional large-size radio-frequency (RF) accelerators, bound to a sizeable footprint as a result of their limited accelerating fields. Here we report the experimental evidence of FEL lasing by a compact (3-cm) particle-beam-driven plasma accelerator. The accelerated beams are completely characterized in the six-dimensional phase space and have high quality, comparable with state-of-the-art accelerators8. This allowed the observation of narrow-band amplified radiation in the infrared range with typical exponential growth of its intensity over six consecutive undulators. This proof-of-principle experiment represents a fundamental milestone in the use of plasma-based accelerators, contributing to the development of next-generation compact facilities for user-oriented applications9.

Relationship between sex and clinical and imaging features of early axial spondyloarthritis: results from a 48 month follow-up (Italian arm of the SPondyloArthritis Caught Early (SPACE) study).

OBJECTIVES: To assess the association between sex and clinical and disease activity indices, and X-rays and magnetic resonance imaging (MRI) features, in early-stage axial spondyloarthritis (axSpA). METHOD: Baseline data analysis was conducted on the Italian SPACE cohort, including patients with chronic back pain (duration ≥ 3 months and ≤ 2 years; onset < 45 years). Patients underwent MRI and X-rays of the sacroiliac joints (SIJs) to establish the diagnosis of axSpA, according to Assessment of SpondyloArthritis international Society criteria and physician's judgement. Clinical features, disease activity and functional indices, and images were collected at baseline and yearly during 48 months. Spinal and SIJ X-rays and MRI images were scored by two readers following Spondyloarthritis Research Consortium of Canada (SPARCC), modified Stoke Ankylosing Spondylitis Spinal Score, and modified New York criteria. Characteristics of axSpA patients according to sex (male/female) were compared over time using descriptive statistics. RESULTS: Ninety-one patients had axSpA (83.5% non-radiographic; 16.5% radiographic); 47.3% were male. Males were younger, with shorter duration of axial symptoms, and more frequently had HLA-B27 positivity, radiographic sacroiliitis with a bilateral/symmetric pattern, and more signs of spondylitis. Females more frequently showed peripheral/entheseal involvement and the non-radiographic phenotype. Males showed increased pelvic/spinal radiographic progression and more often had active sacroiliitis on MRI. Although the frequency of inflammatory corner lesions did not differ between males and females, localization varied, with more cervical/thoracic MRI-spine lesions in females and more lumbar lesions in males. We observed a significant downward trend of SPARCC SIJ/spine scores in all patients, irrespective of sex. More fat lesions were observed on MRI-spine in females and on MRI-SIJ in males. CONCLUSION: Sex was associated with distinct axSpA features: females showed low-grade radiographic sacroiliitis and spinal progression, and a higher prevalence of cervical and thoracic spine MRI signs.

Stable Operation of a Free-Electron Laser Driven by a Plasma Accelerator.

The breakthrough provided by plasma-based accelerators enabled unprecedented accelerating fields by boosting electron beams to gigaelectronvolt energies within a few centimeters [1-4]. This, in turn, allows the realization of ultracompact light sources based on free-electron lasers (FELs) [5], as demonstrated by two pioneering experiments that reported the observation of self-amplified spontaneous emission (SASE) driven by plasma-accelerated beams [6,7]. However, the lack of stability and reproducibility due to the intrinsic nature of the SASE process (whose amplification starts from the shot noise of the electron beam) may hinder their effective implementation for user purposes. Here, we report a proof-of-principle experiment using plasma-accelerated beams to generate stable and reproducible FEL light seeded by an external laser. FEL radiation is emitted in the infrared range, showing the typical exponential growth of its energy over six consecutive undulators. Compared to SASE, the seeded FEL pulses have energies 2 orders of magnitude larger and stability that is 3 times higher.

SARS-CoV-2 infection in patients with autoimmune rheumatic diseases in northeast Italy: A cross-sectional study on 916 patients.

BACKGROUND: Whether patients with autoimmune rheumatic diseases (ARD) have a higher risk for SARS-CoV-2 infection (COVID-19) and how SARS-CoV-2 pandemic impacts on adherence to therapy has not been fully elucidated. We assessed the rate and clinical presentation of COVID-19, and adherence to therapy in a large cohort of patients with ARD followed-up in a tertiary University-Hospital in Northeast Italy. METHODS: Between April 9th and April 25th, 2020, after SARS-CoV-2 infection peak, a telephone survey investigating the impact of COVID-19 on patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), ANCA-associated vasculitis (AAV), and idiopathic inflammatory myopathies (IIM) was administered. Demographics, disease activity status, therapy, occupational exposure, and adherence to social distancing advise were also collected. RESULTS: 916 patients (397 SLE, 182 AAV, 176 SSc, 111 RA, 50 IIM) completed the survey. 148 patients developed at least one symptom compatible with COVID-19 (cough 96, sore throat 64, fever 64, arthromyalgias 59, diarrhea 26, conjunctivitis 18, ageusia/hyposmia, 18). Among the 916 patients, 65 (7.1%) underwent SARS-CoV-2 nasopharyngeal swab (18 symptomatic and 47 asymptomatic), 2 (0.21%) tested positive, a proportion similar to that observed in the general population of the Veneto region. No deaths occurred. 31 patients (3.4%) withdrew ≥1 medication, mainly immunosuppressants or biologics. Adoption of social distancing was observed by 860 patients (93.9%), including 335 (36.6%) who adopted it before official lockdown. CONCLUSIONS: COVID-19 incidence seems to be similar in our cohort compared to the general population. Adherence to therapy and to social distancing advise was high.

A 6-month open-label extension study of the safety and efficacy of subcutaneous belimumab in patients with systemic lupus erythematosus.

Objective To evaluate the safety, tolerability and efficacy of subcutaneous (SC) belimumab in patients with systemic lupus erythematosus (SLE) beyond 1 year. Methods This was a 24-week, open-label extension following a 52-week, double-blind, placebo-controlled trial of belimumab SC. Patients who completed the double-blind phase were eligible to enter the open-label phase. All patients received weekly belimumab 200 mg SC plus standard SLE therapy. Outcome measures included safety and efficacy (SLE Response Index (SRI) and SLE Flare Index (SFI) rates), and changes in biomarker and B cell levels. Results Of 677 patients who completed the 52-week, double-blind phase, 662 entered the open-label phase; 206 had previously received placebo and 456 had previously received belimumab. Despite differences in total belimumab exposure (24 weeks in the placebo-to-belimumab group versus 76 weeks in the belimumab group), the proportions of patients experiencing more than one adverse event (AE) or a serious AE in the open-label phase were similar between groups (placebo-to-belimumab: 51.5 and 6.8%; belimumab: 48.2 and 5.5%, respectively). Most AEs were mild/moderate in severity. Efficacy was maintained through the extension phase. An SRI response was achieved by 16.1% of patients in the placebo-to-belimumab group and 76.3% patients in the belimumab group. Furthermore, 1.0% of patients in the placebo-to-belimumab group and 2.6% of patients in the belimumab group experienced a severe SFI flare. Conclusion Belimumab SC was well tolerated and efficacy was maintained during the extension phase of this study. The safety profile of belimumab SC is consistent with that of previous experience with belimumab. Trial registration ClinicalTrials.gov identifier: NCT01484496.

Early Lupus Project: one-year follow-up of an Italian cohort of patients with systemic lupus erythematosus of recent onset.

Objective To describe the clinical and serological features of a prospectively followed cohort of early diagnosed systemic lupus erythematosus (SLE) patients during a one-year follow-up period. Methods SLE patients with disease duration less than 12 months were consecutively enrolled in a multicentre, prospective study. At study entry and then every 6 months, a large panel of data was recorded. Results Of 260 patients enrolled, 185 had at least 12 months of follow-up; of these, 84.3% were female, 92.4% were Caucasians. Mean diagnostic delay was about 20 months; higher values of European Consensus Lupus Activity Measurement (ECLAM) and of organs/systems involved were both associated with shorter diagnostic delay. Clinical and serological parameters improved after study entry. However, patients' quality of life deteriorated and cardiovascular risk factors significantly increased. About one-third of patients with active disease at study entry went into remission (ECLAM = 0). Negative predictors for remission were: oral ulcers, arthritis, low C4, anti-SSB (Ro) antibodies and therapy with mycophenolate. There was a widespread use of glucocorticoids both at baseline and during follow-up. Conclusion Clinical symptoms and serological parameters improve during the first period after diagnosis. However, patients' quality of life deteriorates. The widespread use of glucocorticoids is probably the reason for the early significant increase of some cardiovascular risk factors.

EULAR recommendations for women's health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and/or antiphospholipid syndrome.

OBJECTIVES: Develop recommendations for women's health issues and family planning in systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS). METHODS: Systematic review of evidence followed by modified Delphi method to compile questions, elicit expert opinions and reach consensus. RESULTS: Family planning should be discussed as early as possible after diagnosis. Most women can have successful pregnancies and measures can be taken to reduce the risks of adverse maternal or fetal outcomes. Risk stratification includes disease activity, autoantibody profile, previous vascular and pregnancy morbidity, hypertension and the use of drugs (emphasis on benefits from hydroxychloroquine and antiplatelets/anticoagulants). Hormonal contraception and menopause replacement therapy can be used in patients with stable/inactive disease and low risk of thrombosis. Fertility preservation with gonadotropin-releasing hormone analogues should be considered prior to the use of alkylating agents. Assisted reproduction techniques can be safely used in patients with stable/inactive disease; patients with positive antiphospholipid antibodies/APS should receive anticoagulation and/or low-dose aspirin. Assessment of disease activity, renal function and serological markers is important for diagnosing disease flares and monitoring for obstetrical adverse outcomes. Fetal monitoring includes Doppler ultrasonography and fetal biometry, particularly in the third trimester, to screen for placental insufficiency and small for gestational age fetuses. Screening for gynaecological malignancies is similar to the general population, with increased vigilance for cervical premalignant lesions if exposed to immunosuppressive drugs. Human papillomavirus immunisation can be used in women with stable/inactive disease. CONCLUSIONS: Recommendations for women's health issues in SLE and/or APS were developed using an evidence-based approach followed by expert consensus.

A systematic review of ultrasound imaging as a tool for evaluating haemophilic arthropathy in children and adults.

The purpose of this study was to semi-quantitatively assess the evidence on the value of ultrasound (US) for assessment of haemophilic arthropathy (HA) in children and adults based on the following questions: (1) Does early diagnosis of pathological findings, using available US techniques, impact the functional status of the joint? (2) Do current available US techniques have the ability to accurately detect pathological changes in target joints in haemophilic patients? (3) Does treatment (prophylaxis) improve US evidence of haemophilic arthropathy in children and adults? (4) Is there any association between various US scoring systems and other clinical/radiological constructs? Of the 6880 citations identified searching databases such as MEDLINE, Embase, CENTRAL and Web of Science, 20 articles investigating either the diagnostic accuracy of US and/or US scanning protocols and scoring systems for assessment of HA met the inclusion criteria for the study. Of these, 14 articles evaluating the diagnostic accuracy of US were assessed by two independent reviewers for reporting quality using the Standards for Reporting of Diagnostic Accuracy (STARD) tool and for methodological quality using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Using STARD, 1/14 studies (7%) was scored as of high reporting quality and 8/14 (57%), of moderate quality. Assessment with QUADAS-2 reported 2/14 (14%) studies as having high methodological quality and 6/14 (43%) as having moderate quality. There is fair evidence (Grade B) to recommend US as an accurate technique for early diagnosis of HA, to demonstrate that US scores correlate with clinical/US constructs and to prove an association between US findings and functional status of the joint. However, there is insufficient evidence (Grade I) to conclude that US-detectable findings in HA are sensitive to changes in therapy.

Pilot study on 18 F-FDG PET/CT for detection of inflammatory changes in blood-induced knee arthropathy in a rabbit model.

RATIONALE: 18 F-FDG-PET/CT has a potential role in the early detection of haemophilic arthritis, at a time when treatment may still avoid further joint degeneration. The purposes of this pilot study were to determine the ability of 18 F-FDG-PET/CT to detect inflammatory changes associated with blood-induced arthropathy in knees of a rabbit model. METHODS: Ten juvenile rabbits were imaged at baseline and weeks 5 and 17 post intraarticular autologous blood injections (ABI). Five rabbits in group 1 (G1) had ABI into the same knee joint every 2 weeks (total, eight injections). Five rabbits in group 2 (G2) had only two injections into the same knee, at weeks 5 and 17. Images were assessed visually and semi-quantitatively by measuring maximal standardized uptake values (SUVmax) and standardized uptake ratio (SUR = SUVmax in affected knee/SUVmax in non-affected knee). RESULTS: More rabbits in G1 than G2 presented with positive chronic inflammatory synovial scores at week 17. Mean iron staining scores in injected knees were greater for G1 than for G2 (P = 0.049). No increased uptake was identified in the injected knees in any of the rabbits at baseline or at week 5. At week 17, all G1 rabbits demonstrated increased uptake in their affected knees with higher mean SUVmax (1.5) than normal knees (1.0) (P < 0.02). None of the G2 rabbits showed asymmetric increased uptake. The SUR of G1 was higher at week 17 compared to baseline (P < 0.01) and week 5 (P < 0.01). The SUR at week 17 was higher for G1 than for G2 (1.13) rabbits (P < 0.01). CONCLUSION: 18 F-FDG-PET is able to detect the inflammatory changes associated with haemophilic arthropathy in this experimental model.

Choosing outcome assessment tools in haemophilia care and research: a multidisciplinary perspective.

INTRODUCTION: The implementation of early long-term, regular clotting factor concentrate (CFC) replacement therapy ('prophylaxis') has made it possible to offer boys with haemophilia a near normal life. Many different regimens have reported favourable results, but the optimum treatment regimens have not been established and the cost of prophylaxis is very high. Both for optimizing treatment and reimbursement issues, there is a need to provide objective evidence of both short- and long-term results and benefits of prophylactic regimens. AIMS: This report presents a critical review of outcome measures for use in the assessment of musculoskeletal health in persons with haemophilia according to the International Classification of Functioning, Disability and Health (ICF). This framework considers structural and functional changes, activities and participation in a context of both personal and environmental factors. METHODS: Results were generated by a combination of a critical review of available literature plus expert opinion derived from a two day consensus conference between 48 health care experts from different disciplines involved in haemophilia assessment and care. Outcome tools used in haemophilia were reviewed for reliability and validity in different patient groups and for resources required. RESULTS AND CONCLUSION: Recommendations for choice of outcome tools were made according to the ICF domains, economic setting, and reason for use (clinical or research). The next step will be to identify a 'core' set of outcome measures for use in clinical care or studies evaluating treatment.

Imaging of haemophilic arthropathy in growing joints: pitfalls in ultrasound and MRI.

The purpose of this review was to summarize the current knowledge on the utilization of magnetic resonance imaging (MRI) and ultrasound (US) for assessing arthropathy in children and adolescents with haemophilia and to recognize the limitations of each imaging modality and pitfalls in the diagnosis of soft tissue and osteochondral abnormalities. Awareness of MRI and US limitations and pitfalls in the assessment of joints in persons with haemophilia is essential for accurate diagnosis and optimal management of haemophilic arthropathy.

Epidemiology behavior of leptospirosis in Ciénaga de Oro, Córdoba (Colombia).

The purpose of this study was to determine the epidemiology of leptospirosis in rural areas of Ciénaga de Oro, Córdoba, Colombia, a convenience sampling was carried out on 13 farms. The sample size was 325 reproductive age cows, 11 canine samples, and 20 humans. The samples were subjected to MAT analysis with 11 serogroups of Leptospira interrogans sensu lato. Once the MAT results were received, urine samples were collected from 78 cows, along with 39 water samples, for bacteriological cultures and PCR for the 16S rRNA gene in L. interrogans sensu lato. Positive PCR samples were sequenced to determine the possible genome species. The leptospirosis seroprevalence was 74.5% in the cattle, 70.0% in the dogs, and 45.5% in the humans. Although isolation was not achieved, L. interrogans sensu lato was detected by PCR in three urine samples and in a sample of wastewater. The sequencing confirmed the circulation of pathogenic species. The high prevalence of antibodies for L. interrogans sensu lato and the molecular evidence led to the inference that the rural areas of Ciénaga de Oro are endemic and that cattle can act as renal carriers and contaminate water sources, which increases the risk of contracting leptospirosis.

Correlating clinical and radiological assessment of joints in haemophilia: results of a cross sectional study.

OBJECTIVES: This study was undertaken to determine the correlation between the radiological changes in haemophilic arthropathy [X-ray, Ultrasound (US) and MRI] and clinical assessment as determined by the Hemophilia Joint Health Score (HJHS); and to document the US and MRI changes in joints that appear normal on plain X-ray and clinical evaluation. MATERIALS AND METHODS: Of 55 study joints (22 knees and 33 ankles) in 51 patients with haemophilia/von Willebrand disease, with a median age of 15 years (range: 5-17) were assessed using X-rays (Pettersson score) and clinical examination (HJHS) at two centres (Toronto, Canada; Vellore, India). MRI and ultrasonographic scoring was done through a consensus assessment by imagers at both centres using the IPSG MRI and US scores. RESULTS: The HJHS had a good correlation with the Pettersson score (rs = 0.66). Though the HJHS had moderate correlation with the osteochondral component of the MRI and US scores (rs 0.51, 0.45 respectively), its correlation with the soft tissue component was poor (rs 0.19; 0.26 respectively). Of the 18 joints with a Pettersson score of zero, 88.9% had changes that were detected clinically by the HJHS. Osteochondral abnormalities were identified in 38.9% of these joints by the MRI, while US images of the same joints were deemed abnormal in 83.3% by the current criteria. US identified haemosiderin and other soft tissue changes in all of the joints, while the same changes were noted in 94.4% of these joints on MRI. There were four joints with a HJHS of zero, all of which had soft tissue changes on MRI (score 1-7) and US (score 2-7). Osteochondral changes were detected in three of these joints by US and in 2 by MRI. There were four joints with an MRI score of 0-1 that had significant US scores (3-5) and HJHS scores (0-6). CONCLUSION: US and MRI are able to identify pathological changes in joints with normal X-ray imaging and clinical examination. However, further studies are required to be able to differentiate early abnormalities from normal. Clinical (HJHS) and radiological assessment (US/MRI) provide complimentary information and should be considered conjointly in the assessment of early joint arthropathy.

Relationships among growth mechanism, structure and morphology of PEALD TiO2 films: the influence of O2 plasma power, precursor chemistry and plasma exposure mode.

Titanium dioxide (TiO2) thin films have generated considerable interest over recent years, because they are functional materials suitable for a wide range of applications. The efficient use of the outstanding functional properties of these films relies strongly on their basic characteristics, such as structure and morphology, which are affected by deposition parameters. Here, we report on the influence of plasma power and precursor chemistry on the growth kinetics, structure and morphology of TiO2 thin films grown on Si(100) by plasma-enhanced atomic layer deposition (PEALD). For this, remote capacitively coupled 13.56 MHz oxygen plasma was used to act as a co-reactant during the ALD process using two different metal precursors: titanium tetrachloride (TiCl4) and titanium tetraisopropoxide (TTIP). Furthermore, we investigate the effect of direct plasma exposure during the co-reactant pulse on the aforementioned material properties. The extensive characterization of TiO2 films using Rutherford backscattering spectroscopy, ellipsometry, x-ray diffraction (XRD), field-emission scanning electron microscopy, and atomic force microscopy (AFM) have revealed how the investigated process parameters affect their growth per cycle (GPC), crystallization and morphology. The GPC tends to increase with plasma power for both precursors, however, for the TTIP precursor, it starts decreasing when the plasma power is greater than 100 W. From XRD analysis, we found a good correlation between film crystallinity and GPC behavior, mainly for the TTIP process. The AFM images indicated the formation of films with grain size higher than film thickness (grain size/film thickness ratio ≈20) for both precursors, and plasma power analysis allows us to infer that this phenomenon can be directly related to the increase of the flux of energetic oxygen species on the substrate/growing film surface. Finally, the effect of direct plasma exposure on film structure and morphology was evidenced showing that the grid removal causes a drastic reduction in the grain size, particularly for TiO2 synthesized using TiCl4.

Longitudinal assessment of bone loss using quantitative ultrasound in a blood-induced arthritis rabbit model.

INTRODUCTION: Osteoporosis is common in haemophilic arthropathy. Quantitative ultrasound (QUS) can be a suitable alternative for dual-energy x-ray absorptiometry for diagnosing osteoporosis in haemophiliacs due to its lack of ionizing radiation, and ease to use. AIM: We investigated the intra- and inter-operator reliability of QUS, its responsiveness to bone growth, its ability to differentiate bone adjacent to blood-injected vs. control joints, and the effect of soft tissues on the speed of sound (SOS) QUS values in a juvenile white New Zealand rabbit model of blood-induced arthritis. METHODS: Eight of 16 rabbits were injected with autologous blood (0.1 mL kg(-1) ) 8 times over a 17-week period, the remaining eight rabbits served as controls. SOS was measured at baseline, weeks 8 and 17 in vivo and after the bones were excised on week 17. RESULTS: Intra- and inter-operator coefficients of variation for QUS data were <5% and intraclass correlation coefficients were >60% for 22/27 (81.5%) of bones assessed. The level of interval increase in SOS values from baseline to week 17 was significantly different in tibiae of injected, contralateral to injected and non-injected knee groups by anova (P = 0.01). In vivo (mean ± SD, 4147.17 ± 96.27 m s(-1) ) and postmortem (4457.85 ± 104.00 m s(-1) ) measurements on week 17 differed (P < 0.01) indicating an effect of soft tissues on SOS. CONCLUSION: In conclusion, QUS' acceptable reliability, its responsiveness to growth-related changes and its ability to discriminate injected and non-injected joints make this technique a plausible candidate as a diagnostic tool for osteoporosis in the paediatric haemophilic population if these results are confirmed upon animal-human translation.

USPIO-related T1 and T2 mapping MRI of cartilage in a rabbit model of blood-induced arthritis: a pilot study.

Ultrasmall paramagnetic iron oxide (USPIO)-enhanced MRI is promising for evaluating inflammation. The aims of this study were to investigate the effect of USPIO on cartilage T1 and T2 mapping, and to evaluate a proposed rapid vs. conventional T2 map method for imaging cartilage in a blood-induced arthritis model. Knees of nine arthritic (induction by intra-articular autologous blood injection) and six control rabbits were imaged over time (baseline, weeks 1, 5, 10) by 1.5 T MRI. All rabbits had USPIO (35-75 µmol Fe/kg)-enhanced MRI at each time point. T1 and T2 (conventional and rapid) maps and signal-to-noise ratios (SNR) were obtained pre- and post-USPIO administration. Cartilage biochemistry and histology were compared with MRI. Excellent correlations were noted between T1 map values and histologic scores at week 10 pre-USPIO (medial, r = 0.93, P = 0.0007; lateral, r = 0.87, P = 0.005) in the arthritic group, but not between T2 map and histology. Marginally and significant differences were observed between pre- and post-USPIO T2 values at weeks 5 (P = 0.06) and 10 (P = 0.02), but only with the administration of high USPIO doses in the arthritic group using the conventional method. No significant differences were noted between pre- and post-USPIO T1 values at any imaging time points. Cartilage T2 maps with short-TR and conventional protocols provided similar T2 values [(decreased trend)] (P > 0.05). Concomitant use of USPIO to T1 and T2 mapping of cartilage would not impair the identification of interval changes of T1 and T2 maps. Rapid T2 map provides similar results compared to conventional method, but its validation warrants further investigation.

Ultrasound and magnetic resonance imaging of healthy paediatric ankles and knees: a baseline for comparison with haemophilic joints.

The study was undertaken to document cartilage and soft tissue changes/findings in ankles and knees of normal children of different age groups to be used for comparison in the assessment of children with haemophilia. Cartilage thickness and soft tissue changes were recorded at predetermined sites of ankles/knees on both US and MRI in healthy boys in three age groups: 7-9; 10-14; and 15-18 years. To assess the validity of the ultrasound and MRI measurements, an ex vivo study was done using agar phantoms with techniques and scanners similar to those applied in vivo. Twenty (48%) knees and 22 (52%) ankles of 42 boys, were evaluated. There was a reduction in the thickness of joint cartilage with age. A difference in cartilage measurements was noted in most sites between the age groups on both US and MRI (P < 0.05 each), but such difference was not noted for joint fluid in ankles or knees (P = 0.20, P = 0.68 or P = 0.75, P = 0.63 for US, MRI, respectively). Although cartilage measurements were smaller on US than on MRI for both ankles and knees (P < 0.05 each), this observation was not recorded for fluid in knees (P = 0.02). For diminutive measurements (2 mm) mean US measurements were smaller than corresponding phantom's measurements, P = 0.02. Age-related measurements were noted for cartilage thickness on US and MRI in ankles and knees. US measurements were smaller than corresponding MRI measurements at most joint sites, which were supported by results on small-diameter phantoms.

Value and goals of treat-to-target in systemic lupus erythematosus: knowledge and foresight.

Treat-to-target is a therapeutic strategy aimed at improving disease outcome through the achievement of shared treatment goals, which has dramatically ameliorated the prognosis of widespread disorders, such as hypertension or diabetes. Conversely, efforts to delineate treat-to-target in systemic lupus erythematosus (SLE) have failed in pinpointing common goals and treatment strategies, probably because of disease heterogeneity and lack of measurable biomarkers predicting disease course and ensuring a safe treatment tapering during quiescence. Given the detrimental effects of persistent disease activity and protracted corticosteroid therapy on patients' outcome in lupus, disease remission should be pursued whenever possible. Fortunately, clinical remission is currently realistic for a greater number of patients than it was in the past, yet tight monitoring is required in order for patients to benefit from disease- and corticosteroid-free intervals, while minimizing the risk of disease flares. In everyday practice, patients should be brought to the lowest level of disease activity ensuring a significant benefit over a persistently active disease, being either clinical remission or low disease activity.

17-ß-estradiol affects BLyS serum levels and the nephritogenic autoantibody network accelerating glomerulonephritis in NZB/WF1 mice.

Systemic lupus erythematosus (SLE) is an autoimmune disease that predominantly affects fertile women, suggesting sex hormones are involved in disease pathogenesis. B lymphocyte stimulator (BLyS) has been found to be elevated in SLE patients and to drive a lupus-like syndrome in transgenic mice. Our aim was to evaluate the effects of estrogen administration on BLyS and nephritogenic anti-C1q and anti-dsDNA antibodies in lupus-prone NZB/WF1 mice. We implanted pellets releasing 17-ß-estradiol (18.8 µg/day) on the back side the ear of 10 NZB/WF1 mice (group 1), and compared them with 10 mice intraperitoneally injected with PBS 200 µl twice a week (group 2), as controls. We evaluated BLyS, anti-dsDNA and anti-C1q serum levels starting one week after pellet implantation. We also analyzed time to proteinuria onset, proteinuria-free survival and overall survival. Kidneys, spleen, liver and lungs were harvested for histological analysis. Mice were bred until natural death. BLyS serum levels were higher in group 1 than in group 2 mice at each evaluation. Group 1 mice developed nephritogenic antibodies and proteinuria significantly earlier and at higher levels than controls. Direct correlation between BLyS and anti-C1q (R (2 )= 0.6962, p < 0.0001) or anti-dsDNA (R (2 )= 0.5953, p < 0.0001), and between anti-C1q and anti-dsDNA autoantibodies (R (2 )= 0.5615, p < 0.0001) were found. Proteinuria-free and global survival rates were significantly lower in group 1 than in controls. Histological analyses showed more severe abnormalities in group 1 mice. Estrogen administration is associated with increased levels of BLyS as well as of anti-C1q and anti-dsDNA antibodies, leading to accelerated glomerulonephritis and disease progression in NZB/WF1 mice.