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Previous PhD dissertations

PhD disserations from Health, Aarhus University. Physical copies of disserations can be founds at AU Library, Health Sciences, Vennelyst Boulevard 4, 8000 Aarhus C.

Registration of PhD disserations started 1 September 2024. Previous copies of disserations can be found via AU Library, Health Sciences. 

Dissertations 2024

Name Dissertation title Defended Abstract
Mette Lauge Kristensen,
Department of Clinical Medicine
The influence of cervical intraepithelial neoplasia, cervical surgery, and human papillomavirus vaccination on female fertility 04/12/2024 Human Papillomavirus (HPV) is a sexually transmitted virus. Persistent HPV infection can lead to cervical intraepithelial neoplasia (CIN). A new Ph.D. project from Aarhus University, Health, has investigated the influence of CIN on female fertility, including whether CIN increases the risk of spontaneous abortion and whether HPV vaccination has a protective effect on fertility.
Camilla Rahr Tatar, 
Department of Clinical Medicine
A qualitative study of cancer screening participation among people in vulnerable positions: potential for tailored interventions 02/12/2024

Participation in cancer screening plays an important role in reducing morbidity and mortality from several types of cancer. However, people in socially vulnerable positions often participate to a lesser extent than others. A new PhD project focuses on examining the barriers to participation in cancer screening among different vulnerable groups and investigates the potential to develop tailored programmes that can ensure more inclusive access to healthcare. The project includes three groups of vulnerable people: men in drop-in centres, marginalised Greenlanders, and those experiencing involuntary loneliness.

Through a qualitative study, the challenges faced by people in socially vulnerable positions regarding cancer screening are revealed. The research incorporates the experiences and perspectives of these people themselves to understand the factors influencing their participation.

Whilst there are both similarities and differences across these groups, the research highlights their distinct needs and specific barriers. This underscores the importance of involving the people concerned in developing solutions that empower them to make informed choices and support them in accessing screening if they so choose.

Jasper Carlsen, 
Department of Clinical Medicine
Molecular Disease Phenotyping and Treatment Evaluation in Ethylmalonic Encephalopathy and Alzheimer’s Disease using Mass Spectrometry Omics 29/11/2024

Rethinking Ethylmalonic Encephalopathy
Ethylmalonic Encephalopathy (EE) is a rare disorder caused by an inability to break down sulfide, a natural chemical that in normal levels helps relax blood vessels. In EE, sulfide builds up to toxic levels, blocking the body’s energy production and causing serious symptoms early in life. The project explored the use of cobinamide, a natural compound related to vitamin B12, to clear excess sulfide from the body. In laboratory and animal models, cobinamide has shown potential in neutralizing sulfide safely. However, despite its success in these models, cobinamide had limited effect in tests with cells and mice affected by EE. This unexpected result led to a re-evaluation of what drives EE, suggesting that the disease may involve more than just sulfide buildup and highligting new mechanisms that might give rise to the symptoms. This research could open new directions for understanding and treating EE by focusing on other underlying mechanisms of the disease.

Protecting Brain Health in Alzheimer’s Disease
Alzheimer’s disease is often accompanied by accumulation of protein debris around brain blood vessels. This can worsen disease progression and complicate treatment. To understand the effects of this buildup, brain tissue from a mouse model that mimics this disease feature was examined. To counteract these damaging changes, a class of well tolerated drugs used for treating mountain sickness and glaucoma, was tested. Remarkably, in agreement with recent reports, both drugs from this class reduced many of the harmful protein changes, helping to preserve vital brain connections in the Alzheimer’s model. This suggests that these repurposed drugs could be effective in slowing down the disease’s progression by maintaining brain health longer, potentially offering a new avenue for Alzheimer’s treatment.

Emilie Grarup Jensen,
Department of Biomedicine
Complement-inhibiting nanobodies as a novel therapeutic strategy for age-related macular degeneration 29/11/2024 Age-related macular degeneration is a common retinal disease affecting the elderly. The disease may progress into advanced stages with severe central vision loss. Current therapeutic options are limited and suboptimal, highlighting the need for new, more efficient and long-lasting treatment strategies. AMD is strongly associated with an overactive complement system, which is why this ph.d. project investigates a complement inhibitor as a potential treatment for AMD. This complement inhibitor is a unique, small and highly stable single-domain antibody, termed a nanobody (Nb), originating from a speciel antibody discovered in lamas. The Nb was tested as a long-term therapeutic strategy, as a gene therapy, in which specific eye cells are enabled to stably produce the treatment. A Nb called hC3Nb1, targeting complement component C3, was selected and tested in disease-relevant cell systems and mouse models to assess its potential as a complement-inhibiting gene therapy for AMD. In conclusion, the obtained results demonstrate hC3Nb1-based gene therapy as a potential treatment for AMD.
Kristoffer Skaalum Hansen, 
Department of Clinical Medicine
Experimental treatment, immunological and genomic investigations in long COVID 29/11/2024

Long COVID is a global health issue, and up to 10% of individuals infected with SARS-CoV-2 develop prolonged symptoms. There is currently no treatment, and the reason why some develop long-term effects is unknown. This project includes the world’s first treatment with a medication targeting long COVID. Furthermore, the project examines the presence of specific antibodies against the patient's own immune system and explores a genetic basis for the development of long-term effects after COVID-19.

Maya Graham Noer
Department of Clinical Medicine
Generation of anti-FLT3 CAR T-cells by CRISPR/Cas9-editing for the treatment of Acute Myeloid Leukemia 22/11/2024

This new doctoral study has focused on developing a novel CAR T-cell therapy to treat acute myeloid leukemia (AML), a difficult to treat blood cancer. The research investigates a targeted approach using CRISPR gene-editing to engineer CAR T-cells that specifically recognize the FLT3 mutation, often found in relapsed AML cases.

The study compares CRISPR-based method with the more traditional virus based approach, aiming to create a more effective and stable CAR T-cell therapy. By integrating the CAR gene into a specific region of the T-cell DNA, the research seeks to improve therapy options for AML patients facing limited treatments.

This research adds to the growing field of precision immunotherapies and offers a promising step toward advancing leukemia treatment.
Clara Elbæk Mistegård, 
Department of Clinical Medicine
The Lectin Pathway of the Complement System in Axial Spondyloarthritis - Investigations into Diagnosis, Treatment Response, and Prognosis 22/11/2024

Axial spondyloarthritis pathogenesis remains poorly understood and is difficult to diagnose in the early stages of the disease. While effective therapy is available, early disease identification continues to pose a challenge. The PhD study explores the complement system concerning diagnosis, disease activity, treatment response, and radiographic progression in patients with axial spondyloarthritis. The research involves cross-sectional and longitudinal cohorts conducted in collaboration with partners at COPECARE, CeVig, and Charité.

Anne Catrine Daugaard Mikkelse, 
Department of Clinical Medicine
Brain dysfunction in experimental metabolic dysfunction-associated steatotic liver disease 22/11/2024 Metabolic dysfunction-associated steatotic liver disease currently affects 30% of the global population, and this prevalence is predicted to increase further. Cognitive dysfunction is a newly recognized potential comorbidity, but the underlying mechanisms are still unclear, and there exists no treatment. The aim of this PhD project at Aarhus University was to investigate the underlying mechanisms for brain dysfunction in experimental MASLD and to explore the effects of a novel treatment.
Olivia Lisa Wagman,
Department of Biomedicine
The role of the quiescent endothelium during STING-driven inflammation and the crosstalk with endothelial metabolism 22/11/2024

Endothelial cells (ECs), which line blood vessels, are essential in regulating immune responses by facilitating the passage of immune cells from the bloodstream to infection sites. This process increases vessel permeability and requires the rearrangement of junctional proteins between ECs, the expression of adhesion markers on their surface, and the release of inflammatory molecules. Moreover, these changes often require metabolic shifts in the ECs to support their activated state.

The cGAS-STING pathway plays a critical role in regulating innate immune responses, and its dysregulation can lead to pathological conditions such as autoinflammatory diseases and cancer. In this dissertation, the role of ECs during STING-mediated inflammation was explored using different models of inflammation in vivo and assessing markers of vascular inflammatory activation. Moreover, the molecular mechanisms of endothelial STING activation were examined in vitro through genetic deletion strategies. In addition, the effects of STING activation on endothelial metabolism were studied both in vivo and in vitro using different genetic deletion strategies to explore if targeting endothelial metabolism could be a therapeutic strategy for treating STING-mediated diseases.
Kathrine Synne Weile,
Department of Clinical Medicine
Early diagnosis of childhood CNS tumors; setting up a CNS tumor initiative 21/11/2024

The aim of this PhD study was to map diagnostic intervals among Danish patients and to develop and implement the Danish Brain Tumor Awareness Initiative, hjernetegn.dk. In Denmark, approximately 50 children under the age of 18 are diagnosed each year with a tumor in the central nervous system (CNS). Primary CNS tumors are the second most common type of tumors in children. The five-year survival rate now exceeds 75% in Denmark, but long-term survivors face a high risk of late effects that impact their daily lives as a result of extensive and intensive treatments. Early diagnosis is crucial in reducing the long-term sequelae in survivors of childhood cancer. The collective studies provide insight into the current diagnostic intervals for CNS tumors in children in a Danish context, as well as the impact of the COVID-19 pandemic. Additionally, the phd-project covered the design, development, implementation, and digital impact of hjernetegn.dk, a digital diagnostic support tool intended to assist clinicians when confronted with a child presenting symptoms that may be indicative of a CNS tumor.

Gregory Wood,
Department of Clinical Medicine
Coronary Magnetic Resonance Angiography for the detection of Coronary Artery Disease 21/11/2024

Coronary Magnetic Resonance Angiography (CMRA) is a non-invasive modality that can investigate Coronary Artery Disease (CAD) without the use of ionising radiation or iodinated contrast agents. However, prior clinical use has been inhibited by the long acquisition times, substantial technical expertise requirements and comparatively poor spatial resolution compared to other methods. Development of deep learning (DL) based automated software for planning and acquisition may overcome some of these challenges.

Recent studies at Aarhus University and the Department of Cardiology, Aarhus University Hospital have investigated the efficacy of these technological developments, as well as whether CMRA is approaching suffient quality for routine use in clinical practice. The aims were threefold: (1) to assess whether DL software can be integrated into a clinical CMRA workflow; (2) to establish if this software can be utilised to enable acquisition of CMRA at a higher spatial resolution; and (3) to determine whether the improvement in spatial resolution improves the diagnostic performance of CMRA.
Lise Qvirin Krogh,
Department of Clinical Medicine
Induction of labor versus expectant management in women with obesity: Assessing the risk of cesarean delivery and other maternal and neonatal outcomes 15/11/2024 Pregnant women with obesity have a higher risk of developing complications during pregnancy and of having a cesarean section compared to pregnant women without obesity. This risk increases in the last weeks of pregnancy. The PhD project investigates, using different research methods, how the risk of complications and cesarean sections is affected in women with obesity when labor is induced one week before the due date, compared to waiting for labor to start naturally. The project also looks at how obesity affects the chances of an induced labor reaching the active phase, which is necessary for a vaginal birth.
Lene Ugilt Pagter Ludvigsen,
Department of Clinical Medicine
Epstein-Barr virus infection in kidney transplant recipients – Investigating the clinical relevance and the prospects for prevention of post-transplant lymphoproliferative disorder 15/11/2024

Epstein-Barr virus (EBV) is associated with the development of a wide range of cancers, including post-transplant lymphoproliferative disorder (PTLD) among solid organ transplant recipients. Consequently, screening for EBV-DNA in blood compartments (EBV-DNAaemia) is now included in international guidelines for transplant recipients. However, the clinical significance of EBV-DNAaemia in plasma and whole blood is yet to be determined, and evidence-based therapeutic preventive strategies against PTLD remain scarce.

This PhD project aimed to investigate 1) the clinical spectrum of EBV-associated disease in patients from the Central Denmark Region and to assess the diagnostic accuracy of EBV-DNAaemia in this population, 2) to estimate the incidence and risk factors for PTLD in EBV-seronegative kidney transplant recipients in the contemporary era of immunosuppression, and 3) to investigate the incidence of EBV-DNA in both plasma and whole blood as a predictor for PTLD in kidney transplant recipients.

Angela Anna Paula Victoria Herengt, 
Department of Biomedicine
Study on the molecular anti-viral mechanism of 4-octyl itaconate (4-OI) via its induction of the Nuclear Factor Erythroid 2-Related Factor 2 (NRF2) in keratinocyte cell line infected with Herpes Simplex
Virus 1
13/11/2024

In 2018, researchers discovered that a chemical compound called 4-octyl itaconate (4-OI) can trigger an antiviral response in cells without relying on the body’s typical immune response. This finding raised questions about how exactly 4-OI works at a molecular level, leading to a PhD project aimed at uncovering its mechanism.

Initially, it was believed that 4-OI acted by activating a protein known as NRF2, which plays a role in regulating genes linked to the body's defense systems. The research involved testing various potential targets to see if they contributed to the antiviral effects of 4-OI on skin cells infected with the herpes simplex virus (HSV1). However, these tests did not reveal significant roles for those targets.

Despite this uncertainty, interest in 4-OI has surged in recent years, with numerous studies highlighting its diverse actions. Interestingly, some recent findings suggest that the antiviral effects of 4-OI may not depend on NRF2.
Sofine Heilskov, 
Department of Clinical Medicine
Skin changes in children under the age of five, hospitalised with Severe Acute Malnutrition 06/11/2024

Malnutrition requiring hospitalization, among children under 5 years of age, remains a major problem globally. Mortality is high and up to 2 out of 10 children die during hospitalisation. If this high mortality is to be lowered, it is necessary to find new treatment strategies to improve hospital management. The acute malnourished children can develop severe wounds and peeling of the skin, among other things. This is a symptom of malnutrition for which the cause is not yet known and for which the World Health Organization's (WHO) treatment guidelines do not yet provide an evidence-based management.

This PhD study is an investigation of skin changes in severe acute malnutrition. Published knowledge is reviewed, nomenclature is established and a scoring tool for clinical documentation of the skin changes is developed through a prospective observatory study. The prognostic effect of the skin changes is investigated and an exploratory study of the immune status of the patient group is included. Finally, a qualitative study of the challenges among health personnel illustrates the use of methods from health anthropology to identify the local agenda within the subject.

Asta M. Rasmussen, 
Department of Clinical Medicine
Uncovering the role and prognostic potential of regulatory non-coding RNA during health and disease 6/11/2024

Regulatory RNA that does not code for proteins (ncRNA) is an increasingly appreciated class of functional molecules essential for maintaining healthy cells. However, much is still unknown regarding their abundance, function, and clinical value.

During this PhD study, a subset of ncRNAs, namely a subclass of circular RNAs and small microRNAs, was studied in cancer using RNA-sequencing data from tumor biopsies. Computational methods were utilized and developed to better detect and characterize these RNAs across cancer types and at the single-cell level. The findings provide new insights into the mode of stability, clinical correlations, and activity of these ncRNAs, which can help propose novel prognostic biomarkers for better patient stratification for the risk of cancer progression.

Josephine Hyldgaard,
Department of Clinical Medicine
Influence of Anti-Hormonal Treatment in Bladder Cancer Incidence and Mortality - A Nationwide Cohort Study 05/11/2024
Uwe M. Pommerich,
Department of Clinical Medicine
Using personal health data for the prognosis of functional independence and beyond - Experiences from a specialised neurorehabilitation clinic treating patients with acquired brain injury 04/11/2024 In Denmark, 20,000 persons are affected by brain injury annually. Functional independence is related to quality of life and participation in society, and hence an important goal during rehabilitation. A central idea in the project was the circular repurposing of electronic health data for prognosis research, including e.g. the most likely level of functional independence after rehabilitation. Thus, the rehabilitation of previous patients may systematically inform future rehabilitation therapies and benefit future patients by e.g. supporting realistic goal setting, clinical expertise and the preparation for a life after discharge from rehabilitation.  The project entails four studies. Herein, for example, the feasibility of existing prognostic models was systematically investigated; and the prognosis for the level of functional independence estimated based on approximately 6,500 previous rehabilitation admissions.      
Stine Sofie Frank Lende,
Department of Clinical Medicine
SARS-CoV-2 Neutralizing Antibodies - Discovery, Characterization and Delivery 01/11/2024

Coronavirus infections typically give rise to common cold symptoms. However, rare viral variants emerge, causing severe respiratory disease. At the outbreak of the SARS-CoV-2 pandemic in 2020, the lack of specific prophylactic and therapeutic treatment options was limiting for patient care. This PhD thesis explores the development of novel SARS-CoV-2 specific monoclonal antibodies for SARS-CoV-2 prophylaxis, through three stages: 1) Discovery of neutralizing monoclonal antibodies from convalescent individuals. 2)  In depth characterization of antibody potency, sensitivity to viral variants, and therapeutic potential of preventing infections in mice. 3) Investigation of the possibility of delivering antibody genetic sequences through Adeno Associated Virus for long-term expression and passive immune-prophylaxis.

Rikke Vilsbøll Milling,
Department of Clinical Medicine

Assessing the Impact of Late Effects on Quality of Life after Bladder Cancer Treatment 01/11 2024

Bladder cancer is a commonly diagnosed cancer worldwide. In Denmark, approximately 2000 new cases of bladder cancer are diagnosed every year. Approximately 75% presents with non-muscle invasive bladder cancer, and 25% with muscle-invasive bladder cancer. Subsequently, treatment of bladder cancer varies greatly, spanning from transurethral resection of the bladder tumour, to adjuvant intravesical instillation therapy, to removing the bladder by performing a radical cystectomy, to radiotherapy, and systemic oncological therapy. 

Each of these treatments hold the potential of affecting the patient’s life with long-term complications also known as late effects. Any of these late effects can potentially impact the quality of life of the patients. However, knowledge on the correlation between late effects and quality of life among bladder cancer patients is sparse.

This PhD defence is based on four papers with the overall aim to describe late effects and their impact on quality of life following bladder cancer treatment.
Ida Stisen Fogh-Andersen,
Department of Clinical Medicine
Treatment of Chronic Cluster Headache with Transcutaneous Electrical Nerve Stimulation and Occipital Nerve Stimulation 31/10/2024

Chronic cluster headache ranks among the most severe pain conditions known to man. Patients experience excruciatingly painful headache attacks, often described as a knife stabbing the eye. Sometimes, patients suffer from these headache attacks multiple times a day. For some patients, the conventional medical treatment options fail to provide sufficient relief. For this group of patients, a treatment modality called neuromodulation may be an option. Neuromodulation is a therapy where a nerve structure stimulated by weak electrical currents. Several smaller studies have shown that electrical stimulation of the so-called occipital nerves at the back of the head - occipital nerve stimulation (ONS), where a stimulation electrode in implanted under the scalp - can prevent the painful cluster headache attacks in patients where other treatment options seem exhausted.

A new Ph.D. project from Aarhus University, Health, systematically investigates the effect of ONS as a preventive treatment for patients with severe chronic cluster headache. The dissertation presents a database study of the clinical effect on patients already undergoing ONS treatment. It also includes an examination of the efficacy of a simpler, non-invasive stimulation, where the occipital nerves are stimulated through the skin of the scalp, and whether the effect of this transcutaneous stimulation can predict the effect of the implanted ONS electrode. 

Finally, the results of a large randomized, placebo-controlled trial, the first of its kind, are presented, where ONS is compared to an inactive placebo treatment.
Line Mathilde Brostrup Hansen,
Department of Biomedicine 
Futile reperfusion in acute ischemic stroke: An insight from upstream pial arteries to downstream parenchymal arterioles 31/10/2024

Cerebral blood flow regulation is crucial for maintaining brain function; however, complications arise when adequate blood flow is acutely disrupted, e.g., by the incidence of stroke. Stroke is the third leading cause of death and disability globally, with acute ischemic stroke, characterized by the acute obstruction of the blood supply to a brain region, being the most prevalent type. Despite advances in stroke treatment, a large proportion of the patients experience futile reperfusion, where the patients experience poor recovery outcomes despite successful restoration of blood flow.

The dissertation explores the mechanisms behind futile reperfusion in the peri-ischemic area, focusing on structural differences between pial arteries, penetration arterioles, and capillaries. Utilizing spatial transcriptomics, real-time monitoring of blood perfusion imaging, and two models for middle cerebral artery occlusion-reperfusion, the study offers deeper insights into blood flow alterations in mice across different ages and sexes, with respect to the biological variation, using the contralateral hemisphere as a control. in addition, the study addresses the potential treatment of pNaKtide, a potential modulator of cerebral perfusion following ischemic stroke.
Nadia Roldsgaard Gadgaard,
Department of Clinical Medicine
Infection after surgery for hip fracture: inequality according to comorbidity & socioeconomic position 31/10/2024

Hip fracture is a devastating and common injury among older adults. The incidence rate of hip fracture in Denmark is among the highest globally and has increased in recent years. Despite infection being a potentially preventable and treatable condition, it remains one of the most frequent complications and causes of death following hip fracture surgery. Risk of infection after hip fracture has also increased.

The ageing of the population, the comorbidity burden, and socioeconomic inequalities in health are considered major challenges in healthcare. For instance, there is limited knowledge about the interplay between comorbidity and socioeconomic position in the context of infection after hip fracture surgery. Utilizing Danish national health registries, this PhD project aimed to address current knowledge gaps within this topic.

Mette Søeby,
Department of Clinical Medicine

Health consequences of Anorexia Nervosa: Epidemiological studies of fracture risk, mortality, and comorbidities" 31/10/2024

Anorexia nervosa is a serious eating disorder that often leads to both physical and psychological complications and increased mortality risk. The disorder is often diagnosed during adolescence and primarily affects young women, but it can also occur in men. Anorexia nervosa is marked by extreme underweight, which can lead to serious health complications. The low body weight affects all organ systems, increasing the risk of bone fractures and premature death.The current PhD project, conducted through three large register-based studies on all Danish patients diagnosed with anorexia nervosa over a 40-year period, has examined the relationship between anorexia nervosa and the somatic and psychiatric diagnoses made prior to diagnosis, the long-term risk of bone fractures, as well as the risk of death and the impact of psychiatric comorbidities on mortality. The studies reveal that patients with anorexia nervosa face a significantly higher risk of bone fractures for up to 40 years after diagnosis, particularly of the hip and spine. Furthermore, the disorder is associated with a 4.5 times higher risk of death compared to the general population, with suicide being one of the most common causes of death. Mortality is even higher in patients with other current or past psychiatric disorders.

These findings underscore the critical importance of early detection and a multidisciplinary approach to reduce the serious health consequences of anorexia nervosa.
Tua Gyldenholm, 
Department of Clinical Medicine
Coagulation and thromboprophylaxis in oesophageal cancer patients undergoing surgery 25/10/2024 Venous blood clots is the most common potentially preventable cause of death in cancer patients undergoing surgery. To prevent blood clots, all patients receive blood-thinning medication during their hospital stay following cancer surgery. This PhD project investigates patients undergoing surgery for oesophageal cancer with the aim of determining whether extended preventive treatment with blood-thinning medication can further reduce the risk of blood clots after surgery. Furthermore, the project incvestigates if a blood sample taken before surgery may help predict which patients are at increased risk of developing blood clots.
Pia Boxy,
Department of Biomedicine
The role of autism risk gene SorCS2 in cerebellar development 25/10/2024

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder (NDD), characterized by disrupted social interactions and repetitive behaviors, that affects approximately 1% of children worldwide. While the exact causes remain uncertain, ASD is often linked to abnormal neural circuit function and cerebellar abnormalities. A new PhD project at Aarhus University, Health, investigates the role of the sortilin receptor family member, SORCS2, a gene associated with ASD and other NDDs, in cerebellar development and circuit formation. This research highlights the cerebellum's role in higher-order cognitive functioning and provides valuable insights for future studies on cerebellar dysfunction in ASD and similar disorders.

Kristian Wiborg Antonsen, 
Department of Clinical Medicine
Targeted inhibition of phagocytosis checkpoints in tumor-associated macrophages 25/10/2024

What determines if the immune system can attack cancer cells? And how can we support it? This has been investigated in a new PhD project from Aarhus University, Health. 

The immune system plays an important role in cancer and represents a potential source of future treatments. One the constituents of the immune system, cells known as macrophages, are able to attack and kill cancer cells under the right conditions. This PhD project has investigated which factors regulate the ability of macrophages to destroy cancer cells, and how these factors can be medically influenced. The results of the project suggest that new techniques can potentially be used to support macrophage killing of cancer cells, and are based on laboratory experiments performed at the Department of Clinical Biochemistry at Aarhus University Hospital.

Emma Skarsø Buh, 
Department of Clinical Medicine
DBCG RT Nation Automation: National consistency in delineation in breast cancer patients 14/10/2024

Radiotherapy improves survival of breast cancer patients. However, the radiotherapy treatment planning consists of time-consuming manual processes, such as delineation of organs at risk and treatment area on CT-scans. Large databases and modern techonology, such as artificial intelligence, enable the analysis of nationwide delineation trends and automating the delineation process. This forms the background for a new PhD project from Aarhus University, Health.

In the study, deep learning models for automatical delineation of both organs at risk and treatment areas in breast cancer patients are developed and comprehensively tested for national clinical implementation. Additionally, the models are used to demonstrate methods to do both large scale national retrospective dose audits of patients treated, as well as investigating the impact of delineation differences on the resulting radiotherapy treatment plan given to the patients. 

Marie Beck Hairing Enemark, 
Department of Clinical Medicine
Identifying predictive biomarkers of histological transformation in follicular lymphoma:  unravelling biological differences as means for patient-specific risk stratification 11/10/2024

Follicular lymphoma (FL) is a lymphoid malignancy derived from germinal center B cells. Despite advancements in treatment, the disease remains generally incurable with recurrent relapses. Furthermore, a subset of patients will experience treatment refractoriness, early disease progression, and histological transformation into a more aggressive lymphoma type, most often diffuse large B-cell lymphoma. This event is manifested by a rapid clinical course, often with unresponsiveness to treatment, and shortened survival. Thus, transformation marks a pivotal change in disease trajectory, yet reliable predictors for subsequent progression or transformation remain elusive.

This Ph.d. project describes the transformation of FL, with the aim to unravel pre-treatment biological differences underlying the diverse disease course for upfront personalized risk stratification and improved patient care.

The dissertation comprises eight original papers. These include several molecular biological investigations of proteins and gene expression thoroughly examined in relation to transformation of FL, revealing predictive potential of several proteins in the neoplastic cells as well as the tumor microenvironment.

Collectively, the results emphasize the substantial complexity and heterogeneity of FL and highlights the need for more in-depth evaluations correlating molecular markers with disease outcomes. We provide new clues and insights into FL’s molecular landscape, with the aim of paving the way for novel personalized therapeutic and prognostic strategies, ultimately improving patient outcomes and quality of life with this new Ph.d. project from Aarhus University.
Søren Skou Lomholt, 
Department of Biomedicine
Synovial fibroblasts in immune mediated arthritis - A story of kids, chemokines, and complex in vitro models 11/10/2024

PhD defence on connective tissue cells in child and adult arthritis

Arthritis in children and adults is a collective term for number of chronic diseases that typically affect joints and tendons. While at the same time, increase the patient's risk of chronic pain, reduced quality of life and disability. Researchers have therefore become more and more aware that the type of activated cells in the disease affected joint is important for both disease activity and treatment success. Among these disease-active cells, especially connective tissue cells, have received attention, as they can both contribute to driving disease activity and destruction of the joint.

A new PhD project at Aarhus University, Health, examines these issues. The thesis presents both a detailed analysis of cell types, including connective tissue cells, in disease affected joints in children with juvenile arthritis. The scientific studies that form the basis of the thesis also show that the connective tissue cell-related, CXCL12 and CXCL14, signaling proteins in the blood cannot be used to predict the long-term prognosis for disease activity in adults with rheumatoid arthritis. The thesis also presents a new and optimized method for analysing the joint's connective tissue cells, as well as a method for building miniature joints for scientific studies in the laboratory.

Jane Lauridsen, 
Department of Clinical Medicine

Workplace intervention to reduce sick leave among pregnant hospital employees – a cluster randomized trial.

10/10/2024

In a recently completed Ph.D. project from Occupational Medicine, Aarhus University Hospital and Aarhus University, Jane Lauridsen evaluated an intervention with occupational midwifery support on pregnant employees' sick leave and well-being.

Sick leave during pregnancy is common and 36% of all pregnant employees are absent for more than two weeks. Sick leave can be associated with individual and occupational factors. Occupational factors can be exposure to harmful agents or strenuous working conditions such as walking and standing, heavy lifting, or shift work. Work adjustment is associated with reduced sick leave.
This project evaluates an intervention aiming to reduce strenuous occupational exposures. The overall aim was to evaluate the effect of occupational midwifery support, where midwives facilitated risk assessment and work adjustment in meetings with pregnant employees and their managers.
The study was conducted at Aarhus Universityhospital as a cluster-randomised trial with hospital departments allocated to intervention or reference.
In addition to evaluating midwifery support, the projct also investigated managers´ perspectives and engagement in pregnancy policy.

Lotte Veddum, 
Department of Clinical Medicine
Social responsiveness and theory of mind in children at familial high-risk of schizophrenia or bipolar disorder: Behavioral assessment and functional neuroimaging 08/10/2024

Schizophrenia and bipolar disorder are highly heritable and severe mental disorders associated with marked social cognitive impairments, and it has been suggested that social cognitive impairments constitute vulnerability markers presenting before illness onset. Additionally, previous research of both disorders indicates that disruptions of brain development early in life underlies the emergence of symptoms later in life. Children born to parents with schizophrenia or bipolar disorder constitute a unique study group in the investigation of the etiology and pathogenesis of these two mental disorders. However, studies investigating social responsiveness and theory of mind (i.e., mentalizing) in young offspring at familial high-risk of schizophrenia or bipolar disorder are lacking. Therefore this was investigated in a recent Ph.d. project from Aarhus Universiy, Health, Department of Clinical Medicine. The Ph.d. project was carried out by psychologist Lotte Veddum.

The aim of this Ph.d. project was to elucidate whether social responsiveness impairments and ToM deficits constitute potential early vulnerability markers of schizophrenia or bipolar disorder. The Ph.d. project constitute as part of The Danish High Risk and Resilience Study - VIA, which is a transdiagnostic, longitudinal, and prospective cohort study of same-aged children born to parents diagnosed with schizophrenia, bipolar disorder, or neither of these two mental disorders. Social responsiveness and theory of mind were investigated from a behavioral, developmental, neurobiological, and transgenerational perspective. Overall, the results revealed that social responsiveness impariments may constitute an early behavioral and transgenerational vulnerability marker, while aberrant effective connectivity within the mentalizing network may constitute an early neurobiological vulnerability marker, emerging before alterations in regional brain activation and behavioral theory of mind deficits.
Sham Al-Mashadi Dahl, 
Department of Clinical Medicine
Risk and prognosis of infections in cancer patients with inflammatory bowel disease 04/10/2024

The intricate interplay between inflammatory bowel disease (IBD), cancer, infections, and mortality is explored in a new PhD project at Aarhus University, Health.

IBD are chronic, immune-mediated inflammatory disorders encompassing Crohn’s disease and ulcerative colitis. Patients with IBD face an increased risk of developing colorectal cancer, as well as several other types of cancer.

When patients with IBD develop colorectal cancer, their prognosis is typically worse compared to those without IBD, which may be exacerbated by their inherent increased risk of infections. Serious infections are a leading cause of hospitalization and mortality among IBD patients. Moreover, infections account for more than half of all oncology-related hospital admissions, negatively affecting cancer-specific survival rates.

This PhD project provides novel insights into the association between IBD and post-cancer infection risk, as well as the link between IBD and post-colorectal cancer mortality, based on data from a Danish cancer cohort.

Lasse Hansen, 
Department of Clinical Medicine
Prediction of Diagnostic Progression to Bipolar Disorder or Schizophrenia Using Machine Learning on Electronic Health Records 04/10/2024

The possibilites of machine learning for prediction of severe mental disorders was investigated in a new ph.d project from Aarhus University, Health.

Schizophrenia and bipolar disorder are severe mental disorders that are often diagnosed and treated several years after their onset. Using machine learning (ML) to analyze data from electronic health records (EHRs) might help identify early signs of these disorders, enabling earlier diagnosis and targeted treatment. While research on AI in healthcare is growing rapidly, relatively few studies have explored its use in psychiatry. This ph.d. project aimed to predict the diagnostic progression to schizophrenia or bipolar disorder in patients attending psychiatric services for treatment of less severe mental illness. The study used routinely collected information from EHRs, such as diagnoses, medication, and clinical notes as input to ML models. The findings revealed that schizophrenia was easier to predict than bipolar disorder and that incorporating text data was particular important for prediction.

Marie Høst Pahus, 
Department of Clinical Medicine
Broadly neutralizing antibodies in HIV-1 clinical trial 02/10/2024

Broadly neutralizing antibodies (bNAbs) are being used in clinical studies which seeks to lower the viral reservoir in persons living with HIV-1. bNAbs have shown to be able to neutralize cell-free virusparticles and activate the immune system and thereby increase the pressure on HIV-1 infected cells. Due to a high mutation rate in HIV-1, the bNAbs do not have an effect in all persons living with HIV-1, which makes it important to screen virus from the participants prior to inclusion in a study using bNAbs. 

In this PhD project a published clinical study is presented, in which persons with HIV-1 were randomised to receive two bNAbs and a drug (Lefitolimod), which have shown to reactivate virus in HIV-1 infected cells. The participants stopped their normal antiviral treatment and the study showed that participants who received the bNAbs had longer time before virus was detectable in the blood, than participants who did not receive the bNAbs.  

Addtionally, a study in which methods to screen participant-specific HIV-1 for sensitivity toward the bNAbs were compared. The study showed that there can be differences in the methods which are being used for sensitivity assessment for the bNAbs.

Sofie Andersen, 
Department of Biomedicine
Delivery of genome editing tools in lentivirus-derived nanoparticles for gene editing based on non-homologous end joining and homology directed repair 01/10/2024

A new PhD project from Aarhus University, Health, is exploring packaging and delivery of genome editing tools for presice gene editing in lentivirus-derived nanoparticles.

Many hereditary monogenic diseases of the blood can be cured by gene editing, where the mutated gene will be edited back to a functional one. Current treatment strategies rely on harvest of the patients own cells and culturing and editing in the laboratory following reinfusion back to the patient. This treatment is time consuming and expensive, and the patient need to go through several severe treatment regimens.  This project explored a genome editing tool delivery strategy that may be applicable to use directly in the patint, which would also allow the same treatment to be used in several patients, thereby reducing the costs. The project resulted in one published article showing efficient packaging and delivery of genome editing tools in lentivirus-derived nanoparticles for gene disruption in the eye of a mouse, and one article that is hopefully soon published. Additionally, the project initiated two still ongoing projects. 

Donato Sardella, 
Department of Biomedicine
Intravital Microscopy of the Kidney in Small Rodents for the Investigation of Renal Physiology in Health and Disease 30/09/2024

Fluorescence Microscopy of the Living Kidney to Visualize and Understand Renal Physiology

The dissertation is centered around a cutting-edge microscopy technique that allows the real-time visualization and assessment of kidney function in living small rodents. The research introduces key advancements aimed at overcoming the challenges of data acquisition and processing in this complex field. In addition, the study highlights two practical applications of this technology, offering new insights into renal physiology and potential implications for future medical research.

Sara Bønløkke Lindved,
Department of Clinical Medicine
Circulating Human Papillomavirus - diagnostic value and clinical implications in cervical cancer patients 27/09/2024 This project investigated whether HPV DNA is released into the bloodstream as circulating HPV DNA (ccfHPV DNA) of cervical cancer patinets and the potential of measuring ccfHPV DNA in these women. We developed assays based on two different platforms: one based on digital droplet PCR (ddPCR) for detecting and quantifying ccfHPV DNA, and two based on Next Generation Sequencing (NGS) for detecting ccfHPV DNA and identifying HPV genotypes and integration status in both tissue and blood samples. Among 139 women included, ccfHPV DNA was detected in most advanced cases but rarely in early-stage cases. The presence of ccfHPV DNA correlated with disease stage and recurrence, with 100% recurrence rate in patients with detectable ccfHPV DNA three months after treatment. Additionally, HPV was found to be an essential driver in loco-regional and distant recurrences of cervical cancer, with TP53 mutations potentially being linked to HPV-independent cervical cancer.
Peter Kolind Brask-Thomsen,
Department of Clinical Medicine
Natural History of Painful and Non-Painful Diabetic Polyneuropathy 27/09/2024

Diabetic polyneuropathy is a common and debilitating complication to diabetes that affects up to 50% of all patients with diabetes. It affects the long nerves of the body, causing loss of sensation as well as unpleasant sensory disturbances in the feet and legs. Between 10-35 % of patients with diabetic polyneuropathy suffer from pain. It is currently unknown what causes pain to develop. This condition, especially with concurrent pain, impacts the quality of life of patients in various negative ways, and no satisfactory treatment exists. Despite this, diabetic polyneuropathy has often been considered an overlooked complication to diabetes, which may be the reason that there are few detailed studies on its development over time.

This PhD project followed patients with diabetic polyneuropathy and type 2 diabetes over five years using state-of-the-art diagnostic methods to determine how both diabetic polyneuropathy and pain develops over time, which patients develop pain, what impacts this development, and how these changes affect patient quality of life and mental health.

Josephine Therkildsen, 
Department of Clinical Medicine
Bone Erosions in Rheumatoid Arthritis - Characterization and Early Detection of Progression 27/09/2024

Rheumatoid arthritis (RA) may lead to bone erosions, which can accumulate over time and severely affect joint function. Effective treatment options exists, however it remains challenging to identify patients with erosive progression and to detect erosive progression at an early stage due to low sensitivity by conventional radiography (CR).

A new PhD project from Aarhus University, Health investigates this problem.

This thesis is based on a clinical one-year cohort study investigating a high-resolution imaging modality (HR-pQCT) compared to CR in patients with RA. Furthermore,  a blood biomarker is investigated for detecting short-term erosive progression in patients with RA.
Layla Pohl, 
Department of Biomedicine
T-Follicular Regulatory Cell Participation in Autoreactive Germinal Center Reactions 27/09/2024

Autoimmune diseases are rising in society and a huge burden to patients. The main characteristic shared by all of them is the patient’s own immune system attacking the body and damaging organs, up to the point of failure. However, current treatment options are limited and come with severe side effects such as infections and even cancer.

The development and progression of autoimmune diseases is complex, long-lasting and not fully understood – including the emergence and shutdown of autoreactive germinal centers, which are presumably contributing to disease progression, especially the germinal centers in the spleen.

The emergence and shutdown of germinal centers are week-long dynamic processes and therefore difficult to capture and understand. Thus the development of novel techniques is necessary to study germinal center dynamics to help understand the development and progression of autoimmunity to one day hopefully being able to develop better treatment.

In my PhD defense, I will present a newly developed and validated approach to study autoreactive germinal center dynamics over two weeks in a living organism by using serial intravital microscopy of the spleen. I will furthermore present how we are exploiting this technique to shed more light on the development of autoimmunity.

Erik Kaadt, 
Department of Clinical Medicine
Novel Drug Targets of Depression - Focusing on Non-Coding RNAs 26/09/2024

Depression is a debilitating mental illness that imposes a significant burden on affected individuals, their families, and society as a whole. The incomplete understanding of the pathophysiological mechanisms underlying depression, has made the development of universally effective pharmacological treatments challenging. As a result, currently available treatments often come with delayed onset of effect and more than 30% of patients being classified as treatment resistant.

In parallel, it has been demonstrated that a large portion of the human genome expresses transcripts that do not code for proteins. These non-coding RNAs (ncRNAs) are estimated to constitute up to 90% of the human genome and are abundantly expressed in the brain. Cumulating evidence has suggested that ncRNAs play a central role in the etiology and treatment efficacy of depression and thus offer a novel approach to investigate the molecular mechanisms underlying depression.

This PhD study aimed to identify novel mechanisms underlying the pathophysiology of depression, focusing on ncRNAs, with the goal of contributing to the development of novel treatment strategies.

The study utilized the nCounter Nanostring technology, to investigate ncRNA expression profiles across various organisms (human, pig, rat), with a central focus on samples from The Danish Brain Collection. The focus was on both depressed patients and animal models of depression, as well as ncRNA regulations induced by novel, relatively unexplored compounds expected to provide rapid and improved antidepressant effects in treatment-resistant patients.
Pernille Thordal Larsen, 
Department of Clinical Medicine
Detection of Colorectal cancer after a positive FIT screening with no malignant findings - An evaluation of the Danish surveillance and screening guidelines 25/09/2024

A positive screening test for colorectal cancer, but no cancer - What now?

In a recently completed Ph.D. project from Aarhus University and Randers Regional Hospital, Pernille Thordal Larsen investigated how many people are diagnosed with colorectal cancer after initially being screened without any findings of cancer. 

The evidence supporting the Danish recommendations for follow-up after a screening-derived colonoscopy is limited, despite the fact that since 2014, these recommendations for colonoscopy follow-ups have led to a significant increase in the number of colonoscopies performed in Denmark. This Ph.D. project utilized Danish health registers and databases to investigate how many people are diagnosed with cancer after initially undergoing a screening process that did not result in a cancer diagnosis. The project found that, in general, there were few cases of cancer, but the number of polyps found during the colonoscopy was a poor indicator of the risk at the next screening or follow-up examination. Therefore, it is concluded that screening recommendations should be based on risk factors that consider more than just the results of the colonoscopy, and further efforts should be made to ensure high-quality colonoscopies for all screening participants in Denmark.

Helga Haahr-Lillevang, 
Department of Clinical Medicine
Sex Hormones, Diagnostic Validation and Epidemiology in Chronic Inflammatory Demyelinating Polyneuropathy 25/09/2024

New research in a rare neurological disorder.

Incidence, diagnostic validity, thromboembolic risk, association with cancer and hormonal levels was investigated in patients with Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) in Denmark.

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) is a disabling disease predominantly diagnosed in men around the age of 50 years and above. But how many patients who are diagnosed every year in Denmark, has up until now remained unknown. This has now been studied, together with the validity of the diagnosis, the risk of thrombosis in association to treatment and the association between CIDP and cancer. Furthermore a suspected association between sex hormone levels and CIDP have been investigated during this PhD. 

Sarah Marie Bjørnhol, 
Department of Clinical Medicine

Towards more accurate and gentle surgery for women with endometrial cancer - The SENTIREC-endo study

20/09/2024

In endometrial cancer, the presence of lymph node metastasis is the most significant negative prognostic factor. Surgical staging is performed to identify women with lymph node metastasis to allocate them to adjuvant therapy, with the overall purpose to improve survival. Sentinel lymph node (SLN) mapping represents an accurate and minimally invasive staging technique, with the potential to increase the identification of lymph node metastases. This PhD thesis is based on two national prospective studies, SENTIREC-endo I and II, that investigated aspects of SLN mapping implementation in women with endometrial cancer. SENTIREC-endo I presents the result of a national protocolled implementation of SLN mapping in women with low- and intermediate-risk endometrial cancer. We conclude that SLN mapping, in a centralized setting, carries a very low risk of peri- and postoperative complications and that women benefit from the procedure in terms of increased detection of lymph node metastases compared to previous standards. Despite more comprehensive surgery for a large proportion of women, SLN mapping was not associated with an increased risk of clinically significant lymphoedema. SENTIREC-endo II, investigated diagnostically safe SLN mapping algorithms to replace the standard of pelvic and paraaortic lymphadenectomy in women with high-risk endometrial cancer. We identified two safe surgical algorithms. The SENTIREC-endo studies have changed clinical guidelines towards more gentle and accurate surgery for women with endometrial cancer and lead to new international evidence.

Merete Nørgaard Madsen, 
Department of Clinical Medicine
Physical rehabilitation exercise early after total hip arthroplasty - effectiveness and patient perspectives 20/09/2024

Physical rehabilitation exercise is recommended and commonly prescribed in clinical practice after total hip arthroplasty. However, it can be questioned, whether this practice is based on high-quality research and if the use of physical rehabilitation exercise lead to better patient results than a pathway without the prescription of exercises. In the four studies of this PhD project, we used different methodologies to investigate the preliminary effect of and patient views on early initiated physical rehabilitation exercise after total hip arthroplasty. This included; a summary of existing research trials comparing patient pathways with and without physical rehabilitation exercises, a clinical study investigating if patients who perform more exercises achieve better results than those exercising less, and an interview study exploring how physical rehabilitation exercise is perceived by patients and physiotherapists. Finally, a plan is outlined for a future study aiming to determine if a patient pathway without the prescription of exercises is feasible.

Pernille Gro Thrane, 
Department of Clinical Medicine
Cardiovascular Outcomes in ST-segment Elevation Myocardial Infarction Following Implementation of a Primary Percutaneous Coronary Intervention Strategy 20/09/2024 During the last two decades, management of ST-elevation myocardial infarction (STEMI) has changed substantially. Today direct transport to coronary reperfusion with primary percutaneous coronary intervention (pPCI) is recommended. A recommendation based on the DANAMI-2 trial, which also carried the implementation of pPCI in Denmark and the subsequent changes in prehospital management. Furthermore, new pharmacological treatments and interventional strategies have been implemented. Through four observational studies, this ph.d.-project from Aarhus University, Health  evaluates I) the 16-year outcomes of the DANAMI-2 trial, II and III) temporal trends in 1-year mortality and risk of major adverse cardiovascular events after pPCI-treated STEMI from 2003 to 2018, and IV) excess 10-year mortality after STEMI compared to an age- and sex-matched general population.
Mikkel Lundbech, 
Department of Clinical Medicine
Coagulation and Fibrinolysis in Colorectal Cancer Surgery 18/09/2024 Patients undergoing surgery for cancer face an increased risk of blood clots. Colorectal cancer can usually be removed using laparoscopic surgery, which is considered to have a lower risk of blood clots compared to traditional open surgery. If colorectal cancer has spread to the peritoneum, selected patients can be offered curatively intended cytoreductive surgery where all visible cancer within the peritoneum is removed through open surgery. Despite the different types of surgery and risks of blood clots, the same extended anticoagulant medication for 28 days is recommended for all colorectal cancer patients after surgery. This PhD project investigated whether cytoreductive surgery with HIPEC increases the risk of blood clots compared to laparoscopic surgery in colorectal cancer patients. We found that cytoreductive surgery with HIPEC increases blood clotting and thus raises the risk of blood clots more than laparoscopic surgery. The frequency of blood clots within 30 days after cytoreductive surgery with HIPEC was significantly higher than previously reported. We also observed that neither the extent of colorectal cancer spread to the peritoneum nor HIPEC itself had a significant effect on blood clotting.
Cecilie Blenstrup Patsche, 
Department of Public Health
Nutritional Challenges in Tuberculosis Care in Guinea-Bissau 18/09/2024

Tuberculosis is an infectious disease that is especially prevalent in low-income countries, where poverty and crowded living conditions contribute to disease transmission. Although tuberculosis can be cured with antibiotics, it is estimated that over 10 million people develop tuberculosis, and over 1 million people die from tuberculosis every year worldwide.

Malnutrition, especially undernutrition, is a well-known risk factor for developing tuberculosis. An insufficient intake of energy, protein, and micronutrients, weakens the immune system and thereby increases the risk of developing tuberculosis. Malnutrition may be a result of food insecurity in low-income countries. Furthermore, tuberculosis disease causes malnutrition through various disease-specific effects on the body. It is often difficult to ascertain which comes first - malnutrition or tuberculosis - and which makes the other worse.

The West African country Guinea-Bissau is one of the poorest countries in the world. It has a high prevalence of both food insecurity and tuberculosis. The Ph.d. project explores the relationships between malnutrition and tuberculosis in Guinea-Bissau, and examines if a combined treatment of both malnutrition and tuberculosis is beneficial to patients.

Kristoffer Kallesøe Berg-Hansen, 
Department of Clinical Medicine
Cardiogenic Shock and Chronic Heart Failure: Prognostic Evaluations and Ketone-Based Therapeutic Interventions 13/09/2024

Heart failure ranges from stable chronic heart failure to the critical condition of cardiogenic shock, which is characterized by high mortality and limited treatment options. This Ph.D. dissertation sheds light on the risk stratification and treatment of heart failure. The research has investigated global longitudinal strain measured by transthoracic echocardiography as a risk marker in patients with cardiogenic shock, demonstrating that this metric is a significant predictor of mortality both during hospitalization and up to one year after. Additionally, the study explored the effects of ketone supplementation with ketone ester on cardiac function in patients with cardiogenic shock and stable chronic heart failure. Treatment with ketone ester showed a significant improvement in cardiac function in both patient groups, with a sustained positive effect after 14 days of treatment in patients with chronic heart failure. These findings suggest new opportunities for improved risk assessment and treatment of heart failure patients. 

Fernando Valentim Bitencourt, Department of Dentistry

Diabetes complications, dyslipidaemia and the burden of periodontitis 06/09/2024

The prevalence of periodontitis, an inflammatory condition that affects the tissues supporting teeth, is three times greater in individuals with Type 2 Diabetes Mellitus (T2DM) than in those without T2DM. Despite this prevalence, the relationship between periodontitis and diabetes-related complications has remained unclear until now. The PhD studies, conducted through population-based studies, analyzed data from participants across US and Denmark: the National Health and Nutrition Examination Survey (NHANES) and the Health in Central Denmark (HICD) study. The findings reveal that periodontitis co-occurs with other diabetes-related complications, influenced by factors such as age, sex, obesity, physical activity, diet, socioeconomic status, smoking, HbA1c levels, and dyslipidaemia. The study also demonstrated that higher HbA1c levels and obesity had a significant indirect effect on periodontitis through dyslipidaemia. In addition, diabetic retinopathy, neuropathy, and both complications increase the likelihood of developing periodontitis by 1.2 to 1.5 times. Furthermore, dyslipidaemia was shown to significantly modify the odds of 'moderate/severe' periodontitis, particularly when multiple diabetic microvascular complications are present.

These findings underscore the need to include periodontitis in prevention and management strategies for diabetes-related complications, especially for patients with dyslipidaemia.
Emil Nielsen Holck, Department of Clinical Medicine Percutaneous Coronary Interventions for Chronic Total Occluded Coronary Arteries 06/09/2024

A new PhD thesis from Aarhus University investigates the treatment of a severe form of atherosclerosis in the heart, where one of the coronary arteries is completely blocked. This condition, known as chronic total occlusion (CTO), makes treatment more challenging, and it is uncertain whether the standard treatment with balloon angioplasty and stent placement is effective for these patients.

What is the research about? The research examined whether patients with CTO who have undergone balloon angioplasty have the same long-term prognosis as patients without CTO. Additionally, the study investigated whether it matters which coronary artery is treated and whether the treatment is cost-effective.

How was the research conducted? Two of the studies followed over 21,000 patients in the Central Denmark Region who were treated from 2009 to 2019, comparing the outcomes for those with and without CTO. The cost-effectiveness was analyzed with the help of both international and national registries. Finally, the results were used to design a randomized controlled trial that currently includes patients across Europe.

Why is it important? The results show that patients with successful CTO treatment have the same prognosis as patients without CTO. However, if the treatment is unsuccessful, especially in a specific coronary artery, the left anterior descending artery, the prognosis is worse. The research also shows that successful treatment is more cost-effective than unsuccessful treatment due to better long-term prognosis.

Anders Dahl Kramer, Department of Clinical Medicine Left Atrial Appendage Closure - Diagnosis and Prevention of Device-Related Thrombosis 06/09/2024 Left atrial appendage closure (LAAC) has become an increasingly utilized stroke preventive therapy among patients with atrial fibrillation (AF) unsuitable for long-term oral anticoagulation. However, device-related thrombosis (DRT) appears across the surface of 1-5% of implanted devices. This incidence varies greatly across published studies, in part, due to variations in DRT detection and postprocedural antithrombotic strategies. Through three retrospectice studies, a new phd-project from Aarhus University, Health and the Mayo Clinic establishes and evaluates new methods for assessment and prevention of DRT-suspect findings on follow-up imaging.
Mathias Møller Thygesen, Department of Clinical Medicine Spinal perfusion pressure – a novel treatment target in traumatic spinal cord injury 05/09/2024

The ph.d-project investigated whether pressure increases within and round the spinal cord, following traumatic spinal cord injury. Contrarty to already published litterature, the study did not spinal cord injury to cause pressure to increse.

Traumatic spinal cord injury is typically caused by high-energy trauma inflicting damage to the spinal cord. During the last decade, multiple studies have shown that the spinal cord is damaged even further during the folloiwing hours and days. This has been suggested to be caused by an increase in the pressure within the spinal cord, reuding the blood flow. In this ph.d.-project it was invesigated whether this pressure increase was caused by the spinal cord injury. The study found that meanwhile pressure did increase, it did no increase more, than following conventional spinal surgery.

Anne Karmisholt Grosen, Department of Clinical Medicine Optimising faeces donor screening and selection by establishing evidence-based donor criteria 04/09/2024

Faecal microbiota transplantation (FMT) involves the transfer of intestinal microbiota from a healthy donor to a patient. The choice of donor is crucial to ensure a safe and possible also effective treatment. Despite this, faeces donation criteria are not based on evidence.

The aim of this project was to produce knowledge that will contribute to establishing evidence-based criteria for faeces donation. A wide range of donor criteria are addressed, including gastrointestinal symptoms and bowel habits, asymptomatic Helicobacter pylori carriage, and an assessment of whether donor factors affect the clinical effect of FMT in patients with Clostridioides difficile infection.

Using data on a healthy reference, we describe common gastrointestinal symptoms and common bowel habits in healthy adults. We found no evidence of H. pylori transmission from donors to recipients by FMT administered via oral capsules. The project provides new insights into associations between donor factors and the clinical effect of FMT that may optimise donor selection. Altogether, the project contributes important insights into aspects of FMT safety and efficacy that contribute to establishing evidence-based donor criteria.
Kathrine Ravn Kjær, Department of Clinical Medicine The HIV-1 Reservoir: Exploring Proviral Persistence and Transcription Dynamics 03/09/2024

A new PhD dissertation from Aarhus University, Health, sheds light on the challenges of combating HIV-1, which remains a chronic infection despite lifelong treatment with antiretroviral therapy. The key obstacle to curing HIV-1 is a reservoir of latent, infected cells that evade detection by the immune system. The research project, conducted by Kathrine Kjær, investigates the efficacy of the drug romidepsin in reactivating latent viruses so they can be detected and destroyed by the immune system, as well as the role of monocytes in sustaining viral persistence.

The project has developed new tests based on digital droplet PCR technology to assess the activation of individual latent viruses. These tests revealed the extent of activation of individual proviruses by romidepsin and provided a detailed understanding of the overall viral activation. Additionally, digital droplet PCR was employed to evaluate the stability of the HIV-1 reservoir in monocytes and CD4+ T cells over time

The results of the research project demonstrate that romidepsin only activates a small fraction of latent viruses, which explains its limited success in clinical trials. Although CD4+ T cells remain the main reservoir, other cells such as monocytes may also contribute to the persistence of HIV-1 infection. This research offers valuable insights into the complexities of eradicating HIV-1.
Anne Dorte Lerche Helgestad, Department of Clinical Medicine Cross-programme synergies in the three cancer screening programmes in Denmark 30/08/2024

Screening for breast, colorectal, and cervical cancer can reduce morbidity and mortality from these three types of cancer, but participation in the three national screening programmes varies.

The aim of the PhD project was to investigate cross-programme synergies and correlations across the three cancer screening programmes in Denmark.

In a clinical intervention study, women attending breast cancer screening in the Central denmark Region were offered an administrative check-up on their screening status for cervical and colorectal cancer. Women who were not up-to-date with their screenings were subsequently offered the opportunity to perfom self-collected screening for cervical and colorectal cancer.

In two register-based studies, the relationship between screening participation and both sociodemographic data and level of health literacy was examioned to better understand the characteristics of those who do not participate in all three screening programmes.