Is entheses ultrasound reliable? A reading Latin American exercise.

The objective of this study is to evaluate inter-reader entheses ultrasound (US) reliability and the influence of the type of image or degree of sonographer experience on US reliability in patients with spondyloarthritis (SpA). Eighteen Latin American ultrasonographers with different experience took part in an US reading exercise evaluating 60 entheseal images (50 % static images and 50 % videos) from healthy controls and SpA patients. The following sonographic lesions were assessed: structure, thickness, bone proliferation/tendon calcification, erosions, bursitis, and Doppler signal. Another group of three experts with significant experience in entheses US read all images too. Inter-reader reliability among participants and experts was calculated by the Cohen's kappa coefficient. Thresholds for kappa values were <0.2 poor, 0.21-0.4 fair, 0.41-0.6 moderate, 0.61-0.8 good, and 0.81-1 excellent. Furthermore, the results for the expert group were stratified based on the type of image. Kappa correlation coefficients among participants, showed variability depending on the type of lesion, being fair for structure and thickness, moderate for calcifications, erosions, and bursitis, and excellent for Doppler signal. Inter-reader reliability among experts was higher, being moderate for structure and thickness, good for calcifications and bursitis, and excellent for erosions and Doppler. Inter-reader reliability for assessing calcification and structure using static images was significantly higher than for videos. Overall inter-reader reliability for assessing entheses by US in SpA is moderate to excellent for most of the lesions. However, special training seems fundamental to achieve better inter-reader reliability. Moreover, the type of image influenced these results, where evaluation of entheses by videos was more difficult than by static images.

Factors associated with arterial vascular events in PROFILE: a Multiethnic Lupus Cohort.

The objective of this study was to determine the factors associated with the occurrence of arterial vascular events in a multiethnic systemic lupus erythematosus (SLE) cohort. The PROFILE cohort, comprised SLE patients (n = 1333) of defined ethnicity from five different US institutions, was studied to determine demographic, clinical and biological variables associated with vascular events. An arterial vascular event (first episode) was either a myocardial infarction, angina pectoris and/or a vascular procedure for myocardial infarction, stroke, claudication and/or evidence of gangrene. Patient characteristics were analyzed by univariable and multivariable Cox proportional hazards regression analyses. One-hundred twenty-three (9.8%) patients had at least one incident arterial event. Age at cohort enrollment (HR = 1.04, 95% CI 1.03-1.06), smoking (HR = 2.20, 95% CI 1.40-3.46) and the CRP2* C alleles (HR = 1.91, 95% CI 1.04-3.49) were associated with a shorter time-to-the occurrence of arterial vascular events. Some clinical manifestations of disease activity were associated with a shorter time-to-occurrence [psychosis (HR = 2.21, 95% CI 1.10-4.44), seizures (HR = 1.85, 95% CI 1.00-3.24) and anaemia (HR = 1.83, 95% CI 1.02-3.31)], but others were not [arthritis (HR = 0.32, 95% CI 0.18-0.58)]. In conclusion, older patients, especially in the context of a predisposing environmental factor (smoking) and severe clinical manifestations, are at higher risk of having arterial vascular events. The genetic contribution of the variation at the CRP locus was not obscured by demographic or clinical variables. Awareness of these factors should lead to more effective management strategies of patients at risk for arterial vascular events.

Adverse pregnancy outcomes in women with systemic lupus erythematosus from a multiethnic US cohort: LUMINA (LVI) [corrected].

OBJECTIVE: To study the factors associated with an adverse pregnancy outcome in women with systemic lupus erythematosus (SLE). METHODS: SLE women from LUMINA of Hispanic, African American and Caucasian ethnicity were studied. Adverse pregnancy outcome was a miscarriage or abortion (<20 weeks), a stillbirth (> or = 20) and/or a moderate to severe preterm-baby (<34 weeks); good outcome was either a mild preterm-baby (> or = 34 weeks) or a full-term baby [C-section or vaginal delivery (38-42 weeks)]. Pregnancies occurring after SLE diagnosis (TD) were included; pregnancy outcome was the unit of analyses. The relationship between selected variables and pregnancy outcomes was examined by univariable and multivariable analyses. RESULTS: Adverse outcomes occurred in 63.7% of 102 pregnancies. In the univariable analyses, Texan Hispanic and African American ethnicities, fewer years of education, higher number of ACR criteria, renal involvement, glucocorticoid exposure and the maximum dose of glucocorticoids used prior to the pregnancy outcome were associated with an adverse pregnancy outcome. Renal involvement was independently associated with an adverse pregnancy outcome [Odds ratio (OR)=5.219 (95% Confidence Interval (CI) 1.416-19.239, p=0.0131] as were the maximum dose of glucocorticoids used prior to the pregnancy outcome (OR=1.028; CI:1.002-1.054; p=0.0315) and fewer years of education (OR=1.204; CI:1.006-1.472; p=0.0437). Ethnicity was not retained in the multivariable model. CONCLUSION: Renal involvement, the maximum dose of glucocorticoids used prior to pregnancy and fewer years of education were associated with adverse pregnancy outcomes. These data have implications for the management of women with lupus planning to become pregnant.

Systemic lupus erythaematosus in a multiethnic US cohort (LUMINA) LIII: disease expression and outcome in acute onset lupus.

OBJECTIVE: To determine the features associated with acute onset systemic lupus erythaematosus (SLE). METHODS: A total of 631 SLE patients from LUMINA (for "lupus in minority populations: nature vs nurture"), a multiethnic (Hispanics, African-Americans and Caucasians) cohort, were studied. Acute disease onset was defined as the accrual of > or = 4 American College of Rheumatology (ACR) criteria for the classification of SLE in < or = 4 weeks. Socioeconomic demographic features, clinical manifestations, disease activity, damage accrual, mortality, autoantibodies, HLA class II and FCGR alleles, behavioural/psychological variables were compared between patients with acute and insidious disease onset by univariable (chi(2) and Student t test) and multivariable (stepwise logistic regression) analyses. RESULTS: A total of 94 (15%) patients had acute disease onset. In the multivariable analysis, patients with acute onset lupus had more renal involvement (odds ratio (OR) = 1.845, 95% CI 1.076-3.162; p = 0.026) and higher disease activity (OR = 1.057, 95% CI 1.005-1.112; p = 0.030). By contrast, age (OR = 0.976, 95% CI 0.956-0.997; p = 0.025), education (OR = 0.901, 95% CI 0.827-0.983, p = 0.019), health insurance (OR = 0.423, 95% CI 0.249-0.718; p = 0.001) and skin involvement (OR = 0.346, 95% CI 0.142-0.843; p = 0.019) were negatively associated with acute onset lupus. No differences were found regarding the serological, genetic and behavioural/psychological features; this was also the case for damage accrual and mortality. CONCLUSIONS: Patients with acute onset lupus seem to be younger, have a lower socio-economic status and display more severe disease in terms of clinical manifestations and disease activity. However, intermediate (damage) and long-term (mortality) outcomes appear not to be influenced by the type of disease onset in SLE.

Systemic lupus erythematosus in a multiethnic US Cohort LUMINA XLVIII: factors predictive of pulmonary damage.

The objective of this study was to determine the factors predictive of time to the occurrence of pulmonary damage in systemic lupus erythematosus (SLE). Six-hundred and twenty-six SLE patients from a multiethnic (Hispanics, African Americans and Caucasians) longitudinal study of outcome were studied. Pulmonary damage was defined as per the Systemic Lupus International Collaborating Clinics Damage Index. Socioeconomic-demographic, clinical, genetic, serological features, pharmacologic treatments, behavioural, psychological and disease activity [as per the Systemic Lupus Activity Measure-Revised (SLAM-R)] were examined. Factors associated with time to the occurrence of pulmonary damage were examined by Cox proportional hazards regressions. A Kaplan-Meier survival curve was also examined. Forty-six (7.3%) patients had pulmonary damage after a mean (SD) total disease duration of 5.3 (3.6) years. Among those patients, 25 had pulmonary fibrosis, 12 pulmonary hypertension, eight pleural fibrosis, four pulmonary infarction and four shrinking lung syndrome. Seven patients had more than one type of lung damage. Cumulative rates of pulmonary damage at five and 10 years were 7.6% and 11.6%, respectively. In the multivariable analyses, age (HR = 1.033, 95% CI 1.006-1.060; P = 0.0170), pneumonitis (HR = 2.307, 95% CI 1.123-4.739; P = 0.0229) and anti-RNP antibodies (HR = 2.344, 95% CI 1.190-4.618; P = 0.0138) were associated with a shorter time to the occurrence of pulmonary damage while photosensitivity (HR = 0.388, 95% CI 0.184-0.818; P = 0.0128) and oral ulcers (HR = 0.466, 95% CI 0.230-0.942; P = 0.0335) with a longer time. Pulmonary damage is relatively common in SLE. Age, pneumonitis and anti-RNP antibodies were associated with a shorter time to the development of permanent lung disease.

Systemic lupus erythematosus in a multiethnic US cohort LUMINA LI: anaemia as a predictor of disease activity and damage accrual.

OBJECTIVE: To examine if anaemia (and its severity) is associated with disease activity and damage accrual in systemic lupus erythematosus (SLE). METHODS: Four thousand four-hundred study visits in 613 SLE patients enrolled in LUMINA were studied. Anaemia was expressed in four categories of haematocrit (Hct) as defined by the Systemic Lupus Activity Measure-Revised (SLAM-R): no anaemia (Hct >35%), mild (Hct = 30-35%), moderate (Hct = 25-29%) and severe (Hct <25%). Anti-dsDNA antibodies were measured at baseline. Disease activity was assessed with the SLAM-R and damage with the Systemic Lupus International Collaborating Clinics Damage Index (SDI). The relationship between anaemia and anti-dsDNA antibodies with the SLAM and SDI scores was examined by univariate (one-way ANOVA) and multivariate (generalized linear models and generalized estimating equation regression) analyses. RESULTS: All categories of anaemia and anti-ds DNA were significantly associated with the SLAM-R at baseline and over time. However, only moderate and severe anaemia were associated with the SDI at baseline and over time, while the presence of anti-ds DNA was only associated with the SDI over time but not at baseline. Several clinical domains of the SLAM-R and SDI were associated with anaemia at baseline and over time. CONCLUSIONS: Mild, moderate and marked anaemia are strongly associated with disease activity in SLE. Moderate and marked anaemia are associated with damage accrual. These associations are observed both early and during the course of SLE. Different levels of anaemia could be used to monitor disease activity and predict organ/system damage in SLE.

Systemic lupus erythematosus in a multiethnic US cohort LUMINA (XLI): factors predictive of self-reported work disability.

OBJECTIVE: To examine the risk factors for self-reported work disability in patients from the LUpus in MInorities: NAture vs. Nurture cohort with systemic lupus erythematosus (SLE). METHODS: Patients with SLE of Hispanic (Texas and Puerto Rico), African American and Caucasian ethnicity were studied. Work disability was defined by patients' self-report. Only patients known to be employed at the baseline visit were included. The probabilities of self-reporting work disability over time were examined by the Kaplan-Meier method; differences between ethnic groups were examined by the log-rank test. The relationship of baseline socioeconomic-demographic, clinical, behavioural and psychological features with work disability was examined by standard statistical tests. Variables with p

Predictors of post-partum damage accrual in systemic lupus erythematosus: data from LUMINA, a multiethnic US cohort (XXXVIII).

OBJECTIVE: To determine the impact of pregnancy on systemic lupus erythematosus (SLE) outcome. METHODS: SLE patients, age >or=16 yrs, disease duration

Systemic lupus erythematosus in a multiethnic U.S. cohort (LUMINA) XXVII: factors predictive of a decline to low levels of disease activity.

The objective of this study was to examine factors predictive of a decline to low levels of disease activity in a cohort of systemic lupus erythematosus (SLE) patients. Patients with SLE of Hispanic (from Texas or Puerto Rico), African-American or Caucasian ethnicity from a multiethnic cohort were included. A decline to low levels of disease activity was defined as a score < or =5 as per the Systemic Lupus Activity Measure-Revised (SLAM-R) at any annual study visit if preceded by a SLAM-R > or =8. Using Generalized Estimating Equation (GEE), socioeconomic-demographic, behavioral, function, psychological, laboratory and clinical data [disease manifestations, number of ACR criteria accrued at diagnosis and damage accrual as per the Systemic Lupus International Collaborating Clinics (SLICC) Damage Index (SDI)] from the visit preceding that meeting the definition were examined as predictors of decline to low levels of disease activity. Two-hundred and eighty-seven patients (67 Hispanics from Texas, 32 Hispanics form Puerto Rico, 120 African-Americans and 68 Caucasians), accounting for 632 visits were analyzed. In the GEE multivariable analysis, higher degrees of social support (OR = 1.208, 95% CI 1.059-1.379; P = 0.005) were predictive of a decline to low levels of disease activity, while the number of ACR criteria accrued at diagnosis (OR = 0.765, 95% CI 0.631-0.927; P = 0.006) and damage (OR = 0.850, 95% CI 0.743-0.972, P = 0.018) were negatively associated. These data suggest that a decline to low levels of disease activity in lupus patients seems to be multifactorial; this study also underscores the importance of social support for lupus patients.

Systemic lupus erythematosus in a multiethnic U.S. cohort (LUMINA) XXXI: factors associated with patients being lost to follow-up.

The objective of this study was to determine the frequency of loss to follow-up and the factors predictive of its occurrence in a systemic lupus erythematosus (SLE) multiethnic cohort. We studied SLE patients from the LUMINA cohort (Hispanics from Texas and from the Island of Puerto Rico, African-Americans and Caucasians). Loss to follow-up was defined as subjects who failed to attend two or more of the latest consecutive yearly study visits. The relationship between baseline features and loss to follow-up was examined by univariable and multivariable Cox regression analyses with loss to follow-up as the dependent variable. The retention rate in the cohort was estimated by the Kaplan-Meier method. Five-hundred and fifty-four patients with a mean (SD) follow-up of 3.4 (2.9) years were studied. One-hundred and fifty-eight (29%) met the definition of lost to follow-up. The cumulative loss to follow-up rate at five years was 36%. The cumulative loss to follow-up rate at five years was higher for the African-Americans. Patients lost to follow-up tended to be younger and more likely to have poor social support and higher levels of helplessness. They also tended to have more renal involvement and more active disease as per the Systemic Lupus Activity Measure-Revised. Disease activity (hazard ratio = 1.04, 95% confidence interval 1.01-1.07, P = 0.02) was the only variable independently contributing to loss to follow-up. Our data suggest that in longitudinal SLE studies, loss to follow-up does not occur at random and it differs between ethnic groups and is also particularly higher among patients with more active disease. Pro-active measures may need to be applied to decrease the probability of patients 'at risk' of becoming lost to follow-up and to preserve the integrity of the cohort.

Uso de infliximab en pacientes de un centro reumatologico / Use of infliximab in patients of a rheumatologic center

The objective of this study was to obtain post-marketing information about the use of infliximab in an ambulatory setting. We studied--retrospectively and prospectively--the case records of patients with rheumatoid arthritis (n=37), psoriatic arthritis (n=5), mixed connective tissue disease (n=1), and ankylosing spondylitis (n=2) who received infliximab (3 mg/kg) from August 2000 to January 2003. Descriptive values were given as percentage, mean or median, and standard deviation or interquartile range. Wilcoxon test was used for paired analysis of pre/post doses of corticosteroids, non-steroidal anti-inflammatory drugs, and methotrexate therapy. A p value < or = 0.05 was considered significant. Forty-five patients were included. A total of 207 infusions were administered. In 4 patients the treatment was permanently discontinued due to severe back pain during the infusion (2 cases) and serious anaphylactic reactions (2 cases). Other adverse reactions occurring during infusions were mild and successfully managed with standard treatment. A case of staphylococcal septic arthritis resolved with standard antibiotic treatment. No patient had evidence of active tuberculosis. One patient with rheumatoid arthritis and chronic renal insufficiency, received treatment with infliximab 1.9 mg/kg, every 30 days, with no changes in renal function. Due to improvement of symptoms, 14/39 (35.9%) patients could decrease the doses of corticosteroids, 15/43 (34.8%) decreased the doses of antiinflammatory drugs and 12/34 (35.3%) decreased methotrexate dosage. Although some questions remain to be elucidated, this case series shows the drug safety profile, the possibility to reduce concomitant drug doses, as well as individual approaches for situations where there are not yet guidelines available, so that rheumatologists have to make decisions based on clinical needs.

El objetivo de este estudio fue obtener informacion postmarketing sobre el uso de infliximab en un centro reumatologico de atencion ambulatoria. Se realizo un analisis retrospectivo y prospectivo de las historias clinicas de pacientes con diagnostico de artritis reumatoidea (n=37), artritis psoriasica (n=5),enfermedad mixta del tejido conectivo (n=1) y espondilitis anquilosante (n=2) que recibieron infliximab (3 mg/kg) desde agosto de 2000 a junio de 2003. El analisis descriptivo se realizo con porcentajes, media o medianay desviacion estandar o intervalo intercuartilo. La prueba de Wilcoxon se utilizo para el analisis apareado dedosis de antiinflamatorios no esteroideos y metotrexato, anterior y posterior a la administracion de infliximab. Se consideraron significativos valores de p < o = 0.05. Se incluyeron 45 pacientes a los que se les administraron un total de 207 infusiones. En 2 pacientes el infliximab se discontinuó debido a lumbalgia severa durante la infusion y en otros 2 por anafilaxia intrainfusional. Otras reacciones adversas ocurridas durante las infusiones fueron moderadas y respondieron adecuadamente al tratamiento estandar. Se presento un caso de artritis septica de rodilla por estafilococos. Un caso de artritis reumatoidea con insuficiencia renal compensada recibio infliximab en dosis de 1.9 mg/kg cada 30 dias, sin cambios en la funcion renal. Al momento, ningun paciente ha desarrollado tuberculosis activa. Debido a la mejoria clinica, se redujo la dosis de corticoides en 14/39 (35.9%) pacientes, de antiinflamatorios no esteroideos en 15/43 (34.8%) y de metotrexato en 12/34 (35.3%). En estaserie de casos se muestra el perfil de seguridad de infliximab, la posibilidad de reducir la dosis de drogas concomitantes,asi como algunos enfoques individuales sobre situaciones para las cuales no disponemos de guias basadas en la evidencia medica, y en las que los reumatologos debemos tomar decisiones segun las necesidades clinicas.

Attitudes and knowledge about presymptomatic genetic testing among individuals at high risk for familial, early-onset Alzheimer's disease.

The study was conducted in a large Cuban family with early-onset familial Alzheimer's disease (AD). Fifty-six first-degree relatives of familial cases with AD were interviewed concerning their clinical and genetic knowledge about AD and their attitudes toward the possible use of presymptomatic genetic testing of AD. The individuals had only limited knowledge about their personal risk of developing AD. All 56 family members would use presymptomatic testing to know their own risk of AD. Confronted with a hypothetical reproductive choice, 50% would choose not to have children if they themselves had the mutation. A positive prenatal test would lead 48.2% of the participants to have an abortion, and 19.7% would continue the pregnancy regardless of the positive test result.

Lung cavitation in primary antiphospholipid syndrome.

Pulmonary complications of primary antiphospholipid syndrome are common and diverse, with thromboembolic events counting as the most frequent manifestation. We present the case of a female patient with a diagnosis of primary antiphospholipid syndrome, pulmonary thromboembolism and infarction followed by lung cavitation.

IL2-R alpha chain inhibitory factor (p29) produced by HIV-infected macrophages: cell target and mode of action.

We recently reported that HIV-infected adherent cells spontaneously produce a 29-kDa protein (p29), most probably of nonviral origin, which inhibits expression of the IL2R alpha chain on activated normal T cells. Studying the mode of action of this molecule, we observed that monocyte depletion of normal PBMC either by plastic adherence or by complement-mediated cytotoxicity using macrophage-specific monoclonal antibodies abrogated the inhibitory effect of p29. The biological activity of p29 in adherent cell-depleted PBMC could be restored either with rIL1 or with as little as 10(5) autologous adherent cells/ml. Moreover, p29 could not inhibit IL1 biologic activity, nor its binding to IL1 receptor. In addition, p29 could not inhibit the production of IL1 and TNF alpha by normal adherent cells. Positive and negative cell sorting of normal T cells as well as two-color immunofluorescence studies revealed that CD8+ subsets are the main cell targets of p29, which also mediated an impaired generation of alloantigen-specific CTL. Conversely, only a slight inhibitory activity could be detected in highly purified CD4+ cells. Our findings suggest that HIV-induced production of p29 inhibitory factor by adherent cells may be involved in mechanisms responsible for some of the impaired cytotoxic functions observed in AIDS patients.

Human immunodeficiency virus-infected adherent cell-derived inhibitory factor (p29) inhibits normal T cell proliferation through decreased expression of high affinity interleukin-2 receptors and production of interleukin-2.

Adherent cells from HIV-infected subjects as well as in vitro HIV-infected normal adherent cells produce spontaneously a 29-kD (p29) factor that inhibits mitogen-induced proliferation of normal T cells. p29 mediates a partial dose-dependent inhibition of total protein synthesis in both nonstimulated and PHA-activated cells that is associated with impaired PHA-induced expression of IL-2 receptor (IL-2R)alpha chain, HLA-class II molecules, and production of IL-2 by these cells; conversely, p29 does not modify the expression of IL-2R beta chain, 4F2, CD9, or transferrin receptor, or the production of IL-1 and TNF alpha by the cells. 1 h preincubation of the cells with p29 is sufficient to detect its biologic activity and added rIL-2 abrogates p29-induced inhibition of IL-2R alpha chain expression; however, p29 does not display any biologic effect on already expressed IL-2R alpha chains. The impaired expression of IL-2R alpha chain mediated by p29 is not due to a decreased accumulation of the corresponding mRNA transcripts, but is associated with a two-fold increase of intracellular cAMP. Binding experiments with 125I-rIL-2 reveals that p29 induces a 50% decrease in the number of both high and low affinity IL-2R per cell. p29 also inhibits alloantigen-induced proliferation of PBMC, whereas it does not modify IL-2-dependent proliferation of 48-h PHA-blasts that already express high affinity IL-2R. These findings indicate that p29 mediates its biologic activity during early stages of T cell activation affecting the expression of high affinity IL-2R and production of IL-2, through a nontranscriptional mechanism involving an increase of intracellular cAMP.