A Randomized, Placebo-Controlled Phase III Extension Trial of the Long-Term Safety and Tolerability of Anifrolumab in Active Systemic Lupus Erythematosus.

Objective: To explore long-term safety and tolerability of anifrolumab 300 mg compared with placebo in patients with systemic lupus erythematosus (SLE) who completed a Treatment of Uncontrolled Lupus via the Interferon Pathway (TULIP) trial and enrolled in the placebo-controlled 3-year long-term extension (LTE) study (ClinicalTrials.gov identifier: NCT02794285).

Methods: In the blinded LTE study, patients continued anifrolumab 300 mg, switched from anifrolumab 150 mg to 300 mg, or were re-randomized from placebo to receive either anifrolumab 300 mg or to continue placebo, administered every 4 weeks.

POP1 inhibits MSU-induced inflammasome activation and ameliorates gout.

Canonical inflammasomes are innate immune protein scaffolds that enable the activation of inflammatory caspase-1, and subsequently the processing and release of interleukin (IL)-1β, IL-18, and danger signals, as well as the induction of pyroptotic cell death. Inflammasome assembly and activation occurs in response to sensing of infectious, sterile and self-derived molecular patterns by cytosolic pattern recognition receptors, including the Nod-like receptor NLRP3. While these responses are essential for host defense, excessive and uncontrolled NLRP3 inflammasome responses cause and contribute to a wide spectrum of inflammatory diseases, including gout.

Sustained glucocorticoid tapering in the phase 3 trials of anifrolumab: a post hoc analysis of the TULIP-1 and TULIP-2 trials.

Objectives: Glucocorticoid sparing is a key priority for SLE management. We evaluated the effects of sustained glucocorticoid tapering in patients with SLE.

Material And Methods: This was a post hoc analysis of the randomized, placebo-controlled, 52-week phase 3 Treatment of Uncontrolled Lupus via the Interferon Pathway (TULIP)-1 and TULIP-2 trials of anifrolumab (300 mg i.

Concordance and discordance in SLE clinical trial outcome measures: analysis of three anifrolumab phase 2/3 trials.

Objectives: In the anifrolumab systemic lupus erythematosus (SLE) trial programme, there was one trial (TULIP-1) in which BILAG-based Composite Lupus Assessment (BICLA) responses favoured anifrolumab over placebo, but the SLE Responder Index (SRI(4)) treatment difference was not significant. We investigated the degree of concordance between BICLA and SRI(4) across anifrolumab trials in order to better understand drivers of discrepant SLE trial results.

Methods: TULIP-1, TULIP-2 (both phase 3) and MUSE (phase 2b) were randomised, 52-week trials of intravenous anifrolumab (300 mg every 4 weeks, 48 weeks; TULIP-1/TULIP-2: n=180; MUSE: n=99) or placebo (TULIP-1: n=184, TULIP-2: n=182; MUSE: n=102).

Anifrolumab efficacy and safety by type I interferon gene signature and clinical subgroups in patients with SLE: post hoc analysis of pooled data from two phase III trials.

Objectives: To characterise the efficacy and safety of anifrolumab in patients with systemic lupus erythematosus (SLE) according to interferon gene signature (IFNGS), demographic and clinical subgroups.

Methods: We performed post hoc analyses of pooled data from the 52-week phase III TULIP-1/TULIP-2 placebo-controlled trials of intravenous anifrolumab in moderate-to-severe SLE. Outcomes were assessed in predefined subgroups: IFNGS (high/low), age, sex, body mass index, race, geographic region, age of onset, glucocorticoid use, disease activity and serological markers.

Perspectives of Health Care Providers in an Integrated Health Care Delivery Network on Inpatient Electronic Consultation (e-Consult) Use During the COVID-19 Pandemic.

A large academic hospital system (Allegheny Health Network) introduced inpatient electronic consultations (e-Consults) during the COVID-19 crisis. Providers were invited to complete an anonymous survey on their perceptions of e-Consults. Descriptive statistics were used to analyze Likert-scale data.

Anti-beta 2 glycoprotein I IgA in the SLICC classification criteria dataset.

Objective: Anti-beta 2 glycoprotein I IgA is a common isotype of anti-beta 2 glycoprotein I in SLE. Anti-beta 2 glycoprotein I was not included in the American College of Rheumatology (ACR) SLE classification criteria, but was included in the Systemic Lupus International Collaborating Clinics (SLICC) criteria. We aimed to evaluate the prevalence of anti-beta 2-glycoprotein I IgA in SLE versus other rheumatic diseases.

Coronavirus Disease-2019: Implication for the care and management of patients with systemic lupus erythematosus.

Systemic lupus erythematosus is a chronic remitting-relapsing autoimmune disease that affects multiple organ systems. In this article we discuss aspects in the management of lupus patients that are particularly relevant during the current SARS-CoV-2 pandemic. We speculate that lupus patients might be more susceptible for a more severe COVID-19 disease course and emphasize the importance of maintaining remission in lupus patients.

Type I interferon inhibitor anifrolumab in active systemic lupus erythematosus (TULIP-1): a randomised, controlled, phase 3 trial.

Background: Type I interferons are involved in systemic lupus erythematosus (SLE) pathogenesis. In a phase 2 trial, anifrolumab, a human monoclonal antibody to type I interferon receptor subunit 1, suppressed interferon gene signatures and substantially reduced SLE disease activity. Here, we sought to confirm the efficacy of anifrolumab versus placebo in a phase 3 trial of adult patients with SLE and moderate-to-severe disease activity despite standard-of-care treatment.

Soluble urokinase plasminogen activator receptor (suPAR) levels predict damage accrual in patients with recent-onset systemic lupus erythematosus.

Objective: The soluble urokinase plasminogen activator receptor (suPAR) has potential as a prognosis and severity biomarker in several inflammatory and infectious diseases. In a previous cross-sectional study, suPAR levels were shown to reflect damage accrual in cases of systemic lupus erythematosus (SLE). Herein, we evaluated suPAR as a predictor of future organ damage in recent-onset SLE.

Osteopontin and Disease Activity in Patients with Recent-onset Systemic Lupus Erythematosus: Results from the SLICC Inception Cohort.

Objective: In cross-sectional studies, elevated osteopontin (OPN) levels have been proposed to reflect, and/or precede, progressive organ damage and disease severity in systemic lupus erythematosus (SLE). We aimed, in a cohort of patients with recent-onset SLE, to determine whether raised serum OPN levels precede damage and/or are associated with disease activity or certain disease phenotypes.

Methods: We included 344 patients from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort who had 5 years of followup data available.

Associations of cardiovascular fat radiodensity and vascular calcification in midlife women: The SWAN cardiovascular fat ancillary study.

Background And Aims: Fat radiodensity, measured via CT Hounsfield units (HU), is a potential marker of fat quality. We sought to determine the cross-sectional associations of total heart fat (TAT) and aortic perivascular fat (PVAT) radiodensity with cardiovascular risk factors, coronary artery calcification (CAC), and aortic calcification (AC) in midlife women.

Methods: Fat radiodensity, CAC, and AC were quantified using CT scans.

Impact of an antimicrobial stewardship program on healthcare-associated rates at a community-based teaching hospital.

We conducted a pre-intervention/post-intervention study to assess the rate of healthcare-associated infections (HA-CDI) before and after the implementation of an antimicrobial stewardship program (ASP). Upon implementation of our ASP, the usage of targeted antimicrobials, including ceftriaxone, clindamycin, fluoroquinolones and carbapenem antibiotics, were significantly reduced. There was also a significant reduction in HA-CDI/1000 patient-days following ASP implementation (0.

3D MicroCT spatial and temporal characterization of thoracic aorta perivascular adipose tissue and plaque volumes in the ApoE-/- mouse model.

Perivascular adipose tissue (PVAT) influences vascular function and pathology. We present a protocol using micro-computed tomography (microCT), a novel imaging technique typically used for hard biological tissue, to characterize the temporal and spatial development of aorta PVAT and luminal plaque soft tissue. Apolipoprotein E deficient (ApoE) and C57Bl/6J (control) mice were fed a high fat western diet up to 30 weeks.

CRISPR-Cas9 HDR system enhances AQP1 gene expression.

Ionizing radiation (IR) isthe primarytherapeutic tool to treat patients with cancerous lesions located in the head and neck. In many patients, IR results in irreversible and severe salivary gland dysfunction or xerostomia. Currently there are no effective treatment options to reduce the effects of xerostomia.

Cell-bound complement activation products as lupus biomarkers: diagnosis, monitoring and stratification.

Cell-bound complement activation products (CB-CAPs) were first reported in 2004, since which time multiple laboratories have demonstrated their value as biomarkers for diagnosis, monitoring, and stratification of patients with systemic lupus erythematosus. Areas covered: This review summarizes the highlights of these 14 years of CB-CAPs discovery and validation, concluding with a view toward their future potential for precision medicine. Expert commentary: The practice of medicine is both art and science and each physician can be considered both artist and scientist with a variable blend of the two skill sets.

Differential Adipose Tissue Proteomics.

Differential proteomic analysis (comparative quantitative proteomics) is a robust quantitative technique used to detect and identify the proteome of selected tissues. The expression levels (upregulated vs. downregulated) of proteins in tissue samples that differ by experimental design or anatomic location are determined by a series of assays including (1) 2D difference gel electrophoresis (2D-DiGE), (2) protein spot picking based on a priori thresholds, (3) Mass Spectrometry, and (4) follow-up Western Blot for antibody validation (Chen et al.

Potential Roles of Antiphospholipid Antibodies in Generating Platelet-C4d in Systemic Lupus Erythematosus.

Premature, accelerated onset of atherothrombotic disease is prevalent in patients with systemic lupus erythematosus (SLE). Most, if not all, atherothrombotic diseases are likely to involve platelets and complement. Previously, we discovered that platelets bearing complement activation product C4d (P-C4d) are present in SLE patients, and are significantly associated with antiphospholipid (aPL) antibody positivity and stroke in SLE patients.

MicroCT analysis of vascular morphometry: a comparison of right lung lobes in the SUGEN/hypoxic rat model of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a rare disease characterized by significant vascular remodeling within the lung. Clinical computed tomography (CT) scans are routinely used to aid in PAH diagnosis. Animal models, including the Sugen-hypoxic rat model (SU/hyp), of PAH closely mimic human PAH development.

Immune-mediated syndromes following intravenous bisphosphonate therapy.

Objectives: Intravenous (IV) infusion of aminobisphosphonates (ABP) induces cytokine release by peripheral blood Vγ9δ2 T cells, resulting in an immediate short-term inflammatory response in up to 50% of patients. We evaluated possible long-term pro-inflammatory effects of IV ABP.

Methods: Retrospective case-series study from one rheumatology specialist's clinic.

In vivo Endocrine Secretion of Prostacyclin Following Expression of a Cyclooxygenase-1/Prostacyclin Fusion Protein in the Salivary Glands of Rats Via Nonviral Gene Therapy.

Pulmonary arterial hypertension (PAH) is a progressive disease that culminates in right heart failure and death. Prostacyclin (PGI2) and its derivatives are effective treatments for PAH when administered as continuous parenteral infusions. This treatment paradigm requires medical sophistication, and patients are at risk for complications from an indewelling catheter; drug interruptions may result in rebound pulmonary hypertension and death.

Association of aortic perivascular adipose tissue density with aortic calcification in women with systemic lupus erythematosus.

Background And Aims: Women with systemic lupus erythematosus (SLE) have an increased risk of cardiovascular disease (CVD). Perivascular adipose tissue (PVAT) surrounds the vascular wall, is associated with CVD risk factors, and may contribute to premature CVD in SLE. We previously found greater volumes of aortic PVAT associated with aortic calcification (AC) in female SLE patients.

Plasma complement and vascular complement deposition in patients with coronary artery disease with and without inflammatory rheumatic diseases.

Purpose: Inflammatory rheumatic diseases (IRD) are associated with accelerated coronary artery disease (CAD), which may result from both systemic and vascular wall inflammation. There are indications that complement may be involved in the pathogenesis of CAD in Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA). This study aimed to evaluate the associations between circulating complement and complement activation products with mononuclear cell infiltrates (MCI, surrogate marker of vascular inflammation) in the aortic media and adventitia in IRDCAD and non-IRDCAD patients undergoing coronary artery bypass grafting (CABG).

Postmenopausal Women With Greater Paracardial Fat Have More Coronary Artery Calcification Than Premenopausal Women: The Study of Women's Health Across the Nation (SWAN) Cardiovascular Fat Ancillary Study.

Background: Volumes of paracardial adipose tissue (PAT) and epicardial adipose tissue (EAT) are greater after menopause. Interestingly, PAT but not EAT is associated with estradiol decline, suggesting a potential role of menopause in PAT accumulation. We assessed whether volumes of heart fat depot (EAT and PAT) were associated with coronary artery calcification (CAC) in women at midlife and whether these associations were modified by menopausal status and estradiol levels.