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Objective: To define the frequency of the exon 6 tumor necrosis factor-alpha (TNF-alpha) receptor II (TNFRII) gene polymorphism in severe and mild-moderate rheumatoid arthritis (RA) and its possible influence on anti-TNF-alpha treatment responsiveness., Methods: Two cohorts of patients with RA, the first (n = 97) defined as methotrexate responders (MTX-R) with mild-moderate synovitis, and the second (n = 78) defined as nonresponders to combination therapy and receiving anti-TNF-alpha treatment because of their severe and aggressive disease (TNF-T), were studied retrospectively and compared to age, sex, and ethnically matched controls (n = 84). In the prospective study, 66 patients with severe RA were followed over the first 6 months of anti-TNF-alpha therapy and their response was examined according to genotype., Results: We observed a trend towards an increased frequency of the GG genotype in patients with severe RA (6.4%) in comparison with patients with mild-moderate disease (3.1%) and controls (1.2%). When looking at the response to anti-TNF-alpha therapy, we observed that after 12 weeks of treatment, 37.8% of the TT versus 10.7% of the TG/GG patients passed from high to medium-low disease activity (p = 0.03)., Conclusion: In our cohorts of patients selected by response to the conventional therapy and by disease severity, our preliminary study results showed a trend towards a higher prevalence of the GG genotype for the exon 6 TNFRII polymorphism in the less responsive patients with more aggressive disease. We also found a lower degree of response to anti-TNF-alpha treatments in patients carrying the G allele.

Background: While inflammation has been shown to play an important etiologic role in ovarian carcinogenesis, little is known about the association between inflammatory properties of diet and ovarian cancer risk.Methods: We explored the association between the dietary inflammatory index (DII) and ovarian cancer risk in a multicentric Italian case-control study conducted between 1992 and 1999. Cases were 1,031 women with incident, histologically confirmed ovarian cancer from four areas in Italy. Controls were 2,411 women admitted to the same network of hospitals as the cases for acute, non-malignant and non-gynecological conditions, unrelated to hormonal or digestive-tract diseases or committed to long-term modifications of diet. DII scores were computed based on 31 nutrients and food items assessed using a reproducible and validated 78-item food frequency questionnaire. Odds ratios (ORs) were estimated through logistic regression models adjusting for age, total energy intake and other recognized confounding factors.Results: Subjects in the highest quartile of DII scores (i.e., with the most pro-inflammatory diets) had a higher risk of ovarian cancer compared to subjects in the lowest quartile (i.e., with an anti-inflammatory diet) (ORQuartile4vs1 1.47, 95% confidence interval, CI, 1.07, 2.01; p trend = 0.009). When analyses were carried out using continuous DII, a significant positive association with ovarian cancer was observed: the OR for one-unit increment in DII score (corresponding to approximately 8 % of its range in the current study, +6.0 to -6.20) was 1.08 (95% CI 1.02, 1.14).Conclusion: A pro-inflammatory diet as indicated by higher DII scores is associated with increased ovarian cancer risk. [ABSTRACT FROM AUTHOR]

Background: Poor muscle strength is a major public health concern in older persons, predisposing to functional limitations, increased fall risk, and higher mortality. Understanding risk factors for muscle strength decline may offer opportunities for prevention and treatment. One of the possible causes of muscle strength decline is imbalance between catabolic and anabolic signaling. This study aims to examine whether high levels of multiple catabolic and low levels of multiple anabolic biomarkers predict accelerated decline of muscle strength., Methods: In a representative sample of 716 men and women aged >or=65 years in the InCHIANTI study we measured C-reactive protein, interleukin-6 (IL-6), IL-1 receptor antagonist (IL-1RA), tumor necrosis factor-alpha receptor 1 as well as dehydroepiandrosterone sulfate (DHEA-S), insulin-like growth factor-1, and bioavailable testosterone. Biomarker values were divided into tertiles and the numbers of catabolic/anabolic biomarkers in the highest/lowest tertile were calculated. Hand-grip strength was measured at baseline and 3- and 6-year follow up., Results: In adjusted linear mixed models, higher concentration of IL-6 (p = 0.02) and IL-1RA (p = 0.04) as well as lower levels of DHEA-S (p = 0.01) predicted muscle strength decline. After combining all inflammatory markers, the rate of decline in grip strength was progressively greater with the increasing number of dysregulated catabolic biomarkers (p = 0.01). No effect on accelerated muscle strength decline was seen according to number of dysregulated anabolic hormones., Conclusions: Having multiple elevated catabolic biomarkers is a better predictor of muscle strength decline than a single biomarker alone, suggesting that a catabolic dysregulation is at the core of the mechanism leading to muscle strength decline with aging.