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OBJECTIVE: Signal regulatory protein α (SIRPα) is found primarily on myeloid cells, including macrophages and neutrophils; binds to CD47; and regulates phagocytosis, antigen presentation, cellular fusion, cell proliferation, and migration. Therefore, SIRPα may be involved in the pathogenesis of autoimmune diseases, including systemic vasculitis. This study aimed to assess SIRPα expression in tissue samples from patients with vasculitis. METHODS: Immunohistochemical staining for SIRPα was performed on temporal artery (TA), kidney, and lung biopsy samples from patients with giant cell arteritis (GCA), patients with microscopic polyangiitis (MPA), patients with granulomatosis with polyangiitis (GPA), and patients without vasculitis. A score of SIRPα+ expression was calculated, derived from the percentages of monocytes, macrophages, and dendritic cells and neutrophils with different staining intensities in affected tissues. RESULTS: A total of 46 samples from patients with different vasculitides (GCA, MPA, and GPA) were included in the study. Tissue samples included TA samples from 15 patients with GCA; kidney samples from 11 and 9 patients with GPA and MPA, respectively; and lung samples from 11 patients with GPA. Most tissue samples from patients with active vasculitis (15 of 15 TA samples, 17 of 20 kidney samples, and 9 of 11 lung samples) showed SIRPα staining. SIRPα staining intensity was less in kidney samples compared to TA and lung samples. CONCLUSION: This study demonstrates high-level expression of SIRPα in macrophages and monocytes in affected tissue in systemic vasculitis. These findings provide a foundation for further studies exploring the role of the SIRPα-CD47 pathway in the pathogenesis of systemic vasculitis and the potential for the blockade of SIRPα and/or the depletion of SIRPα+ cells as treatment of systemic vasculitis.
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BACKGROUND: Whether tumor necrosis factor inhibitor (TNFi) use is cardioprotective among individuals with radiographic axial spondyloarthritis (r-axSpA), who have heightened cardiovascular (CV) risk, is unclear. We tested the association of TNFi use with incident CV outcomes in r-axSpA. METHODS: We identified a r-axSpA cohort within a Veterans Affairs database between 2002 and 2019 using novel phenotyping methods and secondarily using ICD codes. TNFi use was assessed as a time-varying exposure using pharmacy dispense records. The primary outcome was incident CV disease identified using ICD codes for coronary artery disease, myocardial infarction or stroke. We fit Cox models with inverse probability weights to estimate the risk of each outcome with TNFi use versus non-use. Analyses were performed in the overall cohort, and separately in two periods (2002-2010, 2011-2019) to account for secular trends. RESULTS: Using phenotyping we identified 26,928 individuals with an r-axSpA diagnosis (mean age 63.4 years, 94 % male); at baseline 3633 were TNFi users and 23,295 were non-users. During follow-up of a mean 3.3 ± 4.2 years, 674 (18.6 %) TNFi users had incident CVD versus 11,838 (50.8 %) non-users. In adjusted analyses, TNFi use versus non-use was associated with lower risk of incident CVD (HR 0.34, 95 % CI 0.29-0.40) in the cohort overall, and in the two time periods separately. CONCLUSION: In this r-axSpA cohort identified using phenotyping methods, TNFi use versus non-use had a lower risk of incident CVD. These findings provide reassurance regarding the CV safety of TNFi agents for r-axSpA treatment. Replication of these results in other cohorts is needed.
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OBJECTIVES: To evaluate damage and clinical characteristics associated with damage in Takayasu's arteritis (TAK). METHODS: Patients with TAK enrolled in a multicentre, prospective, observational study underwent standardized damage assessment every 6 months using the Vasculitis Damage Index (VDI) and the Large-Vessel Vasculitis Index of Damage (LVVID). RESULTS: The study included 236 patients with TAK: 92% female, 81% Caucasian; median (25th, 75th percentile) disease duration = 2.6 (0.12, 6.9) years. Eighty-four percent had follow-up: median (25th, 75th) duration 4.1 (1.9, 7.5) years.Items of damage were present in 89% on VDI, 87% on LVVID, in the peripheral vascular (76% VDI, 74% LVVID), cardiac (40% VDI, 45% LVVID) systems. During follow-up, 42% patients had new damage;, including major vessel stenosis/arterial occlusion (8%), limb claudication (6%), hypertension (7%), aortic aneurysm (4%), and bypass surgery (4%). Disease-specific damage accounted for >90% new items. Older age, relapse, and longer duration of follow-up were associated with new damage items; a higher proportion of patients without new damage were on methotrexate (p< 0.05). Among 48 patients diagnosed with TAK within 180 days of enrolment, new damage occurred in 31% on VDI and 52% on LVVID. History of relapse was associated with new damage in the entire cohort while in patients with a recent diagnosis, older age at diagnosis was associated with new damage. CONCLUSION: Damage is present in > 80% of patients with TAK even with recent diagnosis and >40% of patients accrue new, mainly disease-specific damage. Therapies for TAK that better control disease activity and prevent damage should be prioritized.
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OBJECTIVE: The objective of this study is to determine the associations of protein-specific anti-malondialdehyde-acetaldehyde (MAA) antibodies with prevalent and incident rheumatoid arthritis-interstitial lung disease (RA-ILD). METHODS: Within a multicenter, prospective cohort of US veterans with RA, RA-ILD was validated by medical record review of clinical diagnoses, chest imaging, and pathology. Serum antibodies to MAA-albumin, MAA-collagen, MAA-fibrinogen, and MAA-vimentin (IgA, IgM, and IgG) were measured by a standardized enzyme-linked immunosorbent assay. Associations of anti-MAA antibodies with prevalent and incident RA-ILD were assessed using multivariable regression models adjusting for established RA-ILD risk factors. RESULTS: Among 2,739 participants with RA (88% male, mean age of 64 years), there were 114 with prevalent and 136 with incident RA-ILD (average time to diagnosis: 6.6 years). Higher IgM anti-MAA-collagen (per 1 SD: adjusted odds ratio [aOR] 1.28, 95% confidence interval [CI] 1.02-1.61), IgA anti-MAA-fibrinogen (aOR 1.48, 95% CI 1.14-1.92), and IgA (aOR 1.78, 95% CI 1.34-2.37) and IgG (aOR 1.48, 95% CI 1.14-1.92) anti-MAA-vimentin antibodies were associated with prevalent RA-ILD. In incident analyses, higher IgA (per one SD: adjusted hazards ratio [aHR] 1.40, 95% CI 1.11-1.76) and IgM (aHR 1.29, 95% CI 1.04-1.60) anti-MAA-albumin antibody concentrations were associated with increased ILD risk. Participants with IgA (aHR 2.13, 95% CI 1.16-3.90) or IgM (aHR 1.98, 95% CI 1.08-3.64) anti-MAA-albumin antibody concentrations in the highest quartile had an approximately two-fold increased risk of incident RA-ILD. Across all isotypes, anti-MAA-fibrinogen, anti-MAA-collagen, and anti-MAA-vimentin antibodies were not significantly associated with incident RA-ILD. CONCLUSION: Protein-specific anti-MAA antibodies to collagen, fibrinogen, and vimentin were associated with prevalent RA-ILD. IgA and IgM anti-MAA-albumin antibodies were associated with a higher risk of incident RA-ILD. These findings suggest that MAA modifications and resultant immune responses may contribute to RA-ILD pathogenesis.
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Importance: With SARS-CoV-2 transforming into an endemic disease and with antiviral treatments available, it is important to establish which patients remain at risk of severe COVID-19 despite vaccination. Objective: To quantify the associations of clinical and demographic variables with odds of severe COVID-19 among patients with hematologic cancers. Design, Setting, and Participants: This case-control study included all patients with hematologic malignant neoplasms in the national Veterans Health Administration (VHA) who had documented SARS-CoV-2 infection after vaccination. Groups of patients with severe (cases) vs nonsevere (controls) COVID-19 were compared. Data were collected between January 1, 2020, and April 5, 2023, with data on infection collected between January 1, 2021, and September 30, 2022. All patients with diagnostic codes for hematologic malignant neoplasms who had documented vaccination followed by documented SARS-CoV-2 infection and for whom disease severity could be assessed were included. Data were analyzed from July 28 to December 30, 2023. Exposures: Clinical (comorbidities, predominant viral variant, treatment for malignant neoplasm, booster vaccination, and antiviral treatment) and demographic (age and sex) variables shown in prior studies to be associated with higher or lower rates of severe COVID-19. Comorbidities included Alzheimer disease or dementia, chronic kidney disease, chronic obstructive pulmonary disease, diabetes, heart failure, and peripheral vascular disease. Main Outcome and Measures: The main outcome was severe COVID-19 compared with nonsevere SARS-CoV-2 infection. Severe COVID-19 was defined as death within 28 days, mechanical ventilation, or hospitalization with use of dexamethasone or evidence of hypoxemia or use of supplemental oxygen. Multivariable logistic regression was used to estimate the associations of demographic and clinical variables with the odds of severe COVID-19, expressed as adjusted odds ratios (aORs) with 95% CIs. Results: Among 6122 patients (5844 [95.5%] male, mean [SD] age, 70.89 [11.57] years), 1301 (21.3%) had severe COVID-19. Age (aOR per 1-year increase, 1.05; 95% CI, 1.04-1.06), treatment with antineoplastic or immune-suppressive drugs (eg, in combination with glucocorticoids: aOR, 2.32; 95% CI, 1.93-2.80), and comorbidities (aOR per comorbidity, 1.35; 95% CI, 1.29-1.43) were associated with higher odds of severe disease, whereas booster vaccination was associated with lower odds (aOR, 0.73; 95% CI, 0.62-0.86). After oral antiviral drugs became widely used in March 2022, 20 of 538 patients (3.7%) with SARS-CoV-2 infection during this period had progression to severe COVID-19. Conclusions and Relevance: In this case-control study of patients with hematologic cancers, odds of severe COVID-19 remained high through mid-2022 despite vaccination, especially in patients requiring treatment.
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COVID-19 , Neoplasias Hematológicas , Adulto , Humanos , Masculino , Idoso , Feminino , COVID-19/epidemiologia , SARS-CoV-2 , Estudos de Casos e Controles , Saúde dos Veteranos , Neoplasias Hematológicas/epidemiologia , AntiviraisRESUMO
OBJECTIVE: We describe the demographics, clinical features, disease course, and survival of polyarteritis nodosa (PAN) through an international collaboration (GLOBAL-PAN). METHODS: Patients with PAN were recruited between 1990 and 2020 from observational cohorts of nine countries across Europe, Japan, and North America. Eligibility was retrospectively defined using the European Medicines Agency classification algorithm. Patients with PAN related to hepatitis B virus (n = 12) and two monogenic diseases mimicking PAN, deficiency of adenosine deaminase 2 enzyme (n = 16) or familial Mediterranean fever (n = 11), were excluded. Data regarding organ involvement, relapse, disease-related damage, and survival were analyzed. RESULTS: Three hundred fifty-eight patients (female:male ratio 174:184), including those with systemic PAN (sPAN, n = 282) and cutaneous PAN (n = 76), were included. Twenty-five were pediatric onset. Mean ± SD age at diagnosis was 44.3 ± 18.1 years. Constitutional symptoms (71.5%), cutaneous involvement (70.5%), musculoskeletal findings (69.1%), and neurologic features (48.0%) were common manifestations. Among patients with sPAN, gastrointestinal involvement and proteinuria over 400 mg/day were reported in 52.2% and 11.2%, respectively. During a median (interquartile range) 59.6 (99.5) months of follow-up, relapse occurred in 48.5% of patients. One, 5- and 10-year survival rates for sPAN were 97.1%, 94.0%, and 89.0%, respectively. Predictors of death for sPAN included age ≥65 years at diagnosis, serum creatinine at diagnosis >140 µmol/L, gastrointestinal manifestations, and central nervous system (CNS) involvement. CONCLUSION: The spectrum of PAN remains a complex, multifaceted disease. Relapse is common. Age ≥65 years and serum creatinine >140 µmol/L at diagnosis, as well as gastrointestinal and CNS involvement, are independent predictors of death in sPAN.
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Poliarterite Nodosa , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Estudos Retrospectivos , Europa (Continente)/epidemiologia , Idoso , América do Norte/epidemiologia , Japão/epidemiologia , Adulto Jovem , Proteinúria/etiologia , Recidiva , Taxa de SobrevidaRESUMO
OBJECTIVE: Although clinical and genetic risk factors have been identified for rheumatoid arthritis-associated interstitial lung disease (RA-ILD), there are no current tools allowing for risk stratification. We sought to develop and validate an ILD risk model in a large, multicentre, prospective RA cohort. METHODS: Participants in the Veterans Affairs RA (VARA) registry were genotyped for 12 single nucleotide polymorphisms (SNPs) associated with idiopathic pulmonary fibrosis. ILD was validated through systematic record review. A genetic risk score (GRS) was computed from minor alleles weighted by effect size with ILD, using backward selection. The GRS was combined with clinical risk factors within a logistic regression model. Internal validation was completed using bootstrapping, and model performance was assessed by the area under the receiver operating curve (AUC). RESULTS: Of 2,386 participants (89% male, mean age 69.5 years), 9.4% had ILD. Following backward selection, five SNPs contributed to the GRS. The GRS and clinical factors outperformed clinical factors alone in discriminating ILD (AUC 0.675 vs 0.635, p< 0.001). The shrinkage-corrected performance for combined and clinical-only models was 0.667 (95% CI 0.628, 0.712) and 0.623 (95% CI 0.584, 0.651), respectively. Twenty percent of the cohort had a combined risk score below a cut-point with >90% sensitivity. CONCLUSION: A clinical and genetic risk model discriminated ILD in a large, multicentre RA cohort better than a clinical-only model, excluding 20% of the cohort from low-yield testing. These results demonstrate the potential utility of a GRS in RA-ILD and support further investigation into individualized risk stratification and screening.
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Antiviral drugs reduce the rate of progression to severe COVID-19 when given to patients with mild-to-moderate disease within 5 days of symptom onset. Despite being recommended for patients at high risk for progression to severe COVID-19 because of age or chronic conditions, reported antiviral use among the general adult population has been ≤35%. To ascertain reasons for underuse of antiviral medications to prevent severe COVID-19 and propose interventions accordingly, a detailed review was conducted of 110 Veterans Health Administration patients with mild-to-moderate infection at high risk for progression because of underlying conditions (organ transplantation or hematologic malignancies) who did not receive an antiviral drug. Among these 110 patients, all of whom had received COVID-19 vaccine, 22 (20.0%) were offered treatment but declined, and 88 (80.0%) were not offered treatment. Among the 88 patients not offered treatment, provider reasons included symptom duration of >5 days (22.7%), concern about possible drug interactions (5.7%), or absence of symptoms (22.7%); however, among nearly one half (43 of 88; 48.9%) of these patients, no reason other than mild symptoms was given. Among 24 (55.8%) of those 43 patients, follow-up was limited to telephone calls to report test results and inquire about symptom evolution, with no documentation of treatment being offered. These findings suggest that education of patients, providers, and medical personnel tasked with follow-up calls, combined with advance planning in the event of a positive test result, might improve the rate of recommended antiviral medication use to prevent severe COVID-19-associated illness, including death.
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COVID-19 , Adulto , Humanos , SARS-CoV-2 , Vacinas contra COVID-19 , Saúde dos Veteranos , Antivirais/uso terapêuticoRESUMO
OBJECTIVE: To evaluate the associations of plasma matrix metalloproteinases (MMPs) with prevalent and incident interstitial lung disease (ILD) in people with rheumatoid arthritis (RA). METHODS: Within a multicenter, prospective cohort of US veterans with RA, we performed a cross-sectional study of prevalent ILD and cohort study of incident ILD. ILD diagnoses were validated by medical record review of provider diagnoses and chest imaging and/or pathology reports. MMP-1, 3, 7, and 9 concentrations were measured in plasma samples, then standardized and categorized into quartiles. The associations of MMPs with prevalent and incident ILD were assessed with logistic (prevalent) and Cox (incident) regression models adjusted for RA-ILD risk factors. RESULTS: Among 2,312 participants (88.9% male; mean age 63.8 years), 96 had prevalent ILD. Incident ILD developed in 130 participants over 17,378 person-years of follow-up (crude incidence rate 7.5/1,000 person-years). Participants with the highest quartile of MMP-7 concentrations had a nearly four-fold increased odds of prevalent ILD (adjusted odds ratio 3.78 [95% confidence interval (95% CI) 1.86-7.65]) and over two-fold increased risk of incident ILD (adjusted hazard ratio 2.33 [95% CI 1.35-4.02]). Higher MMP-9 concentrations were also associated with prevalent and incident ILD, as well as negatively correlated with forced vital capacity among those with prevalent ILD (r = -0.30, P = 0.005). CONCLUSION: MMP-7 and MMP-9 were strongly associated with both prevalent and incident ILD in this large, multicenter RA cohort after adjustment for other RA-ILD risk factors. These population-level findings further support a potential pathogenic role for MMPs in RA-ILD and suggest that their measurement could facilitate RA-ILD risk stratification.
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Artrite Reumatoide , Doenças Pulmonares Intersticiais , Metaloproteinase 7 da Matriz , Humanos , Doenças Pulmonares Intersticiais/sangue , Doenças Pulmonares Intersticiais/epidemiologia , Artrite Reumatoide/sangue , Artrite Reumatoide/complicações , Artrite Reumatoide/epidemiologia , Masculino , Pessoa de Meia-Idade , Feminino , Estudos Prospectivos , Metaloproteinase 7 da Matriz/sangue , Idoso , Estudos Transversais , Incidência , Fatores de Risco , Metaloproteinase 1 da Matriz/sangue , Metaloproteinase 9 da Matriz/sangue , Metaloproteinase 3 da Matriz/sangue , Prevalência , Estudos de Coortes , Metaloproteinases da Matriz/sangue , Estados Unidos/epidemiologia , Modelos de Riscos ProporcionaisRESUMO
BACKGROUND: Patients taking immune-suppressive drugs are at increased risk of severe coronavirus disease 2019 (COVID-19), not fully ameliorated by vaccination. We assessed the contributions of clinical and demographic factors to the risk of severe disease despite vaccination in patients taking immune-suppressive medications for solid organ transplantation (SOT), rheumatoid arthritis (RA), inflammatory bowel disease (IBD), or psoriasis. METHODS: Veterans Health Administration electronic health records were used to identify patients diagnosed with RA, IBD, psoriasis, or SOT who had been vaccinated against severe acute respiratory syndrome coronavirus 2, were subsequently infected, and had received immune-suppressive drugs within 3 months before infection. The association of severe (defined as hypoxemia, mechanical ventilation, dexamethasone use, or death) versus non-severe COVID-19 with the use of immune-suppressive and antiviral drugs and clinical covariates was assessed by multivariable logistic regression. RESULTS: Severe COVID-19 was more common in patients with SOT (230/1011, 22.7%) than RA (173/1355, 12.8%), IBD (51/742, 6.9%), or psoriasis (82/1125, 7.3%). Age was strongly associated with severe COVID-19, adjusted odds ratio (aOR) of 1.04 (CI 1.03-1.05) per year. Comorbidities indicating chronic brain, heart, lung, or kidney damage were also associated with severity, aOR 1.35-2.38. The use of glucocorticoids was associated with increased risk (aOR 1.66, CI 1.39-2.18). Treatment with antivirals was associated with reduced severity, for example, aOR 0.28 (CI 0.13-0.62) for nirmatrelvir/ritonavir. CONCLUSION: The risk of severe COVID-19 despite vaccination is substantial in patients taking immune-suppressive drugs, more so in patients with SOT than in patients with inflammatory diseases. Age and severe comorbidities contribute to risk, as in the general population. Oral antivirals were very beneficial but not widely used.
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Artrite Reumatoide , COVID-19 , Doenças Inflamatórias Intestinais , Psoríase , Veteranos , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Estudos de Coortes , Preparações Farmacêuticas , Artrite Reumatoide/tratamento farmacológico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Psoríase/tratamento farmacológico , Antivirais/uso terapêutico , VacinaçãoRESUMO
The role of complement in human autoimmune, inflammatory, and infectious diseases is reviewed, focusing on clinical applicability. A typical case is presented in which serum testing for C3 and C4 is performed to help assess a syndrome with a broad differential diagnosis. The review includes a discussion of complement deficiency states, consumption of complement by diseases characterized by immune-complex formation and deposition, usefulness and interpretation of laboratory tests for complement, and development of drugs targeting specific components of the complement pathway for a growing number of indications.
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Complemento C3 , Complemento C4 , Humanos , Proteínas do Sistema Complemento , SíndromeRESUMO
Introduction: Although the alternative complement pathway has been implicated in the pathogenesis of antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV), the specific nature of its involvement is unclear. This study measured levels of urine and plasma complement fragment Ba at multiple time points in a group of patients with AAV. Methods: The complement fragment Ba was measured by enzyme-linked immunosorbent assay in serial urine and plasma samples from 21 patients with AAV who developed a renal flare, 19 who developed a nonrenal flare, and 20 in long-term remission. Urine Ba levels were corrected for urine creatinine concentration. Changes in Ba levels were modeled using mixed linear-effect models. A logistic regression model was fit to predict a renal flare using Ba levels at the time of flare versus the nonrenal flare and long-term remission groups. Results: Data from 60 patients with AAV were used for this analysis; 53% were male, 93% were White, and 74% had antiproteinase3-ANCA. Urine Ba levels increased at renal flare (P < 0.001) but remained stable during a nonrenal flare or long-term remission. Plasma Ba levels were stable over time in all groups. Urine Ba levels predicted a renal flare with an area under the curve of 0.76 (P < 0.001), with a cutoff of 12.53 ng/mg urine creatinine yielding a sensitivity of 76.2% and a specificity of 68.4%. Conclusion: Urine Ba levels, but not plasma Ba levels, are increased at the time of a renal flare in AAV, suggesting intrarenal complement activation and highlighting the potential use of this biomarker for surveillance of active renal vasculitis.
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Markers of extracellular mitochondria are present in giant cell arteritis (GCA) patients. However, their role in promoting inflammation and platelet activation is no known. To investigate this, isolated mitochondria were opsonized with plasma from GCA patients or healthy individuals and incubated with peripheral blood mononuclear cells (PBMCs) or platelets and assessed for inflammatory cytokine production and platelet activation. Plasma from GCA patients promoted increased mitochondrial-mediated cytokine production by PBMCs as compared to healthy controls (p < 0.05). Mitochondria opsonized with plasma factors from patients with GCA induced higher platelet activation as compared to mitochondria opsonized with plasma factors from healthy individuals (p = 0.0015). Platelet levels of P-selectin were associated with disease activity in GCA (r = 0.34, p = 0.01). GCA patients have impaired ability to regulate the clearance of extracellular mitochondria, possibly contributing to excessive inflammation and platelet activation. Targeting key drivers of mitochondrial extrusion and/or their clearance could lead to new therapeutic interventions in GCA.
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Arterite de Células Gigantes , Humanos , Leucócitos Mononucleares , Inflamação , Ativação Plaquetária , CitocinasAssuntos
COVID-19 , Humanos , SARS-CoV-2 , Infecções Irruptivas , Plasmócitos , Vacinas contra COVID-19RESUMO
OBJECTIVE: This study examined the relationship between age at diagnosis and disease characteristics and damage in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: Analysis of a prospective longitudinal cohort of patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic GPA (EGPA) in the Vasculitis Clinical Research Consortium (2013-2021). Disease cohorts were divided by age at diagnosis (years): children (<18), young adults (18-40), middle-aged adults (41-65), and older adults (>65). Data included demographics, ANCA type, clinical characteristics, Vasculitis Damage Index (VDI) scores, ANCA Vasculitis Index of Damage (AVID) scores, and novel disease-specific and non-disease-specific damage scores built from VDI and AVID items. RESULTS: Analysis included data from 1020 patients with GPA/MPA and 357 with EGPA. Female predominance in GPA/MPA decreased with age at diagnosis. AAV in childhood was more often GPA and proteinase 3-ANCA positive. Children with GPA/MPA experienced more subglottic stenosis and alveolar hemorrhage; children and young adults with EGPA experienced more alveolar hemorrhage, need for intubation, and gastrointestinal involvement. Older adults (GPA/MPA) had more neurologic manifestations. After adjusting for disease duration, medications, tobacco, and ANCA, all damage scores increased with age at diagnosis for GPA/MPA (P < 0.001) except the disease-specific damage score, which did not differ (P = 0.44). For EGPA, VDI scores increased with age at diagnosis (P < 0.009), whereas all other scores were not significantly different. CONCLUSION: Age at diagnosis is associated with clinical characteristics in AAV. Although VDI and AVID scores increase with age at diagnosis, this is driven by non-disease-specific damage items.
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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Síndrome de Churg-Strauss , Granulomatose com Poliangiite , Poliangiite Microscópica , Criança , Pessoa de Meia-Idade , Adulto Jovem , Humanos , Feminino , Idoso , Masculino , Anticorpos Anticitoplasma de Neutrófilos , Estudos Prospectivos , Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/epidemiologia , Granulomatose com Poliangiite/tratamento farmacológico , Poliangiite Microscópica/complicações , Poliangiite Microscópica/epidemiologia , HemorragiaRESUMO
Predictions for a general path forward in vasculitis care and research are provided based on advances made in the past 20 years. Prospects for advances in translational research with potential to improve care are highlighted, including identification of hemato-inflammatory diseases, autoantigens, disease mechanisms in animal models, and biomarkers. A list of active randomized trials is provided, and areas of potential paradigm shifts in care are highlighted. The importance of patient involvement and international collaboration is noted, and a plea is made for innovative trial designs that would improve access of patients to trials and to clinical experts at referral centers.
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Arterite de Células Gigantes , Arterite de Takayasu , Animais , Humanos , Biomarcadores , PrevisõesRESUMO
BACKGROUND: Death within a specified time window following a positive SARS-CoV-2 test is used by some agencies for attributing death to COVID-19. With Omicron variants, widespread immunity, and asymptomatic screening, there is cause to re-evaluate COVID-19 death attribution methods and develop tools to improve case ascertainment. METHODS: All patients who died following microbiologically confirmed SARS-CoV-2 in the Veterans Health Administration (VA) and at Tufts Medical Center (TMC) were identified. Records of selected vaccinated VA patients with positive tests in 2022, and of all TMC patients with positive tests in 2021-2022, were manually reviewed to classify deaths as COVID-19-related (either directly caused by or contributed to), focused on deaths within 30 days. Logistic regression was used to develop and validate a surveillance model for identifying deaths in which COVID-19 was causal or contributory. RESULTS: Among vaccinated VA patients who died ≤30 days after a positive test in January-February 2022, death was COVID-19-related in 103/150 cases (69%) (55% causal, 14% contributory). In June-August 2022, death was COVID-19-related in 70/150 cases (47%) (22% causal, 25% contributory). Similar results were seen among the 71 patients who died at TMC. A model including hypoxemia, remdesivir, and anti-inflammatory drugs had positive and negative predictive values of 0.82-0.95 and 0.64-0.83, respectively. CONCLUSIONS: By mid-2022, "death within 30 days" did not provide an accurate estimate of COVID-19-related death in 2 US healthcare systems with routine admission screening. Hypoxemia and use of antiviral and anti-inflammatory drugs-variables feasible for reporting to public health agencies-would improve classification of death as COVID-19-related.
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COVID-19 , Humanos , SARS-CoV-2 , Pandemias , Anti-Inflamatórios , HipóxiaRESUMO
Measurement of the burden of COVID-19 on U.S. hospitals has been an important element of the public health response to the pandemic. However, because of variation in testing density and policies, the metric is not standardized across facilities. Two types of burdens exist, one related to the infection control measures that patients who test positive for SARS-CoV-2 require and one from the care of severely ill patients receiving treatment of COVID-19. With rising population immunity from vaccination and infection, as well as the availability of therapeutics, severity of illness has declined. Prior research showed that dexamethasone administration was highly correlated with other disease severity metrics and sensitive to the changing epidemiology associated with the emergence of immune-evasive variants.On 10 January 2022, the Massachusetts Department of Public Health began requiring hospitals to expand surveillance to include reports of both the total number of "COVID-19 hospitalizations" daily and the number of inpatients who received dexamethasone at any point during their hospital stay. All 68 acute care hospitals in Massachusetts submitted COVID-19 hospitalization and dexamethasone data daily to the Massachusetts Department of Public Health over a 1-year period. A total of 44 196 COVID-19 hospitalizations were recorded during 10 January 2022 to 9 January 2023, of which 34% were associated with dexamethasone administration. The proportion of patients hospitalized with COVID-19 who had received dexamethasone was 49.6% during the first month of surveillance and decreased to a monthly average of approximately 33% by April 2022, where it has remained since (range, 28.7% to 33%).Adding a single data element to mandated reporting to estimate the frequency of severe COVID-19 in hospitalized patients was feasible and provided actionable information for health authorities and policy makers. Updates to surveillance methods are necessary to match data collection with public health response needs.
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COVID-19 , Humanos , COVID-19/epidemiologia , SARS-CoV-2 , Gravidade do Paciente , Hospitais , Dexametasona/uso terapêuticoRESUMO
BACKGROUND: Rheumatoid arthritis (RA) shares genetic variants with other autoimmune conditions, but existing studies test the association between RA variants with a pre-defined set of phenotypes. The objective of this study was to perform a large-scale, systemic screen to determine phenotypes that share genetic architecture with RA to inform our understanding of shared pathways. METHODS: In the UK Biobank (UKB), we constructed RA genetic risk scores (GRS) incorporating human leukocyte antigen (HLA) and non-HLA risk alleles. Phenotypes were defined using groupings of International Classification of Diseases (ICD) codes. Patients with an RA code were excluded to mitigate the possibility of associations being driven by the diagnosis or management of RA. We performed a phenome-wide association study, testing the association between the RA GRS with phenotypes using multivariate generalized estimating equations that adjusted for age, sex, and first five principal components. Statistical significance was defined using Bonferroni correction. Results were replicated in an independent cohort and replicated phenotypes were validated using medical record review of patients. FINDINGS: We studied n = 316,166 subjects from UKB without evidence of RA and screened for association between the RA GRS and n = 1317 phenotypes. In the UKB, 20 phenotypes were significantly associated with the RA GRS, of which 13 (65%) were immune mediated conditions including polymyalgia rheumatica, granulomatosis with polyangiitis (GPA), type 1 diabetes, and multiple sclerosis. We further identified a novel association in Celiac disease where the HLA and non-HLA alleles had strong associations in opposite directions. Strikingly, we observed that the non-HLA GRS was exclusively associated with greater risk of the validated conditions, suggesting shared underlying pathways outside the HLA region. INTERPRETATION: This study replicated and identified novel autoimmune phenotypes verified by medical record review that share immune pathways with RA and may inform opportunities for shared treatment targets, as well as risk assessment for conditions with a paucity of genomic data, such as GPA. FUNDING: This research was funded by the US National Institutes of Health (P30AR072577, R21AR078339, R35GM142879, T32AR007530) and the Harold and DuVal Bowen Fund.