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Background: Only two previous studies in systemic lupus erythematosus (SLE) patients have identified that the blood concentrations of uromodulin are lower in nephritis. However, none of them had evaluated whether a low serum uromodulin adjusted by the glomerular filtration rate (sUromod/eGFR index) contributed to identify patients in risk of lupus nephritis (LN) using multivariable models. Aim: Therefore, this study aimed two objectives to evaluate the association between low serum uromodulin levels and low sUromod adjusted by eGFR with renal flares in SLE excluding effects of potential confounders in multivariable analyses; and to identify the value of low sUmod and low sUmod/eGFR index as a potential diagnostic marker of LN. Patients and methods: Design: Cross-sectional study. SLE patients (n = 114) were investigated for lupus flare with renal SLEDAI. Two groups: a) SLE with renal flare (renal-SLEDAI≥4, n = 41) and b) SLE non-renal flare (renal SLEDAI<4, n = 73). SLE patients were evaluated by other indices including a global disease activity index (SLEDAI) and SLICC renal disease activity score. Serum uromodulin levels (ng/mL) were quantified by ELISA. Serum uromodulin was adjusted by eGFR (sUromod/eGFR index). Cutt-offs of low sUromodulin and low sUromod/eGFR index were computed, ROC curves were performed and values of diagnostic tests were obtained. Multivariable logistic regression models were performed to identify if low sUromod/eGFR index is associated to renal flares. Results: Low serum uromodulin and low sUromod/eGFR index correlated to high scores of renal-SLEDAI, SLICC-renal and proteinuria. SLE patients with a renal flare had lower uromodulin levels compared to SLE patients without renal flare (p = 0.004). After adjusting by potential confounders, the low sUromod/eGFR index (<0.80 ng/mL) increased the risk of a renal flare (OR, 2.91; 95%CI, 1.21 to 6.98; p = 0.02). Conclusions: We propose the low sUromod/eGFR index as a potential new marker of renal disease activity in SLE. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the utility of elevated serum P-glycoprotein (P-gp) as a risk marker of therapeutic response failure in rheumatoid arthritis (RA) patients treated with disease-modifying antirheumatic drugs (DMARDs).Methods: A cross-sectional study was conducted in 151 RA patients. Patients were classified into two groups according to the response achieved in terms of the disease activity score (DAS)28 after ≥ 6 months: (1) patients with a therapeutic response to DMARDs, with DAS28 < 3.2; and (2) patients without a response to DMARDs, with persistent DAS28 ≥ 3.2. We explored a wide group of clinical factors associated with therapeutic resistance. Serum P-gp levels were measured by ELISA. The risk of P-gp elevation as a marker of failure to achieve a therapeutic response to DMARDs was computed using multivariate logistic regression.Results: Serum P-gp levels were significantly higher in RA patients (n = 151) than in the controls (n = 30) (158.70 ± 182.71 ng/mL vs. 14.12 ± 8.97 ng/mL, p < 0.001). The P-gp level was correlated with the DAS28 score (r = 0.39, p < 0.001). RA patients with DMARD failure had higher serum P-gp levels than patients with a therapeutic response (206 ± 21.47 ng/mL vs 120.60 ± 15.70 ng/mL; p = 0.001). High P-gp levels increased the risk of DMARD failure (OR 3.36, 95% CI 1.54-7.27, p = 0.001). After adjusting for confounding variables, elevated P-gp remained associated with DMARD failure (OR 2.64, 95% CI 1.29-5.40, p = 0.01).Conclusion: Elevated serum P-gp is associated with DMARD failure. The P-gp level can be considered a clinical tool for evaluating the risk of DMARD failure in patients; however, future prospective studies should be performed to evaluate the utility of this marker in predicting long-term responses. [ABSTRACT FROM AUTHOR]

Bone disease in rheumatoid arthritis (RA) is a complex phenomenon where genetic risk factors have been partially evaluated. The system formed by receptor activator for nuclear factor-κB (RANK), receptor activator for nuclear factor-κB ligand (RANKL), and osteoprotegerin (OPG): RANK/RANKL/OPG is a crucial molecular pathway for coupling between osteoblasts and osteoclasts, since OPG is able to inhibit osteoclast differentiation and activation. We aim to evaluate the association between SNPs C950T (rs2073617), C209T (rs3134069), T245G (rs3134070) in the TNFRSF11B (OPG) gene, and osteoporosis in RA. We included 81 women with RA and 52 healthy subjects in a cross-sectional study, genotyped them, and measured bone mineral density (BMD) at the lumbar spine and the femoral neck. Mean age in RA was 50±12 with disease duration of 12±8 years. According to BMD results, 23 (33.3%) were normal and 46 (66.7%) had osteopenia/osteoporosis. We found a higher prevalence of C allele for C950T SNP in RA. Polymorphisms C209T and T245G did not reach statistical significance in allele distribution. Further studies including patients from other regions of Latin America with a multicenter design to increase the sample size are required to confirm our findings and elucidate if C950T SNP could be associated with osteoporosis in RA. [ABSTRACT FROM AUTHOR]

Objective. To compare the modifications in lipids between patients with rheumatoid arthritis (RA) receiving etanercept plus methotrexate (ETA + MTX) versus methotrexate (MTX) and their relationship with serum levels of tumor necrosis factor-alpha (TNF-α). Methods. In an observational cohort study, we compared changes in lipid levels in patients receiving ETA + MTX versus MTX in RA. These groups were assessed at baseline and at 4 and 24 weeks, measuring clinical outcomes, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, and TNF-α. Results. Baseline values for lipid levels were similar in both groups. HDL-C levels increased significantly only in the ETA + MTX group (from 45.5 to 50.0mg/dL at 4 weeks, a 10.2% increase, P < 0.001, and to 56.0mg/dL at 24 weeks, a 25.1% increase, P < 0.001), while other lipids underwent no significant changes. ETA +MTX also exhibited a significant increase in TNF-α (44.8 pg/mL at baseline versus 281.4 pg/mL at 24 weeks, P < 0.001). The MTX group had no significant changes in lipids or TNF-α. Significant differences in HDL-C between groups were observed at 24 weeks (P = 0.04) and also in TNF-α (P = 0.01). Conclusion. HDL-C levels increased significantly following treatment with ETA + MTX, without a relationship with decrease of TNF-α. [ABSTRACT FROM AUTHOR]

In this cross-sectional study, we assessed the relationship between circulating TNF-α and E-selectin (sE-selectin) with extraarticular involvement and severity of joint disease in RA. We compared 56 patients who had RA and extraarticular involvement (ExRA) with a group of 84 patients with only articular involvement (non-ExRA). ExRA had higher circulating TNF-α than non-ExRA (32 ± 9 vs. 28 ± 6 pg/mL, P = 0.002). sE-selectin levels did not differ between both groups. sE-selectin correlated with tender joint count (rho = 0.19, P = 0.03), morning stiffness (rho = 0.19, P = 0.03), severity of pain (rho = 0.21, P = 0.02), disease activity (assessed by the patient) (rho = 0.21, P = 0.02), HAQ-DI (rho = 0.29, P = 0.004), and rheumatoid factor titers (rho = 0.31, P = <0.001). Circulating TNF-α had no correlation with sE-selectin or disease activity. We concluded that sE-selectin correlated with severity of joint disease, further follow-up studies should evaluate if sE-selectin is useful as prognosis marker for progression of articular damage. [ABSTRACT FROM AUTHOR]

We evaluated the prevalence and characteristics associated with hyperhomocysteinemia in ankylosing spondylitis (AS). Ninety-seven patients with AS were compared with 97 controls. The assessment included clinical characteristics, disease activity (BASDAI), functioning (BASFI), history of drugs, and erythrocyte sedimentation rate (ESR). Total serum homocysteine (tHcy) was determined by fluorescence polarization immunoassay. A higher frequency of hyperhomocysteinemia (>15 μmol/L) was observed in AS (12 vs. 1%, P = 0.002). In the multivariate analysis the risk for hyperhomocysteinemia was increased in patients with higher score of HAQ-S (OR = 5.27, 95% CI: 1.29–21.44) and higher ESR (OR = 1.09, 95% CI: 1.02–1.18). No statistical associations was observed between hyperhomocysteinemia with other variables including methotrexate or sulfasalazine utilization. In conclusion, this study found a significant prevalence of hyperhomocysteinemia in Mexican patients with AS mainly associated to a worst functional impairment. Further follow-up studies are required to evaluate the risk of cardiovascular disease in these patients. [ABSTRACT FROM AUTHOR]

Objective. The authors developed a Markov decision model to evaluate the health implications of testing for mutations in the BRCA1 and BRCA2 breast-ovarian cancer susceptibility genes. Prophylactic measures considered included various combinations of immediate and delayed bilateral mastectomy and oophorectomy or taking no action. Methods. The model incorporated the likelihood of developing breast and/or ovarian cancer, survival, and quality of life. Parameter values were taken from public data bases, the published literature, and a survey of cancer experts. Outcomes considered were additional life expectancy and quality-adjusted life years (QALYs). Results are reported for 30-year-old cancer-free women at various levels of hereditary risk. Results and conclusions. The vast majority of women will not benefit from testing because their pre-test risks are low and surgical prophylaxis is undesirable. However, women who have family histories of early breast and/or ovarian cancer may gain up to 2 QALYs by allowing genetic testing to inform their decisions. Key words: BRCA1; BRCA2; ge netic testing; breast cancer; ovarian cancer; decision analysis. (Med Decis Making 1998;18:365-375) [ABSTRACT FROM PUBLISHER]

Bone disease in rheumatoid arthritis (RA) is a complex phenomenon where genetic risk factors have been partially evaluated. The system formed by receptor activator for nuclear factor-κB (RANK), receptor activator for nuclear factor-κB ligand (RANKL), and osteoprotegerin (OPG): RANK/RANKL/OPG is a crucial molecular pathway for coupling between osteoblasts and osteoclasts, since OPG is able to inhibit osteoclast differentiation and activation. We aim to evaluate the association between SNPs C950T (rs2073617), C209T (rs3134069), T245G (rs3134070) in the TNFRSF11B (OPG) gene, and osteoporosis in RA. We included 81 women with RA and 52 healthy subjects in a cross-sectional study, genotyped them, and measured bone mineral density (BMD) at the lumbar spine and the femoral neck. Mean age in RA was 50 ± 12 with disease duration of 12 ± 8 years. According to BMD results, 23 (33.3%) were normal and 46 (66.7%) had osteopenia/osteoporosis. We found a higher prevalence of C allele for C950T SNP in RA. Polymorphisms C209T and T245G did not reach statistical significance in allele distribution. Further studies including patients from other regions of Latin America with a multicenter design to increase the sample size are required to confirm our findings and elucidate if C950T SNP could be associated with osteoporosis in RA. [ABSTRACT FROM AUTHOR]