Near-infrared (NIR) fluorescence imaging with indocyanine green (ICG) is a promising imaging technique for the assessment of tissue perfusion. This thesis describes the quest for valid and reliable... Show moreNear-infrared (NIR) fluorescence imaging with indocyanine green (ICG) is a promising imaging technique for the assessment of tissue perfusion. This thesis describes the quest for valid and reliable quantitative assessment of tissue perfusion using this technique, predominantly in patients with lower extremity arterial disease. Two systematic reviews were performed, describing the experience with ICG NIR fluorescence imaging within various surgical fields. In three original studies, perfusion patterns were described in various groups, including lower extremity arterial disease, healthy controls and in patients undergoing free flap reconstructive breast surgery. By applying normalization to the quantitative assessment, an increased validity and reliability was seen. To describe potential clinical applications, the use of ICG NIR fluorescence imaging was described for two indications. In patients undergoing unilateral revascularization, quantitative assessment showed an increase of inflow parameters, whilst parameters in the untreated side remained unchanged. In a cohort of patients undergoing amputation surgery, ICG NIR fluorescence imaging was able to predict postoperative skin necrosis in all four cases. Future use of ICG NIR fluorescence imaging should focus on improving validity and reliability of quantitative perfusion assessment. Show less
Willems, S.A.; Brouwers, J.J.W.M.; Eefting, D. 2022
Objective: Brucellosis is the most common zoonosis worldwide. Although cardiovascular complications in human brucellosis comprise only 3% of morbidity, they are the principal cause of death.... Show moreObjective: Brucellosis is the most common zoonosis worldwide. Although cardiovascular complications in human brucellosis comprise only 3% of morbidity, they are the principal cause of death. Endocarditis covers the majority of these cases. Infected aneurysms and ulcerative processes of the aorta are rare but can be life threatening as well. Currently, limited information is available about aortic and iliac involvement in brucellosis.Methods: A PubMed, Web of Science, and AccessMedicine search (without restriction on language or year of publication) was performed to identify relevant articles on aortic and iliac involvement in brucellosis. Case reports were eligible for inclusion if they reported on thoracic, abdominal, or iliac aortic pathology caused by Brucella.Results: Seventy-one cases were identified over the last 70 years, with an overall mortality rate of 22%. Most of the patients were male (86%) and had a history of Brucella exposure (66%). Approximately one quarter (23%) contracted Brucella while travelling in a (hyper)endemic region. Almost half of the infections were located in the abdominal aorta (49%), followed by the ascending (37%) and descending (13%) thoracic aorta. Infected aneurysms (61%) and ulcerative processes (16%) were seen most frequently. Aortic rupture was present in 31% of cases and occurred mainly in the abdominal (49%) and descending thoracic aorta (44%). The majority of all patients (59%) underwent open surgery combined with long term antibiotics. Over the past 15 years, a trend towards endovascular treatment was observed.Conclusion: Although aortic and iliac involvement in brucellosis is rare, it can be a life threatening manifestation. Due to low awareness, this infection may represent an under reported disease. The therapeutic cornerstone in these cases remains open surgery combined with antibiotics. The role of endovascular treatment is yet to be decided, in which the condition of the patient and the risks of long term complications need to be considered. Show less
Abdominal aortic aneurysms (AAAs) are potentially lethal due to rupture. Rupture occurs mainly in AAA greater than 55mm and acute repair still results in mortality over 30%. Although the... Show moreAbdominal aortic aneurysms (AAAs) are potentially lethal due to rupture. Rupture occurs mainly in AAA greater than 55mm and acute repair still results in mortality over 30%. Although the results of elective treatment have significantly improved over the years and mortality is low (<3%), there is a considerable risk of morbidity. AAAs are prevalent mostly in elderly patients and generally only progress slowly in size. Therefore, treatment that slows aneurysm growth would allow patients to avoid aneurysm repair, in particularly elderly patients. Insight into the pathophysiology of the disease has improved over the past few years and continuing research has led the focus towards finding pharmaceutical means to inhibit or even abrogate aneurysm growth. The aim of this thesis was to identify new possible targets for pharmacological treatment of AAAs and to apply this insight to the development of new therapies in a preclinical setting. Besides, understanding the cause of AAA progression can help identify secondary prevention strategies aimed at slowing down expansion. Show less
The studies described in this thesis focus on gene therapeutic strategies to target pathological vascular wall remodeling after PT(C)A or bypass surgery. Inflammatory processes and extracellular... Show moreThe studies described in this thesis focus on gene therapeutic strategies to target pathological vascular wall remodeling after PT(C)A or bypass surgery. Inflammatory processes and extracellular proteases, both activated by mechanical and vascular injury caused by these interventions, are thought to contribute largely to the development of post-angioplasty restenosis and vein graft disease. Therefore, viral and non-viral gene therapy techniques were used in these studies to deliver genes encoding protective as well as inhibiting proteins in order to modulate the inflammatory cascade (i.e. IL-10 and the MCP-1/CCR-2 pathway) in the first part of this thesis and the plasminogen activator and MMP-system in the second part. Finally, the expression of several involving genes was blocked locally by RNA interference techniques in the last part of this thesis. The possibilities and effects of these gene therapy applications were studied in cell cultures, in a human saphenous vein organ culture model and in two mouse models of restenosis and vein graft disease. Altogether, these studies provided more insight into the pathophysiology of post-interventional remodeling and several potential therapeutic strategies were assessed. Show less
The aim of this thesis was to gain more insight in the involvement of inflammatory processes in vessel wall remodeling seen after PTA or bypass surgery and put these processes in the perspective of... Show moreThe aim of this thesis was to gain more insight in the involvement of inflammatory processes in vessel wall remodeling seen after PTA or bypass surgery and put these processes in the perspective of restenosis, vein graft failure and potential therapeutic preventive strategies. Therefore, we firstly focused on inflammation in general, using the anti-inflammatory agent Dexamethasone, assessing the effects of such a broad approach on restenosis and vein graft remodeling. Then, we further focused on some specific parts of the immune system, namely Interleukin 10 (IL10), chemokines and the complement cascade. Il10 was chosen because it is one of the most studied anti-inflammatory cytokines and this property makes it a potential candidate for ant-restenosis therapy. Furthermore, it was hypothesized that chemokines are involved in vascular remodeling, since they are generally known for their regulatory properties regarding influx of inflammatory cells to tissues and this is one of the first phenomena seen in vascular remodeling. The complement cascade was studied in this context since it contains pro-inflammatory activity and some end-products of the cascade, like chemokines, are potent chemotactic agents. Show less
