Heart abnormalities in children with neuromuscular diseases

Neuromuscular diseases are a large group of diseases that are characterized by defective functions of peripheral nervous system, neuromuscular junction and/or muscle. Due to the similar structure of skeletal and cardiac muscles it is possible to associate neuromuscular diseases with cardiac disorders. The aim of the work was to identify the incidence rate of cardiovascular abnormalities in children with neuromuscular diseases. During the period from January to December 2008 at the Clinic of Neurology and Psychiatry for children and Youth the Faculty of Medicine in Belgrade, 44 patients with neuromuscular diseases had cardiovascular examination (physical, electrocardiographic and echocardiographic). All of the examined patients fell ill before turning 18 years of age. The patients’ ages (M: 25, F: 19) ranged from 3 to 38 years (X = 16 ± 8.35) at the time of cardiovascular examination. High incidence rate of mitral valve dysplasia, without haemodynamic changes, has been diagnosed (38.6%). Patients with distrophinopathy are often referred to cardiovascular examination. Five (26.3%) of the patients with distrophinopathy have dilated cardiomyopathy, and two patients with distrophinopathy have congenital heart disease and diseases of the valve. One of the examined patients had congenital heart disease as well as nondistrophinopathic dystrophy (LGM.D.), and spinal muscular atrophy (SMA) while patients with peripheral neuropathy hadn’t been diagnosed with pathological cardiovascular findings. Two out of five examined patients with disease of neuromuscular junction had results of the cardiovascular examination that matches the ones found in heart valve diseases. Dilatated cardiomyopathy, isolated or associated with other cardiology abnormalities can only be diagnosed in distrophinopathy. In other forms of dystrophy, as well as other neuromuscle diseases occurrence of described diseases of valve and congenital heart diseases has been diagnosed

Classifications and imaging of juvenile spondyloarthritis

Juvenile spondyloarthritis may be present in at least 3 subtypes of juvenile idiopathic arthritis according to the classification of the International League of Associations for Rheumatology. By contrast with spondyloarthritis in adults, juvenile spondyloarthritis starts with inflammation of peripheral joints and entheses in the majority of children, whereas sacroiliitis and spondylitis may develop many years after the disease onset. Peripheral joint involvement makes it difficult to differentiate juvenile spondyloarthritis from other juvenile idiopathic arthritis subtypes. Sacroiliitis, and especially spondylitis, although infrequent in childhood, may manifest as low back pain. In clinical practice, radiographs of the sacroiliac joints or pelvis are performed in most of the cases even though magnetic resonance imaging offers more accurate diagnosis of sacroiliitis. Neither disease classification criteria nor imaging recommendations have taken this advantage into account in patients with juvenile spondyloarthritis. The use of magnetic resonance imaging in evaluation of children and adolescents with a clinical suspicion of sacroiliitis would improve early diagnosis, identification of inflammatory changes and treatment. In this paper, we present the imaging features of juvenile spondyloarthritis in juvenile ankylosing spondylitis, juvenile psoriatic arthritis, reactive arthritis with spondyloarthritis, and juvenile arthropathies associated with inflammatory bowel disease

The Serbian version of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR)

The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient-reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Serbian language. The reading comprehension of the questionnaire was tested in 10 JIA parents and patients. Each participating centre was asked to collect demographic, clinical data and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling effects, internal consistency, Cronbach\u2019s alpha, interscale correlations, test\u2013retest reliability, and construct validity (convergent and discriminant validity). A total of 248 JIA patients (5.2% systemic, 44.3% oligoarticular, 23.8% RF-negative polyarthritis, 26.7% other categories) and 100 healthy children were enrolled in three centres. The JAMAR components discriminated healthy subjects from JIA patients. All JAMAR components revealed good psychometric performances. In conclusion, the Serbian version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and clinical research

Augmented thrombin formation is related to circulating levels of extracellular vesicles exposing tissue factor and citrullinated histone-3 in anti-neutrophil cytoplasmic antibody-associated vasculitides

Publisher Copyright: Copyright © 2023 Jonasdottir, Manojlovic, Vojinovic, Nordin, Bruchfeld, Gunnarsson, Mobarrez and Antovic.Objectives: To study circulating myeloperoxidase (MPO)-positive extracellular vesicles (MPO+EVs) exposing citrullinated histone-3 (H3Cit), tissue factor (TF), and plasminogen (Plg) in association to thrombin generation in patients with anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV). Methods: We have involved well-characterized patients with AAV together with population-based controls. Flow cytometry was used to assess the levels of MPO+EVs in citrated plasma. MPO+EVs were phenotyped by anti-MPO-antibodies together with anti-CD142 (anti-TF), anti-H3Cit, and anti-Plg antibodies. A modified Calibrated Automated Thrombogram (CAT) assay was utilized to measure thrombin generation in plasma initiated by EVs-enriched pellets. The activity of AAV was evaluated with the Birmingham Vasculitis Activity Score (BVAS). Results: This study comprised 46 AAV patients, 23 in the active stage of the disease and 23 in remission, as well as 23 age- and sex matched population-based controls. Augmented levels of all investigated MPO+ EVs were found in active AAV patients in comparison to the subgroup of patients in remission and controls. Thrombin generation, measured by endogenous thrombin potential (ETP) and peak of thrombin formation, was higher in plasma when triggered by EVs-enriched pellet from AAV patients. ETP and peak were associated with the levels of MPO+TF+ and MPO+H3Cit+ EVs. Additionally, MPO+TF+ EVs correlated with the disease activity evaluated with BVAS. Conclusion: Augmented thrombin generation is found in AAV patients regardless of disease activity and is associated with higher exposure of TF and H3Cit on MPO+EVs. This may contribute to the increased risk of thrombosis seen in AAV patients.Peer reviewe

MDCT: Angiography of anatomical variations of the celiac trunk and superior mesenteric artery

The aim of this study was to detect and describe the existence and incidence of anatomical variations of the celiac trunk and superior mesenteric artery. The study was conducted on 150 persons, who underwent abdominal Multi- Detector Computer Tomography (MDCT) angiography, from April 2010 until November 2012. CT images were obtained with a 64-row MDCT scanner in order to analyze the vascular anatomy and anatomical variations of the celiac trunk and superior mesenteric artery. In our study, we found that 78% of patients have a classic anatomy of the celiac trunk and superior mesenteric artery. The most frequent variation was the origin of the common hepatic artery from the superior mesenteric artery (10%). The next variation, according to frequency, was the origin of the left gastric artery direct from the abdominal aorta (4%). The arc of Buhler as an anastomosis between the celiac trunk and superior mesenteric artery, was detected in 3% of cases, as was the presence of a common trunk of the celiac trunk and superior mesenteric artery (in 3% of cases). Separate origin of the splenic artery and the common hepatic artery was present in 2% of patients. The MDCT scanner gives us an insight into normal anatomy and variations of the abdominal blood vessels, which is very important in the planning of surgical interventions, especially transplantation, as well as in the prevention of complications due to ischemia

Real-world comparison of the effects of etanercept and adalimumab on well-being in non-systemic juvenile idiopathic arthritis: a propensity score matched cohort study

Background: Etanercept (ETN) and adalimumab (ADA) are considered equally efective biologicals in the treat‑ ment of arthritis in juvenile idiopathic arthritis (JIA) but no studies have compared their impact on patient-reported well-being. The objective of this study was to determine whether ETN and ADA have a diferential efect on patientreported well-being in non-systemic JIA using real-world data. Methods: Biological-naive patients without a history of uveitis were selected from the international Pharmachild registry. Patients starting ETN were matched to patients starting ADA based on propensity score and outcomes were collected at time of therapy initiation and 3–12 months afterwards. Primary outcome at follow-up was the improve‑ ment in Juvenile Arthritis Multidimensional Assessment Report (JAMAR) visual analogue scale (VAS) well-being score from baseline. Secondary outcomes at follow-up were decrease in active joint count, adverse events and uveitis events. Outcomes were analyzed using linear and logistic mixed efects models. Results: Out of 158 eligible patients, 45 ETN starters and 45 ADA starters could be propensity score matched result‑ ing in similar VAS well-being scores at baseline. At follow-up, the median improvement in VAS well-being was 2 (inter‑ quartile range (IQR): 0.0 – 4.0) and scores were signifcantly better (P=0.01) for ETN starters (median 0.0, IQR: 0.0 – 1.0) compared to ADA starters (median 1.0, IQR: 0.0 – 3.5). The estimated mean diference in VAS well-being improvement from baseline for ETN versus ADA was 0.89 (95% CI: -0.01 – 1.78; P=0.06). The estimated mean diference in active joint count decrease was -0.36 (95% CI: -1.02 – 0.30; P=0.28) and odds ratio for adverse events was 0.48 (95% CI: 0.16 –1.44; P=0.19). One uveitis event was observed in the ETN group. Conclusions: Both ETN and ADA improve well-being in non-systemic JIA. Our data might indicate a trend towards a slightly stronger efect for ETN, but larger studies are needed to confrm this given the lack of statistical signifcance

Efficacy and safety of open-label etanercept on extended oligoarticular juvenile idiopathic arthritis, enthesitis-related arthritis and psoriatic arthritis: part 1 (week 12) of the CLIPPER study

OBJECTIVE: To investigate the efficacy and safety of etanercept (ETN) in paediatric subjects with extended oligoarticular juvenile idiopathic arthritis (eoJIA), enthesitis-related arthritis (ERA), or psoriatic arthritis (PsA). METHODS: CLIPPER is an ongoing, Phase 3b, open-label, multicentre study; the 12-week (Part 1) data are reported here. Subjects with eoJIA (2-17 years), ERA (12-17 years), or PsA (12-17 years) received ETN 0.8 mg/kg once weekly (maximum 50 mg). Primary endpoint was the percentage of subjects achieving JIA American College of Rheumatology (ACR) 30 criteria at week 12; secondary outcomes included JIA ACR 50/70/90 and inactive disease. RESULTS: 122/127 (96.1%) subjects completed the study (mean age 11.7 years). JIA ACR 30 (95% CI) was achieved by 88.6% (81.6% to 93.6%) of subjects overall; 89.7% (78.8% to 96.1%) with eoJIA, 83.3% (67.2% to 93.6%) with ERA and 93.1% (77.2% to 99.2%) with PsA. For eoJIA, ERA, or PsA categories, the ORs of ETN vs the historical placebo data were 26.2, 15.1 and 40.7, respectively. Overall JIA ACR 50, 70, 90 and inactive disease were achieved by 81.1, 61.5, 29.8 and 12.1%, respectively. Treatment-emergent adverse events (AEs), infections, and serious AEs, were reported in 45 (35.4%), 58 (45.7%), and 4 (3.1%), subjects, respectively. Serious AEs were one case each of abdominal pain, bronchopneumonia, gastroenteritis and pyelocystitis. One subject reported herpes zoster and another varicella. No differences in safety were observed across the JIA categories. CONCLUSIONS: ETN treatment for 12 weeks was effective and well tolerated in paediatric subjects with eoJIA, ERA and PsA, with no unexpected safety findings

Educational initiatives and training for paediatric rheumatology in Europe

The Paediatric Rheumatology European Society (PReS) has over many years, developed a portfolio of educational activities to address increasing educational needs of workforce and support young clinicians to acquire skills to develop new knowledge and deliver clinical care in the future. These educational activities aim to facilitate growth of paediatric rheumatology and ultimately improve the clinical care for children and families. This article describes the current portfolio of PReS educational activities and their relevance to the international paediatric rheumatology community

Search for new particles in events with energetic jets and large missing transverse momentum in proton-proton collisions at root s=13 TeV

A search is presented for new particles produced at the LHC in proton-proton collisions at root s = 13 TeV, using events with energetic jets and large missing transverse momentum. The analysis is based on a data sample corresponding to an integrated luminosity of 101 fb(-1), collected in 2017-2018 with the CMS detector. Machine learning techniques are used to define separate categories for events with narrow jets from initial-state radiation and events with large-radius jets consistent with a hadronic decay of a W or Z boson. A statistical combination is made with an earlier search based on a data sample of 36 fb(-1), collected in 2016. No significant excess of events is observed with respect to the standard model background expectation determined from control samples in data. The results are interpreted in terms of limits on the branching fraction of an invisible decay of the Higgs boson, as well as constraints on simplified models of dark matter, on first-generation scalar leptoquarks decaying to quarks and neutrinos, and on models with large extra dimensions. Several of the new limits, specifically for spin-1 dark matter mediators, pseudoscalar mediators, colored mediators, and leptoquarks, are the most restrictive to date.Peer reviewe