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Sökning: WFRF:(Andreasson I)

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1.
  • Elhai, Muriel, et al. (författare)
  • Outcomes of patients with systemic sclerosis treated with rituximab in contemporary practice: a prospective cohort study
  • 2019
  • Ingår i: Annals of the rheumatic diseases. - 1468-2060. ; 78:7, s. 979-987
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To assess the safety and efficacy of rituximab in systemic sclerosis (SSc) in clinical practice. Methods: We performed a prospective study including patients with SSc from the European Scleroderma Trials and Research (EUSTAR) network treated with rituximab and matched with untreated patients with SSc. The main outcomes measures were adverse events, skin fibrosis improvement, lung fibrosis worsening and steroids use among propensity score-matched patients treated or not with rituximab. Results: 254 patients were treated with rituximab, in 58% for lung and in 32% for skin involvement. After a median follow-up of 2 years, about 70% of the patients had no side effect. Comparison of treated patients with 9575 propensity-score matched patients showed that patients treated with rituximab were more likely to have skin fibrosis improvement (22.7 vs 14.03 events per 100 person-years; OR: 2.79 [1.47-5.32]; p=0.002). Treated patients did not have significantly different rates of decrease in forced vital capacity (FVC)>10% (OR: 1.03 [0.55-1.94]; p=0.93) nor in carbon monoxide diffusing capacity (DLCO) decrease. Patients having received rituximab were more prone to stop or decrease steroids (OR: 2.34 [1.56-3.53], p<0.0001). Patients treated concomitantly with mycophenolate mofetil had a trend for better outcomes as compared with patients receiving rituximab alone (delta FVC: 5.22 [0.83-9.62]; p=0.019 as compared with controls vs 3 [0.66-5.35]; p=0.012). Conclusion: Rituximab use was associated with a good safety profile in this large SSc-cohort. Significant change was observed on skin fibrosis, but not on lung. However, the limitation is the observational design. The potential stabilisation of lung fibrosis by rituximab has to be addressed by a randomised trial.
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2.
  • Lewczuk, Piotr, et al. (författare)
  • Cerebrospinal fluid and blood biomarkers for neurodegenerative dementias: An update of the Consensus of the Task Force on Biological Markers in Psychiatry of the World Federation of Societies of Biological Psychiatry.
  • 2018
  • Ingår i: The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry. - 1814-1412. ; 19:4, s. 244-328
  • Tidskriftsartikel (refereegranskat)abstract
    • In the 12 years since the publication of the first Consensus Paper of the WFSBP on biomarkers of neurodegenerative dementias, enormous advancement has taken place in the field, and the Task Force takes now the opportunity to extend and update the original paper. New concepts of Alzheimer's disease (AD) and the conceptual interactions between AD and dementia due to AD were developed, resulting in two sets for diagnostic/research criteria. Procedures for pre-analytical sample handling, biobanking, analyses and post-analytical interpretation of the results were intensively studied and optimised. A global quality control project was introduced to evaluate and monitor the inter-centre variability in measurements with the goal of harmonisation of results. Contexts of use and how to approach candidate biomarkers in biological specimens other than cerebrospinal fluid (CSF), e.g. blood, were precisely defined. Important development was achieved in neuroimaging techniques, including studies comparing amyloid-β positron emission tomography results to fluid-based modalities. Similarly, development in research laboratory technologies, such as ultra-sensitive methods, raises our hopes to further improve analytical and diagnostic accuracy of classic and novel candidate biomarkers. Synergistically, advancement in clinical trials of anti-dementia therapies energises and motivates the efforts to find and optimise the most reliable early diagnostic modalities. Finally, the first studies were published addressing the potential of cost-effectiveness of the biomarkers-based diagnosis of neurodegenerative disorders.
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3.
  • Bos, I., et al. (författare)
  • Cerebrospinal fluid biomarkers of neurodegeneration, synaptic integrity, and astroglial activation across the clinical Alzheimer's disease spectrum
  • 2019
  • Ingår i: Alzheimers & Dementia. - 1552-5260. ; 15:5, s. 644-654
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: We investigated relations between amyloid-beta (A beta) status, apolipoprotein E (APOE) e4, and cognition, with cerebrospinal fluid markers of neurogranin (Ng), neurofilament light (NFL), YKL-40, and total tau (T-tau). Methods: We included 770 individuals with normal cognition, mild cognitive impairment, and Alzheimer's disease (AD)-type dementia from the EMIF-AD Multimodal Biomarker Discovery study. We tested the association of Ng, NFL, YKL-40, and T-tau with A beta status (Ab beta- vs. A beta+), clinical diagnosis APOE epsilon 4 carriership, baseline cognition, and change in cognition. Results: Ng and T-tau distinguished between A beta+ from A beta- individuals in each clinical group, whereas NFL and YKL-40 were associated with A beta+ in nondemented individuals only. APOE epsilon 4 carriership did not influence NFL, Ng, and YKL-40 in A beta+ individuals. NFL was the best predictor of cognitive decline in A beta+ individuals across the cognitive spectrum. Discussion: Axonal degeneration, synaptic dysfunction, astroglial activation, and altered tau metabolism are involved already in preclinical AD. NFL may be a useful prognostic marker. (C) 2019 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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6.
  • Hansson, Sarah, 1976-, et al. (författare)
  • Reduced levels of amyloid-beta-binding proteins in cerebrospinal fluid from Alzheimer's disease patients.
  • 2009
  • Ingår i: Journal of Alzheimer's disease : JAD. - 1387-2877. ; 16:2, s. 389-97
  • Tidskriftsartikel (refereegranskat)abstract
    • Amyloid-beta(Abeta) aggregation is a major hallmark of Alzheimer's disease (AD). Previous studies have suggested that only unbound Abeta can take part in the aggregation process. Therefore, endogenous Abeta-binding proteins may have an important role in preventing AD. Here, we analyzed cerebrospinal fluid (CSF) samples from 35 subjects with AD, 18 subjects with frontotemporal dementia (FTD) and 29 non-demented controls to test if reduced Abeta-binding capacity in CSF is a specific feature of AD. A panel of known Abeta-binding CSF proteins, including beta-trace/prostaglandin D2 synthase (beta-trace), transthyretin (TTR), cystatin C (CysC) and alpha(1)-antitrypsin (AAT), were quantified and related to diagnosis and CSF levels of Abeta(1-38), Abeta(1-40) and Abeta(1-42). AD patients displayed a mild reduction in the CSF levels of beta-trace (p=0.020), CysC (p=0.017), AAT (p=0.019) and TTR (p=0.012) compared with controls. While the reductions in AAT and TTR were AD-specific, the levels of beta-trace and CysC were also reduced in FTD. As expected, CSF Abeta(1-42) was reduced in AD compared with controls (p=0.00005) and with FTD patients (p=0.015). Positive correlations between Abeta(1-42) and beta-trace, CysC and TTR, respectively, were seen only in the AD group, suggesting that deficient Abeta-binding capacity in CSF may contribute to the amyloidogenic process in AD.
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7.
  • Kern, Silke, et al. (författare)
  • Prevalence of preclinical Alzheimer disease Comparison of current classification systems
  • 2018
  • Ingår i: Neurology. - 0028-3878. ; 90:19, s. E1682-E1691
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To determine the prevalence of preclinical Alzheimer disease (AD) according to current classification systems by examining CSF from a representative general population sample of 70-year-olds from Gothenburg, Sweden. The sample was derived from the population-based H70 Gothenburg Birth Cohort Studies in Gothenburg, Sweden. The participants (n = 322, age 70 years) underwent comprehensive neuropsychiatric, cognitive, and somatic examinations. CSF levels of beta-amyloid (A beta)(42), A beta(40), total tau, and phosphorylated tau were measured. Preclinical AD was classified according to criteria of the A/T/N system, Dubois 2016, National Institute on Aging-Alzheimer's Association (NIA-AA) criteria, and International Working Group-2 (IWG-2) criteria. Individuals with Clinical Dementia Rating score > 0 were excluded, leaving 259 cognitively unimpaired individuals. The prevalence of amyloid pathology was 22.8%, of total tau pathology was 33.2%, and of phosphorylated tau pathology was 6.9%. With the A/T/N system, the prevalence of A+/T-/N- was 13.1%, A+/T-/N+ was 7.3%, A+/T+/N+ was 2.3%, A-/T-/N+ was 18.9%, and A-/T+/N+ was 4.6%. When the Dubois criteria were applied, the prevalence of asymptomatic at risk for AD was 36.7% and of preclinical AD was 9.7%. With the NIA-AA criteria, the prevalence of stage 1 was 13.1% and stage 2 was 9.7%. With the IWG-2 criteria, the prevalence of asymptomatic at risk for AD was 9.7%. The APOE epsilon 4 allele was associated with several of the categories. Men more often had total tau pathology, A+/T-/N+, preclinical AD according to Dubois 2016, asymptomatic at risk for AD according to the IWG-2 criteria, and NIA-AA stage 2. The prevalence of pathologic AD markers was very common (46%) in a representative population sample of 70-year-olds. The clinical implications of these findings need to be scrutinized further in longitudinal studies.
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8.
  • Källström, Eva, et al. (författare)
  • Decreased frequency of intracellular IFN-gamma producing T cells in whole blood preparations from patients with atopic dermatitis.
  • 2002
  • Ingår i: Experimental Dermatology. - Wiley-Blackwell. - 0906-6705. ; 11:6, s. 556-563
  • Tidskriftsartikel (refereegranskat)abstract
    • There have been contradictory reports on the shift in the T-cell cytokine expression pattern of peripheral blood mononuclear cells from patients with atopic dermatitis (AD); more specifically the interleukin (IL)-4 and interferon (IFN)-gamma profiles. The aim of this study was to shed further light on this contradiction by measuring the intracellular cytokines IL-4 and IFN-gamma by flow cytometry on unseparated whole blood to obtain results that, as accurately as possible, reflect the situation in circulating cells in vivo. The patient group including 64 patients with AD was compared with 18 nonatopic healthy adults. The results showed that the percentage of CD4+ T cells expressing IFN-gamma was significantly decreased (P <= 0.001), as well as the percentage expressing IL-4 (P < 0.05) in AD patients compared with healthy controls. Furthermore, in supernatants from whole blood samples stimulated with phorbol 12-myristate 13-acetate and ionomycin, production of IFN-gamma was significantly decreased, while IL-4 production remained unchanged in AD patients compared with healthy controls. We also investigated if there was a relationship between serum IgE level and Phadiatop®, a screening test for atopy, vs. the levels of IL-4 and IFN-gamma , but found no correlation with either. However, there was a significant correlation between disease severity and the level of total IgE (r = 0.67, P < 0.05). In conclusion, our results support the evidence for a decreased ability of peripheral CD4+ T cells to produce IFN-gamma among AD patients.
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