Background: Patients and clinicians report pain and fatigue as key outcome measures in rheumatoid arthritis. Fatigue and pain are a major concern to patients. Aim: The objective of this study was to ...examine fatigue and pain in adult patients with rheumatoid arthritis (RA) and to investigate the association between pain and fatigue with body awareness, demographic, disease-related, emotional and psychosocial factors. Method: Data were collected from a sample of patients with RA (n= 120) recruited from a Rheumatology clinic in a large university hospital in Stockholm, Sweden. Eligible for inclusion were patients between 20 -80 years of age and with a confirmed diagnosis of RA. Fatigue was measured using the Multidimensional Assessment of Fatigue (MAF) scale, while the Visual Analogue Scale (VAS) was used to assess components of pain. A multiple stepwise regression analysis was performed to evaluate factors related to fatigue and pain. In the first step a univariate analysis of variance (ANOVA) was used for all relevant independent factors. In the next step backwards stepwise regression was applied. Result: Fatigue was significantly associated with the Disease Activity Score 28-joints (DAS 28) (p = 0.049), the Body Awareness Questionnaire (BAQ) (p = 0.006), the Positive Affect (PA) scale (p = 0.008) and no smoking (p = 0.021). Pain was significantly associated with the EuroQol EQ-5D (p = 0.008) and the DAS 28 (p = 0.001). The adjusted R-square was 28.6% for fatigue and 50.0% for pain. Conclusion: This study clearly demonstrates that fatigue and pain in patients with RA appear to be associated with disease-related factors. Furthermore, fatigue was related to body awareness and emotional factors, and pain was related to health related quality of life.
Hemangioblastomas of the central nervous system are a prominent feature of von Hippel-Lindau-disease (vHL). Hemangioblastomas are known to secrete vascular endothelial growth factor (VEGF), ...suggesting a potential role of VEGF as a biomarker for tumor growth.
Plasma VEGF samples from 24 patients with von Hippel-Lindau disease were analyzed by solid-phase proximity ligation assay (PLA). Levels were monitored over time together with numeric and volumetric CNS tumor burden, and compared to plasma VEGF levels in healthy controls.
The mean yearly progression in tumor volume was 65.5%. Yearly risk of developing one or several new CNS tumor(s) was 50%. No significant correlation between tumor burden and levels of VEGF was seen. VEGF levels in patients (31.55-92.04; mean 55.83, median 56.41) as measured by immunodetection in a solid-phase PLA did not differ significantly from controls (37.38-104.56; mean 58.89, median 54.12) (p = 0,266).
The increase in total CNS tumor volume in vHL occurred in a saltatory manner. The risk of developing a new lesion was 50% per year. We found no evidence for VEGF secretion from CNS hemangioblastomas in vHL in circulating blood. Other potential biomarkers should be explored to assess progression of tumor burden in vHL.
BackgroundHemangioblastomas of the central nervous system are a prominent feature of von Hippel-Lindau-disease (vHL). Hemangioblastomas are known to secrete vascular endothelial growth factor (VEGF), ...suggesting a potential role of VEGF as a biomarker for tumor growth.MethodsPlasma VEGF samples from 24 patients with von Hippel-Lindau disease were analyzed by solid-phase proximity ligation assay (PLA). Levels were monitored over time together with numeric and volumetric CNS tumor burden, and compared to plasma VEGF levels in healthy controls.ResultsThe mean yearly progression in tumor volume was 65.5%. Yearly risk of developing one or several new CNS tumor(s) was 50%. No significant correlation between tumor burden and levels of VEGF was seen. VEGF levels in patients (31.55-92.04; mean 55.83, median 56.41) as measured by immunodetection in a solid-phase PLA did not differ significantly from controls (37.38-104.56; mean 58.89, median 54.12) (p = 0,266).ConclusionThe increase in total CNS tumor volume in vHL occurred in a saltatory manner. The risk of developing a new lesion was 50% per year. We found no evidence for VEGF secretion from CNS hemangioblastomas in vHL in circulating blood. Other potential biomarkers should be explored to assess progression of tumor burden in vHL.
is a major cause of skin and soft tissue infection. The bacterium expresses four major proteases that are emerging as virulence factors: aureolysin (Aur), V8 protease (SspA), staphopain A (ScpA), and ...staphopain B (SspB). We hypothesized that human galectin-3, a β-galactoside-binding lectin involved in immune regulation and antimicrobial defense, is a target for these proteases and that proteolysis of galectin-3 is a novel immune evasion mechanism. Indeed, supernatants from laboratory strains and clinical isolates of
caused galectin-3 degradation. Similar proteolytic capacities were found in
isolates but not in
Galectin-3-induced activation of the neutrophil NADPH oxidase was abrogated by bacterium-derived proteolysis of galectin-3, and SspB was identified as the major protease responsible. The impact of galectin-3 and protease expression on
virulence was studied in a murine skin infection model. In galectin-3
mice, SspB-expressing
caused larger lesions and resulted in higher bacterial loads than protease-lacking bacteria. No such difference in bacterial load or lesion size was detected in galectin-3
mice, which overall showed smaller lesion sizes than the galectin-3
animals. In conclusion, the staphylococcal protease SspB inactivates galectin-3, abrogating its stimulation of oxygen radical production in human neutrophils and increasing tissue damage during skin infection.
Interleukin-1 receptor antagonist (IL-1Ra) is the primary therapy against autoinflammatory syndromes with robust efficacy in reducing systemic inflammation and associated organ injury. However, ...patients receiving IL-1Ra might be at increased risk of acquiring serious infections.
To study whether IL-1Ra treatment deteriorates Staphylococcus aureus (S. aureus) septic arthritis and sepsis in mice.
NMRI mice were treated with anakinra (IL-1Ra) daily for 7 days before intravenous inoculation with S. aureus strain Newman in both arthritogenic and lethal doses. The clinical course of septic arthritis, histopathological and radiological changes of the joints, as well as the mortality were compared between IL-1Ra treated and control groups.
IL-1Ra treated mice developed more frequent and severe clinical septic arthritis. Also, the frequency of polyarthritis was significantly higher in the mice receiving IL-1Ra therapy. In line with the data from clinical arthritis, both histological and radiological signs of septic arthritis were more pronounced in IL-1Ra treated group compared to controls. Importantly, the mortality of IL-1Ra treated mice was significantly higher than PBS treated controls.
IL-1Ra treatment significantly aggravated S. aureus induced septic arthritis and increased the mortality in these mice.
We aimed to assess the feasibility of a simple new fifteen-item FFQ as a tool for screening risk of poor dietary patterns in a healthy middle-aged population and to investigate how the results of the ...FFQ correlated with cardiovascular risk factors and socio-economic factors.
A randomized population-based cross-sectional study. Metabolic measurements for cardiovascular risk factors and information about lifestyle were collected. A fifteen-item FFQ was created to obtain information about dietary patterns. From the FFQ, a healthy eating index was created with three dietary groups: good, average and poor. Multivariate logistic regression was used to assess relationships between dietary patterns and cardiovascular risk factors.
Sweden.
Men and women aged 50 years and living in Gothenburg, Sweden.
In total, 521 middle-aged adults (257 men, 264 women) were examined. With good dietary pattern as the reference, there was a gradient association of having obesity, hypertension and high serum TAG in those with average and poor dietary patterns. After adjustment for education and lifestyle factors, individuals with a poor dietary pattern still had significantly higher risk (OR; 95 % CI) of obesity (2·33; 1·10, 4·94), hypertension (2·73; 1·44, 5·20) and high serum TAG (2·62; 1·33, 5·14) compared with those with a good dietary pattern.
Baseline data collected by a short FFQ can predict cardiovascular risk factors in middle-aged Swedish men and women. The FFQ could be a useful tool in health-care settings, when screening for risk of poor dietary patterns.
Background. The development of biologies has greatly increased the quality of life and the life expectancy of many patients with rheumatoid arthritis. However, a large number of these patients have ...an increased risk of developing serious infections. The aim of this study was to examine differential effects of anti-tumor necrosis factor (TNF) treatment and CTLA4 immunoglobulin (Ig) treatment on both immunological response and host defense in a murine model of septic arthritis. Methods. Abatacept (CTLA4-Ig), etanercept (anti-TNF), or phosphate-buffered saline were given to NMRI mice intravenously inoculated with Staphylococcus aureus. The clinical course of septic arthritis and histopathological and radiological changes of joints were compared among the groups. Results. Mice receiving CTLA4-Ig treatment had more-severe septic arthritis, compared with controls and mice receiving anti-TNF treatment. Anti-TNF treatment led to more-severe weight loss and kidney abscesses, as well as a higher bacterial burden in the kidneys. Mice receiving CTLA4-Ig therapy had lower serum levels of interleukin 4, whereas mice receiving anti-TNF therapy had higher levels of TNF-α. Both iNOS and arginase-1 expression were reduced in peritoneal macrophages from mice receiving CTLA4-Ig, compared with expression in the anti-TNF group. Conclusions. CTLA4-Ig therapy significantly increased the susceptibility to S. aureus septic arthritis in mice, whereas anti-TNF therapy deteriorated host bacterial clearance, resulting in more-severe weight loss and kidney abscesses.
The development of biologics has greatly increased the quality of life as well as the life expectancy of many RA patients. However, a large number of these patients are at an increased risk of ...developing serious infections. The aim of this study was to examine differential effects of anti-TNF versus CTLA4-Ig treatment on both immunological response and host defense in a murine model of septic arthritis.
Background Interleukin-1 receptor antagonist (IL-1Ra) is the primary therapy against autoinflammatory syndromes with robust efficacy in reducing systemic inflammation and associated organ injury. ...However, patients receiving IL-1Ra might be at increased risk of acquiring serious infections. Aims To study whether IL-1Ra treatment deteriorates Staphylococcus aureus (S. aureus) septic arthritis and sepsis in mice. Method NMRI mice were treated with anakinra (IL-1Ra) daily for 7 days before intravenous inoculation with S. aureus strain Newman in both arthritogenic and lethal doses. The clinical course of septic arthritis, histopathological and radiological changes of the joints, as well as the mortality were compared between IL-1Ra treated and control groups. Results IL-1Ra treated mice developed more frequent and severe clinical septic arthritis. Also, the frequency of polyarthritis was significantly higher in the mice receiving IL-1Ra therapy. In line with the data from clinical arthritis, both histological and radiological signs of septic arthritis were more pronounced in IL-1Ra treated group compared to controls. Importantly, the mortality of IL-1Ra treated mice was significantly higher than PBS treated controls. Conclusion IL-1Ra treatment significantly aggravated S. aureus induced septic arthritis and increased the mortality in these mice.
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