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Coming theses from other universities

  • Health economic aspects of emotional problems and pain symptoms in childhood and adolescence, Long-term outcomes, efficacy and cost-effectiveness of interventions Author: Anna Philipson Link: Publication date: 2021-12-07 12:01
  • Thoracic Endovascular Aortic Repair : Clinical and morphological outcomes Author: Tina Hellgren Link: Publication date: 2021-11-25 12:11

    In the years following its introduction in the late 1980’s, thoracic endovascular aortic repair (TEVAR) rose as a minimally invasive alternative to open surgical repair of thoracic aortic disease. As a result, an expanding group of patients are receiving invasive treatment, even though evidence in the area is still scarce. The overall aim of this thesis was to study the outcomes of modern treatment of thoracic aortic disease – TEVAR and hybrid repair – by analyzing data from local and international cohorts.

    Paper I includes an evaluation of outcomes of TEVAR for intact and ruptured thoracic aortic aneurysm (TAA) at a tertiary referral center (1999 to 2014). Survival was unexpectedly poor after ruptured TAA repair, only one third of the patients were alive at 3-years follow-up. Intact TAA repair was associated with low perioperative mortality and acceptable 5-year survival.

    Paper II analyses aortic remodelling, complications, reinterventions and survival after TEVAR for subacute and chronic type B aortic dissection at a tertiary aortic center (1999-2015). TEVAR induced positive remodelling, characterized by false lumen thrombosis and shrinkage accompanied by true lumen expansion, of the thoracic but not the abdominal aorta. Reintervention due to aortic dilatation distal to the stent graft was common.

    Paper III, an international registry-based multicenter study of 9518 TEVAR cases from 2012 to 2016, demonstrated substantial international differences in practice patterns. The large dataset provides a point of reference for short-term outcome after TEVAR in current practice.   

    Paper IV, a single-center study of 50 consecutive patients who underwent frozen elephant trunk repair of the aortic arch (2006 to 2020), confirmed that whilst this procedure is associated with morbidity and mortality, the technique provides an adequate bridge to endovascular repair of the downstream aortic segments, which was common during follow-up. The repair was shown to induce positive aortic remodeling in the thoracic but not abdominal aorta, in patients with chronic aortic dissection.

    In conclusion, this thesis provides insights into the rapidly evolving field of TEVAR, including an overview of current practice as well as clinical and morphological outcomes.

  • Exploring the interactions of antibiotic combinations against multidrug-resistant Gram-negative bacteria Author: Anna Olsson Link: Publication date: 2021-11-25 09:05

    Antimicrobial resistance is emerging and available treatment options are lacking. Antibiotics is a cornerstone in modern medicine where medical procedures such as surgery, care of premature babies or treatment of cancer is dependent on efficient drugs. The need for novel treatment alternatives is increasing as bacteria continue to develop new resistance mechanisms.

    The main goal of this thesis was to screen for antimicrobial combinations efficient against Gram-negative bacteria. The complex membrane structure of Gram-negative bacteria is very protective against antimicrobial activity making many antibiotics ineffective. Polymyxin B was therefore used as a main component in the combinations evaluated due to its membrane disruptive mode of action. Previously neglected or disused antibiotics was used in combination with polymyxin B as a part of a Joint Programming Initiative on Antimicrobial Resistance (JPIAMR) called CO-ACTION. The prevailing theory of polymyxin B combinations is that the membrane disruptive effect will facilitate entry of a second antibiotic and reduce efflux activity. In contrast, the combination will not be as efficient in the presence of bacterial enzymatic activity as the resistance mechanism is not affected by changes in the membrane composition. To increase knowledge on underlying mechanisms behind the success of antimicrobial combinations an extensive genetic analysis was performed. 

    Several promising polymyxin B combinations were found which could offer a treatment option in caring for severely ill patients for which few alternatives exist. Associations between genetic background and efficient bacterial killing was also established. The chance of synergistic effect by the combination was increased if the antibiotic used in combination with polymyxin B could normally not enter the bacterial cell or in presence of resistance mechanisms increasing efflux activity. This thesis highlights the fact that only phenotypical antimicrobial susceptibility testing would not be used in forecasting the success of antimicrobial combinations. Information on antimicrobial susceptibility in combination with knowledge on resistance mechanisms present and how it influences the antibiotics used in combination is equally important.  

    With this work increased knowledge on genetic background of resistance mechanisms and bacterial killing by polymyxin B combinations and was provided. Antimicrobial combinations offer an interesting feature when no other treatment alternatives are available. The lack of diagnostics in forecasting the success of combination therapy in a clinical microbiology lab is of concern. The knowledge obtained in this work contributes to the general knowledge on antimicrobial combinations and provides an example of how to evaluate their effect.