Type I interferon biomarker in idiopathic inflammatory myopathies: associations of Siglec-1 with disease activity and treatment response.

Objectives: Novel biomarkers are needed to guide therapy in idiopathic inflammatory myopathies (IIM). Expression of Siglec-1, a type I interferon biomarker, was examined in adult patients with IIM in relation to disease activity and treatment response.

Methods: We analysed PBMC samples from 19 newly diagnosed adult IIM patients who participated in a phase-2 pilot study on efficacy of intravenous immunoglobulin (IVIG) monotherapy, and from 9 healthy controls.

Pharmacokinetics and Pharmacodynamics of Systemic Corticosteroids in Autoimmune and Inflammatory Diseases: A Review of Current Evidence.

Background And Objective: Systemic corticosteroids have a long history of use in the treatment of autoimmune and inflammatory diseases. Both efficacy and safety show large interindividual variability (IIV), suggesting that corticosteroids may have the potential for individualised dosing strategies to optimise therapy. This systematic review aims to provide an overview of current evidence on the pharmacokinetic (PK) and pharmacodynamic (PD) relationships of systemic corticosteroids in patients with autoimmune and inflammatory diseases.

Personalised medicine in juvenile dermatomyositis: From novel insights in disease mechanisms to changes in clinical practice.

Juvenile dermatomyositis is characterized by childhood-onset chronic inflammation of the muscles and skin, with potential involvement of other organs. Patients are at risk for long-term morbidity due to insufficient disease control and steroid-related toxicity. Personalised treatment is challenged by a lack of validated tools that can reliably predict treatment response and monitor ongoing (subclinical) inflammation, and by a lack of evidence regarding the best choice of medication for individual patients.

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.

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.

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.

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.

Recombinant Interleukin-1 Receptor Antagonist Is an Effective First-Line Treatment Strategy in New-Onset Systemic Juvenile Idiopathic Arthritis, Irrespective of HLA-DRB1 Background and IL1RN Variants.

Objective: Human leukocyte antigen (HLA)-DRB1*15:01 has been recently associated with interstitial lung disease (LD), eosinophilia, and drug reactions in systemic juvenile idiopathic arthritis (sJIA). Additionally, genetic variants in IL1RN have been linked to poor response to anakinra. We sought to reproduce these findings in a prospective cohort study of patients with new-onset sJIA treated with anakinra as first-line therapy.

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.

Safety of Measles-Mumps-Rubella booster vaccination in patients with juvenile idiopathic arthritis: A long-term follow-up study.

Objectives: To study short and long-term disease activity and vaccine-related adverse events in a cohort of JIA patients who received the live attenuated measles-mumps-rubella (MMR) booster vaccine while being treated with immunosuppressive and immunomodulatory therapies.

Methods: A retrospective study was performed in the UMC Utrecht, clinical and therapeutic data were collected from electronic medical records for two visits before and two visits after the MMR booster vaccine of JIA patients. Drug therapy was collected and adverse events related to the vaccine were requested from the patients during clinical visits or by short phone interviews.

Vaccinology in pediatric rheumatology: Past, present and future.

With the introduction of biological disease-modifying antirheumatic drugs (bDMARDs), the treatment of pediatric patients with autoimmune/inflammatory rheumatic diseases (pedAIIRD) has advanced from the "Stone Age" to modern times, resulting in much better clinical outcomes. However, everything comes with a price, and use of new bDMARDs has resulted in an increased risk of infections. Therefore, preventing infections in pedAIIRD patients is one of the top priorities.

Efficacy, Immunogenicity and Safety of Vaccination in Pediatric Patients With Autoimmune Inflammatory Rheumatic Diseases (pedAIIRD): A Systematic Literature Review for the 2021 Update of the EULAR/PRES Recommendations.

Background: In 2011, the first European League Against Rheumatism (EULAR) vaccination recommendations for pediatric patients with autoimmune inflammatory rheumatic diseases (pedAIIRD) were published. The past decade numerous new studies were performed to assess the safety, efficacy and immunogenicity of vaccinations in pedAIIRD. A systematic literature review (SLR) was therefore performed to serve as the basis for the updated 2021 EULAR/PRES recommendations.

EULAR/PRES recommendations for vaccination of paediatric patients with autoimmune inflammatory rheumatic diseases: update 2021.

Objectives: Recent insights supporting the safety of live-attenuated vaccines and novel studies on the immunogenicity of vaccinations in the era of biological disease-modifying antirheumatic drugs in paediatric patients with autoimmune/inflammatory rheumatic diseases (pedAIIRD) necessitated updating the EULAR recommendations.

Methods: Recommendations were developed using the EULAR standard operating procedures. Two international expert committees were formed to update the vaccination recommendations for both paediatric and adult patients with AIIRD.

Anti-C2 Antibody ARGX-117 Inhibits Complement in a Disease Model for Multifocal Motor Neuropathy.

Background And Objectives: To determine the role of complement in the disease pathology of multifocal motor neuropathy (MMN), we investigated complement activation, and inhibition, on binding of MMN patient-derived immunoglobulin M (IgM) antibodies in an induced pluripotent stem cell (iPSC)-derived motor neuron (MN) model for MMN.

Methods: iPSC-derived MNs were characterized for the expression of complement receptors and membrane-bound regulators, for the binding of circulating IgM anti-GM1 from patients with MMN, and for subsequent fixation of C4 and C3 on incubation with fresh serum. The potency of ARGX-117, a novel inhibitory monoclonal antibody targeting C2, to inhibit fixation of complement was assessed.

Siglec-1 expression on monocytes is associated with the interferon signature in juvenile dermatomyositis and can predict treatment response.

Objective: JDM is a rare chronic immune-mediated inflammatory disease with a predominant role for type I IFN responses. We aimed to determine the potential of Siglec-1 expression on monocytes as a novel IFN-inducible biomarker for disease activity monitoring and prediction of treatment response in patients with JDM.

Methods: Siglec-1 was measured by flow cytometry on circulating monocytes of 21 newly diagnosed JDM patients before start of treatment and, for 10 of these, also during follow-up.

A phase I/II study of bevacizumab, irinotecan and erlotinib in children with progressive diffuse intrinsic pontine glioma.

Introduction: This study investigates the safety, tolerability, and preliminary efficacy of combined treatment with VEGF inhibitor bevacizumab, topoisomerase I inhibitor irinotecan, and EGFR inhibitor erlotinib in children with progressive diffuse intrinsic pontine glioma (DIPG).

Methods: Biweekly bevacizumab (10 mg/kg) and irinotecan (125 mg/m) were combined with daily erlotinib. Two cohorts received increasing doses of erlotinib (65 and 85 mg/m) following a 3 + 3 dose-escalation schedule, until disease progression with a maximum of one year.

Intragenic and structural variation in the locus and clinical variability in spinal muscular atrophy.

Clinical severity and treatment response vary significantly between patients with spinal muscular atrophy. The approval of therapies and the emergence of neonatal screening programmes urgently require a more detailed understanding of the genetic variants that underlie this clinical heterogeneity. We systematically investigated genetic variation other than copy number in the locus.

Plant, space and time - linked together in an integrative and scalable data management system for phenomic approaches in agronomic field trials.

Background: To ensure further genetic gain, genomic approaches in plant breeding rely on precise phenotypic data, describing plant structure, function and performance. A more precise characterization of the environment will allow a better dealing with genotype-by-environment-by-management interactions. Therefore, space and time dependencies of the crop production processes have to be considered.

Analysis of , , and as potential disease severity modifiers in spinal muscular atrophy.

Objective: To investigate mutations in genes that are potential modifiers of spinal muscular atrophy (SMA) severity.

Methods: We performed a hypothesis-based search into the presence of variants in fused in sarcoma () transactive response DNA-binding protein 43 (), plastin 3 (), and profilin 2 () in a cohort of 153 patients with SMA types 1-4, including 19 families. Variants were detected with targeted next-generation sequencing and confirmed with Sanger sequencing.

Pharmacogenetic interactions in amyotrophic lateral sclerosis: a step closer to a cure?

Genetic mutations related to amyotrophic lateral sclerosis (ALS) act through distinct pathophysiological pathways, which may lead to varying treatment responses. Here we assess the genetic interaction between C9orf72, UNC13A, and MOBP with creatine and valproic acid treatment in two clinical trials. Genotypic data was available for 309 of the 338 participants (91.

Incisional Hernia Repair of Medium- and Large-Sized Defects: Laparoscopic IPOM Versus Open SUBLAY Technique.

Small incisional hernias can be repaired laparoscopically with low morbidity and reasonable recurrence rates. The aim of this study was to compare laparoscopic with open technique in medium- and large-sized defects regarding postoperative complications and recurrence rates. Between 2012 and 2016, 102 patients with medium- or large-sized defects according to EHS classification underwent incisional hernia repair.

Using attractiveness model for actors ranking in social media networks.

Background: Influential actors detection in social media such as Twitter or Facebook can play a major role in gathering opinions on particular topics, improving the marketing efficiency, predicting the trends, etc.

Proposed Methods: This work aims to extend our formally defined measure to present a new measure aiming to recognize the actor's influence by the strength of attracting new important actors into a networked community. Therefore, we propose a model of the actor's influence based on the attractiveness of the actor in relation to the number of other attractors with whom he/she has established connections over time.

Impact of obesity on postoperative complications after laparoscopic and open incisional hernia repair - A prospective cohort study.

Background: Obese patients are often required to lose weight prior to incisional hernia repair as obesity is thought to increase postoperative complications and recurrence rates. The aim of this study was to determine the impact of BMI on the outcome after laparoscopic and open incisional hernia repair.

Materials And Methods: In a cohort study from May 2012 to August 2016, 178 patients underwent incisional hernia repair: 90 patients open SUBLAY and 88 patients laparoscopic intraperitoneal onlay mesh (IPOM).