Showing papers by "Rosalind Ramsey-Goldman published in 2018"
Maastricht University1, King's College London2, Ghent University3, University of Colorado Denver4, National Institutes of Health5, Leiden University Medical Center6, University of Utah7, University of Texas Health Science Center at Houston8, Medical University of South Carolina9, San Francisco General Hospital10, Albert Einstein College of Medicine11, University of Edinburgh12, Northwestern University13, Indiana University14, University of Helsinki15, Hebrew University of Jerusalem16, Triemli Hospital17, University of New South Wales18, University of Cambridge19, Georgetown University Medical Center20, University of Padua21, University of Minnesota22, Copenhagen University Hospital23, University of Chile24, University College London25, Mayo Clinic26, University of Navarra27, Carlos III Health Institute28, University of Michigan29, Vanderbilt University Medical Center30, Seconda Università degli Studi di Napoli31, University of Southern Denmark32, University of California, Los Angeles33, Stanford University34, University Medical Center Groningen35, Erasmus University Rotterdam36, Innsbruck Medical University37, Helsinki University Central Hospital38, University of Washington39, Fred Hutchinson Cancer Research Center40, VU University Medical Center41, University of Siena42, University of São Paulo43, Federation University Australia44, Manchester Academic Health Science Centre45, University of Manchester46, German Cancer Research Center47, Humboldt University of Berlin48, University of Buenos Aires49, Sichuan University50, Montreal Heart Institute51, Medical University of Łódź52, Cardiff Metropolitan University53, National University of Singapore54, Lund University55, Population Health Research Institute56
TL;DR: In this paper, a collaborative cross-sectional meta-analysis of observational studies was conducted to investigate the associations between BMI and leukocyte telomere length across the life span.
107 citations
Brigham and Women's Hospital1, Toronto Western Hospital2, University of Crete3, University of California, San Francisco4, Charité5, University of Cambridge6, Medical University of South Carolina7, University of Pisa8, Northwestern University9, Medical University of Vienna10, McMaster University11, Dresden University of Technology12
TL;DR: To define candidate criteria within multiphase development of systemic lupus erythematosus (SLE) classification criteria, and to develop hierarchical organization of criteria within domains.
Abstract: Objectives. We aimed to define candidate criteria within multi-phase development of SLE classification criteria, jointly supported by EULAR and ACR. Prior steps included item generation and reduction by Delphi exercise, further narrowed to 21 items in a Nominal Group Technique exercise. Our objectives were to apply an evidence-based approach to the 21 candidate criteria, and to develop hierarchical organization of criteria within domains.
Methods. A literature review identified the sensitivity and specificity of the 21 candidate criteria. Data on the performance of ANA as an entry criteria and operating characteristics of the candidate criteria in early SLE patients were evaluated. Candidate criteria were hierarchically organized into clinical and immunologic domains, and definitions were refined in an iterative process.
Results. Based on the data, consensus was reached to use a positive ANA of ≥1:80 titer (HEp2 cells immunofluorescence) as an entry criterion and to have seven clinical and three immunologic domains, with hierarchical organization of criteria within domains. Definitions of the candidate criteria were specified.
Conclusion. Using a data-driven process, consensus was reached on new, refined criteria definitions and organization based on operating characteristics. This work will be followed by a multicriteria decision analysis exercise to weight criteria and to identify a threshold score for classification on a continuous probability scale. This article is protected by copyright. All rights reserved.
93 citations
01 Jan 2018
TL;DR: A higher BMI is associated with shorter telomeres, especially in younger individuals, and meta-analyses of longitudinal studies evaluating change in body weight alongside change in TL are warranted.
80 citations
Queen Elizabeth II Health Sciences Centre1, University of Cambridge2, University of Toronto3, University of Birmingham4, Hanyang University5, Toronto Western Hospital6, McGill University7, University of Calgary8, University of California, Los Angeles9, University College London10, Oklahoma Medical Research Foundation11, Laval University12, Central Manchester University Hospitals NHS Foundation Trust13, Johns Hopkins University School of Medicine14, SUNY Downstate Medical Center15, University of North Carolina at Chapel Hill16, Northwestern University17, Hairmyres Hospital18, Allegheny Health Network19, Lund University20, King's College London21, University of Alabama at Birmingham22, Karolinska Institutet23, The Feinstein Institute for Medical Research24, University of the Basque Country25, Emory University26, Istanbul University27, University of California, San Diego28, Copenhagen University Hospital29, University of Manitoba30, Medical University of South Carolina31, New York University32
TL;DR: To determine the frequency, characteristics, and outcomes of cerebrovascular events (CerVEs), as well as clinical and autoantibody associations in a multiethnic/racial inception cohort of patients with systemic lupus erythematosus (SLE).
Abstract: OBJECTIVE: To determine the frequency, associations and outcomes of cerebrovascular events (CerVEs) in a multi-ethnic/racial, prospective, SLE disease inception cohort. METHODS: Patients were assessed annually for 19 neuropsychiatric (NP) events including 5 types of CerVEs: (i) Stroke; (ii) Transient ischemia; (iii) Chronic multifocal ischemia; (iv) Subarachnoid/intracranial hemorrhage; (v) Sinus thrombosis. Global disease activity (SLEDAI-2K), SLICC/ACR damage index (SDI) and SF-36 scores were collected. Time to event, linear and logistic regressions and multi-state models were used as appropriate. RESULTS: Of 1,826 SLE patients, 88.8% were female, 48.8% Caucasian, mean±SD age 35.1±13.3 years, disease duration 5.6±4.2 months and follow-up 6.6±4.1 years. CerVEs were the fourth most frequent NP event: 82/1,826 (4.5%) patients had 109 events, 103/109 (94.5%) were attributed to SLE and 44/109 (40.4%) were identified at enrollment. The predominant events were stroke [60/109 (55.0%)] and transient ischemia [28/109 (25.7%)]. CerVEs were associated with other NP events attributed to SLE (HR (95% CI): (3.16; 1.73-5.75) (p<0.001), non-SLE NP (2.60; 1.49-4.51) (p<0.001), African ancestry at US SLICC sites (2.04; 1.01-4.13) (p=0.047) and organ damage (p=0.041). Lupus anticoagulant increased the risk of first stroke and sinus thrombosis [2.23 (1.11, 4.45) p=.024] and TIA [3.01 (1.15, 7.90) p=0.025]. Physician assessment indicated resolution or improvement in the majority but patients reported sustained reduction in SF-36 summary and subscale scores following CerVEs (P<0.0001). CONCLUSION: CerVEs, the fourth most frequent NP event in SLE, are usually attributable to lupus. In contrast to good physician reported outcomes, patients report a sustained reduction in health-related quality of life following CerVEs. This article is protected by copyright. All rights reserved.
48 citations
King's College London1, Children's Hospital Oakland Research Institute2, Wellcome Trust Centre for Human Genetics3, Cincinnati Children's Hospital Medical Center4, Wake Forest University5, University of Granada6, Karolinska Institutet7, Oklahoma Medical Research Foundation8, University of Southern California9, Medical University of South Carolina10, University of Alabama at Birmingham11, Cedars-Sinai Medical Center12, Johns Hopkins University School of Medicine13, Northwestern University14, University of Texas at Austin15, Hospital for Special Surgery16, University of Oklahoma Health Sciences Center17, University of Chicago18, University of California, San Francisco19
TL;DR: Despite some differences in underlying HLA allele risk models in EUR and AA, SNP signals across the extended MHC showed remarkable similarity and significant concordance in direction of effect for risk‐associated variants.
Abstract: Genetic variation within the major histocompatibility complex (MHC) contributes substantial risk for systemic lupus erythematosus, but high gene density, extreme polymorphism and extensive linkage disequilibrium (LD) have made fine mapping challenging. To address the problem, we compared two association techniques in two ancestrally diverse populations, African Americans (AAs) and Europeans (EURs). We observed a greater number of Human Leucocyte Antigen (HLA) alleles in AA consistent with the elevated level of recombination in this population. In EUR we observed 50 different A-C-B-DRB1-DQA-DQB multilocus haplotype sequences per hundred individuals; in the AA sample, these multilocus haplotypes were twice as common compared to Europeans. We also observed a strong narrow class II signal in AA as opposed to the long-range LD observed in EUR that includes class I alleles. We performed a Bayesian model choice of the classical HLA alleles and a frequentist analysis that combined both single nucleotide polymorphisms (SNPs) and classical HLA alleles. Both analyses converged on a similar subset of risk HLA alleles: in EUR HLA- B*08:01 + B*18:01 + (DRB1*15:01 frequentist only) + DQA*01:02 + DQB*02:01 + DRB3*02 and in AA HLA-C*17:01 + B*08:01 + DRB1*15:03 + (DQA*01:02 frequentist only) + DQA*02:01 + DQA*05:01+ DQA*05:05 + DQB*03:19 + DQB*02:02. We observed two additional independent SNP associations in both populations: EUR rs146903072 and rs501480; AA rs389883 and rs114118665. The DR2 serotype was best explained by DRB1*15:03 + DQA*01:02 in AA and by DRB1*15:01 + DQA*01:02 in EUR. The DR3 serotype was best explained by DQA*05:01 in AA and by DQB*02:01 in EUR. Despite some differences in underlying HLA allele risk models in EUR and AA, SNP signals across the extended MHC showed remarkable similarity and significant concordance in direction of effect for risk-associated variants.
36 citations
University of Cincinnati1, Cincinnati Children's Hospital Medical Center2, Wake Forest University3, Oklahoma Medical Research Foundation4, Shanghai Jiao Tong University5, University of Washington6, Boston Children's Hospital7, Medical University of South Carolina8, University of Southern California9, University of Alabama at Birmingham10, Spanish National Research Council11, University of Texas Health Science Center at Houston12, Del Rosario University13, University of Oklahoma14, University of California, San Francisco15, University of Puerto Rico, Medical Sciences Campus16, Johns Hopkins University School of Medicine17, Veterans Health Administration18, Northwestern University19, Hanyang University20, University of Colorado Denver21, King's College London22, New York University23, University of Toronto24, Cedars-Sinai Medical Center25, University of Texas Southwestern Medical Center26, University of Granada27, Karolinska Institutet28
TL;DR: A plausible molecular mechanism for increased lupus risk at the STAT1-STAT4 locus is presented in which the risk allele of rs11889341, the most probable causal variant, leads to elevated STAT1 expression in B cells due to decreased repressor activity mediated by increased binding of HMGA1.
Abstract: Systemic lupus erythematosus (SLE or lupus) (OMIM: 152700) is a chronic autoimmune disease with debilitating inflammation that affects multiple organ systems. The STAT1-STAT4 locus is one of the first and most highly replicated genetic loci associated with lupus risk. We performed a fine-mapping study to identify plausible causal variants within the STAT1-STAT4 locus associated with increased lupus disease risk. Using complementary frequentist and Bayesian approaches in trans-ancestral Discovery and Replication cohorts, we found one variant whose association with lupus risk is supported across ancestries in both the Discovery and Replication cohorts: rs11889341. In B cell lines from patients with lupus and healthy controls, the lupus risk allele of rs11889341 was associated with increased STAT1 expression. We demonstrated that the transcription factor HMGA1, a member of the HMG transcription factor family with an AT-hook DNA-binding domain, has enriched binding to the risk allele compared with the non-risk allele of rs11889341. We identified a genotype-dependent repressive element in the DNA within the intron of STAT4 surrounding rs11889341. Consistent with expression quantitative trait locus (eQTL) analysis, the lupus risk allele of rs11889341 decreased the activity of this putative repressor. Altogether, we present a plausible molecular mechanism for increased lupus risk at the STAT1-STAT4 locus in which the risk allele of rs11889341, the most probable causal variant, leads to elevated STAT1 expression in B cells due to decreased repressor activity mediated by increased binding of HMGA1.
35 citations
Harvard University1, Kaiser Permanente2, Massachusetts Eye and Ear Infirmary3, Brigham and Women's Hospital4, Northwestern University5, Emory University6, University of Calgary7, Toronto Western Hospital8, Columbia University9, The Feinstein Institute for Medical Research10, Johns Hopkins University School of Medicine11
TL;DR: A substantial proportion of HCQ users in the UK, particularly women, may have excess HCQ dosing per the previous or recent weight-based guidelines despite a modest decline in recent years, suggesting the potential need to reduce dosing for many patients.
Abstract: Hydroxychloroquine (HCQ) retinopathy may be more common than previously recognized; recent ophthalmology guidelines have revised recommendations from ideal body weight (IBW)-based dosing to actual body weight (ABW)-based dosing However, contemporary HCQ prescribing trends in the UK remain unknown We examined a UK general population database to investigate HCQ dosing between 2007 and 2016 We studied trends of excess HCQ dosing per ophthalmology guidelines (defined by exceeding 65 mg/kg of IBW and 50 mg/kg of ABW) and determined their independent predictors using multivariable logistic regression analyses Among 20,933 new HCQ users (78% female), the proportions of initial HCQ excess dosing declined from 40% to 36% using IBW and 38% to 30% using ABW, between 2007 and 2016 Among these, 47% of women were excess-dosed (multivariable OR 1252; 95% CI 1099–1426) using IBW and 38% (multivariable OR 198; 95% CI,181–215) using ABW Applying IBW, 37% of normal and 44% of obese patients were excess-dosed; however, applying ABW, 53% of normal and 10% of obese patients were excess-dosed (multivariable ORs = 161 and 01 (reference = normal); both p < 001) Long-term HCQ users showed similar excess dosing A substantial proportion of HCQ users in the UK, particularly women, may have excess HCQ dosing per the previous or recent weight-based guidelines despite a modest decline in recent years Over half of normal-BMI individuals were excess-dosed per the latest guidelines This implies the potential need to reduce dosing for many patients but also calls for further research to establish unifying evidence-based safe and effective dosing strategies
33 citations
University of Manchester1, Central Manchester University Hospitals NHS Foundation Trust2, Queen Elizabeth II Health Sciences Centre3, University of Toronto4, University of Calgary5, University of Birmingham6, Hanyang University7, McGill University Health Centre8, University of California, Los Angeles9, Oklahoma Medical Research Foundation10, New York University11, University College London12, SUNY Downstate Medical Center13, Johns Hopkins University School of Medicine14, University of North Carolina at Chapel Hill15, Laval University16, Northwestern University17, King's College London18, The Feinstein Institute for Medical Research19, University of Alabama at Birmingham20, Allegheny Health Network21, Lund University22, Hairmyres Hospital23, Karolinska Institutet24, University of the Basque Country25, Emory University26, University of California, San Diego27, Istanbul University28, Medical University of South Carolina29, University of Manitoba30, Copenhagen University Hospital31, University Health Network32
TL;DR: While patient and disease factors contribute to the variation in GC use, between-centre differences suggest that physician-related factors also contribute, evidence-based treatment algorithms are needed to inform a more standardized approach to GC use in SLE.
Abstract: Objectives. To describe glucocorticoid (GC) use in the SLICC inception cohort and to explore factors associated with GC use. In particular we aimed to assess temporal trends in GC use and to what extent physician-related factors may influence use. Methods. Patients were recruited within 15 months of diagnosis of SLE from 33 centres between 1999 and 2011 and continue to be reviewed annually. Descriptive statistics were used to detail oral and parenteral GC use. Cross sectional and longitudinal analyses were performed to explore factors associated with GC use at enrolment and over time. Results. We studied 1700 patients with a mean (S.D.) follow-up duration of 7.26 (3.82) years. Over the entire study period, 1365 (81.3%) patients received oral GCs and 447 (26.3%) received parenteral GCs at some point. GC use was strongly associated with treatment centre, age, race/ethnicity, sex, disease duration and disease activity. There was no change in the proportion of patients on GCs or the average doses of GC used over time according to year of diagnosis. Conclusion. GCs remain a cornerstone in SLE management and there have been no significant changes in their use over the past 10-15 years. While patient and disease factors contribute to the variation in GC use, between-centre differences suggest that physician-related factors also contribute. Evidence-based treatment algorithms are needed to inform a more standardized approach to GC use in SLE.
32 citations
University of Calgary1, Queen Elizabeth II Health Sciences Centre2, University of Cambridge3, Toronto Western Hospital4, McGill University5, University of Birmingham6, Hanyang University7, McGill University Health Centre8, University of California, Los Angeles9, University College London10, SUNY Downstate Medical Center11, Johns Hopkins University School of Medicine12, Manchester Academic Health Science Centre13, Laval University14, Northwestern University15, King's College London16, The Feinstein Institute for Medical Research17, University of Alabama at Birmingham18, University of Pittsburgh19, Lund University20, Hairmyres Hospital21, Karolinska Institutet22, University of the Basque Country23, Emory University24, Istanbul University25, Medical University of South Carolina26, University of Manitoba27, Copenhagen University Hospital28, New York University29
TL;DR: The costs were compared between patients with and without LN using multistate modeling and it was found that patients with LN are more likely to have poorer quality of life and suffer from higher costs of care.
Abstract: OBJECTIVE Little is known about the long-term costs of lupus nephritis (LN). The costs were compared between patients with and without LN using multistate modeling. METHODS Patients from 32 centers in 11 countries were enrolled in the Systemic Lupus International Collaborating Clinics inception cohort within 15 months of diagnosis and provided annual data on renal function, hospitalizations, medications, dialysis, and selected procedures. LN was diagnosed by renal biopsy or the American College of Rheumatology classification criteria. Renal function was assessed annually using the estimated glomerular filtration rate (GFR) or estimated proteinuria. A multistate model was used to predict 10-year cumulative costs by multiplying annual costs associated with each renal state by the expected state duration. RESULTS A total of 1,545 patients participated; 89.3% were women, the mean ± age at diagnosis was 35.2 ± 13.4 years, 49% were white, and the mean followup duration was 6.3 ± 3.3 years. LN developed in 39.4% of these patients by the end of followup. Ten-year cumulative costs were greater in those with LN and an estimated glomerular filtration rate (GFR) 60 ml/minute) or with LN and estimated proteinuria >3 gm/day ($84,040 versus $20,499 if no LN and estimated proteinuria <0.25 gm/day). CONCLUSION Patients with estimated GFR <30 ml/minute incurred 10-year costs 15-fold higher than those with normal estimated GFR. By estimating the expected duration in each renal state and incorporating associated annual costs, disease severity at presentation can be used to anticipate future health care costs. This is critical knowledge for cost-effectiveness evaluations of novel therapies.
24 citations
University College London1, The Feinstein Institute for Medical Research2, Columbia University3, Hanyang University4, McGill University5, University of Manchester6, University of Barcelona7, University of Calgary8, University of North Carolina at Chapel Hill9, Laval University10, SUNY Downstate Medical Center11, University of Toronto12, Halifax13, Istanbul University14, Medical University of South Carolina15, King's College London16, Emory University17, Allegheny Health Network18, Lund University19, University of Manitoba20, Johns Hopkins University21, University of California, San Diego22, Northwestern University23, University of the Basque Country24, Karolinska University Hospital25, University of California, Los Angeles26, Hairmyres Hospital27, Oklahoma Medical Research Foundation28, University of Birmingham29
TL;DR: To determine the level of agreement of disease flare severity (distinguishing severe, moderate, and mild flare and persistent disease activity) in a large paper‐patient exercise involving 988 individual cases of systemic lupus erythematosus, a large study of large numbers of patients is conducted.
Abstract: Objective: To determine the level of agreement of disease flare severity (distinguishing severe, moderate, and mild flare and persistent disease activity) in a large paper-patient exercise involving 988 individual cases of systemic lupus erythematosus. Methods: A total of 988 individual lupus case histories were assessed by 3 individual physicians. Complete agreement about the degree of flare (or persistent disease activity) was obtained in 451 cases (46%), and these provided the reference standard for the second part of the study. This component used 3 flare activity instruments (the British Isles Lupus Assessment Group [BILAG] 2004, Safety of Estrogens in Lupus Erythematosus National Assessment [SELENA] flare index [SFI] and the revised SELENA flare index [rSFI]). The 451 patient case histories were distributed to 18 pairs of physicians, carefully randomized in a manner designed to ensure a fair case mix and equal distribution of flare according to severity. Results: The 3-physician assessment of flare matched the level of flare using the 3 indices, with 67% for BILAG 2004, 72% for SFI, and 70% for rSFI. The corresponding weighted kappa coefficients for each instrument were 0.82, 0.59, and 0.74, respectively. We undertook a detailed analysis of the discrepant cases and several factors emerged, including a tendency to score moderate flares as severe and persistent activity as flare, especially when the SFI and rSFI instruments were used. Overscoring was also driven by scoring treatment change as flare, even if there were no new or worsening clinical features. Conclusion: Given the complexity of assessing lupus flare, we were encouraged by the overall results reported. However, the problem of capturing lupus flare accurately is not completely solved.
23 citations
McGill University Health Centre1, Toronto Western Hospital2, Dalhousie University3, University of Manitoba4, University of Calgary5, Northwestern University6, Johns Hopkins University School of Medicine7, University of California, San Francisco8, SUNY Downstate Medical Center9, The Feinstein Institute for Medical Research10, Yale University11, University of Birmingham12, University College London13, Lund University14, Hanyang University15, McGill University16
TL;DR: No clear evidence for drugs as a trigger for lung cancer risk in SLE was seen, although drug risk estimates were relatively imprecise, and smoking may be the most significant modifiable lungcancer risk factor in Sle.
Abstract: Objective. To assess lung cancer risk in systemic lupus erythematosus (SLE), relative to demographics, drug exposures, smoking, and disease activity. Methods. We analyzed data from 14 SLE cohorts. We calculated adjusted HR estimates for lung cancer in SLE, relative to demographics, smoking, time-dependent medication exposures, and cumulative disease activity [mean adjusted SLE Disease Activity Index (SLEDAI) scores]. This project was approved by the ethics boards of all participating institutions, including the Institutional Review Board of the McGill University Health Centre. The ethics approval number for the Cancer Risk study is GEN-06-031. Results. Within these 14 SLE cohorts, 49 incident lung cancers occurred. Among lung cancer cases, 59.0% were in the highest SLEDAI quartile at baseline versus 40.8% of lung cancer–free SLE controls. The vast majority (84.2%) of SLE lung cancer cases were ever-smokers at baseline, versus 40.1% of those without lung cancer. In adjusted models, the principal factors associated with lung cancer were ever smoking (at cohort entry) and current age. Estimated adjusted effects of all drugs were relatively imprecise, but did not point toward any drug exposures as strong lung cancer risk factors. Conclusion. We saw no clear evidence for drugs as a trigger for lung cancer risk in SLE, although drug risk estimates were relatively imprecise. Smoking may be the most significant modifiable lung cancer risk factor in SLE.
TL;DR: A novel Lupus Multivariable Outcome Score (LuMOS) is developed and its performance is assessed using data from 2 randomized controlled trials of belimumab in patients with SLE.
Abstract: OBJECTIVE Trials of new systemic lupus erythematosus (SLE) treatments are hampered by the lack of effective outcome measures. To address this, we developed a novel Lupus Multivariable Outcome Score (LuMOS) and assessed its performance using data from 2 randomized controlled trials of belimumab in patients with SLE. METHODS The LuMOS formula was developed by analyzing raw data from 2 pivotal trials, the Study of Belimumab in Subjects with SLE 52-week (BLISS-52) and 76-week (BLISS-76) trials, which are the basis for approval of belimumab. Using the BLISS-76 trial data as the learning data set, we carried out multivariable logistic regression analyses to optimize discrimination of outcomes between patients treated with 10 mg/kg belimumab and patients receiving placebo over the first 52 weeks of follow-up. In addition, the performance of LuMOS was assessed using an independent validation data set from the BLISS-52 trial. RESULTS The LuMOS model incorporated the following response criteria: a ≥4-point reduction on the Safety of Estrogens in Lupus Erythematosus National Assessment version of the SLE Disease Activity Index, an increase in C4 levels, a decrease in anti-double-stranded DNA titers, and changes in the British Isles Lupus Assessment Group scores for organ system manifestations (no worsening in renal components, and improvements in mucocutaneous components). A decrease in the prednisone dose and increase in C3 levels had very minor impacts on the total LuMOS score. In all analyses of the BLISS-76 and BLISS-52 trial data sets, the mean LuMOS scores were significantly higher (P < 0.0001) in patients treated with 1 mg or 10 mg belimumab compared to placebo. In contrast to the performance of the SLE Responder Index 4 (SRI-4), the LuMOS revealed significant differences between the active treatment group (1 mg belimumab in the BLISS-76 cohort) and placebo group. The effect sizes were significantly much higher with the LuMOS than with the SRI-4. CONCLUSION The evidenced-based LuMOS outcome scoring system, developed with data from the BLISS-76 trial of belimumab in patients with SLE and validated with data from the BLISS-52 trial, exhibits a superior capacity to discriminate responders from nonresponders when compared to the SRI-4. Use of the LuMOS may improve the efficiency and power of analyses in future lupus trials.
TL;DR: The association of EC4d with disease activity regardless of complement C3/C4 status and its usefulness in monitoring SLE disease are supported.
Abstract: Background We examined the usefulness of erythrocyte-bound C4d (EC4d) to monitor disease activity in SLE. Methods Data and blood samples were collected from three different studies, each of which included longitudinal evaluations using the Physicians Global Assessment (PGA) of disease activity and the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) SLE Disease Activity Index (SLEDAI), which was assessed without anti-double-stranded DNA (dsDNA) and low complement C3/C4 (clinical SELENA-SLEDAI). EC4d levels were determined using flow cytometry; other laboratory measures included antibodies to dsDNA, C3 and C4 proteins. Relationships between clinical SELENA-SLEDAI, PGA and the laboratory measures were analysed using linear mixed effect models. Results The three studies combined enrolled 124 patients with SLE (mean age 42 years, 97% women, 31% Caucasians and 34% African-Americans) followed for an average of 5 consecutive visits (range 2–13 visits). EC4d levels and low C3/C4 status were significantly associated the clinical SELENA-SLEDAI or PGA in each of the three study groups (p Conclusion These data support the association of EC4d with disease activity regardless of complement C3/C4 status and its usefulness in monitoring SLE disease. Additional studies will be required to support these validation data.
McGill University1, University of Calgary2, Northwestern University3, BC Cancer Agency4, University of Toronto5, Johns Hopkins University School of Medicine6, SUNY Downstate Medical Center7, Laval University8, Hanyang University9, University of California, Los Angeles10, University of California, San Francisco11, McGill University Health Centre12
TL;DR: Breast cancer positivity for estrogen receptors (ER), progesterone receptors (PR), and/or Human Epidermal Growth Factor Receptor 2 (HER2) was similar to historical general population figures, with a trend toward a higher proportion of triple-negative breast cancers in SLE.
Abstract: Objective There is a decreased risk of breast cancer in systemic lupus erythematosus (SLE) versus the general population; little is known regarding the receptor status of breast cancers in SLE, or treatment. Methods Breast cancer cases occurring after SLE diagnosis were ascertained through linkage with tumor registries. We determined breast cancer positivity for estrogen receptors (ER), progesterone receptors (PR), and/or Human Epidermal Growth Factor Receptor 2 (HER2), as well as cancer treatment. Results We obtained information on ER, PR, and/or HER2 status for 63 SLE patients with breast cancer. Fifty-three had information on ER and/or PR status; 36 of these (69%) were ER positive. Thirty-six of the 63 had information on HER2 status; of these, 26 had complete information on all three receptors. Twenty-one of these 26 (81%) were HER2 negative; seven of 26(27%) were triple negative. All but one patient underwent surgery; 11.5% received both non-tamoxifen chemotherapy and radiotherapy, 16.4% radiotherapy without non-tamoxifen chemotherapy, and 14.7% received non-tamoxifen chemotherapy without radiotherapy. Conclusion ER positivity was similar to historical general population figures, with a trend toward a higher proportion of triple-negative breast cancers in SLE (possibly reflecting the relatively young age of our SLE patients).
TL;DR: Cross-sectional associations between adipokines and fatigue, physical activity, and SLE disease activity are described and adipokines were correlated with physical activity (leptin, adiponectin, L/A ratio), but most of these associations were explained by BMI.
Abstract: Physical activity ameliorates fatigue in systemic lupus erythematosus (SLE) patients by an unknown mechanism. Adipokines, which are influenced by adiposity and physical activity, may be associated with patient-reported fatigue. We describe cross-sectional associations between adipokines and fatigue, physical activity, and SLE disease activity. We measured adipokines, self-reported fatigue, and objective physical activity in 129 SLE patients. Fatigue was assessed with the Fatigue Severity Scale (FSS) and Patient Reported Outcomes Measurement Information System® (PROMIS®) Fatigue score. Disease activity was measured with the Safety of Estrogens in Systemic Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI). Participants wore an accelerometer for 7 days to measure physical activity. Leptin, adiponectin, and resistin were measured in stored serum with a Luminex bead-based assay. Multivariable regression models assessed relationships between fatigue and adipokines, and Spearman correlation coefficients summarized associations between adipokines, physical activity, and SELENA-SLEDAI. Median adipokine levels were: leptin 30.5 ng/ml (Interquartile Range 14.0, 56.6), adiponectin 11.6 μg/ml (7.2, 16.8) and resistin 1.4 ng/ml (1.0, 2.2). Associations between adipokines and FSS or PROMIS fatigue were not significant. Body mass index (BMI) ≥ 30 kg/m2 was associated with FSS and PROMIS fatigue in regression analyses (p < 0.05). Weak correlations between leptin, adiponectin, leptin/adiponectin (L/A) ratio, and physical activity and between adiponectin and SELENA-SLEDAI score were not significant after adjusting for BMI. Adipokines were not associated with fatigue in SLE. Adipokines were correlated with physical activity (leptin, adiponectin, L/A ratio) and SLE disease activity (adiponectin), but most of these associations were explained by BMI.
TL;DR: A better understanding of the elements that drive malignancy risk in systemic autoimmune rheumatic diseases may permit the further development of guidelines (regarding cancer screening) for SLE patients.
Abstract: Introduction: Numerous studies have clearly demonstrated that there is an altered cancer risk profile in patients with systemic lupus erythematous (SLE) versus the general population. This includes...
TL;DR: The cross-sectional results suggest that higher OPG levels are related to higher CAC levels among women with SLE vs. healthy controls.
Abstract: ObjectiveWe tested the hypothesis that higher circulating levels of osteoprotegerin (OPG) are related to higher levels of coronary artery calcification (CAC) among women with systemic lupus erythem...
TL;DR: In this review, three organ systems that are often affected in SLE, but have the potential to present as medical emergencies are explored; these are the kidney, the central nervous system, and the hematologic system.
Abstract: Introduction: Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder with systemic manifestations and multiorgan involvement. Although primarily diagnosed, and managed in the outpatien...