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  • 251.
    Ivarsson, Magnus
    et al.
    Swedish Museum Nat Hist, Sweden; Swedish Museum Nat Hist, Sweden.
    Broman, Curt
    Stockholm University, Sweden.
    Gustafsson, Håkan
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Biomedical Engineering.
    Holm, Nils G.
    Stockholm University, Sweden.
    Biogenic Mn-Oxides in Subseafloor Basalts2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 6, p. e0128863-Article in journal (Refereed)
    Abstract [en]

    The deep biosphere of the subseafloor basalts is recognized as a major scientific frontier in disciplines like biology, geology, and oceanography. Recently, the presence of fungi in these environments has involved a change of view regarding diversity and ecology. Here, we describe fossilized fungal communities in vugs in subseafloor basalts from a depth of 936.65 metres below seafloor at the Detroit Seamount, Pacific Ocean. These fungal communities are closely associated with botryoidal Mn oxides composed of todorokite. Analyses of the Mn oxides by Electron Paramagnetic Resonance spectroscopy (EPR) indicate a biogenic signature. We suggest, based on mineralogical, morphological and EPR data, a biological origin of the botryoidal Mn oxides. Our results show that fungi are involved in Mn cycling at great depths in the seafloor and we introduce EPR as a means to easily identify biogenic Mn oxides in these environments.

  • 252.
    Jacobsson, Stefan
    et al.
    Avdelningen för Klinisk kemi och transfusionsmedicin, Institutionen för biomedicin, Sahlgrenska akademin, Göteborgs universitet.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Anemier2018In: Laurells klinisk kemi i praktisk medicin / [ed] Elvar Theodorsson, Maria Berggren Söderlund, Lund: Studentlitteratur AB, 2018, 10, p. 209-264Chapter in book (Other academic)
  • 253.
    Jakobsen Falk, Ingrid
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Willander, Kerstin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Chaireti, Roza
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine. Karolinska University Hospital, Sweden.
    Lund, Johan
    Huddinge University Hospital, Sweden.
    Nahi, Hareth
    Huddinge University Hospital, Sweden.
    Hermanson, Monica
    Uppsala University, Sweden.
    Green, Henrik
    National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Lotfi, Kourosh
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    TP53 mutations and MDM2(SNP309) identify subgroups of AML patients with impaired outcome2015In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 94, no 4, p. 355-362Article in journal (Refereed)
    Abstract [en]

    BackgroundTP53 is commonly mutated in several cancers and confers treatment resistance and poor prognosis. Altered expression of mouse double minute 2 (MDM2), a negative regulator of p53, may also attenuate normal p53 signaling, thereby enhancing tumor transformation and resistance to apoptosis. The single nucleotide polymorphism (SNP) 309 has been reported to increase MDM2 expression and impair normal p53 response. Experimental designWe investigated the frequency and impact of TP53 mutations (TP53mut) and MDM2(SNP309) on treatment outcome and overall survival (OS) in 189 Swedish acute myeloid leukemia patients. The genetic analyses were performed using SSCA and direct sequencing (for mutations in exon 5-8 of TP53) and Pyrosequencing (for the MDM2(SNP309)). ResultsWe found a high frequency (22%) of TP53mut in patients with cytogenetic aberrations, with association to high-risk cytogenetics (Pless than0.001). TP53mut patients had lower response rates (22% compared with 76% CR in TP53 wild-type (wt) patients, Pless than0.001) and reduced OS (2 and 16months, respectively, Pless than0.001). In TP53wt patients with high or intermediate risk cytogenetic aberrations, the MDM2(SNP309) conferred an impaired outcome, with patients carrying the alternative G-allele having shorter OS compared with T/T patients (median 9 vs. 50months, P=0.020). ConclusionsOur results show that TP53mut analysis and MDM2(SNP309) genotyping may be useful tools for prognostication, risk stratification, and selection of patients most likely to benefit from new drugs targeting the p53 signaling pathway.

  • 254.
    Jedlinski, Adam
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping.
    Garvin, Stina
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology.
    Johansson, Ann-Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Edqvist, Per-Henrik
    Uppsala University, Uppsala, Sweden.
    Pontén, Fredrik
    Uppsala University, Uppsala, Sweden.
    Roberg, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping.
    Cetuximab sensitivity of head and neck squamous cell carcinoma xenografts is associated with treatment-induced reduction of EGFR, pEGFR, and pSrc2017In: Journal of Oral Pathology & Medicine, ISSN 0904-2512, E-ISSN 1600-0714, no 9, p. 717-724Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The aim of this study was to validate in vitro drug sensitivity testing of head and neck squamous cell carcinoma (HNSCC)cell lines in an in vivo xenograft model, and to identify treatment-induced changes in the EGFR signaling pathway that could be used as markersfor cetuximab treatment response.

    METHODS: The in vitro cetuximab sensitivity of two HNSCC cell lines, UT-SCC-14 and UTSCC-45, was assessed using a crystal violet assay. In order to determine the corresponding in vivo sensitivity, UT-SCC-14 and UT-SCC-45 xenografts were generated in female BALB/c (nu/nu) nude mice. Mice were given three injections of intraperitoneal cetuximab or PBS and the tumor volume was recorded continuously. The expression of epidermal growth factor receptor (EGFR), phosphorylated EGFR (pEGFR), phosphorylated Src (pSrc), and Ki67 was investigated by immunohistochemistry.

    RESULTS: The treatment sensitive UT-SCC-14 cells were found to have an intrinsic cetuximab sensitivity (ICmabS) of 0.15 whereas the ICmabS of the insensitive cell line UT-SCC-45 was 0.78. The corresponding size ratio between untreated and cetuximab treated xenografts was 0.22 and 0.83 for UT-SCC-14 and UT-SCC-45, respectively. UT-SCC-14 cells had a higher baseline expression of pEGFR as compared to UT-SCC-45. Furthermore, in UT-SCC-14 xenografts there was a decrease in EGFR, pEGFR and pSrc upon cetuximab treatment. In contrast, a slight cetuximab-induced increase in EGFR, pEGFR and pSrc was observed in treatment-resistant UT-SCC-45 xenografts.

    CONCLUSIONS: The in vitro treatment sensitivity was reproduced in the in vivo model and cetuximab sensitivity was found to associate with a treatment-induced reduction in pEGFR and pSrc.

  • 255.
    Jensen, Lasse
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Karolinska Institute, Sweden.
    Editorial Material: A circadian prelude to regulation of angiogenesis and thrombosis by prolactin and plasminogen activator inhibitor-1 in TRANSLATIONAL CANCER RESEARCH, vol 5, issue 1, pp 79-822016In: TRANSLATIONAL CANCER RESEARCH, ISSN 2218-676X, Vol. 5, no 1, p. 79-82Article in journal (Other academic)
    Abstract [en]

    n/a

  • 256.
    Jensen, Lasse
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Karolinska Institute, Sweden.
    Editorial Material: When tumors are (co-) opting to resist anti-angiogenic treatment in TRANSLATIONAL CANCER RESEARCH, vol 5, issue , pp S1433-S14362016In: TRANSLATIONAL CANCER RESEARCH, ISSN 2218-676X, Vol. 5, p. S1433-S1436Article in journal (Other academic)
    Abstract [en]

    n/a

  • 257.
    Jensen, Lasse
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Hot, Belma
    Karolinska Inst, Sweden; Ludwig Inst Canc Res Ltd, Sweden.
    Ramskold, Daniel
    Karolinska Inst, Sweden; Ludwig Inst Canc Res Ltd, Sweden.
    Germano, Raoul F. V.
    Univ Libre Bruxelles, Belgium.
    Yokota, Chika
    Ludwig Inst Canc Res Ltd, Sweden; Stockholm Univ, Sweden.
    Giatrellis, Sarantis
    Karolinska Inst, Sweden.
    Lauschke, Volker M.
    Karolinska Inst, Sweden.
    Hubmacher, Dirk
    Icahn Sch Med Mt Sinai, NY 10029 USA.
    Li, Minerva X.
    Ludwig Inst Canc Res Ltd, Sweden; Lund Univ, Sweden.
    Hupe, Mike
    Ludwig Inst Canc Res Ltd, Sweden; Univ Wurzburg, Germany.
    Arnold, Thomas D.
    Univ Calif San Francisco, CA 94143 USA.
    Sandberg, Rickard
    Karolinska Inst, Sweden; Ludwig Inst Canc Res Ltd, Sweden.
    Frisen, Jonas
    Karolinska Inst, Sweden.
    Trusohamn, Marta
    Karolinska Inst, Sweden.
    Martowicz, Agnieszka
    Karolinska Inst, Sweden.
    Wisniewska-Kruk, Joanna
    Karolinska Inst, Sweden.
    Nyqvist, Daniel
    Karolinska Inst, Sweden.
    Adams, Ralf H.
    Univ Munster, Germany.
    Apte, Suneel S.
    Cleveland Clin Fdn, OH 44195 USA.
    Vanhollebeke, Benoit
    Univ Libre Bruxelles, Belgium; Walloon Excellence Life Sci and Biotechnol WELBIO, Belgium.
    Stenman, Jan M.
    Ludwig Inst Canc Res Ltd, Sweden.
    Kele, Julianna
    Karolinska Inst, Sweden; Ludwig Inst Canc Res Ltd, Sweden.
    Disruption of the Extracellular Matrix Progressively Impairs Central Nervous System Vascular Maturation Downstream of beta-Catenin Signaling2019In: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 39, no 7, p. 1432-1447Article in journal (Refereed)
    Abstract [en]

    Objective- The Wnt/beta-catenin pathway orchestrates development of the blood-brain barrier, but the downstream mechanisms involved at different developmental windows and in different central nervous system (CNS) tissues have remained elusive. Approach and Results- Here, we create a new mouse model allowing spatiotemporal investigations of Wnt/beta-catenin signaling by induced overexpression of Axin1, an inhibitor of beta-catenin signaling, specifically in endothelial cells (Axin1(iEC)-(OE)). AOE (Axin1 overexpression) in Axin1(iEC)-(OE) mice at stages following the initial vascular invasion of the CNS did not impair angiogenesis but led to premature vascular regression followed by progressive dilation and inhibition of vascular maturation resulting in forebrain-specific hemorrhage 4 days post-AOE. Analysis of the temporal Wnt/beta-catenin driven CNS vascular development in zebrafish also suggested that Axin1(iEC)-(OE) led to CNS vascular regression and impaired maturation but not inhibition of ongoing angiogenesis within the CNS. Transcriptomic profiling of isolated, beta-catenin signaling-deficient endothelial cells during early blood-brain barrier-development (E11.5) revealed ECM (extracellular matrix) proteins as one of the most severely deregulated clusters. Among the 20 genes constituting the forebrain endothelial cell-specific response signature, 8 (Adamtsl2, Apod, Ctsw, Htra3, Pglyrp1, Spock2, Ttyh2, and Wfdc1) encoded bona fide ECM proteins. This specific beta-catenin-responsive ECM signature was also repressed in Axin1(iEC)-(OE) and endothelial cell-specific beta-catenin-knockout mice (Ctnnb1-KOiEC) during initial blood-brain barrier maturation (E14.5), consistent with an important role of Wnt/beta-catenin signaling in orchestrating the development of the forebrain vascular ECM. Conclusions- These results suggest a novel mechanism of establishing a CNS endothelium-specific ECM signature downstream of Wnt-beta-catenin that impact spatiotemporally on blood-brain barrier differentiation during forebrain vessel development.

  • 258.
    Jia, Min
    et al.
    Karolinska Institute, Sweden.
    Andreassen, Trygve
    Norwegian University of Science and Technology, Norway.
    Jensen, Lasse
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Karolinska Institute, Sweden.
    Frost Bathen, Tone
    Norwegian University of Science and Technology, Norway.
    Sinha, Indranil
    Karolinska Institute, Sweden.
    Gao, Hui
    Karolinska Institute, Sweden.
    Zhao, Chunyan
    Karolinska Institute, Sweden.
    Haldosen, Lars-Arne
    Karolinska Institute, Sweden.
    Cao, Yihai
    Karolinska Institute, Sweden.
    Girnita, Leonard
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Andreas Moestue, Siver
    Norwegian University of Science and Technology, Norway.
    Dahlman-Wright, Karin
    Karolinska Institute, Sweden.
    Estrogen Receptor a Promotes Breast Cancer by Reprogramming Choline Metabolism2016In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 76, no 19, p. 5634-5646Article in journal (Refereed)
    Abstract [en]

    Estrogen receptor alpha (ER alpha) is a key regulator of breast growth and breast cancer development. Here, we report how ER alpha impacts these processes by reprogramming metabolism in malignant breast cells. We employed an integrated approach, combining genome-wide mapping of chromatin-bound ER alpha with estrogeninduced transcript and metabolic profiling, to demonstrate that ER alpha reprograms metabolism upon estrogen stimulation, including changes in aerobic glycolysis, nucleotide and amino acid synthesis, and choline (Cho) metabolism. Cho phosphotransfse CHPT1, identified as a direct era-regulated gene, was required for estrogen- induced effects on Cho metabolism, including increased phosphatidylcholine synthesis. CHPT1 silencing inhibited anchorage- independent growth and cell proliferation, also suppressing early-stage metastasis of tamoxifen-resistant breast cancer cells in a zebrafish xenograft model. Our results showed that era promotes metabolic alterations in breast cancer cells mediated by its target CHPT1, which this study implicates as a candidate therapeutic target. (C) 2016 AACR.

  • 259.
    Jogestrand, Tomas
    et al.
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Freden-Lindqvist, Johan
    Sahlgrens University Hospital, Sweden.
    Lindqvist, Madeleine
    Karolinska University Hospital, Sweden.
    Lundgren, Susanne
    Blekingesjukhuset, Sweden.
    Tillman, Ann-Sofie
    Region Östergötland, Center for Diagnostics, Department of Clinical Physiology in Norrköping.
    Zachrisson, Helene
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Discrepancies in recommended criteria for grading of carotid stenosis with ultrasound2016In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 36, no 4, p. 326-329Article in journal (Refereed)
    Abstract [en]

    The accuracy of duplex ultrasound for grading of internal carotid artery stenosis has been widely tested and shown to be high. However, different methods for measurement of the degree of carotid stenosis with the golden standard conventional angiography have been used in the different studies. This, together with other factors, has led to some confusion regarding the relation between the ultrasonographically measured flow velocity and the angiographically measured degree of stenosis. The ultrasound criteria that are used in Sweden (and in Germany) differ in an important way from the criteria recommended in North America and the United Kingdom for the same degree of angiographic stenoses. Possible reasons for the discrepancies are discussed in this article. The authors recommend absolute agreement locally whether ECST or NASCET criteria shall be used in the communication between radiologists, clinical physiologists, vascular surgeons, neurologists and other physicians involved in patient management decisions. Angle-dependent ultrasound criteria should be used and flow velocity measurements with ultrasound should be combined with assessment of plaque burden on 2D picture.

  • 260.
    Johansson, Joel
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Björnsson, Bergthor
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Ignatova, Simone
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Sandström, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Ekstedt, Mattias
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Littoral cell angioma in a patient with Crohn's disease.2015In: Case Reports in Gastrointestinal Medicine, ISSN 2090-6528, E-ISSN 2090-6536, Vol. 2015, p. 1-4, article id 474969Article in journal (Refereed)
    Abstract [en]

    Littoral cell angioma is a rare vascular tumor of the spleen. The pathogenesis is unknown but the lesion is associated with several malignancies and immunological disorders. The diagnosis requires histopathological examination. The malignant potential of this lesion is unknown, which is why splenectomy is recommend for all cases. Symptomatic cases generally suffer from hypersplenism and pyrexia. A previously healthy 20-year-old female was diagnosed with colonic Crohn's disease; as part of the work-up a magnetic resonance enterography was performed which showed multiple signal changes of the spleen. The patient reported chronic abdominal pain in the left upper quadrant, malaise, and fever. The unknown splenic lesions prompted a laparoscopic splenectomy; pathology revealed a littoral cell angioma. The abdominal pain and malaise remitted but the fever persisted one year despite adequate treatment of the patient's Crohn's disease. Littoral cell angioma is associated with immune-dysregulation including Crohn's disease with several reported cases. Signs and symptoms of hypersplenism and splenic lesions on imaging should raise suspicion of littoral cell angioma in patients with Crohn's disease. Magnetic resonance enterography to assess disease severity in Crohn's disease may provide an opportunity to study the prevalence and natural history of this rare splenic tumor.

  • 261.
    Johansson, Joel
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Sahin, Christofer
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Pestoff, Rebecka
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Ignatova, Simone
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Edsjö, Anders
    Sahlgrenska University Hospital Göteborg .
    Ekstedt, Mattias
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Stenmark Askmalm, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    A Novel SMAD4 Mutation Causing Severe Juvenile Polyposis Syndrome with Protein Losing Enteropathy, Immunodeficiency, and Hereditary Haemorrhagic Telangiectasia.2015In: Case Reports in Gastrointestinal Medicine, ISSN 2090-6528, E-ISSN 2090-6536, Vol. 2015, p. 1-5, article id 140616Article in journal (Refereed)
    Abstract [en]

    Juvenile polyposis syndrome (JPS) is a rare genetic disorder characterized by juvenile polyps of the gastrointestinal tract. We present a new pathogenic mutation of the SMAD4 gene and illustrate the need for a multidisciplinary health care approach to facilitate the correct diagnosis. The patient, a 47-year-old Caucasian woman, was diagnosed with anaemia at the age of 12. During the following 30 years, she developed numerous gastrointestinal polyps. The patient underwent several operations, and suffered chronic abdominal pain, malnutrition, and multiple infections. Screening of the SMAD4 gene revealed a novel, disease-causing mutation. In 2012, the patient suffered hypoalbuminemia and a large polyp in the small bowel was found. Gamma globulin was given but the patient responded with fever and influenza-like symptoms and refused more treatment. The patient underwent surgery in 2014 and made an uneventful recovery. At follow-up two months later albumin was 38 g/L and IgG was 6.9 g/L. Accurate diagnosis is essential for medical care. For patients with complex symptomatology, often with rare diseases, this is best provided by multidisciplinary teams including representatives from clinical genetics. Patients with a SMAD4 mutation should be followed up both for JPS and haemorrhagic hereditary telangiectasia and may develop protein loosing enteropathy and immunodeficiency.

  • 262.
    Jones, A Wayne
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Holmgren, A.
    Natl Board Forens Toxicol, Div Forens Toxicol, S-58758 Linkoping, Sweden.
    Kugelberg, Fredrik
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Toxicol, Div Forens Toxicol, S-58758 Linkoping, Sweden.
    Busardo, F. P.
    Sapienza Univ Rome, Italy.
    Relationship Between Postmortem Urine and Blood Concentrations of GHB Furnishes Useful Information to Help Interpret Drug Intoxication Deaths2018In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 42, no 9, p. 587-591Article in journal (Refereed)
    Abstract [en]

    This article reports the concentrations of gamma-hydroxybutyrate (GHB) in femoral blood and bladder urine in a case series of drug intoxication deaths (N = 37). GHB was determined in blood (B-GHB) and urine (U-GHB) by a GC-FID-GBL method and 30 mg/L was used as a cut-off concentration for reporting positive results. The mean (median) and range of GHB concentrations in bladder urine were 2,818 mg/L (1,900 mg/L) and 120-13,000 mg/L, respectively. These concentrations were appreciably higher than those in femoral blood, 637 mg/L (260 mg/L) and 30-9,200 mg/L, respectively. Urine/blood ratios of GHB were highly variable (mean 8.99, median 5.33 and range 0.16-29.3). GHB is rapidly metabolized and cleared from the bloodstream, whereas there is no metabolism occurring in the urinary bladder. In five autopsy cases, U-GHB was lower than B-GHB, which suggests that these individuals died before equilibration of the drug in all body fluids and tissues. In the other 32 deaths, U-GHB was higher than B-GHB, sometimes appreciably higher, which points towards a longer survival time after intake or administration of GHB. The analysis of urine extends the window of detection of GHB by several hours compared with blood samples, depending in part on when the bladder was last voided before death. Furthermore, the urinary concentration of GHB gives a hint about the concentration in blood during the time that the urine was produced in the kidney and stored in the bladder since the previous void.

  • 263.
    Jonsson, Anna K.
    et al.
    National Board Forens Med, Department Forens Genet and Forens Toxicol, S-58758 Linkoping, Sweden.
    Lövborg, Henrik
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Lohr, Wolfgang
    Umeå University, Sweden.
    Ekman, Bertil
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Rocklov, Joacim
    Umeå University, Sweden; Heidelberg University, Germany.
    Increased Risk of Drug-Induced Hyponatremia during High Temperatures2017In: International Journal of Environmental Research and Public Health, ISSN 1661-7827, E-ISSN 1660-4601, Vol. 14, no 7, article id 827Article in journal (Refereed)
    Abstract [en]

    Purpose: To investigate the relationship between outdoor temperature in Sweden and the reporting of drug-induced hyponatremia to the Medical Products Agency (MPA). Methods: All individual adverse drug reactions (ADR) reported to MPA from 1 January 2010 to 31 October 2013 of suspected drug-induced hyponatremia and random controls were identified. Reports where the ADR had been assessed as having at least a possible relation to the suspected drug were included. Information on administered drugs, onset date, causality assessment, sodium levels, and the geographical origin of the reports was extracted. A case-crossover design was used to ascertain the association between heat exposure and drug-induced hyponatremia at the individual level, while linear regression was used to study its relationship to sodium concentration in blood. Temperature exposure data were obtained from the nearest observation station to the reported cases. Results: During the study period, 280 reports of hyponatremia were identified. More cases of drug-induced hyponatremia were reported in the warmer season, with a peak in June, while other ADRs showed an opposite annual pattern. The distributed lag non-linear model indicated an increasing odds ratio (OR) with increasing temperature in the warm season with a highest odds ratio, with delays of 1-5 days after heat exposure. A cumulative OR for a lag time of 1 to 3 days was estimated at 2.21 at an average daily temperature of 20 degrees C. The change in sodium per 1 degrees C increase in temperature was estimated to be -0.37 mmol/L (95% CI: -0.02, -0.72). Conclusions: Warm weather appears to increase the risk of drug-induced hyponatremia.

  • 264.
    Jönsson, Anna K
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Natl Board Forens Med, Dept Forens Genet and Forens Chem, Linkoping, Sweden.
    Schill, Johan
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Jönköping, Sweden.
    Olsson, Hans
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry. Region Jönköping, Sweden.
    Spigset, Olav
    St Olavs Univ Hosp, Norway; Norwegian Univ Sci and Technol, Norway.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Venous Thromboembolism During Treatment with Antipsychotics: A Review of Current Evidence2018In: CNS Drugs, ISSN 1172-7047, E-ISSN 1179-1934, Vol. 32, no 1, p. 47-64Article, review/survey (Refereed)
    Abstract [en]

    This article summarises the current evidence on the risk of venous thromboembolism (VTE) with the use of antipsychotics. An increasing number of observational studies indicate an elevated risk of VTE in antipsychotic drug users. Although the use of certain antipsychotics has been associated with VTE, current data can neither conclusively verify differences in occurrence rates of VTE between first- and second-generation antipsychotics or between individual compounds, nor identify which antipsychotic drugs have the lowest risk of VTE. The biological mechanisms involved in the pathogenesis of this adverse drug reaction are still to be clarified but hypotheses such as drug-induced sedation, obesity, increased levels of antiphospholipid antibodies, enhanced platelet aggregation, hyperhomocysteinaemia and hyperprolactinaemia have been suggested. Risk factors associated with the underlying psychiatric disorder may at least partly explain the increased risk. Physicians should be aware of this potentially serious and even sometimes fatal adverse drug reaction and should consider discontinuing or switching the antipsychotic treatment in patients experiencing a VTE. Even though supporting evidence is limited, prophylactic antithrombotic treatment should be considered in risk situations for VTE.

  • 265.
    Kabakci, Zeynep
    et al.
    Univ Zurich, Switzerland.
    Kappeli, Simon
    Univ Zurich, Switzerland.
    Cantù, Claudio
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Univ Zurich, Switzerland.
    Jensen, Lasse
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Konig, Christiane
    Univ Zurich, Switzerland.
    Toggweiler, Janine
    Univ Zurich, Switzerland.
    Gentili, Christian
    Univ Zurich, Switzerland.
    Ribaudo, Giovanni
    Univ Padua, Italy.
    Zagotto, Giuseppe
    Univ Padua, Italy.
    Basler, Konrad
    Univ Zurich, Switzerland.
    Pinna, Lorenzo A.
    Univ Padua, Italy.
    Cozza, Giorgio
    Univ Padua, Italy.
    Ferrari, Stefano
    Univ Zurich, Switzerland.
    Pharmacophore-guided discovery of CDC25 inhibitors causing cell cycle arrest and tumor regression2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 1335Article in journal (Refereed)
    Abstract [en]

    CDC25 phosphatases play a key role in cell cycle transitions and are important targets for cancer therapy. Here, we set out to discover novel CDC25 inhibitors. Using a combination of computational methods, we defined a minimal common pharmacophore in established CDC25 inhibitors and performed virtual screening of a proprietary library. Based on the availability of crystal structures for CDC25A and CDC25B, we implemented a molecular docking strategy and carried out hit expansion/optimization. Enzymatic assays revealed that naphthoquinone scaffolds were the most promising CDC25 inhibitors among selected hits. At the molecular level, the compounds acted through a mixed-type mechanism of inhibition of phosphatase activity, involving reversible oxidation of cysteine residues. In 2D cell cultures, the compounds caused arrest of the cell cycle at the G1/S or at the G2/M transition. Mitotic markers analysis and time-lapse microscopy confirmed that CDK1 activity was impaired and that mitotic arrest was followed by death. Finally, the compounds induced differentiation, accompanied by decreased stemness properties, in intestinal crypt stem cell-derived Apc/K-Ras-mutant mouse organoids, and led to tumor regression and reduction of metastatic potential in zebrafish embryo xenografts used as in vivo model.

  • 266.
    Kalaiarasi, Arunachalam
    et al.
    Bharathidasan Univ, India.
    Sankar, Renu
    Bharathidasan Univ, India; Ohio State Univ, OH 44691 USA.
    Anusha, Chidambaram
    Bharathidasan Univ, India.
    Saravanan, Kandasamy
    Bharathidasan Univ, India.
    Aarthy, Kalyanasundaram
    Bharathidasan Univ, India.
    Karthic, Selvaraj
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Mathuram, Theodore Lemuel
    Univ Madras, India.
    Ravikumar, Vilwanathan
    Bharathidasan Univ, India.
    Copper oxide nanoparticles induce anticancer activity in A549 lung cancer cells by inhibition of histone deacetylase2018In: Biotechnology letters, ISSN 0141-5492, E-ISSN 1573-6776, Vol. 40, no 2, p. 249-256Article in journal (Refereed)
    Abstract [en]

    Copper oxide nanoparticles (CuO NPs) promoting anticancer activity may be due to the regulation of various classes of histone deacetylases (HDACs). Green-synthesized CuO NPs significantly arrested total HDAC level and also suppressed class I, II and IV HDACs mRNA expression in A549 cells. A549 cells treated with CuO NPs downregulated oncogenes and upregulated tumor suppressor protein expression. CuO NPs positively regulated both mitochondrial and death receptor-mediated apoptosis caspase cascade pathway in A549 cells. Green-synthesized CuO NPs inhibited HDAC and therefore shown apoptosis mediated anticancer activity in A549 lung cancer cell line.

  • 267.
    Kander, Thomas
    et al.
    Lund University, Sweden; Skåne University Hospital Lund, Sweden.
    Larsson, Anna
    Lund University, Sweden.
    Taune, Victor
    Lund University, Sweden.
    Schott, Ulf
    Lund University, Sweden; Skåne University Hospital Lund, Sweden.
    Tynngård, Nahreen
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Assessment of Haemostasis in Disseminated Intravascular Coagulation by Use of Point-of-Care Assays and Routine Coagulation Tests, in Critically Ill Patients; A Prospective Observational Study2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 3, p. e0151202-Article in journal (Refereed)
    Abstract [en]

    Background Disseminated intravascular coagulopathy (DIC) relates to the consumption of coagulation factors and platelets with bleeding and micro thrombosis events. Aim The aim of this study was to compare haemostasis parameters in critically ill patients with DIC versus patients without DIC, and in survivors versus non-survivors over time. Correlations between the DIC-score, the degree of organ failure and the haemostasis were assessed. Method Patients admitted to the intensive care unit with a condition known to be associated with DIC and with an expected length of stay of >3 days were included. Routine laboratory tests, prothrombin time, activated partial thromboplastin time, platelet count, fibrinogen concentration and D-dimer were measured. Coagulation and platelet function were assessed with two point-of-care devices; Multiplate and ROTEM. DIC scores were calculated according to the International Society on Thrombosis and Haemostasis and Japanese Association for Acute Medicine. Results Blood was sampled on days 0-1, 2-3 and 4-10 from 136 patients with mixed diagnoses during 290 sampling events. The point-of-care assays indicated a hypocoagulative response (decreased platelet aggregation and reduced clot strength) in patients with DIC and, over time, in non-survivors compared to survivors. Patients with DIC as well as non-survivors had decreased fibrinolysis as shown by ROTEM. DIC scores were higher in non-survivors than in survivors. Conclusions Patients with DIC displayed signs of a hypocoagulative response and impaired fibrinolysis, which was also evident over time in non-survivors. Patients with DIC had a higher mortality rate than non-DIC patients, and DIC scores were higher in non-survivors than in survivors.

  • 268.
    Kang Lim, Che
    et al.
    Karolinska University, Sweden; Singapore Gen Hospital, Singapore.
    Dahle, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Elvin, Kerstin
    Karolinska Institute, Sweden.
    Andersson, Bengt A.
    Sahlgrens University Hospital, Sweden.
    Ronnelid, Johan
    Uppsala University, Sweden.
    Melen, Erik
    Karolinska Institute, Sweden; Stockholm South Gen Hospital, Sweden.
    Bergstrom, Anna
    Karolinska Institute, Sweden.
    Truedsson, Lennart
    Lund University, Sweden.
    Hammarstrom, Lennart
    Karolinska University, Sweden.
    Reversal of Immunoglobulin A Deficiency in Children2015In: Journal of Clinical Immunology, ISSN 0271-9142, E-ISSN 1573-2592, Vol. 35, no 1, p. 87-91Article in journal (Refereed)
    Abstract [en]

    Immunoglobulin A deficiency (IgAD) is the most common primary immunodeficiency in the general population. It is defined as a serum IgA level below or equal to 0.07 g/l with normal IgM and IgG levels in children over the age of 4. However, a few cases of reversal of IgAD at later ages have been observed previously, especially in pediatric patients. This study aimed at investigating the frequency of reversal in a large cohort of children and young adults in order to evaluate the present definition of IgAD. Clinical laboratory records from 654 pediatric IgA deficient patients, 4-13 years of age, were retrieved from five university hospitals in Sweden. Follow up in the children where IgA serum levels had been routinely measured was subsequently performed. In addition, follow up of the IgA-levels was also performed at 4, 8 and 16 years of age in children who were IgA deficient at the age of 4 years in a Swedish population-based birth cohort study in Stockholm (BAMSE). Nine out of 39 (23.1 %) children who were identified as IgAD at 4 years of age subsequently increased their serum IgA level above 0.07 g/L. The average age of reversal was 9.53 +/- 2.91 years. In addition, 30 out of the 131 (22.9 %) children with serum IgAD when sampled between 5 and 9.99 years of age reversed their serum IgA level with time. The BAMSE follow up study showed a reversal of IgAD noted at 4 years of age in 8 out of 14 IgAD children at 16 years of age (5 at 8 years of age) where 4 were normalized their serum IgA levels while 4 still showed low serum levels of IgA, yet above the level defining IgAD. The results indicate that using 4 years of age, as a cut off for a diagnosis of IgAD may not be appropriate. Our findings suggest that a diagnosis of IgAD should not be made before the early teens using 0.07 g/L of IgA in serum as a cut off.

  • 269.
    Karimi, Masoud
    et al.
    Department of Oncology, Karolinska University Hospital, Stockholm, Sweden.
    von Salomé, Jenny
    Department of Clinical Genetics, Karolinska University Hospital, Solna, 171 76 Stockholm, Sweden; 3Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Aravidis, Christos
    Department of Clinical Genetics, Akademiska University Hospital, Uppsala, Sweden.
    Silander, Gustav
    Department of Clinical Genetics, Norrlands University Hospital, Umeå, Sweden.
    Stenmark Askmalm, Marie
    Region Östergötland, Center for Diagnostics, Clinical genetics. Department of Clinical Genetics, Office for Medical Services, Division of Laboratory Medicine, Lund, Sweden.
    Henriksson, Isabelle
    Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden; 8Department of Clinical Genetics, Office for Medical Services, Division of Laboratory Medicine, Lund, Sweden.
    Gebre-Medhin, Samuel
    Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden; 8Department of Clinical Genetics, Office for Medical Services, Division of Laboratory Medicine, Lund, Sweden.
    Frödin, Jan-Erik
    Department of Oncology, Karolinska University Hospital, Stockholm, Sweden.
    Björck, Erik
    Department of Clinical Genetics, Karolinska University Hospital, Solna, 171 76 Stockholm, Sweden; 3Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Lagerstedt-Robinson, Kristina
    Department of Clinical Genetics, Karolinska University Hospital, Solna, 171 76 Stockholm, Sweden; 3Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Lindblom, Annika
    Department of Clinical Genetics, Karolinska University Hospital, Solna, 171 76 Stockholm, Sweden; 3Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Tham, Emma
    Department of Clinical Genetics, Karolinska University Hospital, Solna, 171 76 Stockholm, Sweden; 3Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    A retrospective study of extracolonic, non-endometrial cancer in Swedish Lynch syndrome families2018In: Hereditary Cancer in Clinical Practice, ISSN 1731-2302, E-ISSN 1897-4287, Vol. 16, article id 16Article in journal (Refereed)
    Abstract [en]

    Lynch Syndrome is an autosomal dominant cancer syndrome caused by pathogenic germ-line variants in one of the DNA-mismatch-repair (MMR) genes MLH1, MSH2, MSH6 or PMS2. Carriers are predisposed to colorectal and endometrial cancer, but also other cancer types. The purpose of this retrospective study was to characterize the tumour spectrum of the Swedish Lynch syndrome families.

  • 270.
    Karlsson, Anette
    et al.
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Dahlqvist Leinhard, Olof
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Åslund, Ulrika
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences.
    West, Janne
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences.
    Romu, Thobias
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Smedby, Örjan
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV). KTH Royal Institute Technology, Sweden.
    Zsigmond, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Peolsson, Anneli
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences.
    An Investigation of Fat Infiltration of the Multifidus Muscle in Patients With Severe Neck Symptoms Associated With Chronic Whiplash-Associated Disorder2016In: Journal of Orthopaedic and Sports Physical Therapy, ISSN 0190-6011, E-ISSN 1938-1344, Vol. 46, no 10, p. 886-893Article in journal (Refereed)
    Abstract [en]

    STUDY DESIGN: Cross-sectional study. BACKGROUND: Findings of fat infiltration in cervical spine multifidus, as a sign of degenerative morphometric changes due to whiplash injury, need to be verified. OBJECTIVES: To develop a method using water/fat magnetic resonance imaging (MRI) to investigate fat infiltration and cross-sectional area of multifidus muscle in individuals with whiplash associated disorders (WADS) compared to healthy controls. METHODS: Fat infiltration and cross-sectional area in the multifidus muscles spanning the C4 to C7 segmental levels were investigated by manual segmentation using water/fat-separated MRI in 31 participants with WAD and 31 controls, matched for age and sex. RESULTS: Based on average values for data spanning C4 to C7, participants with severe disability related to WAD had 38% greater muscular fat infiltration compared to healthy controls (P = .03) and 45% greater fat infiltration compared to those with mild to moderate disability related to WAD (P = .02). There were no significant differences between those with mild to moderate disability and healthy controls. No significant differences between groups were found for multifidus cross-sectional area. Significant differences were observed for both cross-sectional area and fat infiltration between segmental levels. CONCLUSION: Participants with severe disability after a whiplash injury had higher fat infiltration in the multifidus compared to controls and to those with mild/moderate disability secondary to WAD. Earlier reported findings using T1-weighted MRI were reproduced using refined imaging technology. The results of the study also indicate a risk when segmenting single cross-sectional slices, as both cross-sectional area and fat infiltration differ between cervical levels.

  • 271.
    Karlsson, Anna
    et al.
    Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Medicon Village, Lund, Sweden.
    Cirenajwis, Helena
    Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Medicon Village, Lund, Sweden.
    Ericson-Lindquist, Kajsa
    Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden; Department of Pathology, Regional Laboratories Region Skåne, Lund, Sweden.
    Brunnstrom, Hans
    Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden; Department of Pathology, Regional Laboratories Region Skåne, Lund, Sweden.
    Reutersward, Christel
    Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Medicon Village, Lund, Sweden.
    Jönsson, Mats
    Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Medicon Village, Lund, Sweden.
    Ortiz-Villalon, Cristian
    Department of Pathology, Karolinska University Hospital, Stockholm, Sweden.
    Hussein, Aziz
    Department of Pathology and cytology, Sahlgrenska university hospital, Gothenburg, Sweden.
    Bergman, Bengt
    Department of Respiratory Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Vikström, Anders
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Respiratory Medicine.
    Monsef, Nastaran
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology.
    Branden, Eva
    Respiratory Medicine Unit, Department of Medicine Solna and CMM, Karolinska Institutet and Karolinska University Hospital Solna, Stockholm, Sweden; Centre for Research and Development, Uppsala University/Region Gävleborg, Gävle, Sweden.
    Koyi, Hirsh
    Respiratory Medicine Unit, Department of Medicine Solna and CMM, Karolinska Institutet and Karolinska University Hospital Solna, Stockholm, Sweden; Centre for Research and Development, Uppsala University/Region Gävleborg, Gävle, Sweden.
    de Petris, Luigi
    Thoracic Oncology Unit, Karolinska University Hospital and Department Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
    Micke, Patrick
    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Patthey, Annika
    Department of Pathology, Umeå University Hospital, Umeå, Sweden.
    Behndig, Annelie F.
    Department of Public Health and Clinical Medicine, Division of Medicine, Umeå University, Umeå, Sweden.
    Johansson, Mikael
    Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
    Planck, Maria
    Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Medicon Village, Lund, Sweden; Department of Respiratory Medicine and Allergology, Skåne University Hospital, Lund, Sweden.
    Staaf, Johan
    Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Medicon Village, Lund, Sweden.
    A combined gene expression tool for parallel histological prediction and gene fusion detection in non-small cell lung cancer2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 5207Article in journal (Refereed)
    Abstract [en]

    Accurate histological classification and identification of fusion genes represent two cornerstones of clinical diagnostics in non-small cell lung cancer (NSCLC). Here, we present a NanoString gene expression platform and a novel platform-independent, single sample predictor (SSP) of NSCLC histology for combined, simultaneous, histological classification and fusion gene detection in minimal formalin fixed paraffin embedded (FFPE) tissue. The SSP was developed in 68 NSCLC tumors of adenocarcinoma (AC), squamous cell carcinoma (SqCC) and large-cell neuroendocrine carcinoma (LCNEC) histology, based on NanoString expression of 11 (CHGA, SYP, CD56, SFTPG, NAPSA, TTF-1, TP73L, KRT6A, KRT5, KRT40, KRT16) relevant genes for IHC-based NSCLC histology classification. The SSP was combined with a gene fusion detection module (analyzing ALK, RET, ROS1, MET, NRG1, and NTRK1) into a multicomponent NanoString assay. The histological SSP was validated in six cohorts varying in size (n = 11-199), tissue origin (early or advanced disease), histological composition (including undifferentiated cancer), and gene expression platform. Fusion gene detection revealed five EML4-ALK fusions, four KIF5B-RET fusions, two CD74-NRG1 fusion and three MET exon 14 skipping events among 131 tested cases. The histological SSP was successfully trained and tested in the development cohort (mean AUC = 0.96 in iterated test sets). The SSP proved successful in predicting histology of NSCLC tumors of well-defined subgroups and difficult undifferentiated morphology irrespective of gene expression data platform. Discrepancies between gene expression prediction and histologic diagnosis included cases with mixed histologies, true large cell carcinomas, or poorly differentiated adenocarcinomas with mucin expression. In summary, we present a proof-of-concept multicomponent assay for parallel histological classification and multiplexed fusion gene detection in archival tissue, including a novel platform-independent histological SSP classifier. The assay and SSP could serve as a promising complement in the routine evaluation of diagnostic lung cancer biopsies.

  • 272.
    Karlsson, Jan Olof
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Jynge, Per
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Lundström, Ingemar
    Linköping University, Department of Physics, Chemistry and Biology, Sensor and Actuator Systems. Linköping University, Faculty of Science & Engineering.
    Ignarro, Louis J.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Letter in response to: "Randomised open label exploratory, safety and tolerability study with calmangafodipir in patients treated with the 12-h regimen of N acetylcysteine for paracetamol overdosethe PP100-01 for Overdose of Paracetamol (POP) trial: study protocol for a randomised controlled trial"2019In: Trials, ISSN 1745-6215, E-ISSN 1745-6215, Vol. 20, article id 380Article in journal (Other academic)
    Abstract [en]

    n/a

  • 273.
    Karlsson, Louise
    et al.
    Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Zackrisson, Anna Lena
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
    Josefsson, M
    Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden; 3Department of Physics, Chemistry and Biology, Linköping University, Linköping, Sweden.
    Carlsson, Björn
    Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Green, Henrik
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Department of Forensic Genetics andForensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
    Kugelberg, Fredrik C
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
    Influence of CYP2D6 and CYP2C19 genotypes on venlafaxine metabolic ratios and stereoselective metabolism in forensic autopsy cases.2015In: The Pharmacogenomics Journal, ISSN 1470-269X, E-ISSN 1473-1150, Vol. 15, no 2, p. 165-71Article in journal (Refereed)
    Abstract [en]

    We investigated whether polymorphisms in the CYP2D6 and CYP2C19 genes influence the metabolic ratios and enantiomeric S/R ratios of venlafaxine (VEN) and its metabolites O-desmethylvenlafaxine (ODV), N-desmethylvenlafaxine (NDV) and N,O-didesmethylvenlafaxine (DDV) in blood from forensic autopsy cases. In all, 94 postmortem cases found positive for VEN during toxicological screening were included. The CYP2D6 genotype was shown to significantly influence the ODV/VEN (P=0.003), DDV/NDV (P=0.010) and DDV/ODV (P=0.034) ratios. The DDV/ODV (P=0.013) and DDV/VEN (P=0.021) ratios were significantly influenced by the CYP2C19 genotype. The S/R ratios of VEN were significantly influenced by both CYP2D6 and CYP2C19 genotypes. CYP2D6 poor metabolizers (PMs) had lower S/R VEN ratios and CYP2C19 PMs had high S/R ratios of VEN in comparison. Our results show that the CYP2D6 genotype influences the O-demethylation whereas CYP2C19 influences the N-demethylation of VEN and its metabolites. In addition, we show a stereoselective metabolism where CYP2D6 favours the R-enantiomer whereas CYP2C19 favours the S-enantiomer.

  • 274.
    Karlsson, Markus
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Ekstedt, Mattias
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Dahlström, Nils
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Forsgren, Mikael
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Ignatova, Simone
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology.
    Norén, Bengt
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Dahlqvist Leinhard, Olof
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Kechagias, Stergios
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Medical radiation physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Liver R2*is affected by both iron and fat: A dual biopsy-validated study of chronic liver disease2019In: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 50, no 1, p. 325-333Article in journal (Refereed)
    Abstract [en]

    Background Liver iron content (LIC) in chronic liver disease (CLD) is currently determined by performing an invasive liver biopsy. MRI using R2* relaxometry is a noninvasive alternative for estimating LIC. Fat accumulation in the liver, or proton density fat fraction (PDFF), may be a possible confounder of R2* measurements. Previous studies of the effect of PDFF on R2* have not used quantitative LIC measurement. Purpose To assess the associations between R2*, LIC, PDFF, and liver histology in patients with suspected CLD. Study Type Prospective. Population Eighty-one patients with suspected CLD. Field Strength/Sequence 1.5 T. Multiecho turbo field echo to quantify R2*. PRESS MRS to quantify PDFF. Assessment Each patient underwent an MR examination, followed by two needle biopsies immediately following the MR examination. The first biopsy was used for conventional histological assessment of LIC, whereas the second biopsy was used to quantitatively measure LIC using mass spectrometry. R2* was correlated with both LIC and PDFF. A correction for the influence of fat on R2* was calculated. Statistical Tests Pearson correlation, linear regression, and area under the receiver operating curve. Results There was a positive linear correlation between R2* and PDFF (R = 0.69), after removing data from patients with elevated iron levels, as defined by LIC. R2*, corrected for PDFF, was the best method for identifying patients with elevated iron levels, with a correlation of R = 0.87 and a sensitivity and specificity of 87.5% and 98.6%, respectively. Data Conclusion PDFF increases R2*. Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:325-333.

    The full text will be freely available from 2020-09-13 14:26
  • 275.
    Karlsson, Markus
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Forsgren, Mikael
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Dahlström, Nils
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Leinhard Dahlqvist, Olof
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    Norén, Bengt
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Ekstedt, Mattias
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Kechagias, Stergios
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Diffuse Liver Disease: Measurements of Liver Trace Metal Concentrations and R2* Relaxation Rates2016Conference paper (Refereed)
    Abstract [en]

    Introduction

    Over the past decade, several methods for measuring of liver iron content (LIC) non-invasively with MRI have been developed and verified. The most promising methods uses relaxometry, measuring either R2- or R2* relaxation rate in the liver1,2. For instance, several studies have shown that there seems to be a linear relationship between R2* and LIC1. However, few of these studies have measured the liver content of other metals, which could also affect the relaxation rates. The goal of this study was to investigate if any trace metals, other than iron could affect the R2* relaxation rate in liver tissue in a patients with diffuse liver disease.

    Subjects and methods

    75 patients with suspected diffuse liver disease underwent an MRI examination followed by a liver biopsy the same day. The R2* relaxation rate of the water protons in the liver was measured using an axial 3D multi-slice fat-saturated multi-echo turbo field echo sequence (TE=4.60/9.20/13.80/18.40/23.00ms). Regions of interest (ROI) were drawn and R2* was estimated by fitting the mean signal intensity from the ROIs to a mono-exponential decay model. The biopsies were freeze dried and the concentrations of iron, manganese, copper, cobalt and gadolinium were measured using Inductively Coupled Plasma Sector Field Mass Spectrometry (ICP-SFMS). A multiple linear regression analysis was applied to determine which of the measured metals significantly affected the relaxation rate.

    Results

    A linear regression with the LIC and R2* showed a reasonable fit (Figure 1). The multiple linear regression analysis (Table 1) showed that iron as well as manganese had a significant affect on R2*. Unlike iron however, the regression coefficient of manganese was negative, meaning that an increasing manganese concentration gave a shorter R2* relaxation rate. The same trend can be seen when plotting the manganese concentration against R2* (Figure 2).

  • 276.
    Karlsson, Sofia A.
    et al.
    University of Gothenburg, Sweden.
    Jacobsson, Ingela
    Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Danell Boman, Marit
    University of Umeå Hospital, Sweden.
    Hakkarainen, Katja M.
    Nordic School Public Health NHV, Sweden; Jonköping County Council, Sweden.
    Lövborg, Henrik
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Linköping University, Faculty of Medicine and Health Sciences.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Jönköping County Council, Jönköping, Sweden.
    Jönsson, Anna K
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    The impact of a changed legislation on reporting of adverse drug reactions in Sweden, with focus on nurses reporting2015In: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 71, no 5, p. 631-636Article in journal (Refereed)
    Abstract [en]

    In March 2007, a legislative amendment was issued in Sweden compelling nurses to report all suspected adverse drug reactions (ADRs) to the national pharmacovigilance system. The aims of this study were to describe the status of ADR reporting, before and after the implementation of the legislative changes, and to describe the general characteristics of suspected ADRs reported by nurses. The Swedish pharmacovigilance system during the study period constituted six regional centres responsible for the handling of all spontaneous ADR reports within their region. In this study, we identified all individual ADR reports from 2005 and 2010, analysed in depth the ADR reports from two regional centres and collated information about the reporter and the nature of the reported ADR. From the two regional centres, a total of 898 and 1074 reports were submitted in 2005 and 2010 respectively. Nurses submitted 31 % (275 reports) of the reports in 2005 and 24 % (260 reports) in 2010. Nurses reporting of serious ADRs was 3 % (seven reports) in 2005 and 7 % (17 reports) in 2010 with reporting of unlabelled ADRs at 4 % (11 reports) in 2005 and 17 % (45 reports) in 2010. Most of the serious and/or unlabelled reactions were related to vaccine administration (14 reports in 2005 and 36 reports in 2010). The overall ADR reporting by nurses did not appear to increase after the change in reporting legislation. The proportion of serious and/or unlabelled ADRs reported by nurses did however appear to increase during the same period. Taken together, our data suggests that further pro-active measures should be considered in order to involve nurses in the reporting of suspected ADRs.

  • 277.
    Karlén, Jerker
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Hedmark, Max
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Olsen Faresjö, Åshild
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Faresjö, Tomas
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Early Psychosocial Exposures, Hair Cortisol Levels, and Disease Risk2015In: Pediatrics, ISSN 0031-4005, E-ISSN 1098-4275, Vol. 135, no 6, p. E1450-E1457Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Early psychosocial exposures are increasingly recognized as being crucial to health throughout life. A possible mechanism could be physiologic dysregulation due to stress. Cortisol in hair is a new biomarker assessing long-term hypothalamic-pituitary-adrenal axis activity. The objective was to investigate whether early-life adverse psychosocial circumstances influence infant cortisol levels in hair and health outcomes in children prospectively until age 10. METHODS: A cohort study in the general community using a questionnaire covering 11 psychosocial items in the family during pregnancy and the cumulative incidence of diagnoses until age 10 years in 1876 children. Cortisol levels in hair were measured by using a radioimmunoassay in those with sufficient hair samples at age 1, yielding a subsample of n = 209. RESULTS: Children with added psychosocial exposures had higher infant cortisol levels in hair (B = 0.40, P less than .0001, adjusted for gender and size for gestational age) in a cumulative manner and were significantly more often affected by 12 of the 14 most common childhood diseases, with a general pattern of increasing odds ratios. CONCLUSIONS: The findings support the model of physiologic dysregulation as a plausible mechanism by which the duration and number of early detrimental psychosocial exposures determine health outcomes. The model indicates that the multiplicity of adversities should be targeted in future interventions and could help to identify children who are at high risk of poor health. Furthermore, given the prolonged nature of exposure to a stressful social environment, the novel biomarker of cortisol in hair could be of major importance.

  • 278.
    Kataria, Bharti
    et al.
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsson Althen, Jonas
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Medical radiation physics.
    Smedby, Örjan
    School of Technology and Health (STH), KTH Royal Institute, Stockholm, Sweden.
    Persson, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Sökjer, Hannibal
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Sandborg, Michael
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Medical radiation physics.
    Assessment of image quality in abdominal CT: potential dose reduction with model-based iterative reconstruction2018In: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084Article in journal (Refereed)
    Abstract [en]

    Purpose To estimate potential dose reduction in abdominal CT by visually comparing images reconstructed with filtered back projection (FBP) and strengths of 3 and 5 of a specific MBIR.

    Material and methods A dual-source scanner was used to obtain three data sets each for 50 recruited patients with 30, 70 and 100% tube loads (mean CTDIvol 1.9, 3.4 and 6.2 mGy). Six image criteria were assessed independently by five radiologists. Potential dose reduction was estimated with Visual Grading Regression (VGR).

    Results Comparing 30 and 70% tube load, improved image quality was observed as a significant strong effect of log tube load and reconstruction method with potential dose reduction relative to FBP of 22–47% for MBIR strength 3 (p < 0.001). For MBIR strength 5 no dose reduction was possible for image criteria 1 (liver parenchyma), but dose reduction between 34 and 74% was achieved for other criteria. Interobserver reliability showed agreement of 71–76% (κw 0.201–0.286) and intra-observer reliability of 82–96% (κw 0.525–0.783).

    Conclusion MBIR showed improved image quality compared to FBP with positive correlation between MBIR strength and increasing potential dose reduction for all but one image criterion.

  • 279.
    Kataria, Bharti
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Nilsson Althen, Jonas
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Medical radiation physics.
    Smedby, Örjan
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Persson, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Sökjer, Hannibal
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Sandborg, Michael
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Diagnostics, Medical radiation physics.
    Image quality and pathology assessment in CT Urography: when is the low-dose seriessufficient?2019In: BMC Medical Imaging, ISSN 1471-2342, E-ISSN 1471-2342, Vol. 19, article id 64Article in journal (Refereed)
    Abstract [en]

    Background

    Our aim was to compare CT images from native, nephrographic and excretory phases using image quality criteria as well as the detection of positive pathological findings in CT Urography, to explore if the radiation burden to the younger group of patients or patients with negative outcomes can be reduced.

    Methods

    This is a retrospective study of 40 patients who underwent a CT Urography examination on a 192-slice dual source scanner. Image quality was assessed for four specific renal image criteria from the European guidelines, together with pathological assessment in three categories: renal, other abdominal, and incidental findings without clinical significance. Each phase was assessed individually by three radiologists with varying experience using a graded scale. Certainty scores were derived based on the graded assessments. Statistical analysis was performed using visual grading regression (VGR). The limit for significance was set at p = 0.05.

    Results

    For visual reproduction of the renal parenchyma and renal arteries, the image quality was judged better for the nephrogram phase (p < 0.001), whereas renal pelvis/calyces and proximal ureters were better reproduced in the excretory phase compared to the native phase (p < 0.001). Similarly, significantly higher certainty scores were obtained in the nephrogram phase for renal parenchyma and renal arteries, but in the excretory phase for renal pelvis/calyxes and proximal ureters. Assessment of pathology in the three categories showed no statistically significant differences between the three phases. Certainty scores for assessment of pathology, however, showed a significantly higher certainty for renal pathology when comparing the native phase to nephrogram and excretory phase and a significantly higher score for nephrographic phase but only for incidental findings.

    Conclusion

    Visualisation of renal anatomy was as expected with each post-contrast phase showing favourable scores compared to the native phase. No statistically significant differences in the assessment of pathology were found between the three phases. The low-dose CT (LDCT) seems to be sufficient in differentiating between normal and pathological examinations. To reduce the radiation burden in certain patient groups, the LDCT could be considered a suitable alternative as a first line imaging method. However, radiologists should be aware of its limitations.

  • 280.
    Kataria, Bharti
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Nilsson Althén, Jonas
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Medical radiation physics.
    Smedby, Örjan
    KTH Royal Inst Technol, Sweden.
    Persson, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Sökjer-Petersen, Hannibal
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Sandborg, Michael
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Medical radiation physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Image quality and pathology assessment in CT Urography: when is the low-dose series sufficient?2019In: BMC Medical Imaging, ISSN 1471-2342, E-ISSN 1471-2342, Vol. 19, no 1, article id 64Article in journal (Refereed)
    Abstract [en]

    Background

    Our aim was to compare CT images from native, nephrographic and excretory phases using image quality criteria as well as the detection of positive pathological findings in CT Urography, to explore if the radiation burden to the younger group of patients or patients with negative outcomes can be reduced.

    Methods

    This is a retrospective study of 40 patients who underwent a CT Urography examination on a 192-slice dual source scanner. Image quality was assessed for four specific renal image criteria from the European guidelines, together with pathological assessment in three categories: renal, other abdominal, and incidental findings without clinical significance. Each phase was assessed individually by three radiologists with varying experience using a graded scale. Certainty scores were derived based on the graded assessments. Statistical analysis was performed using visual grading regression (VGR). The limit for significance was set at p = 0.05.

    Results

    For visual reproduction of the renal parenchyma and renal arteries, the image quality was judged better for the nephrogram phase (p < 0.001), whereas renal pelvis/calyces and proximal ureters were better reproduced in the excretory phase compared to the native phase (p < 0.001). Similarly, significantly higher certainty scores were obtained in the nephrogram phase for renal parenchyma and renal arteries, but in the excretory phase for renal pelvis/calyxes and proximal ureters. Assessment of pathology in the three categories showed no statistically significant differences between the three phases. Certainty scores for assessment of pathology, however, showed a significantly higher certainty for renal pathology when comparing the native phase to nephrogram and excretory phase and a significantly higher score for nephrographic phase but only for incidental findings.

    Conclusion

    Visualisation of renal anatomy was as expected with each post-contrast phase showing favourable scores compared to the native phase. No statistically significant differences in the assessment of pathology were found between the three phases. The low-dose CT (LDCT) seems to be sufficient in differentiating between normal and pathological examinations. To reduce the radiation burden in certain patient groups, the LDCT could be considered a suitable alternative as a first line imaging method. However, radiologists should be aware of its limitations.

  • 281.
    Kataria, Bharti
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Sandborg, Michael
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Nilsson Althen, Jonas
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences.
    IMPLICATIONS OF PATIENT CENTRING ON ORGAN DOSE IN COMPUTED TOMOGRAPHY2016In: Radiation Protection Dosimetry, ISSN 0144-8420, E-ISSN 1742-3406, Vol. 169, no 1-4, p. 130-135Article in journal (Refereed)
    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.

  • 282.
    Kawa, Lizan
    et al.
    Karolinska Institute, Sweden.
    Barde, Swapnali
    Karolinska Institute, Sweden.
    Arborelius, Ulf P.
    Karolinska Institute, Sweden.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    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 injury2016In: Experimental Neurology, ISSN 0014-4886, E-ISSN 1090-2430, Vol. 279, p. 159-167Article in journal (Refereed)
    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.

  • 283.
    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
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. University Vita Salute San Raffaele, Italy.
    Expression and Distribution of Phosphodiesterase Isoenzymes in the Human Male Urethra2015In: Urology, ISSN 0090-4295, E-ISSN 1527-9995, Vol. 85, no 4, p. 964.e1-Article in journal (Refereed)
    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.

  • 284.
    Kempe, Per
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Cty Hosp Sundsvall, Sweden.
    Eklund, Daniel
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Hallin, Agnes
    Not Found:Linkoping Univ, Dept Clin and Expt Med, SE-58185 Linkoping, Sweden.
    Hammar, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Olsson, Tomas
    Karolinska Inst, Sweden.
    Brynhildsen, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Immune profile in relation to sex steroid cyclicity in healthy women and women with multiple sclerosis2018In: Journal of Reproductive Immunology, ISSN 0165-0378, E-ISSN 1872-7603, Vol. 126, p. 53-59Article in journal (Refereed)
    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.

  • 285.
    Kentson, Magnus
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Ryhov County Hospital, Sweden.
    Tödt, Kristina
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Skåne University Hospital, Sweden.
    Skargren, Elisabeth
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences.
    Jakobsson, Per
    Ryhov County Hospital, Sweden.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Unosson, Mitra
    Linköping University, Department of Social and Welfare Studies, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    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 COPD2016In: THERAPEUTIC ADVANCES IN RESPIRATORY DISEASE, ISSN 1753-4658, Vol. 10, no 5, p. 410-424Article in journal (Refereed)
    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

  • 286.
    Khedidja, Hedna
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. 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
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    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
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Jönköping County Council, Jönköping, Sweden.
    Adherence to Antihypertensive Therapy and Elevated Blood Pressure: Should We Consider the Use of Multiple Medications?2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 9, article id e0137451Article in journal (Refereed)
    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.

  • 287.
    Khedidja, Hedna
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. 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
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Petzold, Max
    Centre for Applied Biostatistics, University of Gothenburg,, Gotenburg, Sweden.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Potentially inappropriate prescribing and adverse drug reactions in the elderly: a population-based study2015In: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 71, no 12, p. 1525-1533Article in journal (Refereed)
    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.

  • 288.
    Kihlberg, Johan
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Magnetic Resonance Imaging of Myocardial Deformation and Scarring in Coronary Artery Disease.2017Doctoral thesis, comprehensive summary (Other academic)
    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.

    List of papers
    1. Rapid T1 quantification based on 3D phase sensitive inversion recovery
    Open this publication in new window or tab >>Rapid T1 quantification based on 3D phase sensitive inversion recovery
    2010 (English)In: BMC Medical Imaging, ISSN 1471-2342, E-ISSN 1471-2342, Vol. 10, no 19Article in journal (Refereed) 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.

    National Category
    Engineering and Technology Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-59065 (URN)10.1186/1471-2342-10-19 (DOI)20716333 (PubMedID)
    Available from: 2010-09-08 Created: 2010-09-08 Last updated: 2017-12-12
    2. Clinical experience of strain imaging using DENSE for detecting infarcted cardiac segments
    Open this publication in new window or tab >>Clinical experience of strain imaging using DENSE for detecting infarcted cardiac segments
    Show others...
    2015 (English)In: Journal of Cardiovascular Magnetic Resonance, ISSN 1097-6647, E-ISSN 1532-429X, Vol. 17, article id 50Article in journal (Refereed) 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.

    Place, publisher, year, edition, pages
    BioMed Central, 2015
    National Category
    Radiology, Nuclear Medicine and Medical Imaging
    Identifiers
    urn:nbn:se:liu:diva-119846 (URN)10.1186/s12968-015-0155-8 (DOI)000356652000001 ()26104510 (PubMedID)
    Available from: 2015-06-26 Created: 2015-06-26 Last updated: 2017-12-04
  • 289.
    Kihlberg, Johan
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Gupta, Vikas
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Haraldsson, Henrik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Sigfridsson, Andreas
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Sarvari, Sebastian
    Ebbers, Tino
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Engvall, Jan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Identification of the best CMR technique for quantitative assessment of myocardial salvage using a systematic comparison.2017Conference paper (Refereed)
  • 290.
    Kihlberg, Johan
    et al.
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Diagnostics.
    Haraldsson, Henrik
    Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Ebbers, Tino
    Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Engvall, Jan
    Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Practical Application of DENSE in Ischemic Heart Disease.2013Conference paper (Refereed)
  • 291.
    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
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Swolin-Eide, Diana
    University of Gothenburg, Sweden.
    WHOLE-BODY VIBRATION THERAPY IN CHILDREN WITH SEVERE MOTOR DISABILITIES2015In: Journal of Rehabilitation Medicine, ISSN 1650-1977, E-ISSN 1651-2081, Vol. 47, no 3, p. 223-228Article in journal (Refereed)
    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.

  • 292.
    Kissopoulou, Antheia
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Cty Council Jonkoping, Sweden.
    Trinks, Cecilia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics.
    Gréen, Anna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics.
    Karlsson, Jan-Erik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Cty Council Jonkoping, Sweden.
    Jonasson, Jon
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics.
    Gunnarsson, Cecilia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics. Region Östergötland, Center for Business support and Development.
    Homozygous missense MYBPC3 Pro873His mutation associated with increased risk for heart failure development in hypertrophic cardiomyopathy2018In: ESC Heart Failure, E-ISSN 2055-5822, Vol. 5, no 4, p. 716-723Article in journal (Refereed)
    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.

  • 293.
    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
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Microbiology.
    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 survey2018In: Mycoses (Berlin), ISSN 0933-7407, E-ISSN 1439-0507, Vol. 61, no 10, p. 777-785Article in journal (Refereed)
    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.

  • 294.
    Klintström, Benjamin
    et al.
    Linköping University, Center for Medical Image Science and Visualization (CMIV). KTH Royal Institute of Technology, School of Technology and Health, Sweden.
    Klintström, Eva
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Smedby, Örjan
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (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 segmentation2017In: Image Analysis - 20th Scandinavian Conference on Image Analysis, SCIA 2017, Proceedings / [ed] Sharma P., Bianchi F., Springer, 2017, Vol. 10270, p. 65-70Conference paper (Refereed)
    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.

  • 295.
    Klintström, Eva
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Image Analysis for Trabecular Bone Properties on Cone-Beam CT Data2017Doctoral thesis, comprehensive summary (Other academic)
    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.

    List of papers
    1. Trabecular bone structure parameters from 3D image processing of clinical multi-slice and cone-beam computed tomography data
    Open this publication in new window or tab >>Trabecular bone structure parameters from 3D image processing of clinical multi-slice and cone-beam computed tomography data
    2014 (English)In: Skeletal Radiology, ISSN 0364-2348, E-ISSN 1432-2161, Vol. 43, no 2, p. 197-204Article in journal (Refereed) 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.

    Place, publisher, year, edition, pages
    Springer, 2014
    Keywords
    Trabecular bone structure; Cone-beam computed tomography; Micro computed tomography; Multi-slice computed tomography; Bone segmentation
    National Category
    Radiology, Nuclear Medicine and Medical Imaging
    Identifiers
    urn:nbn:se:liu:diva-102880 (URN)10.1007/s00256-013-1766-5 (DOI)000329108500011 ()
    Available from: 2014-01-07 Created: 2014-01-07 Last updated: 2017-12-06Bibliographically approved
    2. Trabecular bone histomorphometric measurements and contrast-to-noise ratio in CBCT
    Open this publication in new window or tab >>Trabecular bone histomorphometric measurements and contrast-to-noise ratio in CBCT
    Show others...
    2014 (English)In: Dento-Maxillo-Facial Radiology, ISSN 0250-832X, E-ISSN 1476-542X, Vol. 43, no 8, p. 20140196-Article in journal (Refereed) 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.

    Place, publisher, year, edition, pages
    British Institute of Radiology, 2014
    Keywords
    CBCT; micro-computed tomography; trabecular 7 bone; histomorphometry; bone segmentation; osteoporosis
    National Category
    Radiology, Nuclear Medicine and Medical Imaging
    Identifiers
    urn:nbn:se:liu:diva-111163 (URN)10.1259/dmfr.20140196 (DOI)000346231400002 ()25168811 (PubMedID)
    Available from: 2014-10-09 Created: 2014-10-09 Last updated: 2017-12-05Bibliographically approved
    3. Predicting Trabecular Bone Stiffness from Clinical Cone-Beam CT and HR-pQCT Data; an In Vitro Study Using Finite Element Analysis
    Open this publication in new window or tab >>Predicting Trabecular Bone Stiffness from Clinical Cone-Beam CT and HR-pQCT Data; an In Vitro Study Using Finite Element Analysis
    Show others...
    2016 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 8, article id e0161101Article in journal (Refereed) 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.

    Place, publisher, year, edition, pages
    Public library of science, 2016
    National Category
    Clinical Medicine
    Identifiers
    urn:nbn:se:liu:diva-130798 (URN)10.1371/journal.pone.0161101 (DOI)000381381100120 ()27513664 (PubMedID)
    Available from: 2016-08-24 Created: 2016-08-24 Last updated: 2018-03-26Bibliographically approved
  • 296.
    Klintström, Eva
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (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
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV). KTH Royal Inst Technol, Sweden.
    Moreno, Rodrigo
    KTH Royal Inst Technol, Sweden.
    Direct estimation of human trabecular bone stiffness using cone beam computed tomography2018In: Oral surgery, oral medicine, oral pathology and oral radiology, ISSN 2212-4403, E-ISSN 2212-4411, Vol. 126, no 1, p. 72-82Article in journal (Refereed)
    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.

  • 297.
    Klintström, Eva
    et al.
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Klintström, Benjamin
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Brismar, Torkel
    Karolinska Institutet, Stockholm, Sweden.
    Smedby, Örjan
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. KTH Royal Institute of Technology, Stockholm, Sweden.
    Moreno, Rodrigo
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. KTH Royal Institute of Technology, Stockholm, Sweden.
    Clinical dental cone beam computed tomography - a tool for monitoring trabecular bone structure?2015Conference paper (Refereed)
    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.

     

  • 298.
    Klintström, Eva
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Klintström, Benjamin
    Linköping University, Center for Medical Image Science and Visualization (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
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Predicting Trabecular Bone Stiffness from Clinical Cone-Beam CT and HR-pQCT Data; an In Vitro Study Using Finite Element Analysis2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 8, article id e0161101Article in journal (Refereed)
    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.

  • 299.
    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
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Kågedal, Katarina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Kurz, Tino
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Mohseni, Simin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Öllinger, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    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)2016In: Autophagy, ISSN 1554-8627, E-ISSN 1554-8635, Vol. 2, no 1, p. 1-222Article, review/survey (Refereed)
  • 300.
    Koppal, Sandeep
    et al.
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Warntjes, Marcel
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. SyntheticMR AB, Linköping, Sweden.
    Swann, Jeremy
    School of Computing, University of Leeds, Leeds, United Kingdom.
    Dyverfeldt, Petter
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Kihlberg, Johan
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Moreno, Rodrigo
    Linköping University, Center for Medical Image Science and Visualization (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
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Forssell, Claes
    Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Länne, Toste
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Treanor, Darren
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Department of Pathology and Tumour Biology, Leeds Institute of Molecular Medicine, University of Leeds, Leeds, United Kingdom.
    de Muinck, Ebo
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Quantitative Fat and R2* Mapping In Vivo to Measure Lipid-Rich Necrotic Core and Intraplaque Hemorrhage in Carotid Atherosclerosis2017In: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 78, no 1, p. 285-296Article in journal (Refereed)
    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.

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