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2.
  • Bydén, Moa, et al. (author)
  • Cerebrovascular Reserve Capacity as a Predictor of Postoperative Delirium : A Pilot Study
  • 2021
  • In: Frontiers in Surgery. - : Frontiers Media S.A.. - 2296-875X. ; 8
  • Journal article (peer-reviewed)abstract
    • Introduction: Postoperative delirium is a common complication after cardiac surgery with cardiopulmonary bypass (CPB). Compromised regulation of the cerebral circulation may be a predisposing factor for delirium. However, the potential relationship between cerebrovascular reserve capacity and delirium is unknown. The aim of this study was to investigate if impaired cerebrovascular reserve capacity was associated with postoperative delirium.Methods: Forty-two patients scheduled for cardiac surgery with CPB were recruited consecutively. All patients underwent preoperative transcranial Doppler (TCD) ultrasound with calculation of breath-hold index (BHI). BHI < 0.69 indicated impaired cerebrovascular reserve capacity. In addition, patients were examined with preoperative neuropsychological tests such as MMSE (Mini Mental State Examination) and AQT (A Quick Test of cognitive speed). Postoperative delirium was assessed using Nursing Delirium Screening Scale (Nu-DESC) in which a score of >= 2 was considered as delirium.Results: Six patients (14%) scored high for postoperative delirium and all demonstrated impaired preoperative cerebrovascular reserve capacity. Median (25th-75th percentile) BHI in patients with postoperative delirium was significantly lower compared to the non-delirium group [0.26 (-0.08-0.44) vs. 0.83 (0.57-1.08), p = 0.002]. Preoperative MMSE score was lower in patients who developed postoperative delirium (median, 25th-75th percentile; 26.5, 24-28 vs. 28.5, 27-29, p = 0.024). Similarly, patients with postoperative delirium also displayed a slower performance during the preoperative cognitive speed test AQT color and form (mean +/- SD; 85.8 s +/- 19.3 vs. 69.6 s +/- 15.8, p = 0.043).Conclusion: The present findings suggest that an extended preoperative ultrasound protocol with TCD evaluation of cerebrovascular reserve capacity and neuropsychological tests may be valuable in identifying patients with increased risk of developing delirium after cardiac surgery.
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  • Davidsson, Anette, et al. (author)
  • Comparison between visual assessment of dopaminergic degeneration pattern and semi-quantitative ratio calculations in patients with Parkinson's disease and Atypical Parkinsonian snydromes using DaTSCAN SPECT
  • 2014
  • Conference paper (other academic/artistic)abstract
    • Background: Parkinson's disease (PD) is a degenerative disorder characterized by the progressive degeneration of dopamine-containing cells in substantia nigra, and it is the second most common neurodegenerative disorder worldwide. It can be difficult to differentiate between idiopathic PD and Atypical Parkinsonian syndromes (APS). In a high percentage of APS patients, the right diagnosis is not established even during late stages of the disease. Currently there is no specific test to verify PD, especially in the early stages of the disease.The aim was to verify if 123I-FP-CIT, DaTSCAN ® can differentiate early stages of Parkinson's disease as well as patients with Atypical Parkinsonian syndromes from manifest Parkinson's disease.Materials and methods: 121 consecutive patients were investigated with 123I-FP-CIT SPECT, during a four year period. All patients were diagnosed according to the established consensus criteria for diagnosis of Parkinson's disease (PD), (n=53), Atypical Parkinsonian syndromes (APS) (n=18). Remaining patients were grouped early PD (before onset the of L-dopa medication), (n=20), and non-PD syndromes (n=30). SPECT images were analysed visually according to a predefined ranking scale of dopaminergic degeneration, distinguishing a posterior-anterior degeneration pattern (egg shape) to a more global and severe degeneration pattern (burst striatum). Striatum ratios were quantitatively analysed with the 3D software, EXINI.Results: In the group of APS patients the burst striatum pattern was most frequent and found in 61% (11/18 patients). In PD patients the egg shape pattern was dominating, especially in early PD where it was present in 95% (19/20 patients). The sensitivity of burst striatum degeneration pattern was 61% (95%-CI 36-83%), specificity 90% (95%-CI 81-96%). The sensitivity of egg shape pattern was 74% (95%-CI 62-84%), specificity 90% (95%-CI 47-90%). The uptake ratios were reduced in both PD and APS patients and closely related to the image pattern. The lowest putamen/caudate ratio was found in early PD.Conclusion: In this study we found that in more than half of the patients it was possible to differentiate between PD and APS by visual interpretation only. Similar results were obtained using semi-quantitative uptake ratios, but combining visual assessment with uptake ratios did not add to the discriminating power of DATSCAN ® SPECT in this materialReferences: Kahraman D, Eggers C, Schicha H, Timmermann L, Schmidt M. Visual assessment of dopaminergic degeneration pattern in 123I-FP-CIT SPECT differentiates patients with atypical parkinsonian syndromes and idiopathic Parkinson's disease. J Neurol. 2012;259:251-60
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  • Davidsson, Anette, et al. (author)
  • Comparison between visual assessment of dopaminergic degeneration pattern and semi-quantitative ratio calculations in patients with Parkinsons disease and Atypical Parkinsonian syndromes using DaTSCAN (R) SPECT
  • 2014
  • In: Annals of Nuclear Medicine. - : Springer Verlag (Germany). - 0914-7187 .- 1864-6433. ; 28:9, s. 851-859
  • Journal article (peer-reviewed)abstract
    • Objective To verify if I-123-FP-CIT, DaTSCAN (R) can differentiate early stages of Parkinsons disease (PD) as well as patients with Atypical Parkinsonian syndromes (APS) from manifest Parkinsons disease. Methods 128 consecutive patients were investigated with I-123-FP-CIT SPECT during a 4-year period. All patients were diagnosed according to the established consensus criteria for diagnosis of PD (n = 53) and APS (n = 19). Remaining patients were grouped early PD (before onset of L-DOPA medication), (n = 20), vascular PD (n = 6), and non-PD syndromes (n = 30) and SWEDD (n = 1). SPECT images were analyzed visually according to a predefined ranking scale of dopaminergic nerve cell degeneration, distinguishing a posterior-anterior degeneration pattern (egg shape) from a more global and severe degeneration pattern (burst striatum). Striatum uptake ratios were quantitatively analyzed with the 3D software, EXINI. Results In the group of APS patients, the burst striatum pattern was most frequent and found in 61 % (11/18 patients). In PD patients, the egg shape pattern was dominating, especially in early PD where it was present in 95 % (19/20 patients). The positive predictive value for the egg shape pattern to diagnose PD was 92 % in this material (APS and all PD patients) and the specificity 90 % for the burst striatum pattern to exclude APS. The uptake ratios were reduced in both PD and APS patients and closely related to the image ranking. Conclusion In this study, we found that in more than half of the patients it was possible to differentiate between PD and APS by visual interpretation only. Similar results were obtained using semi-quantitative uptake ratios. Combining visual assessment with uptake ratios did not add to the discriminating power of DaTSCAN (R) SPECT in this material.
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  • Georgiopoulos, Charalampos, et al. (author)
  • A study of neural activity and functional connectivity within the olfactory brain network in Parkinson's disease
  • 2019
  • In: NeuroImage. - : Elsevier. - 2213-1582. ; 23
  • Journal article (peer-reviewed)abstract
    • Olfactory dysfunction is an early manifestation of Parkinson's disease (PD). The present study aimed to illustrate potential differences between PD patients and healthy controls in terms of neural activity and functional connectivity within the olfactory brain network. Twenty PD patients and twenty healthy controls were examined with olfactory fMRI and resting-state fMRI. Data analysis of olfactory fMRI included data-driven tensorial independent component (ICA) and task-driven general linear model (GLM) analyses. Data analysis of resting-state fMRI included probabilistic ICA based on temporal concatenation and functional connectivity analysis within the olfactory network. ICA of olfactory fMRI identified an olfactory network consisting of the posterior piriform cortex, insula, right orbitofrontal cortex and thalamus. Recruitment of this network was less significant for PD patients. GLM analysis revealed significantly lower activity in the insula bilaterally and the right orbitofrontal cortex in PD compared to healthy controls but no significant differences in the olfactory cortex itself. Analysis of resting-state fMRI did not reveal any differences in the functional connectivity within the olfactory, default mode, salience or central executive networks between the two groups. In conclusion, olfactory dysfunction in PD is associated with less significant recruitment of the olfactory brain network. ICA could demonstrate differences in both the olfactory cortex and its main projections, compared to GLM that revealed differences only on the latter. Resting-state fMRI did not reveal any significant differences in functional connectivity within the olfactory, default mode, salience and central executive networks in this cohort.
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  • Georgiopoulos, Charalampos, et al. (author)
  • DaTSCAN SPECT EVALUATION OF PATIENTS WITH MOVEMENT DISORDERS
  • 2011
  • In: EUROPEAN JOURNAL OF NEUROLOGY. - : Wiley-Blackwell. ; , s. 567-567
  • Conference paper (other academic/artistic)abstract
    • Introduction: Molecular imaging with DaTSCAN SPECTis widely used as a diagnostic tool in patients with movementdisorders in the form of Parkinson's Disease (PD),Parkinson-plus syndromes and Tremor. In the present studythe potency of DATScan SPECT to detect degeneration inthe basal ganglia in early stages of PD, before the onset ofmedication, is evaluated. In addition the efficacy ofDaTSCAN for differential diagnosis between patients withidiopathic PD and patients with Parkinson-plus syndromesis examined.Methodology: Participants: 21 patients with PD in earlystages, before the onset of medication, 20 patients withidiopathic PD and 6 patients with Parkinson-plussyndromes. 15 participants with normal results ofDaTSCAN SPECT and a clinical diagnosis different fromPD or Parkinson-plus were used as control.DaTSCAN SPECT: In the present study the quantificationof Striatum Occipital/Occipital and the Xeleris workstation(GE) were used.Results: The quantification for patients with idiopathic PD(1.185±0.05687) was significantly lower (p<0.0001) fromthe control (2.369±0.1258) and significantly lower (p<0.05)from that of patients in early stages of PD, before the onsetof medication (1.359±0.05324). There was no significantdifference between the idiopathic PD and Parkinson-plussyndromes (1.103±0.2442).Conclusion: DaTSCAN SPECT can detect efficiently earlydegeneration in the basal ganglia before the onset ofmedication is needed. Its efficacy for the differentialdiagnosis between idiopathic PD and Parkinson-plussyndromes is questioned. The combination of imaging andclinical examination is mandatory for a certain diagnosis.
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  • Georgiopoulos, Charalampos, 1984- (author)
  • Imaging Studies of Olfaction in Health and Parkinsonism
  • 2019
  • Doctoral thesis (other academic/artistic)abstract
    • Olfactory loss is a common non-motor symptom of Parkinson’s disease (PD), often preceding the cardinal motor symptoms of the disease. The aim of this thesis was to: (a) evaluate whether olfactory examination can increase diagnostic accuracy, and (b) study the structural and functional neural basis of olfactory dysfunction in PD with different applications of Magnetic Resonance Imaging (MRI).Paper I was a comparison of the diagnostic accuracy between a simple smell identification test and DaTSCAN Single Photon Emission Computerized Tomography (SPECT), a nuclear medicine tomographic imaging technique that is commonly used in patients with suspected parkinsonism. The results indicate that smell test is inferior to DaTSCAN SPECT, but the combination of these two methods can lead to improved diagnostic accuracy.Paper II showed that diffusion MRI could detect discrete microstructural changes in the white matter of brain areas that participate in higher order olfactory neurotransmission, whereas MRI with Magnetization Transfer contrast could not.Paper III was a methodological study on how two different acquisition parameters can affect the activation pattern of olfactory brain areas, as observed with functional MRI (fMRI). The results indicate that brief olfactory stimulation and fast sampling rate should be preferred on olfactory fMRI studies.Paper IV used olfactory fMRI and resting-state fMRI in order to elucidate potentially altered activation patterns and functional connectivity within olfactory brain areas, between PD patients and healthy controls. Olfactory fMRI showed that olfactory impairment in PD is associated with significantly lower recruitment of the olfactory network. Resting-state fMRI did not detect any significant changes in the functional connectivity within the olfactory network of PD patients.In conclusion, the included studies provide evidence of: (a) disease-related structural and functional changes in olfactory brain areas, and (b) beneficial addition of olfactory tests in the clinical work-up of patients with parkinsonism.
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  • Georgiopoulos, Charalampos, et al. (author)
  • Olfactory fMRI: Implications of Stimulation Length and Repetition Time
  • 2018
  • In: Chemical Senses. - : OXFORD UNIV PRESS. - 0379-864X .- 1464-3553. ; 43:6, s. 389-398
  • Journal article (peer-reviewed)abstract
    • Studying olfaction with functional magnetic resonance imaging (fMRI) poses various methodological challenges. This study aimed to investigate the effects of stimulation length and repetition time (TR) on the activation pattern of 4 olfactory brain regions: the anterior and the posterior piriform cortex, the orbitofrontal cortex, and the insula. Twenty-two healthy participants with normal olfaction were examined with fMRI, with 2 stimulation lengths (6 s and 15 s) and 2 TRs (0.901 s and 1.34 s). Data were analyzed using General Linear Model (GLM), Tensorial Independent Component Analysis (TICA), and by plotting the event-related time course of brain activation in the 4 olfactory regions of interest. The statistical analysis of the time courses revealed that short TR was associated with more pronounced signal increase and short stimulation was associated with shorter time to peak signal. Additionally, both long stimulation and short TR were associated with oscillatory time courses, whereas both short stimulation and short TR resulted in more typical time courses. GLM analysis showed that the combination of short stimulation and short TR could result in visually larger activation within these olfactory areas. TICA validated that the tested paradigm was spatially and temporally associated with a functionally connected network that included all 4 olfactory regions. In conclusion, the combination of short stimulation and short TR is associated with higher signal increase and shorter time to peak, making it more amenable to standard GLM-type analyses than long stimulation and long TR, and it should, thus, be preferable for olfactory fMRI.
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  • Georgiopoulos, Charalampos, et al. (author)
  • Olfactory Impairment in Parkinson's Disease Studied with Diffusion Tensor and Magnetization Transfer Imaging.
  • 2017
  • In: Journal of Parkinson's Disease. - : IOS PRESS. - 1877-7171 .- 1877-718X. ; 7:2, s. 301-311
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Olfactory impairment is an early manifestation of Parkinson's disease (PD). Diffusion Tensor Imaging (DTI) and Magnetization Transfer (MT) are two imaging techniques that allow noninvasive detection of microstructural changes in the cerebral white matter.OBJECTIVE: To assess white matter alterations associated with olfactory impairment in PD, using a binary imaging approach with DTI and MT.METHODS: 22 PD patients and 13 healthy controls were examined with DTI, MT and an odor discrimination test. DTI data were first analyzed with tract-based spatial statistics (TBSS) in order to detect differences in fractional anisotropy, mean, radial and axial diffusivity between PD patients and controls. Voxelwise randomized permutation was employed for the MT analysis, after spatial and intensity normalization. Additionally, ROI analysis was performed on both the DTI and MT data, focused on the white matter adjacent to olfactory brain regions.RESULTS: Whole brain voxelwise analysis revealed decreased axial diffusivity in the left uncinate fasciculus and the white matter adjacent to the left olfactory sulcus of PD patients. ROI analysis demonstrated decreased axial diffusivity in the right orbitofrontal cortex, as well as decreased mean diffusivity and axial diffusivity in the white matter of the left entorhinal cortex of PD patients. There were no significant differences regarding fractional anisotropy, radial diffusivity or MT between patients and controls.CONCLUSIONS: ROI analysis of DTI could detect microstructural changes in the white matter adjacent to olfactory areas in PD patients, whereas MT imaging could not.
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  • Georgiopoulos, Charalampos, et al. (author)
  • The diagnostic value of dopamine transporter imaging and olfactory testing in patients with parkinsonian syndromes.
  • 2015
  • In: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 262:9, s. 2154-2163
  • Journal article (peer-reviewed)abstract
    • The aim of the study was to compare the efficacy of olfactory testing and presynaptic dopamine imaging in diagnosing Parkinson's disease (PD) and atypical parkinsonian syndromes (APS); to evaluate if the combination of these two diagnostic tools can improve their diagnostic value. A prospective investigation of 24 PD patients, 16 APS patients and 15 patients with non-parkinsonian syndromes was performed during an 18-month period. Single photon emission computed tomography with the presynaptic radioligand (123)I-FP-CIT (DaTSCAN(®)) and olfactory testing with the Brief 12-item Smell Identification Test (B-SIT) were performed in all patients. DaTSCAN was analysed semi-quantitatively, by calculating two different striatal uptake ratios, and visually according to a predefined ranking scale. B-SIT score was significantly lower for PD patients, but not significantly different between APS and non-parkinsonism. The visual assessment of DaTSCAN had higher sensitivity, specificity and diagnostic accuracy compared to olfactory testing. Most PD patients (75 %) had visually predominant dopamine depletion in putamen, while most APS patients (56 %) had visually severe dopamine depletion both in putamen and in caudate nucleus. The combination of DaTSCAN and B-SIT led to a higher rate of correctly classified patients. Olfactory testing can distinguish PD from non-parkinsonism, but not PD from APS or APS from non-parkinsonism. DaTSCAN is more efficient than olfactory testing and can be valuable in differentiating PD from APS. However, combining olfactory testing and DaTSCAN imaging has a higher predictive value than these two methods separately.
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  • Gustafsson, Håkan, et al. (author)
  • Fe(III) distribution varies substantially within and between atherosclerotic plaques
  • 2014
  • In: Magnetic Resonance in Medicine. - United States : John Wiley & Sons. - 0740-3194 .- 1522-2594. ; 2:71, s. 885-892
  • Journal article (peer-reviewed)abstract
    • PURPOSE:Vulnerable atherosclerotic plaques are structurally weak and prone to rupture, presumably due to local oxidative stress. Redox active iron is linked to oxidative stress and the aim of this study was to investigate the distribution of Fe(III) in carotid plaques and its relation to vulnerability for rupture.METHODS:Atherosclerotic plaques from 10 patients (three asymptomatic and seven symptomatic) were investigated. Plaque vulnerability was classified using ultrasound and immunohistochemistry and correlated to Fe(III) measured by electron paramagnetic resonance spectroscopy.RESULTS:Large intra-plaque Fe(III) variations were found. Plaques from symptomatic patients had a higher Fe(III) concentration as compared with asymptomatic plaques (0.36 ± 0.21 vs. 0.06 ± 0.04 nmol Fe(III)/mg tissue, P < 0.05, in sections adjoining narrowest part of the plaques). All but one plaque from symptomatic patients showed signs of cap rupture. No plaque from asymptomatic patients showed signs of cap rupture. There was a significant increase in cap macrophages in plaques from symptomatic patients compared with asymptomatic patients (31 ± 11% vs. 2.3 ± 2.3%, P < 0.01).CONCLUSION:Fe(III) distribution varies substantially within atherosclerotic plaques. Plaques from symptomatic patients had significantly higher concentrations of Fe(III), signs of cap rupture and increased cap macrophage activity.
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  • Gustafsson, Håkan, 1976-, et al. (author)
  • Is vulnerability for carotid plaque rupture related to intrinsic Fe (III) distribution
  • 2012
  • Conference paper (other academic/artistic)abstract
    • Atherosclerotic plaques vulnerable for rupture are characterised by e.g., a large lipid pole, a high concentration of inflammatory cells and a thin fibrous cap. Recent research has showed that vulnerable plaques are structurally weaker and therefore more likely to rupture in response to physical forces; possible due to high local concentrations of macrophages and reactive oxygen species (ROS).  It is well known that redox active iron catalyses production of ROS and that the presence of Fe(III) is linked to ROS production. The aim of this study was to investigate the distribution of Fe(III) in carotid plaques.
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  • Gustafsson, Håkan, et al. (author)
  • Visualization of oxidative stress in ex vivo biopsies using electron paramagnetic resonance imaging
  • 2015
  • In: Magnetic Resonance in Medicine. - : Wiley. - 0740-3194 .- 1522-2594. ; 73:4, s. 1682-1691
  • Journal article (peer-reviewed)abstract
    • PURPOSE: The purpose of this study was to develop an X-Band electron paramagnetic resonance imaging protocol for visualization of oxidative stress in biopsies.METHODS: The developed electron paramagnetic resonance imaging protocol was based on spin trapping with the cyclic hydroxylamine spin probe 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine and X-Band EPR imaging. Computer software was developed for deconvolution and back-projection of the EPR image. A phantom containing radicals of known spatial characteristic was used for evaluation of the developed protocol. As a demonstration of the technique electron paramagnetic resonance imaging of oxidative stress was performed in six sections of atherosclerotic plaques. Histopathological analyses were performed on adjoining sections.RESULTS: The developed computer software for deconvolution and back-projection of the EPR images could accurately reproduce the shape of a phantom of known spatial distribution of radicals. The developed protocol could successfully be used to image oxidative stress in six sections of the three ex vivo atherosclerotic plaques.CONCLUSIONS: We have shown that oxidative stress can be imaged using a combination of spin trapping with the cyclic hydroxylamine spin probe cyclic hydroxylamine spin probe 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine and X-Band EPR imaging. A thorough and systematic evaluation on different types of biopsies must be performed in the future to validate the proposed technique. Magn Reson Med, 2014.
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  • Hasib, Lekbira, et al. (author)
  • Functional and homeostatic defects of regulatory T cells in patients with coronary artery disease
  • 2016
  • In: Journal of Internal Medicine. - : WILEY-BLACKWELL. - 0954-6820 .- 1365-2796. ; 279:1, s. 63-77
  • Journal article (peer-reviewed)abstract
    • ObjectiveRegulatory T cells (Tregs) are considered atheroprotective, and low levels have been associated with the acute coronary syndrome (ACS), particularly non-ST elevation (NSTE)-ACS. However, the functional properties as well as homeostasis of Tregs are mainly unknown in coronary artery disease (CAD). Here, we investigated the composition and functional properties of naive (n) and memory (m)Tregs in patients with NSTE-ACS and in patients 6-12months post-ACS. MethodsBased on the expression of CD25, FOXP3, CD127, CD45RA, CD39 and CTLA-4, Tregsubsets were defined by flow cytometry in whole blood or isolated CD4(+) T cells. The functional properties of nTregs and mTregs were examined in terms of proliferative capacity and modulation of cytokine secretion. To understand the potential consequences of Treg defects, we also investigated correlations with lipopolysaccharide (LPS)-induced cytokine secretion and ultrasound-defined carotid atherosclerosis. ResultsBoth NSTE-ACS and post-ACS patients exhibited reduced levels of nTregs (P<0.001) compared with healthy control subjects, but without compensatory increases in mTregs. Both nTregs and mTregs from patients showed significantly lower replicative rates and impaired capacity to modulate T-cell proliferation and secretion of interferon-gamma and IL-10. The Treg defect was also associated with LPS-induced cytokine secretion and increased burden of carotid atherosclerosis. ConclusionOur results demonstrate a functional and homeostatic Treg defect in patients with NSTE-ACS and also in stabilized patients 6-12months after ACS. Moreover, this defect was associated with a subclinical proinflammatory and atherogenic state. We believe that the failure to preserve Treg function and homeostasis reflects a need for immune-restoring strategies in CAD.
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  • Hultman, Martin, 1992-, et al. (author)
  • Comprehensive imaging of microcirculatory changes in the foot during endovascular intervention - A technical feasibility study
  • 2022
  • In: Microvascular Research. - Maryland Heights, MO, United States : Academic Press. - 0026-2862 .- 1095-9319. ; 141
  • Journal article (peer-reviewed)abstract
    • Chronic limb-threatening ischemia (CLTI) has a major impact on patient's lives and is associated with a heavy health care burden with high morbidity and mortality. Treatment by endovascular intervention is mostly based on macrocirculatory information from angiography and does not consider the microcirculation. Despite successful endovascular intervention according to angiographic criteria, a proportion of patients fail to heal ischemic lesions. This might be due to impaired microvascular perfusion and variations in the supply to different angiosomes. Non-invasive optical techniques for microcirculatory perfusion and oxygen saturation imaging have the potential to provide the interventionist with additional information in real-time, supporting clinical decisions during the intervention. This study presents a novel multimodal imaging system, based on multi-exposure laser speckle contrast imaging and multi-spectral imaging, for continuous use during endovascular intervention. The results during intervention display spatiotemporal changes in the microcirculation compatible with expected physiological reactions during balloon dilation, with initially induced ischemia followed by a restored perfusion, and local administration of a vasodilator inducing hyperemia. We also present perioperative and postoperative follow-up measurements with a pulsatile microcirculation perfusion. Finally, cases of spatial heterogeneity in the observed oxygen saturation and perfusion are discussed. In conclusion, this technical feasibility study shows the potential of the methodology to characterize changes in microcirculation before, during, and after endovascular intervention.
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  • Jatuzis, D, et al. (author)
  • Evaluation of posterior cerebral artery blood flow with transcranial Doppler sonography : value and risk of common carotid artery compression.
  • 2000
  • In: Journal of Clinical Ultrasound. - 0091-2751 .- 1097-0096. ; 28:9, s. 452-460
  • Journal article (peer-reviewed)abstract
    • PURPOSE: Investigations of the posterior cerebral arteries (PCA) by transcranial Doppler sonography (TCD) may be less reliable than investigations of the anterior part of the circle of Willis. Nevertheless, a true PCA may be identified by manual compression of the proximal common carotid artery (CCA) during TCD. Therefore, we used CCA compression in clinically indicated TCD studies and assessed retrospectively its risks and prospectively its benefits for PCA evaluations.METHODS: Using the transtemporal approach, we prospectively assessed flow velocities in posteriorly located blood vessels in 180 consecutive patients before and during CCA compression. The complications of CCA compression were retrospectively reviewed in all 3,383 clinical TCD investigations performed over an 8-year period.RESULTS: Decreased flow velocities during ipsilateral CCA compression occurred in 17% of patients. A PCA-like vessel with perfusion from the carotid artery or PCA supply from the carotid circulation was unmasked. Mixed distal PCA support by the posterior communicating artery and proximal PCA could not be shown by TCD. Transient cerebral symptoms occurred in less than 0.4% of the 3,383 retrospectively reviewed TCD investigations; no other adverse effects were seen.CONCLUSIONS: TCD without CCA compression may lead to false identification of the PCA. Since transient cerebral symptoms during CCA compression are rare, CCA compression can be used when a clinical TCD investigation of intracranial collateral blood flow compensation is indicated or when the identification of a cerebral artery is uncertain.
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  • Jogestrand, Tomas, et al. (author)
  • Discrepancies in recommended criteria for grading of carotid stenosis with ultrasound
  • 2016
  • In: Clinical Physiology and Functional Imaging. - : WILEY-BLACKWELL. - 1475-0961 .- 1475-097X. ; 36:4, s. 326-329
  • Journal article (peer-reviewed)abstract
    • The accuracy of duplex ultrasound for grading of internal carotid artery stenosis has been widely tested and shown to be high. However, different methods for measurement of the degree of carotid stenosis with the golden standard conventional angiography have been used in the different studies. This, together with other factors, has led to some confusion regarding the relation between the ultrasonographically measured flow velocity and the angiographically measured degree of stenosis. The ultrasound criteria that are used in Sweden (and in Germany) differ in an important way from the criteria recommended in North America and the United Kingdom for the same degree of angiographic stenoses. Possible reasons for the discrepancies are discussed in this article. The authors recommend absolute agreement locally whether ECST or NASCET criteria shall be used in the communication between radiologists, clinical physiologists, vascular surgeons, neurologists and other physicians involved in patient management decisions. Angle-dependent ultrasound criteria should be used and flow velocity measurements with ultrasound should be combined with assessment of plaque burden on 2D picture.
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  • Jogestrand, T., et al. (author)
  • Equalis kriterier för karotisdiagnostik – under kontinuerlig uppgradering
  • 2012
  • In: Läkartidningen. - 0023-7205 .- 1652-7518. ; 109:13, s. 702-703
  • Journal article (peer-reviewed)abstract
    • Ultraljudsundersökning av karotisartärerna med så­­ ­kallad duplexteknik har använts i Sverige sedan början av 1980-talet. Equalis expertgrupp för ­fysiologisk kärldia­gnostik har nyligen presen­terat sina rekommendationer för karotisdiagnostik med ultra­ljudsteknik.
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  • Koppal, Sandeep, et al. (author)
  • Quantitative fat and R2* mapping in vivo to measure lipid-rich necrotic core and intraplaque hemorrhage in carotid atherosclerosis
  • 2017
  • In: Magnetic Resonance in Medicine. - : John Wiley & Sons. - 0740-3194 .- 1522-2594. ; 78:1, s. 285-296
  • Journal article (peer-reviewed)abstract
    • Purpose: The aim of this work was to quantify the extent of lipid-rich necrotic core (LRNC) and intraplaque hemorrhage (IPH) in atherosclerotic plaques. Methods: Patients scheduled for carotid endarterectomy underwent four-point Dixon and T1-weighted magnetic resonance imaging (MRI) at 3 Tesla. Fat and R2* maps were generated from the Dixon sequence at the acquired spatial resolution of 0.60×0.60×0.70mm voxel size. MRI and three-dimensional (3D) histology volumes of plaques were registered. The registration matrix was applied to segmentations denoting LRNC and IPH in 3D histology to split plaque volumes in regions with and without LRNC and IPH. Results: Five patients were included. Regarding volumes of LRNC identified by 3D histology, the average fat fraction by MRI was significantly higher inside LRNC than outside: 12.64±0.2737% versus 9.294±0.1762% (mean±standard error of the mean [SEM]; P<0.001). The same was true for IPH identified by 3D histology, R2* inside versus outside IPH was: 71.81±1.276 s-1 versus 56.94±0.9095 s-1 (mean±SEM; P<0.001). There was a strong correlation between the cumulative fat and the volume of LRNC from 3D histology (R2=0.92) as well as between cumulative R2* and IPH (R2=0.94). Conclusion: Quantitative mapping of fat and R2* from Dixon MRI reliably quantifies the extent of LRNC and IPH.
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  • Lilledahl, Magnus B., et al. (author)
  • Combined imaging of oxidative stress and microscopic structure reveals new features in human atherosclerotic plaques
  • 2015
  • In: Journal of Biomedical Optics. - : Society of Photo-optical Instrumentation Engineers (SPIE). - 1083-3668 .- 1560-2281. ; 20:2, s. 020503-
  • Journal article (peer-reviewed)abstract
    • Human atherosclerotic samples collected by carotid endarterectomy were investigated using electronic paramagnetic resonance imaging (EPRI) for visualization of reactive oxygen species, and nonlinear optical microscopy (NLOM) to study structural features. Regions of strong EPRI signal, indicating a higher concentration of reactive oxygen species and increased inflammation, were found to colocalize with regions dense in cholesterol crystals as revealed by NLOM.
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  • Lundberg, Anna K, et al. (author)
  • Inflammatory response to acute mental stress is associated with altered cortisol reactivity and telomere shortening in patients with coronary artery disease
  • Other publication (other academic/artistic)abstract
    • Background: Psychological stress and inflammation are both important risk factors for coronary artery disease (CAD). Susceptibility to mental stress-induced inflammation has been little explored in patients with CAD. Here, we investigated whether stress-induced inflammatory response, more precisely neutrophil activation, was associated with cortisol reactivity, leukocyte telomere length (TL) and carotid atherosclerotic burden in CAD.Methods: Sixty-four patients with stable CAD underwent a laboratory stress test. Matrix metalloproteinase (MMP)-9, MMP-8, tissue inhibitors (TIMP)-1 and -2, myeloperoxidase (MPO) and salivary cortisol were measured before and 20 min after stress. Leukocyte TL was assessed as well as basal cortisol levels, background psychological factors and atherosclerosis in carotid arteries.Results: The variation in stress-induced release of neutrophil markers was substantial. Patients were therefore divided into lower and upper tertiles depending on changes in serum MMP-9, T1: -12 %, T3: +27 %, with corresponding changes in MMP-8 and MPO. Clinical or psychological characteristics did not differ between groups, neither did basal levels of neutrophil markers or cortisol. Cardiovascular reactivity during stress was similar in T1 and T3, while cortisol declined after stress only in T3 (-30 %). Leukocyte TL was shorter in T3 than in T1, 0.78 vs 0.88, p = 0.006. Moreover, presence of plaques in right carotid artery differed between T1 and T3, 66 % vs 100 %, p = 0.004.Conclusion: Stress-induced neutrophil activation in CAD patients was associated with altered cortisol reactivity, leukocyte telomere attrition and increased subclinical atherosclerosis. Data suggest that mental stress testing can identify high-risk patients in need of novel prevention and treatment strategies.
  •  
29.
  • Lundin, Evelyn S., et al. (author)
  • Single-dose tranexamic acid in advanced ovarian cancer surgery reduces blood loss and transfusions: double-blind placebo-controlled randomized multicenter study
  • 2014
  • In: Acta Obstetricia et Gynecologica Scandinavica. - : Informa Healthcare / Wiley. - 0001-6349 .- 1600-0412. ; 93:4, s. 335-344
  • Journal article (peer-reviewed)abstract
    • ObjectiveTo determine whether single-dose tranexamic acid given intravenously immediately before surgery for presumed advanced ovarian cancer reduces perioperative blood loss and blood transfusions. DesignA randomized double-blind, placebo-controlled multicenter study. SettingTwo university hospitals and two central hospitals in the southeast health region of Sweden. PopulationOne hundred women with presumed advanced ovarian cancer scheduled for radical debulking surgery between March 2008 and May 2012 who complied with inclusion/exclusion criteria were randomized; 50 were allocated to receive tranexamic acid and 50 to receive placebo. Analysis was performed according to intention-to-treat principles. MethodsThe volume of tranexamic acid (15mg/kg body weight, 100mg/mL tranexamic acid) or the same volume of placebo (0.9% NaCl) was added to a 100-mL saline solution plastic bag. The study medication was given immediately before the start of surgery. Data were analyzed by means of non-parametric statistics and multivariate models adjusted for confounding factors. Main outcome measuresBlood loss and red blood cell transfusions. ResultsThe total blood loss volume and transfusion rate were significantly lower in the tranexamic acid group compared with the placebo group. Median total blood loss was 520 and 730mL, respectively (p=0.03). Fifteen (30%) and 22 (44%), respectively received transfusions (odds ratio 0.44; upper 95% CI 0.97; p=0.02). ConclusionA single dose of tranexamic acid given immediately before surgery reduces blood loss and transfusion rates significantly in advanced ovarian cancer surgery. Tranexamic acid may be recommended as standard prophylactic treatment in advanced ovarian cancer surgery.
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30.
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31.
  • Nelzén, Oskar, 1984-, et al. (author)
  • Impact on venous haemodynamics after treatment of great saphenous vein incompetence using plethysmography and duplex ultrasound
  • 2020
  • In: Phlebology. - : Sage Publications. - 0268-3555 .- 1758-1125. ; 35:7, s. 495-504
  • Journal article (peer-reviewed)abstract
    • ObjectivesTo evaluate postoperative venous haemodynamics and quality of life after treatment of great saphenous vein (GSV) incompetence.MethodsRadiofrequency ablation and high ligation and stripping were performed in 62 patients (65 limbs) and 58 (65 limbs), respectively. Phlebectomies were performed in both modalities. Strain-gauge plethysmography on the foot combined with superficial venous occlusion was used to measure refilling time after knee bends. Strain-gauge plethysmography, duplex ultrasound and quality of life were assessed before and one month after treatment.ResultsDuplex ultrasound displayed successful intervention in all but two limbs. Refilling time increased similar in radiofrequency ablation and high ligation and stripping after treatment (p < 0.001). Postoperatively, strain-gauge plethysmography detected remaining reflux in 71% of the patients. Multivariate analysis showed that two or more incompetent calf branches were associated with remaining reflux (OR 4.82 (95% CI: 1.33–17.5), p = 0.02). No difference in quality of life was seen in patients with remaining reflux.ConclusionsDespite successful treatment, a majority of the limbs showed remaining reflux, in which incompetent calf branches appear to play an important role.Clinicaltials.gov: Lower Limb Venous Insufficiency and the Effect of Radiofrequency Treatment Versus Open Surgery. Nr: NCT02397226
  •  
32.
  • Nelzén, Oskar, 1984- (author)
  • Lower limb venous incompetence and the effect of radiofrequency ablation versus open surgery : Focus on haemodynamics, quality of life and health economic aspects
  • 2023
  • Doctoral thesis (other academic/artistic)abstract
    • Chronic venous incompetence (CVI) is a common condition, and varicose vein treatment is one of the most-common surgical procedures performed worldwide. Common symptoms of CVI are pain, cramps, itching, feeling of leg heaviness and venous claudication. Advanced CVI can lead to skin changes, eczema and venous ulcers. While the cause of the disease is un-known, it often starts with venous enlargement and valve dysfunction. The overall aims of this thesis are: 1) to develop quantitative diagnostic measurements using strain-gauge plethysmography (SGP) with standardised superficial venous occlusion and duplex ultrasound (DUS); 2) to evaluate the effects of radiofrequency ablation (RFA) and high ligation/stripping (HL/S) for patients with great saphenous vein (GSV) incompetence; and 3) to evaluate the cost-effectiveness of GSV treatment.   The first of the four studies involved patients with GSV incompetence. For these patients, SGP with superficial venous occlusion was performed before and after GSV treatment. SGP was able to predict the haemodynamic outcome of the treatment in the majority of the limbs examined. The conclusion is that SGP with standardised superficial venous occlusion may be used for predicting the outcome of GSV treatment.   The second study evaluated the short-term outcomes of GSV treatment using RFA and HL/S regarding haemodynamics and quality of life (QoL). Both treatments lead to significant improvements in QoL, with no signifcant differences between the treatments. Despite successful treatment, the majority of the limbs in both treatment groups had significant residual reflux located mainly in the calf (i.e., below the treated area). The residual reflux may be a risk factor for future symptom relapses and need to be examined in more-long-term studies.   The third study examined quantitative DUS and SGP parameters in relation to clinical severity and QoL. DUS-derived volume flow and SGP re-flux time showed weak but significant correlations with clinical severity (C in CEAP). The conclusion is that the current gold standard using the qualitative DUS-derived reflux time for CVI diagnostics should be revised and replaced with a more-relevant quantitative parameter.   The fourth study evaluated the cost-effectiveness of GSV treatment with 1 year of follow-up. Both RFA and HL/S provided significant improvements in QoL. RFA is very cost-effective and is associated with fewer days missed from work compared to HL/S. Cost-wise, both methods are well be-low the national threshold for cost-effective treatment. Due to its higher cost, HL/S should be reserved for cases that require this method.    
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33.
  • Nelzén, Oskar, 1984-, et al. (author)
  • Prediction of Post-interventional Outcome in Great Saphenous Vein Incompetence : The Role of Venous Plethysmography with Selective Superficial Vein Occlusion
  • 2016
  • In: European Journal of Vascular and Endovascular Surgery. - : Elsevier. - 1078-5884 .- 1532-2165. ; 52:3, s. 377-384
  • Journal article (peer-reviewed)abstract
    • Objective/BackgroundTo evaluate whether the outcome of radiofrequency ablation (RFA) treatment of great saphenous vein (GSV) incompetence may be predicted using strain-gauge plethysmography (SGP) with selective occlusion of the superficial venous system.MethodsSeventeen patients (20 limbs) underwent endovenous RFA treatment for GSV incompetence (Clinical Etiology Anatomy Pathophysiology classification C2–C5; “C-group”). Duplex ultrasound (DUS) and SGP were performed with selective occlusion of superficial veins before and after RFA. Selective superficial occlusion was validated, in a control group (C-group) of 12 patients (14 legs), by ascending phlebography. In the RFA group, the time taken to reach 50% and 90% (T50, T90) of maximum venous volume was measured, as well as relative maximal reflux rates (%EV/min). The methodological error and coefficient of variation (CV) were assessed.ResultsNineteen of 20 legs had complete post-operative GSV obliteration using DUS, and refilling times were improved after RFA (T50 11 ± 3 vs. 19 ± 3 s; p < .001; T90 27 ± 5 vs. 47 ± 6 s; p < .001). With SGP, the methodological error and CV for T50 were 4 s and 16%, respectively. Equivalence between pre-operative superficial occlusion and post-operative baseline measurements was achieved in 15 of 17 legs for T50, and 12 of 17 for T90 (three of the 20 legs were excluded due to treatment failure [n = 1], and untreated perforating veins [n = 2]). Mean differences (95% confidence interval) were within the equivalence ranges (T50 1 [–1 to 3] seconds; T90 –3 [–11 to 4] seconds). In the C-group superficial vein occlusion was possible in 12 of 14 legs. The remaining patient (two legs) showed incomplete superficial vein occlusion at ankle level (lipodermatosclerosis) and complete superficial vein occlusion at calf level.ConclusionSGP with standardized superficial venous occlusion seems to be a reliable method for identifying venous reflux and may be useful in predicting the results of successful RFA treatment.
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34.
  • Nelzén, Oskar, 1984-, et al. (author)
  • Relationship between clinical severity and hemodynamic impact of great saphenous vein incompetence using strain gauge plethysmography and duplex ultrasound
  • 2022
  • In: Phlebology. - London, United Kingdom : Sage Publications. - 0268-3555 .- 1758-1125. ; 37:8, s. 579-587
  • Journal article (peer-reviewed)abstract
    • Objectives To evaluate the relation of quantitative Duplex ultrasound (DUS) and strain gauge plethysmography (SGP) parameters with clinical severity and quality of life in patients with superficial venous incompetence.Methods DUS volume flow and distal SGP refilling times (T-50 and T-90) were evaluated in 152 patients (164 Limbs) with superficial incompetence. Clinical severity and quality of life were evaluated with C of the CEAP classification, venous clinical severity score (VCSS), Aberdeen varicose vein questionnaire (AVVQ), and EuroQol 5D-3L.Results Higher DUS volume flow was associated with higher C in CEAP scores. Volume flow was also related to T-50 and T-90. Shorter T-50 and T-90 were associated with higher C in CEAP and VCSS. T-50 was also associated with EQ-5DVAS. Reflux extension to the foot wase associated with shorter T-50 and T-90 and higher DUS volume flow.Conclusions DUS volume flow and SGP refilling times are related with clinical severity and provide quantitative information regarding venous function in patients with superficial incompetence.
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35.
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36.
  • Nelzén, Oskar, 1984-, et al. (author)
  • Short Term Cost Effectiveness of Radiofrequency Ablation and High Ligation and Stripping for Great Saphenous Vein Incompetence
  • 2024
  • In: European Journal of Vascular and Endovascular Surgery. - : Elsevier. - 1078-5884 .- 1532-2165. ; 67:5, s. 811-817
  • Journal article (peer-reviewed)abstract
    • Objective: Superficial venous incompetence (SVI) is a common disease that causes significant quality of life (QoL) impairment. There is a need for more health economic evaluations of SVI treatment. The aim of this study was to perform a cost effectiveness analysis in patients with great saphenous vein (GSV) incompetence comparing radiofrequency ablation (RFA), high ligation and stripping (HL/S), and no treatment or conservative treatment with one year follow up.Methods: Randomised controlled trial economic analysis from an ongoing trial; 143 patients (156 limbs) with GSV incompetence (C in CEAP 2 - 6) were included. Treatment was performed with RFA or HL/S. Follow up was performed up to one year using duplex ultrasound, revised venous clinical severity score (r-VCSS), Aberdeen Varicose Vein Questionnaire (AVVQ), and EuroQol-5D-3L (EQ-5D-3L).Results: Seventy-eight limbs were treated with RFA and HL/S respectively. No treatment or conservative treatment was assumed to have zero in treatment cost and no treatment benefit. In the RFA group, one limb had reflux in the GSV after one month and three limbs after one year. In HL/S, two limbs had remaining reflux in the treated area at one month and one year. Both disease severity (r-VCSS, p = .004) and QoL (AVVQ, p = .021 and EQ-5D-3L, p = .028) were significantly improved over time. The QALY gain was 0.21 for RFA and 0.17 for HL/S. The cost per patient was calculated as €1 292 for RFA and €2 303 for HL/S. The cost per QALY (compared with no treatment or conservative treatment) was €6 155 for RFA and €13 549 for HL/S. With added cost for days absent from work the cost per QALY was €7 358 for RFA and €24 197 for HL/S. The cost per QALY for both methods was well below the threshold suggested by Swedish National Board of Health.Conclusion: RFA is more cost effective than HL/S and no treatment or conservative treatment at one year follow up.
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37.
  • Persson, Anders, 1953-, et al. (author)
  • Advances of dual source, dual-energy imaging in postmortem CT
  • 2008
  • In: European Journal of Radiology. - : Elsevier BV. - 0720-048X .- 1872-7727. ; 68:3, s. 446-455
  • Journal article (peer-reviewed)abstract
    • This paper focuses on the use of multi-detector row dual-energy computed tomography (DECT) in the evaluation of postmortal examinations. The use of dual energy moves postmortem CT to an entirely new dimension of diagnostic sensitivity where contrast in the image is not merely limited to X-ray attenuation differences, but may include elements of functional and tissue characterization. This additional information may be used to improve the benefit postmortem imaging can provide to supplement and simplify the conventional autopsy. © 2008 Elsevier Ireland Ltd. All rights reserved.
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38.
  • Rein-Hedin, Erik, et al. (author)
  • Utilizing venous occlusion plethysmography to assess vascular effects: A study with buloxibutid, an angiotensin II type 2 receptor agonist
  • 2024
  • In: Clinical and Translational Science. - : WILEY. - 1752-8054 .- 1752-8062. ; 17:2
  • Journal article (peer-reviewed)abstract
    • Buloxibutid (also known as C21) is a potent and selective angiotensin II type 2 receptor (AT2R) agonist, in development for oral treatment of fibrotic lung disease. This phase I, open-label, pharmacodynamic study investigated vascular effects of buloxibutid in five healthy male volunteers. Subjects were administered intra-arterial infusions of buloxibutid for 5 min in ascending doses of 3, 10, 30, 100, and 200 mu g/min, infused sequentially in the forearm. Infusions of sodium nitroprusside (SNP) solution in doses of 0.8-3.2 mu g/min were administered as a positive control. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. Safety and tolerability of intra-arterial administrations of buloxibutid were evaluated. Following infusion of buloxibutid in doses of 3-200 mu g/min, the range of increase in FBF was 27.8%, 17.2%, 37.0%, 28.5%, and 60.5%, compared to the respective baseline. The largest increase was observed in the highest dose group. Infusions of SNP as a positive control, increased FBF 230-320% compared to baseline. Three adverse events (AEs) of mild intensity, not related to buloxibutid or SNP, were reported for two subjects. Two of these AEs were related to study procedures. There were no clinically relevant changes in arterial blood pressure during the study period. Intra-arterial infusion of buloxibutid in low, ascending doses increased FBF, indicating that buloxibutid may be effective in conditions associated with endothelial dysfunction. Venous occlusion plethysmography was found to be a useful method to explore pharmacodynamic vascular effects of novel AT2R agonists, while avoiding systemic adverse effects.
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39.
  • Segernäs Kvitting, Anna, et al. (author)
  • Prediction of Postoperative Delirium After Cardiac Surgery with A Quick Test of Cognitive Speed, Mini-Mental State Examination and Hospital Anxiety and Depression Scale
  • 2022
  • In: Clinical Interventions in Aging. - : Dove Medical Press Ltd. - 1176-9092 .- 1178-1998. ; 17, s. 359-368
  • Journal article (peer-reviewed)abstract
    • Purpose: To evaluate if preoperative assessment with A Quick Test of Cognitive Speed (AQT) could increase the accuracy of predicting delirium after cardiac surgery compared to Mini-Mental State Examination (MMSE), and examine if a composite of variables, including cognitive function and depressive symptoms, could be useful to predict delirium. Patients and Methods: Cardiac surgery was performed in 218 patients (mean age 72 years). Preoperative evaluation involved AQT, MMSE and Hospital Anxiety And Depression Scale (HADS). Postoperative delirium was assessed using Nursing Delirium Screening Scale (Nu-DESC) and Confusion Assessment Method-ICU (CAM-ICU). Logistic regression was performed to detect predictors of postoperative delirium and receiver operator characteristic curves (ROC) with area under the curve (AUC) to determine the accuracy. Results: Postoperative delirium occurred in 47 patients (22%) who had lower MMSE scores (median (range), 27 (19-30) vs 28 (20- 30), p=0.009) and slower AQT (median (range), 76 (48-181) vs 70 (40-182) seconds, p=0.030) than patients without delirium. Predictive power measured as AUC (95% CI) was 0.605 (0.51-0.70) for AQT and 0.623 (0.53-0.72) for MMSE. Logistic regression (OR, 95% CI) showed MMSE 27 points (2.72, 1.27-5.86), AQT 70 sec (2.26, 1.03-4.95), HADS-D >4 points (2.60, 1.21-5.58) and longer cardiopulmonary bypass-time (1.007, 1.002-1.013) to be associated with postoperative delirium. Combining these parameters yielded an AUC of 0.736 (0.65-0.82). Conclusion: The ability of predicting delirium using AQT was similar to MMSE, and only slightly higher by combining AQT and MMSE. Adding HADS-D and cardiopulmonary bypass-time to MMSE and AQT increased the predictive power to a borderline acceptable discriminatory value. Preoperative cognitive tests and screening for depressive symptoms may help identify patients at risk of postoperative delirium. Yet, there is still a need to establish useful preoperative tests.
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40.
  • Sjöwall, Johanna, et al. (author)
  • Neoehrlichia mikurensis & nbsp;Causing Thrombosis and Relapsing Fever in a Lymphoma Patient Receiving Rituximab
  • 2021
  • In: Microorganisms. - : MDPI AG. - 2076-2607. ; 9:10
  • Journal article (peer-reviewed)abstract
    • Neoehrlichia (N.) mikurensis, an intracellular tick-borne bacterium not detected by routine blood culture, is prevalent in ticks in Scandinavia, Central Europe and Northern Asia, and may cause long-standing fever, nightly sweats, migrating pain, skin rashes and thromboembolism, especially in patients treated with rituximab. The multiple symptoms may raise suspicion of both infection, inflammation and malignancy, and lead in most cases to extensive medical investigations across many medical specialist areas and a delay of diagnosis. We describe a complex, albeit typical, case of neoehrlichiosis in a middle-aged splenectomised male patient with a malignant lymphoma, receiving treatment with rituximab. The multifaceted clinical picture associated with this tick-borne disease is addressed, and longitudinal clinical and laboratory data, as well as imaging, are provided. Longstanding relapsing fever in combination with thrombosis in superficial and deep veins in an immunocompromised patient living in a tick-endemic region should raise the suspicion of the emerging tick-borne disease neoehrlichiosis. Given the varied clinical presentation and the risk of delay in diagnosis and treatment, we believe it is important to raise clinicians' awareness of this emerging infection, which is successfully treated with doxycycline.
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41.
  • Skoog, Johan, et al. (author)
  • Calf venous compliance measured by venous occlusion plethysmography : methodological aspects.
  • 2015
  • In: European Journal of Applied Physiology. - : Springer Science and Business Media LLC. - 1439-6319 .- 1439-6327. ; 115:2, s. 245-56
  • Journal article (peer-reviewed)abstract
    • PURPOSE: Calf venous compliance (C calf) is commonly evaluated with venous occlusion plethysmography (VOP) during a standard cuff deflation protocol. However, the technique relies on two not previously validated assumptions concerning thigh cuff pressure (P cuff) transmission and the impact of net fluid filtration (F filt) on C calf. The aim was to validate VOP in the lower limb and to develop a model to correct for F filt during VOP.METHODS: Strain-gauge technique was used to study calf volume changes in 15 women and 10 age-matched men. A thigh cuff was inflated to 60 mmHg for 4 and 8 min with a subsequent decrease of 1 mmHg s(-1). Intravenous pressure (P iv) was measured simultaneously. C calf was determined with the commonly used equation [Compliance = β 1 + 2β 2 × P cuff] describing the pressure-compliance relationship. A model was developed to identify and correct for F filt.RESULTS: Transmission of P cuff to P iv was 100 %. The decrease in P cuff correlated well with P iv reduction (r = 0.99, P < 0.001). Overall, our model showed that C calf was underestimated when F filt was not accounted for (all P < 0.01). F filt was higher in women (P < 0.01) and showed a more pronounced effect on C calf compared to men (P < 0.05). The impact of F filt was similar during 4- and 8-min VOP.CONCLUSIONS: P cuff is an adequate substitute for P iv in the lower limb. F filt is associated with an underestimation of C calf and differences in the effect of F filt during VOP can be accounted for with the correction model. Thus, our model seems to be a valuable tool in future studies of venous wall function.
  •  
42.
  • Skoog, Johan (author)
  • Cardiovascular regulation in women with vasovagal syncope : With special reference to the venous system
  • 2016
  • Doctoral thesis (other academic/artistic)abstract
    • Although vasovagal syncope (VVS) is a common clinical condition the mechanisms behind VVS remain elusive. Upright posture is the major trigger of VVS and lower limb blood pooling affecting cardiac output has been proposed as a major determinant. The overall aim of this thesis was twofold. First, to develop new methodology for calculating limb venous compliance. Second, to study lower limb venous volume load and cardiovascular responses during hypovolemic circulatory stress caused by lower body negative pressure (LBNP) in healthy women and women with VVS, emphasizing compensatory mechanisms to maintain central blood volume.Net fluid filtration was associated with an underestimation ofvenous compliance. This could be accounted for with a correctionmodel. Further, a new venous wall model made it possible to adopt thevenous pressure-volume curve through the entire pressure range andthus provide a valid characterization of venous compliance.Calf blood pooling was similar between the groups and was not associated with tolerance to hypovolemic circulatory stress. Venous compliance was reduced at low venous pressures in VVS and correlated with decreased tolerance to circulatory stress. VVS women displayed attenuated sympathetic vasoconstrictor responses during graded circulatory stress, and mobilization of arm capacitance blood as well as capillary fluid absorption from extra- to intravascular space were reduced. Accordingly, more pronounced reductions in cardiac output were found in VVS. Thus, reduced compensatory mechanisms to maintain cardiac output could contribute to the pathogenesis oforthostatic VVS.In healthy women, rapid pooling in the lower limb was associated with higher tolerance to circulatory stress and more efficient cardiovascular responses, in part due to speed-dependent baroreflex-mediated sympathetic activation. In VVS however, rapid lower limb blood pooling was associated with lower tolerance and deficient cardiovascular responses. No speed-dependent baroreflexmediated sympathetic activation was found in VVS, indicating welldefined differences in cardiovascular regulation already in the initial responses to orthostatic stress.
  •  
43.
  • Skoog, Johan, et al. (author)
  • Quantifiable remaining reflux 1 year after treatment of superficial venous incompetence is associated with impaired clinical outcome
  • 2023
  • In: JOURNAL OF VASCULAR SURGERY-VENOUS AND LYMPHATIC DISORDERS. - : ELSEVIER. - 2213-333X. ; 11:6, s. 1130-1138
  • Journal article (peer-reviewed)abstract
    • Objective: Remaining symptoms after treatment of superficial venous incompetence is a common problem. Duplex ultrasound is often used during follow-up, but does not permit an overall quantification of venous function. We have developed a plethysmographic method using occlusion cuffs for separation of superficial and deep venous reflux. By assessing the superficial component it is possible to quantify a potential suboptimal hemodynamic treatment in patients with superficial venous incompetence. The aim was to examine whether patients with hemodynamically quantifiable remaining reflux after treatment experience impaired clinical outcomes.Methods: This single-center prospective cohort study evaluated 156 limbs with great saphenous vein incompetence treated with radiofrequency ablation or high ligation and stripping. Duplex ultrasound and strain-gauge plethysmog-raphy (SGP) with and without selective superficial occlusion were performed before and one-year after treatment. Time taken (seconds) to reach 50% of the venous volume (T-50) was evaluated. A difference in the T(50 )of >5 seconds between postoperative strain-gauge plethysmography with and without superficial occlusion was defined as remaining reflux. The Venous Clinical Severity Score (VCSS) and Aberdeen Varicose Vein Questionnaire (AVVQ) were evaluated and compared between patients with and without remaining reflux. Multivariable logistic regression was used to evaluate risk factors for remaining plethysmographic reflux.Results: In all patients, median (25th, 75th percentile) T-50 increased preoperatively from 7 seconds (3, 12 seconds) to 17 seconds (11, 28 seconds) (P < .001)1 year after treatment. The VCSS and AVVQ were reduced (VCSS, 8.0 [6.0, 10.0] vs 3.0 [1.0, 5.0] [P < .001]; AVVQ, 21.8 [15.8, 32.1] vs 6.4 [2.2, 11.0] [P < .001]). Of the 156 limbs, 87 (56%) demonstrated remaining reflux 1 year after treatment. Patients with remaining plethysmographic reflux displayed higher median (25th, 75th percentile) VCSS (3.0 [2.0, 5.0] vs 2.0 [1.0, 4.0]; P= .012) and AVVQ (7.5 [2.7, 14.9] vs 4.7 [1.6, 9.2]; P= .025). Multivariate logistic regression showed that higher preoperative C in the Clinical Etiology Anatomy Pathophysiology classification (CEAP) (odds ratio [OR], 2.9 [95% confidence interval [CI], 1.34-6.46), age (OR, 1.03; 95% CI, 1.001-1.065), small saphenous vein incompetence (OR, 4.2; 95% CI, 1.30-13.73) and postoperative great saphenous vein reflux below the treated area (OR, 2.16; 95% CI, 1.02-4.56) were significant risk factors for remaining plethysmographic reflux.Conclusions: A majority of treated limbs showed quantifiable reflux 1 year after intervention and these patients displayed worse patient related outcomes assessed with the VCSS and AVVQ. Remaining plethysmographic reflux was associated with preoperative small saphenous vein incompetence and reflux below the treated area as well as advanced age and higher C in CEAP.
  •  
44.
  • Skoog, Johan, 1977-, et al. (author)
  • Reduced compensatory responses to maintain central blood volume during hypovolemic stress in women with vasovagal syncope
  • 2017
  • In: American Journal of Physiology. Regulatory Integrative and Comparative Physiology. - : AMER PHYSIOLOGICAL SOC. - 0363-6119 .- 1522-1490. ; 312:1, s. R55-R61
  • Journal article (peer-reviewed)abstract
    • Although vasovagal syncope (VVS) is a common clinical condition, the underlying pathophysiology is not fully understood. A decrease in cardiac output has recently been suggested as a factor in orthostatic VVS. The aim was to investigate compensatory mechanisms to maintain central blood volume and venous return during hypovolemic stress in women with VVS. Fourteen VVS women (25.7 +/- 5.0 yr) and 15 matched controls (22.8 +/- 3.2 yr) were investigated. Single-step and graded lower body negative pressure (LBNP) to presyncope were used to create hypovolemic stress. Peripheral mobilization of venous blood from the arm (capacitance response and net capillary fluid absorption) and lower limb blood pooling (calf capacitance response) were evaluated using a volumetric technique. Cardiovascular responses and plasma norepinephrine (P-NE) were measured. Resting P-NE was elevated in VVS women (P amp;lt; 0.01). Despite a similar hypovolemic stimulus, the increase in P-NE was blunted (P amp;lt; 0.01) and the maximal percent increase in total peripheral resistance was reduced (P amp;lt; 0.05) during graded LBNP in VVS women. The arm capacitance response was slower (P amp;lt; 0.05) and reduced in VVS women at higher levels of LBNP (P amp;lt; 0.05). Capillary fluid absorption from extra-to intravascular space was reduced by similar to 40% in VVS women (P amp;lt; 0.05). Accordingly, the reduction in cardiac output was more pronounced (P amp;lt; 0.05). In conclusion, in VVS women, mobilization of peripheral venous blood and net fluid absorption from tissue to blood during hypovolemic stress were decreased partly as a result of an attenuated vasoconstrictor response. This may seriously impede maintenance of cardiac output during hypovolemic stress and could contribute to the pathogenesis of VVS.
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45.
  • Skoog, Johan, et al. (author)
  • Reduced venous compliance: an important determinant for orthostatic intolerance in women with vasovagal syncope
  • 2016
  • In: American Journal of Physiology. Regulatory Integrative and Comparative Physiology. - : AMER PHYSIOLOGICAL SOC. - 0363-6119 .- 1522-1490. ; 310:3, s. R253-R261
  • Journal article (peer-reviewed)abstract
    • The influence of lower limb venous compliance on orthostatic vasovagal syncope (VVS) is uncertain. The most widespread technique to calculate venous compliance uses a nonphysiological quadratic regression equation. Our aim was therefore to construct a physiologically derived venous wall model (VWM) for calculation of calf venous compliance and to determine the effect of venous compliance on tolerance to maximal lower body negative pressure (LBNP). Venous occlusion plethysmography was used to study calf volume changes in 15 women with VVS (25.5 +/- 1.3 yr of age) and 15 controls (22.8 +/- 0.8 yr of age). The fit of the VWM and the regression equation to the experimentally induced pressure-volume curve was examined. Venous compliance was calculated as the derivative of the modeled pressure-volume relationship. Graded LBNP to presyncope was used to determine the LBNP tolerance index (LTI). The VWM displayed a better fit to the experimentally induced pressure-volume curve (P < 0.0001). Calf blood pooling was similar in the groups and was not correlated to the LTI (r = 0.204, P = 0.30). Venous compliance was significantly reduced at low venous pressures in women with VVS (P = 0.042) and correlated to the LTI (r = 0.459, P = 0.014) in the low pressure range. No correlation was found between venous compliance at high venous pressures and the LTI. In conclusion, the new VWM accurately adopted the curvilinear pressure-volume curve, providing a valid characterization of venous compliance. Reduced venous compliance at low venous pressures may adversely affect mobilization of peripheral venous blood to the central circulation during hypovolemic circulatory stress in women with VVS.
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46.
  • Skoog, Johan, et al. (author)
  • Slower Lower Limb Blood Pooling Increases Orthostatic Tolerance in Women with Vasovagal Syncope
  • 2016
  • In: Frontiers in Physiology. - : FRONTIERS MEDIA SA. - 1664-042X. ; 7:232
  • Journal article (peer-reviewed)abstract
    • Background and Aim: Slower lower limb blood pooling and associated blunted sympathetic activation has been detected in healthy women prone to orthostatic syncope. Whether these findings are true also for patients with vasovagal syncope (WS) is unknown. The aim was to investigate initial blood pooling time (pooling(time), time to 50% of total blood pooling) together with hemodynamic responses and orthostatic tolerance during lower body negative pressure (LBNP) in WS and healthy controls. Methods and Results: Fourteen WS women (25.7 +/- 1.3 years) and 15 healthy women (22.8 +/- 0.8 years) were subjected to single-step and graded LBNP to pre-syncope. Lower limb blood pooling (ml 100 ml(-1)), poolingtime (s), hemodynamic responses and LBNP-tolerance were evaluated. LBNP induced comparable lower limb blood pooling in both groups (controls, 3.1 +/- 0.3; WS, 2.9 +/- 0.3 ml 100 ml(-1), P = 0.70). In controls, shorter pooling(time) correlated to higher LBNP-tolerance (r = -0.550, P amp;lt; 0.05) as well as better maintained stroke volume (r =-0.698, P amp;lt; 0.01) and cardiac output (r = -0.563, P amp;lt; 0.05). In contrast, shorter poolingtime correlated to lower LBNP-tolerance in VVS (r = 0.821, P amp;lt; 0.001) and larger decline in stroke volume (r = 0.611, P 0.05). Furthermore, in controls, shorter poolingtime correlated to baroreflex-mediated hemodynamic changes during LBNP, e.g., increased vasoconstriction (P amp;lt; 0.001). In VVS, poolingtime was not correlated with LBNP-induced baroreceptor unloading, but rather highly correlated to resting calf blood flow (P amp;lt; 0.001). Conclusions: Shorter poolingtime seems to elicit greater sympathetic activation with a concomitant higher orthostatic tolerance in healthy women. The contrasting findings in AS indicate a deteriorated vascular sympathetic control suggesting well-defined differences already in the initial responses during orthostatic stress.
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47.
  • Skoog, Johan, et al. (author)
  • The Diagnostic Performance of an Extended Ultrasound Protocol in Patients With Clinically Suspected Giant Cell Arteritis
  • 2022
  • In: Frontiers in Medicine. - : Frontiers Media SA. - 2296-858X. ; 8
  • Journal article (peer-reviewed)abstract
    • ObjectiveTo evaluate the diagnostic performance of an extended ultrasound protocol in patients referred under the suspicion of giant cell arteritis (GCA). MethodsConsecutive patients with suspected GCA were examined with an extended color duplex ultrasound (CDU) protocol during a period of 2 years. The extended CDU protocol included temporal, axillary, subclavian, brachiocephalic, and carotid arteries. The reference was clinically diagnosed GCA, confirmed after >= 6-month follow-up. Hypo- or medium-echogenic, circumferential, homogenous wall thickening, and/or a positive compression sign in temporal arteries, were regarded as typical signs of arteritis. ResultsOf the eligible 201 patients, 83 (41%) received a clinical GCA diagnosis at follow-up >= 6 months post CDU examination. Among these cases, 48 (58%) demonstrated inflammation solely in temporal arteries, 8 (10%) showed abnormalities restricted to extra-cranial vessels, and 23 (28%) patients displayed inflammatory changes in both temporal and extra-cranial arteries. Color duplex ultrasound of temporal arteries yielded a diagnostic sensitivity and specificity [95% confidence intervals (CI)] of 86% (76-92%) and 99% (95-99%), respectively. By adding axillary artery examination, the sensitivity increased to 92% (83-97%) while the specificity remained unchanged. Further, inclusion of subclavian artery marginally increased the sensitivity by 1%. Finally, by also including brachiocephalic and common carotid arteries resulted in a sensitivity of 95% (88-99%) and a specificity of 98% (94-99%). ConclusionsColor duplex ultrasound examination demonstrated a high accuracy in diagnosing patients both with cranial and extra-cranial GCA. Further examination of brachiocephalic and common carotid arteries can increase the sensitivity without affecting the specificity when temporal and axillary findings are indecisive. Finally, the extended CDU protocol allows measurement of the general burden of inflammation, which could be relevant for future monitoring purposes.
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48.
  • Skoog, Johan, 1977-, et al. (author)
  • Venous Compliance in Great Saphenous Vein Incompetence : Pre- and Post-interventional Changes
  • 2020
  • In: EJVES Vascular Forum. - : Elsevier. - 2666-688X. ; 47, s. 78-82
  • Journal article (peer-reviewed)abstract
    • Objective: Venous insufficiency is associated with histological changes and structural remodelling of the venous wall. The effects of these changes on global venous function remain uncertain. The aim was to evaluate venous compliance in patients with great saphenous vein (GSV) insufficiency before and after treatment by radiofrequency ablation (RFA) and in controls.Methods: Eleven patients (14 limbs) underwent endovenous RFA treatment for GSV incompetence. Duplex ultrasound and strain gauge plethysmography (SGP) were performed before and after RFA. SGP time (seconds) to reach 50% of maximum venous volume (T50) with and without superficial occlusion was used to assess global venous reflux. Venous occlusion plethysmography was used to evaluate pre- and post-operative calf venous compliance. Venous compliance was also assessed in 12 age and sex matched controls.Results: Pre-operative calf venous compliance was lower in patients than in controls (p < .001). Post-operative calf venous compliance was reduced vs. pre-operative measurements (p < .002). The pre-operative reflux parameter T50 improved from 8.0 ± 2.0 seconds to 17.3 ± 1.9 seconds (p < .001) after RFA. The post-operative T50 without superficial occlusion was similar to pre-operative T50 with superficial occlusion (17.1 ± 2.5 vs. 17.3 ± 1.9 seconds, p = .84).Conclusions: Calf venous compliance is reduced in patients with GSV insufficiency. Venous reflux parameters markedly improved after RFA, whereas venous compliance displayed a further reduction vs. the pre-operative state, implicating generalised changes in the lower limb venous vessel wall.Previous article in issue
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49.
  • Svensson, Christina, et al. (author)
  • Affected Microcirculation and Vascular Hemodynamics in Takayasu Arteritis
  • 2022
  • In: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 13
  • Journal article (peer-reviewed)abstract
    • Introduction: Takayasu arteritis (TAK) is a rare inflammatory disease affecting aorta and its major branches. Ultrasound (US) can detect inflammatory features in the arterial wall, but less is known regarding skin microcirculation and vascular hemodynamics. The aim was to study if assessment of these variables could add valuable information regarding vascular affection in TAK.Methods: 17 patients diagnosed with TAK and 17 age- and sex-matched healthy controls were included. Microcirculatory peak oxygen saturation (OxyP) in the skin after induced ischemia was evaluated with laser Doppler flowmetry/diffuse reflectance spectroscopy. Cerebrovascular reserve capacity (CVR) in the brain was assessed with transcranial Doppler (TCD). Pulse waves were recorded in the radial artery by the aid of applanation tonometry, for calculation of central augmentation index (AIx75). Intima-media thickness (IMT) and stenosis/occlusions were evaluated using US in carotid and central arteries.Results: Reduced OxyP (79 +/- 8% vs. 87 +/- 4%, p < 0.001) was seen in patients with TAK regardless of significant arterial stenosis/occlusion or not. Increased AIx75 (22.3 +/- 13.6 vs. 9.2 +/- 16.3, p = 0.01) was seen in TAK patients without significant stenosis/occlusions. No differences were found in CVR, regardless of proximal stenosis. However, signs of a more high-resistance flow profile were seen in arteria cerebri media.Conclusion: Regardless of arterial stenosis or not, impaired microcirculation of the skin and preserved CVR in the brain were found in subjects with TAK. Signs of increased arterial stiffness in the brain and central arteries were observed. The value of these findings for prediction of future cardiovascular events needs to be clarified in further studies.
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50.
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