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Coming dissertations at MedFak

  • Cardiac Arrest – mechanical chest compressions, gender differences and coronary angiography Author: Erik Lindgren Link: Publication date: 2020-02-14 06:36

    Cardiac arrest is a major health problem with over 6000 cases of out-of-hospital cardiac arrest (OHCA) and 2500 cases of in-hospital cardiac arrest (IHCA) per year in Sweden. Survival are low. Many factors affect the chances of survival, including effective cardiopulmonary resuscitation and optimal post resuscitation care. These thesis involve these areas. Paper I+II describe a randomized clinical trial (n=2589). We compared a novel CPR algorithm with defibrillations during ongoing chest compressions delivered with a mechanical chest compression device and manual CPR according to guidelines. We found no difference in 4-hour survival, 23.6% with mechanical CPR and 23.7% with manual CPR. The vast majority of survivors in both groups had good neurological outcomes by 6 months. Paper III is a registry study (n=1498). We investigated impact of gender in performance and findings of early coronary angiography (CAG) and percutaneous coronary intervention (PCI), comorbidity and outcome among OHCA victims with an initially shockable rhythm. We found no difference between men and women in rates of ST-elevation/left bundle branch block (LBBB), 40% vs. 38% or rates of CAG, 45% vs. 40%. Among patients without ST-elevation/LBBB more men than women had CAG followed by PCI, 59% vs. 42% (P=0.03) and more advanced coronary artery disease. We found no association between gender and use of early CAG. Paper IV is a retrospective observational single centre study (n=423) of ICU treated victims of cardiac arrest. OHCA and IHCA were compared regarding comorbidity, characteristics of the arrest, treatment including CAG and CAG findings and outcome. OHCA patients had less preexisting comorbidity, lower rates of bystander CPR 71% vs 100% (p<0.001) and longer time to return of spontaneous circulation, 20 vs 10 minutes (p<0.001). OHCA patients more often had a shockable first rhythm, 47% vs 13% (p<0.001) and CA without any obvious non-cardiac origin, 77% vs 50% (p<0.001). OHCA patients more often underwent early CAG, 52% vs 25% (p<0.001) but no difference in rates of subsequent PCI or angiogram with at least one significant stenosis was seen. OHCA and IHCA did not differ in 30-days survival, 42% vs 41% or 1-year survival, 39% vs 33% 

  • Registry-Based Studies in Adult Acute Lymphoblastic Leukemia in Sweden : Survival and Quality of Life Author: Emma Bergfelt Lennmyr Link: Publication date: 2020-02-13 14:45

    Acute lymphoblastic leukemia (ALL), a common child malignancy, also constitutes a minor fraction of adult cancer with approximately 50 new cases per year in Sweden. While the five-year overall survival (OS) in pediatric ALL is more than 90%, the prognosis in adults is dismal. Using the Swedish ALL quality registry, this thesis investigates treatment and outcome of adult ALL according to national guidelines. In addition, the introduction of patient-reported outcome in the ALL and Acute Myeloid Leukemia registries is evaluated. 

    In Paper I, measurement of minimal residual disease by flow cytometry was found to be feasible but not consistently applied in the 35 patients with Philadelphia (Ph)-negative B-ALL investigated. In Paper II, treatment, toxicity and outcome of 155 patients, 55-85 years (y) with ALL diagnosis between 2005 and 2012 were studied in detail by patient charts review. An age-adopted protocol recommended from 2009 did not result in better outcome. In Paper III, disease recurrence in the same cohort as Paper II was studied. The median overall survival (OS) after ALL relapse was 3.6 months. In Paper IV, the whole ALL registry was studied and OS was estimated in 930 adult patients diagnosed in the periods 1997-2006 and 2007-2015. Five year OS improved in patients 18-45y from 50% to 65%, in patients 46-65y from 25% to 46%, and in patients >65y from 7% to 11%. This demonstrates that young patients have the best prognosis, in part due to the introduction of a dose-intense “pediatric-like” chemotherapy protocol. Compared to women, middle-aged men were found to have a worse outcome.

    Historically, Philadelphia-positive (Ph-pos) ALL has a poor prognosis compared to Ph-negative ALL. In this material, the frequency of Ph-pos ALL was 34% of examined B-ALL. Analysis of the whole registry revealed that in 2007-2015, i.e. after the introduction of the tyrosine kinase inhibitor imatinib, Ph-pos ALL was no longer associated with inferior OS. In Paper V, ALL and Acute Myeloid Leukemia patients, six months after diagnosis, completed a web or paper questionnaire regarding quality of life, symptoms and experience with care. The response rate was 64%. Depression symptoms were frequent (18%), especially in young women who reported worrying about fertility.

    In summary, although OS in adult ALL has improved, more effective and less toxic therapies in upfront treatment are highly warranted. Collection of patient-reported outcome in a national quality registry is feasible and can add important aspects of cancer care that are not usually addressed.

  • Clinical Bedside Studies of Cerebral Blood Flow in Severe Subarachnoid Hemorrhage Using Xenon CT Author: Henrik Engquist Link: Publication date: 2020-02-10 07:51

    Aneurysmal subarachnoid hemorrhage (SAH) is frequently complicated by delayed cerebral ischemia (DCI), contributing to poor outcome. Particularly for patients in poor neurological state, prediction of the acute clinical course is difficult, as is the early detection of DCI. Repeated measurement of global and regional cerebral blood flow (CBF) could potentially identify patients at risk of deterioration and guide in the clinical management.

    The studies in this thesis are based on bedside measurements of CBF by xenon-enhanced CT with the aim to assess and characterize global and regional CBF disturbances at different phases in the acute course after severe SAH. Furthermore, the effects of hemodynamic augmentation by hypervolemia, hemodilution and hypertension (HHH-therapy) on CBF and cerebral energy metabolism in patients with DCI are addressed.

    In Paper I, CBF disturbances at the early phase (day 0–3) after SAH were found common and often heterogeneous with substantial regions of near ischemic CBF. Older age and more severe hemorrhage (graded according to Fisher from CT) were factors associated with more compromised CBF. In Paper II, exploring the temporal dynamics of CBF, low initial CBF was associated with a persistent low level of CBF at day 4–7. The association was more pronounced when patients receiving HHH-therapy were separated, and indicates that patients with low CBF, even without clinical signs of DCI, could benefit from careful surveillance and optimization of circulation. In Paper III, the effects on CBF from HHH-therapy in patients with DCI was assessed. Hematocrit decreased during treatment, while the increase in systemic blood pressure was modest. Global CBF and CBF of the worst perfused regions increased, and the proportion of regions with critically low flow decreased accordingly. In Paper IV, the effects of HHH was further assessed in patients also monitored with cerebral microdialysis (CMD). CBF improved during HHH-therapy, while the cerebral energy metabolic CMD parameters stayed statistically unchanged. None of the patients developed metabolic signs of severe ischemia, but a disturbed energy metabolic pattern was common, possibly explained by mitochondrial dysfunction.