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  • 301.
    Kataria, Bharti
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Linköping. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Sandborg, Michael
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Radiofysikavdelningen US. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Nilsson Althen, Jonas
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Radiofysikavdelningen US. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper.
    IMPLICATIONS OF PATIENT CENTRING ON ORGAN DOSE IN COMPUTED TOMOGRAPHY2016Ingår i: Radiation Protection Dosimetry, ISSN 0144-8420, E-ISSN 1742-3406, Vol. 169, nr 1-4, s. 130-135Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Automatic exposure control (AEC) in computed tomography (CT) facilitates optimisation of dose absorbed by the patient. The use of AEC requires appropriate ‘patient centring’ within the gantry, since positioning the patient off-centre may affect both image quality and absorbed dose. The aim of this experimental study was to measure the variation in organ and abdominal surface dose during CTexaminations of the head, neck/thorax and abdomen. The dose was compared at the isocenter with two off-centre positions—ventral and dorsal to the isocenter. Measurements were made with an anthropomorphic adult phantom and thermoluminescent dosemeters. Organs and surfaces for ventral regions received lesser dose (5.6–39.0 %) than the isocenter when the phantom was positioned 13 cm off-centre. Similarly, organ and surface doses for dorsal regions were reduced by 5.0–21.0 % at 25 cm off-centre. Therefore, correct vertical positioning of the patient at the gantry isocenter is important to maintain optimal imaging conditions.

  • 302.
    Kawa, Lizan
    et al.
    Karolinska Institute, Sweden.
    Barde, Swapnali
    Karolinska Institute, Sweden.
    Arborelius, Ulf P.
    Karolinska Institute, Sweden.
    Theodorsson, Elvar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Agoston, Denes
    Karolinska Institute, Sweden; Uniformed Serv University of Health Science, MD 20814 USA.
    Risling, Marten
    Karolinska Institute, Sweden.
    Hokfelt, Tomas
    Karolinska Institute, Sweden.
    Expression of galanin and its receptors are perturbed in a rodent model of mild, blast-induced traumatic brain injury2016Ingår i: Experimental Neurology, ISSN 0014-4886, E-ISSN 1090-2430, Vol. 279, s. 159-167Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The symptomatology, mood and cognitive disturbances seen in post-traumatic stress disorder (PTSD) and mild blast-induced traumatic brain injury (mbTBI) overlap considerably. However the pathological mechanisms underlying the two conditions are currently unknown. The neuropeptide galanin has been suggested to play a role in the development of stress and mood disorders. Here we applied bio- and histochemical methods with the aim to elucidate the nature of any changes in the expression of galanin and its receptors in a rodent model of mbTBI. In situ hybridization and quantitative polymerase chain reaction studies revealed significant, injury induced changes, in some cases lasting at least for one week, in the mRNA levels of galanin and/or its three receptors, galanin receptor 1-3 (GalR1-3). Such changes were seen in several forebrain regions, and the locus coeruleus. In the ventral periaqueductal gray GalR1 mRNA levels were increased, while GalR2 were decreased. Analysis of galanin peptide levels using radioimmunoassay demonstrated an increase in several brain regions including the locus coeruleus, dorsal hippocampal formation and amygdala. These findings suggest a role for the galanin system in the endogenous response to mbTBI, and that pharmacological studies of the effects of activation or inhibition of different galanin receptors in combination with functional assays of behavioral recovery may reveal promising targets for new therapeutic strategies in mbTBI. (C) 2016 Elsevier Inc. All rights reserved.

  • 303.
    Kedia, George T.
    et al.
    Hannover Medical School, Germany.
    Ückert, Stefan
    Hannover Medical School, Germany; Institute for Biochemical Research and Analysis, Germany.
    Oelke, Matthias
    Hannover Medical School, Germany.
    Sonnenberg, Joachim E.
    Institute for Biochemical Research and Analysis, Germany.
    Sohn, Michael
    AGAPLESION Markus Hospital, Germany.
    Kuczyk, Markus A.
    Hannover Medical School, Germany.
    Hedlund, Petter
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Hälsouniversitetet. Region Östergötland, Diagnostikcentrum, Klinisk farmakologi. University Vita Salute San Raffaele, Italy.
    Expression and Distribution of Phosphodiesterase Isoenzymes in the Human Male Urethra2015Ingår i: Urology, ISSN 0090-4295, E-ISSN 1527-9995, Vol. 85, nr 4, s. 964.e1-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE To investigate the expression and distribution of phosphodiesterase (PDE) isoenzymes PDE1A, PDE2A, PDE4A, PDE4B, and PDE5A in human urethral tissue. METHODS Specimens of penile urethra were obtained from male subjects who had undergone male-to-female sex reassignment surgery. Using immunohistochemistry (immunofluorescence), the occurrence of PDE1A, PDE2A, PDE4A, PDE4B, and PDE5A, the neuronal nitric oxide synthase, calcitonin gene-related peptide, and vasoactive intestinal polypeptide was examined in urethral sections. Cytosolic supernatants prepared from isolated human urethral tissue were subjected to Western blot analysis using specific anti-PDE antibodies. RESULTS Immunosignals specific for PDE1A, 4A, 4B, and 5A were observed in the urethral smooth musculature. The smooth muscle bundles were seen innervated by slender nerve fibers, characterized by the expression of the neuronal nitric oxide synthase, calcitonin gene-related peptide, and vasoactive intestinal polypeptide. The expression of the PDE isoenzymes mentioned was confirmed by Western blotting. CONCLUSION The results provide evidence for a significance of both the cyclic adenosine monophosphate and cyclic guanosine monophosphate signaling in the control of human urethral smooth muscle. The selective inhibition of PDE isoenzymes might represent a pharmacologic option to influence the function of smooth musculature in the human outflow region.

  • 304.
    Kempe, Per
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Cty Hosp Sundsvall, Sweden.
    Eklund, Daniel
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Hallin, Agnes
    Not Found:Linkoping Univ, Dept Clin and Expt Med, SE-58185 Linkoping, Sweden.
    Hammar, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Olsson, Tomas
    Karolinska Inst, Sweden.
    Brynhildsen, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Immune profile in relation to sex steroid cyclicity in healthy women and women with multiple sclerosis2018Ingår i: Journal of Reproductive Immunology, ISSN 0165-0378, E-ISSN 1872-7603, Vol. 126, s. 53-59Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    To prospectively study systemic in vivo immunological effects of sex hormones, using different phases of oral combined hormonal contraceptives (CHC), and the natural menstrual cycles in both healthy women and in women with multiple sclerosis (MS), blood samples from sixty female MS patients and healthy controls with and without CHC were drawn in high and low estrogenic/progestogenic phases. Expression of Th-associated genes in blood cells was determined by qPCR and a panel of cytokines and chemokines was measured in plasma. High hormone level phases were associated with increases in Th1 (TBX21) and Th2 (GATA3) associated markers, as well as the B cell-associated chemokine CXCL13, while the inhibitory regulator CTLA-4 was decreased. These changes were not observed in MS patients, of whom most were treated with immunomodulatory drugs. Our data indicate immune activating properties in vivo of high steroid sex hormone levels during both CHC and normal menstrual cyclicity.

  • 305.
    Kentson, Magnus
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Medicinska fakulteten. Ryhov County Hospital, Sweden.
    Tödt, Kristina
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för fysioterapi. Skåne University Hospital, Sweden.
    Skargren, Elisabeth
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för medicin och hälsa.
    Jakobsson, Per
    Ryhov County Hospital, Sweden.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Unosson, Mitra
    Linköpings universitet, Institutionen för samhälls- och välfärdsstudier, Avdelningen för omvårdnad. Linköpings universitet, Medicinska fakulteten.
    Theander, Kersti
    Karlstad University, Sweden; County Council Varmland, Sweden.
    Factors associated with experience of fatigue, and functional limitations due to fatigue in patients with stable COPD2016Ingår i: THERAPEUTIC ADVANCES IN RESPIRATORY DISEASE, ISSN 1753-4658, Vol. 10, nr 5, s. 410-424Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The aim of this study was to determine the influence of selected physiological, psychological and situational factors on experience of fatigue, and functional limitations due to fatigue in patients with stable chronic obstructive pulmonary disease (COPD). Methods: In total 101 patients with COPD and 34 control patients were assessed for experience of fatigue, functional limitation due to fatigue (Fatigue Impact Scale), physiological [lung function, 6-minute walk distance (6MWD), body mass index (BMI), dyspnoea, interleukin (IL)-6, IL-8, high sensitivity C-reactive protein (hs-CRP), surfactant protein D], psychological (anxiety, depression, insomnia), situational variables (age, sex, smoking, living alone, education), and quality of life. Results: Fatigue was more common in patients with COPD than in control patients (72% versus 56%, p amp;lt; 0.001). Patients with COPD and fatigue had lower lung function, shorter 6MWD, more dyspnoea, anxiety and depressive symptoms, and worse health status compared with patients without fatigue (all p amp;lt; 0.01). No differences were found for markers of systemic inflammation. In logistic regression, experience of fatigue was associated with depression [odds ratio (OR) 1.69, 95% confidence interval (CI) 1.28-2.25) and insomnia (OR 1.75, 95% CI 1.19-2.54). In linear regression models, depression, surfactant protein D and dyspnoea explained 35% (R-2) of the variation in physical impact of fatigue. Current smoking and depression explained 33% (R-2) of the cognitive impact of fatigue. Depression and surfactant protein D explained 48% (R-2) of the psychosocial impact of fatigue. Conclusions: Experiences of fatigue and functional limitation due to fatigue seem to be related mainly to psychological but also to physiological influencing factors, with depressive symptoms, insomnia problems and dyspnoea as the most prominent factors. Systemic inflammation was not associated with perception of fatigue but surfactant protein D was connected to some dimensions of the impact of fatigue

  • 306.
    Khedidja, Hedna
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Nordic School of Public Health NHV, Gothenburg, Sweden.
    Hakkarainen, Katja M.
    EPID Research, Espoo, Finland, Nordic School of Public Health NHV, Gothenburg, Sweden.
    Gyllensten, Hanna
    Nordic School of Public Health NHV, Gothenburg, Sweden, Division of Insurance Medicine, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Jönsson, Anna K
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk farmakologi.
    Andersson Sundell, Karolina
    Section of Social Medicine, University of Gothenburg, Gothenburg, Sweden.
    Petzold, Max
    Centre for Applied Biostatistics, University of Gothenburg, Gothenburg, Sweden.
    Hägg, Staffan
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk farmakologi. Jönköping County Council, Jönköping, Sweden.
    Adherence to Antihypertensive Therapy and Elevated Blood Pressure: Should We Consider the Use of Multiple Medications?2015Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 9, artikel-id e0137451Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    Although a majority of patients with hypertension require a multidrug therapy, this is rarely considered when measuring adherence from refill data. Moreover, investigating the association between refill non-adherence to antihypertensive therapy (AHT) and elevated blood pressure (BP) has been advocated.

    Objective

    Identify factors associated with non-adherence to AHT, considering the multidrug therapy, and investigate the association between non-adherence to AHT and elevated BP.

    Methods

    A retrospective cohort study including patients with hypertension, identified from a random sample of 5025 Swedish adults. Two measures of adherence were estimated by the proportion of days covered method (PDC≥80%): (1) Adherence to any antihypertensive medication and, (2) adherence to the full AHT regimen. Multiple logistic regressions were performed to investigate the association between sociodemographic factors (age, sex, education, income), clinical factors (user profile, number of antihypertensive medications, healthcare use, cardiovascular comorbidities) and non-adherence. Moreover, the association between non-adherence (long-term and a month prior to BP measurement) and elevated BP was investigated.

    Results

    Non-adherence to any antihypertensive medication was higher among persons < 65 years (Odds Ratio, OR 2.75 [95% CI, 1.18–6.43]) and with the lowest income (OR 2.05 [95% CI, 1.01–4.16]). Non-adherence to the full AHT regimen was higher among new users (OR 2.04 [95% CI, 1.32–3.15]), persons using specialized healthcare (OR 1.63, [95% CI, 1.14–2.32]), and having multiple antihypertensive medications (OR 1.85 [95% CI, 1.25–2.75] and OR 5.22 [95% CI, 3.48–7.83], for 2 and ≥3 antihypertensive medications, respectively). Non-adherence to any antihypertensive medication a month prior to healthcare visit was associated with elevated BP.

    Conclusion

    Sociodemographic factors were associated with non-adherence to any antihypertensive medication while clinical factors with non-adherence to the full AHT regimen. These differing findings support considering the use of multiple antihypertensive medications when measuring refill adherence. Monitoring patients' refill adherence prior to healthcare visit may facilitate interpreting elevated BP.

  • 307.
    Khedidja, Hedna
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Nordic School of Public Health NHV, Gothenburg, Sweden.
    Hakkarainen, Katja M.
    Nordic School of Public Health NHV, Gothenburg, Sweden, EPID Research, Espoo, Finland.
    Gyllensten, Hanna
    Division of Insurance Medicine, Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
    Jönsson, Anna K
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk farmakologi.
    Petzold, Max
    Centre for Applied Biostatistics, University of Gothenburg,, Gotenburg, Sweden.
    Hägg, Staffan
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk farmakologi.
    Potentially inappropriate prescribing and adverse drug reactions in the elderly: a population-based study2015Ingår i: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 71, nr 12, s. 1525-1533Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose

    Potentially inappropriate prescriptions (PIPs) criteria are widely used for evaluating the quality of prescribing in elderly. However, there is limited evidence on their association with adverse drug reactions (ADRs) across healthcare settings. The study aimed to determine the prevalence of PIPs, defined by the Screening Tool of Older Persons’ potentially inappropriate Prescriptions (STOPP) criteria, in the Swedish elderly general population and to investigate the association between PIPs and occurrence of ADRs.

    Method

    Persons ≥65 years old were identified from a random sample of 5025 adults drawn from the Swedish Total Population Register. A retrospective cohort study was conducted among 813 elderly with healthcare encounters in primary and specialised healthcare settings during a 3-month period in 2008. PIPs were identified from the Swedish Prescribed Drug Register, medical records and health administrative data. ADRs were independently identified by expert reviewers in a stepwise manner using the Howard criteria. Multivariable logistic regression examined the association between PIPs and ADRs.

    Results

    Overall, 374 (46.0 %) persons had ≥1 PIPs and 159 (19.5 %) experienced ≥1 ADRs during the study period. In total, 29.8 % of all ADRs was considered caused by PIPs. Persons prescribed with PIPs had more than twofold increased odds of experiencing ADRs (OR 2.47; 95 % CI 1.65–3.69). PIPs were considered the cause of 60 % of ADRs affecting the vascular system, 50 % of ADRs affecting the nervous system and 62.5 % of ADRs resulting in falls.

    Conclusion

    PIPs are common among the Swedish elderly and are associated with increased odds of experiencing ADRs. Thus, interventions to decrease PIPs may contribute to preventing ADRs, in particular ADRs associated with nervous and vascular disorders and falls.

  • 308.
    Kihlberg, Johan
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Linköping.
    Magnetic Resonance Imaging of Myocardial Deformation and Scarring in Coronary Artery Disease.2017Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Although improved treatments have reduced the rates of acute complications from myocardial infarction, sequelae such as heart failure and sudden death threaten the future wellbeing of those patients. Secondary prevention after myocardial infarction is related to cardiovascular risk factors and the effect of the infarct on left ventricular function. Cardiovascular magnetic resonance imaging (CMR) is necessary to determine the size of the infarct scar and can with great precision determine left ventricular volumes, left ventricular ejection fraction, and deformation (strain and torsion). The purpose of this thesis was to improve on CMR methods to facilitate image acquisition and post processing in patients with high risk of coronary artery disease (CAD).

    In Paper 1, a three-dimensional phase-sensitive inversion-recovery (3D PSIR) sequence was modified to measure T1 during a single breath hold. The measured T1 values were used to extrapolate a map of T1 relaxation, which avoided the time-consuming manual determination of the inversion time. The data collection consisted of phantom experiments, Monte Carlo simulations of the effect of various heart rates, and clinical investigation of 18 patients with myocardial infarction. Scar images created with the modified sequence were compared to those created with the standard sequence. The 3D PSIR sequence was able to measure T1 relaxation with a high accuracy up to 800 ms, which is in the suitable range for scar imaging. Simulated arrhythmias showed that the method was robust and able to tolerate some variation in heart rate. The modified sequence provides measurements of inversion time that can be used to facilitate standard scar imaging or to reconstruct synthetic scar images. Images of infarct scar obtained with the 3D PSIR sequence bore striking similarity to images obtained with the standard sequence.

    In Paper 2, 125 patients with high risk of CAD were investigated using the displacement encoding with stimulated echoes (DENSE) sequence. Image segments with infarct scar area >50% (transmurality) could be identified with a sensitivity of 95% and a specificity of 80% based on circumferential strain calculated from the DENSE measurements. The DENSE sequence was also applied in other directions, but its sensitivity and specificity to detect scar was lower than when used for circumferential strain.

    In Paper 3, 90 patients with high risk of CAD were examined by DENSE, tagging with harmonic phase (HARP) imaging and cine imaging with feature tracking (FT), to detect cardiac abnormalities as manifested in end-systolic circumferential strain. Circumferential strain calculated with DENSE had higher sensitivity and specificity than the competing methods to detect infarction with transmurality >50%. Global circumferential strain measured by DENSE correlated better with global parameters such as left ventricular ejection fraction, myocardial wall mass, left ventricular end-diastolic and end-systolic volume; than strain measured by FT or HARP.

    In Paper 4, myocardial torsion was investigated using DENSE, HARP, and FT in 48 patients with high risk of CAD. Torsion measured by each of the three methods was correlated with other global measures such as left ventricular ejection fraction, left ventricular mass, and left ventricular end-diastolic and end-systolic volumes. The torsion measurements obtained with DENSE had a stronger relationship with left ventricular ejection fraction, left ventricular mass, and volumes than those obtained with HARP or FT.

    DENSE was superior to the other methods for strain and torsion measurement and can be used to describe myocardial deformation quantitatively and objectively.

    Delarbeten
    1. Rapid T1 quantification based on 3D phase sensitive inversion recovery
    Öppna denna publikation i ny flik eller fönster >>Rapid T1 quantification based on 3D phase sensitive inversion recovery
    2010 (Engelska)Ingår i: BMC Medical Imaging, ISSN 1471-2342, E-ISSN 1471-2342, Vol. 10, nr 19Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    BACKGROUND: In Contrast Enhanced Magnetic Resonance Imaging fibrotic myocardium can be distinguished from healthy tissue using the difference in the longitudinal T1 relaxation after administration of Gadolinium, the so-called Late Gd Enhancement. The purpose of this work was to measure the myocardial absolute T1 post-Gd from a single breath-hold 3D Phase Sensitivity Inversion Recovery sequence (PSIR). Equations were derived to take the acquisition and saturation effects on the magnetization into account.

    METHODS: The accuracy of the method was investigated on phantoms and using simulations. The method was applied to a group of patients with suspected myocardial infarction where the absolute difference in relaxation of healthy and fibrotic myocardium was measured at about 15 minutes post-contrast. The evolution of the absolute R1 relaxation rate (1/T1) over time after contrast injection was followed for one patient and compared to T1 mapping using Look-Locker. Based on the T1 maps synthetic LGE images were reconstructed and compared to the conventional LGE images.

    RESULTS: The fitting algorithm is robust against variation in acquisition flip angle, the inversion delay time and cardiac arrhythmia. The observed relaxation rate of the myocardium is 1.2 s-1, increasing to 6 - 7 s-1 after contrast injection and decreasing to 2 - 2.5 s-1 for healthy myocardium and to 3.5 - 4 s-1 for fibrotic myocardium. Synthesized images based on the T1 maps correspond very well to actual LGE images.

    CONCLUSIONS: The method provides a robust quantification of post-Gd T1 relaxation for a complete cardiac volume within a single breath-hold.

    Nationell ämneskategori
    Teknik och teknologier Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-59065 (URN)10.1186/1471-2342-10-19 (DOI)20716333 (PubMedID)
    Tillgänglig från: 2010-09-08 Skapad: 2010-09-08 Senast uppdaterad: 2017-12-12
    2. Clinical experience of strain imaging using DENSE for detecting infarcted cardiac segments
    Öppna denna publikation i ny flik eller fönster >>Clinical experience of strain imaging using DENSE for detecting infarcted cardiac segments
    Visa övriga...
    2015 (Engelska)Ingår i: Journal of Cardiovascular Magnetic Resonance, ISSN 1097-6647, E-ISSN 1532-429X, Vol. 17, artikel-id 50Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background

    We hypothesised that myocardial deformation determined with magnetic resonance imaging (MRI) will detect myocardial scar.

    Methods

    Displacement Encoding with Stimulated Echoes (DENSE) was used to calculate left ventricular strain in 125 patients (29 women and 96 men) with suspected coronary artery disease. The patients also underwent cine imaging and late gadolinium enhancement. 57 patients had a scar area >1 % in at least one segment, 23 were considered free from coronary artery disease (control group) and 45 had pathological findings but no scar (mixed group). Peak strain was calculated in eight combinations: radial and circumferential strain in transmural, subendocardial and epicardial layers derived from short axis acquisition, and transmural longitudinal and radial strain derived from long axis acquisitions. In addition, the difference between strain in affected segments and reference segments, “differential strain”, from the control group was analysed.

    Results

    In receiver-operator-characteristic analysis for the detection of 50 % transmurality, circumferential strain performed best with area-under-curve (AUC) of 0.94. Using a cut-off value of -17 %, sensitivity was 95 % at a specificity of 80 %. AUC did not further improve with differential strain. There were significant differences between the control group and global strain circumferential direction (-17 % versus -12 %) and in the longitudinal direction (-13 % versus -10 %). Interobserver and scan-rescan reproducibility was high with an intraclass correlation coefficient (ICC) >0.93.

    Conclusions

    DENSE-derived circumferential strain may be used for the detection of myocardial segments with >50 % scar area. The repeatability of strain is satisfactory. DENSE-derived global strain agrees with other global measures of left ventricular ejection fraction.

    Ort, förlag, år, upplaga, sidor
    BioMed Central, 2015
    Nationell ämneskategori
    Radiologi och bildbehandling
    Identifikatorer
    urn:nbn:se:liu:diva-119846 (URN)10.1186/s12968-015-0155-8 (DOI)000356652000001 ()26104510 (PubMedID)
    Tillgänglig från: 2015-06-26 Skapad: 2015-06-26 Senast uppdaterad: 2017-12-04
  • 309.
    Kihlberg, Johan
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Linköping. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Gupta, Vikas
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten.
    Haraldsson, Henrik
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Sigfridsson, Andreas
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Sarvari, Sebastian
    Ebbers, Tino
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Fysiologiska kliniken US. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Engvall, Jan
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Fysiologiska kliniken US. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Identification of the best CMR technique for quantitative assessment of myocardial salvage using a systematic comparison.2017Konferensbidrag (Refereegranskat)
  • 310.
    Kihlberg, Johan
    et al.
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Östergötlands Läns Landsting, Diagnostikcentrum, Röntgenkliniken i Linköping. Linköpings universitet, Hälsouniversitetet. Region Östergötland, Diagnostikcentrum.
    Haraldsson, Henrik
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Ebbers, Tino
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Engvall, Jan
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Practical Application of DENSE in Ischemic Heart Disease.2013Konferensbidrag (Refereegranskat)
  • 311.
    Kilebrant, Sophie
    et al.
    Regional Vastra Gotaland Child and Youth Habilitat, Sweden.
    Braathen, Gunnar
    Regional Vastra Gotaland Child and Youth Habilitat, Sweden.
    Emilsson, Roger
    Regional Vastra Gotaland Child and Youth Habilitat, Sweden.
    Glansen, Ulla
    Regional Vastra Gotaland Child and Youth Habilitat, Sweden.
    Soderpalm, Ann-Charlott
    University of Gothenburg, Sweden.
    Zetterlund, Bo
    Regional Vastra Gotaland Child and Youth Habilitat, Sweden.
    Westerberg, Barbro
    Regional Vastra Gotaland Child and Youth Habilitat, Sweden.
    Magnusson, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Swolin-Eide, Diana
    University of Gothenburg, Sweden.
    WHOLE-BODY VIBRATION THERAPY IN CHILDREN WITH SEVERE MOTOR DISABILITIES2015Ingår i: Journal of Rehabilitation Medicine, ISSN 1650-1977, E-ISSN 1651-2081, Vol. 47, nr 3, s. 223-228Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To study the effect of whole-body vibration therapy on bone mass, bone turnover and body composition in severely disabled children. Methods: Nineteen non-ambulatory children aged 5.1-16.3 years (6 males, 13 females) with severe motor disabilities participated in an intervention programme with standing exercise on a self-controlled dynamic platform, which included whole-body vibration therapy (vibration, jump and rotation movements). Whole-body vibration therapy was performed at 40-42 Hz, with an oscillation amplitude of 0.2 mm, 5-15 min/treatment, twice/week for 6 months. Bone mass parameters and bone markers were measured at the study start, and after 6 and 12 months. Results: Whole-body vibration therapy was appreciated by the children. Total-body bone mineral density increased during the study period (p less than0.05). Z-scores for total-body bone mineral density ranged from -5.10 to -0.60 at study start and remained unchanged throughout. Approximately 50% of the subjects had increased levels of carboxy-terminal telopeptides of type I collagen and decreased levels of osteocalcin at the start. Body mass index did not change during the intervention period, but had increased by the 12-month follow-up (pless than 0.05). Conclusion: Whole-body vibration therapy appeared to be well tolerated by children with severe motor disabilities. Total-body bone mineral density increased after 6 months of whole-body vibration therapy. Higher carboxy-terminal telopeptides of type I collagen and lower osteocalcin values indicated that severely disabled children have a reduced capacity for bone acquisition.

  • 312.
    Kissopoulou, Antheia
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Cty Council Jonkoping, Sweden.
    Trinks, Cecilia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Gréen, Anna
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Karlsson, Jan-Erik
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Cty Council Jonkoping, Sweden.
    Jonasson, Jon
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Gunnarsson, Cecilia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik. Region Östergötland, Centrum för verksamhetsstöd och utveckling.
    Homozygous missense MYBPC3 Pro873His mutation associated with increased risk for heart failure development in hypertrophic cardiomyopathy2018Ingår i: ESC Heart Failure, E-ISSN 2055-5822, Vol. 5, nr 4, s. 716-723Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Hypertrophic cardiomyopathy (HCM) is a primary autosomal-dominant disorder of the myocardium with variable expressivity and penetrance. Occasionally, homozygous sarcomere genetic variants emerge while genotyping HCM patients. In these cases, a more severe HCM phenotype is generally seen. Here, we report a case of HCM that was diagnosed clinically at 39years of age. Initial symptoms were shortness of breath during exertion. Successively, he developed a wide array of severe clinical manifestations, which progressed to an ominous end-stage heart failure that resulted in heart transplantation. Genotype analysis revealed a missense MYBPC3 variant NM_000256.3:c.2618Camp;gt;A,p.(Pro873His) that presented in the homozygous form. Conflicting interpretations of pathogenicity have been reported for the Pro873His MYBPC3 variant described here. Our patient, presenting with two copies of the variant and devoid of a normal allele, progressed to end-stage heart failure, which supports the notion of a deleterious effect of this variant in the homozygous form.

  • 313.
    Klingspor, Lena
    et al.
    Karolinska Inst, Sweden.
    Ullberg, Mans
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Rydberg, Johan
    Dept Clin Microbiol, Sweden.
    Kondori, Nahid
    Univ Gothenburg, Sweden.
    Serrander, Lena
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk mikrobiologi.
    Swanberg, Jonas
    Ryhov Hosp, Sweden.
    Nilsson, Kenneth
    Uppsala Univ, Sweden.
    Bengten, Cecilia Jendle
    Karlstad Cent Hosp, Sweden.
    Johansson, Marcus
    Kalmar Cty Hosp, Sweden.
    Granlund, Margareta
    Umea Univ, Sweden.
    Tornqvist, Eva
    Orebro Univ Hosp, Sweden.
    Nyberg, Anders
    Cty Hosp Sundsvall Harnosand, Sweden.
    Kindlund, Karin
    Hallands Hosp, Sweden.
    Ygge, Minna
    Sunderby Hosp, Sweden.
    Kartout-Boukdir, Dalila
    Unilabs AB, Sweden.
    Toepfer, Michael
    Unilabs AB, Sweden.
    Halldin, Eva
    Vasteras Hosp, Sweden.
    Kahlmeter, Gunnar
    Cent Hosp Vaxjo, Sweden.
    Ozenci, Volkan
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Epidemiology of fungaemia in Sweden: A nationwide retrospective observational survey2018Ingår i: Mycoses (Berlin), ISSN 0933-7407, E-ISSN 1439-0507, Vol. 61, nr 10, s. 777-785Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    ObjectivesTo identify the epidemiology and antifungal susceptibilities of Candida spp. among blood culture isolates to identify the epidemiology and antifungal susceptibilities of Candida spp. among blood culture isolates in Sweden. MethodsThe study was a retrospective, observational nationwide laboratory-based surveillance for fungaemia and fungal meningitis and was conducted from September 2015 to August 2016. ResultsIn total, 488 Candida blood culture isolates were obtained from 471 patients (58% males). Compared to our previous study, the incidence of candidaemia has increased from 4.2/100000 (2005-2006) to 4.7/100000 population/year (2015-2016). The three most common Candida spp. isolated from blood cultures were Candida albicans (54.7%), Candida glabrata (19.7%) and species in the Candida parapsilosis complex (9.4%). Candida resistance to fluconazole was 2% in C.albicans and between 0% and 100%, in non-albicans species other than C.glabrata and C.krusei. Resistance to voriconazole was rare, except for C.glabrata, C.krusei and C.tropicalis. Resistance to anidulafungin was 3.8% while no Candida isolate was resistant to amphotericin B. ConclusionsWe report an overall increase in candidaemia but a minor decrease of C.albicans while C.glabrata and C.parapsilosis remain constant over this 10-year period.

  • 314.
    Klintström, Benjamin
    et al.
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. KTH Royal Institute of Technology, School of Technology and Health, Sweden.
    Klintström, Eva
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Linköping.
    Smedby, Örjan
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Linköping. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. KTH Royal Institute of Technology, School of Technology and Health, Sweden.
    Moreno, Rodrigo
    KTH Royal Institute of Technology, School of Technology and Health, Sweden.
    Feature space clustering for trabecular bone segmentation2017Ingår i: Image Analysis - 20th Scandinavian Conference on Image Analysis, SCIA 2017, Proceedings / [ed] Sharma P., Bianchi F., Springer, 2017, Vol. 10270, s. 65-70Konferensbidrag (Refereegranskat)
    Abstract [en]

    Trabecular bone structure has been shown to impact bone strength and fracture risk. In vitro, this structure can be measured by micro-computed tomography (micro-CT). For clinical use, it would be valuable if multi-slice computed tomography (MSCT) could be used to analyse trabecular bone structure. One important step in the analysis is image volume segmentation. Previous segmentation techniques have either been computer resource intensive or produced suboptimal results when used on MSCT data. This paper proposes a new segmentation method that tries to balance good results against computational complexity.

  • 315.
    Klintström, Eva
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Linköping.
    Image Analysis for Trabecular Bone Properties on Cone-Beam CT Data2017Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Trabecular bone structure as well as bone mineral density (BMD) have impact on the biomechanical competence of bone. In osteoporosis-related fractures, there have been shown to exist disconnections in the trabecular network as well as low bone mineral density. Imaging of bone parameters is therefore of importance in detecting osteoporosis. One available imaging device is cone-beam computed tomography (CBCT). This device is often used in pre-operative imaging of dental implants, for which the trabecular network also has great importance.

    Fourteen or 15 trabecular bone specimens from the radius were imaged for conducting this in vitro project.

    The imaging data from one dual-energy X-ray absorptiometry (DXA), two multi-slice computed tomography (MSCT), one high-resolution peripheral quantitative computed tomography (HR-pQCT) and four CBCT devices were segmented using an in-house developed code based on homogeneity thresholding. Seven trabecular microarchitecture parameters, as well as two trabecular bone stiffness parameters, were computed from the segmented data. Measurements from micro-computed tomography (micro-CT) data of the same bone specimens were regarded as gold standard.

    Correlations between MSCT and micro-CT data showed great variations, depending on device, imaging parameters and between the bone parameters. Only the bone-volume fraction (BV/TV) parameter was stable with strong correlations. Regarding both HR-pQCT and CBCT, the correlations to micro-CT were strong for bone structure parameters as well as bone stiffness parameters. The CBCT device 3D Accuitomo showed the strongest correlations, but overestimated BV/TV more than three times compared to micro-CT. The imaging protocol most often used in clinical imaging practice at our clinic demonstrated strong correlations as well as low radiation dose.

    CBCT data of trabecular bone can be used for analysing trabecular bone properties, like bone microstructure and bone biomechanics, showing strong correlations to the reference method of micro-CT. The results depend on choice of CBCT device as well as segmentation method used. The in-house developed code based on homogeneity thresholding is appropriate for CBCT data. The overestimations of BV/TV must be considered when estimating bone properties in future clinical dental implant and osteoporosis research.

    Delarbeten
    1. Trabecular bone structure parameters from 3D image processing of clinical multi-slice and cone-beam computed tomography data
    Öppna denna publikation i ny flik eller fönster >>Trabecular bone structure parameters from 3D image processing of clinical multi-slice and cone-beam computed tomography data
    2014 (Engelska)Ingår i: Skeletal Radiology, ISSN 0364-2348, E-ISSN 1432-2161, Vol. 43, nr 2, s. 197-204Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Objective

    Bone strength depends on both mineral content and bone structure. The aim of this in vitro study was to develop a method of quantitatively assessing trabecular bone structure by applying three-dimensional image processing to data acquired with multi-slice and cone-beam computed tomography using micro-computed tomography as a reference.

    Materials and Methods

    Fifteen bone samples from the radius were examined. After segmentation, quantitative measures of bone volume, trabecular thickness, trabecular separation, trabecular number, trabecular nodes, and trabecular termini were obtained.

    Results

    The clinical machines overestimated bone volume and trabecular thickness and underestimated trabecular nodes and number, but cone-beam CT to a lesser extent. Parameters obtained from cone beam CT were strongly correlated with μCT, with correlation coefficients between 0.93 and 0.98 for all parameters except trabecular termini.

    Conclusions

    The high correlation between cone-beam CT and micro-CT suggest the possibility of quantifying and monitoring changes of trabecular bone microarchitecture in vivo using cone beam CT.

    Ort, förlag, år, upplaga, sidor
    Springer, 2014
    Nyckelord
    Trabecular bone structure; Cone-beam computed tomography; Micro computed tomography; Multi-slice computed tomography; Bone segmentation
    Nationell ämneskategori
    Radiologi och bildbehandling
    Identifikatorer
    urn:nbn:se:liu:diva-102880 (URN)10.1007/s00256-013-1766-5 (DOI)000329108500011 ()
    Tillgänglig från: 2014-01-07 Skapad: 2014-01-07 Senast uppdaterad: 2017-12-06Bibliografiskt granskad
    2. Trabecular bone histomorphometric measurements and contrast-to-noise ratio in CBCT
    Öppna denna publikation i ny flik eller fönster >>Trabecular bone histomorphometric measurements and contrast-to-noise ratio in CBCT
    Visa övriga...
    2014 (Engelska)Ingår i: Dento-Maxillo-Facial Radiology, ISSN 0250-832X, E-ISSN 1476-542X, Vol. 43, nr 8, s. 20140196-Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Objectives: The aim of this study was to evaluate how imaging parameters at clinical dental CBCT affect the accuracy in quantifying trabecular bone structures, contrast-to-noise ratio (CNR) and radiation dose.

    Methods: 15 radius samples were examined using CBCT (Accuitomo FPD; J. Morita Mfg., Kyoto, Japan). Nine imaging protocols were used, differing in current, voltage, rotation degree, voxel size, imaging area and rotation time. Radiation doses were measured using a KAP-meter. After segmentation, six bone structure parameters and CNR were quantified. Micro-CT images with an isotropic resolution of 20 microns were used as a gold standard.

    Results: Structure parameters obtained by CBCT were strongly correlated to those by micro CT, with correlation coefficients .0.90 for all studied parameters. Bone volume and trabecular thickness were not affected by changes in imaging parameters. Increased tube current from 5 to 8 mA, decreased isotropic voxel size from 125 to 80 microns and decreased rotation anglefrom 360° to 180° affected correlations for trabecular termini negatively. Decreasing rotation degree also weakened correlations for trabecular separation and trabecular number at 80 microns voxel size. Changes in the rotation degree and tube current affected CNR significantly. The radiation dose varied between 269 and 1284 mGy cm2.

    Conclusions: Trabecular bone structure can be accurately quantified by clinical dental CBCT in vitro, and the obtained structure parameters are strongly related to those obtained by micro CT. A fair CNR and strong correlations can be obtained with a low radiation dose, indicating the possibility for monitoring trabecular bone structure also in vivo.

    Ort, förlag, år, upplaga, sidor
    British Institute of Radiology, 2014
    Nyckelord
    CBCT; micro-computed tomography; trabecular 7 bone; histomorphometry; bone segmentation; osteoporosis
    Nationell ämneskategori
    Radiologi och bildbehandling
    Identifikatorer
    urn:nbn:se:liu:diva-111163 (URN)10.1259/dmfr.20140196 (DOI)000346231400002 ()25168811 (PubMedID)
    Tillgänglig från: 2014-10-09 Skapad: 2014-10-09 Senast uppdaterad: 2017-12-05Bibliografiskt granskad
    3. Predicting Trabecular Bone Stiffness from Clinical Cone-Beam CT and HR-pQCT Data; an In Vitro Study Using Finite Element Analysis
    Öppna denna publikation i ny flik eller fönster >>Predicting Trabecular Bone Stiffness from Clinical Cone-Beam CT and HR-pQCT Data; an In Vitro Study Using Finite Element Analysis
    Visa övriga...
    2016 (Engelska)Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 8, artikel-id e0161101Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Stiffness and shear moduli of human trabecular bone may be analyzed in vivo by finite element (FE) analysis from image data obtained by clinical imaging equipment such as high resolution peripheral quantitative computed tomography (HR-pQCT). In clinical practice today, this is done in the peripheral skeleton like the wrist and heel. In this cadaveric bone study, fourteen bone specimens from the wrist were imaged by two dental cone beam computed tomography (CBCT) devices and one HR-pQCT device as well as by dual energy X-ray absorptiometry (DXA). Histomorphometric measurements from micro-CT data were used as gold standard. The image processing was done with an in-house developed code based on the automated region growing (ARG) algorithm. Evaluation of how well stiffness (Young’s modulus E3) and minimum shear modulus from the 12, 13, or 23 could be predicted from the CBCT and HR-pQCT imaging data was studied and compared to FE analysis from the micro-CT imaging data. Strong correlations were found between the clinical machines and micro-CT regarding trabecular bone structure parameters, such as bone volume over total volume, trabecular thickness, trabecular number and trabecular nodes (varying from 0.79 to 0.96). The two CBCT devices as well as the HR-pQCT showed the ability to predict stiffness and shear, with adjusted R2 -values between 0.78 and 0.92, based on data derived through our in-house developed code based on the ARG algorithm. These findings indicate that clinically used CBCT may be a feasible method for clinical studies of bone structure and mechanical properties in future osteoporosis research.

    Ort, förlag, år, upplaga, sidor
    Public library of science, 2016
    Nationell ämneskategori
    Klinisk medicin
    Identifikatorer
    urn:nbn:se:liu:diva-130798 (URN)10.1371/journal.pone.0161101 (DOI)000381381100120 ()27513664 (PubMedID)
    Tillgänglig från: 2016-08-24 Skapad: 2016-08-24 Senast uppdaterad: 2018-03-26Bibliografiskt granskad
  • 316.
    Klintström, Eva
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Linköping. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Klintstrom, Benjamin
    KTH Royal Inst Technol, Sweden.
    Pahr, Dieter
    Vienna Univ Technol, Austria.
    Brismar, Torkel B.
    Karolinska Univ Hosp, Sweden; Karolinska Univ Hosp, Sweden.
    Smedby, Örjan
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Linköping. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. KTH Royal Inst Technol, Sweden.
    Moreno, Rodrigo
    KTH Royal Inst Technol, Sweden.
    Direct estimation of human trabecular bone stiffness using cone beam computed tomography2018Ingår i: Oral surgery, oral medicine, oral pathology and oral radiology, ISSN 2212-4403, E-ISSN 2212-4411, Vol. 126, nr 1, s. 72-82Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives. The aim of this study was to evaluate the possibility of estimating the biomechanical properties of trabecular bone through finite element simulations by using dental cone beam computed tomography data. Study Design. Fourteen human radius specimens were scanned in 3 cone beam computed tomography devices: 3-D Accuitomo 80 (J. Morita MFG., Kyoto, Japan), NewTom 5 G (QR Verona, Verona, Italy), and Verity (Planmed, Helsinki, Finland). The imaging data were segmented by using 2 different methods. Stiffness (Young modulus), shear moduli, and the size and shape of the stiffness tensor were studied. Corresponding evaluations by using micro-CT were regarded as the reference standard. Results. The 3-D Accuitomo 80 (J. Morita MFG., Kyoto, Japan) showed good performance in estimating stiffness and shear moduli but was sensitive to the choice of segmentation method. Newtom 5 G (QR Verona, Verona, Italy) and Verity (Planmed, Helsinki, Finland) yielded good correlations, but they were not as strong as Accuitomo 80 U. Morita MFG., Kyoto, Japan). The cone beam computed tomography devices overestimated both stiffness and shear compared with the micro-CT estimations. Conclusions. Finite element-based calculations of biomechanics from cone beam computed tomography data are feasible, with strong correlations for the Accuitomo 80 scanner a. Morita MFG., Kyoto, Japan) combined with an appropriate segmentation method. Such measurements might be useful for predicting implant survival by in vivo estimations of bone properties.

  • 317.
    Klintström, Eva
    et al.
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Klintström, Benjamin
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Medicinska fakulteten.
    Brismar, Torkel
    Karolinska Institutet, Stockholm, Sweden.
    Smedby, Örjan
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Linköping. KTH Royal Institute of Technology, Stockholm, Sweden.
    Moreno, Rodrigo
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten. KTH Royal Institute of Technology, Stockholm, Sweden.
    Clinical dental cone beam computed tomography - a tool for monitoring trabecular bone structure?2015Konferensbidrag (Refereegranskat)
    Abstract [en]

    Purpose

    The aim of this in vitro study was to develop a method for quantitative assessment of trabecular bone micro-architecture by using three-dimensional image processing. The imaging data were acquired with cone beam computed tomography (CBCT), traditionally used for facial and temporal bone imaging but also applicable for peripheral skeleton, and with a dedicated high resolution peripheral computed tomograph (HRpQCT), used for in vivo measurements in bone research. The data from micro-computed tomography (µCT) was used as reference.

     

    Methods & Materials

    15 bone samples from the radius, were examined by CBCT and HRpQCT at a resolution of 80 and 82 µm, respectively. After segmentation, the bone structure parameters bone volume (BV/TV), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), trabecular number (Tb.N), trabecular nodes (Tb.Nd) and trabecular termini (Tb.Tm) were quantified. Calculations were performed on an ordinary PC using a MATLAB developed in house.

     

    Results

    CBCT and HRpQCT overestimated BV/TV and Tb.Th approximately three times, compared to µCT. On the other hand Tb.Nd was highly underestimated. All parameters from CBCT were strongly correlated to µCT, with correlation coefficients above 0.91 for all studied parameters (0.92-0.98) except for Tb.Tm with a correlation of 0.83. For HRpQCT the correlations were slightly weaker, varying from 0.78 to 0.95.

     

    Conclusion

    The strong correlations between bone structure parameters computed from CBCT and µCT suggests that CBCT may be a good alternative to HRpQCT for monitoring trabecular bone microarchitecture in vivo.

     

  • 318.
    Klintström, Eva
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Klintström, Benjamin
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Moreno, Rodrigo
    KTH Royal Institute of Technology, School of Technology and Health, Huddinge, Stockholm, Sweden.
    Brismar, Torkel B
    Department of Clinical Science, Intervention and Technology at Karolinska Institutet, Stockholm, Sweden; Department of Radiology, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
    Pahr, Dieter H
    Institute of Lightweight Design and Structural Biomechanics, TU Wien, Vienna, Austria.
    Smedby, Örjan
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Linköping.
    Predicting Trabecular Bone Stiffness from Clinical Cone-Beam CT and HR-pQCT Data; an In Vitro Study Using Finite Element Analysis2016Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 8, artikel-id e0161101Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Stiffness and shear moduli of human trabecular bone may be analyzed in vivo by finite element (FE) analysis from image data obtained by clinical imaging equipment such as high resolution peripheral quantitative computed tomography (HR-pQCT). In clinical practice today, this is done in the peripheral skeleton like the wrist and heel. In this cadaveric bone study, fourteen bone specimens from the wrist were imaged by two dental cone beam computed tomography (CBCT) devices and one HR-pQCT device as well as by dual energy X-ray absorptiometry (DXA). Histomorphometric measurements from micro-CT data were used as gold standard. The image processing was done with an in-house developed code based on the automated region growing (ARG) algorithm. Evaluation of how well stiffness (Young’s modulus E3) and minimum shear modulus from the 12, 13, or 23 could be predicted from the CBCT and HR-pQCT imaging data was studied and compared to FE analysis from the micro-CT imaging data. Strong correlations were found between the clinical machines and micro-CT regarding trabecular bone structure parameters, such as bone volume over total volume, trabecular thickness, trabecular number and trabecular nodes (varying from 0.79 to 0.96). The two CBCT devices as well as the HR-pQCT showed the ability to predict stiffness and shear, with adjusted R2 -values between 0.78 and 0.92, based on data derived through our in-house developed code based on the ARG algorithm. These findings indicate that clinically used CBCT may be a feasible method for clinical studies of bone structure and mechanical properties in future osteoporosis research.

  • 319.
    Klionsky, Daniel J.
    et al.
    University of Michigan, Department of Molecular, Cellular, and Developmental Biology, Ann Arbor, MI, USA; University of Michigan, Life Sciences Institute, Ann Arbor, MI, USA .
    Boman, Andrea
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Kågedal, Katarina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Kurz, Tino
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten.
    Mohseni, Simin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Öllinger, Karin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Zughaier, Susu M.
    Emory University, School of Medicine, Department of Microbiology and Immunology, Atlanta, GA, USA.
    Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)2016Ingår i: Autophagy, ISSN 1554-8627, E-ISSN 1554-8635, Vol. 2, nr 1, s. 1-222Artikel, forskningsöversikt (Refereegranskat)
  • 320.
    Koppal, Sandeep
    et al.
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten.
    Warntjes, Marcel
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Fysiologiska kliniken US. SyntheticMR AB, Linköping, Sweden.
    Swann, Jeremy
    School of Computing, University of Leeds, Leeds, United Kingdom.
    Dyverfeldt, Petter
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Fysiologiska kliniken US.
    Kihlberg, Johan
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Linköping. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Moreno, Rodrigo
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. KTH, Royal Institute of Technology, Stockholm, Sweden.
    Magee, Derek
    School of Computing, University of Leeds, Leeds, United Kingdom.
    Roberts, Nicholas
    Division of Brain Sciences, Department of Medicine, Institute of Neurology, Imperial College, London, United Kingdom.
    Zachrisson, Helene
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Fysiologiska kliniken US.
    Forssell, Claes
    Region Östergötland, Hjärt- och Medicincentrum, Thorax-kärlkliniken i Östergötland.
    Länne, Toste
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Thorax-kärlkliniken i Östergötland.
    Treanor, Darren
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Department of Pathology and Tumour Biology, Leeds Institute of Molecular Medicine, University of Leeds, Leeds, United Kingdom.
    de Muinck, Ebo
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Quantitative Fat and R2* Mapping In Vivo to Measure Lipid-Rich Necrotic Core and Intraplaque Hemorrhage in Carotid Atherosclerosis2017Ingår i: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 78, nr 1, s. 285-296Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: The aim of this work was to quantify the extent of lipid-rich necrotic core (LRNC) and intraplaque hemorrhage (IPH) in atherosclerotic plaques.

    Methods: Patients scheduled for carotid endarterectomy underwent four-point Dixon and T1-weighted magnetic resonance imaging (MRI) at 3 Tesla. Fat and R2* maps were generated from the Dixon sequence at the acquired spatial resolution of 0.60 × 0.60 × 0.70 mm voxel size. MRI and three-dimensional (3D) histology volumes of plaques were registered. The registration matrix was applied to segmentations denoting LRNC and IPH in 3D histology to split plaque volumes in regions with and without LRNC and IPH.

    Results: Five patients were included. Regarding volumes of LRNC identified by 3D histology, the average fat fraction by MRI was significantly higher inside LRNC than outside: 12.64 ± 0.2737% versus 9.294 ± 0.1762% (mean ± standard error of the mean [SEM]; P < 0.001). The same was true for IPH identified by 3D histology, R2* inside versus outside IPH was: 71.81 ± 1.276 s−1 versus 56.94 ± 0.9095 s−1 (mean ± SEM; P < 0.001). There was a strong correlation between the cumulative fat and the volume of LRNC from 3D histology (R2 = 0.92) as well as between cumulative R2* and IPH (R2 = 0.94).

    Conclusion: Quantitative mapping of fat and R2* from Dixon MRI reliably quantifies the extent of LRNC and IPH.

  • 321.
    Kotti, Angeliki
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Linköping. Linköpings universitet, Institutionen för medicin och hälsa.
    Holmqvist, Annica
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US. Linköpings universitet, Medicinska fakulteten.
    Albertsson, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US. Linköpings universitet, Medicinska fakulteten.
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Survival benefit of statins in older patients with rectal cancer: A Swedish population-based cohort study2019Ingår i: Journal of Geriatric Oncology, ISSN 1879-4068, E-ISSN 1879-4076, Vol. 10, nr 5, s. 690-697Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives

    Increasing evidence suggests that statins may have antitumor effects but their rolein rectal cancer appears inconclusive. The aim of this study was to investigate whether statins may have an impact on survival of older and younger patients with rectal cancer.

    Materials and Methods

    This study included 238 patients ≥70 years and 227 patients <70 years old, from the Southeast Health Care Region of Sweden, who were diagnosed with rectal adenocarcinoma between 2004 and 2013.

    Results

    In the older group (n = 238), statin use at the time of diagnosis was related to better cancer-specific survival (CSS) and overall survival (OS), compared to non-use (CSS: Hazard Ratio (HR), 0.37; 95% CI, 0.19–0.72; P = .003; OS: HR, 0.62; 95% CI, 0.39–0.96; P = .032). In the older group with stages I-III disease (n = 199), statin use was associated with better disease-free survival (DFS) compared to non use (HR, 0.18; 95% CI, 0.06–0.59; P = .005). The improvement of CSS, OS and DFS remained significant after adjusting for potential confounders. In the older group with stage III disease, statin users had better CSS and DFS compared to non-users (log rank P = .043; log-rank P = .028, respectively). In the older group with short course radiotherapy, statin use was related to better CSS (log-rank P = .032). No such association was present in the younger group.

    Conclusion

    Statin use was related to improved survival in older patients with rectal cancer.

    This observation is important given the low cost and safety of statins as a drug.

  • 322.
    Krauss, Tobias
    et al.
    Univ Freiburg, Germany.
    Ferrara, Alfonso Massimiliano
    IRCCS, Italy.
    Links, Thera P.
    Univ Groningen, Netherlands.
    Wellner, Ulrich
    Univ Lubeck, Germany.
    Bancoss, Irina
    Mayo Clin, MN USA.
    Kvachenyuk, Andrey
    NAMS Ukraine, Ukraine.
    Gomez de las Heras, Karim Villar
    Serv Salud Castilla La Mancha SESCAM, Spain.
    Yukina, Marina Y.
    Endocrinol Res Ctr, Russia.
    Petrov, Roman
    Bakhrushin Bros Moscow City Hosp, Russia.
    Bullivant, Garrett
    Univ Hlth Network, Canada.
    von Duecker, Laura
    Albert Ludwigs Univ, Germany.
    Jadhav, Swati
    King Edward Mem Hosp, India.
    Ploeckinger, Ursula
    Charite Univ Med Berlin, Germany.
    Welin, Staffan
    Uppsala Univ Hosp, Sweden.
    Schalin-Jantti, Camilla
    Univ Helsinki, Finland; Helsinki Univ Hosp, Finland.
    Gimm, Oliver
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Pfeifer, Marija
    Univ Med Ctr, Slovenia.
    Ngeow, Joanne
    Nanyang Technol Univ, Singapore; Nanyang Technol Univ, Singapore.
    Hasse-Lazar, Kornelia
    MSC Mem Inst, Poland.
    Sanso, Gabriela
    Hosp Ninos Dr Ricardo Gutierrez, Argentina.
    Qi, Xiaoping
    Wenzhou Med Univ, Peoples R China.
    Ugurlu, M. Umit
    Marmara Univ, Turkey.
    Diaz, Rene E.
    Hosp Salvador, Chile.
    Wohllk, Nelson
    Univ Chile, Chile.
    Peczkowska, Mariola
    Inst Cardiol, Poland.
    Aberle, Jens
    Univ Med Ctr Hamburg Eppendorf, Germany.
    Lourenco Jr, Delmar M.
    Univ Sao Paulo, Brazil; Univ Sao Paulo, Brazil.
    Pereira, Maria A. A.
    Univ Sao Paulo, Brazil.
    Fragoso, Maria C. B. V
    Univ Sao Paulo, Brazil; Univ Sao Paulo, Brazil.
    Hoff, Ana O.
    Univ Sao Paulo, Brazil; Univ Sao Paulo, Brazil.
    Almeida, Madson Q.
    Univ Sao Paulo, Brazil; Univ Sao Paulo, Brazil.
    Violante, Alice H. D.
    Univ Fed Rio de Janeiro, Brazil.
    Ouidute, Ana R. P.
    Fed Univ Ceara UFC, Brazil.
    Zhang, Zhewei
    Zhejiang Univ, Peoples R China.
    Recasens, Monica
    Hosp Univ Girona, Spain.
    Robles Diaz, Luis
    Hosp Univ 12 Octubre, Spain.
    Kunavisarut, Tada
    Mahidol Univ, Thailand.
    Wannachalee, Taweesak
    Mahidol Univ, Thailand.
    Sirinvaravong, Sirinart
    Mahidol Univ, Thailand.
    Jonasch, Eric
    Univ Texas MD Anderson Canc Ctr, TX 77030 USA.
    Grozinsky-Glasberg, Simona
    Hadassah Hebrew Univ, Israel.
    Fraenkel, Merav
    Hadassah Hebrew Univ, Israel.
    Beltsevich, Dmitry
    Endocrinol Res Ctr, Russia.
    Egorov, Viacheslav I
    Bakhrushin Bros Moscow City Hosp, Russia.
    Bausch, Dirk
    Univ Lubeck, Germany.
    Schott, Matthias
    Heinrich Heine Univ, Germany.
    Tiling, Nikolaus
    Charite Univ Med Berlin, Germany.
    Pennelli, Gianmaria
    Univ Padua, Italy.
    Zschiedrich, Stefan
    Albert Ludwigs Univ, Germany.
    Daerr, Roland
    Albert Ludwigs Univ, Germany; Univ Freiburg, Germany.
    Ruf, Juri
    Albert Ludwigs Univ, Germany.
    Denecke, Timm
    Charite Univ Med Berlin, Germany.
    Link, Karl-Heinrich
    Asklepios Paulinen Klin, Germany.
    Zovato, Stefania
    IRCCS, Italy.
    von Dobschuetz, Ernst
    Acad Teaching Hosp Univ Hamburg, Germany.
    Yaremchuk, Svetlana
    NAMS Ukraine, Ukraine.
    Amthauer, Holger
    Charite Univ Med Berlin, Germany.
    Makay, Ozer
    Dept Gen Surg, Turkey.
    Patocs, Attila
    Semmelweis Univ, Hungary; Semmelweis Univ, Hungary.
    Walz, Martin K.
    Huyssens Fdn Clin, Germany.
    Huber, Tobias B.
    Univ Med Ctr Hamburg Eppendorf, Germany.
    Seufert, Jochen
    Univ Freiburg, Germany.
    Hellman, Per
    Uppsala Univ, Sweden.
    Ekaterina, Raymond H.
    Univ Toronto, Canada; Mt Sinai Hosp, Canada.
    Kuchinskaya, Ekaterina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Schiavi, Francesca
    IRCCS, Italy.
    Malinoc, Angelica
    Albert Ludwigs Univ, Germany.
    Reisch, Nicole
    Ludwigs Maximilians Univ Munich, Germany.
    Jarzab, Barbara
    MSC Mem Inst, Poland.
    Barontini, Marta
    Hosp Ninos Dr Ricardo Gutierrez, Argentina.
    Januszewicz, Andrzej
    Inst Cardiol, Poland.
    Shah, Nalini
    King Edward Mem Hosp, India.
    Young, William F. Jr.
    Mayo Clin, MN USA.
    Opocher, Giuseppe
    Veneto Inst Oncol IOV IRCCS, Italy.
    Eng, Charis
    Cleveland Clin, OH 44106 USA.
    Neumann, Hartmut P. H.
    Albert Ludwigs Univ, Germany.
    Bausch, Birke
    Univ Freiburg, Germany.
    Preventive medicine of von Hippel-Lindau disease-associated pancreatic neuroendocrine tumors2018Ingår i: Endocrine-Related Cancer, ISSN 1351-0088, E-ISSN 1479-6821, Vol. 25, nr 9, s. 783-793Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Pancreatic neuroendocrine tumors (PanNETs) are rare in von Hippel-Lindau disease (VHL) but cause serious morbidity and mortality. Management guidelines for VHL-PanNETs continue to be based on limited evidence, and survival data to guide surgical management are lacking. We established the European-American-Asian-VHL-PanNET-Registry to assess data for risks for metastases, survival and long-term outcomes to provide best management recommendations. Of 2330 VHL patients, 273 had a total of 484 PanNETs. Median age at diagnosis of PanNET was 35 years (range 10-75). Fifty-five (20%) patients had metastatic PanNETs. Metastatic PanNETs were significantly larger (median size 5 vs 2 cm; P amp;lt; 0.001) and tumor volume doubling time (TVDT) was faster (22 vs 126 months; P = 0.001). All metastatic tumors were amp;gt;= 2.8 cm. Codons 161 and 167 were hotspots for VHL germline mutations with enhanced risk for metastatic PanNETs. Multivariate prediction modeling disclosed maximum tumor diameter and TVDT as significant predictors for metastatic disease (positive and negative predictive values of 51% and 100% for diameter cut-off amp;gt;= 2.8 cm, 44% and 91% for TVDT cut-off of amp;lt;= 24 months). In 117 of 273 patients, PanNETs amp;gt; 1.5 cm in diameter were operated. Ten-year survival was significantly longer in operated vs non-operated patients, in particular for PanNETs amp;lt; 2.8 cm vs amp;gt;= 2.8 cm (94% vs 85% by 10 years; P = 0.020; 80% vs 50% at 10 years; P = 0.030). This study demonstrates that patients with PanNET approaching the cut-off diameter of 2.8 cm should be operated. Mutations in exon 3, especially of codons 161/167 are at enhanced risk for metastatic PanNETs. Survival is significantly longer in operated non-metastatic VHL-PanNETs.

  • 323.
    Krishnan, Harini
    et al.
    SUNY Stony Brook, NY 11794 USA.
    Rayes, Julie
    Univ Birmingham, England.
    Miyashita, Tomoyuki
    Natl Canc Ctr, Japan; Univ Tokyo, Japan.
    Ishii, Genichiro
    Natl Canc Ctr, Japan; Univ Tokyo, Japan.
    Retzbach, Edward P.
    Rowan Univ, NJ USA.
    Sheehan, Stephanie A.
    Rowan Univ, NJ USA.
    Takemoto, Ai
    Japanese Fdn Canc Res, Japan.
    Chang, Yao-Wen
    Chang Gung Univ, Taiwan.
    Yoneda, Kazue
    Univ Occupat and Environm Hlth, Japan.
    Asai, Jun
    Kyoto Prefectural Univ Med, Japan.
    Jensen, Lasse
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk farmakologi.
    Chalise, Lushun
    Nagoya Univ, Japan.
    Natsume, Atsushi
    Nagoya Univ, Japan.
    Goldberg, Gary S.
    Rowan Univ, NJ USA.
    Podoplanin: An emerging cancer biomarker and therapeutic target2018Ingår i: Cancer Science, ISSN 1347-9032, E-ISSN 1349-7006, Vol. 109, nr 5, s. 1292-1299Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Podoplanin (PDPN) is a transmembrane receptor glycoprotein that is upregulated on transformed cells, cancer associated fibroblasts and inflammatory macrophages that contribute to cancer progression. In particular, PDPN increases tumor cell clonal capacity, epithelial mesenchymal transition, migration, invasion, metastasis and inflammation. Antibodies, CAR-T cells, biologics and synthetic compounds that target PDPN can inhibit cancer progression and septic inflammation in preclinical models. This review describes recent advances in how PDPN may be used as a biomarker and therapeutic target for many types of cancer, including glioma, squamous cell carcinoma, mesothelioma and melanoma.

  • 324.
    Kristoffersen, Laila
    et al.
    Department of Neonatology, St. Olavs University Hospital, Trondheim, Norway; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
    Støen, Ragnhild
    Department of Neonatology, St. Olavs University Hospital, Trondheim, Norway; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
    Bergseng, Håkon
    Department of Neonatology, St. Olavs University Hospital, Trondheim, Norway; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
    Follestad, Turid
    Department of Public Health and Nursing, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
    Theodorsson, Elvar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Vederhus, Bente
    Department of Pediatrics, Haukeland University Hospital, Bergen, Norway; Faculty of Health and Social Science, Western Norway University of Applied Sciences, Bergen, Norway.
    Adde, Lars
    Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Clinic of Clinical Services, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
    Austeng, Dordi
    Department of Neuromedicine and Movement Science (INB), Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Department of Ophthalmology, St. Olavs University Hospital, Trondheim, Norway.
    Skin-to-skin contact during eye examination did not reduce pain compared to standard care with parental support in preterm infants2019Ingår i: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 108, nr 8, s. 1434-1440Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIM: We compared the pain relieving effect of skin-to-skin contact versus standard care in the incubator during screening for retinopathy of prematurity.

    METHODS: This randomised crossover study included 35 preterm infants of less than 32 weeks of gestational age admitted to St Olavs University Hospital, Trondheim, Norway, between January 2014 and June 2016. Randomisation was for skin-to-skin with one of the parents or standard care with supportive positioning by parents for the first of two consecutive eye examinations. The pain score was measured twice using the Premature Infant Pain Profile (PIPP) during and after the eye examination. The infants' movement activity was video recorded after the examination.

    RESULTS: There was no difference in mean pain scores with skin-to-skin contact versus standard care during (10.2 vs. 10.3, p = 0.91) or after (7.0 vs. 6.8, p = 0.76) the procedure. Independent of the randomisation group, PIPP scores were lower than previous comparable studies have found. Bouts of movement activity were also the same whether the examination was conducted in skin-to-skin position or in the incubator (p = 0.91).

    CONCLUSION: Skin-to-skin contact during the eye examination did not provide additional pain relief compared to standard care where the parents were already a part of the multidimensional approach.

  • 325.
    Krynitz, B.
    et al.
    Karolinska University of Labs, Sweden; Karolinska Institute, Sweden.
    Olsson, H.
    Karolinska Institute, Sweden.
    Lundh Rozell, Barbro
    Region Östergötland, Diagnostikcentrum, Klinisk patologi och klinisk genetik. Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten.
    Lindelof, B.
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Edgren, G.
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Smedby, K. E.
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Risk of basal cell carcinoma in Swedish organ transplant recipients: a population-based study2016Ingår i: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 174, nr 1, s. 95-103Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Risk of basal cell carcinoma (BCC) has been reported to be several-fold increased among organ transplant recipients (OTRs). However, due to lack of reliable BCC registration, population-based risk estimates are scarce. Objectives To characterize risk of BCC among OTRs compared with the general population, and contrast with risk of cutaneous squamous cell carcinoma (SCC). Subjects and methods OTRs transplanted during 2004-2011 were identified through national healthcare registers and linked with the nationwide Swedish BCC Register initialized in 2004. Relative risk of BCC was expressed as standardized incidence ratios (SIR) with 95% confidence intervals (CI). Results Altogether, 4023 transplanted patients developed 341 BCCs during follow-up. Compared with the general population, the relative risk of BCC was increased sixfold (SIR 6.1, 95% CI 5.4-6.9). The risk was higher in kidney and heart/lung than in liver recipients (SIRkidney 7.2, 6.3-8.3; SIRheart/lung 5.8, 4.0-8.2; SIRliver 2.6, 1.7-4.0), and risk increased with time since transplantation (P-trend &lt; 0.01). The SCC to BCC ratio was 1 : 1.7 and BCC developed earlier after transplantation than SCC. Distribution of anatomical sites and histological types did not differ substantially between OTR- and population-BCCs. Conclusions Risk of BCC was strikingly elevated in OTRs compared with the general population. Risk was higher in kidney recipients and increased with follow-up time. These findings support a tumour-promoting effect of immunosuppressive drugs in BCC development. The low SCC to BCC ratio was possibly attributed to short follow-up time.

  • 326.
    Krynitz, Britta
    et al.
    Karolinska University of Labs, Sweden; Karolinska University, Sweden.
    Lundh Rozell, Barbro
    Region Östergötland, Diagnostikcentrum, Klinisk patologi och klinisk genetik. Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten.
    Lyth, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för hälso- och vårdutveckling, Regionalt cancercentrum.
    Smedby, Karin E.
    Karolinska University Hospital, Sweden.
    Lindelof, Bernt
    Karolinska University, Sweden; Karolinska University, Sweden.
    Cutaneous malignant melanoma in the Swedish organ transplantation cohort: A study of clinicopathological characteristics and mortality2015Ingår i: The Journal of American Academy of Dermatology, ISSN 0190-9622, E-ISSN 1097-6787, Vol. 73, nr 1, s. 106-U190Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Risk of cutaneous melanoma is increased among organ transplant recipients (OTRs) but outcome has rarely been evaluated. Objective: We sought to assess melanoma characteristics and prognosis among OTRs versus the general population. Methods: Using Swedish health care registers, we identified melanomas in OTRs (n = 49) and in the general population (n = 22,496), given a diagnosis between 1984 and 2008 and followed up through December 31, 2012. Tumor slides of posttransplantation melanomas were reviewed. Odds ratios for comparison of histopathological characteristics and hazard ratios of melanoma-specific death were calculated. Results: Among OTRs the trunk was the most common anatomic melanoma site (50% among female vs 51% among male) and 73% (n = 36) of all melanomas were histologically associated with a melanocytic nevus, 63% (n = 31) atypical/dysplastic. Compared with population melanomas, posttransplantation melanomas were more advanced at diagnosis (Clark level III-V: odds ratio 2.2 [95% confidence interval 1.01-4.7, P = .03], clinical stages III-IV: odds ratio 4.2 [1.6-10.8, P = .003]). Risk of melanoma-specific death was increased among OTRs: adjusted hazard ratio 3.0 (1.7-5.3, P = .0002). Limitations: Only posttransplantation melanoma slides were reviewed. Conclusions: Melanomas were more advanced at diagnosis and melanoma-specific survival was poorer in OTRs than in the general population. Prophylactic excision of truncal nevi among OTRs may be advised.

  • 327.
    Kuchenbaecker, Karoline B.
    et al.
    University of Cambridge, England.
    Ramus, Susan J.
    University of So Calif, CA USA.
    Tyrer, Jonathan
    University of Cambridge, England.
    Lee, Andrew
    University of Cambridge, England; University of So Calif, CA USA.
    Shen, Howard C.
    University of So Calif, CA USA.
    Beesley, Jonathan
    QIMR Berghofer Medical Research Institute, Australia.
    Lawrenson, Kate
    University of So Calif, CA USA.
    McGuffog, Lesley
    University of Cambridge, England.
    Healey, Sue
    QIMR Berghofer Medical Research Institute, Australia.
    Lee, Janet M.
    University of So Calif, CA USA.
    Spindler, Tassja J.
    University of So Calif, CA USA.
    Lin, Yvonne G.
    University of So Calif, CA USA.
    Pejovic, Tanja
    Oregon Health and Science University, OR 97201 USA; Knight Cancer Institute, OR USA.
    Bean, Yukie
    Oregon Health and Science University, OR 97201 USA; Knight Cancer Institute, OR USA.
    Li, Qiyuan
    Centre Funct Cancer Epigenet, MA USA.
    Coetzee, Simon
    University of Sao Paulo, Brazil; Centre Integrat Syst Biol, Brazil.
    Hazelett, Dennis
    University of So Calif, CA USA; University of So Calif, CA USA.
    Miron, Alexander
    Case Western Reserve University, OH 44106 USA.
    Southey, Melissa
    University of Melbourne, Australia.
    Beth Terry, Mary
    Columbia University, NY USA.
    Goldgar, David E.
    University of Utah, UT USA.
    Buys, Saundra S.
    University of Utah, UT USA.
    Janavicius, Ramunas
    Vilnius University Hospital Santariskiu Clin, Lithuania; State Research Institute Centre Innovat Med, Lithuania.
    Dorfling, Cecilia M.
    University of Pretoria, South Africa.
    van Rensburg, Elizabeth J.
    University of Pretoria, South Africa.
    Neuhausen, Susan L.
    City Hope National Medical Centre, CA 91010 USA.
    Chun Ding, Yuan
    City Hope National Medical Centre, CA 91010 USA.
    Hansen, Thomas V. O.
    University of Copenhagen Hospital, Denmark.
    Jonson, Lars
    University of Copenhagen Hospital, Denmark.
    Gerdes, Anne-Marie
    University of Copenhagen Hospital, Denmark.
    Ejlertsen, Bent
    University of Copenhagen Hospital, Denmark.
    Barrowdale, Daniel
    University of Cambridge, England.
    Dennis, Joe
    University of Cambridge, England; University of Cambridge, England.
    Benitez, Javier
    Spanish National Cancer Centre CNIO, Spain; CIBERER, Spain.
    Osorio, Ana
    Spanish National Cancer Centre CNIO, Spain; CIBERER, Spain.
    Jose Garcia, Maria
    Spanish National Cancer Centre CNIO, Spain; CIBERER, Spain.
    Komenaka, Ian
    Maricopa County Gen Hospital, CA USA.
    Weitzel, Jeffrey N.
    Clin Cancer Genet, CA USA.
    Ganschow, Pamela
    Cook County Health and Hospital Syst, CA USA.
    Peterlongo, Paolo
    Italian Fdn Cancer Research, Italy.
    Bernard, Loris
    Ist Europeo Oncol, Italy; Cogentech Cancer Genet Test Lab, Italy.
    Viel, Alessandra
    CRO, Italy.
    Bonanni, Bernardo
    Ist Europeo Oncol, Italy.
    Peissel, Bernard
    Italian Research Hospital, Italy.
    Manoukian, Siranoush
    Italian Research Hospital, Italy.
    Radice, Paolo
    Fdn IRCCS, Italy.
    Papi, Laura
    University of Florence, Italy.
    Ottini, Laura
    University of Roma La Sapienza, Italy.
    Fostira, Florentia
    National Centre Science Research Demokritos, Greece.
    Konstantopoulou, Irene
    National Centre Science Research Demokritos, Greece.
    Garber, Judy
    Childrens Hospital, MA 02115 USA.
    Frost, Debra
    University of Cambridge, England.
    Perkins, Jo
    University of Cambridge, England.
    Platte, Radka
    University of Cambridge, England.
    Ellis, Steve
    University of Cambridge, England.
    Godwin, Andrew K.
    University of Kansas, KS 66103 USA.
    Katharina Schmutzler, Rita
    University Hospital Cologne, Germany.
    Meindl, Alfons
    Technical University of Munich, Germany.
    Engel, Christoph
    University of Leipzig, Germany.
    Sutter, Christian
    Heidelberg University, Germany.
    Sinilnikova, Olga M.
    University of Lyon, France; Hospital Civils Lyon, France.
    Damiola, Francesca
    University of Lyon, France.
    Mazoyer, Sylvie
    University of Lyon, France.
    Stoppa-Lyonnet, Dominique
    Institute Curie, France; University of Paris 05, France.
    Claes, Kathleen
    University of Ghent, Belgium.
    De Leeneer, Kim
    University of Ghent, Belgium.
    Kirk, Judy
    Westmead Hospital, Australia; Westmead Hospital, Australia.
    Rodriguez, Gustavo C.
    NorthShore University of HealthSystem, IL USA.
    Piedmonte, Marion
    Roswell Pk Cancer Institute, NY 14263 USA.
    OMalley, David M.
    Ohio State University, OH 43210 USA.
    de la Hoya, Miguel
    Hospital Clin San Carlos, Spain.
    Caldes, Trinidad
    Hospital Clin San Carlos, Spain.
    Aittomaeki, Kristiina
    University of Helsinki, Finland.
    Nevanlinna, Heli
    University of Helsinki, Finland; University of Helsinki, Finland.
    Margriet Collee, J.
    Erasmus University, Netherlands.
    Rookus, Matti A.
    Netherlands Cancer Institute, Netherlands.
    Oosterwijk, Jan C.
    University of Groningen, Netherlands.
    Tihomirova, Laima
    Latvian Biomed Research and Study Centre, Latvia.
    Tung, Nadine
    Beth Israel Deaconess Medical Centre, MA 02215 USA.
    Hamann, Ute
    DKFZ, Germany.
    Isaccs, Claudine
    Georgetown University, DC USA.
    Tischkowitz, Marc
    McGill University, Canada.
    Imyanitov, Evgeny N.
    NN Petrov Institute Oncol, Russia.
    Caligo, Maria A.
    University of Pisa, Italy; University Hospital Pisa, Italy.
    Campbell, Ian G.
    Peter MacCallum Cancer Centre, Australia.
    Hogervorst, Frans B. L.
    Netherlands Cancer Institute, Netherlands.
    Olah, Edith
    National Institute Oncol, Hungary.
    Diez, Orland
    University Hospital Vall Hebron, Spain; University of Autonoma Barcelona, Spain.
    Blanco, Ignacio
    Catalan Institute Oncol, Spain.
    Brunet, Joan
    Catalan Institute Oncol, Spain.
    Lazaroso, Conxi
    Catalan Institute Oncol, Spain.
    Angel Pujana, Miguel
    Catalan Institute Oncol, Spain.
    Jakubowska, Anna
    Pomeranian Medical University, Poland.
    Gronwald, Jacek
    Pomeranian Medical University, Poland.
    Lubinski, Jan
    Pomeranian Medical University, Poland.
    Sukiennicki, Grzegorz
    Pomeranian Medical University, Poland.
    Barkardottir, Rosa B.
    Landspitali University Hospital, Iceland; University of Iceland, Iceland.
    Plante, Marie
    CHUQ, Canada.
    Simard, Jacques
    University of Laval, Canada.
    Soucy, Penny
    University of Laval, Canada.
    Montagna, Marco
    IRCCS, Italy.
    Tognazzo, Silvia
    IRCCS, Italy.
    Teixeira, Manuel R.
    University of Porto, Portugal; Portuguese Oncology Institute, Portugal.
    Pankratz, Vernon S.
    Mayo Clin, MN USA.
    Wang, Xianshu
    Mayo Clin, MN USA.
    Lindor, Noralane
    Mayo Clin, MN USA.
    Szabo, Csilla I.
    NHGRI, MD 20892 USA.
    Kauff, Noah
    Mem Sloan Kettering Cancer Centre, NY 10021 USA.
    Vijai, Joseph
    Mem Sloan Kettering Cancer Centre, NY 10021 USA.
    Aghajanian, Carol A.
    Mem Sloan Kettering Cancer Centre, NY 10021 USA.
    Pfeiler, Georg
    Medical University of Vienna, Austria.
    Berger, Andreas
    Medical University of Vienna, Austria.
    Singer, Christian F.
    Medical University of Vienna, Austria.
    Tea, Muy-Kheng
    Medical University of Vienna, Austria.
    Phelan, Catherine M.
    H Lee Moffitt Cancer Centre and Research Institute, FL USA.
    Greene, Mark H.
    NCI, MD USA.
    Mai, Phuong L.
    NCI, MD USA.
    Rennert, Gad
    Carmel Hospital, Israel.
    Marie Mulligan, Anna
    University of Toronto, Canada; University of Health Network, Canada.
    Tchatchou, Sandrine
    Mt Sinai Hospital, Canada.
    Andrulis, Irene L.
    University of Toronto, Canada; University of Toronto, Canada.
    Glendon, Gord
    Mt Sinai Hospital, Canada.
    Ewart Toland, Amanda
    Ohio State University, OH 43210 USA.
    Birk Jensen, Uffe
    Aarhus University Hospital, Denmark.
    Kruse, Torben A.
    Odense University Hospital, Denmark.
    Thomassen, Mads
    Odense University Hospital, Denmark.
    Bojesen, Anders
    Vejle Hospital, Denmark.
    Zidan, Jamal
    Rivka Ziv Medical Centre, Israel.
    Friedman, Eitan
    Sheba Medical Centre, Israel.
    Laitman, Yael
    Sheba Medical Centre, Israel.
    Soller, Maria
    University of Lund Hospital, Sweden.
    Liljegren, Annelie
    Karolinska University Hospital, Sweden.
    Arver, Brita
    Karolinska University Hospital, Sweden.
    Einbeigi, Zakaria
    Sahlgrens University Hospital, Sweden.
    Askmalm Stenmark, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Region Östergötland, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Olopade, Olufunmilayo I.
    University of Chicago, IL 60637 USA.
    Nussbaum, Robert L.
    University of Calif San Francisco, CA 94143 USA.
    Rebbeck, Timothy R.
    University of Penn, PA 19104 USA.
    Nathanson, Katherine L.
    University of Penn, PA 19104 USA.
    Domchek, Susan M.
    University of Penn, PA 19104 USA.
    Lu, Karen H.
    University of Texas MD Anderson Cancer Centre, TX 77030 USA.
    Karlan, Beth Y.
    Cedars Sinai Medical Centre, CA 90048 USA.
    Walsh, Christine
    Cedars Sinai Medical Centre, CA 90048 USA.
    Lester, Jenny
    Cedars Sinai Medical Centre, CA 90048 USA.
    Hein, Alexander
    University of Erlangen Nurnberg, Germany.
    Ekici, Arif B.
    University of Erlangen Nurnberg, Germany.
    Beckmann, Matthias W.
    University of Erlangen Nurnberg, Germany.
    Fasching, Peter A.
    University of Erlangen Nurnberg, Germany; University of Calif Los Angeles, CA 90095 USA.
    Lambrechts, Diether
    Vesalius Research Centre, Belgium; University of Leuven, Belgium.
    Van Nieuwenhuysen, Els
    University of Leuven, Belgium.
    Vergote, Ignace
    University of Leuven, Belgium.
    Lambrechts, Sandrina
    University of Leuven, Belgium.
    Dicks, Ed
    University of Cambridge, England.
    Doherty, Jennifer A.
    Geisel School Med, NH USA.
    Wicklund, Kristine G.
    Fred Hutchinson Cancer Research Centre, WA 98104 USA.
    Anne Rossing, Mary
    Fred Hutchinson Cancer Research Centre, WA 98104 USA; University of Washington, WA 98195 USA.
    Rudolph, Anja
    German Cancer Research Centre, Germany.
    Chang-Claude, Jenny
    German Cancer Research Centre, Germany.
    Wang-Gohrke, Shan
    University of Ulm, Germany.
    Eilber, Ursula
    German Cancer Research Centre, Germany.
    Moysich, Kirsten B.
    Roswell Pk Cancer Institute, NY 14263 USA.
    Odunsi, Kunle
    Roswell Pk Cancer Institute, NY 14263 USA.
    Sucheston, Lara
    Roswell Pk Cancer Institute, NY 14263 USA.
    Lele, Shashi
    Roswell Pk Cancer Institute, NY 14263 USA.
    Wilkens, Lynne R.
    University of Hawaii Cancer Centre, HI USA.
    Goodman, Marc T.
    Cedars Sinai Medical Centre, CA 90048 USA; Cedars Sinai Medical Centre, CA 90048 USA.
    Thompson, Pamela J.
    Cedars Sinai Medical Centre, CA 90048 USA; Cedars Sinai Medical Centre, CA 90048 USA.
    Shvetsov, Yurii B.
    University of Hawaii Cancer Centre, HI USA.
    Runnebaum, Ingo B.
    University of Jena, Germany.
    Duerst, Matthias
    University of Jena, Germany.
    Hillemanns, Peter
    Hannover Medical Sch, Germany.
    Doerk, Thilo
    Hannover Medical Sch, Germany.
    Antonenkova, Natalia
    Byelorussian Institute Oncology and Medical Radiol Aleksandrov, Byelarus.
    Bogdanova, Natalia
    Hannover Medical Sch, Germany.
    Leminen, Arto
    University of Helsinki, Finland; University of Helsinki, Finland.
    Pelttari, Liisa M.
    University of Helsinki, Finland; University of Helsinki, Finland.
    Butzow, Ralf
    University of Helsinki, Finland; University of Helsinki, Finland; University of Helsinki, Finland.
    Modugno, Francesmary
    University of Pittsburgh, PA USA; Magee Womens Research Institute, PA USA; University of Pittsburgh, PA USA.
    Kelley, Joseph L.
    University of Pittsburgh, PA USA.
    Edwards, Robert P.
    University of Pittsburgh, PA USA; University of Pittsburgh, PA USA.
    Ness, Roberta B.
    University of Texas Houston, TX USA.
    du Bois, Andreas
    Dr Horst Schmidt Klin Wiesbaden, Germany; Klin Essen Mitte, Germany.
    Heitz, Florian
    Dr Horst Schmidt Klin Wiesbaden, Germany; Klin Essen Mitte, Germany.
    Schwaab, Ira
    Institute Humangenetik Wiesbaden, Germany.
    Harter, Philipp
    Dr Horst Schmidt Klin Wiesbaden, Germany; Klin Essen Mitte, Germany.
    Matsuo, Keitaro
    Kyushu University, Japan.
    Hosono, Satoyo
    Aichi Cancer Centre, Japan.
    Orsulic, Sandra
    Cedars Sinai Medical Centre, CA 90048 USA.
    Jensen, Allan
    Danish Cancer Soc, Denmark.
    Kruger Kjaer, Susanne
    Danish Cancer Soc, Denmark; University of Copenhagen, Denmark.
    Hogdall, Estrid
    Danish Cancer Soc, Denmark; University of Copenhagen, Denmark.
    Nazihah Hasmad, Hanis
    Cancer Research Initiat Fdn, Malaysia.
    Adenan Noor Azmi, Mat
    University of Malaya, Malaysia.
    Teo, Soo-Hwang
    Cancer Research Initiat Fdn, Malaysia; University of Malaya, Malaysia.
    Woo, Yin-Ling
    University of Malaya, Malaysia; University of Malaya, Malaysia.
    Fridley, Brooke L.
    University of Kansas, KS 66103 USA.
    Goode, Ellen L.
    Mayo Clin, MN USA.
    Cunningham, Julie M.
    Mayo Clin, MN USA.
    Vierkant, Robert A.
    Mayo Clin, MN USA.
    Bruinsma, Fiona
    Cancer Council Victoria, Australia.
    Giles, Graham G.
    Cancer Council Victoria, Australia.
    Liang, Dong
    Texas So University, TX 77004 USA.
    Hildebrandt, Michelle A. T.
    University of Texas MD Anderson Cancer Centre, TX 77030 USA.
    Wu, Xifeng
    University of Texas MD Anderson Cancer Centre, TX 77030 USA.
    Levine, Douglas A.
    Mem Sloan Kettering Cancer Centre, NY 10021 USA.
    Bisogna, Maria
    Mem Sloan Kettering Cancer Centre, NY 10021 USA.
    Berchuck, Andrew
    Duke University, NC 27710 USA.
    Iversen, Edwin S.
    Duke University, NC USA.
    Schildkraut, Joellen M.
    Duke Cancer Institute, NC USA; Duke University, NC 27710 USA.
    Concannon, Patrick
    University of Florida, FL USA; University of Florida, FL USA.
    Palmieri Weber, Rachel
    Duke University, NC 27710 USA.
    Cramer, Daniel W.
    Harvard University, MA 02115 USA; Harvard University, MA 02115 USA.
    Terry, Kathryn L.
    Harvard University, MA 02115 USA; Harvard University, MA 02115 USA.
    Poole, Elizabeth M.
    Harvard University, MA 02115 USA; Harvard University, MA 02115 USA.
    Tworoger, Shelley S.
    Harvard University, MA 02115 USA; Harvard University, MA 02115 USA.
    Bandera, Elisa V.
    Rutgers Cancer Institute New Jersey, NJ USA.
    Orlow, Irene
    Mem Sloan Kettering Cancer Centre, NY 10021 USA.
    Olson, Sara H.
    Mem Sloan Kettering Cancer Centre, NY 10021 USA.
    Krakstad, Camilla
    University of Bergen, Norway; Haukeland Hospital, Norway.
    Salvesen, Helga B.
    University of Bergen, Norway; Haukeland Hospital, Norway.
    Tangen, Ingvild L.
    University of Bergen, Norway; Haukeland Hospital, Norway.
    Bjorge, Line
    University of Bergen, Norway; Haukeland Hospital, Norway.
    van Altena, Anne M.
    Radboud University of Nijmegen, Netherlands.
    Aben, Katja K. H.
    Centre Comprehens Canc, Netherlands; Radboud University of Nijmegen, Netherlands.
    Kiemeney, Lambertus A.
    Radboud University of Nijmegen, Netherlands; Radboud University of Nijmegen, Netherlands.
    Massuger, Leon F. A. G.
    Radboud University of Nijmegen, Netherlands.
    Kellar, Melissa
    Oregon Health and Science University, OR 97201 USA; Knight Cancer Institute, OR USA.
    Brooks-Wilson, Angela
    British Columbia Cancer Agency, Canada; Simon Fraser University, Canada.
    Kelemen, Linda E.
    Medical University of S Carolina, SC 29425 USA.
    Cook, Linda S.
    University of New Mexico, NM 87131 USA.
    Le, Nhu D.
    British Columbia Cancer Agency, Canada.
    Cybulski, Cezary
    Pomeranian Medical University, Poland.
    Yang, Hannah
    NCI, MD 20892 USA.
    Lissowska, Jolanta
    Maria Sklodowska Curie Mem Cancer Centre, Poland.
    Brinton, Louise A.
    NCI, MD 20892 USA.
    Wentzensen, Nicolas
    NCI, MD 20892 USA.
    Hogdall, Claus
    University of Copenhagen, Denmark.
    Lundvall, Lene
    University of Copenhagen, Denmark.
    Nedergaard, Lotte
    University of Copenhagen, Denmark.
    Baker, Helen
    University of Cambridge, England.
    Song, Honglin
    University of Cambridge, England.
    Eccles, Diana
    Princess Anne Hospital, England.
    McNeish, Ian
    University of Porto, Portugal; University of Glasgow, Scotland.
    Paul, James
    University of Copenhagen, Denmark.
    Carty, Karen
    University of Copenhagen, Denmark.
    Siddiqui, Nadeem
    Glasgow Royal Infirm, Scotland.
    Glasspool, Rosalind
    Beatson West Scotland, Scotland.
    Whittemore, Alice S.
    Stanford University, CA 94305 USA.
    Rothstein, Joseph H.
    Stanford University, CA 94305 USA.
    McGuire, Valerie
    Stanford University, CA 94305 USA.
    Sieh, Weiva
    Stanford University, CA 94305 USA.
    Ji, Bu-Tian
    NCI, MD 20892 USA.
    Zheng, Wei
    Vanderbilt University, TN 37212 USA.
    Shu, Xiao-Ou
    Vanderbilt University, TN 37212 USA.
    Gao, Yu-Tang
    Shanghai Cancer Institute, Peoples R China.
    Rosen, Barry
    University of Toronto, Canada; Princess Margaret Hospital, Canada.
    Risch, Harvey A.
    Yale School Public Heatlh, CT USA.
    McLaughlin, John R.
    Mt Sinai Hospital, Canada.
    Narod, Steven A.
    University of Toronto, Canada.
    Monteiro, Alvaro N.
    H Lee Moffitt Cancer Centre and Research Institute, FL USA.
    Chen, Ann
    H Lee Moffitt Cancer Centre and Research Institute, FL USA.
    Lin, Hui-Yi
    H Lee Moffitt Cancer Centre and Research Institute, FL USA.
    Permuth-Wey, Jenny
    H Lee Moffitt Cancer Centre and Research Institute, FL USA.
    Sellers, Thomas A.
    H Lee Moffitt Cancer Centre and Research Institute, FL USA.
    Tsai, Ya-Yu
    H Lee Moffitt Cancer Centre and Research Institute, FL USA.
    Chen, Zhihua
    H Lee Moffitt Cancer Centre and Research Institute, FL USA.
    Ziogas, Argyrios
    University of Calif Irvine, CA USA.
    Anton-Culver, Hoda
    University of Calif Irvine, CA USA.
    Gentry-Maharaj, Aleksandra
    UCL, England.
    Menon, Usha
    UCL, England.
    Harrington, Patricia
    University of Cambridge, England.
    Lee, Alice W.
    University of Cambridge, England; University of So Calif, CA USA.
    Wu, Anna H.
    University of So Calif, CA USA.
    Pearce, Celeste L.
    University of So Calif, CA USA.
    Coetzee, Gerry
    University of So Calif, CA USA; University of So Calif, CA USA.
    Pike, Malcolm C.
    University of So Calif, CA USA; Mem Sloan Kettering Cancer Centre, NY 10021 USA.
    Dansonka-Mieszkowska, Agnieszka
    Maria Sklodowska Curie Mem Cancer Centre, Poland.
    Timorek, Agnieszka
    Medical University of Warsaw, Poland; Brodnowski Hospital, Poland.
    Rzepecka, Iwona K.
    Maria Sklodowska Curie Mem Cancer Centre, Poland.
    Kupryjanczyk, Jolanta
    Maria Sklodowska Curie Mem Cancer Centre, Poland.
    Freedman, Matt
    Centre Funct Cancer Epigenet, MA USA.
    Noushmehr, Houtan
    University of Sao Paulo, Brazil.
    Easton, Douglas F.
    University of Cambridge, England.
    Offit, Kenneth
    Mem Sloan Kettering Cancer Centre, NY 10021 USA.
    Couch, Fergus J.
    Mayo Clin, MN USA; Mayo Clin, MN USA.
    Gayther, Simon
    University of So Calif, CA USA.
    Pharoah, Paul P.
    University of Cambridge, England.
    Antoniou, Antonis C.
    University of Cambridge, England.
    Chenevix-Trench, Georgia
    QIMR Berghofer Medical Research Institute, Australia.
    Identification of six new susceptibility loci for invasive epithelial ovarian cancer2015Ingår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 47, nr 2, s. 164-171Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P less than 5 x 10(-8). Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.

  • 328.
    Kumar Jeengar, Manish
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. National Institute Pharmaceut Educ and Research Institute, India.
    Thummuri, Dinesh
    National Institute Pharmaceut Educ and Research Institute, India.
    Magnusson, Mattias
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Naidu, V. G. M.
    National Institute Pharmaceut Educ and Research Institute, India; National Institute Pharmaceut Educ and Research Institute, India.
    Uppugunduri, Srinivas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Uridine Ameliorates Dextran Sulfate Sodium (DSS)-Induced Colitis in Mice2017Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, artikel-id 3924Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Uridine, one of the four components that comprise RNA, has attracted attention as a novel therapeutic modulator of inflammation. However, very little is known about its effect on intestinal inflammation. The aim of the present study was to investigate the potential protective effect of intracolonic administered uridine against DSS induced colitis in male C57BL/6 mice. Intracolonic instillation of 3 doses of uridine 1 mg/Kg (lower dose), 5 mg/Kg (medium dose), and 10 mg/Kg (higher dose) in saline was performed daily. Uridine at medium and high dose significantly reduced the severity of colitis (DAI score) and alleviated the macroscopic and microscopic signs of the disease. The levels of proinflammatory cytokines IL-6, IL-1 beta and TNF in serum as well as mRNA expression in colon were significantly reduced in the uridine treated groups. Moreover, colon tissue myloperoxidase activities, protein expression of IL-6, TNF-alpha, COX-2, P-NFkB and P-Ikk-alpha beta in the colon tissues were significantly reduced in medium and high dose groups. These findings demonstrated that local administration of uridine alleviated experimental colitis in male C57BL/6 mice accompanied by the inhibition of neutrophil infiltration and NF-kappa B signaling. Thus, Uridine may be a promising candidate for future use in the treatment of inflammatory bowel disease.

  • 329.
    Kvernby, Sofia
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Region Östergötland, Diagnostikcentrum, Medicinsk strålningsfysik.
    Rönnerfalk, Mattias
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Warntjes, Marcel Jan Bertus
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Fysiologiska kliniken US. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. SyntheticMR AB, Linkoping, Sweden.
    Carlhäll, Carljohan
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Fysiologiska kliniken US. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Nylander, Eva
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Fysiologiska kliniken US.
    Engvall, Jan
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Fysiologiska kliniken US. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Tamas, Eva
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Thorax-kärlkliniken i Östergötland. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Ebbers, Tino
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Fysiologiska kliniken US. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Longitudinal Changes in Myocardial T-1 and T-2 Relaxation Times Related to Diffuse Myocardial Fibrosis in Aortic Stenosis; Before and After Aortic Valve Replacement2018Ingår i: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 48, nr 3, s. 799-807Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Diffuse myocardial fibrosis is associated with adverse outcomes, although detection and quantification is challenging. Cardiac MR relaxation times mapping represents a promising imaging biomarker for diffuse myocardial fibrosis. Purpose: To investigate whether relaxation times can detect longitudinal changes in myocardial tissue composition associated with diffuse fibrosis in patients with severe aortic stenosis (AS) before and after aortic valve replacement (AVR). Study type: Prospective longitudinal study. Population/Subjects/Phantom/Specimen/Animal Model: Fifteen patients with severe AS. Field Strength/Sequence: 3T /3(3) 3(3) 5-MOLLI, T2-GraSE, and 3D-QALAS. Assessment: Patients underwent MR examinations at three timepoints: before AVR, as well as 3 and 12 months after AVR. Data from each patient was analyzed in 16 myocardial segments. Statistical Tests: The segment-wise T1 and T2 data were analyzed over time after surgery using linear mixed models for repeated measures analysis. Results: The results showed that T1 relaxation times were significantly (Pamp;lt; 0.05) shorter 3 and 12 months postoperative than preoperative and that the T2 relaxation times were significantly (Pamp;lt; 0.05) longer 3 and 12 months postoperative than preoperative for both 3D and 2D mapping methods. No significant changes were seen between 3 and 12 months postoperative for any of the methods (P50.06/0.19 for T1 with 3D-QALAS/MOLLI and P50.09/0.25 for T2 with 3DQALAS/ GraSE). Data Conclusion: We demonstrated that changes in myocardial relaxation times and thus tissue characteristics can be observed within 3 months after AVR surgery. The significant changes in relaxation times from preoperative examinations to the follow-up may be interpreted as a reduction of interstitial fibrosis in the left ventricular wall. Level of Evidence: 1 Technical Efficacy: Stage 3

  • 330.
    Lagerstedt-Robinson, Kristina
    et al.
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Rohlin, Anna
    Sahlgrens University Hospital, Sweden; University of Gothenburg, Sweden.
    Aravidis, Christos
    Uppsala University, Sweden.
    Melin, Beatrice
    Umeå University, Sweden.
    Nordling, Margareta
    Sahlgrens University Hospital, Sweden; University of Gothenburg, Sweden.
    Stenmark Askmalm, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi och klinisk genetik. University of Lund Hospital, Sweden.
    Lindblom, Annika
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Nilbert, M. E. F.
    Lund University, Sweden; University of Copenhagen, Denmark.
    Mismatch repair gene mutation spectrum in the Swedish Lynch syndrome population2016Ingår i: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 36, nr 5, s. 2823-2835Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Lynch syndrome caused by constitutional mismatch-repair defects is one of the most common hereditary cancer syndromes with a high risk for colorectal, endometrial, ovarian and urothelial cancer. Lynch syndrome is caused by mutations in the mismatch repair (MMR) genes i.e., MLH1, MSH2, MSH6 and PMS2. After 20 years of genetic counseling and genetic testing for Lynch syndrome, we have compiled the mutation spectrum in Sweden with the aim to provide a population-based perspective on the contribution from the different MMR genes, the various types of mutations and the influence from founder mutations. Mutation data were collected on a national basis from all laboratories involved in genetic testing. Mutation analyses were performed using mainly Sanger sequencing and multiplex ligation-dependent probe amplification. A total of 201 unique disease-predisposing MMR gene mutations were identified in 369 Lynch syndrome families. These mutations affected MLH1 in 40%, MSH2 in 36%, MSH6 in 18% and PMS2 in 6% of the families. A large variety of mutations were identified with splice site mutations being the most common mutation type in MLH1 and frameshift mutations predominating in MSH2 and MSH6. Large deletions of one or several exons accounted for 21% of the mutations in MLH1 and MSH2 and 22% in PMS2, but were rare (4%) in MSH6. In 66% of the Lynch syndrome families the variants identified were private and the effect from founder mutations was limited and predominantly related to a Finnish founder mutation that accounted for 15% of the families with mutations in MLH1. In conclusion, the Swedish Lynch syndrome mutation spectrum is diverse with private MMR gene mutations in two-thirds of the families, has a significant contribution from internationally recognized mutations and a limited effect from founder mutations.

  • 331.
    Lantz, Jonas
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Gupta, Vikas
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Henriksson, Lilian
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Karlsson, Matts
    Linköpings universitet, Institutionen för ekonomisk och industriell utveckling, Mekanisk värmeteori och strömningslära. Linköpings universitet, Tekniska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Persson, Anders
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Linköping.
    Carlhäll, Carljohan
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Region Östergötland, Hjärt- och Medicincentrum, Fysiologiska kliniken US.
    Ebbers, Tino
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Region Östergötland, Hjärt- och Medicincentrum, Fysiologiska kliniken US.
    Characterization of Cardiac Flow in Heart Disease Patients by CFD and 4D Flow MRI2017Ingår i: Bulletin of the Amerian Physcial Society, American Physical Society, 2017Konferensbidrag (Refereegranskat)
    Abstract [en]

    In this study, cardiac blood flow was simulated using Computational Fluid Dynamics and compared to in vivo flow measurements by 4D Flow MRI. In total, nine patients with various heart diseases were studied. Geometry and heart wall motion for the simulations were obtained from clinical CT measurements, with 0.3x0.3x0.3 mm spatial resolution and 20 time frames covering one heartbeat. The CFD simulations included pulmonary veins, left atrium and ventricle, mitral and aortic valve, and ascending aorta. Mesh sizes were on the order of 6-16 million cells, depending on the size of the heart, in order to resolve both papillary muscles and trabeculae. The computed flow field agreed visually very well with 4D Flow MRI, with characteristic vortices and flow structures seen in both techniques. Regression analysis showed that peak flow rate as well as stroke volume had an excellent agreement for the two techniques. We demonstrated the feasibility, and more importantly, fidelity of cardiac flow simulations by comparing CFD results to in vivo measurements. Both qualitative and quantitative results agreed well with the 4D Flow MRI measurements. Also, the developed simulation methodology enables “what if” scenarios, such as optimization of valve replacement and other surgical procedures.

  • 332.
    Lantz, Jonas
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Gupta, Vikas
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Henriksson, Lilian
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Karlsson, Matts
    Linköpings universitet, Institutionen för ekonomisk och industriell utveckling, Mekanisk värmeteori och strömningslära. Linköpings universitet, Tekniska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Persson, Anders
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Linköping.
    Carlhäll, Carljohan
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Fysiologiska kliniken US. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Ebbers, Tino
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Region Östergötland, Hjärt- och Medicincentrum, Fysiologiska kliniken US.
    First Results of CT-derived Cardiac 4D Blood Flow - Comparison With 4D Flow MRI2017Konferensbidrag (Övrigt vetenskapligt)
  • 333.
    Lantz, Jonas
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Gupta, Vikas
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Medicinska fakulteten.
    Henriksson, Lilian
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Karlsson, Matts
    Linköpings universitet, Institutionen för ekonomisk och industriell utveckling, Mekanisk värmeteori och strömningslära. Linköpings universitet, Tekniska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Persson, Anders
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Linköping. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Carlhäll, Carl-Johan
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Region Östergötland, Hjärt- och Medicincentrum, Fysiologiska kliniken US. Linköpings universitet, Medicinska fakulteten.
    Ebbers, Tino
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Fysiologiska kliniken US. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Impact of Pulmonary Venous Inflow on Cardiac Flow Simulations: Comparison with In Vivo 4D Flow MRI2019Ingår i: Annals of Biomedical Engineering, ISSN 0090-6964, E-ISSN 1573-9686, Vol. 47, nr 2, s. 413-424Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Blood flow simulations are making their way into the clinic, and much attention is given to estimation of fractional flow reserve in coronary arteries. Intracardiac blood flow simulations also show promising results, and here the flow field is expected to depend on the pulmonary venous (PV) flow rates. In the absence of in vivo measurements, the distribution of the flow from the individual PVs is often unknown and typically assumed. Here, we performed intracardiac blood flow simulations based on time-resolved computed tomography on three patients, and investigated the effect of the distribution of PV flow rate on the flow field in the left atrium and ventricle. A design-of-experiment approach was used, where PV flow rates were varied in a systematic manner. In total 20 different simulations were performed per patient, and compared to in vivo 4D flow MRI measurements. Results were quantified by kinetic energy, mitral valve velocity profiles and root-mean-square errors of velocity. While large differences in atrial flow were found for varying PV inflow distributions, the effect on ventricular flow was negligible, due to a regularizing effect by mitral valve. Equal flow rate through all PVs most closely resembled in vivo measurements and is recommended in the absence of a priori knowledge.

  • 334.
    Lantz, Jonas
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Gupta, Vikas
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Henriksson, Lilian
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Linköping. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Karlsson, Matts
    Linköpings universitet, Institutionen för ekonomisk och industriell utveckling, Mekanisk värmeteori och strömningslära. Linköpings universitet, Tekniska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Persson, Anders
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Linköping. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Carlhäll, Carljohan
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Fysiologiska kliniken US. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Ebbers, Tino
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Fysiologiska kliniken US. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Intracardiac Flow at 4D CT: Comparison with 4D Flow MRI2018Ingår i: Radiology, ISSN 0033-8419, E-ISSN 1527-1315, Vol. 289, nr 1, s. 51-58Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose

    To investigate four-dimensional (4D) flow CT for the assessment of intracardiac blood flow patterns as compared with 4D flow MRI.

    Materials and Methods

    This prospective study acquired coronary CT angiography and 4D flow MRI data between February and December 2016 in a cohort of 12 participants (age range, 36–74 years; mean age, 57 years; seven men [age range, 36–74 years; mean age, 57 years] and five women [age range, 52–73 years; mean age, 64 years]). Flow simulations based solely on CT-derived cardiac anatomy were assessed together with 4D flow MRI measurements. Flow patterns, flow rates, stroke volume, kinetic energy, and flow components were quantified for both techniques and were compared by using linear regression.

    Results

    Cardiac flow patterns obtained by using 4D flow CT were qualitatively similar to 4D flow MRI measurements, as graded by three independent observers. The Cohen κ score was used to assess intraobserver variability (0.83, 0.79, and 0.70) and a paired Wilcoxon rank-sum test showed no significant change (P > .05) between gradings. Peak flow rate and stroke volumes between 4D flow MRI measurements and 4D flow CT measurements had high correlation (r = 0.98 and r = 0.81, respectively; P < .05 for both). Integrated kinetic energy quantified at peak systole correlated well (r = 0.95, P < .05), while kinetic energy levels at early and late filling showed no correlation. Flow component analysis showed high correlation for the direct and residual components, respectively (r = 0.93, P < .05 and r = 0.87, P < .05), while the retained and delayed components showed no correlation.

    Conclusion

    Four-dimensional flow CT produced qualitatively and quantitatively similar intracardiac blood flow patterns compared with the current reference standard, four-dimensional flow MRI.

  • 335.
    Lantz, Jonas
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Henriksson, Lilian
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Linköping.
    Persson, Anders
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Linköping.
    Karlsson, Matts
    Linköpings universitet, Institutionen för ekonomisk och industriell utveckling, Mekanisk värmeteori och strömningslära. Linköpings universitet, Tekniska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Ebbers, Tino
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Fysiologiska kliniken US.
    Importance Of Including Papillary Muscles And Trabeculae In Cardiac Flow Simulations2016Ingår i: Proceedings of the 2016 Summer Biomechanics, Bioengineering and Biotransport Conference, Organizing Committee for the 2016 Summer Biomechanics, Bioengineering and Biotransport , 2016Konferensbidrag (Övrigt vetenskapligt)
  • 336.
    Lantz, Jonas
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Medicinska fakulteten.
    Henriksson, Lilian
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Persson, Anders
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Linköping.
    Karlsson, Matts
    Linköpings universitet, Institutionen för ekonomisk och industriell utveckling, Mekanisk värmeteori och strömningslära. Linköpings universitet, Tekniska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Ebbers, Tino
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Fysiologiska kliniken US.
    Patient-Specific Simulation of Cardiac Blood Flow From High-Resolution Computed Tomography2016Ingår i: Journal of Biomechanical Engineering, ISSN 0148-0731, E-ISSN 1528-8951, Vol. 138, nr 12Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cardiac hemodynamics can be computed from medical imaging data, and results could potentially aid in cardiac diagnosis and treatment optimization. However, simulations are often based on simplified geometries, ignoring features such as papillary muscles and trabeculae due to their complex shape, limitations in image acquisitions, and challenges in computational modeling. This severely hampers the use of computational fluid dynamics in clinical practice. The overall aim of this study was to develop a novel numerical framework that incorporated these geometrical features. The model included the left atrium, ventricle, ascending aorta, and heart valves. The framework used image registration to obtain patient-specific wall motion, automatic remeshing to handle topological changes due to the complex trabeculae motion, and a fast interpolation routine to obtain intermediate meshes during the simulations. Velocity fields and residence time were evaluated, and they indicated that papillary muscles and trabeculae strongly interacted with the blood, which could not be observed in a simplified model. The framework resulted in a model with outstanding geometrical detail, demonstrating the feasibility as well as the importance of a framework that is capable of simulating blood flow in physiologically realistic hearts.

  • 337.
    Larsson, A.
    et al.
    Lund University, Sweden.
    Tynngård, Nahreen
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Kander, T.
    Lund University, Sweden; Skåne University Hospital Lund, Sweden.
    Bonnevier, J.
    Lund University, Sweden; Skåne University Hospital Lund, Sweden.
    Schott, U.
    Lund University, Sweden; Skåne University Hospital Lund, Sweden.
    Comparison of point-of-care hemostatic assays, routine coagulation tests, and outcome scores in critically ill patients2015Ingår i: Journal of critical care, ISSN 0883-9441, E-ISSN 1557-8615, Vol. 30, nr 5, s. 1032-1038Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: The purposes of the study are to compare point-of-care (POC) hemostatic devices in critically ill patients with routine laboratory tests and intensive care unit (ICU) outcome scoring assessments and to describe the time course of these variables in relation to mortality rate. Materials and methods: Patients admitted to the ICU with a prognosis of more than 3 days of stay were included. The POC devices, Multiplate platelet aggregometry, rotational thromboelastometry, and ReoRox viscoelastic tests, were used. All variables were compared between survivors and nonsurvivors. Point-of-care results were compared to prothrombin time, activated partial thromboplastin time, platelet count, fibrinogen concentration, and Sequential Organ Failure Assessment score and Simplified Acute Physiology Score 3. Results: Blood was sampled on days 0 to 1, 2 to 3, and 4 to 10 from 114 patients with mixed diagnoses during 237 sampling events. Nonsurvivors showed POC and laboratory signs of hypocoagulation and decreased fibrinolysis over time compared to survivors. ReoRox detected differences between survivors and nonsurvivors better than ROTEM and Multiplate. Conclusions: All POC and routine laboratory tests showed a hypocoagulative response in nonsurvivors compared to survivors. ReoRox was better than ROTEM and Multiplate at detecting differences between surviving and nonsurviving ICU patients. However, Simplified Acute Physiology Score 3 showed the best association to mortality outcome.

  • 338.
    Lash, Gendie E.
    et al.
    Newcastle University, England.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin. Linköpings universitet, Medicinska fakulteten.
    Decidual cytokines and pregnancy complications: focus on spontaneous miscarriage2015Ingår i: Journal of Reproductive Immunology, ISSN 0165-0378, E-ISSN 1872-7603, Vol. 108, s. 83-89Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The establishment of pregnancy requires the co-ordinated implantation of the embryo into the receptive decidua, placentation, trophoblast invasion of the maternal decidua and myometrium in addition to remodelling of the uterine spiral arteries. Failure of any of these steps can lead to a range of pregnancy complications, including miscarriage, pre-eclampsia, fetal growth restriction, placenta accreta and pre-term birth. Cytokines are small multifunctional proteins often derived from leucocytes and have primarily been described through their immunomodulatory actions. The maternal-fetal interface is considered to be immunosuppressed to allow development of the semi-allogeneic placental fetal unit. However, cytokine profiles of the decidua and different decidual cell types suggest that the in vivo situation might be more complex. Data suggest that decidual-derived cytokines not only play roles in immunosuppression, but also in other aspects of the establishment of pregnancy, including the regulation of trophoblast invasion and spiral artery remodelling. This review focuses on the potential role of decidua-derived cytokines in the aetiology of unexplained spontaneous miscarriage. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

  • 339.
    Lawrenson, Kate
    et al.
    University of Southern Calif, CA 90033 USA; Cedars Sinai Medical Centre, CA 90048 USA.
    Kar, Siddhartha
    University of Cambridge, England.
    McCue, Karen
    QIMR Berghofer Medical Research Institute, Australia.
    Kuchenbaeker, Karoline
    University of Cambridge, England.
    Michailidou, Kyriaki
    University of Cambridge, England.
    Tyrer, Jonathan
    University of Cambridge, England.
    Beesley, Jonathan
    QIMR Berghofer Medical Research Institute, Australia.
    Ramus, Susan J.
    University of Southern Calif, CA 90033 USA.
    Li, Qiyuan
    Xiamen University, Peoples R China; Dana Farber Cancer Institute, MA 02215 USA.
    Delgado, Melissa K.
    University of Southern Calif, CA 90033 USA.
    Lee, Janet M.
    University of Southern Calif, CA 90033 USA.
    Aittomaki, Kristiina
    University of Helsinki, Finland.
    Andrulis, Irene L.
    Mt Sinai Hospital, Canada; University of Toronto, Canada.
    Anton-Culver, Hoda
    University of Calif Irvine, CA 92697 USA.
    Arndt, Volker
    German Cancer Research Centre, Germany.
    Arun, Banu K.
    University of Texas MD Anderson Cancer Centre, TX 77030 USA.
    Arver, Brita
    Karolinska University Hospital, Sweden.
    Bandera, Elisa V.
    Rutgers Cancer Institute New Jersey, NJ 08903 USA.
    Barile, Monica
    Ist Europeo Oncol, Italy.
    Barkardottir, Rosa B.
    University of Iceland, Iceland; University of Iceland, Iceland.
    Barrowdale, Daniel
    University of Cambridge, England.
    Beckmann, Matthias W.
    University of Erlangen Nurnberg, Germany.
    Benitez, Javier
    Spanish National Cancer Research Centre, Spain; Centre Invest Red Enfermedades Raras, Spain.
    Berchuck, Andrew
    Duke University, NC 27710 USA.
    Bisogna, Maria
    Mem Sloan Kettering Cancer Centre, NY 10065 USA.
    Bjorge, Line
    Haukeland Hospital, Norway; University of Bergen, Norway.
    Blomqvist, Carl
    University of Helsinki, Finland.
    Blot, William
    Vanderbilt University, TN 37203 USA; Int Epidemiol Institute, MD 20850 USA.
    Bogdanova, Natalia
    Hannover Medical Sch, Germany.
    Bojesen, Anders
    Vejle Hospital, Denmark; Seoul National University, South Korea; Lunenfeld Tanenbaum Research Institute Mt Sinai Hospital, Canada.
    Bojesen, Stig E.
    University of Copenhagen, Denmark; Copenhagen University Hospital, Denmark; Copenhagen University Hospital, Denmark.
    Bolla, Manjeet K.
    University of Cambridge, England.
    Bonanni, Bernardo
    Ist Europeo Oncol, Italy.
    Borresen-Dale, Anne-Lise
    Oslo University Hospital, Norway; University of Oslo, Norway.
    Brauch, Hiltrud
    Dr Margarete Fischer Bosch Institute Clin Pharmacol, Germany; University of Tubingen, Germany; German Cancer Research Centre, Germany.
    Brennan, Paul
    Int Agency Research Canc, France.
    Brenner, Hermann
    German Cancer Research Centre, Germany; German Cancer Research Centre, Germany; German Cancer Research Centre, Germany.
    Bruinsma, Fiona
    Cancer Council Victoria, Australia.
    Brunet, Joan
    Catalan Institute Oncol, Spain.
    Ahmad Buhari, Shaik
    National University of Health Syst, Singapore.
    Burwinkel, Barbara
    German Cancer Research Centre, Germany; Heidelberg University, Germany.
    Butzow, Ralf
    University of Helsinki, Finland.
    Buys, Saundra S.
    University of Utah, UT 84112 USA.
    Cai, Qiuyin
    Vanderbilt University, TN 37203 USA.
    Caldes, Trinidad
    IdISSC El Institute Invest Sanitaria Hospital Clin San Car, Spain.
    Campbell, Ian
    Peter MacCallum Cancer Centre, Australia.
    Canniotto, Rikki
    Roswell Pk Cancer Institute, NY 14263 USA.
    Chang-Claude, Jenny
    German Cancer Research Centre, Germany; University of Medical Centre Hamburg Eppendorf, Germany.
    Chiquette, Jocelyne
    University of Quebec, Canada.
    Choi, Ji-Yeob
    Seoul National University, South Korea.
    Claes, Kathleen B. M.
    University of Ghent, Belgium.
    Cook, Linda S.
    University of New Mexico, NM 87131 USA.
    Cox, Angela
    University of Sheffield, England.
    Cramer, Daniel W.
    Harvard University, MA 02115 USA; Brigham and Womens Hospital, MA 02115 USA; Harvard University, MA 02115 USA.
    Cross, Simon S.
    University of Sheffield, England.
    Cybulski, Cezary
    Pomeranian Medical University, Poland.
    Czene, Kamila
    Karolinska Institute, Sweden.
    Daly, Mary B.
    Fox Chase Cancer Centre, PA 19111 USA.
    Damiola, Francesca
    University of Lyon, France.
    Dansonka-Mieszkowska, Agnieszka
    Maria Sklodowska Curie Mem Cancer Centre, Poland; Institute Oncol, Poland.
    Darabi, Hatef
    Karolinska Institute, Sweden.
    Dennis, Joe
    University of Cambridge, England.
    Devilee, Peter
    Leiden University, Netherlands.
    Diez, Orland
    University Hospital Vall Hebron, Spain; University of Autonoma Barcelona, Spain.
    Doherty, Jennifer A.
    Geisel School Medical Dartmouth, NH 03755 USA.
    Domchek, Susan M.
    University of Penn, PA 19104 USA.
    Dorfling, Cecilia M.
    University of Pretoria, South Africa.
    Doerk, Thilo
    Hannover Medical Sch, Germany.
    Dumont, Martine
    University of Laval, Canada.
    Ehrencrona, Hans
    Uppsala University, Sweden; University of Lund Hospital, Sweden.
    Ejlertsen, Bent
    Copenhagen University Hospital, Denmark.
    Ellis, Steve
    University of Cambridge, England.
    Engel, Christoph
    University of Leipzig, Germany.
    Lee, Eunjung
    University of Southern Calif, CA 90033 USA.
    Gareth Evans, D.
    University of Manchester, England.
    Fasching, Peter A.
    University of Erlangen Nurnberg, Germany; University of Calif Los Angeles, CA 90095 USA.
    Feliubadalo, Lidia
    Catalan Institute Oncol, Spain.
    Figueroa, Jonine
    NCI, MD 20892 USA.
    Flesch-Janys, Dieter
    University of Medical Centre Hamburg Eppendorf, Germany; University of Medical Centre Hamburg Eppendorf, Germany.
    Fletcher, Olivia
    Institute Cancer Research, England.
    Flyger, Henrik
    Copenhagen University Hospital, Denmark.
    Foretova, Lenka
    Masaryk Mem Cancer Institute, Czech Republic; Medical Fac MU, Czech Republic.
    Fostira, Florentia
    Aghia Paraskevi Attikis, Greece.
    Foulkes, William D.
    McGill University, Canada.
    Fridley, Brooke L.
    University of Kansas, KS 66103 USA.
    Friedman, Eitan
    Chaim Sheba Medical Centre, Israel.
    Frost, Debra
    University of Cambridge, England.
    Gambino, Gaetana
    University of and University Hospital Pisa, Italy.
    Ganz, Patricia A.
    Jonsson Comprehens Cancer Centre, CA 90024 USA.
    Garber, Judy
    Dana Farber Cancer Institute, MA 02215 USA.
    Garcia-Closas, Montserrat
    NCI, MD 20892 USA; Institute Cancer Research, England.
    Gentry-Maharaj, Aleksandra
    UCL EGA Institute Womens Heatlh, England.
    Ghoussaini, Maya
    University of Cambridge, England.
    Giles, Graham G.
    Cancer Council Victoria, Australia; University of Melbourne, Australia.
    Glasspool, Rosalind
    Beatson West Scotland Cancer Centre, Scotland.
    Godwin, Andrew K.
    University of Kansas, KS 66160 USA.
    Goldberg, Mark S.
    McGill University, Canada; McGill University, Canada.
    Goldgar, David E.
    University of Utah, UT 84132 USA.
    Gonzalez-Neira, Anna
    Spanish National Cancer Research Centre, Spain.
    Goode, Ellen L.
    Mayo Clin, MN 55902 USA.
    Goodman, Marc T.
    Cedars Sinai Medical Centre, CA 90048 USA; Cedars Sinai Medical Centre, CA 90048 USA.
    Greene, Mark H.
    NCI, MD 20892 USA.
    Gronwald, Jacek
    Pomeranian Medical University, Poland.
    Guenel, Pascal
    INSERM, France; University of Paris 11, France.
    Haiman, Christopher A.
    University of Southern Calif, CA 90033 USA.
    Hall, Per
    Karolinska Institute, Sweden.
    Hallberg, Emily
    Mayo Clin, MN 55902 USA.
    Hamann, Ute
    German Cancer Research Centre, Germany.
    Hansen, Thomas V. O.
    Copenhagen University Hospital, Denmark.
    Harrington, Patricia A.
    University of Cambridge, England.
    Hartman, Mikael
    National University of Health Syst, Singapore; National University of Singapore, Singapore.
    Hassan, Norhashimah
    University of Malaya, Malaysia; Cancer Research Initiat Fdn, Malaysia.
    Healey, Sue
    QIMR Berghofer Medical Research Institute, Australia.
    Heitz, Florian
    Kliniken Essen Mitte, Germany; Dr Horst Schmidt Kliniken Wiesbaden, Germany.
    Herzog, Josef
    City Hope Clin Cancer Genet Community Research Network, CA 91010 USA.
    Hogdall, Estrid
    University of Copenhagen, Denmark; Danish Cancer Soc Research Centre, Denmark.
    Hogdall, Claus K.
    University of Copenhagen, Denmark.
    Hogervorst, Frans B. L.
    Netherlands Cancer Institute, Netherlands.
    Hollestelle, Antoinette
    Erasmus MC Cancer Institute, Netherlands.
    Hopper, John L.
    University of Melbourne, Australia.
    Hulick, Peter J.
    NorthShore University of Health Syst, IL 60201 USA.
    Huzarski, Tomasz
    Pomeranian Medical University, Poland.
    Imyanitov, Evgeny N.
    NN Petrov Institute Oncol, Russia.
    Isaacs, Claudine
    Georgetown University, DC 20057 USA.
    Ito, Hidemi
    Aichi Cancer Centre, Japan.
    Jakubowska, Anna
    Pomeranian Medical University, Poland.
    Janavicius, Ramunas
    Centre Innovat Med, Lithuania.
    Jensen, Allan
    University of Copenhagen, Denmark.
    John, Esther M.
    Cancer Prevent Institute Calif, CA 94538 USA.
    Johnson, Nichola
    Institute Cancer Research, England.
    Kabisch, Maria
    German Cancer Research Centre, Germany.
    Kang, Daehee
    Seoul National University, South Korea.
    Kapuscinski, Miroslav
    University of Melbourne, Australia.
    Karlan, Beth Y.
    Cedars Sinai Medical Centre, CA 90048 USA.
    Khan, Sofia
    University of Helsinki, Finland.
    Kiemeney, Lambertus A.
    Radboud University of Nijmegen, Netherlands.
    Kruger Kjaer, Susanne
    Danish Cancer Soc Research Centre, Denmark; University of Copenhagen, Denmark.
    Knight, Julia A.
    Lunenfeld Tanenbaum Research Institute Mt Sinai Hospital, Canada; University of Toronto, Canada.
    Konstantopoulou, Irene
    Aghia Paraskevi Attikis, Greece.
    Kosma, Veli-Matti
    Kuopio University Hospital, Finland; University of Eastern Finland, Finland.
    Kristensen, Vessela
    Oslo University Hospital, Norway; University of Oslo, Norway; University of Oslo, Norway.
    Kupryjanczyk, Jolanta
    Maria Sklodowska Curie Mem Cancer Centre, Poland; Institute Oncol, Poland.
    Kwong, Ava
    Hong Kong Sanat and Hospital, Peoples R China; University of Hong Kong, Peoples R China.
    de la Hoya, Miguel
    IdISSC El Institute Invest Sanitaria Hospital Clin San Car, Spain.
    Laitman, Yael
    Chaim Sheba Medical Centre, Israel.
    Lambrechts, Diether
    VIB, Belgium; University of Leuven, Belgium.
    Le, Nhu
    University of Southern Calif, CA 90033 USA.
    De Leeneer, Kim
    University of Ghent, Belgium.
    Lester, Jenny
    Cedars Sinai Medical Centre, CA 90048 USA.
    Levine, Douglas A.
    Mem Sloan Kettering Cancer Centre, NY 10065 USA.
    Li, Jingmei
    Karolinska Institute, Sweden.
    Lindblom, Annika
    Karolinska Institute, Sweden.
    Long, Jirong
    Vanderbilt University, TN 37203 USA.
    Lophatananon, Artitaya
    University of Warwick, England.
    Loud, Jennifer T.
    NCI, MD 20892 USA.
    Lu, Karen
    University of Texas MD Anderson Cancer Centre, TX 77030 USA.
    Lubinski, Jan
    Pomeranian Medical University, Poland.
    Mannermaa, Arto
    Kuopio University Hospital, Finland; Kuopio University Hospital, Finland; University of Eastern Finland, Finland.
    Manoukian, Siranoush
    Ist Nazl Tumori, Italy.
    Le Marchand, Loic
    University of Hawaii, HI 96813 USA.
    Margolin, Sara
    Karolinska Institute, Sweden.
    Marme, Frederik
    Heidelberg University, Germany; Heidelberg University, Germany.
    Massuger, Leon F. A. G.
    Radboud University of Nijmegen, Netherlands.
    Matsuo, Keitaro
    Kyushu University, Japan.
    Mazoyer, Sylvie
    University of Lyon, France.
    McGuffog, Lesley
    University of Cambridge, England.
    McLean, Catriona
    Alfred Hospital, Australia.
    McNeish, Iain
    University of Glasgow, Scotland.
    Meindl, Alfons
    Technical University of Munich, Germany.
    Menon, Usha
    UCL EGA Institute Womens Heatlh, England.
    Mensenkamp, Arjen R.
    Radboud University of Nijmegen, Netherlands.
    Milne, Roger L.
    Cancer Council Victoria, Australia; University of Melbourne, Australia.
    Montagna, Marco
    IRCCS, Italy.
    Moysich, Kirsten B.
    Roswell Pk Cancer Institute, NY 14263 USA.
    Muir, Kenneth
    University of Warwick, England; University of Manchester, England.
    Mulligan, Anna Marie
    University of Health Network, Canada; University of Toronto, Canada.
    Nathanson, Katherine L.
    University of Penn, PA 19104 USA.
    Ness, Roberta B.
    University of Texas Houston, TX 77030 USA.
    Neuhausen, Susan L.
    Beckman Research Institute City Hope, CA 91010 USA.
    Nevanlinna, Heli
    University of Helsinki, Finland; University of Helsinki, Finland.
    Nord, Silje
    University of Oslo, Norway.
    Nussbaum, Robert L.
    University of Calif San Francisco, CA 94143 USA.
    Odunsi, Kunle
    Roswell Pk Cancer Institute, NY 14263 USA.
    Offit, Kenneth
    Mem Sloan Kettering Cancer Centre, NY 10065 USA.
    Olah, Edith
    National Institute Oncol, Hungary.
    Olopade, Olufunmilayo I.
    University of Chicago, IL 60637 USA.
    Olson, Janet E.
    Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.
    Olswold, Curtis
    Mayo Clin, MN 55902 USA.
    OMalley, David
    Ohio State University, OH 43210 USA; James Graham Brown Cancer Centre, OH 43210 USA.
    Orlow, Irene
    Mem Sloan Kettering Cancer Centre, NY 10017 USA.
    Orr, Nick
    Institute Cancer Research, England.
    Osorio, Ana
    University of Copenhagen, Denmark; Spanish National Cancer Centre CNIO, Spain; Biomed Network Rare Disease CIBERER, Spain.
    Kyung Park, Sue
    Seoul National University, South Korea; Seoul National University, South Korea; Seoul National University, South Korea.
    Pearce, Celeste L.
    University of Southern Calif, CA 90033 USA.
    Pejovic, Tanja
    Oregon Health and Science University, OR 97239 USA; Oregon Health and Science University, OR 97239 USA.
    Peterlongo, Paolo
    FIRC Italian Fdn Cancer Research, Italy.
    Pfeiler, Georg
    Medical University of Vienna, Austria.
    Phelan, Catherine M.
    H Lee Moffitt Cancer Centre and Research Institute, FL 33606 USA.
    Poole, Elizabeth M.
    Harvard University, MA 02115 USA; Brigham and Womens Hospital, MA 02115 USA; Harvard University, MA 02115 USA.
    Pylkas, Katri
    Centre NordLab, Finland; University of Oulu, Finland.
    Radice, Paolo
    Ist Nazl Tumori, Italy.
    Rantala, Johanna
    Karolinska University Hospital, Sweden.
    Usman Rashid, Muhammad
    German Cancer Research Centre, Germany; Shaukat Khanum Mem Cancer Hospital and Research Centre SKMCH and RC, Pakistan.
    Rennert, Gad
    Clalit National Israeli Cancer Control Centre, Israel; Carmel Hospital, Israel.
    Rhenius, Valerie
    University of Cambridge, England.
    Rhiem, Kerstin
    University Hospital Cologne, Germany; University Hospital Cologne, Germany.
    Risch, Harvey A.
    Yale University, CT 06510 USA.
    Rodriguez, Gus
    NorthShore University of HealthSyst, IL 60201 USA.
    Anne Rossing, Mary
    Fred Hutchinson Cancer Research Centre, WA 98109 USA; University of Washington, WA 98109 USA.
    Rudolph, Anja
    German Cancer Research Centre, Germany.
    Salvesen, Helga B.
    Haukeland Hospital, Norway; University of Bergen, Norway.
    Sangrajrang, Suleeporn
    National Cancer Institute, Thailand.
    Sawyer, Elinor J.
    Kings Coll London, England.
    Schildkraut, Joellen M.
    Duke University, NC 27710 USA; Duke Cancer Institute, NC 27710 USA.
    Schmidt, Marjanka K.
    Netherlands Cancer Institute, Netherlands.
    Schmutzler, Rita K.
    University Hospital Cologne, Germany; University Hospital Cologne, Germany; University Hospital Cologne, Germany; University Hospital Cologne, Germany.
    Sellers, Thomas A.
    H Lee Moffitt Cancer Centre and Research Institute, FL 33606 USA.
    Seynaeve, Caroline
    Erasmus MC Cancer Institute, Netherlands.
    Shah, Mitul
    University of Cambridge, England.
    Shen, Chen-Yang
    Academic Sinica, Taiwan; China Medical University, Taiwan.
    Shu, Xiao-Ou
    Vanderbilt University, TN 37203 USA.
    Sieh, Weiva
    Stanford University, CA 94305 USA.
    Singer, Christian F.
    Medical University of Vienna, Austria.
    Sinilnikova, Olga M.
    Centre Leon Berard, France; University of Lyon 1, France.
    Slager, Susan
    Mayo Clin, MN 55902 USA.
    Song, Honglin
    University of Cambridge, England.
    Soucy, Penny
    University of Laval, Canada.
    Southey, Melissa C.
    University of Melbourne, Australia.
    Stenmark Askmalm, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi och klinisk genetik. University of Lund Hospital, Sweden.
    Stoppa-Lyonnet, Dominique
    Institute Curie, France; Institute Curie, France; Sorbonne Paris Cite, France.
    Sutter, Christian
    University of Heidelberg Hospital, Germany.
    Swerdlow, Anthony
    Institute Cancer Research, England; Institute Cancer Research, England.
    Tchatchou, Sandrine
    Mt Sinai Hospital, Canada.
    Teixeira, Manuel R.
    Portuguese Oncology Institute, Portugal; University of Porto, Portugal.
    Teo, Soo H.
    University of Malaya, Malaysia; Cancer Research Initiat Fdn, Malaysia.
    Terry, Kathryn L.
    Harvard University, MA 02115 USA; Brigham and Womens Hospital, MA 02115 USA; Harvard University, MA 02115 USA.
    Beth Terry, Mary
    Columbia University, NY 10027 USA.
    Thomassen, Mads
    Odense University Hospital, Denmark.
    Grazia Tibiletti, Maria
    University of Insubria, Italy.
    Tihomirova, Laima
    Latvian Biomed Research and Study Centre, Latvia.
    Tognazzo, Silvia
    IRCCS, Italy.
    Ewart Toland, Amanda
    Vanderbilt University, TN 37203 USA; IdISSC El Institute Invest Sanitaria Hospital Clin San Car, Spain; Ohio State University, OH 43210 USA.
    Tomlinson, Ian
    University of Oxford, England; University of Oxford, England.
    Torres, Diana
    German Cancer Research Centre, Germany; Pontificia University of Javeriana, Colombia.
    Truong, Therese
    INSERM, France; University of Paris 11, France.
    Tseng, Chiu-chen
    University of Southern Calif, CA 90033 USA.
    Tung, Nadine
    Beth Israel Deaconess Medical Centre, MA 02215 USA.
    Tworoger, Shelley S.
    Harvard University, MA 02115 USA; Brigham and Womens Hospital, MA 02115 USA; Harvard University, MA 02115 USA.
    Vachon, Celine
    Mayo Clin, MN 55902 USA.
    van den Ouweland, Ans M. W.
    Erasmus University, Netherlands.
    van Doorn, Helena C.
    Erasmus MC Cancer Institute, Netherlands.
    van Rensburg, Elizabeth J.
    University of Pretoria, South Africa.
    Vant Veer, Laura J.
    Netherlands Cancer Institute, Netherlands.
    Vanderstichele, Adriaan
    University Hospital Leuven, Belgium.
    Vergote, Ignace
    University Hospital Leuven, Belgium.
    Vijai, Joseph
    Mem Sloan Kettering Cancer Centre, NY 10065 USA.
    Wang, Qin
    University of Cambridge, England.
    Wang-Gohrke, Shan
    University Hospital Ulm, Germany.
    Weitzel, Jeffrey N.
    City Hope Clin Cancer Genet Community Research Network, CA 91010 USA.
    Wentzensen, Nicolas
    NCI, MD 20892 USA.
    Whittemore, Alice S.
    Stanford University, CA 94305 USA.
    Wildiers, Hans
    University Hospital Leuven, Belgium.
    Winqvist, Robert
    Centre NordLab, Finland; University of Oulu, Finland.
    Wu, Anna H.
    University of Southern Calif, CA 90033 USA.
    Yannoukakos, Drakoulis
    National Centre Science Research Demokritos, Greece.
    Yoon, Sook-Yee
    Sime Darby Medical Centre, Malaysia; University of Malaya, Malaysia.
    Yu, Jyh-Cherng
    National Def Medical Centre, Taiwan.
    Zheng, Wei
    Vanderbilt University, TN 37203 USA.
    Zheng, Ying
    Shanghai Centre Disease Control and Prevent, Peoples R China.
    Kum Khanna, Kum
    QIMR Berghofer Medical Research Institute, Australia.
    Simard, Jacques
    University of Laval, Canada.
    Monteiro, Alvaro N.
    H Lee Moffitt Cancer Centre and Research Institute, FL 33612 USA.
    French, Juliet D.
    QIMR Berghofer Medical Research Institute, Australia.
    Couch, Fergus J.
    Mayo Clin, MN 55902 USA; Mayo Clin, MN 55905 USA.
    Freedman, Matthew L.
    Dana Farber Cancer Institute, MA 02215 USA.
    Easton, Douglas F.
    University of Cambridge, England; University of Cambridge, England.
    Dunning, Alison M.
    University of Cambridge, England.
    Pharoah, Paul D.
    University of Cambridge, England.
    Edwards, Stacey L.
    QIMR Berghofer Medical Research Institute, Australia.
    Chenevix-Trench, Georgia
    QIMR Berghofer Medical Research Institute, Australia.
    Antoniou, Antonis C.
    University of Cambridge, England.
    Gayther, Simon A.
    University of Southern Calif, CA 90033 USA; Cedars Sinai Medical Centre, CA 90048 USA.
    Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus2016Ingår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 7, artikel-id 12675Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10−20), ER-negative BC (P=1.1 × 10−13), BRCA1-associated BC (P=7.7 × 10−16) and triple negative BC (P-diff=2 × 10−5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10−3) and ABHD8 (P<2 × 10−3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.

  • 340.
    Lennikov, Anton
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Laboratory of Biomedical Cell Technologies, School of Biomedicine, Far Eastern Federal University, Vladivostok, Russia.
    Mirabelli, Pierfrancesco
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM.
    Mukwaya, Anthony
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Schaupper, Mira
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Thangavelu, Muthukumar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM.
    Lachota, Mieszko
    Department of Immunology, Medical University of Warsaw, Warsaw, Poland.
    Ali, Zaheer
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten.
    Jensen, Lasse
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk farmakologi.
    Lagali, Neil
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM.
    Selective IKK2 inhibitor IMD0354 disrupts NF-kappa B signaling to suppress corneal inflammation and angiogenesis2018Ingår i: Angiogenesis, ISSN 0969-6970, E-ISSN 1573-7209, Vol. 21, nr 2, s. 267-285Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Corneal neovascularization is a sight-threatening condition caused by angiogenesis in the normally avascular cornea. Neovascularization of the cornea is often associated with an inflammatory response, thus targeting VEGF-A alone yields only a limited efficacy. The NF-kappa B signaling pathway plays important roles in inflammation and angiogenesis. Here, we study consequences of the inhibition of NF-kappa B activation through selective blockade of the IKK complex I kappa B kinase beta (IKK2) using the compound IMD0354, focusing on the effects of inflammation and pathological angiogenesis in the cornea. In vitro, IMD0354 treatment diminished HUVEC migration and tube formation without an increase in cell death and arrested rat aortic ring sprouting. In HUVEC, the IMD0354 treatment caused a dose-dependent reduction in VEGF-A expression, suppressed TNF alpha-stimulated expression of chemokines CCL2 and CXCL5, and diminished actin filament fibers and cell filopodia formation. In developing zebrafish embryos, IMD0354 treatment reduced expression of Vegf-a and disrupted retinal angiogenesis. In inflammation-induced angiogenesis in the rat cornea, systemic selective IKK2 inhibition decreased inflammatory cell invasion, suppressed CCL2, CXCL5, Cxcr2, and TNF-alpha expression and exhibited anti-angiogenic effects such as reduced limbal vessel dilation, reduced VEGF-A expression and reduced angiogenic sprouting, without noticeable toxic effect. In summary, targeting NF-kappa B by selective IKK2 inhibition dampened the inflammatory and angiogenic responses in vivo by modulating the endothelial cell expression profile and motility, thus indicating an important role of NF-kappa B signaling in the development of pathologic corneal neovascularization.

  • 341.
    Lewander, Per
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Dahle, Charlotte
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Larsson, B.
    Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Wetterö, Jonas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Skogh, Thomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Circulating cartilage oligomeric matrix protein in juvenile idiopathic arthritis2017Ingår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 46, nr 3, s. 194-197Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: Raised serum cartilage oligomeric matrix protein (sCOMP) has been reported to predict erosive disease in early rheumatoid arthritis (RA). In juvenile idiopathic arthritis (JIA), subnormal sCOMP levels have been associated with ongoing inflammation and growth retardation. In this study we aimed to assess sCOMP, C-reactive protein (CRP), and insulin-like growth factor (IGF)-1 in children/adolescents with JIA and in referents.Method: We enrolled 52 JIA patients at planned outpatient visits and 54 inpatients with ongoing infection (infection referents). A total of 120 referents testing negative for immunoglobulin (Ig)E-mediated allergy (IgE referents) served as controls. All serum samples were analysed for COMP, IGF-1, and CRP.Results: The average sCOMP level was highest among the IgE referents and lowest among the infection referents. In the JIA patients, the level of sCOMP was not associated with the level of CRP or with clinical signs of disease activity.Conclusions: The results of this study do not support routine clinical analysis of sCOMP levels in patients with JIA.

  • 342.
    Lidayova, Kristina
    et al.
    Uppsala University, Sweden.
    Frimmel, Hans
    Uppsala University, Sweden.
    Wang, Chunliang
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. KTH Royal Institute Technology, Sweden.
    Bengtsson, Ewert
    Uppsala University, Sweden.
    Smedby, Örjan
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Linköping. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. KTH Royal Institute Technology, Sweden.
    Fast vascular skeleton extraction algorithm2016Ingår i: Pattern Recognition Letters, ISSN 0167-8655, E-ISSN 1872-7344, Vol. 76, s. 67-75Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Vascular diseases are a common cause of death, particularly in developed countries. Computerized image analysis tools play a potentially important role in diagnosing and quantifying vascular pathologies. Given the size and complexity of modern angiographic data acquisition, fast, automatic and accurate vascular segmentation is a challenging task. In this paper we introduce a fully automatic high-speed vascular skeleton extraction algorithm that is intended as a first step in a complete vascular tree segmentation program. The method takes a 3D unprocessed Computed Tomography Angiography (CTA) scan as input and produces a graph in which the nodes are centrally located artery voxels and the edges represent connections between them. The algorithm works in two passes where the first pass is designed to extract the skeleton of large arteries and the second pass focuses on smaller vascular structures. Each pass consists of three main steps. The first step sets proper parameters automatically using Gaussian curve fitting. In the second step different filters are applied to detect voxels nodes - that are part of arteries. In the last step the nodes are connected in order to obtain a continuous centerline tree for the entire vasculature. Structures found, that do not belong to the arteries, are removed in a final anatomy-based analysis. The proposed method is computationally efficient with an average execution time of 29 s and has been tested on a set of CTA scans of the lower limbs achieving an average overlap rate of 97% and an average detection rate of 71%. (C) 2015 Elsevier B.V. All rights reserved.

  • 343.
    Liest, Lisbeth
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten.
    Omran, Ahmed Shaker
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Mikiver, Rasmus
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för verksamhetsstöd och utveckling, Regionalt Cancercentrum.
    Rosenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Uppugunduri, Srinivas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    RMI and ROMA are equally effective in discriminating between benign and malignant gynecological tumors: A prospective population-based study2019Ingår i: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 98, nr 1, s. 24-33Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction Our primary objective was to test the hypothesis that human epididymal protein 4 (HE4) and risk of ovarian malignancy index outperform the CA 125 and risk of malignancy index tests in categorizing a pelvic mass into high or low risk of malignancy in a Swedish population. Furthermore, cut-off values needed to be defined for HE4 and ROMA in premenopausal and postmenopausal women prior to their introduction to clinical practice. A third objective was to investigate the correlation between HE4 levels in serum and urine. Material and methods Women with a pelvic mass scheduled for surgery were recruited from nine hospitals in south-east Sweden. Preoperative blood samples were taken for analyzing CA125 and HE4 as well as urine samples for analyzing HE4. Results We enrolled a total of 901 women, of whom 784 were evaluable. In the premenopausal and postmenopausal groups, no significant differences were found for sensitivity, positive and negative predictive value, either for RMI vs ROMA or for CA125 vs HE4 using a fixed specificity of 75%. Cut-off values indicating malignancy were established for HE4 and ROMA in premenopausal and postmenopausal women. We found no correlation between HE4 concentration in serum and urine. Conclusions We could not confirm that ROMA had diagnostic superiority over RMI in categorizing women with a pelvic mass into low-risk or high-risk groups for malignancy in a Swedish population. We have defined cut-off values for HE4 and ROMA. The lack of correlation between serum and urine HE4 obviates the introduction of urine HE4 analysis in clinical diagnostics.

  • 344.
    Lill, Christina M.
    et al.
    University of Lubeck, Germany; Max Planck Institute Molecular Genet, Germany.
    Rengmark, Aina
    Oslo University Hospital, Norway.
    Pihlstrom, Lasse
    Oslo University Hospital, Norway.
    Fogh, Isabella
    Kings Coll London, England.
    Shatunov, Aleksey
    Kings Coll London, England.
    Sleiman, Patrick M.
    Childrens Hospital Philadelphia, PA 19104 USA; Childrens Hospital Philadelphia, PA 19104 USA; University of Penn, PA 19104 USA; University of Turin, Italy.
    Wang, Li-San
    University of Penn, PA 19104 USA; University of Turin, Italy.
    Liu, Tian
    Max Planck Institute Human Dev, Germany.
    Lassen, Christina F.
    Danish Cancer Soc, Denmark.
    Meissner, Esther
    Max Planck Institute Molecular Genet, Germany.
    Alexopoulos, Panos
    Technical University of Munich, Germany.
    Calvo, Andrea
    University of Turin, Italy.
    Chio, Adriano
    University of Turin, Italy; Neurosci Institute Turin, Italy.
    Dizdar (Dizdar Segrell), Nil
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Region Östergötland, Diagnostikcentrum, Klinisk kemi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Faltraco, Frank
    Goethe University of Frankfurt, Germany.
    Forsgren, Lars
    Umeå University, Sweden.
    Kirchheiner, Julia
    University of Ulm, Germany.
    Kurz, Alexander
    Technical University of Munich, Germany.
    Larsen, Jan P.
    Stavanger University Hospital, Norway.
    Liebsch, Maria
    Max Planck Institute Molecular Genet, Germany.
    Linder, Jan
    Umeå University, Sweden.
    Morrison, Karen E.
    University of Birmingham, England; University Hospital Birmingham, England.
    Nissbrandt, Hans
    University of Gothenburg, Sweden.
    Otto, Markus
    University of Ulm, Germany.
    Pahnke, Jens
    University of Oslo, Norway; Oslo University Hospital, Norway; University of Lubeck, Germany.
    Partch, Amanda
    University of Penn, PA 19104 USA.
    Restagno, Gabriella
    Azienda Osped Citta Salute and Science, Italy.
    Rujescu, Dan
    University of Halle Wittenberg, Germany.
    Schnack, Cathrin
    University of Ulm, Germany.
    Shaw, Christopher E.
    Kings Coll London, England.
    Shaw, Pamela J.
    University of Sheffield, England.
    Tumani, Hayrettin
    University of Ulm, Germany.
    Tysnes, Ole-Bjorn
    Haukeland Hospital, Norway; University of Bergen, Norway.
    Valladares, Otto
    University of Penn, PA 19104 USA.
    Silani, Vincenzo
    IRCCS Ist Auxol Italiano, Italy; University of Milan, Italy.
    van den Berg, Leonard H.
    University of Medical Centre Utrecht, Netherlands.
    van Rheenen, Wouter
    University of Medical Centre Utrecht, Netherlands.
    Veldink, Jan H.
    University of Medical Centre Utrecht, Netherlands.
    Lindenberger, Ulman
    Max Planck Institute Human Dev, Germany.
    Steinhagen-Thiessen, Elisabeth
    Charite, Germany.
    Teipel, Stefan
    German Centre Neurodegenerat Disease DZNE, Germany; University of Rostock, Germany.
    Perneczky, Robert
    Technical University of Munich, Germany; University of London Imperial Coll Science Technology and Med, England; West London Mental Health Trust, England.
    Hakonarson, Hakon
    Childrens Hospital Philadelphia, PA 19104 USA; Childrens Hospital Philadelphia, PA 19104 USA; University of Penn, PA 19104 USA.
    Hampel, Harald
    AXA Research Fund, France; University of Sorbonne, France.
    von Arnim, Christine A. F.
    University of Ulm, Germany.
    Olsen, Jorgen H.
    Danish Cancer Soc, Denmark.
    Van Deerlin, Vivianna M.
    University of Penn, PA 19104 USA; University of Turin, Italy.
    Al-Chalabi, Ammar
    Kings Coll London, England.
    Toft, Mathias
    Oslo University Hospital, Norway.