Coming dissertations at MedFak
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Necrotizing Enterocolitis in Preterm Infants : Impact on Infant Mortality and a Search for Predictive Biomarkers
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-539265
Necrotizing enterocolitis (NEC) is an intestinal disease with high mortality and morbidity. This thesis aims to identify biomarkers to possibly predict this fatal and increasingly common disease in preterm infants.
In Paper I, we studied cause of death (COD) in preterms treated at in the neonatal intensive care unit at Uppsala University Children’s Hospital, Uppsala, Sweden. From Period 1 (2002-2009; n=105) to Period 2 (2011-2018; n=160), NEC increased as COD. Paper I also found that the autopsy influenced COD determination in 34.9% of cases. In Paper II, we investigated if biomarkers at birth could identify preterms at risk of developing NEC. Blood samples were collected after birth from 40 preterms, gestational age (GA) <28 weeks. 11 infants later developed NEC (NEC-group), while 29 did not (Control-group). 189 biomarkers, reflecting inflammation, apoptosis and vascularisation, were quantified with Proximity Extension Assay (Olink®). No biomarker differed in expression when comparing the NEC-group to the Control-group, and only some biomarkers differed when compared to control sub-groups. These findings suggest that infants may not be predisposed at birth of developing NEC besides being preterm. In Paper III and IV, we analyzed intestinal biopsies from 43 infants operated due to NEC (NEC-group) and 27 infants (Control-group) operated due to conditions such as atresia, volvulus and aganglionosis. The biopsies were immunohistochemically stained for markers of Paneth Cells (DEFA6 and GUCA2A) in Paper III and Goblet cells (REG4) in Paper IV. Marker expression was quantified with a semi-automated digital image analysis (ImageJ®) and compared between the groups. Paper III revealed that the NEC-group had lower DEFA6 expression than the Control-group, while expression of GUCA2A was similar. In a logistic regression analysis, NEC-risk correlated to low DEFA6 expression. This suggests that NEC-infants have intact Paneth cells, as indicated by unaltered GUCA2A expression, but diminished DEFA6 activity. Paper IV showed that low REG4 expression correlated to higher NEC-risk. A multivariable logistic regression analysis with REG4 expression and GA, found that GA and not REG4 correlated to NEC-risk. Thus, low REG4 expression in NEC-patients may be maturity dependent.
In conclusion, our findings suggest that preterms are not predisposed at birth to develop NEC besides being preterm. These studies also deepen our knowledge on Paneth cell and Goblet cell involvement in NEC. Low expression of DEFA6 and REG4 may indicate a risk of developing NEC, and could be further studied as potential blood biomarkers.
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Having a child with non-syndromic craniosynostosis : Parents' experiences of care, need of support and perceived stress
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-539773
Objective: Being a parent of a child with a diagnosis of craniosynostosis that requires surgery can lead to anxiety and emotional distress. The general aim was to explore parents' experiences when their child is diagnosed with and treated for non-syndromic craniosynostosis. This was accomplished by investigating how parents perceived treatment, information, and participation in care, as well as their parental stress, symptoms of anxiety and depression, and health-related quality of life.
Methods: Study I investigated Swedish parents' (n=20) experiences of having a child with craniosynostosis and their perceptions of the care provided by conducting interviews and thematic analysis. Study II explored parents' (n=19) experiences of the time at the hospital and the year after discharge by conducting interviews and content analysis. Study III explored parents´ satisfaction with hospital care and factors that influenced their perception of quality of care using questionnaires (n=98) and interviews (n=19), employing a mixed method. Study IV assessed parents' perceived parental and psychological stress and health-related quality of life before and one year after surgery, using questionnaires (n=29).
Results: Parents rarely had previous knowledge about craniosynostosis. For this reason, the craniofacial team was highlighted as the most important source of information and support. Parents described the time in the hospital and after discharge as challenging but ultimately good, and support from family, peers, and the expert team was considered essential. Parents were generally satisfied with hospital care, and factors existed that either facilitated or impeded their experience of quality of care. No differences regarding parental stress, health-related quality of life, and psychological distress before and one year after the child's surgery were found, but there was an association between parental stress and symptoms of depression both before and one year after surgery.
Conclusions: This thesis provides an understanding of parents' experiences when having a child undergoing craniosynostosis surgery. Most parents were satisfied with the care provided, but areas of improvement were described. There appears to be an association between parental stress and symptoms of depression. The findings highlight that healthcare professionals should be more responsive to parents´ different care needs.
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Contrast agent needle priming : Impact on sonographic needle visibility and potential for CT biopsy site confirmation
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-539719
Needle visualization in ultrasound-guided procedures can be challenging, particularly in contrast-specific imaging-mode. While diagnostic accuracy during CT-guided transthoracic lung biopsies is generally high, non-diagnostic results still occur and could potentially be reduced through image-based confirmation of whether the target was hit as intended. Two needle priming applications aimed at addressing these challenges were evaluated: (1) using the ultrasound contrast agent (USCA) sulfur hexafluoride to enhance needle visibility during ultrasound-guided procedures, and (2) using iodine contrast media to confirm biopsy locations during CT-guided procedures.
Paper I: Fine needles and separable core biopsy needles were primed with USCA. Punctures were performed in butchered bovine liver and a water bath model, followed by an evaluation of needle visibility. Results were mixed in B-mode, while USCA priming consistently improved needle visibility in contrast-specific imaging-mode for core biopsy needles but not for fine needles.
Paper II: Core biopsy needles of the side-notch type (used with reusable instruments) were primed with two different concentrations of iodine contrast media using a membrane device. In CT-guided biopsies with these primed needles, high-attenuation traces at biopsy sites were successfully created in a blood pudding phantom model, with superior results at the higher contrast agent concentration.
Paper III: USCA priming was performed using a 1 mL syringe on difficult-to-separate and non-separable core biopsy needles, as well as coaxial introducer needles. Needle visibility was evaluated in a water bath model. USCA priming, almost without exception, enhanced visibility in contrast-specific imaging-mode.
Paper IV: Non-separable core biopsy needles were primed as in Paper III and evaluated in an in vivo porcine model. USCA priming, with few exceptions, improved needle visibility in contrast-specific imaging-mode but slightly worsened it in B-mode.
These findings support the clinical use of USCA needle priming for ultrasound-guided core biopsy procedures performed in contrast-specific imaging-mode where needle visibility is limited. However, the results do not support its use in B-mode. Iodine contrast agent needle priming showed promise for confirming biopsy locations during CT-guided procedures, but further in vivo validation is required. The method’s clinical value is, however, uncertain, as newer, lighter full-core biopsy guns seem to offer a simpler solution.