Stem cell therapy for cardiovascular disease : answering basic questions regarding cell behavior

Stem cell therapy has raised enthusiasm as a potential treatment for cardiovascular diseases. However, questions remain about the in vivo behavior of the cells after transplantation and the mechanism of action with which the cells could potentially alleviate disease symptoms. The objective of the research as described in this thesis was to visualize survival, proliferation, and migration of embryonic (ESC) and adult stem cells using non-invasive molecular imaging techniques in small animal models of cardiovascular diseases. The major findings can be described as follows: (1) Non-invasive bioluminescence imaging is a validated tool to monitor donor cell survival, proliferation, migration, and misbehavior; (2) ESC are a potential source for true regenerative therapy; (3) ESC form teratomas; (4) Adult stem cell survival is short-lived, but of all cells currently used in the clinic, mononuclear cells show the most prolonged survival; (5) Transplantation of mononuclear cells can preserve cardiac function in the short term after myocardial infarction in mice; (6) Compared to other measurements of murine cardiac function, Micro-CT is a superior method to assess cardiac geometry and function; and (7) Transplantation of mononuclear cells in peripheral artery disease is hampered by dismal cell survival and homing. These findings illustrate the current challenges for optimizing stem cell therapy for cardiovascular disease.Fulbright Foundation, VSB fund, Prof. Michaël-van Vloten Foundation, American Heart Association, Collegium Chirurgicum Neerlandicum, Netherlands Heart Foundation, J.E. Jurriaanse Foundation, ADinstruments, Millar Instruments, Synthes, Triplinq Hosted Solutions, and Servier Nederland Farma B.V.UBL - phd migration 201

Stent graft sizing for endovascular abdominal aneurysm repair using open source image processing software

Introduction: An important step to reach a favorable outcome of abdominal endovascular aneurysm repair (EVAR) is preoperative sizing of the stent graft using computed tomography angiography (CTA) images of the abdominal aorta. A variety of costly image processing software options is available to obtain the necessary aortic measurements. A package that can be used for EVAR sizing is OsiriX Lite (R)-an open source, freely downloadable image processing option. This study assesses the concurrent validity of OsiriX Lite (R) when compared with commercially available 3Mensio Vascular (R) and Siemens Syngo.via (R).Methods: CTA scans of 20 patients that underwent EVAR for abdominal aneurysm were selected, 10 elective and 10 ruptured. For each scan, 6 observers determined 20 parameters needed for proper stent graft sizing, 2 using Osirix Lite (R), 3 using 3Mensio Vascular (R), and 1 using Siemens Syngo.via (R). For each parameter, an intraclass correlation coefficient (ICC) and a P-value were calculated. Interrater agreement was interpreted using the Koo and Li Guidelines. Time needed to perform EVAR planning was compared.Results: Overall interrater agreement between the 3 sizing options was found to be either "good" or "moderate" for 16 out of 20 parameters (80%). Time needed to perform EVAR planning was not significantly different for Osirix Lite (R) (568 sec) when compared with 3Mensio Vascular (R) (603 sec) or Siemens Syngo.via (R) (659 sec) with a P-value of 0.88.Conclusions: The authors conclude that Osirix Lite (R) is an accurate and time-effective image processing option for preoperative sizing of an EVAR stent graft when matched to 3Mensio Vascular (R) and Siemens Syngo.via (R).Development and application of statistical models for medical scientific researc

Arteriovenous Fistula Maturation Failure in a Large Cohort of Hemodialysis Patients in the Netherlands

Vascular Surger

Perfusion parameters in near-infrared fluorescence imaging with indocyanine green: a systematic review of the literature

(1) Background: Near-infrared fluorescence imaging is a technique capable of assessing tissue perfusion and has been adopted in various fields including plastic surgery, vascular surgery, coronary arterial disease, and gastrointestinal surgery. While the usefulness of this technique has been broadly explored, there is a large variety in the calculation of perfusion parameters. In this systematic review, we aim to provide a detailed overview of current perfusion parameters, and determine the perfusion parameters with the most potential for application in near-infrared fluorescence imaging. (2) Methods: A comprehensive search of the literature was performed in Pubmed, Embase, Medline, and Cochrane Review. We included all clinical studies referencing near-infrared perfusion parameters. (3) Results: A total of 1511 articles were found, of which, 113 were suitable for review, with a final selection of 59 articles. Near-infrared fluorescence imaging parameters are heterogeneous in their correlation to perfusion. Time-related parameters appear superior to absolute intensity parameters in a clinical setting. (4) Conclusions: This literature review demonstrates the variety of parameters selected for the quantification of perfusion in near-infrared fluorescence imaging.Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Optimising Access Surgery in Senior Haemodialysis Patients (OASIS): study protocol for a multicentre randomised controlled trial

Introduction Current evidence on vascular access strategies for haemodialysis patients is based on observational studies that are at high risk of selection bias. For elderly patients, autologous arteriovenous fistulas that are typically created in usual care may not be the best option because a significant proportion of fistulas either fail to mature or remain unused. In addition, long-term complications associated with arteriovenous grafts and central venous catheters may be less relevant when considering the limited life expectancy of these patients. Therefore, we designed the Optimising Access Surgery in Senior Haemodialysis Patients (OASIS) trial to determine the best strategy for vascular access creation in elderly haemodialysis patients. Methods and analysis OASIS is a multicentre randomised controlled trial with an equal participant allocation in three treatment arms. Patients aged 70 years or older who are expected to initiate haemodialysis treatment in the next 6 months or who have started haemodialysis urgently with a catheter will be enrolled. To detect and exclude patients with an unusually long life expectancy, we will use a previously published mortality prediction model after external validation. Participants allocated to the usual care arm will be treated according to current guidelines on vascular access creation and will undergo fistula creation. Participants allocated to one of the two intervention arms will undergo graft placement or catheter insertion. The primary outcome is the number of access-related interventions required for each patient-year of haemodialysis treatment. We will enrol 195 patients to have sufficient statistical power to detect an absolute decrease of 0.80 interventions per year. Ethics and dissemination Because of clinical equipoise, we believe it is justified to randomly allocate elderly patients to the different vascular access strategies. The study was approved by an accredited medical ethics review committee. The results will be disseminated through peer-reviewed publications and will be implemented in clinical practice guidelines. Protocol version and date V.5, 25 February 2021.Clinical epidemiolog

Surgical quality in organ procurement during day and night: an analysis of quality forms

OBJECTIVES: To analyse a potential association between surgical quality and time of day. DESIGN: A retrospective analysis of complete sets of quality forms filled out by the procuring and accepting surgeon on organs from deceased donors. SETTING: Procurement procedures in the Netherlands are organised per region. All procedures are performed by an independent, dedicated procurement team that is associated with an academic medical centre in the region. PARTICIPANTS: In 18 months' time, 771 organs were accepted and procured in The Netherlands. Of these, 17 organs were declined before transport and therefore excluded. For the remaining 754 organs, 591 (78%) sets of forms were completed (procurement and transplantation). Baseline characteristics were comparable in both daytime and evening/night-time with the exception of height (p=0.003). PRIMARY OUTCOME MEASURE: All complete sets of quality forms were retrospectively analysed for the primary outcome, procurement-related surgical injury. Organs were categorised based on the starting time of the procurement in either daytime (8:00-17:00) or evening/night-time (17:00-8:00). RESULTS: Out of 591 procured organs, 129 organs (22%) were procured during daytime and 462 organs (78%) during evening/night-time. The incidence of surgical injury was significantly lower during daytime; 22 organs (17%) compared with 126 organs (27%) procured during evening/night-time (p=0.016). This association persists when adjusted for confounders. CONCLUSIONS: This study shows an increased incidence of procurement-related surgical injury in evening/night-time procedures as compared with daytime. Time of day might (in)directly influence surgical performance and should be considered a potential risk factor for injury in organ procurement procedures

Precurved non-tunnelled catheters for haemodialysis are comparable in terms of infections and malfunction as compared to tunnelled catheters: A retrospective cohort study

Background: The main limitations of central venous catheters for haemodialysis access are infections and catheter malfunction. Our objective was to assess whether precurved non-tunnelled central venous catheters are comparable to tunnelled central venous catheters in terms of infection and catheter malfunction and to assess whether precurved non-tunnelled catheters are superior to straight catheters. Materials and methods: In this retrospective, observational cohort study, adult patients in whom a central venous catheter for haemodialysis was inserted between 2012 and 2016 were included. The primary endpoint was a combined endpoint consisting of the first occurrence of either an infection or catheter malfunction. The secondary endpoint was a combined endpoint of the removal of the central venous catheter due to either an infection or a catheter malfunction. Using multivariable analysis, cause-specific hazard ratios for endpoints were calculated for tunnelled catheter versus precurved non-tunnelled catheter, tunnelled catheter versus non-tunnelled catheter, and precurved versus straight nontunnelled catheter. Results: A total of 1603 patients were included. No difference in reaching the primary endpoint was seen between tunnelled catheters, compared to precurved non-tunnelled catheters (hazard ratio, 0.91; 95% confidence interval, 0.70– 1.19, p=0.48). Tunnelled catheters were removed less often, compared to precurved non-tunnelled catheters (hazard ratio, 0.65; 9

Stem cell therapy for cardiovascular disease : answering basic questions regarding cell behavior

Stem cell therapy has raised enthusiasm as a potential treatment for cardiovascular diseases. However, questions remain about the in vivo behavior of the cells after transplantation and the mechanism of action with which the cells could potentially alleviate disease symptoms. The objective of the research as described in this thesis was to visualize survival, proliferation, and migration of embryonic (ESC) and adult stem cells using non-invasive molecular imaging techniques in small animal models of cardiovascular diseases. The major findings can be described as follows: (1) Non-invasive bioluminescence imaging is a validated tool to monitor donor cell survival, proliferation, migration, and misbehavior; (2) ESC are a potential source for true regenerative therapy; (3) ESC form teratomas; (4) Adult stem cell survival is short-lived, but of all cells currently used in the clinic, mononuclear cells show the most prolonged survival; (5) Transplantation of mononuclear cells can preserve cardiac function in the short term after myocardial infarction in mice; (6) Compared to other measurements of murine cardiac function, Micro-CT is a superior method to assess cardiac geometry and function; and (7) Transplantation of mononuclear cells in peripheral artery disease is hampered by dismal cell survival and homing. These findings illustrate the current challenges for optimizing stem cell therapy for cardiovascular disease