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The role of inflammation, iron, and nutritional status in cancer-related anemia: results of a large, prospective, observational study.
Macciò, A, Madeddu, C, Gramignano, G, Mulas, C, Tanca, L, Cherchi, MC, Floris, C, Omoto, I, Barracca, A, Ganz, T
Haematologica. 2015;(1):124-32
Abstract
Anemia in oncology patients is often considered a side effect of cancer therapy; however, it may occur before any antineoplastic treatment (cancer-related anemia). This study was aimed to evaluate the prevalence of cancer-related anemia in a large cohort of oncology patients and whether inflammation and malnutrition were predictive of its development and severity. The present study included 888 patients with cancer at different sites between May 2011 and January 2014. Patients were assessed at diagnosis before any cancer treatment. The prevalence of anemia according to the main clinical factors (tumor site, stage and performance status) was analyzed. In each patient markers of inflammation, iron metabolism, malnutrition and oxidative stress as well as the modified Glasgow prognostic score, a combined index of malnutrition and inflammation, were assessed and their role in predicting hemoglobin level was evaluated. The percentage of anemic patients was 63% with the lowest hemoglobin levels being found in the patients with most advanced cancer and compromised performance status. Hemoglobin concentration differed by tumor site and was lowest in patients with ovarian cancer. Hemoglobin concentration was inversely correlated with inflammatory markers, hepcidin, ferritin, erythropoietin and reactive oxygen species, and positively correlated with leptin, albumin, cholesterol and antioxidant enzymes. In multivariate analysis, stage, interleukin-6 and leptin were independent predictors of hemoglobin concentration. Furthermore, hemoglobin was inversely dependent on modified Glasgow Prognostic Score. In conclusion, cancer-related anemia is a multifactorial problem with immune, nutritional and metabolic components that affect its severity. Only a detailed assessment of the pathogenesis of cancer-related anemia may enable clinicians to provide safe and effective individualized treatment.
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Changes in Inflammation and Immune Activation With Atazanavir-, Raltegravir-, Darunavir-Based Initial Antiviral Therapy: ACTG 5260s.
Kelesidis, T, Tran, TT, Stein, JH, Brown, TT, Moser, C, Ribaudo, HJ, Dube, MP, Murphy, R, Yang, OO, Currier, JS, et al
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2015;(4):651-60
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Abstract
BACKGROUND It is unclear whether the integrase inhibitor raltegravir (RAL) reduces inflammation and immune activation compared with ritonavir-boosted protease inhibitors (PIs). METHODS In a prospective, randomized, multicenter clinical trial that included 328 human immunodeficiency type 1 (HIV-1)-infected, treatment-naive participants were randomized to receive tenofovir disoproxil fumarate-emtricitabine (TDF/FTC) plus atazanavir/ritonavir (ATV/r), darunavir/ritonavir (DRV/r), or RAL. A total of 234 participants (71%) with HIV-1 RNA levels <50 copies/mL by week 24 were included. Plasma biomarkers of inflammation and coagulation that were analysed included high-sensitivity C-reactive protein, interleukin-6 (IL-6), GlycA, D-dimer, soluble CD14 (sCD14), sCD163, and sIL-2r; blood cellular markers included %CD38+DR+ of T-cell subsets and %CD14+CD16+ and%CD14(dim)CD16+ monocyte subsets. Changes from baseline were examined at earlier (24 or 48 weeks) and later (96 weeks) time points, with 95% confidence intervals on fold-change. Pairwise treatment groups were compared using Wilcoxon rank sum tests, with P values adjusted for false discovery rate control. RESULTS Changes in biomarkers varied by regimen during the 96 weeks of follow-up as follows: hsCRP declined with ATV/r and RAL, IL-6 declined only with RAL, and GLycA decreased in all groups. D-dimer declined with ATV/r and DRV/r and was unchanged with RAL. Markers of T-cell activation and sCD163 (but not sCD14 and CD14-+CD16+) declined in all groups. CONCLUSIONS Despite some differences in specific markers of inflammation and immune activation between the antiretroviral therapy (ART) regimens, we found no consistent evidence that the reduction of inflammation and immune activation with ART initiation was different between RAL and PI-based regimens. CLINICAL TRIALS REGISTRATION NCT00811954 and NCT00851799.
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Substitution of standard soybean oil with olive oil-based lipid emulsion in parenteral nutrition: comparison of vascular, metabolic, and inflammatory effects.
Siqueira, J, Smiley, D, Newton, C, Le, NA, Gosmanov, AR, Spiegelman, R, Peng, L, Osteen, SJ, Jones, DP, Quyyumi, AA, et al
The Journal of clinical endocrinology and metabolism. 2011;(10):3207-16
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CONTEXT Soybean oil-based lipid emulsions are the only Food and Drug Administration-approved lipid formulation for clinical use in parenteral nutrition (PN). Recently concerns with its use have been raised due to the proinflammatory effects that may lead to increased complications because they are rich in ω-6 polyunsaturated fatty acids. METHODS This was a prospective, randomized, controlled, crossover study comparing the vascular, metabolic, immune, and inflammatory effects of 24-h infusion of PN containing soybean oil-based lipid emulsion (Intralipid), olive oil-based (ClinOleic), lipid free, and normal saline in 12 healthy subjects. RESULTS Soybean oil-PN increased systolic blood pressure compared with olive oil-PN (P < 0.05). Soybean oil PN reduced brachial artery flow-mediated dilatation from baseline (-23% at 4 h and -25% at 24 h, both P < 0.01); in contrast, olive oil PN, lipid free PN, and saline did not change either systolic blood pressure or flow-mediated dilatation. Compared with saline, soybean oil PN, olive oil PN, and lipid free PN similarly increased glucose and insulin concentrations during infusion (P < 0.05). There were no significant changes in plasma free fatty acids, lipid profile, inflammatory and oxidative stress markers, immune function parameters, or sympathetic activity between soybean oil- and olive oil-based lipid emulsions. CONCLUSION The 24-h infusion of PN containing soybean oil-based lipid emulsion increased blood pressure and impaired endothelial function compared with PN containing olive oil-based lipid emulsion and lipid-free PN in healthy subjects. These vascular changes may have significant implications in worsening outcome in subjects receiving nutrition support. Randomized controlled trials with relevant clinical outcome measures are needed in patients receiving PN with olive oil-based and soybean oil-based lipid emulsions.
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Adult subjects with Prader-Willi syndrome show more low-grade systemic inflammation than matched obese subjects.
Caixàs, A, Giménez-Palop, O, Broch, M, Vilardell, C, Megía, A, Simón, I, Giménez-Pérez, G, Mauricio, D, Vendrell, J, Richart, C, et al
Journal of endocrinological investigation. 2008;(2):169-75
Abstract
AIM: Adult subjects with Prader-Willi syndrome (PWS) may show several conditions that are associated with an activation of innate immunity such as obesity, deficient GH secretion or hypogonadism. Our aim was to study whether obese adult PWS subjects show an additional low-grade systemic inflammation (LGSI) in relation to obese adult non-PWS subjects and lean healthy control subjects before and after a standardized liquid meal. METHODS Seven obese adult PWS subjects, 7 matched obese non-PWS subjects and 7 lean healthy control subjects were studied for 6 h from the administration of a standard liquid meal. RESULTS Compared to non-PWS, PWS subjects showed higher plasma concentrations of C-reactive protein (CRP) (p=0.030), complement component C3 (p=0.018), interleukin(IL)-18 (p=0.048), and IL-6 (p=0.041) that persisted post-prandially elevated for CRP (p<0.0001), C3 (p=0.015), and IL-18 (p=0.003). Tumor necrosis factor(TNF)-alpha did not differ between the 3 groups. These results were independent from IGF-I levels, homeostasis model assessment index, and body mass index (BMI). In male subjects with PWS, testosterone levels correlated to IL-18 (r=-0,646, p=0.041). CONCLUSIONS Compared to matched non-PWS subjects, the obese PWS subjects in this study showed an additional LGSI that persisted postprandially and was independent from BMI, insulin resistance, and deficient GH secretion. However, in PWS males, high IL-18 levels were related to low testosterone concentrations.
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Monocytes from type 2 diabetic patients have a pro-inflammatory profile. 1,25-Dihydroxyvitamin D(3) works as anti-inflammatory.
Giulietti, A, van Etten, E, Overbergh, L, Stoffels, K, Bouillon, R, Mathieu, C
Diabetes research and clinical practice. 2007;(1):47-57
Abstract
The exact factors contributing to the pathogenesis of type 2 diabetes remain elusive. Lately, it was suggested that inflammation and activation of the innate immune system could be linked to type 2 diabetes pathogenesis and also to the development of common diabetic complications, mainly atherosclerosis. The aim of this study was to investigate the role of monocytes in this sub-clinical inflammatory state and test 1,25-dihydroxyvitamin D(3), the active form of Vitamin D, as an anti-inflammatory agent. For this purpose, monocytes from type 2 diabetic patients were compared to monocytes from healthy controls and type 1 diabetic patients. The expression profile of inflammatory markers in freshly isolated and immune-stimulated monocytes was measured by quantitative real-time RT-PCR. Type 2 diabetic patients showed significantly higher expression levels of TNF-alpha, IL-6, IL-1, IL-8, COX-2, ICAM-1 and B7-1 compared to controls and type 1 diabetic patients. 1,25-Dihydroxyvitamin D(3) was able to down-regulate the expression of TNF-alpha, IL-6, IL-1, and IL-8, confirming its immunomodulatory properties. From these data we concluded that monocytes from type 2 diabetic patients have a pro-inflammatory profile. In addition, 1,25-dihydroxyvitamin D(3) was able to modulate inflammation in these monocytes.
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Alcohol inflammation and coronary heart disease.
Imhof, A, Koenig, W
Addiction biology. 2003;(3):271-7
Abstract
This overview summarizes the experimental and epidemiological evidence linking alcohol consumption and the immune system. It focuses on findings supporting the notion that moderate alcohol consumption exerts anti-inflammatory effects which may explain, at least in part, the reduced risk of coronary heart disease morbidity and mortality in these subjects. Alcohol consumption has been shown consistently to be associated with all-cause mortality in a J- or U-shaped manner. This is due primarily to reduced risk of coronary heart disease (CHD)mortality among moderate consumers of alcohol compared to abstainers and heavy drinkers. Several mechanisms have been suggested by which moderate alcohol consumption could lower risk of CHD. However, changes in lipids, such as increased HDL cholesterol and apolipoprotein Al or a favourable haemostatic profile, can only partly explain the beneficial effects. Recently, anti-inflammatory effects of moderate intake of alcohol have been considered as an additional possible explanation, as inflammation has a fundamental role in the initiation, progression and the thrombotic complications of atherosclerosis.