Due to the increased incidence of breast cancer and improved survival, more women are at risk of developing contralateral breast cancer (CBC). The aim of this thesis was to explore risk factors... Show moreDue to the increased incidence of breast cancer and improved survival, more women are at risk of developing contralateral breast cancer (CBC). The aim of this thesis was to explore risk factors associated with CBC. We observed significant associations for a polygenic risk score of common germline variants (PRS313) and for different adjuvant systemic therapy regimens with (subtype-specific) CBC risk. These factors may be incorporated in CBC risk prediction models together with other known and available risk factors. For support of clinical decision making more biological information is needed to understand CBC development in women with invasive breast cancer and DCIS. As a first step towards implementation of a risk prediction model, we performed an exploratory interview study, which showed that patients had varying preferences for graphical presentation of probabilities in a CBC prediction model. In future studies, the prediction model should be incorporated in a decision support tool and implemented in clinical practice. This tool can then help to better identify women at high risk of CBC who may benefit from prophylactic surgery, while the estimates can also be used to reassure patients who are at low risk of developing CBC. Show less
Older emergency department (ED) patients are at high risk of adverse health outcomes, such as mortality or functional decline. Early identification of those patients who are at highest risk gives... Show moreOlder emergency department (ED) patients are at high risk of adverse health outcomes, such as mortality or functional decline. Early identification of those patients who are at highest risk gives an opportunity to target interventions and guide treatment decisions for those who need it most.This thesis describes the clinical value of using geriatric screening in the ED. Geriatric screening identifies older patients at high risk of both short- and long-term poor outcomes and provides valuable information for care providers treating acutely hospitalized older patients. The results from screening could aid in individualized treatment decisions to acquire more personalized care, and therefore gives an opportunity to optimize outcomes for older patients.Implementation of screening programs in the fast-paced environment of everyday ED practice remains scarce. The results of this thesis show that the implementation of a geriatric screening program in routine ED practice is feasible and the use of screening is accepted by both the users (triage nurses) and the older patients.Using geriatric screening in routine care is therefore useful and feasible. More research will be needed to investigate implementation in different hospitals to generate guidance on how geriatric screening tools can be successfully implemented on a wide scale. Show less
The first part of this thesis provides insight in prognostic markers in VSCC to refine clinicopathological risk assessment. One of the most frequently described risk factors for recurrent disease... Show moreThe first part of this thesis provides insight in prognostic markers in VSCC to refine clinicopathological risk assessment. One of the most frequently described risk factors for recurrent disease is the minimal peripheral surgical margin. In order to improve the quality of future studies and clinical recommendations, we provided a practical guideline on how to uniformly measure this margin in chapter 2. We also determined the clinical relevance of the molecular classification of VSCC based on immunohistochemical staining for p16 and p53. In chapter 3 we described the immunohistochemical characterization of these molecular subtypes to aid their detection in routine clinical practice. We utilized this approach to show the difference in clinical outcome between the three distinct molecular subtypes of VSCC in chapter 4.The second part of this thesis contains studies on the tumor microenvironment as a first step towards immunotherapy for VSCC. An overview of the literature concerning immunity in VSCC at the start of our studies is provided in chapter 5. Subsequently, we interrogated the TME of different VSCC subtypes in chapter 6, and showed that high infiltration of CD4+ T cells is important for clinical outcome, irrespective of the molecular subtype of VSCC. In chapter 7 we performed an in-depth analysis on the TME based on RNA profiles and showed that highly T cell infiltrated VSCC are potentially eligible candidates for immunotherapy. In chapter 8 we exploited the expression of CD39 by CD4+ and CD8+ T cells as a marker to identify tumor specific T cells. Finally, in chapter 9 the general aspects and relevance of the studies mentioned in this thesis are combined, discussed, and placed in a broader perspective with suggestions for future research. Show less
In this thesis, i) the role of echocardiography in predicting outcome after cardiac resynchronization therapy (CRT) is investigated, as well as ii) the role of multimodality imaging in the risk... Show moreIn this thesis, i) the role of echocardiography in predicting outcome after cardiac resynchronization therapy (CRT) is investigated, as well as ii) the role of multimodality imaging in the risk-stratification of cardiac disease.The relationship between baseline QRS duration and the presence of a left bundle branch block, and the degree of reverse left ventricular (LV) remodeling and improvement of LV ejection fraction (EF), is discussed in CRT recipients. Results are presented for the interaction of two key determinants of outcome after CRT, namely LV global longitudinal strain and LV reverse remodeling, as well as their impact on survival. The benefits of improved mechanical dyssynchrony (quantified with mechanical dispersion) after CRT are examined, as well as a novel, non-invasive technique for assessing myocardial work in CRT. The prognostic impact of functional mitral regurgitation (FMR) in CRT, and the impact of atrial fibrillation on FMR improvement, are discussed.The role of cardiac imaging in the risk-stratification of genetic dilated cardiomyopathy is discussed, especially when associated with neuromuscular disorders. Specifically, the use of speckle tracking echocardiography in risk-stratification of genetic dilated cardiomyopathy was investigated. Show less
The number of older people in the population is rising and so is the number of older patients in the Emergency Department (ED). Older patients often have complex problems which leads to an... Show moreThe number of older people in the population is rising and so is the number of older patients in the Emergency Department (ED). Older patients often have complex problems which leads to an increased change of repeat ED visits, longer length of stay, higher chance of hospital admission and higher chance of negative health outcomes. Cognitive impairment is a frequent problem in older ED patients but often remains unrecognized and little is known about the association between cognitive impairment and adverse outcomes in older ED patients. In this thesis we show that cognitive impairment is associated with adverse outcomes in acutely presenting older patients. Secondly, we show that routinely collected parameters in addition to cognitive impairment can be used to screen for high risk of adverse outcomes in older ED patients. We investigated two delirium screeners and showed the CAM-ICU might not be suitable for early detection of delirium in the ED. Finally, vital signs that associate with decreased brain perfusion and oxygenation, such as low systolic blood pressure, were associated with cognitive impairment in older ED patients. Next steps would be to investigate if optimal resuscitation might improve cognition and decrease risk of subsequent delirium and adverse outcomes. Show less
The aim of the research described in this thesis was to obtain more insight in the risk factors of BK polyomavirus (BKPyV) infection after kidney transplantation (KTx), with special emphasis on... Show moreThe aim of the research described in this thesis was to obtain more insight in the risk factors of BK polyomavirus (BKPyV) infection after kidney transplantation (KTx), with special emphasis on pretransplantation related risk factors. Both donor and recipient as well as viral factors, were investigated. The ultimate goal was to identify reliable predictive markers of BKPyV infection after KTx, thereby providing opportunities to optimize and personalize the currently recommended BKPyV screening strategy. Chapter Two describes the correlation between pretransplantation donor-recipient pair seroreactivity against BKPyV and development of BKPyV viremia and BKPyVAN after KTx. In Chapter Three the stability of BKPyV seroreactivity in KTRs and healthy blood donors, and the correlation of BKPyV seroreactivity with preceding viremia in KTRs is described. In Chapter Four the reduced risk of BKPyV infection in HLA-B51 positive recipients after KTx is described. Chapter Five describes the development and evaluation of a Luminex bead-based multiplex immunoassay for BKPyV serotyping. In Chapter Six the application of the Luminex bead-based multiplex immunoassay for BKPyV serotyping is described in a cohort of KTx donor-recipient pairs. In the General Discussion implications for prediction of BKPyV infections in recipients after KTx, as well as suggestions for further research are described. Show less
