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author:("lived, O")
1.  Breast Cancer in Systemic Lupus Erythematosus 
Oncology  2013;85(2):117-121.
Objective
Evidence points to a decreased breast cancer risk in systemic lupus erythematosus (SLE). We analyzed data from a large multisite SLE cohort, linked to cancer registries.
Methods
Information on age, SLE duration, cancer date, and histology was available. We analyzed information on histological type and performed multivariate logistic regression analyses of histological types according to age, SLE duration, and calendar year.
Results
We studied 180 breast cancers in the SLE cohort. Of the 155 cases with histology information, 11 were referred to simply as ‘carcinoma not otherwise specified’. In the remaining 144 breast cancers, the most common histological type was ductal carcinoma (n = 95; 66%) followed by lobular adenocarcinoma (n = 11; 8%), 15 cancers were of mixed histology, and the remaining ones were special types. In our regression analyses, the independent risk factors for lobular versus ductal carcinoma was age [odds ratio (OR) 1.07, 95% confidence interval (CI) 1.01–1.14] and for the ‘special’ subtypes it was age (OR 1.06, 95% CI 1.01–1.10) and SLE duration (OR 1.05, 95% CI 1.00–1.11).
Conclusions
Generally, up to 80% of breast cancers are ductal carcinomas. Though our results are not definitive, in the breast cancers that occur in SLE, there may be a slight decrease in the ductal histological type. In our analyses, age and SLE duration were independent predictors of histological status.
doi:10.1159/000353138
PMCID: PMC3934367  PMID: 23887245
Breast cancer; Systemic lupus erythematosus; Histopathology; Epidemiology
2.  SF-36 summary and subscale scores are reliable outcomes of neuropsychiatric events in systemic lupus erythematosus 
Annals of the rheumatic diseases  2011;70(6):961-967.
Objective
To examine change in health-related quality of life (HRQoL) in association with clinical outcomes of neuropsychiatric (NP) events in SLE.
Methods
An international study evaluated newly diagnosed SLE patients for NP events attributed to SLE and non-SLE causes. Outcome of events was determined by physician-completed 7-point scale and compared to patient-completed SF-36 questionnaires. Statistical analysis used linear mixed-effects regression models with patient specific random effects.
Results
274 patients (92% female; 68% Caucasian), from a cohort of 1400, had ≥ 1 NP event where the interval between assessments was 12.3 ± 2 months. The overall difference in change between visits in mental component summary (MCS) scores of the SF-36 was significant (p<0.0001) following adjustments for gender, ethnicity, center and previous score. A consistent improvement in NP status (N=295) was associated with an increase in the mean(SD) adjusted MCS score of 3.66(0.89) in SF-36 scores. Between paired visits where NP status consistently deteriorated (N=30), the adjusted MCS score decreased by 4.00(1.96). For the physical component summary (PCS) scores the corresponding changes were +1.73(0.71) and −0.62(1.58) (p<0.05) respectively. Changes in SF-36 subscales were in the same direction (p<0.05; with the exception of role physical). Sensitivity analyses confirmed these findings. Adjustment for age, education, medications, SLE disease activity, organ damage, disease duration, attribution and characteristics of NP events did not substantially alter the results.
Conclusion
Changes in SF-36 summary and subscale scores, in particular those related to mental health, are strongly associated with the clinical outcome of NP events in SLE patients.
doi:10.1136/ard.2010.138792
PMCID: PMC3795436  PMID: 21342917
Systemic lupus erythematosus; Neuropsychiatric; Inception cohort; Health related quality of life; SF-36
6.  Atherosclerotic Vascular Events in a Multinational Inception Cohort of Systemic Lupus Erythematosus (SLE) 
Arthritis care & research  2010;62(6):881-887.
Objective
To describe vascular events during an 8 year follow-up in a multicentre SLE inception cohort and their attribution to atherosclerosis.
Methods
Clinical data including co-morbidities are recorded yearly. Vascular events are recorded and attributed to atherosclerosis or not. All events met standard clinical criteria. Factors associated with atherosclerotic vascular events were analysed using descriptive statistics, t-tests and χ2. Stepwise multivariate logistic regression was used to assess the association of factors with vascular events attributed to atherosclerosis.
Results
Since 2000, 1249 patients have been entered into the cohort. There have been 97 vascular events in 72 patients. These include: myocardial infarction (13), angina (15), congestive heart failure (24), peripheral vascular disease (8), transient ischemic attack (13), stroke (23), pacemaker insertion (1). Fifty of the events were attributed to active lupus, 31events in 22 patients were attributed to atherosclerosis, and 16 to other causes. Time from diagnosis to first atherosclerotic event was 2.0 ± 1.5 years. Compared to patients followed for 2 years without atherosclerosis events (615), at enrolment patients with AVE were more frequently Caucasian, male, older at diagnosis of SLE, obese, smokers, hypertensive and had a family history of coronary artery disease. On multivariate analysis only male gender and older age at diagnosis were associated factors.
Conclusion
In an inception cohort with SLE followed for up to 8 years there were 97 vascular events but only 31 were attributable to atherosclerosis. Patients with atherosclerotic events were more likely to be male and to be older at diagnosis of SLE.
doi:10.1002/acr.20122
PMCID: PMC2989413  PMID: 20535799
7.  Prospective Analysis Of Neuropsychiatric Events In An International Disease Inception Cohort of SLE Patients 
Annals of the rheumatic diseases  2009;69(3):529-535.
Objectives
To determine the frequency, accrual, attribution and outcome of neuropsychiatric (NP) events and impact on quality of life over 3 years in a large inception cohort of SLE patients.
Methods
The study was conducted by the Systemic Lupus International Collaborating Clinics. Patients were enrolled within 15 months of SLE diagnosis. NP events were identified using the ACR case definitions and decision rules were derived to determine the proportion of NP disease attributable to SLE. The outcome of NP events was recorded and patient perceived impact determined by the SF-36.
Results
There were 1206 patients (89.6% female) with a mean (±SD) age of 34.5±13.2 years. The mean disease duration at enrollment was 5.4±4.2 months. Over a mean follow-up of 1.9±1.2 years 486/1206 (40.3%) patients had ≥1 NP events which were attributed to SLE in 13.0%–23.6% of patients using two a priori decision rules. The frequency of individual NP events varied from 47.1% (headache) to 0% (myasthenia gravis). The outcome was significantly better for those NP events attributed to SLE especially if they occurred within 1.5 years of the diagnosis of SLE. Patients with NP events, regardless of attribution, had significantly lower summary scores for both mental and physical health over the study.
Conclusions
NP events in SLE patients are variable in frequency, most commonly present early in the disease course and adversely impact patients’ quality of life over time. Events attributed to non-SLE causes are more common than those due to SLE, although the latter have a more favourable outcome.
doi:10.1136/ard.2008.106351
PMCID: PMC2929162  PMID: 19359262
Lupus; Neuropsychiatric; Prospective; Inception cohort
8.  Non-Hodgkin's lymphoma in systemic lupus erythematosus 
Annals of the Rheumatic Diseases  2005;64(10):1507-1509.
Objectives: To describe demographic factors, subtypes, and survival of patients with SLE who develop NHL.
Methods: A multi-site cohort of 9547 subjects with definite SLE was assembled. Subjects at each centre were linked to regional tumour registries to determine cancer cases occurring after SLE diagnosis. For the NHL cases ascertained, descriptive statistics were calculated, and NHL subtype frequency and median survival time of patients determined.
Results: 42 cases of NHL occurred in the patients with SLE during the 76 948 patient-years of observation. The median age of patients at NHL diagnosis was 57 years. Thirty six (86%) of the 42 patients developing NHL were women, reflecting the female predominance of the cohort. In the patients, aggressive histological subtypes appeared to predominate, with the most commonly identified NHL subtype being diffuse large B cell (11 out of 21 cases for which histological subtype was available). Twenty two of the patients had died a median of 1.2 years after lymphoma diagnosis.
Conclusions: These data suggest aggressive disease in patients with SLE who develop NHL. Continuing work should provide further insight into the patterns of presentation, prognosis, and aetiology of NHL in SLE.
doi:10.1136/ard.2004.034504
PMCID: PMC1755239  PMID: 16162903
9.  EULAR randomised controlled trial of pulse cyclophosphamide and methylprednisolone versus continuous cyclophosphamide and prednisolone followed by azathioprine and prednisolone in lupus nephritis 
Annals of the Rheumatic Diseases  2004;63(5):525-529.
Objective: To compare the efficacy and side effects of intermittent pulse cyclophosphamide plus methylprednisolone with continuous oral cyclophosphamide plus prednisolone, followed by azathioprine, in patients with proliferative glomerulonephritis caused by systemic lupus erythematosus (SLE).
Methods: A multicentre randomised controlled trial was conducted between June 1992 and May 1996 involving eight European centres. All patients satisfied the American College of Rheumatology criteria for SLE and had biopsy proven proliferative lupus nephritis. All received corticosteroids in addition to cytotoxic drugs, as defined in the protocol, for two years. The trial was terminated after four years as recruitment was disappointing.
Results: 32 SLE patients with lupus nephritis were recruited: 16 were randomised to intermittent pulse cyclophosphamide and 16 to continuous cyclophosphamide plus azathioprine. Mean duration of follow up was 3.7 years in the continuous group (range 0 to 5.6) and 3.3 years in the pulse group (range 0.25 to 6). Three patients were excluded from the pulse therapy group as they were later found to have pure mesangial glomerulonephritis. Two patients in the continuous therapy group developed end stage renal failure requiring dialysis, but none in the intermittent pulse therapy (p = 0.488; NS). There were similar numbers of side effects and withdrawals from treatment in both groups. There were three deaths: two in the intermittent pulse therapy group and one in the continuous therapy group.
Conclusions: There was no statistically significant difference in efficacy and side effects between the two regimens. Infectious complications occurred commonly, so careful monitoring is required during treatment.
doi:10.1136/ard.2002.003574
PMCID: PMC1755006  PMID: 15082482
10.  Transplantation with allogenic bone marrow from a donor with systemic lupus erythematosus (SLE): successful outcome in the recipient and induction of an SLE flare in the donor. 
Annals of the Rheumatic Diseases  1996;55(9):638-641.
OBJECTIVE: To investigate the transfer of autoimmunity by allogenic bone marrow transplantation. METHODS: Bone marrow transplantation was performed in a 43 years old man with acute myeloid leukaemia (AML) in remission. The donor was his HLA identical brother who had a mild systemic lupus erythematosus (SLE). Autoantibodies, including antinuclear, anti-C1q, and anticardiolipin antibodies, were measured before and after transplantation. RESULTS: Transient mild graft versus host disease (GvHD) developed in the recipient in the weeks following transplantation. The donor had persistently high concentrations of anti-C1q antibodies to the collagenous region of the complement component C1q. Three months after transplantation the recipient developed antiC1q antibodies that persisted for two months. No other autoantibodies and no SLE-like manifestations appeared. Chronic GVHD started five months posttransplant and responded to intensified immunosuppressive treatment. Three years post-transplant the patient was in unmaintained remission. Within a few weeks after bone marrow donation the donor's disease was exacerbated with development of severe pulmonary alveolitis which required treatment with cyclophosphamide. CONCLUSIONS: When bone marrow transplantation was performed in a patient with AML with bone marrow from an HLA identical brother who had SLE, no evidence of transfer of disease was obtained. However, the recipient temporarily produced anti-C1q antibodies which was a characteristic feature of the donor's SLE and was probably produced by the transplant. The flare of the donor's SLE might be related to the bone marrow tap.
PMCID: PMC1010261  PMID: 8882135
11.  Significance of anti-entactin antibodies in patients with systemic lupus erythematosus and related disorders. 
Annals of the Rheumatic Diseases  1994;53(10):659-665.
OBJECTIVES--To further evaluate the association of anti-entactin antibodies with clinical manifestations in patients with systemic lupus erythematosus (SLE) and related disorders. METHODS--Sera were analysed for anti-entactin antibodies from 79 patients with SLE, 38 patients with rheumatoid arthritis, 20 patients with progressive systemic sclerosis and five with Behçet's syndrome. Sera from 150 healthy blood donors and 20 patients with pneumonia were analysed as controls. To study the association of anti-entactin antibodies with severity and activity in SLE, 30 patients were assigned into three groups with 10 patients in each: (1) with mild manifestations; (2) severe disease without renal involvement and (3) frank lupus nephritis. Two blood samples from each patient were analysed, one from the active and the other from the inactive phase of the disease. Additionally, serial sera from 12 patients with SLE were also analysed. RESULTS--Thirty one patients with SLE (39%) had IgG, IgM or both anti-entactin antibodies. Twenty three of these patients (29%) had biopsy verified glomerulonephritis and 12 (50%) were positive for anti-entactin antibodies. Of the remaining 56 patients without apparent renal involvement, 18 (36%) were positive for anti-entactin antibodies. (chi squared = 2.77, p > 0.05). With the exception of rheumatoid arthritis where six patients (24%) had IgM anti-entactin antibodies, the antibodies were present much less frequently in other diseases (two patients with systemic vasculitis whilst none of the patients with PSS or Behçet's syndrome). Only one patient with pneumonia and none of the 150 sera from healthy blood donors had anti-entactin antibodies. Among Group 1, three (30%) were positive for IgG or IgM anti-entactin antibodies. Six (60%) patients in group 2, and five patients (50%) in group 3 were positive for anti-entactin antibodies. However, the difference between the presence of anti-entactin antibodies between group 1 and 2 or between group 1 and 3 was not significant (p = 0.15 and 0.19 respectively). There was no significant correlation between the titres of anti-entactin antibodies and total serum concentration of IgG (r = 0.141, p > 0.10) and IgM. (r = 0.130, p > 0.10). Furthermore, no significant correlation was observed between SLE disease activity index (SLEDAI) scores and the titres of IgG (r = 0.067, p > 0.10) or IgM (r = -0.033, p > 0.10) anti-entactin antibodies. CONCLUSION--The study demonstrates that anti-entactin antibodies are present in a significant number of patients with SLE and tend to be more common in those with severe disease, with or without nephritis, than in patients with mild disease manifestations. There is no correlation between the titre of anti-entactin antibodies and severity or activity of SLE.
PMCID: PMC1005432  PMID: 7979578
12.  Effects of ultraviolet irradiation on natural killer cell function in systemic lupus erythematosus. 
Annals of the Rheumatic Diseases  1992;51(6):726-730.
In vitro irradiation with long wavelength ultraviolet light (UV-A), in clinically relevant dosages, of a natural killer cell line containing cell preparations from 17 control subjects reduced natural killer cell cytotoxicity with the cell line K562 as target. The spontaneous function of natural killer cells from 12 patients with systemic lupus erythematosus (SLE) correlated inversely with the one hour erythrocyte sedimentation rate, but not with glucocorticoid doses. After UV-A exposure, natural killer cells from patients with SLE exert either increased or decreased cytotoxicity, and the direction of change is inversely correlated with the spontaneous natural killer cell function.
PMCID: PMC1004734  PMID: 1616354
13.  Recurrent cerebral infarction and the antiphospholipid syndrome: effect of intravenous gammaglobulin in a patient with systemic lupus erythematosus. 
Annals of the Rheumatic Diseases  1990;49(11):939-941.
A 23 year old woman with systemic lupus erythematosus and antiphospholipid syndrome developed severe thrombocytopenia (5-10 X 10(9)/l) and cerebral infarction. Treatment with high doses of corticosteroids and cytostatic drugs was not effective. The condition was successfully treated only when three courses of intravenous gammaglobulin at 400 mg/kg daily was added. A clear relation was found between the immunoglobulin infusions and rising platelet counts, whereas an effect on the levels of anticardiolipin antibodies could not be recorded. The findings suggested that the mechanisms responsible may be modification and solubilisation of immune complexes or interference with anticardiolipin binding to platelet membranes, or both.
PMCID: PMC1004269  PMID: 2256744
15.  Reduced opsonisation of protein A containing Staphylococcus aureus in sera with cryoglobulins from patients with active systemic lupus erythematosus. 
Annals of the Rheumatic Diseases  1985;44(4):252-259.
Among a total of 41 patients with systemic lupus erythematosus (SLE) 11 of 14 patients with active disease had reduced capacity (p less than 0.05) to opsonify Staphylococcus aureus in undiluted sera, as compared with nine of 27 patients with inactive disease (p less than 0.02). The opsonic reduction in the active patients increased with the number of active organ systems (p less than 0.002). No correlation was found between reduced opsonisation and corticosteroid treatment, or serum concentrations of complement components (C) of the classical pathway, or bacteria-associated activated C3. When the cryoglobulin fraction of immune complexes (IC) was removed, normal opsonic capacity was restored, and the opsonic reduction could be transferred with the cryoglobulins to pooled serum. Increased IC values, as measured by C1q binding assay, were found in conjunction with reduced opsonic capacity (p less than 0.04). Since opsonisation in SLE sera of a protein A deficient strain of S. aureus was normal, reduced S. aureus phagocytosis in SLE sera may be explained by IC binding to staphylococcal protein A.
PMCID: PMC1001621  PMID: 3872638

Results 1-16 (16)