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Coming dissertations at MedFak

  • Internet-based treatment for vulvodynia Author: Andrea Hess Engström Link: Publication date: 2022-09-29 12:53

    Localized provoked vulvodynia is the most common cause of sexual pain and most often affects women between 20 and 30 years old. The etiology of provoked vulvodynia remains unclear, but an interplay of biomedical and psychosocial mechanisms is believed to contribute to the onset. The choice of treatment for provoked vulvodynia depends on locally available resources. Internet interventions can reach patients in distant geographical areas and may thus promote equal access to healthcare services. A few studies have investigated the effects of cognitive behavioral therapy on provoked vulvodynia. However, there appear to be no studies of the effects of an internet intervention using an acceptance and commitment therapy approach, also called third-wave cognitive behavioral therapy, for women with provoked vulvodynia.

    The aim of this thesis was to investigate the effects and patient experiences of a guided internet-based intervention for women with provoked vulvodynia during the waiting period for clinical treatment. All four studies included in this thesis were tied to a multicenter randomized controlled study: the EMBLA study. Participants were randomized to a six-week guided internet intervention or a waiting list before treatment as usual. Pain during intercourse, other pain-related variables, and pain acceptance were variables used to assess the effects of the intervention. Later, interviews were carried out with participants to ascertain their experiences of this internet-based treatment. Lastly, health-related quality of life and healthcare utilization were assessed to obtain a health economic evaluation of the intervention. 

    Internet-based treatment had a positive effect on pain during intercourse and pain acceptance, but the results should be interpreted with caution due to the small sample size. This form of treatment was perceived as credible and helpful for managing provoked vulvodynia, but some difficulties related to the internet-based treatment were also reported. The intervention contributed to meaningful clinical effects at low costs per patient, indicating that internet-based treatment is not inferior to the standard of care. Internet-based treatment may serve as a complement to regular care, especially for patients living in geographical locations with low access to specialized care or where there are long waiting lists to initiate treatment.

  • On Pathophysiology and Treatment of Aortic Disease Author: Marek Kuzniar Link: Publication date: 2022-09-26 13:25

    Pathophysiological processes underlying abdominal aortic aneurysm (AAA) formation and aortic dissections (AD) are largely unknown. Molecular imaging of the inflammatory component may improve our understanding of AAA and AD pathophysiology. The aims of this thesis were to evaluate the feasibility of positron emission tomography/magnetic resonance imaging (PET/MRI) to study in vivo pathophysiological changes of these aortic pathologies, and to study the outcomes after complex contemporary endovascular treatment thereof.In Paper I, we evaluated the feasibility of 18-F-fluorodeoxyglucose (FDG) PET/MRI to identify markers for inflammation in asymptomatic medium-large AAA. We identified FDG uptake and gadolinium enhancement (GE) in the aneurysmal wall, however FDG uptake corresponded rarely with mural inflammatory changes on MRI. In Paper II, we investigated whether inflammatory activity by means of FDG-PET/MRI can be detected in small to medium sized AAA, confirming the presence of inflammatory markers in the majority of patients. In Paper III, FDG-PET/MRI was used to characterize the inflammation and its transformation from acute to chronic phase in acute Stanford type B dissections. Highly increased FDG-activity was present in the dissected descending aorta in the acute phase, which markedly decreased over the course of a few months. MRI inflammatory changes were present in 60% of patients.In Paper IV, we evaluated the outcome and aortic remodelling after thoracic endovascular aortic repair (TEVAR) for chronic dissections. High rate of false lumen thrombosis occurred for dissections localized to the thoracic aorta covered by the stent-graft, but was more uncommon for extensive dissections distally. Aortic remodelling and sac shrinkage occurred in the thoracic aorta, but not distally. Reintervention rates were substantial (one third of cases). Paper V evaluated outcome of complex endovascular repair of post-dissection aneurysms of the arch and thoraco-abdominal aorta. Results were comparable to other recent reports using this new approach, however occurrence of retrograde Stanford type A dissection following arch fenestrated repair warrants caution.In conclusion, FDG-PET/MRI is a promising technique for studying inflammation in AAAs and ADs in vivo. For chronic aortic dissections, endovascular treatment results in good short-term outcome, but in the long-term re-interventions were common and adequate follow-up is thus of importance

  • Investigation of immune cell-derived factors as potential biomarkers in patients with colorectal cancer Author: Levar Shamoun Link: Publication date: 2022-09-23 12:38

    Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer related death. It is a heterogeneous disease involving multiple molecular pathways that result in differing phenotypes. 

    Individual variability in CRC susceptibility is influenced by genetic variation, such as single nucleotide polymorphisms (SNPs). Changes in genetics and epigenetics can disrupt intact signalling pathways involved in metabolism, proliferation, differentiation, and apoptosis. Inflammatory factors such as  cytokines and chemokines, as well as their receptors, play important roles in immune regulation.

    In Papers I, II and III, selected SNPs in the genes of interleukin (IL)-4, IL-13, IL-2 or chemokine C-C motif ligand (CCL) 4 in patients with CRC were investigated to determine their prognostic significance by identifying associations with various clinicopathological parameters and long-term survival. The investigated IL-13 and IL-4 SNPs were found to be risk factors for CRC and could be useful potential prognostic markers in CRC patient follow-up and clinical management. The investigated IL-2 SNPs were significantly associated with an increased risk of CRC and worse cancer-specific survival in patients with stage II or stage III CRC.

    In Paper III, levels of CCL4 protein were measured in CRC patients to investigate their prognostic significance for CRC. The data showed that CRC tissue had a higher protein expression than normal paired tissue, and plasma CCL4 levels were higher in patients than in controls, being positively correlated with CRC tissue levels. Further, higher levels of tissue CCL4 protein were linked to a lower disease stage and a better prognosis.

    Paper IV was an investigation of the expression of zinc finger MYND-type containing 15 (zmynd15) and its roles in CRC. In CRC tissue, protein expression was found primarily in cluster of differentiation (CD) 68 positive cells. Zmynd15 messenger ribonucleic acid expression was lower in CRC tissue than in non-cancerous tissue. When zmynd15 was silenced in CRC cell lines, it caused alteration in genes known to be important in CRC, indicating that zmynd15-regulated genes are involved in CRC. Furthermore, tumour development in the colon was higher in zmynd15 knockout mice than in wild-type mice.

    In conclusion, the work presented in this thesis contributes to an understanding of the association of inflammatory markers in CRC with risk and survival, and their potential use as tools for monitoring CRC patients. In addition, it showed that zmynd15, a transcriptional suppressor, plays an important role in the development of CRC.