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  • 401.
    Anderberg, S. B.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Luther, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Frithiof, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Physiological aspects of Toll-like receptor 4 activation in sepsis-induced acute kidney injury2017In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 219, no 3, p. 575-590Article, review/survey (Refereed)
    Abstract [en]

    Sepsis-induced acute kidney injury (SI-AKI) is common and associated with high mortality. Survivors are at increased risk of chronic kidney disease. The precise mechanism underlying SI-AKI is unknown, and no curative treatment exists. Toll-like receptor 4 (TLR4) activates the innate immune system in response to exogenous microbial products. The result is an inflammatory reaction aimed at clearing a potential infection. However, the consequence may also be organ dysfunction as the immune response can cause collateral damage to host tissue. The purpose of this review is to describe the basis for how ligand binding to TLR4 has the potential to cause renal dysfunction and the mechanisms by which this may take place in gram-negative sepsis. In addition, we highlight areas for future research that can further our knowledge of the pathogenesis of SI-AKI in relation to TLR4 activation. TLR4 is expressed in the kidney. Activation of TLR4 causes cytokine and chemokine release as well as renal leucocyte infiltration. It also results in endothelial and tubular dysfunction in addition to altered renal metabolism and circulation. From a physiological standpoint, inhibiting TLR4 in large animal experimental SI-AKI significantly improves renal function. Thus, current evidence indicates that TLR4 has the ability to mediate SI-AKI by a number of mechanisms. The strong experimental evidence supporting a role of TLR4 in the pathogenesis of SI-AKI in combination with the availability of pharmacological tools to target TLR4 warrants future human studies.

  • 402.
    Anderberg, Ulla Maria
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Fibromyalgia syndrome in women - a stress disorder?: Neurobiological and hormonal aspects1999Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The FMS is almost exclusively a female disorder, as 90% of the patients struck by it are women. About 7% of all women in modern society have this disorder.

    The studies in this thesis demonstrated that variations in the female sex hormones over the menstrual cycle and in different hormonal states are important with respect to the severity of pain and other symptoms, global functioning and well being of FMS patients. The hormonal state is also of importance in the inter-connection with the monoaminergic systems, stress systems and pain processing systems. Besides the symptoms, this also appears as perturbed levels of neuropeptide Y (NPY), nociceptin and oxytocin in plasma.

    The importance of estrogen to pain processing peptides was shown in an animal study. In that study it was revealed that estrogen increase reduces pain sensitivity, and that estrogen is also able to change the levels of pain processing peptides such as substance P (SP) and met-enkephalin-Arg-Phe (MEAP) in certain brain areas, spinal cord and serum. It is suggested that stress may elicit pain through several neuroendocrinological mechanisms.

    All FMS patients scored higher than healthy women on mood and tension related symptoms, which is interpreted as an increased sensitivity and reaction to stress. FMS patients at the time of menstruation, and older, postmenopausal FMS patients were the most sensitive to these changes.

    The increased sensitivity to stress was also demonstrated in a personality study using the Temperament and Character Inventory (TCI), which showed that many female FMS patients are more anxious and worried and therefore also become easily fatigued.

    It is likely that development of the FMS is due to numerous biological events occurring in response to long-term stress. Women with stressful life experiences and anxious personality traits are probably more prone to develop this disorder, although various and sufficient stressful events of different origins can most likely lead to this disorder in any woman over the long run.

  • 403. Andersen, Christen Lykkegaard
    et al.
    Bjorn, Mads Emil
    McMullin, Mary Frances
    Harrison, Claire
    Samuelsson, Jan
    Ejerblad, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Zweegman, Sonja
    Fernandes, Savio
    Bareford, David
    Knapper, Steven
    Lofvenberg, Eva
    Linder, Olle
    Andreasson, Bjorn
    Ahlstrand, Erik
    Jensen, Morten Krogh
    Bjerrum, Ole Weis
    Vestergaard, Hanne
    Larsen, Herdis
    Klausen, Tobias Wirenfeldt
    Mourits-Andersen, Torben
    Skov, Vibe
    Thomassen, Mads
    Kruse, Torben
    Gronbaek, Kirsten
    Hasselbalch, Hans Carl
    Circulating YKL-40 in patients with essential thrombocythemia and polycythemia vera treated with the novel histone deacetylase inhibitor vorinostat2014In: Leukemia research: a Forum for Studies on Leukemia and Normal Hemopoiesis, ISSN 0145-2126, E-ISSN 1873-5835, Vol. 38, no 7, p. 816-821Article in journal (Refereed)
    Abstract [en]

    YKL-40 regulates vascular endothelial growth factors and induces tumor proliferation. We investigated YKL-40 before and after treatment with vorinostat in 31 polycythemia vera (PV) and 16 essential thrombocythemia (ET) patients. Baseline PV patient levels were 2 times higher than in healthy controls (P<0.0001) and 1.7 times higher than in ET (P = 0.02). A significant correlation between YKL-40 at baseline and neutrophils, CRP, LDH, JAK2V617F and platelets in PV patients was observed, as well as a significantly greater reduction of YKL-40 levels in PV patients responding to therapy. YKL-40 might be a novel marker of disease burden and progression in myeloproliferative neoplasms. (C) 2014 Elsevier Ltd. All rights reserved.

  • 404. Andersen, Janice
    et al.
    Nordin, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Lifestyle and rehabilitation in long term illness.
    Sandberg, Sverre
    Illness Perception and Psychological Distress in Persons with Porphyria Cutanea Tarda2016In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 96, no 5, p. 674-678Article in journal (Refereed)
    Abstract [en]

    Porphyria cutanea tarda (PCT) requires long-term treatment and follow-up, although many patients experience life-long remission. The aim of this cross-sectional postal survey was to describe and investigate the association between illness perception, health complaints, self-reported symptoms and distress in persons with PCT. The participants perceived PCT as a chronic condition with high levels of personal and treatment control. Persons who reported active symptoms scored higher on perceived illness threat, total health complaints and psychological distress compared with those in remission or latent phases. However, a higher perception of illness threat and the total burden of health complaints were more closely associated with psychological distress than were perceived PCT symptoms activity. This has implications for clinical consultation; dermatologists should be attentive to symptoms activity, but also recognize that patients in remission with a high perceived illness threat and multiple health complaints might be especially vulnerable to psychological distress with regards to PCT.

  • 405.
    Andersen, Kasper
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Physical Activity and Cardiovascular Disease2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aim was to investigate associations of fitness and types and levels of physical activity with subsequent risk of cardiovascular disease.

    Four large-scale longitudinal cohort studies were used. The exposures were different measures related to physical activity and the outcomes were obtained through linkage to the Swedish In-Patient Register. In a cohort of 466 elderly men without pre-existing cardiovascular disease, we found that skeletal muscle morphology was associated with risk of cardiovascular events. A high amount of type I (slow-twitch, oxidative) skeletal muscle fibres was associated with lower risk of cardiovascular events and high amount of type IIx was associated with higher risk of cardiovascular events. This association was only seen among physically active men. Among 39,805 participants in a fundraising event, higher levels of both total and leisure time physical activity were associated with lower risk of heart failure. The associations were strongest for leisure time physical activity. In a cohort of 53,755 participants in the 90 km skiing event Vasaloppet, a higher number of completed races was associated with higher risk of atrial fibrillation and a higher risk of bradyarrhythmias. Further, better relative performance was associated with a higher risk of bradyarrhythmias. Among 1,26 million Swedish 18-year-old men, exercise capacity and muscle strength were independently associated with lower risk of vascular disease. The associations were seen across a range of major vascular disease events (ischemic heart disease, heart failure, stroke and cardiovascular death). Further, high exercise capacity was associated with higher risk of atrial fibrillation and a U-shaped association with bradyarrhythmias was found. Higher muscle strength was associated with lower risk of bradyarrhythmias and lower risk of ventricular arrhythmias.

    These findings suggest a higher rate of atrial fibrillation with higher levels of physical activity. The higher risk of atrial fibrillation does not appear to lead to a higher risk of stroke. In contrast, we found a strong inverse association of higher exercise capacity and muscle strength with vascular disease. Further, high exercise capacity and muscle strength are related to lower risk of cardiovascular death, including arrhythmia deaths. From a population perspective, the total impact of physical activity on cardiovascular disease is positive.

    List of papers
    1. Skeletal muscle morphology and risk of cardiovascular disease in elderly men
    Open this publication in new window or tab >>Skeletal muscle morphology and risk of cardiovascular disease in elderly men
    Show others...
    2015 (English)In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 22, no 2, p. 231-239Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND:

    While it is well known that physical inactivity is a major risk factor for cardiovascular disease, there is still a search for the mechanisms by which exercise exerts its positive effect. Skeletal muscle fibre type can be affected to some extent by exercise, and different fibre types possess different anti-inflammatory and glucometabolic properties that may influence cardiovascular disease risk.

    DESIGN:

    Population-based cohort study.

    METHODS:

    We investigated relations of skeletal muscle morphology to risk of cardiovascular events in a sample of 466 71-year-old men without cardiovascular disease, of which 295 were physically active (strenuous physical activity at least 3 h/week).

    RESULTS:

    During a median of 13.1 years of follow up, 173 major cardiovascular events occurred. Among physically active men, 10% higher proportion of type-I (slow-twitch oxidative) fibres was associated with a hazard ratio (HR) of 0.84 (95% confidence interval 0.74-0.95) for cardiovascular events, and 10% higher proportion of type-IIx (fast-twitch glycolytic) fibres was associated with a HR of 1.24 (1.06-1.45), adjusting for age. Similar results were observed in several sets of multivariable-adjusted models. No association of muscle fibre type with risk of cardiovascular events was observed among physically inactive men.

    CONCLUSIONS:

    Higher skeletal muscle proportion of type-I fibres was associated with lower risk of cardiovascular events and a higher proportion of type-IIx fibres was associated with higher risk of cardiovascular events. These relations were only observed in physically active men. Skeletal muscle fibre composition may be a mediator of the protective effects of exercise against cardiovascular disease.

    National Category
    Cardiac and Cardiovascular Systems
    Identifiers
    urn:nbn:se:uu:diva-210441 (URN)10.1177/2047487313506828 (DOI)000348115400014 ()24092874 (PubMedID)
    Available from: 2013-11-08 Created: 2013-11-08 Last updated: 2018-08-24Bibliographically approved
    2. Dose–Response Relationship of Total and Leisure Time Physical Activity to Risk of Heart Failure: a prospective cohort study
    Open this publication in new window or tab >>Dose–Response Relationship of Total and Leisure Time Physical Activity to Risk of Heart Failure: a prospective cohort study
    Show others...
    2014 (English)In: Circulation Heart Failure, ISSN 1941-3289, E-ISSN 1941-3297, Vol. 7, no 5, p. 16p. 701-708Article in journal (Refereed) Published
    Abstract [en]

    Background—The nature of the association between levels of physical activity and risk of heart failure is little known. We investigated nonlinear associations of total and leisure time physical activity with risk of heart failure.

    Methods and Results—In 1997, 39 805 persons without heart failure completed a questionnaire of lifestyle factors and medical history. We used Cox regression models to investigate total (adjusting for education and previous myocardial infarction) and direct (multivariable-adjusted) effects of self-reported total and leisure time physical activity on risk of heart failure of any cause and heart failure of nonischemic origin. Heart failure diagnoses were obtained until December 31, 2010. Higher leisure time physical activity was associated with lower risk of heart failure of any cause; hazard ratio of the total effect of leisure time physical activity was for fifth versus first quintile 0.54; 95% confidence interval was 0.44 to 0.66. The direct effect was similar. High total daily physical activity level was associated with lower risk of heart failure, although the effect was less pronounced than for leisure time physical activity (total effect hazard ratio, 0.81; 95% confidence interval, 0.69–0.95; fifth versus first quintile). A similar direct effect observed.

    Conclusions—Leisure time physical activity was inversely related to risk of developing heart failure in a dose–response fashion. This was reflected in a similar but less pronounced association of total physical activity with risk of heart failure. Only part of the effects appeared to be mediated by traditional risk factors.

    Publisher
    p. 16
    Keywords
    heart failure, physical exercise, cohort study, primary prevention, epidemiology
    National Category
    Cardiac and Cardiovascular Systems
    Research subject
    Cardiology; Epidemiology
    Identifiers
    urn:nbn:se:uu:diva-216862 (URN)10.1161/CIRCHEARTFAILURE.113.001010 (DOI)000342490900003 ()25185250 (PubMedID)
    Available from: 2014-02-01 Created: 2014-01-27 Last updated: 2017-12-06Bibliographically approved
    3. Risk of arrhythmias in 52 755 long-distance cross-country skiers: a cohort study
    Open this publication in new window or tab >>Risk of arrhythmias in 52 755 long-distance cross-country skiers: a cohort study
    Show others...
    2013 (English)In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 34, no 47, p. 3624-3631Article in journal (Refereed) Published
    Abstract [en]

    AIMS:

    We aimed to investigate the association of number of completed races and finishing time with risk of arrhythmias among participants of Vasaloppet, a 90 km cross-country skiing event.

    METHODS AND RESULTS:

    All the participants without cardiovascular disease who completed Vasaloppet during 1989-98 were followed through national registries until December 2005. Primary outcome was hospitalization for any arrhythmia and secondary outcomes were atrial fibrillation/flutter (AF), bradyarrhythmias, other supraventricular tachycardias (SVT), and ventricular tachycardia/ventricular fibrillation/cardiac arrest (VT/VF/CA). Among 52 755 participants, 919 experienced arrhythmia during follow-up. Adjusting for age, education, and occupational status, those who completed the highest number of races during the period had higher risk of any arrhythmias [hazard ratio (HR)1.30; 95% CI 1.08-1.58; for ≥5 vs. 1 completed race], AF (HR 1.29; 95% CI 1.04-1.61), and bradyarrhythmias (HR 2.10; 95% CI 1.28-3.47). Those who had the fastest relative finishing time also had higher risk of any arrhythmias (HR 1.30; 95% CI 1.04-1.62; for 100-160% vs. >240% of winning time), AF (1.20; 95% CI 0.93-1.55), and bradyarrhythmias (HR 1.85; 95% CI 0.97-3.54). SVT or VT/VF/CA was not associated with finishing time or number of completed races.

    CONCLUSIONS:

    Among male participants of a 90 km cross-country skiing event, a faster finishing time and a high number of completed races were associated with higher risk of arrhythmias. This was mainly driven by a higher incidence of AF and bradyarrhythmias. No association with SVT or VT/VF/CA was found.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-205089 (URN)10.1093/eurheartj/eht188 (DOI)000329134300012 ()23756332 (PubMedID)
    Available from: 2013-08-13 Created: 2013-08-13 Last updated: 2017-12-06Bibliographically approved
    4. Exercise capacity and muscle strength and risk of vascular disease and arrhythmias: A cohort study of 1.26 million young men
    Open this publication in new window or tab >>Exercise capacity and muscle strength and risk of vascular disease and arrhythmias: A cohort study of 1.26 million young men
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background:

    While physical activity and exercise protects against cardiovascular disease, athletes have higher risk of atrial fibrillation and other arrhythmias. Graded independent and joint influences of exercise capacity and muscle strength on these diseases are unknown.

    Methods:

    All 1.26 million Swedish men who participated in mandatory military conscription between 1972 and 1995 (at a median age of 18.2 years) contributed. Multivariable-adjusted Cox proportional hazards models were used to evaluate the associations of maximal exercise capacity and muscle strength at conscription to subsequent risk of vascular disease and arrhythmias, as identified in national registries.

    Results:

    During a median follow-up of 26.3 years, about 26,000 hospitalizations for vascular disease events and 17,000 for arrhythmias occurred. Exercise capacity was inversely associated with risk of vascular disease (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.61-0.67]; for 5th vs. 1st quintile) and so was muscle strength (HR 0.79; 0.76-0.83; for 5th vs. 1st quintile ). Similar associations were seen across a range of major vascular disease events. Exercise capacity was associated with incidence of arrhythmias in a U-shaped fashion (HR 0.91; 0.86-0.96; for 3rd vs. 1st quintile, and 0.99; 0.94-1.04; for 5th vs. 1st quintile). Higher muscle strength was associated with lower risk of arrhythmias (HR 0.87; 0.83-0.91; for 5th vs. 1st quintile). 

    Conclusion:

    Exercise capacity and muscle strength in late adolescence are independently and jointly associated with long-term risk of vascular disease and arrhythmias. The lower risk of vascular events with higher exercise capacity was not outweighed by higher risk of arrhythmias.

    National Category
    Medical and Health Sciences Cardiac and Cardiovascular Systems
    Research subject
    Cardiology; Epidemiology
    Identifiers
    urn:nbn:se:uu:diva-217308 (URN)
    Available from: 2014-02-01 Created: 2014-02-01 Last updated: 2016-01-18Bibliographically approved
  • 406.
    Andersen, Kasper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Daniela, Mariosa
    Adami, Hans-Olov
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Lagerros, Ylva Trolle
    Nyren, Olof
    Ye, Weimin
    Bellocco, Rino
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Dose–Response Relationship of Total and Leisure Time Physical Activity to Risk of Heart Failure: a prospective cohort study2014In: Circulation Heart Failure, ISSN 1941-3289, E-ISSN 1941-3297, Vol. 7, no 5, p. 16p. 701-708Article in journal (Refereed)
    Abstract [en]

    Background—The nature of the association between levels of physical activity and risk of heart failure is little known. We investigated nonlinear associations of total and leisure time physical activity with risk of heart failure.

    Methods and Results—In 1997, 39 805 persons without heart failure completed a questionnaire of lifestyle factors and medical history. We used Cox regression models to investigate total (adjusting for education and previous myocardial infarction) and direct (multivariable-adjusted) effects of self-reported total and leisure time physical activity on risk of heart failure of any cause and heart failure of nonischemic origin. Heart failure diagnoses were obtained until December 31, 2010. Higher leisure time physical activity was associated with lower risk of heart failure of any cause; hazard ratio of the total effect of leisure time physical activity was for fifth versus first quintile 0.54; 95% confidence interval was 0.44 to 0.66. The direct effect was similar. High total daily physical activity level was associated with lower risk of heart failure, although the effect was less pronounced than for leisure time physical activity (total effect hazard ratio, 0.81; 95% confidence interval, 0.69–0.95; fifth versus first quintile). A similar direct effect observed.

    Conclusions—Leisure time physical activity was inversely related to risk of developing heart failure in a dose–response fashion. This was reflected in a similar but less pronounced association of total physical activity with risk of heart failure. Only part of the effects appeared to be mediated by traditional risk factors.

  • 407.
    Andersen, Kasper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Neovius, Martin
    Tynelius, Per
    Rasmussen, Finn
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Exercise capacity and muscle strength and risk of vascular disease and arrhythmias: A cohort study of 1.26 million young menManuscript (preprint) (Other academic)
    Abstract [en]

    Background:

    While physical activity and exercise protects against cardiovascular disease, athletes have higher risk of atrial fibrillation and other arrhythmias. Graded independent and joint influences of exercise capacity and muscle strength on these diseases are unknown.

    Methods:

    All 1.26 million Swedish men who participated in mandatory military conscription between 1972 and 1995 (at a median age of 18.2 years) contributed. Multivariable-adjusted Cox proportional hazards models were used to evaluate the associations of maximal exercise capacity and muscle strength at conscription to subsequent risk of vascular disease and arrhythmias, as identified in national registries.

    Results:

    During a median follow-up of 26.3 years, about 26,000 hospitalizations for vascular disease events and 17,000 for arrhythmias occurred. Exercise capacity was inversely associated with risk of vascular disease (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.61-0.67]; for 5th vs. 1st quintile) and so was muscle strength (HR 0.79; 0.76-0.83; for 5th vs. 1st quintile ). Similar associations were seen across a range of major vascular disease events. Exercise capacity was associated with incidence of arrhythmias in a U-shaped fashion (HR 0.91; 0.86-0.96; for 3rd vs. 1st quintile, and 0.99; 0.94-1.04; for 5th vs. 1st quintile). Higher muscle strength was associated with lower risk of arrhythmias (HR 0.87; 0.83-0.91; for 5th vs. 1st quintile). 

    Conclusion:

    Exercise capacity and muscle strength in late adolescence are independently and jointly associated with long-term risk of vascular disease and arrhythmias. The lower risk of vascular events with higher exercise capacity was not outweighed by higher risk of arrhythmias.

  • 408.
    Andersen, Kasper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Skeletal muscle morphology and risk of cardiovascular disease in elderly men2015In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 22, no 2, p. 231-239Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    While it is well known that physical inactivity is a major risk factor for cardiovascular disease, there is still a search for the mechanisms by which exercise exerts its positive effect. Skeletal muscle fibre type can be affected to some extent by exercise, and different fibre types possess different anti-inflammatory and glucometabolic properties that may influence cardiovascular disease risk.

    DESIGN:

    Population-based cohort study.

    METHODS:

    We investigated relations of skeletal muscle morphology to risk of cardiovascular events in a sample of 466 71-year-old men without cardiovascular disease, of which 295 were physically active (strenuous physical activity at least 3 h/week).

    RESULTS:

    During a median of 13.1 years of follow up, 173 major cardiovascular events occurred. Among physically active men, 10% higher proportion of type-I (slow-twitch oxidative) fibres was associated with a hazard ratio (HR) of 0.84 (95% confidence interval 0.74-0.95) for cardiovascular events, and 10% higher proportion of type-IIx (fast-twitch glycolytic) fibres was associated with a HR of 1.24 (1.06-1.45), adjusting for age. Similar results were observed in several sets of multivariable-adjusted models. No association of muscle fibre type with risk of cardiovascular events was observed among physically inactive men.

    CONCLUSIONS:

    Higher skeletal muscle proportion of type-I fibres was associated with lower risk of cardiovascular events and a higher proportion of type-IIx fibres was associated with higher risk of cardiovascular events. These relations were only observed in physically active men. Skeletal muscle fibre composition may be a mediator of the protective effects of exercise against cardiovascular disease.

  • 409.
    Andersen, Kasper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Rasmussen, F.
    Karolinska Inst, Dept Publ Hlth Sci, Stockholm, Sweden..
    Neovius, M.
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden..
    Tynelius, P.
    Karolinska Inst, Dept Publ Hlth Sci, Stockholm, Sweden..
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Anthropometric measures and risk of atrial fibrillation - a cohort study of 1.2 million young men2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, no Suppl. 1, p. 910-910Article in journal (Other academic)
  • 410.
    Andersen, Kasper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Rasmussen, F.
    Lund Univ, Dept Hlth Sci, Lund, Sweden.
    Neovius, M.
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden.
    Tynelius, P.
    Karolinska Inst, Dept Publ Hlth Sci, Stockholm, Sweden;Stockholm Cty Council, Ctr Epidemiol & Community Med, Stockholm, Sweden.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Body size and risk of atrial fibrillation: a cohort study of 1.1 million young men2018In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 283, no 4, p. 346-355Article in journal (Refereed)
    Abstract [en]

    Background: Whilst tall stature has been related to lower risk of vascular disease, it has been proposed as a risk factor for atrial fibrillation. Little is known about other anthropometric measures and their joint effects on risk of atrial fibrillation.

    Objectives: We aim to investigate associations and potential joint effects of height, weight, body surface area (BSA) and body mass index (BMI) with risk of atrial fibrillation.

    Methods: In a cohort covering 1 153 151 18-year-old men participating in the Swedish military conscription (1972-1995), Cox regression was used to investigate associations of height, weight, BSA and BMI with risk of atrial fibrillation.

    Results: During a median of 26.3 years of follow-up, higher height was associated with higher risk of atrial fibrillation (hazard ratio [HR] 2.80; 95% CI 2.63-2.98; for 5th vs. 1st quintile) and so was larger BSA (HR 3.05; 95% CI 2.82-3.28; for 5th vs. 1st quintile). Higher weight and BMI were to a lesser extent associated with risk of atrial fibrillation (BMI: 1.42; 95% CI 1.33-1.52, for 5th vs. 1st quintile). We found a multiplicative joint effect of height and weight. Adjusting for muscle strength, exercise capacity and diseases related to atrial fibrillation attenuated these measures.

    Conclusions: Higher height and weight are strongly associated with higher risk of atrial fibrillation. These associations are multiplicative and independent of each other and are summarized in a strong association of body surface area with risk of atrial fibrillation. The mechanisms remain unknown but may involve increased atrial volume load with larger body size.

  • 411.
    Andersen, Kasper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Rasmussen, Finn
    Karolinska Inst, Dept Publ Hlth Sci, Child & Adolescent Publ Hlth Epidemiol Unit, Stockholm, Sweden..
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Neovius, Martin
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden..
    Tynelius, Per
    Karolinska Inst, Dept Publ Hlth Sci, Child & Adolescent Publ Hlth Epidemiol Unit, Stockholm, Sweden..
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Exercise capacity and muscle strength and risk of vascular disease and arrhythmia in 1.1 million young Swedish men: cohort study2015In: BMJ-BRITISH MEDICAL JOURNAL, ISSN 1756-1833, Vol. 351, article id h4543Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE To investigate the associations of exercise capacity and muscle strength in late adolescence with risk of vascular disease and arrhythmia. DESIGN Cohort study. SETTING General population in Sweden. PARTICIPANTS 1.1 million men who participated in mandatory military conscription between 1 August 1972 and 31 December 1995, at a median age of 18.2 years. Participants were followed until 31 December 2010. MAIN OUTCOMES Associations between exercise capacity and muscle strength with risk of vascular disease and subgroups (ischaemic heart disease, heart failure, stroke, and cardiovascular death) and risk of arrhythmia and subgroups (atrial fibrillation or flutter, bradyarrhythmia, supraventricular tachycardia, and ventricular arrhythmia or sudden cardiac death). Maximum exercise capacity was estimated by the ergometer bicycle test, and muscle strength was measured as handgrip strength by a hand dynamometer. High exercise capacity or muscle strength was deemed as above the median level. RESULTS During a median follow-up of 26.3 years, 26 088 vascular disease events and 17 312 arrhythmia events were recorded. Exercise capacity was inversely associated with risk of vascular disease and its subgroups. Muscle strength was also inversely associated with vascular disease risk, driven by associations of higher muscle strength with lower risk of heart failure and cardiovascular death. Exercise capacity had a U shaped association with risk of arrhythmia, driven by a direct association with risk of atrial fibrillation and a U shaped association with bradyarrhythmia. Higher muscle strength was associated with lower risk of arrhythmia (specifically, lower risk of bradyarrhythmia and ventricular arrhythmia). The combination of high exercise capacity and high muscle strength was associated with a hazard ratio of 0.67 (95% confidence interval 0.65 to 0.70) for vascular events and 0.92 (0.88 to 0.97) for arrhythmia compared with the combination of low exercise capacity and low muscle strength. CONCLUSIONS Exercise capacity and muscle strength in late adolescence are independently and jointly associated with long term risk of vascular disease and arrhythmia. The health benefit of lower risk of vascular events with higher exercise capacity was not outweighed by higher risk of arrhythmia.

  • 412. Andersen, Lise Geisler
    et al.
    Ängquist, Lars
    Gamborg, Michael
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Bengtsson, Calle
    Canoy, Dexter
    Eriksson, Johan G.
    Eriksson, Marit
    Järvelin, Marjo-Riitta
    Lissner, Lauren
    Nilsen, Tom I.
    Osler, Merete
    Overvad, Kim
    Rasmussen, Finn
    Salonen, Minna K.
    Schack-Nielsen, Lene
    Tammelin, Tuija H.
    Tuomainen, Tomi-Pekka
    Sørensen, Thorkild I. A.
    Baker, Jennifer L.
    Birth weight in relation to leisure time physical activity in adolescence and adulthood: meta-analysis of results from 13 nordic cohorts2009In: PloS one, ISSN 1932-6203, Vol. 4, no 12, p. e8192-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Prenatal life exposures, potentially manifested as altered birth size, may influence the later risk of major chronic diseases through direct biologic effects on disease processes, but also by modifying adult behaviors such as physical activity that may influence later disease risk. METHODS/PRINCIPAL FINDINGS: We investigated the association between birth weight and leisure time physical activity (LTPA) in 43,482 adolescents and adults from 13 Nordic cohorts. Random effects meta-analyses were performed on categorical estimates from cohort-, age-, sex- and birth weight specific analyses. Birth weight showed a reverse U-shaped association with later LTPA; within the range of normal weight the association was negligible but weights below and above this range were associated with a lower probability of undertaking LTPA. Compared with the reference category (3.26-3.75 kg), the birth weight categories of 1.26-1.75, 1.76-2.25, 2.26-2.75, and 4.76-5.25 kg, had odds ratios of 0.67 (95% confidence interval: 0.47, 0.94), 0.72 (0.59, 0.88), 0.89 (0.79, 0.99), and 0.65 (0.50, 0.86), respectively. The shape and strength of the birth weight-LTPA association was virtually independent of sex, age, gestational age, educational level, concurrent body mass index, and smoking. CONCLUSIONS/SIGNIFICANCE: The association between birth weight and undertaking LTPA is very weak within the normal birth weight range, but both low and high birth weights are associated with a lower probability of undertaking LTPA, which hence may be a mediator between prenatal influences and later disease risk.

  • 413.
    Andersen, M.
    et al.
    Aalborg Univ, Hlth Sci & Technol, Aalborg, Denmark..
    Meyer, M. K.
    Aalborg Univ, Hlth Sci & Technol, Aalborg, Denmark..
    Nagaev, I.
    Nagaeva, O.
    Wikberg, Jarl E. S.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Mincheva-Nilsson, L.
    Andersen, G. N.
    Aalborg Univ, Clin Med, Aalborg, Denmark..
    Resistin Gene Transcription Is Regulated in Adaptive and Innate Immunity in Rheumatoid Arthritis2016In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 75, p. 904-904Article in journal (Other academic)
  • 414.
    Andersen, M.
    et al.
    Aalborg Univ, Hlth Sci & Technol, Aalborg, Denmark..
    Meyer, M. K.
    Aalborg Univ, Hlth Sci & Technol, Aalborg, Denmark..
    Nagaev, I.
    Nagaeva, O.
    Wikberg, Jarl E. S.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Mincheva-Nilsson, L.
    Andersen, G. N.
    Aalborg Univ, Clin Med, Aalborg, Denmark..
    The Melanocortin System Is Responsive in Disease Driving Immune Cells in Rheumatoid Arthritis and May Offer A Pathway To Curative Treatment2016In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 75, p. 903-904Article in journal (Other academic)
  • 415. Andersen, M.
    et al.
    Olesen, M. K.
    Nagaev, I.
    Nagaeva, O.
    Wikberg, Jarl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Mincheva-Nilsson, L.
    Andersen, G. N.
    Adalimumab (Humira (R)) normalizes melanocortin receptor subtype 2, 3, and 4 expression in CD8+, CD14+, and CD19+leucocyte subsets in rheumatoid arthritis2014In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 43, p. 25-26Article in journal (Other academic)
  • 416.
    Andersen, Maria Goul
    et al.
    Aarhus Univ Hosp, Dept Infect Dis, Aarhus, Denmark.
    Thorsted, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Storgaard, Merete
    Aarhus Univ Hosp, Dept Infect Dis, Aarhus, Denmark.
    Kristoffersson, Anders N.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Friberg, Lena E
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Öbrink-Hansen, Kristina
    Aarhus Univ Hosp, Dept Infect Dis, Aarhus, Denmark.
    Population Pharmacokinetics of Piperacillin in Sepsis Patients: Should Alternative Dosing Strategies Be Considered?2018In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 62, no 5, article id e02306Article in journal (Refereed)
    Abstract [en]

    Sufficient antibiotic dosing in septic patients is essential for reducing mortality. Piperacillin-tazobactam is often used for empirical treatment, but due to the pharmacokinetic (PK) variability seen in septic patients, optimal dosing may be a challenge. We determined the PK profile for piperacillin given at 4 g every 8 h in 22 septic patients admitted to a medical ward. Piperacillin concentrations were compared to the clinical breakpoint MIC for Pseudomonas aeruginosa (16 mg/liter), and the following PK/pharmacodynamic (PD) targets were evaluated: the percentage of the dosing interval that the free drug concentration is maintained above the MIC (fTMIC) of 50% and 100%. A two-compartment population PK model described the data well, with clearance being divided into renal and nonrenal components. The renal component was proportional to the estimated creatinine clearance (eCLCR) and constituted 74% of the total clearance in a typical individual (eCLCR, 83.9 ml/min). Patients with a high eCLCR (>130 ml/min) were at risk of subtherapeutic concentrations for the current regimen, with a 90% probability of target attainment being reached at MICs of 2.0 (50% fTMIC) and 0.125 mg/liter (100% fTMIC). Simulations of alternative dosing regimens and modes of administration showed that dose increment and prolonged infusion increased the chance of achieving predefined PK/PD targets. Alternative dosing strategies may therefore be needed to optimize piperacillin exposure in septic patients. (This study has been registered at ClinicalTrials.gov under identifier NCT02569086.)

  • 417. Andersen, Niels S.
    et al.
    Pedersen, Lone B.
    Laurell, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Elonen, Erkki
    Kolstad, Arne
    Boesen, Anne Marie
    Pedersen, Lars M.
    Lauritzsen, Grete F.
    Ekanger, Roald
    Nilsson-Ehle, Herman
    Nordstrom, Marie
    Freden, Susanne
    Jerkeman, Mats
    Eriksson, Mikael
    Vaart, Jaan
    Malmer, Beatrice
    Geisler, Christian H.
    Pre-Emptive Treatment With Rituximab of Molecular Relapse After Autologous Stem Cell Transplantation in Mantle Cell Lymphoma2009In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 27, no 26, p. 4365-4370Article in journal (Refereed)
    Abstract [en]

    Purpose Minimal residual disease (MRD) is predictive of clinical progression in mantle-cell lymphoma (MCL). According to the Nordic MCL-2 protocol we prospectively analyzed the efficacy of pre-emptive treatment using rituximab to MCL patients in molecular relapse after autologous stem cell transplantation (ASCT). Patients and Materials MCL patients enrolled onto the study, who had polymerase chain reaction (PCR) detectable molecular markers and underwent ASCT, were followed with serial PCR assessments of MRD in consecutive bone marrow and peripheral blood samples after ASCT. In case of molecular relapse with increasing MRD levels, patients were offered pre-emptive treatment with rituximab 375 mg/m(2) weekly for 4 weeks. Results Of 160 MCL patients enrolled, 145 underwent ASCT, of whom 78 had a molecular marker. Of these, 74 were in complete remission (CR) and four had progressive disease after ASCT. Of the CR patients, 36 underwent a molecular relapse up to 6 years (mean, 18.5 months) after ASCT. Ten patients did not receive pre-emptive treatment mainly due to a simultaneous molecular and clinical relapse, while 26 patients underwent pre-emptive treatment leading to reinduction of molecular remission in 92%. Median molecular and clinical relapse-free survival after pre-emptive treatment were 1.5 and 3.7 years, respectively. Of the 38 patients who remain in molecular remission for now for a median of 3.3 years (range, 0.4 to 6.6 years), 33 are still in clinical CR. Conclusion Molecular relapse may occur many years after ASCT in MCL, and PCR based pre-emptive treatment using rituximab is feasible, reinduce molecular remission, and may prevent clinical relapse.

  • 418.
    Andersen, Thomas
    et al.
    Stavanger Univ Hosp, Dept Anaesthesiol, Stavanger, Norway.
    Ueland, Thor
    Univ Oslo, Natl Hosp, Res Inst Internal Med, Oslo, Norway;Univ Oslo, KG Jebsen Inflammatory Res Ctr, Oslo, Norway;Univ Oslo, Fac Med, Oslo, Norway;Univ Tromso, Jebsen Thrombosis Res & Expertise Ctr TREC, Tromso, Norway.
    Ghukasyan Lakic, Tatevik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Åkerblom, Axel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Bertilsson, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Aukrust, Pal
    Univ Oslo, Natl Hosp, Res Inst Internal Med, Oslo, Norway;Univ Oslo, KG Jebsen Inflammatory Res Ctr, Oslo, Norway;Univ Oslo, Fac Med, Oslo, Norway;Univ Tromso, Jebsen Thrombosis Res & Expertise Ctr TREC, Tromso, Norway;Natl Hosp Norway, Oslo Univ Hosp, Sect Clin Immunol & Infect Dis, Oslo, Norway.
    Michelsen, Annika E.
    Univ Oslo, Natl Hosp, Res Inst Internal Med, Oslo, Norway;Univ Oslo, Fac Med, Oslo, Norway.
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Becker, Richard C.
    Univ Cincinnati, Coll Med, Heart Lung & Vasc Inst, Div Cardiovasc Hlth & Dis, Cincinnati, OH USA.
    Storey, Robert F.
    Univ Sheffield, Dept Infect Immun & Cardiovasc Dis, Sheffield, S Yorkshire, England.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Kontny, Frederic
    Stavanger Univ Hosp, Dept Cardiol, Stavanger, Norway;Drammen Heart Ctr, Drammen, Norway.
    C-X-C Ligand 16 Is an Independent Predictor of Cardiovascular Death and Morbidity in Acute Coronary Syndromes2019In: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 39, no 11, p. 2402-2410Article in journal (Refereed)
    Abstract [en]

    Objective:

    The chemokine CXCL16 (C-X-C motif ligand 16) is a scavenger receptor for OxLDL (oxidized low-density lipoproteins) and involved in inflammation at sites of atherosclerosis. This study aimed to investigate the association of CXCL16 with clinical outcome in patients with acute coronary syndrome.

    Approach and Results:

    Serial measurements of CXCL16 were performed in a subgroup of 5142 patients randomized in the PLATO trial (Platelet Inhibition and Patient Outcome). Associations between CXCL16 and a composite of cardiovascular death, spontaneous myocardial infarction or stroke, and the individual components were assessed by multivariable Cox regression analyses. The hazard ratio per 50% increase in admission levels of CXCL16 analyzed as continuous variable was 1.64 (95% CI, 1.44-1.88), P<0.0001. This association remained statistically significant after adjustment for randomized treatment, clinical variables, CRP (C-reactive protein), leukocytes, cystatin C, NT-proBNP (N-terminal pro-brain natriuretic peptide), troponin T, GDF-15 (growth differentiation factor 15), and other biomarkers; hazard ratio 1.23 (1.05-1.45), P=0.0126. The admission level of CXCL16 was independently associated with cardiovascular death (1.50 [1.17-1.92], P=0.0014) but not with ischemic events alone, in fully adjusted analyses. No statistically independent association was found between CXCL16 measured at 1 month, or change in CXCL16 from admission to 1 month, and clinical outcomes.

    Conclusions:

    In patients with acute coronary syndrome, admission level of CXCL16 is independently related to adverse clinical outcomes, mainly driven by an association to cardiovascular death. Thus, CXCL16 measurement may enhance risk stratification in patients with this condition.

  • 419.
    Andersson, Camilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Johansson, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala Univ, Oncol, Uppsala, Sweden..
    Patient experience of 18F-FDG-PET/CT in a mask fixation2016In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 43, p. S666-S666Article in journal (Refereed)
  • 420.
    Andersson, Camilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Johansson, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Wassberg, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Johansson, Silvia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wikehult, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Patient Experience of an 18F-FDG-PET/CT Examination:: Need for Improvements in Patient Care2015In: Journal of Radiology Nursing, ISSN 1546-0843, Vol. 34, no 2, p. 100-108Article in journal (Refereed)
    Abstract [en]

    The aims of this study were to investigate the patients' knowledge about and experience of an 18F-fluoro-deoxy-glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) examination and to investigate the self-reported feelings of stress, level of physical activity, and health-related quality of life (HRQoL) and to find out if this was related to how they experienced the examination. A cross-sectional survey was used to collect information on 198 patients with known or suspected malignancy. As many as 32% to 63% were satisfied with the nursing staff, the communication, and the professional skills. Most patients did not know beforehand what an FDG-PET/CT examination was. The HRQoL, level of perceived stress, and physical activity were relatively low. A better HRQoL, lower level of perceived stress, and a higher level of physical activity were correlated to a more positive experience and higher education to more knowledge about the examination (p < .01–.05). The information before the examination needs to be improved. The results may be used to improve patient care and optimize imaging procedures.

  • 421.
    Andersson, Camilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Johansson, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Wassberg, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Johansson, Silvia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ahlström, Häkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Assessment of Whether Patients' Knowledge, Satisfaction, and Experience Regarding Their 18F-Fluoride PET/CT Examination Affects Image Quality.2016In: Journal of Nuclear Medicine Technology, ISSN 0091-4916, E-ISSN 1535-5675, Vol. 44, no 1, p. 21-5Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to investigate patients’ previous knowledge, satisfaction and experience regarding a (18F)-fluoride positron emission tomography / computed tomography examination ((18F)-fluoride PET/CT) and to explore whether experienced discomfort during the examination or pain was associated with reduced image quality. A further aim was to explore whether patients’ health-related quality of life (HRQoL) was associated with their satisfaction and experiences of the examination. Methods: Fifty consecutive patients with a histopathological diagnosis of prostate cancer who were scheduled for (18F)-fluoride PET/CT were asked to participate in the study, which was performed between November 2011 and April 2013. A questionnaire was used to collect information regarding the patients’ previous knowledge and experience of the examination. Image quality assessment was performed according to an arbitrary scale. The EORTC-QLQ-C30 and QLQ-PR25 were used to assess HRQoL. Results: Forty-six patients (96%) completed the questionnaires. Twenty-six per cent of participants did not know at all what a (18F)-fluoride PET/CT examination was. The majority (52-70%) were to a very high degree satisfied with the care provided by the nursing staff but less satisfied with the information given prior to the examination. The image quality was similar in patients who were exhausted or claustrophobic during the examination and those who were not. No correlations between HRQoL and the participants’ experience of (18F)-fluoride PET/CT were found. Conclusion: The majority of participants were satisfied with the care provided by the nursing staff, but there is still room for improvement especially regarding the information prior to the examination. Long examination time may be strenuous, for the patient but there was no difference in image quality between patients who felt discomfort during the examination or pain and those who did not.

  • 422.
    Andersson, Camilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Trampal Pulido, Carlos
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Johansson, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Effects of web-based information on patient satisfaction and image quality in patients undergoing an 18F-FDG PET/CT examination: a randomized controlled trial2018In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 45, no Suppl 1, p. S783-S784Article in journal (Other academic)
  • 423.
    Andersson, Camilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Trampal Pulido, Carlos
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Johansson, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Randomized Controlled Trial Examining Effects of Web-Based Information on Patient Satisfaction and Image Quality in 18F-FDG PET/CT Examinations2019In: Journal of Nuclear Medicine Technology, ISSN 0091-4916, E-ISSN 1535-5675, no 1, p. 36-46Article in journal (Refereed)
    Abstract [en]

    Our aim was to compare the effect that having access, versus not having access, to web-based patient information on 18F-FDG PET/CT has on image quality and on patient satisfaction with their care during and knowledge about the examination, as well as to explore whether patients utilized and were satisfied with the web-based information.

    Methods: We recruited 148 patients between October 2015 and December 2016 and randomly assigned them to a standard-care group or an intervention group. Both groups received standard information about the 18F-FDG PET/CT examination, but the intervention group also received access to web-based information. A questionnaire was used to evaluate patient satisfaction with, knowledge about, and discomfort during the examination, and a masked assessment of image quality was conducted.

    Results: Overall satisfaction was high in both groups. The lowest satisfaction was with information about how the patients would receive the results of the examination. More patients in the intervention group than in the standard-care group knew how the 18F-FDG PET/CT examination would be conducted. Descriptive data suggest that image quality was slightly better in the intervention group than in the standard-care group, but none of the outcomes significantly differed between the groups. However, several obstacles were encountered during recruitment that led to insufficient power to detect differences. Also, only 54 of 75 patients (72%) in the intervention group utilized the web-based information. However, those who did utilize the information were satisfied with it and found it helpful.

    Conclusion: The effects of web-based information need to be investigated in a larger sample of patients. Having access to improved information before undergoing 18F-FDG PET/CT may help patients prepare for and undergo the examination. It may also improve image quality. However, this possibility needs to be investigated using image quality as the primary outcome. The results may be used to improve patient information and care and thereby optimize the 18F-FDG PET/CT procedure.

  • 424.
    Andersson, Dan
    Socialstyrelsens regionala tillsynsenhet i Örebro.
    Fick ingen akuttid - drabbades av diabeteskoma: Distriktsläkare gav 10-åring besökstid om två veckor [The patient didn't get an emergency appointment--suffered from diabetic coma. The family practitioner scheduled 10-year old for a visit in two weeks]2007In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 104, no 4, p. 240-241Article in journal (Other academic)
  • 425.
    Andersson, Dan
    Socialstyrelsens regionala tillsynsenhet i Örebro.
    Högst angeläget fokusera på tre områden: rådgivning, diagnostiska åtgärder och läkemedelsordination [Important to focus on three issues. Counseling, diagnostic measures and drug prescription]2007In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 104, no 4, p. 238-239Article in journal (Refereed)
  • 426.
    Andersson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    TaqMan® Sample-to-SNP Kit™: evaluation of kit for low-cost and fast preparing of DNA-samples before genotype analysis2009Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

     

    Genotyping can be used to link genetic variation among individuals to certain diseases or conditions. Some known disorders and states that are dependent on single nucleotide polymorphism (SNPs) are lactose intolerance, venous thrombosis, hereditary hemochromatosis and the difference in sensibility among people to metabolise drugs.

    In this project a new kit, TaqManÒ Sample-to-SNP KitÔ for extraction of DNA and preparation of the extract for genotyping with real-time PCR and allelic discrimination, was evaluated. QIAamp® DNA Blood Biorobot® MDx Kit was used as the reference method.

    The purpose of the comparison was to find a method that makes DNA extraction from blood samples cheaper and faster, but with the same reliability as the reference procedure.

    The results of the evaluation showed a complete agreement of the genotype results between the methods tested, which means that the new method was as reliable as the reference method. The costs of reagents and material would be reduced with 52% if the new method is adopted, that alone would result in a cost reduction of 144 000SEK a year with a sample volume of 650 samples/month. The time for DNA extraction would also be reduced with the new procedure.

     

  • 427.
    Andersson, Gerhard
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Clinical Aspects of Tinnitus- Course, Cognition, PET, and the Internet2000Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The purpose of this thesis was to develop novel ways to study tinnitus, to investigate the course of tinnitus, and to study the effects of cognitive-behaviour therapy on tinnitus related distress. Data from 377 tinnitus patients were collected.

    A group of 216 patients completed audiological measures and were assessed in a structured interview. The Klockhoff and Lindblom's grading system was used and its inter-rater reliability assessed in a subsample showing a high degree of correspondence. A discriminant analysis showed that a substantial proportion of patients could be correctly classified into grade II or III, by measures of pitch, minimal masking level of tinnitus, avoidance of situations because of tinnitus, and tolerance in relation to onset.

    Using tests developed in cognitive psychology, it was found that tinnitus patients had impaired performance. There was no evidence for an attentional bias towards tinnitus related words using a computerized emotional Stroop task, but masking sounds of an "on-and-off" character were more disruptive than constant masking when patients performed the digit-symbol test. It is suggested that tinnitus distress may be increased by the 'changing-state' character of the tinnitus signal, or alternatively by intermittent masking sounds.

    In a case-study a patient received an i.v. injection of lidocaine while Positron Emission Tomograpy was conducted. The brain activity associated with tinnitus included the left primary, secondary and integrative auditory brain areas, as well as right paralimbic areas related to negative feelings. The precuneus (Brodmann area 7) might be a brain area involved in the aversiveness associated with tinnitus.

    Using a tinnitus questionnaire as the dependent measure it was found that tinnitus maskability at admission predicted distress at follow-up for an average of five years following admission. Some improvement in tinnitus occurred over time, but this was more evident in patients who had received a cognitive-behavioural treatment program.

    The effect of an Internet based cognitive-behavioural self-help treatment program for tinnitus was investigated showing a high dropout rate, but with positive results in that the treated patients improved.

  • 428. Andersson, Gustav
    et al.
    Wennersten, Christoffer
    Gaber, Alexander
    Boman, Karolina
    Nodin, Bjorn
    Uhlen, Mathias
    Segersten, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Malmström, Per-Uno
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Jirstrom, Karin
    Reduced expression of ezrin in urothelial bladder cancer signifies more advanced tumours and an impaired survival: validatory study of two independent patient cohorts2014In: BMC Urology, ISSN 1471-2490, E-ISSN 1471-2490, Vol. 14, p. 36-Article in journal (Refereed)
    Abstract [en]

    Background: Reduced membranous expression of the cytoskeleton-associated protein ezrin has previously been demonstrated to correlate with tumour progression and poor prognosis in patients with T1G3 urothelial cell carcinoma of the bladder treated with non-maintenance Bacillus Calmette-Guerin (n = 92), and the associations with adverse clinicopathological factors have been validated in another, unselected, cohort (n = 104). In the present study, we examined the prognostic significance of ezrin expression in urothelial bladder cancer in a total number of 442 tumours from two independent patient cohorts. Methods: Immunohistochemical expression of ezrin was evaluated in tissue microarrays with tumours from one retrospective cohort of bladder cancer (n = 110; cohort I) and one population-based cohort (n = 342; cohort II). Classification regression tree analysis was applied for selection of prognostic cutoff. Kaplan-Meier analysis, log rank test and Cox regression proportional hazards' modeling were used to evaluate the impact of ezrin on 5-year overall survival (OS), disease-specific survival (DSS) and progression-free survival (PFS). Results: Ezrin expression could be evaluated in tumours from 100 and 342 cases, respectively. In both cohorts, reduced membranous ezrin expression was significantly associated with more advanced T-stage (p < 0.001), high grade tumours (p < 0.001), female sex (p = 0.040 and p = 0.013), and membranous expression of podocalyxin-like protein (p < 0.001 and p = 0.009). Moreover, reduced ezrin expression was associated with a significantly reduced 5-year OS in both cohorts (HR = 3.09 95% CI 1.71-5.58 and HR = 2.15(1.51-3.06), and with DSS in cohort II (HR = 2.77, 95% CI 1.78-4.31). This association also remained significant in adjusted analysis in Cohort I (HR1.99, 95% CI 1.05-3.77) but not in Cohort II. In pTa and pT1 tumours in cohort II, there was no significant association between ezrin expression and time to progression. Conclusions: The results from this study validate previous findings of reduced membranous ezrin expression in urothelial bladder cancer being associated with unfavourable clinicopathological characteristics and an impaired survival. The utility of ezrin as a prognostic biomarker in transurethral resection specimens merits further investigation.

  • 429.
    Andersson, Hanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Reduced Preoperative Fasting in Children2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Preoperative fasting is recommended in order to reduce the risk of perioperative pulmonary aspiration. However, preoperative fasting may have negative effects on patient wellbeing and homeostasis. In this thesis, more lenient regimens for preoperative fasting in elective paediatric patients were assessed, with the aim to further improve preoperative fasting regimens.

    Paper I investigated if paediatric patients allowed to drink clear fluids until called to surgery, had an increased risk of pulmonary aspiration. The incidence of perioperative pulmonary aspiration in children allowed free clear fluids until called to surgery was 3 in 10 000, as compared to 1-10 in 10 000 in previous studies where longer fasting intervals were studied. Hence, no increase of incidence for pulmonary aspiration was found.

    Paper II investigated actual fasting times for clear fluids when applying two-hour fasting for clear fluids, and zero-hour fasting for clear fluids. When applying two-hour fasting, children were fasted median four hours for clear fluids. After transitioning to zero-hour fasting, median fasting time decreased to one hour, and the incidence of children fasting for more than six hours decreased from 35 % to 6 %. Abandoning the time limit for clear fluids significantly reduced the proportion of patients fasting for extended periods.

    Paper III assessed gastric content volume after a light breakfast in children scheduled for elective general anaesthesia. Patients were examined with gastric ultrasound four hours after a light breakfast. Of the 20 patients included in the study, 15 had an empty stomach, 4 had clear fluids < 0.5 ml kg-1 and one had solid content in the stomach. A light breakfast preoperatively might be safe, but amount and caloric restriction is needed to avoid the risk of perioperative pulmonary aspiration.

    Paper IV investigated preoperative weight loss, glucose level and ketone bodies in paediatric patients presenting for elective surgery. The outcomes were tested for correlation to preoperative fasting times. Of the 43 children enrolled in the study, three had weight loss of more than 5 %, five children presented with blood glucose level < 3.3 mmol l-1, and 11 children presented with ketone bodies > 0.6 mmol l-1. There was no correlation between fasting time, and the respective outcomes. Even with a lenient fasting regimen, there is risk of mild preoperative dehydration, hypoglycaemia and ketogenesis.

    In conclusion, the results obtained in the present thesis supports the shift to more lenient preoperative fasting regimens for clear fluids in elective paediatric patients.

    List of papers
    1. Low incidence of pulmonary aspiration in children allowed intake of clear fluids until called to the operating suite
    Open this publication in new window or tab >>Low incidence of pulmonary aspiration in children allowed intake of clear fluids until called to the operating suite
    2015 (English)In: Pediatric Anaesthesia, ISSN 1155-5645, E-ISSN 1460-9592, Vol. 25, no 8, p. 770-777Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: International guidelines recommend 2 h of clear fluid fasting prior to general anesthesia. The pediatric anesthesia unit of Uppsala University Hospital has been implementing a more liberal fasting regime for more than a decade; thus, children scheduled for elective procedures are allowed to drink clear fluids until called to the operating suite.

    AIM: To determine the incidence of perioperative pulmonary aspiration in pediatric patients allowed unlimited intake of clear fluids prior to general anesthesia.

    METHOD: Elective pediatric procedures between January 2008 and December 2013 were examined retrospectively by reviewing anesthesia charts and discharge notes in the electronic medical record system. All notes from the care event and available chest x-rays were examined for cases showing vomiting, regurgitation, and/or aspiration. Pulmonary aspiration was defined as radiological findings consistent with aspiration and/or postoperative symptoms of respiratory distress after vomiting during anesthesia.

    RESULTS: Of the 10 015 pediatric anesthetics included, aspiration occurred in three (0.03% or 3 in 10 000) cases. No case required cancellation of the surgical procedure, intensive care or ventilation support, and no deaths attributable to aspiration were found. Pulmonary aspiration was suspected, but not confirmed by radiology or continuing symptoms, in an additional 14 cases.

    CONCLUSION: Shortened fasting times may improve the perioperative experience for parents and children with a low risk of aspiration.

    National Category
    Pediatrics Anesthesiology and Intensive Care
    Identifiers
    urn:nbn:se:uu:diva-256491 (URN)10.1111/pan.12667 (DOI)000357730600003 ()25940831 (PubMedID)
    Available from: 2015-06-24 Created: 2015-06-24 Last updated: 2019-10-06Bibliographically approved
    2. Introducing the 6-4-0 fasting regimen and the incidence of prolonged preoperative fasting in children
    Open this publication in new window or tab >>Introducing the 6-4-0 fasting regimen and the incidence of prolonged preoperative fasting in children
    2018 (English)In: Pediatric Anaesthesia, ISSN 1155-5645, E-ISSN 1460-9592, Vol. 28, no 1, p. 46-52Article in journal (Refereed) Published
    Abstract [en]

    Background

    Children often starve for longer than recommended by current preoperative fasting guidelines.

    Aims

    We studied the effects of implementing a more lenient fasting regimen on the duration of clear fluid fasting, as well as the incidence of extended fasting in children.

    Methods

    Preoperative duration of clear fluid fasting was recorded for patients scheduled for procedures in a unit applying the standard 6-4-2 fasting regimen. This group was compared with a cohort in the same unit 1year after transitioning to a 6-4-0 fasting regimen. The latter includes no limitations on clear fluid intake until the child is called to theater. A third cohort from a unit in which the 6-4-0 fasting regimen has been implemented for over a decade was also studied for comparison.

    Results

    Patients fasting according to the 6-4-2 fasting regimen (n=66) had a median fasting time for clear fluids of 4.0h and a 33.3% incidence of fasting more than 6h. After transitioning to the 6-4-0 fasting regimen (n=64), median duration of fasting for clear fluids decreased to 1.0h, and the incidence of fasting more than 6h decreased to 6.3%. In the second unit (n=73), median fasting time was 2.2h and the proportion of patients fasting more than 6h was 21.9%.

    Conclusion

    The introduction and implementation of the 6-4-0 fasting regimen reduces median fluid fasting duration and the number of children subjected to extended fasting.

    Keywords
    anesthesia, children, fasting, fluids, preoperative
    National Category
    Anesthesiology and Intensive Care Pediatrics
    Identifiers
    urn:nbn:se:uu:diva-343890 (URN)10.1111/pan.13282 (DOI)000417604600008 ()29168341 (PubMedID)
    Available from: 2018-03-05 Created: 2018-03-05 Last updated: 2019-10-06Bibliographically approved
    3. Gastric content assessed with gastric ultrasound in paediatric patients prescribed a light breakfast prior to general anaesthesia. A prospective observational study.
    Open this publication in new window or tab >>Gastric content assessed with gastric ultrasound in paediatric patients prescribed a light breakfast prior to general anaesthesia. A prospective observational study.
    (English)In: Article in journal (Other academic) Accepted
    Abstract [en]

    Background:

    A light breakfast has been found to empty from the stomach within four hours in healthy volunteers.

    Aim

    The aim of this study was to investigate if a light breakfast of yoghurt or gruel empties from the stomach within four hours, in children scheduled for general anaesthesia.

    Method:

    In this observational cohort study, children aged 1-6 years, scheduled for elective general anaesthesia were prescribed free intake of yoghurt or gruel four hours prior to induction. They were subsequently examined with gastric ultrasound within four hours of ingestion. In case of gastric contents, the gastric antral area was measured, and gastric content volume was calculated.

    Results:

    Twenty children were included in the study and the ingested amount of gruel or yoghurt ranged 2.5-25 ml kg-1. In 15 cases, the stomach was empty with juxtaposed walls and no further measurements were made. In four cases, there was fluid present in the stomach, but the calculated gastric contents were < 0.5 ml kg-1. One patient had solids in the stomach and gastric content volume in this patient was calculated to 2.1 ml kg-1. The patient with solids present had ingested 25 ml kg-1 of gruel four hours prior to assessment. The planned procedure was therefore delayed one hour. There were no cases of pulmonary aspiration or vomiting.

    Conclusion:

    A light breakfast four hours prior to induction may be considered, but there is need for further studies on safe limits for the volume ingested.

    Keywords
    Ultrasound, General anesthesia, child < Age
    National Category
    Anesthesiology and Intensive Care
    Research subject
    Anaesthesiology and Intensive Care
    Identifiers
    urn:nbn:se:uu:diva-394230 (URN)
    Available from: 2019-10-05 Created: 2019-10-05 Last updated: 2019-10-10
    4. Preoperative weight loss, hypoglycaemia and ketosis in elective paediatric patients, preliminary results from a prospective observational study
    Open this publication in new window or tab >>Preoperative weight loss, hypoglycaemia and ketosis in elective paediatric patients, preliminary results from a prospective observational study
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background

    New paediatric fasting guidelines allow free clear fluids up until one hour prior to surgery. At the paediatric anaesthesia department of Uppsala University Hospital, children are fasted six hours for solids, four hours for breast milk and are allowed free clear fluids up until called to theatre. Preoperative fasting is necessary to avoid perioperative pulmonary aspiration. However, extended fasting times have detrimental effects for fluid homeostasis and may cause hypoglycaemia and ketone bodies.

    Aim

    The aim of the current study was to investigate if preoperative weight loss, glucose level and ketone bodies were related to preoperative fasting times.

    Methods

    Paediatric patients aged 0-72 months were included in this prospective, observational study. All children included were instructed to fast from midnight for solids, four hours for breast milk or semi-solids and from when they are called to theatre for clear fluids. Fasting times were registered, and patient weight was measured in the evening prior to surgery, and before induction. Blood glucose and ketone body levels were measured before induction. Multiple regression was used to determine how fasting time affected the outcomes weight change, blood glucose level and ketone bodies, respectively.

    Results

    43 patients were enrolled. Three children had a weight loss of more than 5 %, five children presented with blood glucose level < 3.3 mmol l-1, and 11 children presented with ketone bodies > 0.6 mmol l-1. There was no correlation between fasting time and the respective outcomes.

    Conclusion

    Even with a lenient preoperative fasting regimen, mild dehydration or hypoglycaemia may occur. This methodology may be used in further studies of the effects of preoperative fasting in settings where dehydration may be more significant.

    Keywords
    General Anesthesia, child < Age, Dehydration, Fasting, Hypoglycaemia, Ketosis
    National Category
    Anesthesiology and Intensive Care
    Research subject
    Anaesthesiology and Intensive Care; Anaesthesiology and Intensive Care
    Identifiers
    urn:nbn:se:uu:diva-394231 (URN)
    Available from: 2019-10-05 Created: 2019-10-05 Last updated: 2019-10-06
  • 430.
    Andersson, Hanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Elias, Eerola
    Frykholm, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Preoperative weight loss, hypoglycaemia and ketosis in elective paediatric patients, preliminary results from a prospective observational studyManuscript (preprint) (Other academic)
    Abstract [en]

    Background

    New paediatric fasting guidelines allow free clear fluids up until one hour prior to surgery. At the paediatric anaesthesia department of Uppsala University Hospital, children are fasted six hours for solids, four hours for breast milk and are allowed free clear fluids up until called to theatre. Preoperative fasting is necessary to avoid perioperative pulmonary aspiration. However, extended fasting times have detrimental effects for fluid homeostasis and may cause hypoglycaemia and ketone bodies.

    Aim

    The aim of the current study was to investigate if preoperative weight loss, glucose level and ketone bodies were related to preoperative fasting times.

    Methods

    Paediatric patients aged 0-72 months were included in this prospective, observational study. All children included were instructed to fast from midnight for solids, four hours for breast milk or semi-solids and from when they are called to theatre for clear fluids. Fasting times were registered, and patient weight was measured in the evening prior to surgery, and before induction. Blood glucose and ketone body levels were measured before induction. Multiple regression was used to determine how fasting time affected the outcomes weight change, blood glucose level and ketone bodies, respectively.

    Results

    43 patients were enrolled. Three children had a weight loss of more than 5 %, five children presented with blood glucose level < 3.3 mmol l-1, and 11 children presented with ketone bodies > 0.6 mmol l-1. There was no correlation between fasting time and the respective outcomes.

    Conclusion

    Even with a lenient preoperative fasting regimen, mild dehydration or hypoglycaemia may occur. This methodology may be used in further studies of the effects of preoperative fasting in settings where dehydration may be more significant.

  • 431.
    Andersson, Hanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Frykholm, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Gastric content assessed with gastric ultrasound in paediatric patients prescribed a light breakfast prior to general anaesthesia. A prospective observational study.In: Article in journal (Other academic)
    Abstract [en]

    Background:

    A light breakfast has been found to empty from the stomach within four hours in healthy volunteers.

    Aim

    The aim of this study was to investigate if a light breakfast of yoghurt or gruel empties from the stomach within four hours, in children scheduled for general anaesthesia.

    Method:

    In this observational cohort study, children aged 1-6 years, scheduled for elective general anaesthesia were prescribed free intake of yoghurt or gruel four hours prior to induction. They were subsequently examined with gastric ultrasound within four hours of ingestion. In case of gastric contents, the gastric antral area was measured, and gastric content volume was calculated.

    Results:

    Twenty children were included in the study and the ingested amount of gruel or yoghurt ranged 2.5-25 ml kg-1. In 15 cases, the stomach was empty with juxtaposed walls and no further measurements were made. In four cases, there was fluid present in the stomach, but the calculated gastric contents were < 0.5 ml kg-1. One patient had solids in the stomach and gastric content volume in this patient was calculated to 2.1 ml kg-1. The patient with solids present had ingested 25 ml kg-1 of gruel four hours prior to assessment. The planned procedure was therefore delayed one hour. There were no cases of pulmonary aspiration or vomiting.

    Conclusion:

    A light breakfast four hours prior to induction may be considered, but there is need for further studies on safe limits for the volume ingested.

  • 432.
    Andersson, Hanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Hellström, Per M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Frykholm, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Introducing the 6-4-0 fasting regimen and the incidence of prolonged preoperative fasting in children2018In: Pediatric Anaesthesia, ISSN 1155-5645, E-ISSN 1460-9592, Vol. 28, no 1, p. 46-52Article in journal (Refereed)
    Abstract [en]

    Background

    Children often starve for longer than recommended by current preoperative fasting guidelines.

    Aims

    We studied the effects of implementing a more lenient fasting regimen on the duration of clear fluid fasting, as well as the incidence of extended fasting in children.

    Methods

    Preoperative duration of clear fluid fasting was recorded for patients scheduled for procedures in a unit applying the standard 6-4-2 fasting regimen. This group was compared with a cohort in the same unit 1year after transitioning to a 6-4-0 fasting regimen. The latter includes no limitations on clear fluid intake until the child is called to theater. A third cohort from a unit in which the 6-4-0 fasting regimen has been implemented for over a decade was also studied for comparison.

    Results

    Patients fasting according to the 6-4-2 fasting regimen (n=66) had a median fasting time for clear fluids of 4.0h and a 33.3% incidence of fasting more than 6h. After transitioning to the 6-4-0 fasting regimen (n=64), median duration of fasting for clear fluids decreased to 1.0h, and the incidence of fasting more than 6h decreased to 6.3%. In the second unit (n=73), median fasting time was 2.2h and the proportion of patients fasting more than 6h was 21.9%.

    Conclusion

    The introduction and implementation of the 6-4-0 fasting regimen reduces median fluid fasting duration and the number of children subjected to extended fasting.

  • 433.
    Andersson, Hanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Schmitz, Achim
    Univ Childrens Hosp Zürich, Dept Anesthesiol, Zürich, Switzerland.
    Frykholm, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Preoperative fasting guidelines in pediatric anesthesia: are we ready for a change?2018In: Current Opinion in Anaesthesiology, ISSN 0952-7907, E-ISSN 1473-6500, Vol. 31, no 3, p. 342-348Article, review/survey (Refereed)
    Abstract [en]

    Purpose of review: Study after study shows that prolonged fasting before anesthesia is common in children. Pediatric anesthesiologists around the world are concerned that the current guidelines may be part of the problem. This review focuses on what can be done about it.

    Recent findings: We discuss new insights into the physiology of gastric emptying of different categories of food and drink. The evidence for negative effects of prolonged fasting occurring in spite of implementation of the current guidelines is examined. We also critically appraise the concept of a strict association between fasting time and the risk of aspiration and discuss recent studies in which children have been allowed clear fluids less than 2 h before anesthesia induction.

    Summary: Accumulating evidence indicates that changes of the current guidelines for preoperative fasting should be considered for children undergoing elective procedures.

    Video abstract: http://links.lww.com/COAN/A50

  • 434.
    Andersson, Hanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Zarén, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Frykholm, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Low incidence of pulmonary aspiration in children allowed intake of clear fluids until called to the operating suite2015In: Pediatric Anaesthesia, ISSN 1155-5645, E-ISSN 1460-9592, Vol. 25, no 8, p. 770-777Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: International guidelines recommend 2 h of clear fluid fasting prior to general anesthesia. The pediatric anesthesia unit of Uppsala University Hospital has been implementing a more liberal fasting regime for more than a decade; thus, children scheduled for elective procedures are allowed to drink clear fluids until called to the operating suite.

    AIM: To determine the incidence of perioperative pulmonary aspiration in pediatric patients allowed unlimited intake of clear fluids prior to general anesthesia.

    METHOD: Elective pediatric procedures between January 2008 and December 2013 were examined retrospectively by reviewing anesthesia charts and discharge notes in the electronic medical record system. All notes from the care event and available chest x-rays were examined for cases showing vomiting, regurgitation, and/or aspiration. Pulmonary aspiration was defined as radiological findings consistent with aspiration and/or postoperative symptoms of respiratory distress after vomiting during anesthesia.

    RESULTS: Of the 10 015 pediatric anesthetics included, aspiration occurred in three (0.03% or 3 in 10 000) cases. No case required cancellation of the surgical procedure, intensive care or ventilation support, and no deaths attributable to aspiration were found. Pulmonary aspiration was suspected, but not confirmed by radiology or continuing symptoms, in an additional 14 cases.

    CONCLUSION: Shortened fasting times may improve the perioperative experience for parents and children with a low risk of aspiration.

  • 435.
    Andersson, Jacob
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Forensic Medicine.
    Thiblin, Ingemar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Forensic Medicine.
    It is important not to assume an aetiology for the triad before the outcomes of diagnostic investigations2018In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 107, no 8, p. 1308-1309Article in journal (Other academic)
  • 436.
    Andersson, Jennie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Rosestedt, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Asplund, Veronika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Yavari, Nazila
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Orlova, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    In Vitro Therapy Modeling of HER2 Targeting Therapy in Disseminated Prostate Cancer2014In: International Journal of Oncology, ISSN 1019-6439, Vol. 45, no 5, p. 2153-2158Article in journal (Refereed)
    Abstract [en]

    Prostate cancer (PCa) is the most common cancer type among men. Treatments against advanced PCa are limited and in many cases only palliative. In a later, androgent independent, stage of PCa androgen receptors can be activated without interaction with ligand, i.e., by receptors of tyrosine kinase (RTK) family in the outlaw pathway. Human epidermal growth factor receptors HER2 and EGFR belong to RTK-family. HER2 is one of the main actors in the outlaw pathway with EGFR as the preferable heterodimerizing partner. We hypothesized that information on HER2 expression in advanced PCa could be useful for selection of patients for anti-RTK therapy and monitoring of therapy response. A panel of PCa cell lines (LNCap, PC3, DU-145) was subjected to a 8-week treatment using drugs influencing the RTK: trastuzumab (anti‑HER2), 17-DMAG (Hsp90 inhibitor), alone or in combination, and their HER2 and EGFR expressions were compared with non-treated cells. Treatment with trastuzumab decreased proliferation of LNCap and DU-145 cell lines, while 17-DMAG and trastuzumab/17‑DMAG combination affected all three cell lines. HER2 expression was significantly increased in PC3 cells, the most resistant cell line. On the contrary, in responding cells (LNCap and DU-145) HER2 expression decreased, accompanied by increased EGFR expression. However, additional treatment of cells with cetuximab (anti‑EGFR) did not give any additive effect to trastuzumab. In this study the response to anti-RTK therapy proved to vary between different PCa cell lines. We have demonstrated that RTK targeting treatments may affect the phenotypic profile of PCa tumor cells that correlates with therapy outcome. Observation of such changes during treatment could be used for monitoring and an improved therapy outcome.

  • 437.
    Andersson, Jennie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Rosestedt, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Orlova, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Imaging of HER2 may improve the outcome of external irradiation therapy for prostate cancer patients2015In: Oncology Letters, ISSN 1792-1074, E-ISSN 1792-1082, Vol. 9, no 2, p. 950-954Article in journal (Refereed)
    Abstract [en]

    Prostate cancer (PCa) is the most common type of cancer among males. Human epidermal growth factor receptor type 2 (HER2) expression in PCa has been reported by several studies and its involvement in the progression towards androgen-independent PCa has been discussed. External irradiation is one of the existing therapies, which has been demonstrated to be efficient in combination with androgen deprivation therapy for the treatment of advanced PCa. However, 20-40% of patients develop recurrent and more aggressive PCa within 10 years. The current study investigates the involvement of HER2 in survival and radioresistance in PCa cells and we hypothesized that, by monitoring HER2 expression, treatment may be personalized. The PCa cell lines, LNCap, PC3 and DU-145, received a 6 Gy single dose of external irradiation. The number of PC3 cells was not affected by a single dose of radiation, whereas a 5-fold decrease in cell number was detected in LNCap (P<0.00001) and DU-145 (P<0.0001) cells. The HER2 expression in PC3 exhibited a significant increase post irradiation, however, the expression was stable in the remaining cell lines. The administration of trastuzumab post-irradiation resulted in a 2-fold decrease in the PC3 cell number, while the drug did not demonstrate additional effects in LNCap and DU-145 cells, when compared with that of irradiation treatment alone. The results of the present study demonstrated that an increase in membranous HER2 expression in response to external irradiation may indicate cell radioresistance. Furthermore, imaging of HER2 expression prior to and following external irradiation may present a step towards personalized therapy in PCa.

  • 438. Andersson, Jesper L
    et al.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Valind, Sven
    A method for coregistration of PET and MR brain images1995In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 36, no 7, p. 1307-1315Article in journal (Refereed)
    Abstract [en]

    Combining MRI morphological data with functional PET data offers significant advantages in research as well as in many clinical situations. Automatic methods are needed, however, to coregister the data from the two modalities.

    METHODS:

    Simulated PET images were created by simple and automatic segmentation of MR images followed by the assignment of different uptake values to various tissue types. The simulated PET images were registered to actual PET images using a pixel-by-pixel, PET-PET registration method. The transformation matrix was then applied to the MR images. The method was used to register MRI data to PET transmission scans and emission scans obtained with FDG, nomifensine and raclopride. Validation was performed by comparing the results to those obtained by matching internal points manually defined in both volumes.

    RESULTS:

    Emission and transmission PET images were successfully registered to MR data. Comparison to the manual method indicated a registration accuracy on the order of 1-2 mm in each direction. No difference in accuracy between the different tracers was found. The error sensitivity for the method's assumptions seemed to be sufficiently low to allow complete automation of the method.

    CONCLUSION:

    We present a rapid, robust and fully automated method to register PET and MR brain images with sufficient accuracy for most clinical applications.

  • 439.
    Andersson, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Water–fat separation in magnetic resonance imaging and its application in studies of brown adipose tissue2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Virtually all the magnetic resonance imaging (MRI) signal of a human originates from water and fat molecules. By utilizing the property chemical shift the signal can be separated, creating water- and fat-only images. From these images it is possible to calculate quantitative fat fraction (FF) images, where the value of each voxel is equal to the percentage of its signal originating from fat. In papers I and II methods for water–fat signal separation are presented and evaluated.

    The method in paper I utilizes a graph-cut to separate the signal and was designed to perform well even for a low signal-to-noise ratio (SNR). The method was shown to perform as well as previous methods at high SNRs, and better at low SNRs.

    The method presented in paper II uses convolutional neural networks to perform the signal separation. The method was shown to perform similarly to a previous method using a graph-cut when provided non-undersampled input data. Furthermore, the method was shown to be able to separate the signal using undersampled data. This may allow for accelerated MRI scans in the future.

    Brown adipose tissue (BAT) is a thermogenic organ with the main purpose of expending chemical energy to prevent the body temperature from falling too low. Its energy expending capability makes it a potential target for treating overweight/obesity and metabolic dysfunctions, such as type 2 diabetes. The most well-established way of estimating the metabolic potential of BAT is through measuring glucose uptake using 18F-fludeoxyglucose (18F-FDG) positron emission tomography (PET) during cooling. This technique exposes subjects to potentially harmful ionizing radiation, and alternative methods are desired. One alternative method is measuring the BAT FF using MRI.

    In paper III the BAT FF in 7-year olds was shown to be negatively associated with blood serum levels of the bone-specific protein osteocalcin and, after correction for adiposity, thigh muscle volume. This may have implications for how BAT interacts with both bone and muscle tissue.

    In paper IV the glucose uptake of BAT during cooling of adult humans was measured using 18F-FDG PET. Additionally, their BAT FF was measured using MRI, and their skin temperature during cooling near a major BAT depot was measured using infrared thermography (IRT). It was found that both the BAT FF and the temperature measured using IRT correlated with the BAT glucose uptake, meaning these measurements could be potential alternatives to 18F-FDG PET in future studies of BAT.

    List of papers
    1. Water-fat separation incorporating spatial smoothing is robust to noise
    Open this publication in new window or tab >>Water-fat separation incorporating spatial smoothing is robust to noise
    2018 (English)In: Magnetic Resonance Imaging, ISSN 0730-725X, E-ISSN 1873-5894, Vol. 50, p. 78-83, article id S0730-725X(18)30040-7Article in journal (Refereed) Published
    Abstract [en]

    PURPOSE: To develop and evaluate a noise-robust method for reconstruction of water and fat images for spoiled gradient multi-echo sequences.

    METHODS: The proposed method performs water-fat separation by using a graph cut to minimize an energy function consisting of unary and binary terms. Spatial smoothing is incorporated to increase robustness to noise. The graph cut can fail to find a solution covering the entire image, in which case the relative weighting of the unary term is iteratively increased until a complete solution is found. The proposed method was compared to two previously published methods. Reconstructions were performed on 16 cases taken from the 2012 ISMRM water-fat reconstruction challenge dataset, for which reference reconstructions were provided. Robustness towards noise was evaluated by reconstructing images with different levels of noise added. The percentage of water-fat swaps were calculated to measure performance.

    RESULTS: At low noise levels the proposed method produced similar results to one of the previously published methods, while outperforming the other. The proposed method significantly outperformed both of the previously published methods at moderate and high noise levels.

    CONCLUSION: By incorporating spatial smoothing, an increased robustness towards noise is achieved when performing water-fat reconstruction of spoiled gradient multi-echo sequences.

    Keywords
    Chemical shift imaging, Dixon, Graph cuts, Multi-scale, Quadratic pseudo-Boolean optimization, Water-fat separation
    National Category
    Radiology, Nuclear Medicine and Medical Imaging
    Identifiers
    urn:nbn:se:uu:diva-347450 (URN)10.1016/j.mri.2018.03.015 (DOI)000434750700011 ()29601865 (PubMedID)
    Funder
    Swedish Research Council, 2016-01040
    Available from: 2018-04-03 Created: 2018-04-03 Last updated: 2019-08-14Bibliographically approved
    2. Separation of water and fat signal in whole-body gradient echo scans using convolutional neural networks
    Open this publication in new window or tab >>Separation of water and fat signal in whole-body gradient echo scans using convolutional neural networks
    2019 (English)In: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 82, no 3, p. 1177-1186Article in journal (Refereed) Published
    Abstract [en]

    Purpose: To perform and evaluate water–fat signal separation of whole‐body gradient echo scans using convolutional neural networks.

    Methods: Whole‐body gradient echo scans of 240 subjects, each consisting of 5 bipolar echoes, were used. Reference fat fraction maps were created using a conventional method. Convolutional neural networks, more specifically 2D U‐nets, were trained using 5‐fold cross‐validation with 1 or several echoes as input, using the squared difference between the output and the reference fat fraction maps as the loss function. The outputs of the networks were assessed by the loss function, measured liver fat fractions, and visually. Training was performed using a graphics processing unit (GPU). Inference was performed using the GPU as well as a central processing unit (CPU).

    Results: The loss curves indicated convergence, and the final loss of the validation data decreased when using more echoes as input. The liver fat fractions could be estimated using only 1 echo, but results were improved by use of more echoes. Visual assessment found the quality of the outputs of the networks to be similar to the reference even when using only 1 echo, with slight improvements when using more echoes. Training a network took at most 28.6 h. Inference time of a whole‐body scan took at most 3.7 s using the GPU and 5.8 min using the CPU.

    Conclusion: It is possible to perform water–fat signal separation of whole‐body gradient echo scans using convolutional neural networks. Separation was possible using only 1 echo, although using more echoes improved the results.

    Keywords
    Dixon, convolutional neural network, deep learning, magnetic resonance imaging, neural network, water-fat separation
    National Category
    Radiology, Nuclear Medicine and Medical Imaging
    Identifiers
    urn:nbn:se:uu:diva-382933 (URN)10.1002/mrm.27786 (DOI)000485077600026 ()31033022 (PubMedID)
    Funder
    Swedish Research Council, 2016-01040
    Available from: 2019-05-07 Created: 2019-05-07 Last updated: 2019-10-15Bibliographically approved
    3. MRI estimates of brown adipose tissue in children - Associations to adiposity, osteocalcin, and thigh muscle volume
    Open this publication in new window or tab >>MRI estimates of brown adipose tissue in children - Associations to adiposity, osteocalcin, and thigh muscle volume
    Show others...
    2019 (English)In: Magnetic Resonance Imaging, ISSN 0730-725X, E-ISSN 1873-5894, Vol. 58, p. 135-142Article in journal (Refereed) Published
    Abstract [en]

    Context: Brown adipose tissue is of metabolic interest. The tissue is however poorly explored in children.

    Methods: Sixty-three 7-year old subjects from the Swedish birth-cohort Halland Health and Growth Study were recruited. Care was taken to include both normal weight and overweight children, but the subjects were otherwise healthy. Only children born full term were included. Water-fat separated whole-body MRI scans, anthropometric measurements, and measurements of fasting glucose and levels of energy homeostasis related hormones, including the insulin-sensitizer osteocalcin, were performed. The fat fraction (FF) and effective transverse relaxation time (T-2(star)) of suspected brown adipose tissue in the cervical-supraclavicular-axillary fat depot (sBAT) and the FFs of abdominal visceral (VAT) and subcutaneous adipose tissue (SAT) were measured. Volumes of sBAT, abdominal VAT and SAT, and thigh muscle volumes were measured.

    Results: The FF in the sBAT depot was lower than in VAT and SAT for all children. In linear correlations including sex and age as explanatory variables, sBAT FF correlated positively with all measures of adiposity (p < 0.01), except for VAT FF and weight, positively with sBAT T-2* (p = 0.036), and negatively with osteocalcin (p = 0.017). When adding measures of adiposity as explanatory variables, sBAT FF also correlated negatively with thigh muscle volume (p < 0.01).

    Conclusions: Whole-body water-fat MRI of children allows for measurements of sBAT. The FF of sBAT was lower than that of VAT and SAT, indicating presence of BAT. Future studies could confirm whether the observed correlations corresponds to a hormonally active BAT.

    Place, publisher, year, edition, pages
    ELSEVIER SCIENCE INC, 2019
    Keywords
    Brown adipose tissue, Magnetic resonance imaging, Adiposity, Osteocalcin, Muscle volume, Quantitative MRI
    National Category
    Radiology, Nuclear Medicine and Medical Imaging
    Identifiers
    urn:nbn:se:uu:diva-380416 (URN)10.1016/j.mri.2019.02.001 (DOI)000461412300018 ()30742901 (PubMedID)
    Funder
    Swedish Research Council, 2013-3013Swedish Research Council, 2016-01040Region Västra Götaland
    Available from: 2019-04-02 Created: 2019-04-02 Last updated: 2019-08-14Bibliographically approved
    4. Estimating the cold-induced brown adipose tissue glucose uptake rate measured by 18F-FDG PET using infrared thermography and water-fat separated MRI
    Open this publication in new window or tab >>Estimating the cold-induced brown adipose tissue glucose uptake rate measured by 18F-FDG PET using infrared thermography and water-fat separated MRI
    Show others...
    2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 12358Article in journal (Refereed) Published
    Abstract [en]

    Brown adipose tissue (BAT) expends chemical energy to produce heat, which makes it a potential therapeutic target for combating metabolic dysfunction and overweight/obesity by increasing its metabolic activity. The most well-established method for measuring BAT metabolic activity is glucose uptake rate (GUR) measured using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET). However, this is expensive and exposes the subjects to potentially harmful radiation. Cheaper and safer methods are warranted for large-scale or longitudinal studies. Potential alternatives include infrared thermography (IRT) and magnetic resonance imaging (MRI). The aim of this study was to evaluate and further develop these techniques. Twelve healthy adult subjects were studied. The BAT GUR was measured using 18F-FDG PET during individualized cooling. The temperatures of the supraclavicular fossae and a control region were measured using IRT during a simple cooling protocol. The fat fraction and effective transverse relaxation rate of BAT were measured using MRI without any cooling intervention. Simple and multiple linear regressions were employed to evaluate how well the MRI and IRT measurements could estimate the GUR. Results showed that both IRT and MRI measurements correlated with the GUR. This suggest that these measurements may be suitable for estimating the cold-induced BAT GUR in future studies.

    Keywords
    brown adipose tissue, 18F-FDG positron emission tomography, infrared thermography, magnetic resonance imagingm PET/MRI, water–fat signal separation
    National Category
    Radiology, Nuclear Medicine and Medical Imaging
    Research subject
    Radiology
    Identifiers
    urn:nbn:se:uu:diva-390410 (URN)10.1038/s41598-019-48879-7 (DOI)000482564800014 ()31451711 (PubMedID)
    Funder
    Swedish Research Council, 2016-01040Swedish Heart Lung Foundation, 2170492EXODIAB - Excellence of Diabetes Research in Sweden
    Available from: 2019-08-09 Created: 2019-08-09 Last updated: 2019-10-18Bibliographically approved
  • 440.
    Andersson, Jonathan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Med, Mölndal, Sweden.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Med, Mölndal, Sweden.
    Separation of water and fat signal in whole-body gradient echo scans using convolutional neural networks2019In: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 82, no 3, p. 1177-1186Article in journal (Refereed)
    Abstract [en]

    Purpose: To perform and evaluate water–fat signal separation of whole‐body gradient echo scans using convolutional neural networks.

    Methods: Whole‐body gradient echo scans of 240 subjects, each consisting of 5 bipolar echoes, were used. Reference fat fraction maps were created using a conventional method. Convolutional neural networks, more specifically 2D U‐nets, were trained using 5‐fold cross‐validation with 1 or several echoes as input, using the squared difference between the output and the reference fat fraction maps as the loss function. The outputs of the networks were assessed by the loss function, measured liver fat fractions, and visually. Training was performed using a graphics processing unit (GPU). Inference was performed using the GPU as well as a central processing unit (CPU).

    Results: The loss curves indicated convergence, and the final loss of the validation data decreased when using more echoes as input. The liver fat fractions could be estimated using only 1 echo, but results were improved by use of more echoes. Visual assessment found the quality of the outputs of the networks to be similar to the reference even when using only 1 echo, with slight improvements when using more echoes. Training a network took at most 28.6 h. Inference time of a whole‐body scan took at most 3.7 s using the GPU and 5.8 min using the CPU.

    Conclusion: It is possible to perform water–fat signal separation of whole‐body gradient echo scans using convolutional neural networks. Separation was possible using only 1 echo, although using more echoes improved the results.

  • 441.
    Andersson, Jonathan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Med, Molndal, Sweden.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Med, Molndal, Sweden.
    Water-fat separation incorporating spatial smoothing is robust to noise2018In: Magnetic Resonance Imaging, ISSN 0730-725X, E-ISSN 1873-5894, Vol. 50, p. 78-83, article id S0730-725X(18)30040-7Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To develop and evaluate a noise-robust method for reconstruction of water and fat images for spoiled gradient multi-echo sequences.

    METHODS: The proposed method performs water-fat separation by using a graph cut to minimize an energy function consisting of unary and binary terms. Spatial smoothing is incorporated to increase robustness to noise. The graph cut can fail to find a solution covering the entire image, in which case the relative weighting of the unary term is iteratively increased until a complete solution is found. The proposed method was compared to two previously published methods. Reconstructions were performed on 16 cases taken from the 2012 ISMRM water-fat reconstruction challenge dataset, for which reference reconstructions were provided. Robustness towards noise was evaluated by reconstructing images with different levels of noise added. The percentage of water-fat swaps were calculated to measure performance.

    RESULTS: At low noise levels the proposed method produced similar results to one of the previously published methods, while outperforming the other. The proposed method significantly outperformed both of the previously published methods at moderate and high noise levels.

    CONCLUSION: By incorporating spatial smoothing, an increased robustness towards noise is achieved when performing water-fat reconstruction of spoiled gradient multi-echo sequences.

  • 442.
    Andersson, Jonathan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lundström, Elin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Engström, Mathias
    GE Healthcare.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Medical.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Medical.
    Estimating the cold-induced brown adipose tissue glucose uptake rate measured by 18F-FDG PET using infrared thermography and water-fat separated MRI2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 12358Article in journal (Refereed)
    Abstract [en]

    Brown adipose tissue (BAT) expends chemical energy to produce heat, which makes it a potential therapeutic target for combating metabolic dysfunction and overweight/obesity by increasing its metabolic activity. The most well-established method for measuring BAT metabolic activity is glucose uptake rate (GUR) measured using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET). However, this is expensive and exposes the subjects to potentially harmful radiation. Cheaper and safer methods are warranted for large-scale or longitudinal studies. Potential alternatives include infrared thermography (IRT) and magnetic resonance imaging (MRI). The aim of this study was to evaluate and further develop these techniques. Twelve healthy adult subjects were studied. The BAT GUR was measured using 18F-FDG PET during individualized cooling. The temperatures of the supraclavicular fossae and a control region were measured using IRT during a simple cooling protocol. The fat fraction and effective transverse relaxation rate of BAT were measured using MRI without any cooling intervention. Simple and multiple linear regressions were employed to evaluate how well the MRI and IRT measurements could estimate the GUR. Results showed that both IRT and MRI measurements correlated with the GUR. This suggest that these measurements may be suitable for estimating the cold-induced BAT GUR in future studies.

  • 443.
    Andersson, Jonathan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Roswall, Josefine
    Hallands Hosp Halmstad, Dept Pediat, Halmstad, Sweden;Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Pediat, Gothenburg, Sweden.
    Kjellberg, Emma
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Pediat, Gothenburg, Sweden.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Med, Molndal, Sweden.
    Dahlgren, Jovanna
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Pediat, Gothenburg, Sweden.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Med, Molndal, Sweden.
    MRI estimates of brown adipose tissue in children - Associations to adiposity, osteocalcin, and thigh muscle volume2019In: Magnetic Resonance Imaging, ISSN 0730-725X, E-ISSN 1873-5894, Vol. 58, p. 135-142Article in journal (Refereed)
    Abstract [en]

    Context: Brown adipose tissue is of metabolic interest. The tissue is however poorly explored in children.

    Methods: Sixty-three 7-year old subjects from the Swedish birth-cohort Halland Health and Growth Study were recruited. Care was taken to include both normal weight and overweight children, but the subjects were otherwise healthy. Only children born full term were included. Water-fat separated whole-body MRI scans, anthropometric measurements, and measurements of fasting glucose and levels of energy homeostasis related hormones, including the insulin-sensitizer osteocalcin, were performed. The fat fraction (FF) and effective transverse relaxation time (T-2(star)) of suspected brown adipose tissue in the cervical-supraclavicular-axillary fat depot (sBAT) and the FFs of abdominal visceral (VAT) and subcutaneous adipose tissue (SAT) were measured. Volumes of sBAT, abdominal VAT and SAT, and thigh muscle volumes were measured.

    Results: The FF in the sBAT depot was lower than in VAT and SAT for all children. In linear correlations including sex and age as explanatory variables, sBAT FF correlated positively with all measures of adiposity (p < 0.01), except for VAT FF and weight, positively with sBAT T-2* (p = 0.036), and negatively with osteocalcin (p = 0.017). When adding measures of adiposity as explanatory variables, sBAT FF also correlated negatively with thigh muscle volume (p < 0.01).

    Conclusions: Whole-body water-fat MRI of children allows for measurements of sBAT. The FF of sBAT was lower than that of VAT and SAT, indicating presence of BAT. Future studies could confirm whether the observed correlations corresponds to a hormonally active BAT.

  • 444. Andersson, K. G.
    et al.
    Varasteh, Zohreh
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Rosestedt, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Malm, M.
    Sandström, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Medical Radiation Sciences.
    Tolmachev, Vladimir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
    Lofblom, J.
    Stahl, S.
    Orlova, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    111In-labeled NOTA-conjugated Affibody molecules for visualization of HER3 expression in malignant tumors2014In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 41, no S2, p. S311-S311, article id OP681Article in journal (Other academic)
  • 445.
    Andersson Kallin, Sandra
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Sommar, Johan Nilsson
    Umeå Univ, Dept Publ Hlth & Clin Med, Occupat & Environm Med, Umeå, Sweden.
    Bossios, Apostolos
    Univ Gothenburg, Sahlgrenska Acad, Krefting Res Ctr, Dept Internal Med & Clin Nutr, Gothenburg, Sweden.
    Ekerljung, Linda
    Univ Gothenburg, Sahlgrenska Acad, Krefting Res Ctr, Dept Internal Med & Clin Nutr, Gothenburg, Sweden.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Middelveld, Roelinde
    Karolinska Inst, Ctr Allergy Res, Stockholm, Sweden; Karolinska Inst, Inst Environm Med, Stockholm, Sweden.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Excessive daytime sleepiness in asthma: what are the risk factors?2018In: Journal of Asthma, ISSN 0277-0903, E-ISSN 1532-4303, Vol. 55, no 8, p. 844-850Article in journal (Refereed)
    Abstract [en]

    Objective: Previous studies have found that excessive daytime sleepiness (EDS) is a more common problem in asthmatic subjects than in the general population. The aim of this study was to investigate whether the prevalence of EDS is increased in asthmatic subjects and, if so, to analyse the occurrence of potential risk factors for EDS in asthmatics.

    Methods: Cross-sectional epidemiological study. In 2008, a postal questionnaire was sent out to a random sample of 45,000 individuals aged 16–75 years in four Swedish cities.

    Results: Of the 25,160 persons who participated, 7.3% were defined as having asthma. The prevalence of EDS was significantly higher in asthmatic subjects (42.1% vs. 28.5%, p < 0.001) compared with non-asthmatic subjects. Asthma was an independent risk factor for EDS (adjusted OR 1.29) and the risk of having EDS increased with asthma severity. Risk factors for EDS in subjects with asthma included insomnia (OR, 3.87; 95% CI, 3.10–4.84); chronic rhinosinusitis (OR, 2.00; 95% CI, 1.53–2.62); current smoking (OR, 1.60; 95% CI, 1.15–2.22) and obesity (OR, 1.53; 95% CI, 1.09–2.13).

    Conclusions: EDS is a common problem among subjects with asthma. Asthma is an independent risk factor for having EDS. Furthermore, subjects with asthma often have other risk factors for EDS, many of them potentially modifiable.

  • 446. Andersson, Karin M.
    et al.
    Ahnesjö, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Medical Radiation Sciences.
    Dahlgren, Christina Vallhagen
    Evaluation of a metal artifact reduction algorithm in CT studies used for proton radiotherapy treatment planning2014In: Journal of Applied Clinical Medical Physics, ISSN 1526-9914, E-ISSN 1526-9914, Vol. 15, no 5, p. 112-119Article in journal (Refereed)
    Abstract [en]

    Metal objects in the body such as hip prostheses cause artifacts in CT images. When CT images degraded by artifacts are used for treatment planning of radiotherapy, the artifacts can yield inaccurate dose calculations and, for particle beams, erroneous penetration depths. A metal artifact reduction software (O-MAR) installed on a Philips Brilliance Big Bore CT has been tested for applications in treatment planning of proton radiotherapy. Hip prostheses mounted in a water phantom were used as test objects. Images without metal objects were acquired and used as reference data for the analysis of artifact-affected regions outside of the metal objects in both the O-MAR corrected and the uncorrected images. Water equivalent thicknesses (WET) based on proton stopping power data were calculated to quantify differences in the calculated proton beam penetration for the different image sets. The WET to a selected point of interest between the hip prostheses was calculated for several beam directions of clinical relevance. The results show that the calculated differences in WET relative to the reference case were decreased when the O-MAR algorithm was applied. WET differences up to 2.0 cm were seen in the uncorrected case while, for the O-MAR corrected case, the maximum difference was decreased to 0.4 cm. The O-MAR algorithm can significantly improve the accuracy in proton range calculations. However, there are some residual effects, and the use of proton beam directions along artifact streaks should only be used with caution and appropriate margins.

  • 447.
    Andersson, Karin M.
    et al.
    Skand Clin, Uppsala, Sweden; Örebro Univ, Sch Hlth & Med Sci, Örebro, Sweden.
    Dahlgren, Christina Vallhagen
    Skand Clin, Uppsala, Sweden.
    Reizenstein, Johan
    Örebro Univ, Fac Med & Hlth, Dept Oncol, Örebro, Sweden.
    Cao, Yang
    Örebro Univ, Sch Med Sci, Clin Epidemiol & Biostat, Örebro, Sweden; Karolinska Inst, Inst Environm Med, Unit Biostat, Stockholm, Sweden.
    Ahnesjö, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Thunberg, Per
    Örebro Univ, Fac Med & Hlth, Dept Med Phys, Örebro, Sweden.
    Evaluation of two commercial CT metal artifact reduction algorithms for use in proton radiotherapy treatment planning in the head and neck area2018In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 45, no 10, p. 4329-4344Article in journal (Refereed)
    Abstract [en]

    Purpose: To evaluate two commercial CT metal artifact reduction (MAR) algorithms for use in proton treatment planning in the head and neck (H&N) area.

    Methods: An anthropomorphic head phantom with removable metallic implants (dental fillings or neck implant) was CT-scanned to evaluate the O-MAR (Philips) and the iMAR (Siemens) algorithms. Reference images were acquired without any metallic implants in place. Water equivalent thickness (WET) was calculated for different path directions and compared between image sets. Images were also evaluated for use in proton treatment planning for parotid, tonsil, tongue base, and neck node targets. The beams were arranged so as to not traverse any metal prior to the target, enabling evaluation of the impact on dose calculation accuracy from artifacts surrounding the metal volume. Plans were compared based on analysis (1 mm distance-to-agreement/1% difference in local dose) and dose volume histogram metrics for targets and organs at risk (OARs). Visual grading evaluation of 30 dental implant patient MAR images was performed by three radiation oncologists.

    Results: In the dental fillings images, WET along a low-density streak was reduced from -17.0 to -4.3 mm with O-MAR and from -16.1 mm to -2.3 mm with iMAR, while for other directions the deviations were increased or approximately unchanged when the MAR algorithms were used. For the neck implant images, WET was generally reduced with MAR but residual deviations remained (of up to -2.3 mm with O-MAR and of up to -1.5 mm with iMAR). The analysis comparing proton dose distributions for uncorrected/MAR plans and corresponding reference plans showed passing rates >98% of the voxels for all phantom plans. However, substantial dose differences were seen in areas of most severe artifacts ( passing rates of down to 89% for some cases). MAR reduced the deviations in some cases, but not for all plans. For a single patient case dosimetrically evaluated, minor dose differences were seen between the uncorrected and MAR plans ( passing rate approximately 97%). The visual grading of patient images showed that MAR significantly improved image quality (P < 0.001).

    Conclusions: O-MAR and iMAR significantly improved image quality in terms of anatomical visualization for target and OAR delineation in dental implant patient images. WET calculations along several directions, all outside the metallic regions, showed that both uncorrected and MAR images contained metal artifacts which could potentially lead to unacceptable errors in proton treatment planning. WET was reduced by MAR in some areas, while increased or unchanged deviations were seen for other path directions. The proton treatment plans created for the phantom images showed overall acceptable dose distributions differences when compared to the reference cases, both for the uncorrected and MAR images. However, substantial dose distribution differences in the areas of most severe artifacts were seen for some plans, which were reduced by MAR in some cases but not all. In conclusion, MAR could be beneficial to use for proton treatment planning; however, case-by-case evaluations of the metal artifact-degraded images are always recommended.

  • 448. Andersson, Ken G.
    et al.
    Rosestedt, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Varasteh, Zohreh
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Malm, Magdalena
    Sandström, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Tolmachev, Vladimir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Lofblom, John
    Stahl, Stefan
    Orlova, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Comparative evaluation of 111In-labeled NOTA‑conjugated affibody molecules for visualization of HER3 expression in malignant tumors2015In: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 34, no 2, p. 1042-1048Article in journal (Refereed)
    Abstract [en]

    Expression of human epidermal growth factor receptor type 3 (HER3) in malignant tumors has been associated with resistance to a variety of anticancer therapies. Several anti-HER3 monoclonal antibodies are currently under pre-clinical and clinical development aiming to overcome HER3-mediated resistance. Radionuclide molecular imaging of HER3 expression may improve treatment by allowing the selection of suitable patients for HER3-targeted therapy. Affibody molecules are a class of small (7 kDa) high-affinity targeting proteins with appreciable potential as molecular imaging probes. In a recent study, we selected affibody molecules with affinity to HER3 at a low picomolar range. The aim of the present study was to develop an anti-HER3 affibody molecule suitable for labeling with radiometals. The HEHEHE-Z08698-NOTA and HEHEHE-Z08699-NOTA HER3-specific affibody molecules were labeled with indium-111 (In-111) and assessed in vitro and in vivo for imaging properties using single photon emission computed tomography (SPECT). Labeling of HEHEHE-Z08698-NOTA and HEHEHE-Z08699-NOTA with In-111 provided stable conjugates. In vitro cell tests demonstrated specific binding of the two conjugates to HER3-expressing BT-474 breast carcinoma cells. In mice bearing BT-474 xenografts, the tumor uptake of the two conjugates was receptor-specific. Direct in vivo comparison of In-111-HEHEHE-Z08698-NOTA and In-111-HEHEHE-Z08699-NOTA demonstrated that the two conjugates provided equal radioactivity uptake in tumors, although the tumor-to-blood ratio was improved for In-111-HEHEHE-Z08698-NOTA [12 +/- 3 vs. 8 +/- 1,4 h post injection (p.i)] due to more efficient blood clearance. In-111-HEHEHE-Z08698-NOTA is a promising candidate for imaging of HER3-expression in malignant tumors using SPECT. Results of the present study indicate that this conjugate could be used for patient stratification for anti-HER3 therapy.

  • 449.
    Andersson, Lena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Vårdcentralen Centrum Flen, Sweden; Research and Development Centre, Sörmland County Council.
    Nordgren, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Research and Development Centre, Sörmland County Council.
    Heart Failure Patients' Perceptions of Received and Wanted Information: A Cross-Sectional Study2019In: Clinical Nursing Research, ISSN 1054-7738, E-ISSN 1552-3799, Vol. 28, no 3, p. 340-355Article in journal (Refereed)
    Abstract [en]

    This study aimed to investigate heart failure patients’ perceptions of received and wanted information and to identify differences regarding received and wanted information in relation to sociodemographic variables. A cross-sectional descriptive design was used. Patients with heart failure (n = 192) were recruited from six primary health care centers in Sweden. Data were collected by a postal questionnaire. A majority of the respondents had received information about the condition and the medication. Within primary health care, most respondents had been informed about medication. The respondents wanted more information about continued care and treatment, medication, and the condition. There were significant differences between sociodemographic groups concerning what information they wanted. Clinical nurses can support patients with heart failure by using evidence-based methods that strengthen the patients’ self-efficacy and by individualized information that increases patients’ knowledge and improves their self-care behaviors. Future studies are needed to identify informational needs of particular fragile groups of patients.

  • 450.
    Andersson, Madelen
    et al.
    Blekinge Hosp, Dept Infect Dis, Karlskrona, Sweden..
    Resman, Fredrik
    Lund Univ, Dept Translat Med Med Microbiol, Malmo, Sweden..
    Eitrem, Rickard
    Dept Communicable Dis Control Cty Blekinge, Karlskrona, Sweden..
    Drobni, Peter
    Dept Clin Microbiol Cty Kronoberg, Vaxjo Karlskrona, Sweden..
    Riesbeck, Kristian
    Lund Univ, Dept Translat Med Med Microbiol, Malmo, Sweden..
    Kahlmeter, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology. Dept Clin Microbiol Cty Kronoberg, Vaxjo Karlskrona, Sweden..
    Sundqvist, Martin
    Dept Clin Microbiol Cty Kronoberg, Vaxjo Karlskrona, Sweden.;Univ Orebro, Fac Med & Hlth, Dept Lab Med Clin Microbiol, SE-70182 Orebro, Sweden..
    Outbreak of a beta-lactam resistant non-typeable Haemophilus influenzae sequence type 14 associated with severe clinical outcomes2015In: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 15, article id 581Article in journal (Refereed)
    Abstract [en]

    Background: During October 2011 several residents and staff members at a long-term care facility (LTCF) for elderly fell ill with respiratory symptoms. Several of the residents required hospitalization and one died. Non-typeable Haemophilus influenzae (NTHi) was identified as the causative pathogen. Methods: A descriptive analysis of the outbreak and countermeasures was performed. For each identified bacterial isolate implied in the outbreak, standard laboratory resistance testing was performed, as well as molecular typing and phylogenetic analysis. Results: The identified H. influenzae was beta-lactamase negative but had strikingly high MIC-values of ampicillin, cefuroxime and cefotaxime. All isolates displayed the same mutation in the ftsI gene encoding penicillin-binding protein (PBP) 3, and all but one were identified as sequence type 14 by Multilocus Sequence Typing (MLST). In total 15 individuals in connection to the LTCF; 8 residents, 6 staff members and one partner to a staff member were colonized with the strain. Conclusion: This report illustrates the existence of non-typeable H. influenzae with high virulence, and furthermore emphasizes the importance of continuous surveillance of possible outbreaks in health care facilities and prompt measures when outbreaks occur.

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