Publications by authors named "Philip M. Carlucci"

Objectives: Glucagon-like peptide-1 receptor agonists (GLP1-RA) are an emerging class of medications with demonstrated promise in improving cardiometabolic outcomes. Whether these drugs may be useful in mitigating the cardiac risk associated with SLE remains unknown, and a recent case of drug induced lupus secondary to GLP1-RA use calls the safety of GLP1-RAs in SLE patients into question. Accordingly, this retrospective analysis was initiated to evaluate outcomes of GLP1-RAs in SLE.

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  • The study investigates how isolated lupus nephritis (LN) impacts health-related quality of life (HRQOL) compared to patients with additional extrarenal symptoms.
  • It involved 181 LN patients who completed the PROMIS-29 questionnaire, revealing that those with extrarenal symptoms reported worse pain, social participation, physical function, and fatigue than those with just renal symptoms.
  • The findings emphasize the need for treatment approaches that consider both renal and extrarenal issues to enhance overall patient well-being.
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  • The study utilized the Manhattan Lupus Surveillance Program (MLSP) to analyze the prevalence of systemic lupus erythematosus (SLE) along with related rheumatic diseases like Sjögren's disease, antiphospholipid syndrome, and fibromyalgia among different demographics.
  • A total of 1,342 SLE patients were examined, with findings indicating that Sjögren's disease (11.0%) and antiphospholipid syndrome (8.9%) were notably common among Latino and Asian patients, while fibromyalgia also affected 8.9% of patients, particularly among non-Latino White and Latino populations.
  • The research revealed significant differences in autoantibody profiles associated with S
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Background: Leveraging the Accelerating Medicines Partnership (AMP) Lupus Nephritis (LN) dataset, we evaluated longitudinal patterns, rates, and predictors of response to standard-of-care therapy in patients with lupus nephritis.

Methods: Patients from US academic medical centers with class III, IV, and/or V LN and a baseline urine protein/creatinine (UPCR) ratio ≥ 1.0 (n = 180) were eligible for this analysis.

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Objective: Given fibromyalgia (FM) frequently co-occurs with autoimmune disease, this study was initiated to objectively evaluate FM in a multiracial/ethnic cohort of patients with systemic lupus erythematosus (SLE).

Methods: Patients with SLE were screened for FM using the 2016 FM classification criteria during an in-person rheumatologist visit. We evaluated hybrid Safety of Estrogens in Lupus National Assessment (SELENA)-SLE Disease Activity Index (SLEDAI) scores, SLE classification criteria, and Systemic Lupus International Collaborating Clinics damage index.

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Objective: This prospective study of pregnant patients, Surveillance To Prevent AV Block Likely to Occur Quickly (STOP BLOQ), addresses the impact of anti-SSA/Ro titers and utility of ambulatory monitoring in the detection of fetal second-degree atrioventricular block (AVB).

Methods: Women with anti-SSA/Ro autoantibodies by commercial testing were stratified into high and low anti-52-kD and/or 60-kD SSA/Ro titers applying at-risk thresholds defined by previous evaluation of AVB pregnancies. The high-titer group performed fetal heart rate and rhythm monitoring (FHRM) thrice daily and weekly/biweekly echocardiography from 17-26 weeks.

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  • The study examines how urine protein:creatinine ratios (UPCR) relate to kidney histology and outcomes in patients with lupus nephritis (LN), focusing on cases with UPCR between 0.5 and 1.
  • Researchers analyzed data from 275 SLE patients undergoing renal biopsy, finding that a significant majority had severe histological classes despite low UPCR levels.
  • The findings suggest that renal biopsies should be performed even when UPCR is below 1, as many patients still exhibit concerning histological features and activity.
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Objectives: In lupus nephritis the pathological diagnosis from tissue retrieved during kidney biopsy drives treatment and management. Despite recent approval of new drugs, complete remission rates remain well under aspirational levels, necessitating identification of new therapeutic targets by greater dissection of the pathways to tissue inflammation and injury. This study assessed the safety of kidney biopsies in patients with SLE enrolled in the Accelerating Medicines Partnership, a consortium formed to molecularly deconstruct nephritis.

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Increased risk of premature cardiovascular disease (CVD) is well recognized in systemic lupus erythematosus (SLE). Aberrant type I-Interferon (IFN)-neutrophil interactions contribute to this enhanced CVD risk. In lupus animal models, the Janus kinase (JAK) inhibitor tofacitinib improves clinical features, immune dysregulation and vascular dysfunction.

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  • Neutrophil extracellular traps (NETs) contain nucleic material and proteins that may worsen autoimmune diseases like systemic lupus erythematosus (SLE) by triggering type I interferon (IFN) responses due to oxidized DNA.* -
  • The study found that RNA in NETs from lupus patients could be taken up by endothelial cells (ECs), enhancing inflammation, especially when the RNA is oxidized, with this process reliant on specific receptors and cellular structures.* -
  • Key findings point to the small RNA let-7b in NETs as a significant factor in activating proinflammatory pathways in vascular cells, suggesting its role in the complications associated with lupus vasculopathy.*
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COVID-19 has rapidly emerged as a pandemic infection that has caused significant mortality and economic losses. Potential therapies and prophylaxis against COVID-19 are urgently needed to combat this novel infection. As a result of evidence suggesting zinc sulphate may be efficacious against COVID-19, our hospitals began using zinc sulphate as add-on therapy to hydroxychloroquine and azithromycin.

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Objective: Neutrophil dysregulation and the type I interferon (IFN) axis have been proposed to contribute to premature cardiovascular disease, a leading cause of mortality in patients with systemic lupus erythematosus (SLE). In the present study, we evaluated the ability of anifrolumab, a type I IFN receptor-blocking antibody, to reduce neutrophil extracellular trap (NET) formation and modulate cardiometabolic disease markers in comparison to placebo.

Methods: Study subjects comprised patients with moderate-to-severe SLE who were enrolled in phase IIb of the MUSE trial (A Phase II, Randomized Study to Evaluate the Efficacy and Safety of MEDI-546 in Subjects with Systemic Lupus Erythematosus), with healthy individuals as controls.

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Background: People living with human immunodeficiency virus (HIV) may have numerous risk factors for acquiring coronavirus disease 2019 (COVID-19) and developing severe outcomes, but current data are conflicting.

Methods: Health-care providers enrolled consecutively, by nonrandom sampling, people living with HIV (PWH) with lab-confirmed COVID-19, diagnosed at their facilities between 1 April and 1 July 2020. Deidentified data were entered into an electronic Research Electronic Data Capture (REDCap) system.

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Objective: To characterize patients with systemic lupus erythematosus (SLE) affected by coronavirus disease 2019 (COVID-19) and to analyze associations of comorbidities and medications on infection outcomes.

Methods: Patients with SLE and reverse transcriptase-polymerase chain reaction-confirmed COVID-19 were identified through an established New York University lupus cohort, query of 2 hospital systems, and referrals from rheumatologists. Data were prospectively collected via a web-based questionnaire and review of medical records.

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Background: SARS-CoV-2 infection continues to cause significant morbidity and mortality worldwide. Preliminary data on SARS-CoV-2 infection suggest that some immunocompromised hosts experience worse outcomes. We performed a retrospective matched cohort study to characterize outcomes in HIV-positive patients with SARS-CoV-2 infection.

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Rheumatoid arthritis (RA) is characterized by synovial joint inflammation, cartilage damage, and dysregulation of the adaptive immune system. While neutrophil extracellular traps (NETs) have been proposed to play a role in the generation of modified autoantigens and in the activation of synovial fibroblasts, it remains unknown whether NETs are directly involved in cartilage damage. Here, we report a new mechanism by which NET-derived elastase disrupts cartilage matrix and induces release of membrane-bound peptidylarginine deiminase-2 by fibroblast-like synoviocytes (FLSs).

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Neutrophil dysregulation is implicated in the pathogenesis of systemic lupus erythematosus (SLE). SLE is characterized by elevated levels of a pathogenic neutrophil subset known as low-density granulocytes (LDGs). The origin and phenotypic, functional, and pathogenic heterogeneity of LDGs remain to be systematically determined.

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Hidradenitis suppurativa (HS), also known as acne inversa, is an incapacitating skin disorder of unknown etiology manifested as abscess-like nodules and boils resulting in fistulas and tissue scarring as it progresses. Given that neutrophils are the predominant leukocyte infiltrate in HS lesions, the role of neutrophil extracellular traps (NETs) in the induction of local and systemic immune dysregulation in this disease was examined. Immunofluorescence microscopy was performed in HS lesions and detected the prominent presence of NETs.

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Article Synopsis
  • Subjects with systemic lupus erythematosus (SLE) have a higher risk of cardiovascular disease (CVD) that isn't fully captured by traditional risk assessments, prompting this study to explore nuclear MR (NMR) spectroscopy for evaluating lipoprotein levels and GlycA.
  • The study used coronary CT angiography to assess plaque burden in SLE patients and healthy controls, finding significant differences in lipoprotein particle counts and sizes between the two groups.
  • Results indicate that SLE patients exhibit a harmful lipoprotein profile, with decreased high-density lipoprotein (HDL) and increased very low-density lipoprotein (VLDL), suggesting that NMR measurements of GlycA and lipoproteins could better
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Background: Systemic lupus erythematosus (SLE) is associated with enhanced risk of atherosclerotic cardiovascular disease not explained by Framingham risk score (FRS). Immune dysregulation associated to a distinct subset of lupus proinflammatory neutrophils (low density granulocytes; LDGs) may play key roles in conferring enhanced CV risk. This study assessed if lupus LDGs are associated with in vivo vascular dysfunction and inflammation and coronary plaque.

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Rheumatoid arthritis (RA) is characterized by synovial joint inflammation and by development of pathogenic humoral and cellular autoimmunity to citrullinated proteins. Neutrophil extracellular traps (NETs) are a source of citrullinated autoantigens and activate RA synovial fibroblasts (FLS), cells crucial in joint damage. We investigated the molecular mechanisms by which NETs promote proinflammatory phenotypes in FLS, and whether these interactions generate pathogenic anti-citrulline adaptive immune responses.

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