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Coming dissertations at MedFak

  • Popliteal Artery Aneurysms : - epidemiology, treatment and results Author: Anne Cervin Link: Publication date: 2019-05-07 11:12

    Popliteal aneurysms (PA) are limb threatening, since the aneurysm thrombose and emboli from the aneurysm sac occlude the distal vessels, resulting in chronic or acute limb ischaemia. Open surgical repair (OSR) has been challenged by endovascular repair (ER), a minimal invasive technique. Little is known of long-term result, and comparisons of the methods have been difficult, since patients chosen for ER are mainly asymptomatic and have better outflow.

    The overall aim of this thesis was to study epidemiology and risk factors to optimize patient selection and techniques for surgical treatment of PA.

    Papers I and II: Data on all patients treated 2008-2012 (592 PAs in 499 patients) were analysed in the Swedish Vascular registry, Swedvasc. Patency was inferior after ER, in particular for patients with acute ischaemia. Nested in this cohort, a case-control study was performed, and the legs treated by ER (77) were matched, by indication, with twice the number treated with OSR (154). Medical records and radiologic images were collected and examined in a core-lab. In this matched cohort, the only independent risk factors for occlusion were ER and poor outflow. In a sub-group analysis of ER, risk factors for occlusion were acute ischaemia, poor out-flow, smaller stent graft diameter and elongation.

    Paper III: Prevalence of PA was studied in men, screened for abdominal aortic aneurysm (AAA) and of sub aneurysmal aorta, 25-29 mm. Prevalence of PA was high, 14.2%, and correlated with dilatation of the iliac arteries.

    Paper IV: Operations for ruptured PA (rPA) were identified in Swedvasc 1987-2012, medical records were reviewed. Compared with patients treated for other indications, they were 8 years older, had twice as large aneurysms (mean 64 mm) and many were treated with anticoagulants. The initial clinical picture was misleading.

    In conclusion, when treating PA the preferred surgical technique is OSR with a vein graft. Anatomical features of the popliteal artery and outflow vessels affect outcome. These findings are important for future surgical decision making.

  • Molecular detection and epidemiological studies of atypical bacteria causing respiratory tract infections Author: Karolina Gullsby Link: Publication date: 2019-05-06 12:00

    Respiratory infections are common causes of morbidity and mortality. Chlamydia pneumoniae, Mycoplasma pneumoniae and Bordetella pertussis cause respiratory infection, often with similar symptoms. Molecular diagnostic methods are preferred since these bacteria are difficult to culture. The aim of this thesis was to evaluate and improve the diagnostics and knowledge of the epidemiology of these bacteria.

    A real-time polymerase chain reaction (PCR) method targeting the IS481 element present in the genome of B. pertussis was compared to culture and serology results, and a duplex real-time PCR method was constructed for detecting C. pneumoniae and M. pneumoniae, which was compared to two endpoint PCR methods. Both real-time PCR methods showed high sensitivity and specificity.

    Typing of 624 M. pneumoniae samples, collected from 1996 to 2017 from four counties, was performed by P1 typing and multiple-locus variable number tandem repeat analysis (MLVA). A polyclonal distribution of strains was seen over all epidemic periods, but strains of P1 type 2/variant 2 and MLVA types 3-5-6-2 and 4-5-7-2 predominated in 2010−2013. A shift from type 2 strains to different variant 2 strains was seen and a new variant, 2e, was detected in 2016−2017. An A2063G mutation associated with macrolide resistance was detected by a fluorescence resonance energy transfer (FRET) PCR method in one (0.16%) of 608 M. pneumoniae strains.

    Molecular characterisation using whole-genome sequencing of 93 B. pertussis isolates, collected between 1986 and 2016 from three counties showed that there were polyclonal strains in the county of Dalarna, Gävleborg and Uppsala in the years 2014−2016. Changes in virulence-related genes were detected: a shift from isolates harbouring the ptxP3 allele in favour of ptxP1 was seen, and almost all isolates had a disrupted prn gene. No detection of macrolide resistance in B. pertussis was detected.

    In conclusion, the validated real-time PCR methods for detection of B. pertussis, C. pneumoniae and M. pneumoniae have led to improved diagnostic methods for use in clinical laboratories. The molecular characterisation of M. pneumoniae and B. pertussis strains has contributed to the wider understanding of the genetic changes that has occurred over the epidemic periods, but further studies is needed.

  • Impact of the inflammatory response on specific immunity in neurosurgical patients Author: Anna Ljunghill Hedberg Link: Publication date: 2019-05-06 10:41

    Vaccination with a T-cell-dependent pneumococcal conjugate vaccine (PCV) followed by a T-cell-independent pneumococcal polysaccharide vaccine (PPSV) is recommended after basilar skull fracture to reduce the risk of meningitis. The optimal time frame for vaccination has not yet been established and varies widely in practice. Because the risk of meningitis is at its peak shortly after the trauma incident, early vaccination might be more desirable. After trauma and central nervous system (CNS) injury, T-cell defects leading to trauma and CNS injury-induced immune deficiency syndromes may affect the vaccine response. In light of the above information, the overall aim of this thesis was to investigate the impact of neurotrauma and neurosurgery on the response to T-cell-dependent and T-cell-independent vaccines.

    In Paper I, we compared the antibody response to a T-cell-dependent conjugate vaccine in patients vaccinated within 10 days after neurotrauma or neurosurgery with those vaccinated after >3 weeks. To avoid interference with pneumococcal vaccination, a conjugate vaccine against Haemophilus influenzae type b (Hib) was chosen for the study. The majority of the patients responded to the vaccination, although the number of responders was significantly lower in patients vaccinated early.

    In Paper II, we investigated the antibody response to the T-cell-independent vaccine PPSV in patients vaccinated within 10 days after neurotrauma or neurosurgery and in patients vaccinated after >3 weeks. Patients vaccinated early responded similarly to those vaccinated after the acute period, indicating that PPSV can be administered early after neurotrauma or neurosurgery.

    In Paper III, we compared the response to Hib vaccine with the response to PPSV. We also examined whether individual clinical or immunological parameters might predict the response to T-cell-dependent vaccine and thereby help identify non-responders before vaccination. No correlation between Hib vaccine and PPSV responses was found, indicating that B-cell function is not similarly depressed as T-cell function. It was not possible to predict the T-cell-dependent vaccine response by standardized grading of the trauma or by parameters reflecting the innate immune response.

    In Paper IV, we found a significant reduction in the ex vivo CD4+ T-lymphocyte response to PCV in patients after neurotrauma or neurosurgery as compared with healthy controls.

    Our results suggest that PPSV might be a viable alternative to T-cell-dependent PCV in early vaccination after neurotrauma.