| 1. |
- de Peppo, Giuseppe Maria, 1981, et al.
(author)
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Human embryonic mesodermal progenitors highly resemble human mesenchymal stem cells and display high potential for tissue engineering applications.
- 2010
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In: Tissue engineering. Part A. - : Mary Ann Liebert Inc. - 1937-335X .- 1937-3341. ; 16:7, s. 2161-82
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Journal article (peer-reviewed)abstract
- Adult stem cells, such as human mesenchymal stem cells (hMSCs), show limited proliferative capacity and, after long-term culture, lose their differentiation capacity and are therefore not an optimal cell source for tissue engineering. Human embryonic stem cells (hESCs) constitute an important new resource in this field, but one major drawback is the risk of tumor formation in the recipients. One alternative is to use progenitor cells derived from hESCs that are more lineage restricted but do not form teratomas. We have recently derived a cell line from hESCs denoted hESC-derived mesodermal progenitors (hES-MPs), and here, using genome-wide microarray analysis, we report that the process of hES-MPs derivation results in a significantly altered expression of hESC characteristic genes to an expression level highly similar to that of hMSCs. However, hES-MPs displayed a significantly higher proliferative capacity and longer telomeres. The hES-MPs also displayed lower expression of HLA class II proteins before and after interferon-gamma treatment, indicating that these cells may somewhat be immunoprivileged and potentially used for HLA-incompatible transplantation. The hES-MPs are thus an appealing alternative to hMSCs in tissue engineering applications and stem-cell-based therapies for mesodermal tissues.
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| 2. |
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| 3. |
- Svensson, Sara, 1981, et al.
(author)
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Monocytes and pyrophosphate promote mesenchymal stem cell viability and early osteogenic differentiation
- 2022
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In: Journal of Materials Science-Materials in Medicine. - : Springer Science and Business Media LLC. - 0957-4530 .- 1573-4838. ; 33:1
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Journal article (peer-reviewed)abstract
- Pyrophosphate-containing calcium phosphate implants promote osteoinduction and bone regeneration. The role of pyrophosphate for inflammatory cell-mesenchymal stem cell (MSC) cross-talk during osteogenesis is not known. In the present work, the effects of lipopolysaccharide (LPS) and pyrophosphate (PPi) on primary human monocytes and on osteogenic gene expression in human adipose-derived MSCs were evaluated in vitro, using conditioned media transfer as well as direct effect systems. Direct exposure to pyrophosphate increased nonadherent monocyte survival (by 120% without LPS and 235% with LPS) and MSC viability (LDH) (by 16-19% with and without LPS). Conditioned media from LPS-primed monocytes significantly upregulated osteogenic genes (ALP and RUNX2) and downregulated adipogenic (PPAR-gamma) and chondrogenic (SOX9) genes in recipient MSCs. Moreover, the inclusion of PPi (250 mu M) resulted in a 1.2- to 2-fold significant downregulation of SOX9 in the recipient MSCs, irrespective of LPS stimulation or culture media type. These results indicate that conditioned media from LPS-stimulated inflammatory monocytes potentiates the early MSCs commitment towards the osteogenic lineage and that direct pyrophosphate exposure to MSCs can promote their viability and reduce their chondrogenic gene expression. These results are the first to show that pyrophosphate can act as a survival factor for both human MSCs and primary monocytes and can influence the early MSC gene expression.
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| 4. |
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| 5. |
- Atefyekta, Saba, 1987, et al.
(author)
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Antimicrobial Peptide-Functionalized Mesoporous Hydrogels
- 2021
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In: ACS Biomaterials Science & Engineering. - : American Chemical Society (ACS). - 2373-9878. ; 7:4, s. 1693-1702
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Journal article (peer-reviewed)abstract
- Antimicrobial peptides (AMPs) are seen as a promising replacement to conventional antibiotics for the prevention of skin wound infections. However, due to the short half-life of AMPs in biological environments, such as blood, their use in clinical applications has been limited. The covalent immobilization of AMPs onto suitable substrates is an effective solution to create contact-killing surfaces with increased long-term stability. In this work, an antimicrobial peptide, RRPRPRPRPWWWW-NH2 (RRP9W4N), was covalently attached to amphiphilic and ordered mesoporous Pluronic F127 hydrogels made of cross-linked lyotropic liquid crystals through 1-ethyl-3-(3-(dimethylamino)propyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS) chemistry. The AMP-hydrogels showed high antibacterial activity against Staphylococcus epidermidis, Staphylococcus aureus, Pseudomonas aeruginosa, methicillin-resistant S. aureus (MRSA), and multidrug-resistant Escherichia coli for up to 24 h. Furthermore, the AMP-hydrogels did not present any toxicity to human fibroblasts. The AMPs retained their antimicrobial activity up to 48 h in human blood serum, which is a significant increase in stability compared to when used in dissolved state. A pilot in vivo rat model showed 10-100x less viable counts of S. aureus on AMP-hydrogels compared with control hydrogels during the first 3 days of infection. Studies performed on human whole blood showed that blood coagulated more readily in the presence of AMP-hydrogels as compared to hydrogels without AMPs, indicating potential hemostatic activity. Overall, the results suggest that the combination of amphiphilic hydrogels with covalently bonded AMPs has potential to be used as antibacterial wound dressing material to reduce infections and promote hemostatic activity as an alternative to antibiotics or other antimicrobial agents, whose use should be restricted.
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| 9. |
- Broom, M., et al.
(author)
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Outcomes of adults with invasive meningococcal disease with reduced penicillin susceptibility in Auckland 2004-2017
- 2023
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In: Infection. - : Springer Science and Business Media LLC. - 0300-8126 .- 1439-0973. ; 51:2, s. 425-432
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Journal article (peer-reviewed)abstract
- Purpose The purpose of this study was to assess the clinical outcomes of adults with invasive meningococcal disease (IMD) and to compare the outcomes of patients with IMD caused by a penicillin susceptible isolate (minimum inhibitory concentration (MIC) <= 0.06 mg/L) with patients with IMD caused by an isolate with reduced penicillin susceptibility (MIC > 0.06 mg/L). We also assessed the outcomes of patients with IMD caused by an isolate with reduced penicillin susceptibility who were treated exclusively with intravenous (IV) benzylpenicillin. Methods Retrospective study of all culture positive IMD in adult patients (age >= 15 years) in the Auckland region from 2004 to 2017. Results One hundred and thirty-nine patients were included; 94 had penicillin susceptible isolates (88 cured, 6 died), and 45 had an isolate with reduced penicillin susceptibility (41 cured, 1 possible relapse, 3 died). The median benzylpenicillin/ceftriaxone treatment duration was 3 days for both groups. There was no difference in the patient outcomes of both groups. Eighteen patients with IMD caused by an isolate with reduced penicillin susceptibility received benzylpenicillin alone and were cured. Conclusions This study provides further support to existing data that has shown that short duration IV beta-lactam treatment is effective for IMD in adults. Only a small number of patients with meningitis caused by an isolate with reduced penicillin susceptibility received benzylpenicillin alone, limiting its evaluation. For Neisseria meningitidis meningitis, we recommend ceftriaxone as empiric treatment and as definitive treatment when this is caused by an isolate with reduced penicillin susceptibility.
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| 19. |
- Irenaeus, Sandra, et al.
(author)
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Local irradiation does not enhance the effect of immunostimulatory AdCD40L gene therapy combined with low dose cyclophosphamide in melanoma patients
- 2017
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In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 8:45, s. 78573-78587
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Journal article (peer-reviewed)abstract
- Background: AdCD40L is an immunostimulatory gene therapy under evaluation for advanced melanoma, including ocular melanoma. Herein, we present the final data of a Phase I/IIa trial using AdCD40L alone or in combination with low dose cyclophosphamide +/- radiation therapy.Methods: AdCD40L is a replication-deficient adenovirus carrying the gene for CD40 ligand (CD40L). Twenty-four patients with advanced melanoma were enrolled and treated with AdCD40L monotherapy, or combined with cyclophosphamide +/- single fraction radiotherapy. The patients were monitored for 10 weeks using immunological and radiological evaluations and thereafter for survival.Results: AdCD40L treatment was safe and well tolerated both alone and in combination with cyclophosphamide as well as local radiotherapy. Four out of twenty-four patients had >1 year survival. Addition of cyclophosphamide was beneficial but adding radiotherapy did not further extend survival. High initial plasma levels of IL12 and MIP3b correlated to overall survival, whereas IL8 responses post-treatment correlated negatively with survival. Interestingly, antibody reactions to the virus correlated negatively with post IL6 and pre IL1b levels in blood.Conclusions: AdCD40L was safely administered to patients and effect was improved by cyclophosphamide but not by radiotherapy. Immune activation profile at baseline may predict responders better than shortly after treatment.
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| 20. |
- Jacobson, Sara, et al.
(author)
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Hyperglycemia as a risk factor in pancreatic cancer : A nested case-control study using prediagnostic blood glucose levels
- 2021
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In: Pancreatology (Print). - : Elsevier. - 1424-3903 .- 1424-3911. ; 21:6, s. 1112-1118
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To determine the risk association between fasting glucose levels and pancreatic cancer using systematically collected prediagnostic blood glucose samples.METHODS: Prospective nested case-control study of participants from the Northern Sweden Health and Disease Study, including 182 cases that developed pancreatic cancer and four matched controls per case. Blood glucose levels collected up to 24 years before pancreatic cancer diagnosis were analyzed. The association between fasting glucose levels and pancreatic cancer risk was determined using unconditional and conditional logistic regression models. The association between fasting glucose and the time to pancreatic cancer diagnosis, tumor stage and survival was determined using likelihood-ratio test, t-test and log rank test.RESULTS: The unadjusted risk of developing pancreatic cancer increased with increasing fasting glucose levels (OR 1.30, 95% CI 1.05-1.60, P = .015). Impaired fasting glucose (≥6.1 mmol/L) was associated with an adjusted risk of 1.77 for developing pancreatic cancer (95% CI 1.05-2.99, P = .032). In subgroup analysis, fasting glucose levels were associated with an increased risk in never-smokers (OR 4.02, 95% CI 1.26-12.77, P = .018) and non-diabetics (OR 3.08, 95% CI 1.08-8.79, P = .035) (non-significant for interaction). The ratio between fasting glucose and BMI was higher among future pancreatic cancer patients and an increased ratio was associated with elevated risk of pancreatic cancer (OR 1.66, 95% CI 1.04-2.66, P = .034). Fasting glucose levels were not associated with TNM stage at diagnosis or survival.CONCLUSIONS: High fasting glucose is associated with an increased risk of being diagnosed with pancreatic cancer.
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| 21. |
- Joffrin, E., et al.
(author)
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Overview of the JET preparation for deuterium-tritium operation with the ITER like-wall
- 2019
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In: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 59:11
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Research review (peer-reviewed)abstract
- For the past several years, the JET scientific programme (Pamela et al 2007 Fusion Eng. Des. 82 590) has been engaged in a multi-campaign effort, including experiments in D, H and T, leading up to 2020 and the first experiments with 50%/50% D-T mixtures since 1997 and the first ever D-T plasmas with the ITER mix of plasma-facing component materials. For this purpose, a concerted physics and technology programme was launched with a view to prepare the D-T campaign (DTE2). This paper addresses the key elements developed by the JET programme directly contributing to the D-T preparation. This intense preparation includes the review of the physics basis for the D-T operational scenarios, including the fusion power predictions through first principle and integrated modelling, and the impact of isotopes in the operation and physics of D-T plasmas (thermal and particle transport, high confinement mode (H-mode) access, Be and W erosion, fuel recovery, etc). This effort also requires improving several aspects of plasma operation for DTE2, such as real time control schemes, heat load control, disruption avoidance and a mitigation system (including the installation of a new shattered pellet injector), novel ion cyclotron resonance heating schemes (such as the three-ions scheme), new diagnostics (neutron camera and spectrometer, active Alfven eigenmode antennas, neutral gauges, radiation hard imaging systems...) and the calibration of the JET neutron diagnostics at 14 MeV for accurate fusion power measurement. The active preparation of JET for the 2020 D-T campaign provides an incomparable source of information and a basis for the future D-T operation of ITER, and it is also foreseen that a large number of key physics issues will be addressed in support of burning plasmas.
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| 22. |
- Juhlin, Annika, et al.
(author)
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Staphylococcal biofilm gene expression on biomaterials - A methodological study
- 2017
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In: Journal of Biomedical Materials Research Part A. - : Wiley. - 1549-3296. ; 105:12, s. 3400-3412
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Journal article (peer-reviewed)abstract
- The combination of increased healthcare access, universal aging, and infallible therapy demands, synergistically drive the need for the development of biomaterial technologies that mitigate the challenge of biomaterial-associated infections (BAI). Staphylococcus epidermidis and Staphylococcus aureus account for the majority of BAI due to their ability to accumulate in adherent multilayered biofilm. This investigation details the development of gene expression assays to evaluate the genetic processes of attachment, accumulation, maturation, and dispersal phases of biofilms on biomaterials in vitro, while abiding by the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines. The biofilm formation of S. epidermidis on polyurethane (PU) central venous catheters and S. aureus on machined titanium (Ti) was examined in terms of gene expression at early and late time points. The results provided insight into how each stage of biofilm formation is orchestrated over time on these biomaterials in vitro. Furthermore, the results suggested that mechanical RNA extraction, organic solvents, elimination of genomic DNA, and preamplification are advisable strategies to implement for biofilm gene expression analysis. It is concluded that this method can be employed for the assessment of biofilm-biomaterial interactions at the molecular level. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3400-3412, 2017.
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| 23. |
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| 24. |
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| 25. |
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| 26. |
- Krasilnikov, A., et al.
(author)
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Evidence of 9 Be + p nuclear reactions during 2ω CH and hydrogen minority ICRH in JET-ILW hydrogen and deuterium plasmas
- 2018
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In: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 58:2
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Journal article (peer-reviewed)abstract
- The intensity of 9Be + p nuclear fusion reactions was experimentally studied during second harmonic (2ω CH) ion-cyclotron resonance heating (ICRH) and further analyzed during fundamental hydrogen minority ICRH of JET-ILW hydrogen and deuterium plasmas. In relatively low-density plasmas with a high ICRH power, a population of fast H+ ions was created and measured by neutral particle analyzers. Primary and secondary nuclear reaction products, due to 9Be + p interaction, were observed with fast ion loss detectors, γ-ray spectrometers and neutron flux monitors and spectrometers. The possibility of using 9Be(p, d)2α and 9Be(p, α)6Li nuclear reactions to create a population of fast alpha particles and study their behaviour in non-active stage of ITER operation is discussed in the paper.
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| 27. |
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| 29. |
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| 30. |
- Mahmoud, Sara, 1988-, et al.
(author)
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How to train a self-driving vehicle : On the added value (or lack thereof) of curriculum learning and replay buffers
- 2023
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In: Frontiers in Artificial Intelligence. - : Frontiers Media S.A.. - 2624-8212. ; 6
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Journal article (peer-reviewed)abstract
- Learning from only real-world collected data can be unrealistic and time consuming in many scenario. One alternative is to use synthetic data as learning environments to learn rare situations and replay buffers to speed up the learning. In this work, we examine the hypothesis of how the creation of the environment affects the training of reinforcement learning agent through auto-generated environment mechanisms. We take the autonomous vehicle as an application. We compare the effect of two approaches to generate training data for artificial cognitive agents. We consider the added value of curriculum learning—just as in human learning—as a way to structure novel training data that the agent has not seen before as well as that of using a replay buffer to train further on data the agent has seen before. In other words, the focus of this paper is on characteristics of the training data rather than on learning algorithms. We therefore use two tasks that are commonly trained early on in autonomous vehicle research: lane keeping and pedestrian avoidance. Our main results show that curriculum learning indeed offers an additional benefit over a vanilla reinforcement learning approach (using Deep-Q Learning), but the replay buffer actually has a detrimental effect in most (but not all) combinations of data generation approaches we considered here. The benefit of curriculum learning does depend on the existence of a well-defined difficulty metric with which various training scenarios can be ordered. In the lane-keeping task, we can define it as a function of the curvature of the road, in which the steeper and more occurring curves on the road, the more difficult it gets. Defining such a difficulty metric in other scenarios is not always trivial. In general, the results of this paper emphasize both the importance of considering data characterization, such as curriculum learning, and the importance of defining an appropriate metric for the task.
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| 31. |
- Mahmoud, Sara, 1988-, et al.
(author)
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Where to from here? : On the future development of autonomous vehicles from a cognitive systems perspective
- 2022
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In: Cognitive Systems Research. - : Elsevier. - 2214-4366 .- 1389-0417. ; 76, s. 63-77
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Journal article (peer-reviewed)abstract
- Self-driving cars not only solve the problem of navigating safely from location A to location B; they also have to deal with an abundance of (sometimes unpredictable) factors, such as traffic rules, weather conditions, and interactions with humans. Over the last decades, different approaches have been proposed to design intelligent driving systems for self-driving cars that can deal with an uncontrolled environment. Some of them are derived from computationalist paradigms, formulating mathematical models that define the driving agent, while other approaches take inspiration from biological cognition. However, despite the extensive work in the field of self-driving cars, many open questions remain. Here, we discuss the different approaches for implementing driving systems for self-driving cars, as well as the computational paradigms from which they originate. In doing so, we highlight two key messages: First, further progress in the field might depend on adapting new paradigms as opposed to pushing technical innovations in those currently used. Specifically, we discuss how paradigms from cognitive systems research can be a source of inspiration for further development in modeling driving systems, highlighting emergent approaches as a possible starting point. Second, self-driving cars can themselves be considered cognitive systems in a meaningful sense, and are therefore a relevant, yet underutilised resource in the study of cognitive mechanisms. Overall, we argue for a stronger synergy between the fields of cognitive systems and self-driving vehicles.
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| 32. |
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| 33. |
- Murari, A., et al.
(author)
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A control oriented strategy of disruption prediction to avoid the configuration collapse of tokamak reactors
- 2024
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In: Nature Communications. - 2041-1723 .- 2041-1723. ; 15:1
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Journal article (peer-reviewed)abstract
- The objective of thermonuclear fusion consists of producing electricity from the coalescence of light nuclei in high temperature plasmas. The most promising route to fusion envisages the confinement of such plasmas with magnetic fields, whose most studied configuration is the tokamak. Disruptions are catastrophic collapses affecting all tokamak devices and one of the main potential showstoppers on the route to a commercial reactor. In this work we report how, deploying innovative analysis methods on thousands of JET experiments covering the isotopic compositions from hydrogen to full tritium and including the major D-T campaign, the nature of the various forms of collapse is investigated in all phases of the discharges. An original approach to proximity detection has been developed, which allows determining both the probability of and the time interval remaining before an incoming disruption, with adaptive, from scratch, real time compatible techniques. The results indicate that physics based prediction and control tools can be developed, to deploy realistic strategies of disruption avoidance and prevention, meeting the requirements of the next generation of devices.
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| 34. |
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| 35. |
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| 36. |
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| 37. |
- Omar, Omar, et al.
(author)
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In vivo gene expression in response to anodically oxidized versus machined titanium implants.
- 2010
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In: Journal of biomedical materials research. Part A. - : Wiley. - 1552-4965 .- 1549-3296. ; 92:4, s. 1552-1566
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Journal article (peer-reviewed)abstract
- A quantitative polymerase chain reaction technique (qPCR) in combination with scanning electron microscopy was applied for the evaluation of early gene expression response and cellular reactions close to titanium implants. Anodically oxidized and machined titanium miniscrews were inserted in rat tibiae. After 1, 3, and 6 days the implants were unscrewed and the surrounding bone was retrieved using trephines. Both the implants and bone were analyzed with qPCR. A greater amount of cells, as indicated with higher expression of 18S, was detected on the oxidized surface after 1 and 6 days. Significantly higher osteocalcin (at day 6), alkaline phosphatase (at days 3 and 6), and cathepsin K (at day 3) expression was demonstrated for the oxidized surface. Higher expression of tumor necrosis factor-alpha (at day 1) and interleukin-1beta (at days 1 and 6) was detected on the machined surfaces. SEM revealed a higher amount of mesenchymal-like cells on the oxidized surface. The results show that the rapid recruitment of mesenchymal cells, the rapid triggering of gene expression crucial for bone remodeling and the transient nature of inflammation, constitute biological mechanisms for osseointegration, and high implant stability associated with anodically oxidized implants. (c) 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2009.
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| 38. |
- Omar, Omar, et al.
(author)
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Integrin and chemokine receptor gene expression in implant-adherent cells during early osseointegration.
- 2010
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In: Journal of materials science. Materials in medicine. - : Springer Science and Business Media LLC. - 1573-4838 .- 0957-4530. ; 21:3, s. 969-80
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Journal article (peer-reviewed)abstract
- The mechanisms of early cellular recruitment and interaction to titanium implants are not well understood. The aim of this study was to investigate the expression of pro-inflammatory cytokines, chemokines and adhesion markers during the first 24 h of implantation. Anodically oxidized and machined titanium implants were inserted in rat tibia. After 3, 12, and 24 h the implants were unscrewed and analyzed with quantitative polymerase chain reaction. Immunohistochemistry and scanning electron microscopy revealed different cell types, morphology and adhesion at the two implant surfaces. A greater amount of cells, as indicated by higher expression of small subunit ribosomal RNA (18S), was detected on the oxidized surface. Higher expression of CXC chemokine receptor-4 (at 12 h) and integrins, alphav (at 12 h), beta1 (at 24 h) and beta2 (at 12 and 24 h) was detected at the oxidized surfaces. Significantly higher tumor necrosis factor-alpha (at 3 h) and interleukin-1beta (at 24 h) expression was demonstrated for the machined surface. It is concluded that material surface properties rapidly modulate the expression of receptors important for the recruitment and adhesion of cells which are crucial for the inflammatory and regenerative processes at implant surfaces in vivo.
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| 44. |
- Schiza, Aglaia, et al.
(author)
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Adenovirus-mediated CD40L gene transfer increases Teffector/Tregulatory cell ratio and upregulates death receptors in metastatic melanoma patients
- 2017
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In: Journal of Translational Medicine. - : Springer Science and Business Media LLC. - 1479-5876. ; 15:79
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Journal article (peer-reviewed)abstract
- Background and aims: Malignant melanoma is an aggressive tumor sensitive for immunotherapy such as checkpoint blockade antibodies. Still, most patients with late stage disease do not respond, and the side effects can be severe. Stimulation of the CD40 pathway to initiate anti-tumor immunity is a promising alternative. Herein, we demonstrate immune profiling data from melanoma patients treated with an adenovirus-based CD40 ligand gene therapy (AdCD40L). Methods: Peripheral blood mononuclear cells and plasma were collected from malignant melanoma patients (n = 15) enrolled in a phase I/IIa study investigating intratumoral delivery of AdCD40L with or without low dose cyclophosphamide. Cells were analyzed by flow cytometry while plasma samples were analyzed by a multi-array proteomics. Results: All patients had an increased Teffector/Tregulatory cell ratio post therapy. Simultaneously, the death receptors TNFR1 and TRAIL-R2 were significantly up-regulated post treatment. Stem cell factor (SCF), E-selectin, and CD6 correlated to enhanced overall survival while a high level of granulocytic myeloid-derived suppressor cells (gMDSCs), IL8, IL10, TGFb1, CCL4, PlGF and Fl3t ligand was highest in patients with short survival. Conclusions: AdCD40L intratumoral injection induced desirable systemic immune effects that correlated to prolonged survival. Further studies using CD40 stimulation in malignant melanoma are warranted.
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| 45. |
- Själander, Sara, 1981-
(author)
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Stroke prevention in atrial fibrillation
- 2016
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Doctoral thesis (other academic/artistic)abstract
- Background: The Framingham Study from 1991 showed a clear correlation between atrial fibrillation (AF) and ischemic stroke, where patients with AF had an almost fivefold increase in risk of stroke compared with patients without AF. Since then, several trials have evaluated different antithrombotic treatments to reduce the risk of stroke in patients with AF. Other trials have investigated factors that increase the risk of stroke in patients with AF and risk score systems have been developed to categorize patients into low or increased risk of stroke to help clinicians to decide which patients benefit from antithrombotic treatment and in whom it can be abstained, not to expose patients with low stroke risk to an increased risk of bleeding conferred by antithrombotic treatment. The aims of this thesis were: [1] to evaluate if a warfarin dosing algorithm can increase hit rate and decrease mean error compared with manually changed doses; [2] to assess the prevalence and net clinical benefit of aspirin as monotherapy for stroke prevention in AF; [3] to investigate the risk of thromboembolic and haemorrhagic complications within 30 days after electrical cardioversion (ECV) of AF in patients with and without oral anticoagulation (OAC) pre-treatment; and [4] to assess the proportion of patients discontinuing OAC after pulmonary vein isolation (PVI), identify factors predicting stroke after PVI and to investigate risk of complications after PVI with and without OAC.Materials and methods: All studies are retrospective and based on data from Swedish national quality registries. In paper I, data from Auricula was used to compare the resulting INR values after algorithmic warfarin dose suggestions and manually changed doses. In paper II data was extracted from the Swedish National Patient Register, the Dispensed Drugs Register and the Cause of Death Register. Patients with aspirin treatment were compared with patients without any antithrombotic treatment regarding risk of thromboembolic and haemorrhagic complications. In paper III data was collected from the Swedish National Patient Register and the Dispensed Drugs Register to examine risk of complications (thromboembolic and haemorrhagic events) within 30 days after cardioversion, comparing patients with and without oral anticoagulation pre-treatment. In paper IV data from six different Swedish national quality registries were used (Swedish Catheter Ablation Register, Auricula, Swedish National Patient Register, Dispensed Drugs Register, Cause of Death Register and Riksstroke). Patients undergoing pulmonary vein isolation (PVI) were investigated for adherence to guidelines regarding oral anticoagulation, predictors for stroke after PVI, as well as risk of ischemic stroke or intracranial haemorrhage after PVI in patients with and without treatment.Results: Paper I showed that a computerized dosing algorithm for warfarin in most cases perform as well or better compared with doses that have been changed manually, with a better hit-rate (0.72 vs. 0.67) and a lower mean error (0.44 vs. 0.48). Paper II showed that 32% of 182.678 patients with a diagnosis of AF were on monotherapy with aspirin for stroke prevention. A total of 115.185 patients were included, 58.671 with aspirin treatment and 56.514 without antithrombotic treatment at baseline. After stratification after CHA2DS2-VASc score and after multivariable adjustment, aspirin treatment did not confer a decrease in thromboembolic events. After propensity score mathcing, rate of ischemic stroke was 7.4%/year (95% CI 7.1-7.6) in aspirin treated patients and 6.6%/year (95% CI 6.4-6.9) in patients without antithrombotic treatment. In paper III 22.874 patients undergoing electrical cardioversion were included, 10.722 with and 12.152 without OAC pre-treatment. In patients with low stroke risk (CHA2DS2-VASc 0-1), no thromboembolic complication was seen within 30 days after cardioversion. In patients with CHA2DS2-VASc ≥2, the risk of thromboembolic complications was increased when no oral anticoagulation pre-treatment was used, results that remained after propensity score matching. No difference regarding haemorrhagic complications was seen. Paper IV included a total of 1585 patients undergoing PVI with a mean follow up of 2.6 years. Adherence to current guidelines regarding oral anticoagulation was good in patients with CHA2DS2-VASc ≥2. Previous ischemic stroke was a predictor for a new stroke after PVI. In patients with CHA2DS2-VASc ≥2 stroke risk was increased in patients discontinuing OAC compared to those continuing OAC (1,60%/year vs. 0.34%/year).Conclusion: Oral anticoagulation is still underutilized for prevention of stroke and systemic embolism in patients with atrial fibrillation. Patients with risk factors for stroke (CHA2DS2-VASc ≥2p) benefit from continuous oral anticoagulation treatment to prevent stroke, also in conjunction with electrical cardioversion and after pulmonary vein isolation. If warfarin is chosen, a computerised dosing algorithm can facilitate and standardize warfarin dosing and lead to better resulting INR values than manually changed doses. Aspirin should not be used for stroke prevention in patients with atrial fibrillation.
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| 46. |
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| 47. |
- Suska, Felicia, 1974, et al.
(author)
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In vivo evaluation of noble metal coatings
- 2010
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In: Journal of Biomedical Materials Research Part B: Applied Biomaterials. - 1552-4981. ; 92B:1, s. 86-94
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Journal article (peer-reviewed)abstract
- A nanotopographic noble metal (Ag, Au, Pd) coating has been applied on commercial urinary catheters and used in more than 80,000 patients, with good clinical results. We have previously evaluated the biocompatibility of different variations of this coating, showing high cellular viability and function in vitro. However, the reasons for good clinical and preclinical behavior are not known. This in vivo study aimed to investigate the soft tissue peri-implant reaction to five coatings with systematically altered noble metal ratios after 1, 3, and 21 days of implantation in rats. The results show that coatings of silver only, or silver with medium amounts of gold and low-medium palladium content were superior to other tested coatings. Such surfaces were during the first days after implantation associated with a decreased recruitment of inflammatory cells to implant close exudates, a lower percentage of neutrophils, higher cell viability, and lower production of monocyte chemoattractant protein-1 (MCP-1), compared to the other coatings and uncoated silicone (PDMS) control. In contrast, the addition of higher concentrations of gold and palladium to silver induced a thicker soft tissue capsule. Coatings with high concentration of palladium induced the thickest fibrouscapsule after 21 days of implantation. The study demonstrates that by varying the noble metal ratio at implant surfaces it is possible to modulate inflammation and fibrosis in soft tissue.
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| 48. |
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| 49. |
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| 50. |
- Svensson, Sara, 1981, et al.
(author)
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A novel soft tissue model for biomaterial-associated infection and inflammation - Bacteriological, morphological and molecular observations
- 2015
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In: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 41, s. 106-121
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Journal article (peer-reviewed)abstract
- Infection constitutes a major risk for implant failure, but the reasons why biomaterial sites are more vulnerable than normal tissue are not fully elucidated. In this study, a soft tissue infection model was developed, allowing the analysis of cellular and molecular responses in each of the sub-compartments of the implant-tissue interface (on the implant surface, in the surrounding exudate and in the tissue). Smooth and nanostructured titanium disks with or without noble metal chemistry (silver, gold, palladium), and sham sites, were inoculated with Staphylococcus epidermidis and analysed with respect to number of viable bacteria, number, viability and gene expression of host cells, and using different morphological techniques after 4 h, 24 h and 72 h. Non-infected rats were controls. Results showed a transient inflammatory response at control sites, whereas bacterial administration resulted in higher recruitment of inflammatory cells (mainly polymorphonuclear), higher, continuous cell death and higher gene expression of tumour necrosis factor-alpha, interleukin-6, interleukin-8, Toll-like receptor 2 and elastase. At all time points, S. epidermidis was predominantly located in the interface zone, extra- and intracellularly, and lower levels were detected on the implants compared with surrounding exudate. This model allows detailed analysis of early events in inflammation and infection associated to biomaterials in vivo leading to insights into host defence mechanisms in biomaterial-associated infections.
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