Lower hair cortisol concentration in adolescent and young adult patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Q-Fever Fatigue Syndrome compared to controls.

BACKGROUND: In patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), momentary cortisol concentrations in blood, urine, and saliva are lower compared to healthy controls. Long-term cortisol concentration can be assessed through hair, but it is unclear whether these concentrations are also lower. Additionally, it is unknown if lower cortisol extends to other patients suffering from persistent fatigue and how hair cortisol concentration (HCC) relates to fatigue levels. Therefore, this study examines HCC in fatigued patients with ME/CFS, Q fever Fatigue Syndrome (QFS), Post-COVID-19 condition (PCC), and Juvenile Idiopathic Arthritis (JIA). METHODS: Adolescent and young adult patients with ME/CFS (n=12), QFS (n=20), PCC (n=8), JIA (n=19), and controls (n=57) were included. Patients participated in a randomized cross-over trial (RCT) targeting fatigue through lifestyle and dietary self-management strategies. HCC was measured pre-post RCT in patients and once in controls, quantified using a LC-MS/MS-based method. Fatigue severity was measured with the Checklist Individual Strength-8. HCC was compared between groups with ANOVAs. Relations between HCC, fatigue severity, and other variables were investigated using linear regression analyses. RESULTS: The ME/CFS (p=.009) and QFS (p=.047) groups had lower HCC compared to controls. Overall, HCC was negatively associated with the presence of symptoms related to chronic fatigue syndromes (e.g., sleeping issues, often feeling tired, trouble thinking clearly; ß=-0.018, p=.035), except in the QFS group (ß=.063, p<.001). Baseline HCC did not predict fatigue improvement during the RCT (p=.449), and HCC increased during the trial (Mdif=.076, p=.021) regardless of clinically relevant fatigue improvement (p=.658). CONCLUSION: Lower cortisol concentration can also be observed in the long-term. Lower HCC is not limited to ME/CFS, as it was also observed in QFS. The role of cortisol may differ between these diagnoses and appears to be unrelated to fatigue levels.

The reliability and validity of the juvenile idiopathic arthritis magnetic resonance scoring system for temporomandibular joints.

In children with juvenile idiopathic arthritis (JIA), the temporomandibular joint (TMJ) can be involved. To prevent TMJ damage due to inflammation, early recognition is important, for which contrast-enhanced magnetic resonance imaging (MRI) is the gold standard. In this study, the interobserver reliability and construct validity of the Juvenile Idiopathic Arthritis Magnetic Resonance Scoring System for Temporomandibular Joints (JAMRIS-TMJ) was assessed. Two radiologists independently examined 38 MRIs using the JAMRIS-TMJ scoring system. Inter-observer reliability was assessed by Cohen's (weighted) kappa (κ), 95% confidence intervals (CIs) and absolute agreement (%). Construct validity was assessed by correlation between the JAMRIS-TMJ items and TMJ involvement, active maximum interincisal mouth opening (AMIO), and anterior maximum voluntary bite force (AMVBF). The interobserver reliability for the JAMRIS-TMJ items varied from poor to good (κ = 0.18-0.61). Joint enhancement had the highest reliability (κ = 0.61). Correlations were found between TMJ involvement, AMIO, and the JAMRIS-TMJ items, although variation between radiologists and TMJ side existed. No correlation was found between AMVBF and the JAMRIS-TMJ items for both radiologists. The strongest correlations were found between most of the JAMRIS-TMJ items and AMIO. Our findings support the utility of AMIO as a clinical measure of TMJ status in children with JIA.

Bupivacaine pleural effusion mimicking a hemothorax after a thoracoscopic microdiscectomy with epidural anesthesia.

PURPOSE: Post-operative pain after video-assisted thoracoscopic surgery is often treated using thoracic epidural analgesics or thoracic paravertebral analgesics. This article describes a case where a thoracic disc herniation is treated with a thoracoscopic microdiscectomy with post-operative thoracic epidural analgesics. The patient developed a bupivacaine pleural effusion which mimicked a hemothorax on computed tomography (CT). METHODS: The presence of bupivacaine in the pleural effusion was confirmed using a high performance liquid chromatography method. RESULTS: The patient underwent a re-exploration to relieve the pleural effusion. The patient showed a long-term recovery similar to what can be expected from an uncomplicated thoracoscopic microdiscectomy. CONCLUSION: A pleural effusion may occur when thoracic epidural analgesics are used in patents with a corridor between the pleural cavity and epidural space.

The outcomes of children born to mothers with autoimmune rheumatic diseases.

Maternal autoimmune rheumatic diseases can influence the outcomes of children through several life stages. During pregnancy, maternal inflammation and autoantibodies can hinder fetal development and lead to growth restriction, preterm birth, and low birth weight; prematurity, especially at extreme gestational ages, can in turn impair future child health. Treatment with compatible immunomodulatory drugs and preventive medications aims to keep maternal disease under control and minimise the risk of adverse pregnancy outcomes. However, concerns have been raised about the effects of immunomodulatory drugs on neonatal conditions (ie, the risk of serious infections, inadequate responses to vaccinations, and organ toxicity) and long-term outcomes (metabolic and cardiovascular problems and neurodevelopmental disorders). Among the unmet needs of parents with autoimmune rheumatic diseases, there is the estimation of risk for the children to develop autoimmune disorders and the need for reassurance about parenting capacity while living with a chronic condition. This Series paper provides a comprehensive overview of the literature and guidance on discussing these topics with patients.

The Mosquito Fauna of Arizona: Species Composition and Public Health Implications.

Arizona is home to many mosquito species, some of which are known vectors of infectious diseases that harm both humans and animals. Here, we provide an overview of the 56 mosquito species that have been identified in the State to date, but also discuss their known feeding preference and the diseases they can (potentially) transmit to humans and animals. This list is unlikely to be complete for several reasons: (i) Arizona's mosquitoes are not systematically surveyed in many areas, (ii) surveillance efforts often target specific species of interest, and (iii) doubts have been raised by one or more scientists about the accuracy of some collection records, which has been noted in this article. There needs to be an integrated and multifaceted surveillance approach that involves entomologists and epidemiologists, but also social scientists, wildlife ecologists, ornithologists, representatives from the agricultural department, and irrigation and drainage districts. This will allow public health officials to (i) monitor changes in current mosquito species diversity and abundance, (ii) monitor the introduction of new or invasive species, (iii) identify locations or specific populations that are more at risk for mosquito-borne diseases, and (iv) effectively guide vector control.

Reliability of mandibular range of motion measurements in healthy children.

BACKGROUND: Mandibular range of motion (MROM) variables are widely used to evaluate oral function. OBJECTIVE: The aim of this study was to establish the reliability of MROM variables in healthy children. METHODS: In this cross-sectional study, healthy children were examined 2 weeks apart. The following MROM variables were established: active maximum interincisal opening (AMIO), passive maximum interincisal opening (PMIO), protrusion and left and right laterotrusion. The reliability of the MROM measurements was determined by analysing the intra-class correlation coefficient (ICC), standard error of measurement (SEM), smallest detectable change (SDC) and limits of agreement (LoA). RESULTS: A total of 167 healthy children were examined. The ICC indicated good reliability for AMIO (0.885); excellent reliability for PMIO (0.925); and moderate reliability for protrusion (0.578), laterotrusion left (0.601) and laterotrusion right (0.634). The SDC was 0.9 mm for AMIO, 0.4 mm for PMIO, 2.2 mm for protrusion, 1.6 mm for laterotrusion left and 1.4 mm for laterotrusion right. The LoA was -5.67 to 5.82 for AMIO, -3.90 to 3.57 for PMIO, -3.89 to 3.55 for protrusion, -2.99 to 2.77 for laterotrusion left, and - 2.71 to 2.77 for laterotrusion right. CONCLUSIONS: AMIO and PMIO measurements are both highly reliable in healthy children. The low SDC indicate that AMIO and PMIO are promising longitudinal measurements. Protrusion and laterotrusion measurements had moderate reliability. These results support our clinical recommendation to measure AMIO rather than PMIO, as PMIO is more difficult and more time-consuming to perform than AMIO.

Electroporation of mRNA as a Universal Technology Platform to Transfect a Variety of Primary Cells with Antigens and Functional Proteins.

Electroporation (EP) of mRNA into human cells is a broadly applicable method to transiently express proteins of choice in a variety of different cell types. We have spent more than two decades to optimize and adapt this method, first for antigen-loading of dendritic cells (DCs) and subsequently for T cells, B cells, bulk PBMCs, and several cell lines. In this regard, antigens were introduced, processed, and presented in context of MHC class I and II. Next to that, functional proteins like adhesion receptors, T-cell receptors (TCRs), chimeric antigen receptors (CARs), constitutively active signal transducers (i.e. caIKK), and others were successfully expressed. We have also established this protocol under full GMP compliance as part of a manufacturing license to produce mRNA-electroporated DCs and mRNA-electroporated T cells for therapeutic applications in clinical trials. Therefore, we here want to share our universal mRNA electroporation protocol and the experience we have gathered with this method. The advantages of the transfection method presented here are: (1) easy adaptation to different cell types; (2) scalability from 106 to approximately 108 cells per shot; (3) high transfection efficiency (80-99%); (4) homogenous protein expression; (5) GMP compliance if the EP is performed in a class A clean room; and (6) no transgene integration into the genome. The provided protocol involves: OptiMEM® as EP medium, a square-wave pulse with 500 V, and 4 mm cuvettes. To adapt the protocol to differently sized cells, simply the pulse time has to be altered. Thus, we share an overview of proven electroporation settings (including recovery media), which we have established for various cell types. Next to the basic protocol, we also provide an extensive list of hints and tricks, which, in our opinion, are of great value for everyone who intends to use this transfection technique.

Individual outcomes after tailored versus generic self-management strategies for persistent fatigue in youth with a fatigue syndrome or rheumatic condition: A multiple single-case study.

OBJECTIVE: To examine individual outcomes after tailored lifestyle (PROfeel) or generic dietary advice as self-management intervention for persistent fatigue in adolescents and young adults with a chronic condition, to compare participants who did and did not benefit and to explore changes to factors in the biopsychosocial model of fatigue after PROfeel. METHOD: A multiple single-case AB-phase design was embedded in a randomized crossover trial (N = 45). Intensive longitudinal data (ILD) on outcomes 'fatigue severity', 'self-efficacy' and 'quality of life' (QoL) were collected through weekly smartphone measurement for 20 weeks. ILD on biopsychosocial factors were collected through experience sampling methodology for 28 days pre-post first intervention. Baseline characteristics were compared with t-tests and chi-square tests. Permutation distancing tests were used to assess change over time in all ILD. RESULTS: Regarding weekly measurements, nineteen participants (42.22%) showed small to large positive outcomes (drange = .05 to 2.59), mostly after PROfeel. Eleven participants (24.44%) showed small to moderate negative outcomes (drange = -.02 to -2.46), mostly after dietary advice. Fatigue severity improved most, followed by self-efficacy. Participants who benefitted showed higher QoL levels and lower fatigue and pain levels compared with others at baseline (all p < .02). When positive outcomes were observed after PROfeel, typically ≥1 biopsychosocial factor had been targeted successfully. CONCLUSION: Self-management advice has more potential when tailored to individual characteristics, including the biopsychosocial model of fatigue. PROfeel appears particularly useful as fatigue intervention for individuals with relatively less severe symptoms.

Humoral and cellular immunogenicity, effectiveness and safety of COVID-19 mRNA vaccination in patients with pediatric rheumatic diseases: A prospective cohort study.

OBJECTIVES: To evaluate immunogenicity, effectiveness and safety of COVID-19 vaccination in patients with pediatric autoimmune inflammatory rheumatic disease (pedAIIRD). METHODS: A prospective cohort study was performed at the pediatric rheumatology department of the Wilhelmina Children's Hospital in Utrecht, the Netherlands. Vaccination dates, COVID-19 cases and vaccine-related adverse events (AEs) were registered for all pedAIIRD patients during regular clinic visits from March 2021 - August 2022. SARS-CoV-2 IgG antibody levels and T-cell responses were measured from serum samples after vaccination, and clinical and drug therapy data were collected from electronic medical records. Rate of COVID-19 disease was compared between vaccinated and unvaccinated patients in a time-varying Cox regression analysis. RESULTS: A total of 157 patients were included in this study and 88 % had juvenile idiopathic arthritis (JIA). One hundred thirty-seven patients were fully vaccinated, of which 47 % used biological agents at the time of vaccination, and 20 patients were unvaccinated. Geometric mean concentrations (GMCs) of post-vaccine antibody levels against SARS-CoV-2 were above the threshold for positivity in patients who did and did not use biological agents at the time of vaccination, although biological users demonstrated significantly lower antibody levels (adjusted GMC ratio: 0.38, 95 % CI: 0.21 - 0.70). T-cell responses were adequate in all but two patients (9 %). The adjusted rate of reported COVID-19 was significantly lower for fully vaccinated patients compared to non-vaccinated patients (HR: 0.53, 95 % CI: 0.29 - 0.97). JIA disease activity scores were not significantly different after vaccination, and no serious AEs were reported. CONCLUSIONS: COVID-19 mRNA vaccines were immunogenic (both cellular and humoral), effective and safe in a large cohort of pedAIIRD patients despite their use of immunosuppressive medication.

Quantifying hospital-associated costs, and accompanying travel costs and productivity losses, before and after withdrawing TNF-α inhibitors in juvenile idiopathic arthritis.

OBJECTIVE: To quantify differences in hospital-associated costs, and accompanying travel costs and productivity losses, before and after withdrawing TNF-α inhibitors (TNFi) in JIA patients. METHODS: This was a retrospective analysis of prospectively collected data from electronic medical records of paediatric JIA patients treated with TNFi, which were immediately discontinued, spaced (increased treatment interval) or tapered (reduced subsequent doses). Costs of hospital-associated resource use (consultations, medication, radiology procedures, laboratory testing, procedures under general anaesthesia, hospitalization) and associated travel costs and productivity losses were quantified during clinically inactive disease until TNFi withdrawal (pre-withdrawal period) and compared with costs during the first and second year after withdrawal initiation (first and second year post-withdrawal). RESULTS: Fifty-six patients were included of whom 26 immediately discontinued TNFi, 30 spaced and zero tapered. Mean annual costs were €9165/patient on active treatment (pre-withdrawal) and decreased significantly to €5063/patient (-44.8%) and €6569/patient (-28.3%) in the first and second year post-withdrawal, respectively (P < 0.05). Of these total annual costs, travel costs plus productivity losses were €834/patient, €1180/patient, and €1320/patient in the three periods respectively. Medication comprised 80.7%, 61.5% and 72.4% of total annual costs in the pre-withdrawal, first and second year post-withdrawal period, respectively. CONCLUSION: In the first two years after initiating withdrawal, the total annual costs were decreased compared with the pre-withdrawal period. However, cost reductions were lower in the second year compared with the first year post-withdrawal, primarily due to restarting or intensifying biologics. To support biologic withdrawal decisions, future research should assess the full long-term societal cost impacts, and include all biologics.

Targeting persistent fatigue with tailored versus generic self-management strategies in adolescents and young adults with a fatigue syndrome or rheumatic condition: A randomized crossover trial.

OBJECTIVES: To evaluate the use of two self-management intervention strategies for persistent fatigue in adolescents and young adults with a fatigue syndrome or rheumatic condition. DESIGN: A randomized crossover trial administering tailored lifestyle advice and generic dietary advice, each 12 weeks, with a four-week washout period between. METHODS: Sixty participants (aged 12-29) were included. Tailoring was achieved through the PROfeel method. Dietary guidelines were conceptualized by the Netherlands Nutrition Centre. Questionnaires were used pre-post-interventions to measure primary outcome 'fatigue severity' (Checklist Individual Strength-8) and secondary outcomes 'self-efficacy' (Self-Efficacy Scale-28) and 'quality of life' (QoL) (Paediatric Quality of Life Inventory 4.0). Feasibility and adherence were self-rated on a scale of 1 to 10 (low to high). Linear mixed modelling was used to assess change over time, compare strategy effectiveness and study the impact of intervention order. RESULTS: Fatigue severity, self-efficacy and QoL regarding 'physical' and 'emotional' functioning improved significantly over time (all p < .015). The average improvement of the two QoL subscales was clinically relevant, as was the fatigue improvement in 20 out of 46 participants who completed the trial and 5 dropouts. The interventions were equally effective, and intervention order did not impact the improvement level (prange = .242-.984). The self-management strategies received similar feasibility (M = 6.45, SD = 1.91) and adherence (M = 7.67, SD = 1.67) ratings. CONCLUSIONS: As small to clinically relevant improvements were observed, self-management strategies might be particularly useful to bridge waiting time for guided treatments such as Cognitive Behavioural Therapy.

Increased local bone turnover in patients with chronic periprosthetic joint infection.

Aims: The management of periprosthetic joint infection (PJI) remains a major challenge in orthopaedic surgery. In this study, we aimed to characterize the local bone microstructure and metabolism in a clinical cohort of patients with chronic PJI. Methods: Periprosthetic femoral trabecular bone specimens were obtained from patients suffering from chronic PJI of the hip and knee (n = 20). Microbiological analysis was performed on preoperative joint aspirates and tissue specimens obtained during revision surgery. Microstructural and cellular bone parameters were analyzed in bone specimens by histomorphometry on undecalcified sections complemented by tartrate-resistant acid phosphatase immunohistochemistry. Data were compared with control specimens obtained during primary arthroplasty (n = 20) and aseptic revision (n = 20). Results: PJI specimens exhibited a higher bone volume, thickened trabeculae, and increased osteoid parameters compared to both control groups, suggesting an accelerated bone turnover with sclerotic microstructure. On the cellular level, osteoblast and osteoclast parameters were markedly increased in the PJI cohort. Furthermore, a positive association between serum (CRP) but not synovial (white blood cell (WBC) count) inflammatory markers and osteoclast indices could be detected. Comparison between different pathogens revealed increased osteoclastic bone resorption parameters without a concomitant increase in osteoblasts in bone specimens from patients with Staphylococcus aureus infection, compared to those with detection of Staphylococcus epidermidis and Cutibacterium spp. Conclusion: This study provides insights into the local bone metabolism in chronic PJI, demonstrating osteosclerosis with high bone turnover. The fact that Staphylococcus aureus was associated with distinctly increased osteoclast indices strongly suggests early surgical treatment to prevent periprosthetic bone alterations.

Nonribosomal Peptide Synthetases in Animals.

Nonribosomal peptide synthetases (NRPSs) are a class of cytosolic enzymes that synthesize a range of bio-active secondary metabolites including antibiotics and siderophores. They are widespread among both prokaryotes and eukaryotes but are considered rare among animals. Recently, several novel NRPS genes have been described in nematodes, schistosomes, and arthropods, which led us to investigate how prevalent NRPS genes are in the animal kingdom. We screened 1059 sequenced animal genomes and showed that NRPSs were present in 7 out of the 19 phyla analyzed. A phylogenetic analysis showed that the identified NRPSs form clades distinct from other adenylate-forming enzymes that contain similar domains such as fatty acid synthases. NRPSs show a remarkably scattered distribution over the animal kingdom. They are especially abundant in rotifers and nematodes. In rotifers, we found a large variety of domain architectures and predicted substrates. In the nematode Plectus sambesii, we identified the beta-lactam biosynthesis genes L-δ-(α-aminoadipoyl)-L-cysteinyl-D-valine synthetase, isopenicillin N synthase, and deacetoxycephalosporin C synthase that catalyze the formation of beta-lactam antibiotics in fungi and bacteria. These genes are also present in several species of Collembola, but not in other hexapods analyzed so far. In conclusion, our survey showed that NRPS genes are more abundant and widespread in animals than previously known.

The protective effect of COVID-19 vaccines on developing multisystem inflammatory syndrome in children (MIS-C): a systematic literature review and meta-analysis.

OBJECTIVE: To review whether the current COVID-19 vaccines can prevent the occurrence of multisystem inflammatory syndrome in children (MIS-C) and adolescents. METHODS: A systematic literature review and meta-analysis were performed. The data were abstracted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Primary outcome was the efficacy of COVID-19 vaccination in preventing MIS-C development. The search was performed in PubMed and Embase. RESULTS: The review yielded 13 studies, which were included for critical appraisal and data extraction. The available studies showed a reduced incidence of MIS-C after mRNA COVID-19 vaccination in children aged 12-18 years. Four studies were eligible for meta-analysis and the pooled odds ratio for MIS-C in vaccinated children compared to unvaccinated children was 0.04 (95% confidence interval: 0.03-0.06). Additionally, the risk of MIS-C as an adverse effect of vaccination was much lower compared to the risk of MIS-C post-infection. CONCLUSIONS: Our systematic review highlights the current available evidence on the efficacy of COVID-19 vaccination in preventing MIS-C. The published studies so far - mainly conducted during the Delta wave - indicate that (original strain) COVID-19 mRNA vaccines in children are safe and associated with significantly less development of MIS-C. These findings further reinforce the recommendation for COVID-19 vaccination in children, which should be promoted and largely supported.

Unified and pluralistic ideals for data sharing and reuse in biodiversity.

How should billions of species observations worldwide be shared and made reusable? Many biodiversity scientists assume the ideal solution is to standardize all datasets according to a single, universal classification and aggregate them into a centralized, global repository. This ideal has known practical and theoretical limitations, however, which justifies investigating alternatives. To support better community deliberation and normative evaluation, we develop a novel conceptual framework showing how different organizational models, regulative ideals and heuristic strategies are combined to form shared infrastructures supporting data reuse. The framework is anchored in a general definition of data pooling as an activity of making a taxonomically standardized body of information available for community reuse via digital infrastructure. We describe and illustrate unified and pluralistic ideals for biodiversity data pooling and show how communities may advance toward these ideals using different heuristic strategies. We present evidence for the strengths and limitations of the unification and pluralistic ideals based on systemic relationships of power, responsibility and benefit they establish among stakeholders, and we conclude the pluralistic ideal is better suited for biodiversity data.

Meningococcal ACWY conjugate vaccine immunogenicity in adolescents with primary or secondary immune deficiencies, a prospective observational cohort study.

BACKGROUND: Immunization with meningococcal ACWY conjugate vaccine induces protective antibodies against invasive meningococcal disease (IMD) caused by serogroups A, C, W and Y. We studied MenACWY-TT vaccine immunogenicity in adolescents with a heterogenous group of primary and secondary immune deficiency including patients with systemic lupus erythematosus, mixed connective tissue disease, vasculitis, uveitis, 22Q11 syndrome, sickle cell disease, and patients who underwent stem cell transplantation for bone marrow failure. FINDINGS: We enrolled 69 individuals aged 14-18 years diagnosed with a primary or secondary immune deficiency in a prospective observational cohort study. All patients received a single dose of MenACWY-TT vaccine during the catch-up campaign 2018-19 because of the IMD-W outbreak in the Netherlands. Capsular polysaccharide-specific (PS) IgG concentrations against MenACWY were measured before and 3-6, 12, and 24 months after vaccination. Overall, geometric mean concentrations (GMCs) of MenACWY-PS-specific IgG were lower in patients compared to data from healthy, aged-matched controls (n = 75) reaching significance at 12 months postvaccination for serogroup A and W (adjusted GMC ratios 0.26 [95% CI: 0.15-0.47] and 0.22 [95% CI: 0.10-0.49], respectively). No serious adverse events were reported by study participants. CONCLUSIONS: The MenACWY conjugate vaccine was less immunogenic in adolescent patients with primary or secondary immunodeficiency compared to healthy controls, urging the need for further surveillance of these patients and supporting considerations for booster MenACWY conjugate vaccinations in these patient groups.

Diagnostic Performance of Multi-Detector Computed Tomography Arthrography and 3-Tesla Magnetic Resonance Imaging to Diagnose Experimentally Created Articular Cartilage Lesions in Equine Cadaver Stifles.

BACKGROUND: The purpose of the study was to determine the diagnostic performance of computed tomographic arthrography (CTA) and 3-Tesla magnetic resonance imaging (MRI) for detecting artificial cartilage lesions in equine femorotibial and femoropatellar joints. METHODS: A total of 79 cartilage defects were created arthroscopically in 15 cadaver stifles from adult horses in eight different locations. In addition, 68 sites served as negative controls. MRI and CTA (80-160 mL iodinated contrast media at 87.5 mg/mL per joint) studies were obtained and evaluated by a radiologist unaware of the lesion distribution. The stifles were macroscopically evaluated, and lesion surface area, depth, and volume were determined. The sensitivity and specificity of MRI and CTA were calculated and compared between modalities. RESULTS: The sensitivity values of CTA (53%) and MRI (66%) were not significantly different (p = 0.09). However, the specificity of CTA (66%) was significantly greater compared to MRI (52%) (p = 0.04). The mean lesion surface area was 11 mm2 (range: 2-54 mm2). Greater lesion surface area resulted in greater odds of lesion detection with CTA but not with MRI. CONCLUSIONS: CTA achieved a similar diagnostic performance compared to high-field MRI in detecting small experimental cartilage lesions. Despite this, CTA showed a higher specificity than MRI, thus making CTA more accurate in diagnosing normal cartilage. Small lesion size was a discriminating factor for lesion detection. In a clinical setting, CTA may be preferred over MRI due to higher availability and easier image acquisition.

Clinically Established Temporomandibular Involvement in Adults With Juvenile Idiopathic Arthritis.

OBJECTIVE: To study clinical variables defining temporomandibular function in adults with juvenile idiopathic arthritis (JIA) and healthy controls. METHODS: In this cross-sectional study, the temporomandibular joint (TMJ) screening protocol, mandibular range of motion (MROM), and anterior maximum voluntary bite force (AMVBF) were compared between adults with JIA and healthy controls. Unadjusted and adjusted models with corrections for sex and disease duration were constructed for active maximum interincisal mouth opening (AMIO) and AMVBF. RESULTS: A total of 100 adults with JIA and 59 healthy adults were included in this study. In adults with JIA, 56% had clinically established TMJ involvement. AMIO was the MROM variable most reduced by TMJ involvement; AMIO was 8.8 mm (95% CI -11.40 to -6.12; P < 0.001) less in adults with JIA with TMJ involvement compared to JIA without TMJ involvement. No differences of AMIO were found between healthy adults and adults with JIA without TMJ involvement (-2.52, 95% CI -5.13 to 0.10; P = 0.06). Male sex was associated with a higher AMIO, and disease duration was associated with a decreased AMIO. Collinearity between the subtype prebiologic era and disease duration was found. AMVBF did not differ between adults with JIA and healthy adults. CONCLUSION: The high prevalence of clinically established TMJ involvement in adults with JIA indicates the need for awareness of TMJ problems in adults with JIA. TMJ involvement negatively influenced AMIO and should therefore be part of the TMJ screening in adults with JIA. AMVBF seems to have less utility for TMJ screening in adult populations.

Long-term immunoprotection after live attenuated measles-mumps-rubella booster vaccination in children with juvenile idiopathic arthritis.

INTRODUCTION: Vaccines, especially live attenuated vaccines, in children with JIA pose a great challenge due to both potential lower immunogenicity and safety as a result of immunosuppressive treatment. For many years, in the Netherlands, JIA patients receive a measles-mumps-rubella (MMR) booster vaccine at the age of nine years as part of the national immunization program. OBJECTIVES: To study long-term humoral immunoprotection in a large cohort of JIA patients who received the MMR booster vaccine while being treated with immunomodulatory therapies at the Wilhelmina Children's Hospital in Utrecht, the Netherlands. METHODS: MMR-specific IgG antibody concentrations in stored serum samples of vaccinated JIA patients were determined with chemiluminescent microparticle immunoassays (CMIA). Samples were analyzed five years after MMR booster vaccination and at last available follow-up visit using both crude and adjusted analyses. Additional clinical data were collected from electronic medical records. RESULTS: In total, 236 samples from 182 patients were analyzed, including 67 samples that were available five years post-vaccination, and an additional 169 samples available from last visits with a median duration after vaccination of 6.9 years (IQR: 2.8-8.8). Twenty-eight patients were using biologic disease-modifying antirheumatic drugs (bDMARDS) of whom 96% anti-TNF agents and 4% tocilizumab. Percentages of protective antibody levels against measles after five years were significantly lower for patients who used bDMARD therapy at vaccination compared to patients who did not: 60% versus 86% (P = 0.03). For mumps (80% versus 94%) and rubella (60% versus 83%) this difference did not reach statistical significance (P = 0.11 and P = 0.07, respectively). Antibody levels post-vaccination decreased over time, albeit not significantly different between bDMARD users and non-bDMARD users. CONCLUSION: The MMR booster vaccine demonstrated long-term immunogenicity in the majority of children with JIA from a large cohort, although lower percentages of protective measles antibody levels were observed in bDMARD users. Hence, it might be indicated to measure antibody levels at least five years after MMR booster vaccination in the latter group and advice an extra booster accordingly.

Meningococcal ACWY conjugate vaccine immunogenicity and safety in adolescents with juvenile idiopathic arthritis and inflammatory bowel disease: A prospective observational cohort study.

BACKGROUND: Immunogenicity to meningococcal serogroup ACWY (MenACWY) conjugate vaccine has not been studied in immunocompromised minors with juvenile idiopathic arthritis (JIA) or inflammatory bowel disease (IBD). We determined immunogenicity of a MenACWY-TT vaccine in JIA and IBD patients at adolescent age and compared results to data from aged-matched healthy controls (HCs). METHODS: We performed a prospective observational cohort study in JIA and IBD patients (14-18 years old), who received a MenACWY vaccination during a nationwide catch-up campaign (2018-2019) in the Netherlands. Primary aim was to compare MenACWY polysaccharide-specific serum IgG geometric mean concentrations (GMCs) in patients with HCs and secondary between patients with or without anti-TNF therapy. GMCs were determined before and 3-6, 12, and 24 months postvaccination and compared with data from HCs at baseline and 12 months postvaccination. Serum bactericidal antibody (SBA) titers were determined in a subset of patients at 12 months postvaccination. RESULTS: We included 226 JIA and IBD patients (66 % and 34 % respectively). GMCs were lower for MenA and MenW (GMC ratio 0·24 [0·17-0·34] and 0·16 [0·10-0·26] respectively, p < 0·01) in patients compared to HCs at 12 months postvaccination. Anti-TNF users had lower MenACWY GMCs postvaccination compared with those without anti-TNF (p < 0·01). The proportion protected (SBA ≥ 8) for MenW was reduced in anti-TNF users (76 % versus 92 % in non-anti-TNF and 100 % in HCs, p < 0.01). CONCLUSION: The MenACWY conjugate vaccine was immunogenic in the vast majority of JIA and IBD patients at adolescent age, but seroprotection was lower in patients using anti-TNF agents. Therefore, an extra booster MenACWY vaccination should be considered.