Prospective SARS-CoV-2 Booster Vaccination in Immunosuppressant-Treated Systemic Autoimmune Disease Patients in a Randomized Controlled Trial.

Background: Autoimmune disease patients on immunosuppressants exhibit reduced humoral responses to primary COVID-19 vaccination. Booster vaccine responses and the effects of holding immunosuppression around vaccination are less studied. We evaluated the efficacy and safety of additional vaccination in mycophenolate mofetil/mycophenolic acid (MMF/MPA)-, methotrexate (MTX)-, and B cell-depleting therapy (BCDT)-treated autoimmune disease patients, including the impact of withholding MMF/MPA and MTX.

Approach to Janus kinase inhibition for juvenile dermatomyositis among CARRA and PReS providers.

Objectives: Janus kinase inhibition (JAKi) has been proposed as a treatment for idiopathic inflammatory myopathies to target increased interferon signalling. Predominantly retrospective reports have demonstrated effectiveness of JAKi in refractory JDM. However, JAKi remains an off-label treatment for JDM and there may be variation in use worldwide.

Meeting report: Hidden links in autoimmunity.

A NIAID-sponsored workshop was held in September 2024, where challenges to understanding common mechanisms in autoimmune disease were discussed as opportunities to advance research.

Myositis-Associated Autoantibodies in Patients With Juvenile Myositis Are Associated With Refractory Disease and Mortality.

Objective: Myositis-associated autoantibodies (MAAs) have been associated with overlap myositis, certain disease manifestations such as interstitial lung disease (ILD), and worse prognosis in the idiopathic inflammatory myopathies. MAAs overall remain largely uncharacterized in patients with juvenile-onset myositis. Moreover, it is unknown whether the number of MAAs is associated with disease severity.

Clinical Features and Immunogenetic Risk Factors Associated With Additional Autoantibodies in Anti-Transcriptional Intermediary Factor 1γ Juvenile-Onset Dermatomyositis.

Objective: Novel autoantibody specificities including anti-CCAR1 were recently discovered in adult patients with anti-transcriptional intermediary factor (TIF1)-positive dermatomyositis (DM) and were associated with attenuated cancer emergence. The aims of the present study were to examine whether these autoantibodies occur in patients with juvenile-onset DM (JDM) and to determine their associated features.

Methods: Sera from 150 patients with anti-TIF1γ autoantibody-positive JDM in a cross-sectional cohort and 90 juvenile healthy controls were assayed for anti-CCAR1, anti-C1Z1, anti-IMMT, anti-TBL1XR1, and anti-Sp4 autoantibodies.

Clinical outcomes and safety of anakinra in the treatment of multisystem inflammatory syndrome in children: a single center observational study.

Background And Objective: Evidence for the treatment of multisystem inflammatory syndrome in children (MIS-C) is lacking. Anakinra, which targets IL-1-mediated inflammation, is reserved for refractory cases of MIS-C; however, its use in the treatment of MIS-C is not clearly established.

Patients And Methods: To examine a role for anakinra in MIS-C, we performed a single center observational cohort study of all MIS-C patients diagnosed at our children's hospital from May 15 to November 15, 2020.

Autoantibodies Recognizing Specificity Protein 4 Co-occur With Anti-Transcription Intermediary Factor 1 and Are Associated With Distinct Clinical Features and Immunogenetic Risk Factors in Juvenile Myositis.

Objective: Autoantibodies recognizing specificity protein 4 (Sp4) were recently discovered in adults with idiopathic inflammatory myopathies (IIM). Anti-Sp4 autoantibodies co-occurred in patients with anti-transcription intermediary factor 1 (anti-TIF1) autoantibody-positive dermatomyositis (DM) and were associated with a reduced risk of cancer. In the present study, the prevalence and clinical features associated with anti-Sp4 autoantibodies in juvenile-onset IIM were investigated.

Treatment escalation patterns to start biologics in refractory moderate juvenile dermatomyositis among members of the Childhood Arthritis and Rheumatology Research Alliance.

Background: Despite new and better treatments for juvenile dermatomyositis (JDM), not all patients with moderate severity disease respond adequately to first-line therapy. Those with refractory disease remain at higher risk for disease and glucocorticoid-related complications. Biologic disease-modifying antirheumatic drugs (DMARDs) have become part of the arsenal of treatments for JDM.

Anti-FHL1 autoantibodies in juvenile myositis are associated with anti-Ro52 autoantibodies but not with severe disease features.

Objectives: Four-and-a-half LIM domains 1 (FHL1) is a muscle-specific protein. Autoantibodies against FHL1 were recently discovered in adults with idiopathic inflammatory myopathies (IIMs) and were found to be associated with clinical features and outcomes indicative of increased disease severity. Anti-FHL1 autoantibodies have not been described in children.

Autoantibody cluster analysis in juvenile lupus nephritis.

Objective: Demographics, clinical features, and biomarkers do not consistently anticipate risk of end-stage renal disease (ESRD) in juvenile lupus nephritis (LN). Here, the existence of autoantibody clusters predictive of ESRD was explored in a cohort of biopsy-proven juvenile LN.

Methods: A retrospective chart review was performed of patients with juvenile systemic lupus erythematosus (jSLE) and biopsy-confirmed LN.

Direct pulmonary delivery of solubilized curcumin reduces severity of lethal pneumonia.

Acute respiratory distress syndrome (ARDS), the most severe form of acute lung injury, is associated with reduced lung compliance and hypoxemia. Curcumin exhibits potent anti-inflammatory properties but has poor solubility and rapid plasma clearance. To overcome these physiochemical limitations and uncover the full therapeutic potential of curcumin in lung inflammation, in this study we utilized a novel water-soluble curcumin formulation (CDC) and delivered it directly into the lungs of C57BL/6 mice inoculated with a lethal dose of ().

The natural history and outcomes of line-associated upper extremity deep venous thromboses in critically ill patients.

Objective: Anticoagulation remains the standard of care for line-associated upper extremity deep venous thrombosis (UEDVT). This treatment carries the risk of hemorrhagic complications, possibly more so in surgical patients. Considering the low-risk profile of UEDVT-which is associated with fewer, less severe pulmonary emboli than lower extremity deep venous thrombosis-current UEDVT treatment guidelines may be overly aggressive.

Molecular Characterization of Hypoxic Alveolar Epithelial Cells After Lung Contusion Indicates an Important Role for HIF-1α.

Objective: To understand the fate and regulation of hypoxic type II alveolar epithelial cells (AECs) after lung contusion (LC).

Background: LC due to thoracic trauma is a major risk factor for the development of acute respiratory distress syndrome. AECs have recently been implicated as a primary driver of inflammation in LC.

Double-Stranded RNA Interacts With Toll-Like Receptor 3 in Driving the Acute Inflammatory Response Following Lung Contusion.

Objectives: Lung contusion is a major risk factor for the development of acute respiratory distress syndrome. We set to determine the role of toll-like receptor 3 and the binding of double-stranded RNA in the pathogenesis of sterile injury following lung contusion.

Design: Toll-like receptor 3 expression was analyzed in postmortem lung samples from patients with lung contusion.

Toll-Like Receptor-9 (TLR9) is Requisite for Acute Inflammatory Response and Injury Following Lung Contusion.

Lung contusion (LC) is a significant risk factor for the development of acute respiratory distress syndrome. Toll-like receptor 9 (TLR9) recognizes specific unmethylated CpG motifs, which are prevalent in microbial but not vertebrate genomic DNA, leading to innate and acquired immune responses. TLR9 signaling has recently been implicated as a critical component of the inflammatory response following lung injury.

Contemporary Management of Secondary Aortoduodenal Fistula.

Background: Secondary aortoduodenal fistula (SADF) is a rare, life-threatening complication of abdominal aortic reconstruction. Clinical presentation varies and treatment requires complex surgical repair associated with considerable morbidity and mortality. This retrospective study examines the contemporary management of SADF at a tertiary vascular surgical practice.

Flow Cytometry Based Detection and Isolation of Plasmodium falciparum Liver Stages In Vitro.

Malaria, the disease caused by Plasmodium parasites, remains a major global health burden. The liver stage of Plasmodium falciparum infection is a leading target for immunological and pharmacological interventions. Therefore, novel approaches providing specific detection and isolation of live P.

Differential activation of human constitutive androstane receptor and its SV23 and SV24 splice variants by rilpivirine and etravirine.

Background And Purpose: Rilpivirine and etravirine are second-generation non-nucleoside reverse transcriptase inhibitors (NNRTIs) indicated for the treatment of HIV/AIDS. The constitutive androstane receptor (CAR) regulates the expression of genes involved in various biological processes, including the transport and biotransformation of drugs. We investigated the effect of rilpivirine and etravirine on the activity of the wild-type human CAR (hCAR-WT) and its hCAR-SV23 and hCAR-SV24 splice variants, and compared it with first-generation NNRTIs (efavirenz, nevirapine, and delavirdine).

Agonism of human pregnane X receptor by rilpivirine and etravirine: comparison with first generation non-nucleoside reverse transcriptase inhibitors.

Rilpivirine and etravirine are second generation non-nucleoside reverse transcriptase inhibitors approved recently by the United States Food and Drug Administration for the treatment of human immunodeficiency virus-1 infection. Pregnane X receptor (PXR) is a member of the superfamily of nuclear receptors that regulate the expression of various genes controlling diverse biological functions. The present study investigated the effects of rilpivirine and etravirine on the activity of human PXR (hPXR), including the mode of activation, and compared them to those of efavirenz, nevirapine, and delavirdine, which are first generation non-nucleoside reverse transcriptase inhibitors.