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  • Myrdal, Gunnar, et al. (author)
  • Regional differences in treatment and outcome in non-small cell lung cancer : a population-based study (Sweden)
  • 2009
  • In: Lung Cancer. - : Elsevier BV. - 0169-5002 .- 1872-8332. ; 63:1, s. 16-22
  • Journal article (peer-reviewed)abstract
    • In the recent decade uniform treatment guidelines for non-small cell lung cancer (NSCLC) have been introduced in Sweden. The objective of this study was to examine time trends and differences in treatment intensity for NSCLC between county clinical centres in Central Sweden. A second aim was to investigate whether any differences in treatment of NSCLC were associated with differences in survival. 4345 patients with a diagnosis of NSCLC between 1995 and 2003 were identified in the population-based Lung Cancer Register of Central Sweden. Multivariate logistic regression was used to estimate odds ratios to analyse the likelihood of receiving different treatment modalities for NSCLC. Cox proportional hazard models estimating relative hazard ratios were used to identify factors related to death (by any cause). Of all patients, 33.4% received no treatment, and 17.5% underwent surgery. Between 1995 and 2003, the proportion of patients receiving chemotherapy rose from 14.6% to 55%. There were pronounced differences between county centres in treatment policies, especially concerning surgery and radiotherapy. The likelihood of receiving treatment for NSCLC was highest at county centre A where both surgical treatment and chemotherapy were given more often. Compared to this reference county, the risk of death was between 20% and 40% higher in the other counties after adjusting for age, stage, gender, time period, smoking status and histopathological type. When analyses were adjusted for treatment, county of residence was no longer a prognostic factor. Despite common guidelines there were marked differences in treatment activity between the counties. Treatment activity was associated with survival. Survival benefits may follow improvement in compliance to guidelines.
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  • Tovedal, Thomas, et al. (author)
  • Blood Flow Quantitation by Positron Emission Tomography During Selective Antegrade Cerebral Perfusion
  • 2017
  • In: Annals of Thoracic Surgery. - : Elsevier BV. - 0003-4975 .- 1552-6259. ; 103:2, s. 610-616
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Perfusion strategies during aortic surgery usually comprise hypothermic circulatory arrest (HCA), often combined with selective antegrade cerebral perfusion (SACP) or retrograde cerebral perfusion. Cerebral blood flow (CBF) is a fundamental parameter for which the optimal level has not been clearly defined. We sought to determine the CBF at a pump flow level of 6 mL/kg/min, previously shown likely to provide adequate SACP at 20°C in pigs.METHODS: Repeated positron emission tomography (PET) scans were used to quantify the CBF and glucose metabolism throughout HCA and SACP including cooling and rewarming. Eight pigs on cardiopulmonary bypass were assigned to either HCA alone (n = 4) or HCA+SACP (n = 4). The CBF was measured by repeated [(15)O]water PET scans from baseline to rewarming. The cerebral glucose metabolism was examined by [(18)F]fluorodeoxyglucose PET scans after rewarming to 37°C.RESULTS: Cooling to 20°C decreased the cortical CBF from 0.31 ± 0.06 at baseline to 0.10 ± 0.02 mL/cm(3)/min (p = 0.008). The CBF was maintained stable by SACP of 6 mL/kg/min during 45 minutes. After rewarming to 37°C, the mean CBF increased to 0.24 ± 0.07 mL/cm(3)/min, without significant differences between the groups at any time-point exclusive of the HCA period. The net cortical uptake (Ki) of [(18)F]fluorodeoxyglucose after rewarming showed no significant difference between the groups.CONCLUSIONS: Cooling autoregulated the CBF to 0.10 mL/cm(3)/min, and 45 minutes of SACP at 6 mL/kg/min maintained the CBF in the present model. Cerebral glucose metabolism after rewarming was similar in the study groups.
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  • Bagge, Louise, et al. (author)
  • Epicardial off-pump pulmonary vein isolation and vagal denervation improve long-term outcome and quality of life in patients with atrial fibrillation
  • 2009
  • In: Journal of Thoracic and Cardiovascular Surgery. - : Elsevier BV. - 0022-5223 .- 1097-685X. ; 137:5, s. 1265-1271
  • Journal article (peer-reviewed)abstract
    • OBJECTIVES: The limited information available on thoracoscopic pulmonary vein isolation combined with ganglionated plexi ablation and the lack of studies regarding its effect on quality of life and physical capacity urged us to study its acute and long-term results in patients with atrial fibrillation. METHODS: Forty-three patients (mean age 57.1 years) with symptomatic atrial fibrillation referred for thoracoscopic off-pump epicardial pulmonary vein isolation and ganglionated plexi ablation using radiofrequency energy were included. RESULTS: The physical capacity improved significantly at 6-month follow-up compared with baseline (mean +/- standard deviation, 165.2 +/- 65 Watt versus 155.9 +/- 57 Watt, P = .02). Quality of life (Short Form-36 health survey) significantly improved 12 months after surgery compared with baseline in all subscales except for bodily pain. The symptom severity questionnaire score decreased significantly from mean 15.2 +/- 4.0 points to 10.7 +/- 4.8 points (P = .02). Overall, 25 of 33 patients (76%) followed up for 12 months had no symptomatic atrial fibrillation recurrences or atrial fibrillation episodes on 24-hour Holter recordings. The corresponding figures were 79% (19/24) for patients with paroxysmal atrial fibrillation, 100% (2/2) for persistent atrial fibrillation, and 57% (4/7) for permanent atrial fibrillation. The most common complication was bleeding events (9%) during pulmonary vein dissection. CONCLUSIONS: Epicardial off-pump pulmonary vein isolation combined with ganglionated plexi ablation improved quality of life, symptoms, and exercise capacity and therefore may be considered for patients with atrial fibrillation who fail endocardial pulmonary vein ablation or as a first-line procedure if left atrial appendage exclusion is warranted.
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  • Ehrenborg, Christian, et al. (author)
  • First known case of Bartonella quintana endocarditis in Sweden
  • 2009
  • In: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 41:1, s. 73-75
  • Journal article (peer-reviewed)abstract
    • In this report, we present the first known case of Bartonella endocarditis in Sweden. IgG antibody titres to Bartonella spp. were elevated but blood cultures remained negative. Sequencing of a gltA fragment from DNA extracted from heart valve tissue specimens revealed sequence homology with B. quintana.
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  • Granfeldt, Hans, et al. (author)
  • Experience with the Impella (R) recovery axial-flow system for acute heart failure at three cardiothoracic centers in Sweden
  • 2009
  • In: Scandinavian Cardiovascular Journal. - : Informa UK Limited. - 1401-7431 .- 1651-2006. ; 43:4, s. 233-239
  • Journal article (peer-reviewed)abstract
    • Objectives. The Impella (R) recovery axial-flow system is a mechanical assist system for use in acute heart failure. This retrospective study reports the use of the device at three cardiothoracic units in Sweden. Design. Fifty patients (35 men, mean age 55.8 years, range 26 to 84 years) underwent implantation of 26 Impella (R) LP 2.5/5.0 (support-time 0.1 to 14 days), 16 Impella (R) LD (support-time 1 to 7 days) and 8 Impella (R) RD (support-time 0.1 to 8 days) between 2003 and 2007. Implantation was performed because of postcardiotomy heart failure (surgical group, n=33) or for various states of heart failure in cardiological patients (non-surgical group, n=17). The intention for the treatments was mainly to use the pump as a obridge-to-recoveryo. Results. Early mortality in the surgical and non-surgical groups was 45% and 23%, respectively. Complications included infection, 36% and right ventricular failure, 28%. Cardiac output and cardiac power output postoperatively were significantly higher among survivors than non-survivors. Conclusions. The Impella (R) recovery axial-flow system facilitates treatment in acute heart failure. Early intervention in patients with acute heart failure and optimized hemodynamics in the post-implantation period seem to be of importance for long-term survival. Insufficient early response to therapy should urge to consider further treatment options.
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  • Jonsson, Ove, 1966-, et al. (author)
  • Minimal Safe Arterial Blood Flow During Selective Antegrade Cerebral Perfusion at 20° Centigrade
  • 2011
  • In: Annals of Thoracic Surgery. - : Elsevier BV. - 0003-4975 .- 1552-6259. ; 91:4, s. 1198-1205
  • Journal article (peer-reviewed)abstract
    • BackgroundSelective antegrade cerebral perfusion (SACP) enables surgery on the aortic arch, where cerebral ischemia may cause neurologic sequels. This study aims to identify the minimum arterial flow level to maintain adequate cerebral perfusion during SACP in deep hypothermia in the pig.MethodsTwo groups of pigs were subjected to SACP at 20°C α-stat. In group 1 (n = 6), flow was stepwise adjusted from 8-6-4-2-8 mL · kg−1 · min−1 and in group 2 (n = 5), flow was kept constant at 6 mL · kg−1 · min−1. Magnetic resonance imaging and spectroscopy were performed at each flow level together with hemodynamic monitoring and blood gas analysis. The biochemical marker of cerebral damage protein S100β was measured in peripheral blood.ResultsDecreased mixed venous oxygen saturation and increased lactate in magnetic resonance spectroscopy was seen as a sign of anaerobic metabolism below 6 mL · kg−1 · min−1. No ischemic damage was seen on diffusion-weighted imaging, but the concentrations of S100β were significantly elevated in group 1 compared with group 2 at the end of the experiment (p < 0.05). Perfusion-weighted imaging showed coherence between flow setting and cerebral perfusion, increase of blood volume across time, and regional differences in perfusion during SACP.ConclusionsThe findings suggest an ischemic threshold close to 6 mL · kg−1 · min−1 in the present model. Regional differences in perfusion during SACP may be of pathogenic importance to focal cerebral ischemia.
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  • Jonsson, Ove, et al. (author)
  • Selective antegrade cerebral perfusion at two different temperatures compared to hypothermic circulatory arrest : an experimental study in the pig with microdialysis
  • 2009
  • In: Interactive Cardiovascular and Thoracic Surgery. - : Oxford University Press (OUP). - 1569-9293 .- 1569-9285. ; 8:6, s. 647-653
  • Journal article (peer-reviewed)abstract
    • Hypothermic arrest and selective antegrade cerebral perfusion (SACP) is widely used during aortic arch surgery. The microdialysis technique monitors biomarkers of cellular metabolism and cellular integrity over time. In this study, the cerebral changes during hypothermic circulatory arrest (HCA) at 20 degrees C and HCA with SACP at two different temperatures, 20 and 28 degrees C, were monitored. Twenty-three pigs were divided into three groups. A microdialysis probe was fixated into the forebrain. Circulatory arrest started at a brain and body temperature of 20 degrees C or 28 degrees C. Arrest with/without cerebral perfusion (flow 10 ml/kg, max carotid artery pressure 70 mmHg) lasted for 80 min followed by reperfusion and rewarming during 40 min and an observation period of 120 min. The microdialysis markers were registered at six time-points. The lactate/pyruvate ratio (L/P ratio) and the lactate/glucose ratio (L/G ratio) increased significantly (P<0.05), during arrest, in the HCA group. The largest increase of glycerol was found in the group with tepid cerebral perfusion (28 degrees C) and the HCA group (P<0.05). This study supports the use of SACP over arrest. It also suggests that cerebral metabolism and cellular membrane integrity may be better preserved with SACP at 20 degrees C compared to 28 degrees C.
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  • Micke, Patrick, et al. (author)
  • Gene Copy Number Aberrations Are Associated with Survival in Histologic Subgroups of Non-small Cell Lung Cancer
  • 2011
  • In: Journal of Thoracic Oncology. - 1556-0864 .- 1556-1380. ; 6:11, s. 1833-1840
  • Journal article (peer-reviewed)abstract
    • Introduction: Non-small cell lung cancer (NSCLC) is characterized by a multitude of genetic aberrations with unknown clinical impact. In this study, we aimed to identify gene copy number changes that correlate with clinical outcome in NSCLC. To maximize the chance to identify clinically relevant events, we applied a strategy involving two prognostically extreme patient groups. Methods: Short-term (<20 month; n = 53) and long-term survivors (>58 month; n = 47) were selected from a clinically well-characterized NSCLC patient cohort with available fresh frozen tumor specimens. The samples were analyzed using high-resolution single-nucleotide polymorphism array technology to assess gene copy number variations and array-based gene expression profiling. The molecular data were combined with information on clinical parameters. Results: Genetic aberrations were strongly associated with tumor histology. In adenocarcinoma (n = 50), gene copy number gains on chromosome 8q21-q24.3 (177 genes) were more frequent in long-term than in short-term survivors. In squamous cell carcinoma (n = 28), gains on chromosome 14q23.1-24.3 (133 genes) were associated with shorter survival, whereas losses in a neighboring region, 14q31.1-32.33 (110 genes), correlated with favorable outcome. In accordance with copy number gains and losses, messenger RNA expression levels of corresponding genes were increased or decreased, respectively. Conclusion: Comprehensive tumor profiling permits the integration of genomic, histologic, and clinical data. We identified gene copy number gains and losses, with corresponding changes in messenger RNA levels that were associated with prognosis in adenocarcinoma and squamous cell carcinoma of the lung.
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  • Morell, Arvid, et al. (author)
  • Influence of blood/tissue differences in contrast agent relaxivity on tracer based MR perfusion measurements
  • 2015
  • In: Magnetic Resonance Materials in Physics, Biology and Medicine. - : Springer Science and Business Media LLC. - 0968-5243 .- 1352-8661. ; 28:2, s. 135-147
  • Journal article (peer-reviewed)abstract
    • PURPOSE:Perfusion assessment by monitoring the transport of a tracer bolus depends critically on conversion of signal intensity into tracer concentration. Two main assumptions are generally applied for this conversion; (1) contrast agent relaxivity is identical in blood and tissue, (2) change in signal intensity depends only on the primary relaxation effect. The purpose of the study was to assess the validity and influence of these assumptions.MATERIALS AND METHODS:Blood and cerebral tissue relaxivities r1, r2, and r2* for gadodiamide were measured in four pigs at 1.5 T. Gadolinium concentration was determined by inductively coupled plasma atomic emission spectroscopy. Influence of the relaxivities, secondary relaxation effects and choice of singular value decomposition (SVD) regularization threshold was studied by simulations.RESULTS:In vivo relaxivities relative to blood concentration [in s-1 mM-1 for blood, gray matter (GM), white matter (WM)] were for r1 (2.614 ± 1.061, 0.010 ± 0.001, 0.004 ± 0.002), r2 (5.088 ± 0.952, 0.091 ± 0.008, 0.059 ± 0.014), and r2* (13.292 ± 3.928, 1.696 ± 0.157, 0.910 ± 0.139). Although substantial, by a nonparametric test for paired samples, the differences were not statistically significant. The GM to WM blood volume ratio was estimated to 2.6 ± 0.9 by r1, 1.6 ± 0.3 by r2, and 1.9 ± 0.2 by r2*. Secondary relaxation was found to reduce the tissue blood flow, as did the SVD regularization threshold.CONCLUSION:Contrast agent relaxivity is not identical in blood and tissue leading to substantial errors. Further errors are introduced by secondary relaxation effects and the SVD regularization.
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  • Myrdal, Gunnar (author)
  • Lung Cancer : Epidemiological and Clinical Studies with Special Reference to Surgical Treatment
  • 2003
  • Doctoral thesis (other academic/artistic)abstract
    • From being a rare disease in the early 1900s, lung cancer is today the most common forms of cancer worldwide. This development is due to the gradual uptake of cigarette smoking in different populations and birth cohorts during the past 75 years. In spite of different modes of treatment, survival is still poor and surgery remains the prerequisite for cure. National data from the Swedish Cancer Register for the 35-year period 1958-1994 were analysed to estimate the effects of birth cohort, year of diagnosis (period) and age at diagnosis on the time trends in lung cancers. Early mortality, complications, major morbidity during the first 30 days, quality of life and long term survival after lung cancer surgery were assessed to estimate the significance of pre-surgical and tumour-related risk factors. Also, effects of delay in diagnosis and treatment among patients with non-small cell lung cancer were examined.The main results indicate that the overall age-adjusted incidence of lung cancer in Sweden has stabilised in men during the last two decades but has been increasing continuously in women. The fastest rate increase was noted among the youngest women and the incidence of adenocarcinoma is increasing in both sexes. Our results show low early mortality and morbidity after lung cancer surgery. Furthermore, quality of life was comparable with that of CABG patients postoperatively. However, patients with reduced lung capacity and those undergoing pneumonectomy should be treated with great care, as they run a considerable risk of major complications, impaired quality of life or death during the first 30 days postoperatively. Tumour stage (TNM) is the best prognostic indicator for long-term survival following radical surgery, underlying the importance of accurate surgical staging. Factors such as impaired preoperative lung function, older age, and major complications after surgery all negatively influence survival. Current smokers as a group run a significant risk of an adverse outcome (major complication or death), impaired mental health and shortened survival after lung cancer surgery. Waiting time for diagnosis and treatment of lung cancer was longer than recommended; especially among those surgically treated, but prolonged delay did not influence survival adversely.
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  • Tovedal, Thomas, 1955-, et al. (author)
  • Experimental treatment of superior venous congestion during cardiopulmonary bypass
  • 2013
  • In: European Journal of Cardio-Thoracic Surgery. - : Oxford University Press (OUP). - 1010-7940 .- 1873-734X. ; 44:3, s. E239-E244
  • Journal article (peer-reviewed)abstract
    • OBJECTIVES:Superior venous outflow obstruction affects cerebral perfusion negatively by reducing cerebral perfusion pressure (CPP). We present a randomized study designed to compare two alternative strategies to preserve the CPP during superior vena cava (SVC) congestion and cardiopulmonary bypass (CPB).METHODS:Fourteen pigs on bi-caval CPB were subjected to 75% occlusion of the SVC flow. CPP was restored either by vasopressor treatment (VP, n = 7) or by partial relief (PR) of the congestion (n = 7). The cerebral effects of the interventions were studied for 60 min with intracranial pressure (ICP) monitoring, cerebral blood flow measurement, the near-infrared light spectroscopy tissue oxygen saturation index (StO2), arterial and venous blood gas analyses and serial measurements of the glial cell damage marker protein S100β.RESULTS:Both strategies restored the CPP to baseline levels and no signs of severe ischaemia were observed. In the PR group, the venous and ICPs were normalized in response to the intervention, while in the VP group those parameters remained elevated throughout the experiment. The haemoglobin oxygen saturation in the sagittal sinus (SsagO2) was increased by both VP and PR, while significant improvement in the StO2 was observed only in the PR group. The S100β concentrations were similar in the two groups.CONCLUSIONS:Experimental SVC obstruction during CPB may reduce the CPP, resulting in impaired cerebral perfusion. Both vasopressor treatment and improved venous drainage can, in the short term, individually restore the CPP during these circumstances.
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  • Tovedal, Thomas, 1955-, et al. (author)
  • Venous obstruction and cerebral perfusion during experimental cardiopulmonary bypass
  • 2010
  • In: Interactive Cardiovascular and Thoracic Surgery. - : Oxford University Press (OUP). - 1569-9293 .- 1569-9285. ; 11:5, s. 561-566
  • Journal article (peer-reviewed)abstract
    • To investigate the effects on cerebral perfusion by experimental venous congestion of the superior vena cava (SVC) during bicaval cardiopulmonary bypass (CPB) at 34 °C, pigs were subjected to SVC obstruction at levels of 75%, 50%, 25% and 0% of baseline SVC flow at two arterial flow levels (low, LQ, high, HQ). The cerebral perfusion was examined with near-infrared spectroscopy (NIRS), cerebral microdialysis and blood gas analysis. SVC obstruction caused significant decreases in the NIRS tissue oxygenation index (TOI) and in SVC oxygen saturations (P<0.05, both groups), while the mixed venous saturation was decreased only in the LQ group. Sagittal sinus venous saturations were measured in the HQ group and found significantly reduced in response to venous congestion (P<0.05). No microdialysis changes were seen at the group level, however, individual ischemic patterns in terms of concomitant venous desaturation, decreased TOI and increased lactate/pyruvate occurred in both groups. The total venous drainage remained stabile throughout the experiment, indicating increased flow in the inferior vena cava cannula. The results indicate that SVC congestion may impair cerebral perfusion especially in the case of compromised arterial flow during CPB. Reduced SVC cannula flow may pass undetected during bicaval CPB, if SVC flow is not specifically monitored.
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