We used the corneal immunosuppressive environment to test the possibility of inserting a Fish Scale-Derived Collagen Matrix in a corneal pocket, and the excellent results and lack of primary... Show moreWe used the corneal immunosuppressive environment to test the possibility of inserting a Fish Scale-Derived Collagen Matrix in a corneal pocket, and the excellent results and lack of primary and secondary immune responses led to a clinical trial, which is currently underway. The immunosuppressive environment of the eye allows the growth of malignant melanocytes which leads to the formation of uveal melanoma. The association between increased numbers of macrophages and lymphocytes in uveal melanoma and an increased development of uveal melanoma metastases suggest an influence of pro-angiogenic macrophages, The relation between loss of BAP1 expression and a very bad prognosis and the influx of leukocytes into the primary tumor, suggests that BAP1 functions as a regulator of inflammation. Further research will focus on the role of BAP1 in the regulation of inflammation in the uveal melanoma microenvironment. Show less
Bone metastases of the long bones can cause pain and pathologic fractures. Local treatment consists of radiotherapy or surgical stabilisation. The most appropriate treatment depends on many factors... Show moreBone metastases of the long bones can cause pain and pathologic fractures. Local treatment consists of radiotherapy or surgical stabilisation. The most appropriate treatment depends on many factors, including the symptoms, the location and extent of the lesion, the wishes and expectations of the patient, and the expected remaining survival. Survival estimation of patients with symptomatic long bone metastases is crucial to prevent over- and undertreatment. This thesis aimed to develop a prognostic model for estimating survival in patients with cancer and symptomatic metastases of the long bones, evaluate current (surgical) treatment modalities and trends, and provide rationale for future prospective randomized trials. As a result, the OPTIModel was developed: an easy-to-use prognostic model that categorises patients into four clinically relevant survival categories based on only three variables (tumour type, Karnofsky Performance Score, visceral/brain metastases). To enable easy use of the model, an app was created (OPTIModel). Futhermore, this thesis shows that almost all treatments of pathologic fractures are based on expert opinion and small, retrospective cohorts, as opposed to large, prospective (randomized) trials, which is interesting in an era of evidence based medicine. This confirms the need of a prospective, multicenter cohort, which was designed and implemented accordingly. Show less
ANCA-associated vasculitis (AAV) is a systemic autoimmune disease which is associated with increased risk of mortality and morbidity. The outcomes of patients with AAV have improved... Show moreANCA-associated vasculitis (AAV) is a systemic autoimmune disease which is associated with increased risk of mortality and morbidity. The outcomes of patients with AAV have improved substantially as a consequence of earlier detection of the disease and more sophisticated therapy regimens. Despite these advances, the disease influences the lives of patients substantially. Therefore, this thesis focused on prognosis and outcomes with the aim to further improve the outcomes of patients with AAV. Show less
Deseive, S.; Straub, R.; Kupke, M.; Broersen, A.; Kitslaar, P.H.; Massberg, S.; ... ; Hausleiter, J. 2018
Uveal melanoma (UM) is an aggressive intraocular tumor with a high propensity to metastasize. Accurate prognostication is relevant for patient counselling, planning of follow-up and... Show moreUveal melanoma (UM) is an aggressive intraocular tumor with a high propensity to metastasize. Accurate prognostication is relevant for patient counselling, planning of follow-up and stratification of patients in clinical trials. Discoveries of prognostically relevant genetic markers in the last few decades have fuelled the advancement of prognostication in UM considerably. In this thesis, we explored ways of improving genetic prognostication in UM, evaluated the effect of irradiation on chromosome testing, and investigated the association of DNA repair genes and epigenetic regulators with prognosis. We reveal that chromosome markers of high malignancy such as monosomy 3 and chromosome 8q gain are less often observed in patients who die due to metastases at a late stage. We demonstrate that combining the AJCC staging and chromosome 3 and 8q status results in enhanced risk stratification. We provide evidence that supports the taking of biopsies before radiotherapy is applied since chromosome testing seems to fail more often in irradiated tumors. Furthermore, we show that evaluating the role of DNA repair and epigenetics in uveal melanoma can help in unraveling the biology of uveal melanoma and identifying new markers for prognostication. Show less
This thesis has shown that significant lead-induced TR due to the mechanical presence of an RV-lead though the tricuspid valve was associated with worse long-term prognosis. CRT is one of the... Show moreThis thesis has shown that significant lead-induced TR due to the mechanical presence of an RV-lead though the tricuspid valve was associated with worse long-term prognosis. CRT is one of the main therapeutic breakthroughs in heart failure of the last decade but patients included in landmark trials do not completely mirror patients undergoing CRT in the clinical practice, who are usually older and have more frequently associated comorbidities such as renal dysfunction, diabetes or atrial fibrillation. This thesis shows a beneficial, although limited, effect of CRT also in elderly, in patients with diabetes and CKD stage 4, and therefore suggests that this therapy should not be withheld based on certain co-morbidities or on age alone. Furthermore, it shows that RBBB in patients referred to CRT and favourable RV-function improvement after CRT were associated with CRT outcomes. To improve clinical risk-stratification, this thesis proposed a CRT-SCORE using CRT-specific parameters and showed to be valuable in risk-estimation that may assist clinicians in counseling patients and guide clinical shared decision-making. Finally, novel approaches to optimize patient selection are presented in this thesis. SDI, a 3D-echocardiography LV-dyssynchrony measurement and T1-mapping, a novel CMR-technique to quantify diffuse myocardial fibrosis were significantly associated with CRT outcomes. Show less
Background: To investigate the incremental prognostic value of low-attenuation plaque volume (LAPV) from coronary CT angiography datasets.Methods: Quantification of LAPV was performed using... Show moreBackground: To investigate the incremental prognostic value of low-attenuation plaque volume (LAPV) from coronary CT angiography datasets.Methods: Quantification of LAPV was performed using dedicated software equipped with an adaptive plaque tissue algorithm in 1577 patients with suspected CAD. A combination of death and acute coronary syndrome was defined as primary endpoint. To assess the incremental prognostic value of LAPV, parameters were added to a baseline model including clinical risk and obstructive coronary artery disease (CAD), a baseline model including clinical risk and calcium scoring (CACS) and a baseline model including clinical risk and segment involvement score (SIS).Results: Patients were followed for 5.5 years either by telephone contact, mail or clinical visits. The primary endpoint occurred in 30 patients. Quantified LAPV provided incremental prognostic information beyond clinical risk and obstructive CAD (c-index 0.701 vs. 0.767, p<.001), clinical risk and CACS (c-index 0.722 vs. 0.771, p<.01) and clinical risk and SIS (c-index 0.735 vs. 0.771, p<.01. A combined approach using quantified LAPV and clinical risk significantly improved the stratification of patients into different risk categories compared to clinical risk alone (categorical net reclassification index 0.69 with 95% CI 0.27 and 0.96, p<.001). The combined approach classified 846 (53.6%) patients as low risk (annual event rate 0.04%), 439 (27.8%) patients as intermediate risk (annual event rate 0.5%) and 292 (18.5%) patients as high risk (annual event rate 0.99%).Conclusion: Quantification of LAPV provides incremental prognostic information beyond established CT risk patterns and permits improved stratification of patients into different risk categories. Show less
