| 1. |
- Bottai, Matteo, et al.
(författare)
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EULAR/ACR classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups : a methodology report
- 2017
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Ingår i: RMD Open. - : BMJ. - 2056-5933. ; 3:2
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Tidskriftsartikel (refereegranskat)abstract
- Objective To describe the methodology used to develop new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIMs) and their major subgroups.Methods An international, multidisciplinary group of myositis experts produced a set of 93 potentially relevant variables to be tested for inclusion in the criteria. Rheumatology, dermatology, neurology and paediatric clinics worldwide collected data on 976 IIM cases (74% adults, 26% children) and 624 non-IIM comparator cases with mimicking conditions (82% adults, 18% children). The participating clinicians classified each case as IIM or non-IIM. Generally, the classification of any given patient was based on few variables, leaving remaining variables unmeasured. We investigated the strength of the association between all variables and between these and the disease status as determined by the physician. We considered three approaches: (1) a probability-score approach, (2) a sum-of-items approach criteria and (3) a classification-tree approach.Results The approaches yielded several candidate models that were scrutinised with respect to statistical performance and clinical relevance. The probability-score approach showed superior statistical performance and clinical practicability and was therefore preferred over the others. We developed a classification tree for subclassification of patients with IIM. A calculator for electronic devices, such as computers and smartphones, facilitates the use of the European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria.Conclusions The new EULAR/ACR classification criteria provide a patient's probability of having IIM for use in clinical and research settings. The probability is based on a score obtained by summing the weights associated with a set of criteria items.
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| 2. |
- Brook, Adam, et al.
(författare)
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Cell free hemoglobin in the fetoplacental circulation : A novel cause of fetal growth restriction?
- 2018
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Ingår i: FASEB Journal. - 0892-6638. ; 32:10, s. 5436-5446
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Tidskriftsartikel (refereegranskat)abstract
- Cell free hemoglobin impairs vascular function and blood flow in adult cardiovascular disease. In this study, we investigated the hypothesis that free fetal hemoglobin (fHbF) compromises vascular integrity and function in the fetoplacental circulation, contributing to the increased vascular resistance associated with fetal growth restriction (FGR). Women with normal and FGR pregnancies were recruited and their placentas collected freshly postpartum. FGRfetal capillaries showed evidence of erythrocyte vascular packing and extravasation. Fetal cord blood fHbF levels were higher in FGR than in normal pregnancies (P < 0.05) and the elevation of fHbF in relation to heme oxygenase-1 suggests a failure of expected catabolic compensation,which occurs in adults.During ex vivo placental perfusion, pathophysiological fHbF concentrations significantly increased fetal-side microcirculatory resistance (P<0.05). fHbF sequesteredNOinacute andchronic exposuremodels (P<0.001), andfHbF-primed placental endothelial cellsdevelopedaproinflammatoryphenotype,demonstratedby activationofNF-κBpathway, generation of IL-1α and TNF-α (both P < 0.05), uncontrolled angiogenesis, and disruption of endothelial cell flow alignment. Elevated fHbF contributes to increased fetoplacental vascular resistance and impaired endothelial protection.Thisunrecognizedmechanismfor fetal compromise offers a novel insight into FGRaswell as a potential explanation for associated poor fetal outcomes such as fetal demise and stillbirth.
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| 3. |
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| 4. |
- Kobelt, Gisela, et al.
(författare)
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Cost-effectiveness of etanercept treatment in early active rheumatoid arthritis followed by dose adjustment.
- 2011
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Ingår i: International Journal of Technology Assessment in Health Care. - 1471-6348. ; 27:3, s. 193-200
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To explore the cost-effectiveness of early biologic treatment, followed by dose-reduction in the case of remission, of active rheumatoid arthritis (RA), compared with standard treatment with methotrexate (MTX) in Sweden.Methods: Effectiveness (function, disease activity, erosions) in early RA for both alternatives was taken from a clinical trial comparing etanercept (ETA) combined with MTX to MTX alone. Patients discontinuing treatment can switch to another or their first biologic treatment. For patients in remission (Disease Activity Score [DAS28] < 2.6), ETA is reduced to half the dose. Return to full dose occurs when DAS28 reaches ≥ 3.2 again. Costs and utilities by level of functional capacity from an observational study are used. The model is analyzed as a micro-simulation and results are presented from the societal perspective for Sweden, for 10 years; costs (€2008) and effects are discounted at 3 percent. Sensitivity analysis was performed for the perspective, the time horizon, switching, and dose-reduction.Results: The main analysis conservatively assumes 50 percent switching at discontinuation. The cost per quality-adjusted life-year (QALY) gained with early ETA/MTX treatment is €13,500 (societal perspective, incremental cost of €15,500 and incremental QALYs of 1.15). With 75 percent switching, the cost per QALY gained was €10,400. Over 20 years, the cost per QALY gained was €8,200. Results were further sensitive to the time patients remained on half dose and the perspective.Conclusions and Policy Implications: This study combines clinical trial and clinical practice data to explore cost-effective treatment scenarios in early RA, including the use of biologics. Our results indicate that a situation where a considerable proportion of patients achieve remission, dose-adjustments will increase the cost-effectiveness of treatment.
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| 5. |
- Kreimer, Aimee R., et al.
(författare)
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Human Papillomavirus Antibodies and Future Risk of Anogenital Cancer : A Nested Case-Control Study in the European Prospective Investigation Into Cancer and Nutrition Study
- 2015
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Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 33:8, s. 877-884
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Human papillomavirus (HPV) type 16 (HPV16) causes cancer at several anatomic sites. In the European Prospective Investigation Into Cancer and Nutrition study, HPV16 E6 seropositivity was present more than 10 years before oropharyngeal cancer diagnosis and was nearly absent in controls. The current study sought to evaluate the extent to which HPV16 E6 antibodies are present before diagnosis of anogenital cancers within the same cohort. Methods Four hundred incident anogenital cancers (273 cervical, 24 anal, 67 vulvar, 12 vaginal, and 24 penile cancers) with prediagnostic blood samples (collected on average 3 and 8 years before diagnosis for cervix and noncervix cancers, respectively) and 718 matched controls were included. Plasma was analyzed for antibodies against HPV16 E6 and multiple other HPV proteins and genotypes and evaluated in relation to risk using unconditional logistic regression. Results HPV16 E6 seropositivity was present in 29.2% of individuals (seven of 24 individuals) who later developed anal cancer compared with 0.6% of controls (four of 718 controls) who remained cancer free (odds ratio [OR], 75.9; 95% CI, 17.9 to 321). HPV16 E6 seropositivity was less common for cancers of the cervix (3.3%), vagina (8.3%), vulva (1.5%), and penis (8.3%). No associations were seen for non-type 16 HPV E6 antibodies, apart from anti-HPV58 E6 and anal cancer (OR, 6.8; 95% CI, 1.4 to 33.1). HPV16 E6 seropositivity tended to increase in blood samples drawn closer in time to cancer diagnosis. Conclusion HPV16 E6 seropositivity is relatively common before diagnosis of anal cancer but rare for other HPV-related anogenital cancers.
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| 6. |
- König, Julia, 1983-, et al.
(författare)
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Amnion-derived mesenchymal stromal cells show a mesenchymal-epithelial phenotype in culture.
- 2014
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Ingår i: Cell and Tissue Banking. - Dordrecht : Springer Netherlands. - 1389-9333 .- 1573-6814. ; 15:2, s. 193-198
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Tidskriftsartikel (refereegranskat)abstract
- The amnionic membrane is a rich source of multipotent mesenchymal stromal cells (hAMSC), which are readily available and show a potential use in regenerative medicine and tissue engineering. Before these cells can be applied clinically, careful characterization is necessary, especially as primary cells are known to change their phenotype in culture. We analyzed the mesenchymal phenotype of hAMSC at different stages after isolation using immunohistochemistry. Shortly after isolation (1 day), 92 % (±7 %) of the hAMSC expressed the mesenchymal marker vimentin, 2 % (±1 %) stained for the epithelial marker cytokeratin-7 and 5 % (±4 %) co-expressed these markers. After 5 days, the double positive cells slightly increased to 7 % (±3 %), while exclusive expression of cytokeratin-7 or vimentin remained unchanged (1 % ± 2 % and 92 % ± 1 %, respectively). After the first passage, all attached cells were vimentin-positive, while 54 % (±9 %) co-expressed cytokeratin-7 and vimentin. Thus, we conclude that under culture, hAMSC adopt a hybrid mesenchymal-epithelial phenotype. It is also essential to perform microscopical examination during the first days after isolation to detect contaminations with human amnion-derived epithelial cells in cultures of hAMSC.
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| 7. |
- König, Julia, 1983-, et al.
(författare)
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Amnion-derived mesenchymal stromal cells show angiogenic properties but resist differentiation into mature endothelial cells
- 2012
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Ingår i: Stem Cells and Development. - Rochelle, USA : Mary Ann Liebert. - 1547-3287 .- 1557-8534. ; 21:8, s. 1309-1320
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Tidskriftsartikel (refereegranskat)abstract
- Mesenchymal stromal cells derived from the human amnion (hAMSC) currently play an important role in stem cell research, as they are multipotent cells that can be isolated using noninvasive methods and are immunologically tolerated in vivo. The objective of this study was to evaluate their endothelial differentiation potential with regard to a possible therapeutic use in vascular diseases. hAMSC were isolated from human term placentas and cultured in Dulbecco's modified Eagle's medium (DMEM) (non-induced hAMSC) or endothelial growth medium (EGM-2) (induced hAMSC). Induced hAMSC changed their fibroblast-like toward an endothelial-like morphology, and were able to take up acetylated low-density lipoprotein and form endothelial-like networks in the Matrigel assay. However, they did not express the mature endothelial cell markers von Willebrand factor and vascular endothelial-cadherin. Gene expression analysis revealed that induced hAMSC significantly downregulated pro-angiogenic genes such as tenascin C, Tie-2, vascular endothelial growth factor A (VEGF-A), CD146, and fibroblast growth factor 2 (FGF-2), whereas they significantly upregulated anti-angiogenic genes such as serpinF1, sprouty1, and angioarrestin. Analysis of protein expression confirmed the downregulation of FGF-2 and Tie-2 (27%±8% and 13%±1% of non-induced cells, respectively) and upregulation of the anti-angiogenic protein endostatin (226%±4%). Conditioned media collected from hAMSC enhanced viability of endothelial cells and had a stabilizing effect on endothelial network formation as shown by lactate dehydrogenase and Matrigel assay, respectively. In summary, endothelial induced hAMSC acquired some angiogenic properties but resisted undergoing a complete differentiation into mature endothelial cells by upregulation of anti-angiogenic factors. Nevertheless, they had a survival-enhancing effect on endothelial cells that might be useful in a variety of cell therapy or tissue-engineering approaches.
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| 8. |
- König, Julia, et al.
(författare)
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Placental Mesenchymal Stromal Cells Derived from Blood Vessels or Avascular Tissues : What Is the Better Choice to Support Endothelial Cell Function?
- 2014
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Ingår i: Stem Cells and Development. - : Mary Ann Liebert Inc. - 1547-3287 .- 1557-8534. ; 24:1, s. 115-131
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Tidskriftsartikel (refereegranskat)abstract
- Mesenchymal stromal cells (MSCs) are promising tools for therapeutic revascularization of ischemic tissues and for support of vessel formation in engineered tissue constructs. Recently, we could show that avascular-derived MSCs from placental amnion release soluble factors that exhibit survival-enhancing effects on endothelial cells (ECs). We hypothesize that MSCs derived from placental blood vessels might have even more potent angiogenic effects. Therefore, we isolated and characterized MSCs from placental chorionic blood vessels (bv-MSCs) and tested their angiogenic potential in comparison to amnion-derived avascular MSCs (av-MSCs). bv-MSCs express a very similar surface marker profile compared with av-MSCs and could be differentiated toward the adipogenic and osteogenic lineages. bv-MSCs exert immunosuppressive properties on peripheral blood mononuclear cells, suggesting that they are suitable for cell transplantation settings. Conditioned medium (Cdm) from av-MSCs and bv-MSCs significantly enhanced EC viability, whereas only Cdm from bv-MSCs significantly increased EC migration and network formation (Matrigel assay). Angiogenesis array analysis of av- and bv-MSC-Cdm revealed a similar secretion pattern of angiogenic factors, including angiogenin, interleukins-6 and -8, and tissue inhibitors of matrix metalloproteinase-1 and 2. Enzyme-linked immunosorbent assay analysis showed that, in contrast to av-MSCs, bv-MSCs secreted vascular endothelial growth factor. In direct coculture with bv-MSCs, ECs showed a significantly increased formation of vessel-like structures compared with av-MSCs. With regard to therapeutic treatment, bv-MSCs and particularly their Cdm might be valuable to stimulate angiogenesis especially in ischemic tissues. av-MSCs and their Cdm could be beneficial in conditions when it is required to promote the survival and stabilization of blood vessels without the risk of unmeant angiogenesis.
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| 9. |
- Lang, Emma, et al.
(författare)
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Mentorsprojekt på BHS
- 2002
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 10. |
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