This thesis describes the potential use of these cardiac progenitor-derived extracellular vesicles (EVs) for cardiac repair and focused on translational aspects that could accelerate clinical... Show moreThis thesis describes the potential use of these cardiac progenitor-derived extracellular vesicles (EVs) for cardiac repair and focused on translational aspects that could accelerate clinical implementation of EV-based therapeutics. The first steps have been made in optimizing EV production processes such as EV isolation and storage. Furthermore, this thesis described a potential method for sustained EV release and to prolong therapeutic exposure by using a hydrogel. Ultimately, this could contribute to improved efficacy upon local delivery of EV therapeutics. Together, this thesis potentially contributes to fasten clinical adoption of EV-based therapeutics for patients with heart failure. Show less
Background: Although resection of extremity soft tissue sarcomas can occasionally lead to large disabilities, literature regarding the necessity and outcome of functional reconstructions are scarce... Show moreBackground: Although resection of extremity soft tissue sarcomas can occasionally lead to large disabilities, literature regarding the necessity and outcome of functional reconstructions are scarce. The goal of this review is to assess outcomes and usage of functional reconstructions in light of multimodal treatment.Methods: A systematic search was performed in July 2018 in PubMed and Embase databases according to the PRISMA guidelines. Search terms related to 'soft tissue sarcoma' and 'functional reconstruction' were used. Case series evaluating outcomes of functional reconstructions after STS resection were included. Functional reconstructions were limited to free functioning muscle transfers, tendon reconstructions, and nerve reconstructions. Qualitative synthesis was performed on all studies. Tumor grade, multimodal treatment, reconstruction, outcomes, and complications were collected from individual patient data. Results were summarized by tumor site.Results: Fourteen studies were included after full-text screening. A total of 134 patients were described, of which the majority (74.9%) had functional reconstructions in the lower extremity. Radiotherapy and chemotherapy were administered in 60.3% and 49.4% respectively. Free functioning muscle transfers were used in 41.0% of all cases, tendon reconstructions in 58.2%, and nerve reconstructions in only 12.7%. A wide variety of outcome measures were used. Most patients regained good functionality, also after multimodal treatment. Unfavorable outcomes were often related to flap failure or allograft tendon rupture.Conclusion: Functional reconstructions in extremity STS are rarely described, but generally result in good functionality in spite of multimodal treatment. Early participation of reconstructive surgeons may help achieve ideal functional and oncological outcomes. (C) 2019 Published by Elsevier Ltd. Show less
Results from this thesis have elucidated potential genetic markers, which were associated with treatment outcome to MTX and adalimumab. Furthermore, a model for predicting the efficacy of MTX in... Show moreResults from this thesis have elucidated potential genetic markers, which were associated with treatment outcome to MTX and adalimumab. Furthermore, a model for predicting the efficacy of MTX in patients with RA was validated in two cohorts indicating that predicting efficacy by a pharmacogenetic model is feasible in RA patients treated with MTX. Importantly, definitive conclusions about the role of genetic predictive factors in treatment outcome to DMARDS could not be drawn, since these results have to be further validated and replicated in future pharmacogenetic studies. Large randomized prospective studies should be planned to demonstrate its legitimate predictive and cost-effective value before a genetically individualized approach is applicable in daily clinical practice. The potential role of pharmacogenetics in the prediction of efficacy and adverse events in RA patients treated with DMARDs is presented in this thesis. Hereby, new knowledge is added to the relatively young research field of pharmacogenetics, which may hopefully lead to a better treatment strategy for RA patients Show less
