ZonMw grants Clinical Fellowship to 17 medical specialists

17 ZonMw Clinical Fellows projects granted

• Read more about the projects

  MR-guided adaptive stereotactic radiotherapy for endometrial cancer (MASTEC)
  Dr Casper Reijnen, Radboudumc
  Radiotherapy is an important cornerstone in uterine cancer treatment. It is burdensome to the patients because of the bladder/bowel toxicity and duration (25-30 fractions). MR-guided radiotherapy allows for real-time adaptation of the radiotherapy plan according to the daily anatomy (adaptive), taking into account organ filling and other variations. Consequently the irradiation can be delivered more precisely (stereotactic), with smaller safety margins, and in less fractions with a higher fraction dose (hypofractionation). This research line investigates the safety of hypofractionated MR-guided adaptive radiotherapy in uterine cancer. Part 1 consists of planning studies to optimize the MR-guided radiotherapy techniques. Part 2 consists of a prospective phase II trial, in which 70 patients will be treated in only five fractions, with daily adaptation of the treatment plan. It forms the basis for large-scale research on MR-guided adaptive radiotherapy in women with uterine cancer.
  
  Towards improved treatment for unresectable stage III NSCLC via immune and drug mapping - PulmoPrint
  Dr Frederike Bensch, UMCG
  Patients with inoperable stage III non-small cell lung cancer, a type of lung cancer that cannot be removed by surgery, are treated with chemoradiotherapy (CRT) followed by immunotherapy (durvalumab). Despite the addition of immunotherapy, the cancer returns in two out of three patients within 5 years. I want to understand why this treatment often fails to cure patients. In PulmoPrint, I will use a special camera during a lung examination (bronchoscopy) to see where the fluorescent version of durvalumab ends up. I will also collect blood and tissue samples, among other things, to study how the cancer and the immune system change due to CRT. Combining this information will help us to better understand treatment effects and support the development of more personalized treatments in the future, such as delivering medicine directly into the tumor to increase the effectiveness of immunotherapy. 

  Share to Care; sharing contextual information between primary and secondary oncology care
  Dr Mariken Stegmann, UMCG
  Many elderly cancer patients are faced with difficult treatment choices. For a good treatment plan, it is important to include knowledge about the patient's context and preferences. The GP can play a valuable role in this process: he or she has often known the patient for years and knows what is important to him or her. However, this knowledge is not used enough in decision-making in cancer, partly because communication between GPs and specialists is not always optimal.

  In this project "Share to Care" I want to improve this collaboration. I will do this in three steps:
  1. Look at examples from countries with comparable healthcare systems.
  2. Investigate which information should be shared, and when and in what way.
  3. Develop and test a practical communication system together with relevant stakeholders. And make a plan for national implementation of that system.
  The project contributes to better collaboration and thus to more personal care for people with cancer.

  REPAIR – PCD
  Dr Tamara Paff, UMC Utrecht - WKZ
  Primary Ciliary Dyskinesia (PCD) is a rare inherited disorder in which the tiny hairs (cilia) in the airways don't work properly. As a result, mucus and bacteria build up in the lungs, causing serious, recurrent airway infections and permanent lung damage. Currently, there is no treatment that targets the root of the disease. Recent research shows that mRNA therapy might restore cilia function. In this project we are testing different forms of mRNA therapy on cells from patients with severe PCD. We will study whether the cilia regain their normal structure and movement and check for possible side effects. Our goal is to further develop mRNA therapy for future clinical trial and, eventually, create a personalized curative treatment for people with PCD.
  
  Cutting-edge bioinformatics approaches for enhancing infectious diseases surveillance in children
  Dr Joany Zachariasse, Erasmus MC
  Electronic health records contain a wealth of valuable medical information. However, due to technical, legal, and ethical limitations, this data is not yet used to its full potential to improve patient care. In this project, I aim to explore how innovative bioinformatics techniques can make electronic medical data more accessible for research. I will focus on the surveillance of infectious diseases in children. Faster and better insight into infection trends enables more targeted diagnostics and treatment, and more efficient healthcare planning. To achieve this, I will investigate the use of a “common language” for medical data, allowing patient information to be analyzed locally within each hospital using advanced methods. An innovative infrastructure will enable the sharing of aggregated, anonymous data within a Dutch research network, which can later be expanded to other research areas. 

  Assessment of the microcirculation and glycocalyx in subarachnoid hemorrhage patients.
  Dr Roel Haeren, Maastricht University
  An aneurysmal subarachnoid hemorrhages (aSAH) is a common type of brain hemorrhage with devastating consequences: only 1 of 3 patients regains independent functioning after the bleeding. This is mainly due to complications of the bleeding, of which late brain infarction is the most dreadful. 
  My team recently find out that a part of our smallest blood vessels, the glycocalyx, is weakened after an aSAH and contributes to complications of the aSAH. However, only 30 aSAH patients took part in this study, making it difficult to make strong statements about the precise role of the glycocalyx. Therefore, I want to expand this study to 150 patients. In this project, I aim to find that the glycocalyx plays an importat role in the development of late brain infarction. As we can repair the glycocalyx with medication, the results of this project may enable us to finally be able to treat or prevent late brain infarction after an aSAH, and limit the consequences of an aSAH.

  On the Existence and Pathophysiology of True Ischemia in Coronary Microvascular Dysfunction.
  Dr Brian Bingen, Leiden University Medical Center
  The gold standard for diagnostic test for coronary microvascular dysfunction (CMD) is the coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) determined during a coronary function test (CFT). However, the validation of both values is based on a model of macrovascular coronary disease, and the cutoff values are based on the values within which 95% of the healthy population falls. Therefore, it has never been investigated which CFR and IMR values actually correlate with ischemia caused by CMD. In the proposed project, we will measure lactate levels and oxygen saturation in the coronary sinus, as well as pressures in the left and right heart chambers, during a clinically indicated CFT in patients. In this way, ischemia can be definitively proven or ruled out, correlated with the corresponding CFR and IMR values, and linked to the mechanisms leading to ischemia. This is a crucial step in improving the diagnosis of CMD.
  
  Moving towards effective and ethical use of germline data in molecular tumor testing
  Dr Noor Giesbertz, Antoni van Leeuwenhoek – Nederlands Kanker Instituut
  For personalized cancer care, tests that examine tumor characteristics are important. Increasingly, tumor DNA is compared with DNA from normal cells (germline DNA). In germline DNA, it is possible to test if someone has hereditary diseases. This can be important for the patient and family members. However, in the Netherlands, hereditary predispositions are not routinely checked during tumor tests. This is not surprising as there are still ethical questions. For example, do risks of unclear genetic test results outweigh the benefits of reporting on hereditary conditions? How do we ensure that patients can make an informed choice? Should only a hereditary predisposition to breast cancer be reported on in breast cancer patients, or also predispositions to other forms of cancer? In this project, we will answer these type of questions. In part one, we will establish an ethical framework. In part two, we will put the framework into practice and study the experiences of patients and doctors. 

  A Novel Targeted NGS-PCR for Early And Accurate Detection of fungal Infections
  Dr Jochem Buil, Radboudumc
  Fungal infections are an increasing problem, particularly among individuals with weakened immune systems, such as patients with blood cancer or stem cell transplants. Early detection of fungal infections is challenging, as current diagnostic methods are often slow, inaccurate, and burdensome. With this project, we aim to develop a new, sensitive test to detect fungal infections, even before they cause severe symptoms. We will use an innovative technique called targeted Next-Generation Sequencing (NGS), which allows us to specifically detect fungi in blood samples. This approach is faster and more comfortable for patients compared to collecting samples from the lower respiratory tract, a procedure that is often considered highly burdensome. We will develop this test and subsequently validate it using blood samples from various patient groups. Our goal is to achieve a breakthrough in the diagnosis of fungal infections, enabling earlier and more targeted treatment for patients. 

  Autoantibody glycosylation in Neuro Psychiatric Systemic Lupus Erythematosus (GLYCO-NPSLE)
  Dr Jacqueline Dekkers, Leiden University Medical Center
  Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect various organs. In severe cases, the disease impacts the brain and nervous system, leading to neurological and/or psychiatric symptoms (NPSLE). We recently discovered that antibodies in SLE can have different sugar structures (glycosylation), even in the same patient. Antibody glycosylation plays an essential role in antibody effector functions. Antiphospholipid antibodies (aPL), are strongly linked to NPSLE. Currently little is known about the glycosylation of aPL and its relationship with the development of NPSLE. The aim of this research is to 1) characterize the diverse sugar structures of aPL antibodies in NPSLE and 2) to investigate the effect of these sugars on the harmfulness of aPL in these patients. Our unique NPSLE cohort and glycan experience facilitates the analysis of aPL glycan profiles in this disease, allowing to create a glycan fingerprint for early identification of high-risk patients. 

  CLEAR Surgery: Cognitive Longitudinal Evaluation and Assessment of Risk of Surgery in older adults
  Dr Mark van Zuylen, Amsterdam UMC
  Many older adults worry about memory problems after surgery, a condition known as postoperative cognitive dysfunction (POCD). This study looks at whether this decline starts before the surgery or if the surgery itself contributes to it. We will follow older adults who have been on a waiting list for at least three months for a planned hip or knee surgery. Their memory and thinking abilities will be tested several times before and after the surgery. We will also look at factors like frailty, motivation, and muscle strength to see if these are related to memory problems after surgery. With the results, we aim to better identify people at risk and develop strategies to prevent POCD and support faster recovery. This will help doctors provide better care and give patients more confidence about what to expect after surgery. 

  PDCA in PDA - Plan, Do, Check, Act in extreme preterm infants with a Patent Ductus Arteriosus 
  Dr Tim Hundscheid, Radboudumc - Amalia Children’s Hospital
  After extreme preterm birth (<28 weeks gestation) the ductus arteriosus, which connects the pulmonary artery to the aorta, often remains patent after birth. These children more often have an unfavourable outcome. Recent trials have shown that the most commonly used pharmacological treatment with ibuprofen might be more harmfull than the condition itself. In september 2023 the first Dutch national recommendation has been approved, in which it is adviced to refrain from screening and treatment. Nevertheless, some clinicians give paracetamol as pharmacological alternative or perform definitive closure with an endovascular approach. This intended research line aims to gain fundamental insight in the potential risk of paracetamol, the long term consequences on excercise tolerance after different treatment regimens in comparison to an expectant management, changes in diagnosis and prescribed therapy after implemenation of the recommendation and incentives to perform endovascular closure. 

  FOCUS-ID: Framework for Optimizing Care and UnderStanding dementia in Intellectual Disability
  Dr Flora Hillegonde Duits, Amsterdam UMC - VUmc
  People with intellectual disabilities (ID) are living longer, and dementia is an emerging issue. People with Down syndrome have a high risk of Alzheimer’s disease. Research has greatly improved care for this group. But for other syndromes and ID without a known cause, little is known, and research is scarce. Because regular memory clinics are not tailored to this group, referral to the neurologist is often skipped. Yet a correct diagnosis is key for proper care. With FOCUS-ID, I aim to improve diagnostics and better understand causes of dementia in ID. I will launch an interdisciplinary memory clinic specifically for people with ID. This bridges the gap between neurologists, ID physicians, and psychologists. I will ask all patients for consent to use their data for research. Additionally, I will investigate a new blood test for dementia in people with ID. FOCUS-ID will thus contribute to better diagnostics and increased knowledge about dementia in people with ID.
  
  Understanding persistent immune dysfunction and aging after sepsis to improve long-term outcomes
  Dr Wouter van der Heijden, Radboudumc
  Many people who survive sepsis—a serious infection—keep having health problems for a long time. Right now, doctors do not know why some people get sick again or have trouble recovering after sepsis. We hope to find out how the body’s immune system changes after sepsis and which patients are most at risk for recurring health issues. To investigate this, we will follow 200 patients who had sepsis in the ICU. We will collect blood samples and health information at different times: during their hospital stay and after they go home. We will use new laboratory methods to study their blood and look for patterns in their immune system.
  We hope this project will help doctors predict which patients need extra care after sepsis. The results can lead to better check-ups, new treatments, and more support for sepsis survivors in the future.

  Endothelial dysfunction in Fontan failure: underlying hemodynamics and responses to SGLT2i.
  Dr Anastasia Egorova, Leiden University Medical Center
  Congenital heart disease is the most common congenital defect. Some heart defects are so severe that they cannot be repaired towards a two-chamber (biventricular) heart. These patients undergo a staged surgical palliation to create a Fontan circulation. This creates a unique and very vulnerable circulation type that lacks a subpulmonary chamber. Fontan Circulatory Syndrome (FCS), a situation in which the blood circulation fails, often occurs at a young age. This project focuses on an urgent need: understanding the mechanisms of FCS and identifying effective therapeutic strategies to maintain quality of life in these patients. Endothelial cell (EC) dysfunction plays an important role in FCS. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have anti-inflammatory effects and inhibit EC dysfunction. We will evaluate the FCS hemodynamics and, where necessary, treat patients with SGLT2i. The clinical, hemodynamic and EC (dys)function changes will be studied. 

  Automated cardiac arrest detection and alerting integrated into a smartwatch
  Dr Judith Bonnes, Radboudumc
  In the Netherlands, 300 people experience an out-of-hospital cardiac arrest (OHCA) each week. The deployment of citizen responders and the increased availability of automated external defibrillators have improved survival rates. Nevertheless, assistance often arrives too late for nearly half of the victims, who are alone at the time of cardiac arrest. In recent years, the DETECT study has developed a model capable of detecting cardiac arrest via light sensors in a wristband (photoplethysmography). Soon, also data from a motion sensor will be incorporated to determine whether a cardiac arrest has occurred. This project focuses on translating the acquired knowledge and developed technology into practice. The wristband’s effectiveness in automatically detecting cardiac arrest and alerting responders will be studied - both in simulated scenarios and during real cardiac arrests in patients - and where necessary improvements will be implemented.
  
  Pathogenic BRCA1/2 Variants with Reduced Risk: Risk Estimation and Adaptation of Clinical Management
  Dr Setareh Moghadasi, Leiden University Medical Center
  Well-established disease-causing (pathogenic) variants in the BRCA1 and BRCA2 genes are associated with a high-risk of breast and ovarian cancer. However, recent research has identified pathogenic variants in these genes that may confer a lower cancer risk than initially believed. These are referred to as pathogenic variants with reduced penetrance/ risk. This project focuses on determining the risk of breast and ovarian cancer in carriers of these variants, so that they can be offered personalized screening and preventive measures. This will help to avoid unnecessary screening and preventive surgeries. For this project, data will be collected from families with these genetic variants, both in the Netherlands and internationally. These data will be used to determine cancer risks, to develop tailored screening recommendations, and to improve existing risk prediction models.