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  • 51.
    Theodorsson, Elvar
    et al.
    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.
    Berggren Söderlund, Maria
    Region Kronoberg, Klinisk kemi och transfusionsmedicin.
    Laurells klinisk kemi i praktisk medicin2018 (ed. 10)Book (Other academic)
    Abstract [sv]

    Denna tionde upplaga av Laurells Klinisk kemi i praktisk medicin utgör en grundlig bearbetning av det populära verket. Samtliga kapitel har reviderats och kapitlen om tolkning av analysresultat, vatten, elektrolyter, blodgaser, mag–tarmkanalen och immunologi har skrivits om från grunden; allt i samarbete mellan verksamma inom klinisk farmakologi, klinisk immunologi och klinisk kemi.?

    Kunskapsfragment inom medicin, inklusive klinisk kemi, är lättillgängliga på nätet men ger sällan den helhetsbild som behövs för en djupare förståelse och därmed optimal användning av laboratorie­analyser. Denna bok ger en sådan helhetsbild och kan användas såväl för att slå upp fakta om specifika analyser som för att förstå de sjukdomsmekanismer som är av betydelse för beställning och tolkning av laboratorieresultat.?

    Texten är organiserad utifrån kliniska problemområden och i balansgången mellan inslagen av laboratorium och medicin har tonvikten lagts på det medicinskt-diagnostiska snarare än på det laboratorietekniska. Fokus ligger på förståelsen av preanalytiska och analytiska faktorer vid tolkningen av laboratorieresultat samt av förståelsen av prevalens, sensitivitet, specificitet och liknande begrepp i det diagnostiska arbetet.?

    Föreliggande bok förväntas även fortsatt komma till god användning på avdelningar, mottagningar och vårdcentraler – överallt där man behöver ta laboratorieprover och tolka provsvar – men också bland studenter i medicin, biomedicin, biomedicinsk laboratorievetenskap och besläktade kunskapsområden.

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  • 52.
    Theodorsson, Elvar
    et al.
    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.
    Löwbeer, Christian
    Aleris Medilab och Institutionen för laboratoriemedicin, Avdelningen för klinisk kemi, Karolinska institutet, Stockholm.
    Ridefelt, Peter
    Institutionen för medicinska vetenskaper, Klinisk kemi, Uppsala universitet.
    Carlson, Marie
    Institutionen för sociologi och arbetsvetenskap, Göteborgs universitet.
    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.
    Simonsson, Per
    Institutionen för translationell medicin, Medicinska fakulteten, Lunds universitet.
    Digestionsorganens sjukdomar2018In: Laurells klinisk kemi i praktisk medicin, Lund: Studentlitteratur AB, 2018, 10, p. 465-516Chapter in book (Other academic)
  • 53.
    Thorstenson, Sten
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Molin, Jesper
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, The Institute of Technology. Chalmers University of Technology, Göteborg.
    Lundström, Claes
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, The Institute of Technology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Implementation of large‑scale routine diagnostics using whole slideimaging in Sweden: Digital pathology experiences 2006-20132014In: Journal of Pathology Informatics, ISSN 2229-5089, E-ISSN 2153-3539, Vol. 5, no 14Article in journal (Refereed)
    Abstract [en]

    Recent technological advances have improved the whole slide imaging (WSI) scanner quality and reduced the cost of storage, thereby enabling the deployment of digital pathology for routine diagnostics. In this paper we present the experiences from two Swedish sites having deployed routine large-scale WSI for primary review. At Kalmar County Hospital, the digitization process started in 2006 to reduce the time spent at the microscope in order to improve the ergonomics. Since 2008, more than 500,000 glass slides have been scanned in the routine operations of Kalmar and the neighboring Linköping University Hospital. All glass slides are digitally scanned yet they are also physically delivered to the consulting pathologist who can choose to review the slides on screen, in the microscope, or both. The digital operations include regular remote case reporting by a few hospital pathologists, as well as around 150 cases per week where primary review is outsourced to a private clinic. To investigate how the pathologists choose to use the digital slides, a web-based questionnaire was designed and sent out to the pathologists in Kalmar and Linköping. The responses showed that almost all pathologists think that ergonomics have improved and that image quality was sufficient for most histopathologic diagnostic work. 38 ± 28% of the cases were diagnosed digitally, but the survey also revealed that the pathologists commonly switch back and forth between digital and conventional microscopy within the same case. The fact that two full-scale digital systems have been implemented and that a large portion of the primary reporting is voluntarily performed digitally shows that large-scale digitization is possible today.

  • 54.
    Tiiman, Ann
    et al.
    Karolinska Inst, Sweden.
    Jelic, Vesna
    Karolinska Inst, Sweden.
    Jarvet, Juri
    Stockholm Univ, Sweden; NICPB, Estonia.
    Järemo, Petter
    Region Östergötland, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Bogdanovic, Nenad
    Karolinska Inst, Sweden; Univ Oslo, Norway.
    Rigler, Rudolf
    Karolinska Inst, Sweden.
    Terenius, Lars
    Karolinska Inst, Sweden.
    Graslund, Astrid
    Stockholm Univ, Sweden.
    Vukojevic, Vladana
    Karolinska Inst, Sweden.
    Amyloidogenic Nanoplaques in Blood Serum of Patients with Alzheimers Disease Revealed by Time-Resolved Thioflavin T Fluorescence Intensity Fluctuation Analysis2019In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 68, no 2, p. 571-582Article in journal (Refereed)
    Abstract [en]

    Background: Biomarkers are central to current research on molecular mechanisms underlying Alzheimers disease (AD). Their further development is of paramount importance for understanding pathophysiological processes that eventually lead to disease onset. Biomarkers are also crucial for early disease detection, before clinical manifestation, and for development of new disease modifying therapies. Objective: The overall aim of this work is to develop a minimally invasive method for fast, ultra-sensitive and cost-effective detection of structurally modified peptide/protein self-assemblies in the peripheral blood and in other biological fluids. Specifically, we focus here on using this method to detect structured amyloidogenic oligomeric aggregates in the blood serum of apparently healthy individuals and patients in early AD stage, and measure their concentration and size. Methods: Time-resolved detection of Thioflavin T (ThT) fluorescence intensity fluctuations in a sub-femtoliter observation volume element was used to identify in blood serum ThT-active structured amyloidogenic oligomeric aggregates, hereafter called nanoplaques, and measure with single-particle sensitivity their concentration and size. Results: The concentration and size of structured amyloidogenic nanoplaques are significantly higher in the blood serum of individuals diagnosed with AD than in control subjects. Conclusion: A new method with the ultimate, single-particle sensitivity was successfully developed. The proposed approach neither relies on the use of immune-based probes, nor on the use of radiotracers, signal-amplification or protein separation techniques, and provides a minimally invasive test for fast and cost-effective early determination of structurally modified peptides/proteins in the peripheral blood, as shown here, but also in other biological fluids.

  • 55.
    Tjernberg, Ivar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Landstinget i Kalmar län, Kalmar, Sweden.
    Dags för laboratoriesvar 2.0 [Time for laboratory results 2.0]2017In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 114, article id EFDTArticle in journal (Other academic)
    Abstract [sv]

    Det är dags att öka nyttan av laborerandet. Bättre informationssystem och förbättrade beslutsstöd i patientjournalsystemen för laboratorieresultat efterlyses.

  • 56.
    Tjernberg, Ivar
    et al.
    Kalmar County Council, Sweden Kalmar, Sweden.
    Gustafsson, Inger
    Klinisk kemi och transfusionsmedicin, Landstinget i Kalmar län - Kalmar, Sweden Dep of Clinical chemistry and transfusion medicine - Dep of Clinical chemistry and transfusion medicine, Kalmar County Council, Sweden Kalmar, Sweden.
    Falskt förhöjd kreatininnivå orsakades av M-komponent2018In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 115Article in journal (Refereed)
    Abstract [en]

    Falsely elevated plasma creatinine due to monoclonal gammopathy Analytical interference may give rise to falsely elevated as well as reduced clinical biochemical results. Hemolysis, icterus and lipemia in patient samples are well-known causes of analytical interference. Laboratories usually automatically check for these interferences and take them into account. However, other causes of interference are more difficult to detect, such as those caused by heterophilic antibodies and in this case a falsely elevated plasma creatinine level caused by a monoclonal IgM gammopathy. Analytical interference should be considered in cases with unexpected laboratory results and inconsistent pattern of results, in which contact and discussion with the laboratory is advised.

  • 57.
    Tjernberg, Ivar
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Region Kalmar County, Kalmar, Sweden.
    Johansson, Marcus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Region Kalmar County, Kalmar, Sweden.
    Henningsson, Anna J.
    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 Microbiology. Region Jönköping County, Jönköping, Sweden.
    Diagnostic performance of cerebrospinal fluid free light chains in Lyme neuroborreliosis: a pilot study2019In: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 57, no 12, p. 2008-2018Article in journal (Refereed)
    Abstract [en]

    Background

    The aim of this study was to evaluate the diagnostic performance of cerebrospinal fluid (CSF) free light chains (FLCs) in the diagnosis of Lyme neuroborreliosis (LNB).

    Methods

    Serum and CSF levels of κ- and λ-FLC, albumin and total concentration of immunoglobulin M (IgM) were determined together with CSF chemokine CXCL13 in 23 patients with definite LNB, 35 inflammatory neurological disease control (INDC) and 18 non-inflammatory control (NIC) patients. Indices and intrathecal fractions (IFs) of FLC and IgM were calculated.

    Results

    Significant differences in FLC indices and IFs were found between the LNB group and both control groups, p ≤ 0.007. Sensitivity of intrathecal κ- and λ-FLC synthesis reached 78%–87% in LNB patients with a specificity of 94%–100% in NIC patients, whereas specificity in INDC patients was 69%. The corresponding frequencies of positive results for IF and index of IgM and CSF CXCL13 in these three diagnostic groups were 74%–96% in LNB patients, 0% in NIC patients and 3%–6% in INDC patients at the chosen cut-off levels.

    Conclusions

    The findings of this study show a moderate to high sensitivity of CSF κ- and λ-FLC in LNB patients with a high specificity in NIC patients. However, overlap in CSF κ- and λ-FLC levels between LNB and INDC patients calls for caution in the interpretation and limits the diagnostic usefulness in the LNB diagnosis. CSF CXCL13 appears to be the most valuable additional biomarker of LNB aside from routine parameters such as CSF pleocytosis and anti-Borrelia antibody index.

  • 58. Order onlineBuy this publication >>
    Vikingsson, Svante
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Development of new methodology for therapeutic drug monitoring of thiopurine treatment2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The three thiopurine drugs azathioprine (AZA), 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) are used to treat several diseases, including inflammatory bowel disease (IBD). They are pro-drugs and are believed to act through the formation of thioguanine nucleotides (TGNs). Other important metabolites are the methylthioinosine nucleotides (meTINs). These metabolites are active in the white blood cells (WBCs).Most patients respond well to the thiopurine drugs but up to a third have to modify or discontinue their treatment due to adverse events or a lack of therapeutic effects. This could be caused by inter-patient variability in the metabolism of the drugs. Therapeutic drug monitoring (TDM) of thiopurine nucleotides in red blood cells (RBCs) is used to guide treatment. Current routine assays measure the nucleotides after hydrolysation to nucleic bases and are therefore unable to distinguish between mono-, di-, and triphosphates. Recently it was shown that these assays failed to predict the clinical outcome in about 40% of the patients. It has been suggested that measuring thioguanosine triphosphate (TGTP) (believed to be the most active of the TGNs) separately might increase the clinical value.An assay suitable for measuring thioguanosine mono- (TGMP) and diphosphate (TGDP) and TGTP, as well as methylthioinosine mono- (meTIMP), di- (meTIDP) and triphosphate (meTITP) separately in RBCs in clinical samples has been developed. In clinical studies of 82 IBD patients, we found no correlation between the thiopurine dose and metabolite levels in RBCs, thus illustrating the importance of metabolite measurements in the TDM of thiopurines.The TGN peak measured by the routine assay during TDM of patients treated with thiopurines consisted of TGTP and TGDP with a small contribution from TGMP. The meTIN also consisted of mono-, di- and triphosphates, but in different proportions, indicating differences in the formation. The inter-individual differences in nucleotide distribution were very small and a strong correlation between the different nucleotides and their respective sums was observed. As a consequence, measuring the mono-, di- and triphosphates separately was not beneficial in predicting remission, which was confirmed by the results from the clinical study.Further research into the metabolism and mode of action of thiopurine drugs is needed to understand the inter-patient variability in response and metabolite formation. An assay suitable for such studies, measuring TGNs and meTINs in cultured cells, has also been developed.

    List of papers
    1. Monitoring of thiopurine metabolites in patients with inflammatory bowel disease-what is actually measured?
    Open this publication in new window or tab >>Monitoring of thiopurine metabolites in patients with inflammatory bowel disease-what is actually measured?
    2009 (English)In: Therapeutic Drug Monitoring, ISSN 0163-4356, E-ISSN 1536-3694, Vol. 31, no 3, p. 345-50Article in journal (Refereed) Published
    Abstract [en]

    Azathioprine and 6-mercaptopurine are often used in the treatment of patients with inflammatory bowel disease (IBD). They are prodrugs and undergo a complex metabolism to active and inactive metabolites. Thiopurine treatment is monitored in many laboratories by measuring metabolite concentrations in erythrocytes (red blood cells). The metabolites of interest are not measured directly but as hydrolysis products, which can be produced from several metabolites. The aim of this study was to examine which metabolites are actually measured during routine monitoring. Samples from 18 patients treated with a thiopurine were analyzed by a typical routine high-performance liquid chromatography method for therapeutic drug monitoring and by a newly developed specific method measuring thioguanosine monophosphate (TGMP), thioguanosine diphosphate (TGDP), and thioguanosine triphosphate (TGTP), as well as methylthioinosine monophosphate (meTIMP), and the results were compared. 6-Thioguanine nucleotide (TGN) values detected by the routine method were 69% (range 40%-90%) of the sum of TGMP, TGDP, and TGTP measured by the specific method. TGTP and TGDP contributed 85% (range 78%-90%) and 14% (range 10%-21%) of the TGN total, respectively. Thioguanosine was not found in any patient sample. The concentration of meTIMP obtained by the routine method was 548% of the value obtained by the specific method (range 340%-718%). The difference in TGN measurements between the routine and specific methods can be explained by low hydrolysis efficiency in the routine method, although the most likely explanation for the difference in meTIMP values is that not yet identified metabolites are codetermined in the routine high-performance liquid chromatography method. Concentrations reported as TGN during therapeutic drug monitoring of thiopurine metabolites consist of TGDP and TGTP with a minor contribution of the TGMP. Concentrations reported as meTIMP or methyl mercaptopurine consist in part of meTIMP, but other not yet identified metabolites are codetermined.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-18985 (URN)10.1097/FTD.0b013e3181a1ea58 (DOI)19363461 (PubMedID)
    Available from: 2009-06-07 Created: 2009-06-07 Last updated: 2017-12-13Bibliographically approved
    2. Monitoring of thiopurine metabolites: A high-performance liquid chromatography method for clinical use
    Open this publication in new window or tab >>Monitoring of thiopurine metabolites: A high-performance liquid chromatography method for clinical use
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    high-performance liquid chromatography method capable of measuring thiopurine mono-, di-, and triphosphates separately in red blood cells (RBCs) was developed. RBC:s were isolated from whole blood using centrifugation. Proteins were precipitated using dichloromethane and methanol. The thioguanine nucleotides (TGNs) were derivatised using potassium permanganate before analysis. Analytes were separated by ion-pairing liquid chromatography using tetrabutylammonium ions and detected using UV absorption and fluorescence. The method was designed for use in clinical trials in thiopurine therapy and proven valid by analysis of authentic patient samples.

    The method measured thioguanosine mono- (TGMP), di- (TGDP), and triphosphate (TGTP), as well as methylthioinosine mono- (meTIMP), di- (meTIDP) and triphosphate (meTITP) in RBCs collected from patients treated with thiopurine drugs (azathioprine, 6-mercaptopurine, and 6-thioguanine).

    LOQ was 0.3, 3, 2, 30, 30 and 40 pmol/8x10^8 RBC, for TGMP, TGDP, TGTP, meTIMP, meTIDP and meTITP, respectively. Between-day precision were below 14% for all analytes at all concentrations and samples were stable at 5 °C for 8 hours after sampling.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-84843 (URN)
    Available from: 2012-10-24 Created: 2012-10-24 Last updated: 2012-10-24Bibliographically approved
    3. Therapeutic drug monitoring of thiopurines in inflammatory bowel disease: Evaluating the benefit of measuring mono-, di-, and triphosphates separately
    Open this publication in new window or tab >>Therapeutic drug monitoring of thiopurines in inflammatory bowel disease: Evaluating the benefit of measuring mono-, di-, and triphosphates separately
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    The thiopurines are widely used in the treatment of inflammatory bowel diseases but are limited by poor dose-effect relationship and large interindividual variability in clinical effects. Many attempts have been made to predict response by therapeutic drug monitoring of phosphorylated and methylated metabolites grouped together as thioguanine nucleotides and methylthioinosine monophosphate. We have developed a method to determine the individual metabolites, thioguanosine mono-, di-, and triphosphates, as well as methylthioinosine mono-, di-, and triphosphates, separately in red blood cells.

    This aim of this study was to assess the ability of our novel method to predict clinical outcome compared to the routine method in 82 patients with inflammatory bowel diseases.

    TPMT wild-type patients with TGN levels below the cut-off level were more likely to have an active disease when TGN was measured by both the routine method (p < 0.05), the novel method (p<0.05), and when TGTP was measured separately (p < 0.01). TGN levels and TGTP were, however, not correlated to disease activity in TPMT defective patients. Patients with meTIN levels above 1500 pmol were more likely to have an active disease (39%, 18/46 vs. 17%, 5/30; p = 0.02). We observed good correlations between the mono-, di-, and triphosphates and their respective sums (R2 > 0.88) and the TGTP ratio (TGTP/(TGDP+TGTP)) was not different in patients with active disease or in clinical remission.

    Thiopurine metabolites should still be measured by the routine method, since the novel and technically more challenging method, including determination of TGTP and TGTP ratio, does not offer a clinical advantage compared to the routine method.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-84844 (URN)
    Available from: 2012-10-24 Created: 2012-10-24 Last updated: 2012-10-24Bibliographically approved
    4. The Role of Inosine-5'-Monophosphate Dehydrogenase in Thiopurine Metabolism in Patients With Inflammatory Bowel Disease
    Open this publication in new window or tab >>The Role of Inosine-5'-Monophosphate Dehydrogenase in Thiopurine Metabolism in Patients With Inflammatory Bowel Disease
    Show others...
    2011 (English)In: Therapeutic Drug Monitoring, ISSN 0163-4356, E-ISSN 1536-3694, Vol. 33, no 2, p. 200-208Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND:: There is a large interindividual variability in thiopurine metabolism. High concentrations of methylthioinosine-5'-monophosphate (meTIMP) and low concentrations of 6-thioguanine nucleotides (6-TGNs) have been associated with a lower response rate and an increased risk of adverse events. In this study, the role of inosine-5'-monophosphate dehydrogenase (IMPDH) for differences in metabolite patterns of thiopurines was investigated.

    METHODS:: IMPDH activity and thiopurine metabolite concentrations were determined in patients with inflammatory bowel disease and a normal thiopurine methyltransferase (TPMT) phenotype and meTIMP/6-TGN concentration ratio > 20 (n = 26), in patients with a metabolite ratio ≤20 (n = 21), in a subgroup with a metabolite ratio <4 (n = 6), and in 10 patients with reduced TPMT activity. In vitro studies were conducted on human embryonic kidney cells (HEK293) with genetically engineered IMPDH and TPMT activities.

    RESULTS:: Patients with metabolite ratios >20 had lower IMPDH activity than those with ratios ≤20 (P < 0.001). Metabolic ratios >20 were only observed in patients with normal TPMT activity. Downregulation of IMPDH activity in HEK293 cells was associated with an increase in the concentration of meTIMP (fold change: 17 up to 93, P < 0.001) but, unexpectedly, also of 6-thioguanosine monophosphate (fold change: 2.6 up to 5.0, P < 0.001).

    CONCLUSIONS:: These data question the general view of IMPDH as the rate-limiting enzyme in the phosphorylation of thiopurines. Investigations of other mechanisms are needed to more fully explain the various metabolite patterns and outcomes in patients under treatment.

    Place, publisher, year, edition, pages
    Lippincott Williams & Wilkins, 2011
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-66431 (URN)10.1097/FTD.0b013e31820b42bb (DOI)000288498100010 ()21311411 (PubMedID)
    Available from: 2011-03-15 Created: 2011-03-15 Last updated: 2017-12-11Bibliographically approved
    Download full text (pdf)
    Development of new methodology for therapeutic drug monitoringof thiopurine treatment
    Download (pdf)
    omslag
  • 59.
    Walinder, Goran
    et al.
    Karolinska Inst, Sweden; Karolinska Univ Hosp Huddinge, Sweden.
    Samuelsson, Jan
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Nasman, Per
    KTH Royal Inst Technol, Sweden.
    Hansson, Markus
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Juliusson, Gunnar
    Lund Univ, Sweden.
    Forsberg, Karin
    Norrlands Univ Hosp, Sweden.
    Svensson, Ronald
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Linder, Olle
    Orebro Univ Hosp, Sweden.
    Carlson, Kristina
    Uppsala Univ Hosp, Sweden.
    Kristinsson, Sigurdur Y.
    Karolinska Inst, Sweden.
    Mellqvist, Ulf Henrik
    South Elvsborg Hosp, Sweden.
    Blimark, Cecilie Hveding
    Sahlgrens Univ Hosp, Sweden.
    Turesson, Ingemar
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Nahi, Hareth
    Karolinska Inst, Sweden; Karolinska Univ Hosp Huddinge, Sweden.
    Outcome and characteristics of non-measurable myeloma: A cohort study with population-based data from the Swedish Myeloma Registry2020In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 104, no 5, p. 376-382Article in journal (Refereed)
    Abstract [en]

    Objective We describe survival in patients with oligo- and non-secretory multiple myeloma (MM). We refer to the whole group as non-measurable MM and compare it with secretory MM. Methods Oligo-secretory MM was defined as M protein in serum &lt;10 g/L and M protein in urine &lt;200 measured as mg/day, mg/liter or mg/mmol creatinine. If patients had no M protein, they were defined as non-secretory. The groups were also subdivided by Free Light Chains (SFLC) level and ratio. Results Out of 4325 patients with symptomatic MM in the Swedish Myeloma Registry during 2008-2016 eligible for the study, 389 patients (9%) had non-measurable MM. Out of these, 253 patients (6%) had oligo-secretory and 136 (3%) had non-secretory MM. Median survival for secretory MM was 42.7 months, non-measurable MM 40.2 months, oligo-secretory MM 38.6 months, and non-secretory MM 44.6 months. Difference in overall observed survival was non-significant for all groups when compared with secretory MM. Within non-secretory MM, stem cell transplantation (SCT), 95% being auto-SCT, was significant for superior survival in multivariate analysis (HR 0.048. P = .0015). Conclusion In this population-based study, we found no difference in survival between oligo- or non-secretory MM when compared with secretory MM. SCT appears to be important also for patients with non-secretory disease.

  • 60.
    Wirestam, Lina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Frodlund, Martina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Enocsson, Helena
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Skogh, Thomas
    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 Rheumatology.
    Wetterö, Jonas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Sjöwall, Christopher
    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 Rheumatology.
    Osteopontin is associated with disease severity and antiphospholipid syndrome in well characterised Swedish cases of SLE2017In: Lupus Science and Medicine, ISSN 2053-8790, E-ISSN 1625-9823, Vol. 4, no 1, p. 7article id 000225Article in journal (Refereed)
    Abstract [en]

    Objective The variety of disease phenotypes among patients with SLE challenges the identification of new biomarkers reflecting disease activity and/or organ damage. Osteopontin (OPN) is an extracellular matrix protein with immunomodulating properties. Although raised levels have been reported, the pathogenic implications and clinical utility of OPN as a biomarker in SLE are far from clear. Thus, the aim of this study was to characterise OPN in SLE.

    Methods Sera from 240 well-characterised adult SLE cases classified according to the American College of Rheumatology (ACR) and/or the Systemic Lupus International Collaborating Clinics (SLICC) criteria, and 240 population-based controls were immunoassayed for OPN. The SLE Disease Activity Index 2000 (SLEDAI-2K) was used to evaluate disease activity and the SLICC/ACR Damage Index (SDI) to detect damage accrual.

    Results Serum OPN levels were in average raised fourfold in SLE cases compared with the controls (p<0.0001). OPN correlated with SLEDAI-2K, especially in patients with a disease duration of <12 months (r=0.666, p=0.028). OPN was highly associated with SDI (p<0.0001), especially in the renal (p<0.0001), cardiovascular (p<0.0001) and malignancy (p=0.012) domains. Finally, OPN associated with coherent antiphospholipid syndrome (APS; p=0.009), and both clinical and laboratory criteria of APS had significant positive impact on OPN levels.

    Conclusions In this cross-sectional study, circulating OPN correlates with disease activity in recent-onset SLE, reflects global organ damage and associates with APS. Longitudinal studies to dissect whether serum OPN also precedes and predicts future organ damage are most warranted.

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    Osteopontin is associated with disease severity and antiphospholipid syndrome in well characterised Swedish cases of SLE
  • 61.
    Zhang, Huan
    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. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Klareskog, Lars
    Karolinska Inst, Sweden.
    Matussek, Andreas
    Karolinska Univ Hosp Lab, Sweden.
    Pfister, Stefan M.
    Hopp Childrens Canc Ctr Heidelberg KiTZ, Germany; German Canc Res Ctr, Germany; German Canc Consortium DKTK, Germany; Heidelberg Univ Hosp, Germany.
    Benson, Mikael
    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, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Editorial Material: Translating genomic medicine to the clinic: challenges and opportunities in GENOME MEDICINE, vol 11, issue , pp2019In: Genome Medicine, ISSN 1756-994X, E-ISSN 1756-994X, Vol. 11, article id 9Article in journal (Other academic)
    Abstract [en]

    Editorial summaryGenomic medicine has considerable potential to provide novel diagnostic and therapeutic solutions for patients who have molecularly complex diseases and who are not responding to existing therapies. To bridge the gap between genomic medicine and clinical practice, integration of various data types, resources, and joint international initiatives will be required.

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