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  • 1.
    Abdelhadi, Saly
    et al.
    Karolinska Inst, Sweden.
    Nordlind, Klas
    Karolinska Inst, Sweden.
    Johansson, Bjoern
    Karolinska Inst, Sweden; Karolinska Inst, Sweden.
    Theodorsson, Elvar
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Holst, Mikael
    Karolinska Inst, Sweden.
    Loenndahl, Louise
    Karolinska Inst, Sweden.
    Expression of calcitonin gene-related peptide in atopic dermatitis and correlation with distress2024In: Immunopharmacology and immunotoxicology, ISSN 0892-3973, E-ISSN 1532-2513, Vol. 46, no 1, p. 67-72Article in journal (Refereed)
    Abstract [en]

    BackgroundAtopic dermatitis (AD) is a chronic, inflammatory, often severely itching skin disorder. It may worsen due to stress, depression, or anxiety. Calcitonin gene-related peptide (CGRP) may be involved in inflammation signaling. CGRP has also been suggested in relation to stress, depression, and anxiety. This study aimed to investigate the expression of CGRP in the skin of patients with AD.MethodsTwenty-seven adult patients with AD, characterized with clinical and psychodemographic parameters, were investigated regarding CGRP expression in skin biopsies, using an immunohistochemical technique.ResultsThe total number of CGRP-positive nerve-like fibers was found to be higher in lesional skin than in non-lesional skin. Moreover, more inflammatory cells of dendritic shape intruded into the epidermis in lesional skin compared to non-lesional skin. Keratinocytes showing expression of CGRP were also found in lesional skin. Interestingly, the number of CGRP-positive nerve-like fibers in lesional skin correlated with depressive and anxiety scores. Correlation with depressive score was also found for round CGRP-positive inflammatory cells in the epidermis.ConclusionsCGRP may have a role in both the inflammatory process and distress, in AD.

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  • 2.
    Adolfsson, Emma
    et al.
    Orebro Univ, Sweden.
    Kling, Daniel
    Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linkoping, Sweden.
    Gunnarsson, Cecilia
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics.
    Jonasson, Jon
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics.
    Green, Henrik
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linkoping, Sweden.
    Green, Anna
    Orebro Univ, Sweden.
    Whole exome sequencing of FFPE samples - expanding the horizon of forensic molecular autopsies2023In: International journal of legal medicine, ISSN 0937-9827, E-ISSN 1437-1596, Vol. 137, p. 1215-1234Article in journal (Refereed)
    Abstract [en]

    Forensic molecular autopsies have emerged as a tool for medical examiners to establish the cause of death. It is particularly useful in sudden unexplained deaths where the cause of death cannot be determined with a regular medical autopsy. We provide the first study of exome data from formalin-fixed paraffin-embedded samples (FFPE) paired with data from high-quality blood samples in forensic applications. The approach allows exploration of the potential to use FFPE samples for molecular autopsies and identify variants in extensive exome data. We leverage the high uniformity of the hybridization capture approach provided by Twist Bioscience to target the complete exome and sequence the libraries on a NextSeq 550. Our findings suggest that exome sequencing is feasible for 24 out of a total of 35 included FFPE samples. When successful, the coverage across the exome is comparatively high (> 90% covered to 20X) and uniform (fold80 below 1.5). Detailed variant comparisons for matched FFPE and blood samples show high concordance with few false variants (positive predictive value of 0.98 and a sensitivity of 0.97) with no distinct FFPE artefacts. Ultimately, we apply carefully constructed forensic gene panels in a stepwise manner to find genetic variants associated with the clinical phenotype and with relevance to the sudden unexplained death.

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  • 3.
    Adolfsson, Emma
    et al.
    Orebro Univ Hosp, Sweden; Orebro Univ, Sweden.
    Qvick, Alvida
    Orebro Univ Hosp, Sweden; Orebro Univ, Sweden.
    Green, Henrik
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linkoping, Sweden.
    Kling, Daniel
    Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linkoping, Sweden.
    Gunnarsson, Cecilia
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics. Region Östergötland, Regionledningskontoret, Övr Regionledningskontoret.
    Jonasson, Jon
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics. Orebro Univ Hosp, Sweden.
    Green, Anna
    Orebro Univ Hosp, Sweden; Orebro Univ, Sweden.
    Technical in-depth comparison of two massive parallel DNA-sequencing methods for formalin-fixed paraffin-embedded tissue from victims of sudden cardiac death2021In: Forensic Science International: Genetics, ISSN 1872-4973, E-ISSN 1878-0326, Vol. 53, article id 102522Article in journal (Refereed)
    Abstract [en]

    Sudden cardiac death (SCD) is a tragic and traumatic event. SCD is often associated with hereditary genetic disease and in such cases, sequencing of stored formalin fixed paraffin embedded (FFPE) tissue is often crucial in trying to find a causal genetic variant. This study was designed to compare two massive parallel sequencing assays for differences in sensitivity and precision regarding variants related to SCD in FFPE material. From eight cases of SCD where DNA from blood had been sequenced using HaloPlex, corresponding FFPE samples were collected six years later. DNA from FFPE samples were amplified using HaloPlex HS, sequenced on MiSeq, representing the first method, as well as amplified using modified Twist and sequenced on NextSeq, representing the second method. Molecular barcodes were included to distinguish artefacts from true variants. In both approaches, read coverage, uniformity and variant detection were compared using genomic DNA isolated from blood and corresponding FFPE tissue, respectively. In terms of coverage uniformity, Twist performed better than HaloPlex HS for FFPE samples. Despite higher overall coverage, amplicon-based HaloPlex technologies, both for blood and FFPE tissue, suffered from design and/or performance issues resulting in genes lacking complete coverage. Although Twist had considerably lower overall mean coverage, high uniformity resulted in equal or higher fraction of genes covered at >= 20X. By comparing variants found in the matched samples in a pre-defined cardiodiagnostic gene panel, HaloPlex HS for FFPE material resulted in high sensitivity, 98.0% (range 96.6-100%), and high precision, 99.9% (range 99.5-100%) for moderately fragmented samples, but suffered from reduced sensitivity (range 74.2-91.1%) in more severely fragmented samples due to lack of coverage. Twist had high sensitivity, 97.8% (range 96.8-98.7%) and high precision, 99.9% (range 99.3-100%) in all analyzed samples, including the severely fragmented samples.

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  • 4.
    Adori, Csaba
    et al.
    Karolinska Inst, Sweden.
    Daraio, Teresa
    Karolinska Inst, Sweden.
    Kuiper, Raoul
    Karolinska Inst, Sweden.
    Barde, Swapnali
    Karolinska Inst, Sweden.
    Horvathova, Lubica
    Slovak Acad Sci, Slovakia.
    Yoshitake, Takashi
    Karolinska Inst, Sweden.
    Ihnatko, Robert
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Georg August Univ Gottingen, Germany.
    Valladolid-Acebes, Ismael
    Karolinska Inst, Sweden.
    Vercruysse, Pauline
    Karolinska Inst, Sweden.
    Wellendorf, Ashley M.
    Cincinnati Childrens Hosp Med Ctr, OH 45229 USA.
    Gramignoli, Roberto
    Karolinska Inst, Sweden.
    Bozoky, Bela
    Karolinska Univ Hosp, Sweden.
    Kehr, Jan
    Karolinska Inst, Sweden.
    Theodorsson, Elvar
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Cancelas, Jose A.
    Cincinnati Childrens Hosp Med Ctr, OH 45229 USA; Univ Cincinnati, OH 45267 USA.
    Mravec, Boris
    Slovak Acad Sci, Slovakia; Comenius Univ, Slovakia.
    Jorns, Carl
    Karolinska Univ Hosp Huddinge, Sweden.
    Ellis, Ewa
    Karolinska Inst, Sweden; Karolinska Inst, Sweden.
    Mulder, Jan
    Karolinska Inst, Sweden.
    Uhlen, Mathias
    Karolinska Inst, Sweden; Royal Inst Technol, Sweden.
    Bark, Christina
    Karolinska Inst, Sweden.
    Hökfelt, Tomas
    Karolinska Inst, Sweden.
    Disorganization and degeneration of liver sympathetic innervations in nonalcoholic fatty liver disease revealed by 3D imaging2021In: Science Advances, E-ISSN 2375-2548, Vol. 7, no 30, article id eabg5733Article in journal (Refereed)
    Abstract [en]

    Hepatic nerves have a complex role in synchronizing liver metabolism. Here, we used three-dimensional (3D) immunoimaging to explore the integrity of the hepatic nervous system in experimental and human nonalcoholic fatty liver disease (NAFLD). We demonstrate parallel signs of mild degeneration and axonal sprouting of sympathetic innervations in early stages of experimental NAFLD and a collapse of sympathetic arborization in steatohepatitis. Human fatty livers display a similar pattern of sympathetic nerve degeneration, correlating with the severity of NAFLD pathology. We show that chronic sympathetic hyperexcitation is a key factor in the axonal degeneration, here genetically phenocopied in mice deficient of the Rac-1 activator Vav3. In experimental steatohepatitis, 3D imaging reveals a severe portal vein contraction, spatially correlated with the extension of the remaining nerves around the portal vein, enlightening a potential intrahepatic neuronal mechanism of portal hypertension. These fundamental alterations in liver innervation and vasculature uncover previously unidentified neuronal components in NAFLD pathomechanisms.

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  • 5.
    Ahlström, Stina
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Sweden.
    Ahlner, Johan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences.
    Jönsson, Anna K
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, S-58758 Linkoping, Sweden.
    Green, Henrik
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, S-58758 Linkoping, Sweden.
    The Importance of BHB Testing on the Post-Mortem Diagnosis of Ketoacidosis2022In: Biomolecules, E-ISSN 2218-273X, Vol. 12, no 1, article id 9Article in journal (Refereed)
    Abstract [en]

    Although beta-hydroxybutyrate (BHB) analysis has proved its importance in forensic pathology, its effects on cause-of-death diagnostics are unaddressed. Therefore, this study aims at evaluating the effects of BHB analysis on the number of deaths by DKA (diabetes ketoacidosis), AKA (alcoholic ketoacidosis), HHS (hyperosmolar hyperglycaemic state), hypothermia, diabetes, alcoholism, and acidosis NOS (not otherwise specified). All 2900 deaths from 2013 through 2019 in which BHB was analysed at the National Board of Forensic Medicine, and 1069 DKA, AKA, HHS, hypothermia, diabetes, alcoholism, and acidosis cases without BHB analysis were included. The prevalence of BHB-positive cases for each cause of death, and trends and proportions of different BHB concentrations, were investigated. The number of BHB analyses/year increased from 13 to 1417. AKA increased from three to 66 and acidosis from one to 20. The deaths from alcoholism, DKA, and hypothermia remained stable. It is unclear why death from alcoholism remained stable while AKA increased. The increase in unspecific acidosis deaths raises the question why a more specific diagnosis had not been used. In conclusion, BHB analysis is instrumental in detecting AKA and acidosis. The scientific basis for the diagnosis of DKA and hypothermia improved, but the number of cases did not change.

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  • 6.
    Ahlström, Stina
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Sweden.
    Thiblin, Ingemar
    Natl Board Forens Med, Sweden; Uppsala Univ, Sweden.
    Jönsson, Anna K
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linkoping, Sweden.
    Green, Henrik
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linkoping, Sweden.
    Characteristics of post-mortem beta-hydroxybutyrate-positivet cases - A retrospective study on age, sex and BMI in 1407 forensic autopsies2021In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 325, article id 110878Article in journal (Refereed)
    Abstract [en]

    Background: Post-mortem biochemistry, including the analysis of beta-hydroxybutyrate (BHB), is increasingly employed in forensic medicine, especially in conditions such as diabetes and chronic alcoholism. However, not much is known about the associations between age, body mass index (BMI), and sex and BHB concentrations in ketoacidotic conditions. Aim: To retrospectively study the association between age, BMI and sex in several conditions, such as diabetic ketoacidosis (DKA), alcoholic ketoacidosis (AKA), and elevated post-mortem BHB concentrations. Methods: 1407 forensic autopsy cases analysed for BHB were grouped by diagnosis: DKA, AKA, HHS [hyperosmolar hyperglycaemic state], acidosis NOS [not otherwise specified], or hypothermia. Age, sex, BMI and the concentrations of blood alcohol, vitreous glucose and blood BHB were recorded. Results: Cases of AKA and DKA were most numerous (184 and 156, respectively). In DKA and in its male subgroup, cases with severe ketosis (BHB > 1000 mu g/g) were younger and had a lower BMI than those with moderate ketosis (BHB 250-1000 mu g/g) and controls (P < 0.001). In DKA and in its female subgroup, cases with moderate ketosis cases were older (P = 0.0218 and P = 0.0083) than controls. In AKA and in its male subgroup, cases with severe ketosis had a lower BMI than those with moderate ketosis (P = 0.0391 and P = 0.0469) and controls (P < 0.001). Cases with moderate ketosis had a lower BMI than controls (P < 0.001). Conclusions: BHB concentration is associated with BMI in DKA and AKA, and with both BMI and age in DKA. Constitutional factors should, therefore, be considered in potential AKA and DKA cases. (c) 2021 The Authors. Published by Elsevier B.V. CC_BY_4.0

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  • 7.
    Alehagen, Urban
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Aaseth, Jan
    Innlandet Hosp Trust, Norway.
    Lindahl, Tomas
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Larsson, Anders
    Uppsala Univ, Sweden.
    Alexander, Jan
    Norwegian Inst Publ Hlth, Norway.
    Dietary Supplementation with Selenium and Coenzyme Q(10) Prevents Increase in Plasma D-Dimer While Lowering Cardiovascular Mortality in an Elderly Swedish Population2021In: Nutrients, E-ISSN 2072-6643, Vol. 13, no 4, article id 1344Article in journal (Refereed)
    Abstract [en]

    A low intake of selenium is associated with increased cardiovascular mortality. This could be reduced by supplementation with selenium and coenzyme Q(10). D-dimer, a fragment of fibrin mirroring fibrinolysis, is a biomarker of thromboembolism, increased inflammation, endothelial dysfunction and is associated with cardiovascular mortality in ischemic heart disease. The objective was to examine the impact of selenium and coenzyme Q(10) on the level of D-dimer, and its relationship to cardiovascular mortality. D-dimer was measured in 213 individuals at the start and after 48 months of a randomised double-blind placebo-controlled trial with selenium yeast (200 mu g/day) and coenzyme Q(10) (200 mg/day) (n = 106) or placebo (n = 107). The follow-up time was 4.9 years. All included individuals were low in selenium (mean 67 mu g/L, SD 16.8). The differences in D-dimer concentration were evaluated by the use of T-tests, repeated measures of variance and ANCOVA analyses. At the end, a significantly lower D-dimer concentration was observed in the active treatment group in comparison with those on placebo (p = 0.006). Although D-dimer values at baseline were weakly associated with high-sensitive CRP, while being more strongly associated with soluble tumour necrosis factor receptor 1 and sP-selectin, controlling for these in the analysis there was an independent effect on D-dimer. In participants with a D-dimer level above median at baseline, the supplementation resulted in significantly lower cardiovascular mortality compared to those on placebo (p = 0.014). All results were validated with a persisting significant difference between the two groups. Therefore, supplementation with selenium and coenzyme Q(10) in a group of elderly low in selenium and coenzyme Q(10) prevented an increase in D-dimer and reduced the risk of cardiovascular mortality in comparison with the placebo group. The obtained results also illustrate important associations between inflammation, endothelial function and cardiovascular risk.

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  • 8.
    Amirhosseini, Mehdi
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Alkaissi, Hammoudi
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Hultman, Per
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology.
    Havarinasab, Said
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences.
    Autoantibodies in outbred Swiss Webster mice following exposure to gold and mercury2021In: Toxicology and Applied Pharmacology, ISSN 0041-008X, E-ISSN 1096-0333, Vol. 412, article id 115379Article in journal (Refereed)
    Abstract [en]

    Exposure to heavy metals may have toxic effects on several human organs causing morbidity and mortality. Metals may trigger or exacerbate autoimmunity in humans. Inbred mouse strains with certain H-2 haplotypes are susceptible to xenobiotic-induced autoimmunity; and their immune response to metals such as mercury, gold, and silver have been explored. Serum antinuclear antibodies (ANA), polyclonal B-cell activation, hypergammaglobulinemia and tissue immune complex deposition are the main features of metal-induced autoimmunity in inbred mice. However, inbred mouse strains do not represent the genetic heterogeneity in humans. In this study, outbred Swiss Webster (SW) mice exposed to gold or mercury salts showed immune and autoimmune responses. Intramuscular injection of 22.5 mg/kg.bw aurothiomalate (AuTM) induced IgG ANA in SW mice starting after 5 weeks that persisted until week 15 although with a lower intensity. This was accompanied by elevated serum levels of total IgG antibodies against chromatin and total histones. Exposure to gold led to development of serum IgG autoantibodies corresponding to H1 and H2A histones, and dsDNA. Both gold and mercury induced polyclonal B-cell activation. Eight mg/L mercuric chloride (HgCl2) in drinking water, caused IgG antinucleolar antibodies (ANoA) after 5 weeks in SW mice accompanied by immune complex deposition in kidneys and spleen. Serum IgG antibodies corresponding to anti-fibrillarin, and anti-PM/Scl-100 antibodies, were observed in mercury-exposed SW mice. Gold and mercury trigger systemic autoimmune response in genetically heterogeneous outbred SW mice and suggest them as an appropriate model to study xenobiotic-induced autoimmunity.

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  • 9.
    Andreasen, Anne Sofie
    et al.
    Copenhagen Univ Hosp Herlev, Denmark.
    Wetterslev, Mik
    Copenhagen Univ Hosp Rigshosp, Denmark.
    Sigurdsson, Martin Ingi
    Landspitali Natl Univ Hosp Iceland, Iceland; Univ Iceland, Iceland.
    Bove, Jeppe
    Odense Univ Hosp, Denmark.
    Kjaergaard, Jesper
    Copenhagen Univ Hosp Rigshosp, Denmark.
    Aslam, Tayyba Naz
    Oslo Univ Hosp, Norway; Univ Oslo, Norway.
    Jarvela, Kati
    Tampere Univ Hosp, Finland.
    Poulsen, Mette
    Aarhus Univ Hosp, Denmark.
    de Geer, Lina
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, ANOPIVA US.
    Agarwal, Arnav
    McMaster Univ, Canada; McMaster Univ, Canada; MAGIC Evidence Ecosyst Fdn, Norway.
    Kjaer, Maj-Brit Norregaard
    Copenhagen Univ Hosp Rigshosp, Denmark.
    Moller, Morten Hylander
    Copenhagen Univ Hosp Rigshosp, Denmark; Univ Copenhagen, Denmark.
    New-onset atrial fibrillation in critically ill adult patients-an SSAI clinical practice guideline2023In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 67, no 8, p. 1110-1117Article in journal (Refereed)
    Abstract [en]

    Background: Acute or new-onset atrial fibrillation (NOAF) is the most common cardiac arrhythmia in critically ill adult patients, and observational data suggests that NOAF is associated to adverse outcomes. Methods: We prepared this guideline according to the Grading of Recommendations Assessment, Development and Evaluation methodology. We posed the following clinical questions: (1) what is the better first-line pharmacological agent for the treatment of NOAF in critically ill adult patients?, (2) should we use direct current (DC) cardioversion in critically ill adult patients with NOAF and hemodynamic instability caused by atrial fibrillation?, (3) should we use anticoagulant therapy in critically ill adult patients with NOAF?, and (4) should critically ill adult patients with NOAF receive follow-up after discharge from hospital? We assessed patient-important outcomes, including mortality, thromboembolic events, and adverse events. Patients and relatives were part of the guideline panel. Results: The quantity and quality of evidence on the management of NOAF in critically ill adults was very limited, and we did not identify any relevant direct or indirect evidence from randomized clinical trials for the prespecified PICO questions. We were able to propose one weak recommendation against routine use of therapeutic dose anticoagulant therapy, and one best practice statement for routine follow-up by a cardiologist after hospital discharge. We were not able to propose any recommendations on the better first-line pharmacological agent or whether to use DC cardioversion in critically ill patients with hemodynamic instability induced by NOAF. An electronic version of this guideline in layered and interactive format is available in MAGIC: https://app.magicapp.org/#/guideline/7197. Conclusions: The body of evidence on the management of NOAF in critically ill adults is very limited and not informed by direct evidence from randomized clinical trials. Practice variation appears considerable.

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  • 10.
    Aneman, Anders
    et al.
    Liverpool Hosp, Australia; Univ New South Wales, Australia; Macquarie Univ, Australia.
    Wilander, Petter
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Hallands Hosp, Sweden.
    Zoerner, Frank
    Liverpool Hosp, Australia.
    Lipcsey, Miklos
    Uppsala Univ, Sweden.
    Chew, Michelle
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, ANOPIVA US.
    Vasopressor Responsiveness Beyond Arterial Pressure: A Conceptual Systematic Review Using Venous Return Physiology2021In: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 56, no 3, p. 352-359Article, review/survey (Refereed)
    Abstract [en]

    We performed a systematic review to investigate the effects of vasopressor-induced hemodynamic changes in adults with shock. We applied a physiological approach using the interacting domains of intravascular volume, heart pump performance, and vascular resistance to structure the interpretation of responses to vasopressors. We hypothesized that incorporating changes in determinants of cardiac output and vascular resistance better reflect the vasopressor responsiveness beyond mean arterial pressure alone. We identified 28 studies including 678 subjects in Pubmed, EMBASE, and CENTRAL databases. All studies demonstrated significant increases in mean arterial pressure (MAP) and systemic vascular resistance during vasopressor infusion. The calculated mean systemic filling pressure analogue increased (16 +/- 3.3 mmHg to 18 +/- 3.4 mmHg; P = 0.02) by vasopressors with variable effects on central venous pressure and the pump efficiency of the heart leading to heterogenous changes in cardiac output. Changes in the pressure gradient for venous return and cardiac output, scaled by the change in MAP, were positively correlated (r (2) = 0.88, P < 0.001). Changes in the mean systemic filling pressure analogue and heart pump efficiency were negatively correlated (r (2) = 0.57, P < 0.001) while no correlation was found between changes in MAP and heart pump efficiency. We conclude that hemodynamic changes induced by vasopressor therapy are inadequately represented by the change in MAP alone despite its common use as a clinical endpoint. The more comprehensive analysis applied in this review illustrates how vasopressor administration may be optimized.

  • 11. Order onlineBuy this publication >>
    Arbring, Kerstin
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine and Geriatrics.
    Two worlds, one goal: A Clinician’s Perspective on Laboratory Analyses in Anticoagulant Treatment2023Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Almost precisely a century ago, in the 1920s and 1930s, cattle bled to death in North America after being fed moldy hay containing sweet clover, the yellow Melilotus officinalis, and the white Melilotus albus. The toxic substance in the hay inhibiting blood coagulation was identified and named dicumarol. Further development resulted in warfarin, an oral anticoagulant that has been used for over 70 years and still is, even though newer direct-acting oral anticoagulants (DOACs) are mainly replacing it. For some patients, warfarin is still the drug of choice. A safe warfarin treatment needs repeated blood sample analysis (PT-INR), and with the new DOACs come new laboratory challenges. The aim of this thesis was to investigate ways laboratory methods can contribute to improving oral anticoagulant treatment. 

    Paper I explores genetic variants of the enzyme targeted by warfarin, VKORC1. The result shows that the haplotype VKORC1*2 is the most important of the VKORC1 haplotypes for warfarin dosage, with a lower dose requirement. The VKORC1*2 haplotype was also related to more unstable PT-INR levels. 

    Paper II describes a cross-section study comparing warfarin treatment control, as PT-INRs within the intended therapeutic range, in primary health care centers (PHCCs) and specialized anticoagulation clinics (ACCs). Both settings showed good therapeutic control, with at least as good therapeutic control in the PHCCs as in the ACCs. Today, almost all warfarin treatment in our region is centralized to ACCs. 

    Paper III focuses on the modification of a point-of-care PT method. A ratio of PT from two different dilutions of each patient sample was calculated and used as an indirect measure of DOAC activity. There were close correlations between the PT ratio and drug concentrations measured at the hospital laboratory. The detection level varies between DOACs and may limit its use in some situations. 

    Paper IV evaluated the MRX PT DOAC, an assay based on the PT ratio principle. It was found to be able to detect potentially interfering DOAC levels in plasma samples. Confirmatory testing is recommended, as is sensitivity improvement for the detection of specific interferences.   

    List of papers
    1. Main haplotypes and mutational analysis of vitamin K epoxide reductase (VKORC1) in a Swedish population: A retrospective analysis of case records
    Open this publication in new window or tab >>Main haplotypes and mutational analysis of vitamin K epoxide reductase (VKORC1) in a Swedish population: A retrospective analysis of case records
    Show others...
    2006 (English)In: Journal of Thrombosis and Haemostasis, ISSN 1538-7933, Vol. 4, no 8, p. 1723-1729Article in journal (Refereed) Published
    Abstract [en]

    Background: Vitamin K epoxide reductase (VKORC1) is the site of inhibition by coumarins. Several reports have shown that mutations in the gene encoding VKORC1 affect the sensitivity of the enzyme for warfarin. Recently, three main haplotypes of VKORC1; *2, *3 and *4 have been observed, that explain most of the genetic variability in warfarin dose among Caucasians.

    Objectives: We have investigated the main haplotypes of the VKORC1 gene in a Swedish population. Additional objective was to screen the studied population for mutations in the coding region of VKORC1 gene.

    Patients/methods: Warfarin doses and plasma S- and R-warfarin of 98 patients [with a target International Normalized Ratio (INR) of 2.0–3.0] have been correlated to VKORC1 haplotypes. Controls of 180 healthy individuals have also been haplotyped. Furthermore, a retrospective analysis of case records was performed to find any evidence indicating influence of VKORC1 haplotypes on warfarin response in the first 4 weeks (initiation phase) and the latest 12 months of warfarin treatment.

    Results and conclusions: Our result shows that VKORC1*2 is the most important haplotype for warfarin dosage. Patients with VKORC1*2 haplotype had more frequent visits than patients with VKORC1*3 or *4 haplotypes, higher coefficient of variation (CV) of prothrombin time-INR and higher percentage of INR values outside the therapeutic interval (i.e. 2.0–3.0) than patients with VKORC1*3 or *4 haplotypes. Also, there was a statistically significant difference in warfarin dose (P < 0.001) and R-warfarin plasma levels (P < 0.01) between VKORC1*2 and VKORC1*3 or 4 haplotypes. Patients with VKORC1*2 haplotype seem to require much lower warfarin doses than other patients.

    Keywords
    INR, VKORC1, warfarin
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-14488 (URN)10.1111/j.1538-7836.2006.02039.x (DOI)
    Available from: 2007-05-21 Created: 2007-05-21 Last updated: 2023-10-31
    2. Comparison of prothrombin time (INR) results and main characteristics of patients on warfarin treatment in primary health care centers and anticoagulation clinics
    Open this publication in new window or tab >>Comparison of prothrombin time (INR) results and main characteristics of patients on warfarin treatment in primary health care centers and anticoagulation clinics
    2013 (English)In: BMC Health Services Research, E-ISSN 1472-6963, Vol. 13Article in journal (Refereed) Published
    Abstract [en]

    Background

    Oral anticoagulant therapy is used to prevent thrombosis in patients with atrial fibrillation (AF), venous thrombosis and prosthetic heart valves. The introduction of new therapies emphasizes the need to discern the best practice for the patients remaining on warfarin treatment. This study compares patient characteristics and therapeutic control in two settings managing warfarin treatment: Swedish primary health care centers (PHCC) and specialized anticoagulation clinics (ACC).

    Methods

    Prothrombin time (PT) test results reported as International Normalized Ratio (INR) were collected for five consecutive days from patients on warfarin treatment; 564 PHCC and 927 ACC patients. Therapeutic control was calculated as PT test results in relation to intended therapeutic range (TR). Mann–Whitney Rank Sum Test and Chi2 test were used for statistical comparisons.

    Results

    The PHCC patients were older than the ACC patients, 76 v. 70 years (p<0.01) with a predominance of men in both groups. The reasons for treating differed between the groups. Seventy-two percent of PHCC patients and 66% of ACC patients had a PT-INR within the intended TR (p<0.05). Men generally had better results than women (72% v. 63%, p<0.001) and particularly in the PHCC group v. the ACC group (78% v. 69%, p<0.01).

    PT-INR above intended TR was significantly more common in the ACC setting, (p<0.05), for women overall (p<0.01), for women in the PHCC setting, and for ACC men (p<0.05).

    Conclusions

    In this study both settings achieved good therapeutic control of warfarin treatment with a minor advantage for PHCC over ACC, and better results for men, especially in the PHCC setting. As patient characteristics differ between the PHCC and ACC, it is important to conduct further randomized studies to discern the best practice locally for warfarin management also after the introduction of new drugs.

    Place, publisher, year, edition, pages
    BioMed Central, 2013
    Keywords
    Oral anticoagulants, Treatment, Quality control, Warfarin
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-90753 (URN)10.1186/1472-6963-13-85 (DOI)000315994100001 ()
    Note

    Funding Agencies|Medical Research Council of Southeast Sweden (FORSS)||

    Available from: 2013-04-08 Created: 2013-04-05 Last updated: 2023-10-31Bibliographically approved
    3. A novel prothrombin time method to measure all non-vitamin K-dependent oral anticoagulants (NOACs)
    Open this publication in new window or tab >>A novel prothrombin time method to measure all non-vitamin K-dependent oral anticoagulants (NOACs)
    2017 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 122, no 3, p. 171-176Article in journal (Refereed) Published
    Abstract [en]

    Background: There is a clinical need for point-of-care (POC) methods for non-vitamin K-dependent oral anticoagulants (NOACs). We modified a routine POC procedure: Zafena’s Simple Simon™ PT-INR, a room-temperature, wet-chemistry prothrombin time method of the Owren-type.

    Methods: To either increase or decrease NOAC interference, two assay variants were devised by replacing the standard 10 µL end-to-end capillary used to add the citrated plasma sample to 200 µL of prothrombin time (PT) reagent by either a 20 µL or a 5 µL capillary. All assay variants were calibrated to show correct PT results in plasma samples from healthy and warfarin-treated persons.

    Results: For plasmas spiked with dabigatran, apixaban, or rivaroxaban, the 20 µL variant showed markedly higher PT results than the 5 µL. The effects were even more pronounced at room temperature than at +37 °C. In plasmas from patients treated with NOACs (n = 30 for each) there was a strong correlation between the PT results and the concentration of NOACs as determined by the central hospital laboratory. For the 20 µL variant the PT response of linear correlation coefficient averaged 0.90. The PT range was INR 1.1–2.1 for dabigatran and apixaban, and INR 1.1–5.0 for rivaroxaban. Using an INR ratio between the 20 µL and 5 µL variants (PTr20/5) made the NOAC assay more robust and independent of the patient sample INR value in the absence of NOAC. Detection limits were 80 µg/L for apixaban, 60 µg/L for dabigatran, and 20 µg/L for rivaroxaban.

    Conclusions: A wet-chemistry POC PT procedure was modified to measure the concentrations of three NOACs using a single reagent.

    Place, publisher, year, edition, pages
    Taylor & Francis Group, 2017
    Keywords
    Anticoagulant, apixaban, dabigatran, prothrombin time, rivaroxaban
    National Category
    Clinical Medicine
    Identifiers
    urn:nbn:se:liu:diva-141178 (URN)10.1080/03009734.2017.1370040 (DOI)000414107800003 ()28891412 (PubMedID)
    Note

    Funding agencies: county of Ostergotland research funds [LIO-609911]

    Available from: 2017-09-25 Created: 2017-09-25 Last updated: 2023-10-31
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  • 12.
    Ardsby, Malin
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine in Linköping.
    Shayo, Frida
    Kilimanjaro Christian Med Ctr, Tanzania.
    Sakita, Francis M.
    Kilimanjaro Christian Med Ctr, Tanzania; Kilimanjaro Christian Med Univ Coll, Tanzania.
    Wilhelms, Daniel
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine in Linköping.
    Moshi, Baraka
    Kilimanjaro Christian Med Univ Coll, Tanzania.
    Frankiewicz, Parker
    Duke Global Hlth Inst, NC 27710 USA.
    Silva, Lincoln Luis
    Duke Global Hlth Inst, NC 27710 USA.
    Staton, Catherine A.
    Duke Global Hlth Inst, NC 27710 USA; Duke Univ, NC 27708 USA.
    Mmbaga, Blandina
    Kilimanjaro Christian Med Ctr, Tanzania; Kilimanjaro Clin Res Inst, Tanzania.
    Joiner, Anjni
    Duke Global Hlth Inst, NC 27710 USA; Duke Univ, NC 27708 USA.
    Emergency unit capacity in Northern Tanzania: a cross-sectional survey2023In: BMJ Open, E-ISSN 2044-6055, Vol. 13, no 2Article in journal (Refereed)
    Abstract [en]

    IntroductionEmergency medicine (EM) is a growing field in Sub-Saharan Africa. Characterising the current capacity of hospitals to provide emergency care is important in identifying gaps and future directions of growth. This study aimed to characterise the ability of emergency units (EU) to provide emergency care in the Kilimanjaro region in Northern Tanzania.MethodsThis was a cross-sectional study conducted at 11 hospitals with emergency care capacity in three districts in the Kilimanjaro region of Northern Tanzania assessed in May 2021. An exhaustive sampling approach was used, whereby all hospitals within the three-district area were surveyed. Hospital representatives were surveyed by two EM physicians using the Hospital Emergency Assessment tool developed by the WHO; data were analysed in Excel and STATA.ResultsAll hospitals provided emergency services 24 hours a day. Nine had a designated area for emergency care, four had a core of fixed providers assigned to the EU, two lacked a protocol for systematic triage. For Airway and Breathing interventions, oxygen administration was adequate in 10 hospitals, yet manual airway manoeuvres were only adequate in six and needle decompression in two. For Circulation interventions, fluid administration was adequate in all facilities, yet intraosseous access and external defibrillation were each only available in two. Only one facility had an ECG readily available in the EU and none was able to administer thrombolytic therapy. For trauma interventions, all facilities could immobilise fractures, yet lacked interventions such as cervical spinal immobilisation and pelvic binding. These deficiencies were primarily due to lack of training and resources.ConclusionMost facilities perform systematic triage of emergency patients, though major gaps were found in the diagnosis and treatment of acute coronary syndrome and initial stabilisation manoeuvres of patients with trauma. Resource limitations were primarily due to equipment and training deficiencies. We recommend the development of future interventions in all levels of facilities to improve the level of training.

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  • 13.
    Ariander, Annaclara
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center.
    Olaison, Anna
    Linköping University, Department of Culture and Society, Division of Social Work. Linköping University, Faculty of Arts and Sciences.
    Andersson, Christer
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Sjödahl, Rune
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Nilsson, Lena
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, ANOPIVA US.
    Kastbom, Lisa
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Kisa. Region Östergötland, Primary Care Center, Primary Health Care Center Ekholmen.
    Ethical challenges causing moral distress: nursing home staff's experiences of working during the COVID-19 pandemic2024In: Scandinavian Journal of Primary Health Care, ISSN 0281-3432, E-ISSN 1502-7724Article in journal (Refereed)
    Abstract [en]

    ObjectiveTo investigate the experiences of healthcare staff in nursing homes during the COVID-19 pandemic.DesignIndividual interviews. Latent qualitative content analysis.SettingTen nursing homes in Sweden.SubjectsPhysicians, nurses and nurse assistants working in Swedish nursing homes.Main outcome measuresParticipants' experiences of working in nursing homes during the COVID-19 pandemic.ResultsFour manifest categories were found, namely: Balancing restrictions and allocation of scarce resources with care needs; Prioritizing and acting against moral values in advance care planning; Distrust in cooperation and Leadership and staff turnover - a factor for moral distress. The latent theme Experiences of handling ethical challenges caused by the COVID-19 pandemic gave a deeper meaning to the categories.ConclusionDuring the pandemic, nursing home staff encountered ethical challenges that caused moral distress. Moral distress stemmed from not being given adequate conditions to perform their work properly, and thus not being able to give the residents adequate care. Another aspect of moral distress originated from feeling forced to act against their moral values when a course of action was considered to cause discomfort or harm to a resident. Alerting employers and policymakers to the harm and inequality experienced by staff and the difficulty in delivering appropriate care is essential. Making proposals for improvements and developing guidelines together with staff to recognize their role and to develop better guidance for good care is vital in order to support and sustain the nursing home workforce. The COVID-19 pandemic has affected both patients and staff in nursing homes, in Sweden and worldwide.Our study highlights that during the COVID-19 pandemic, nursing home staff encountered several ethical challenges which caused moral distress.Moral distress stemmed from not being given adequate conditions to perform their work, thus not giving the residents appropriate care.Moral distress could also originate from nursing home staff's feeling of being forced to act against their moral values.

  • 14.
    As, Joel
    et al.
    Uppsala Univ, Sweden.
    Bertulyte, Ilma
    Uppsala Univ, Sweden.
    Norgren, Nina
    Uppsala Univ, Sweden.
    Johansson, Anna
    Uppsala Univ, Sweden.
    Eriksson, Niclas
    Uppsala Univ, Sweden; Uppsala Clin Res Ctr, Sweden.
    Green, Henrik
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linkoping, Sweden.
    Wadelius, Mia
    Uppsala Univ, Sweden.
    Hallberg, Paer
    Uppsala Univ, Sweden.
    Whole genome case-control study of central nervous system toxicity due to antimicrobial drugs2024In: PLOS ONE, E-ISSN 1932-6203, Vol. 19, no 2, article id e0299075Article in journal (Refereed)
    Abstract [en]

    A genetic predisposition to central nervous system (CNS) toxicity induced by antimicrobial drugs (antibiotics, antivirals, antifungals, and antiparasitic drugs) has been suspected. Whole genome sequencing of 66 cases and 833 controls was performed to investigate whether antimicrobial drug-induced CNS toxicity was associated with genetic variation. The primary objective was to test whether antimicrobial-induced CNS toxicity was associated with seventeen efflux transporters at the blood-brain barrier. In this study, variants or structural elements in efflux transporters were not significantly associated with CNS toxicity. Secondary objectives were to test whether antimicrobial-induced CNS toxicity was associated with genes over the whole genome, with HLA, or with structural genetic variation. Uncommon variants in and close to three genes were significantly associated with CNS toxicity according to a sequence kernel association test combined with an optimal unified test (SKAT-O). These genes were LCP1 (q = 0.013), RETSAT (q = 0.013) and SFMBT2 (q = 0.035). Two variants were driving the LCP1 association: rs6561297 (p = 1.15x10-6, OR: 4.60 [95% CI: 2.51-8.46]) and the regulatory variant rs10492451 (p = 1.15x10-6, OR: 4.60 [95% CI: 2.51-8.46]). No common genetic variant, HLA-type or structural variation was associated with CNS toxicity. In conclusion, CNS toxicity due to antimicrobial drugs was associated with uncommon variants in LCP1, RETSAT and SFMBT2.

  • 15.
    Aslam, Tayyba N.
    et al.
    Oslo Univ Hosp, Norway; Univ Oslo, Norway.
    Klitgaard, Thomas L.
    Aalborg Univ Hosp, Denmark.
    Ahlstedt, Christian A. O.
    Karolinska Univ, Sweden.
    Andersen, Finn H.
    Alesund Hosp, Norway.
    Chew, Michelle S
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, ANOPIVA US.
    Collet, Marie O.
    Rigshospitalet, Denmark.
    Cronhjort, Maria
    Karolinska Inst, Sweden.
    Estrup, Stine
    Rigshospitalet, Denmark.
    Fossum, Ole K.
    Akershus Univ Hosp, Norway.
    Frisvold, Shirin K.
    Univ Hosp North Norway, Norway.
    Gillmann, Hans-Joerg
    Hannover Med Sch, Germany.
    Granholm, Anders
    Rigshospitalet, Denmark.
    Gundem, Trine M.
    Oslo Univ Hosp, Norway.
    Hauss, Kristin
    Sykehuset Telemark, Norway.
    Hollenberg, Jacob
    Karolinska Inst, Sweden.
    Condori, Maria E. Huanca
    Helse Fonna, Norway.
    Hästbacka, Johanna
    Univ Helsinki, Finland; Helsinki Univ Hosp, Finland.
    Johnstad, Bror A.
    Sykehuset Innlandet Hamar, Norway.
    Keus, Eric
    Univ Med Ctr Groningen, Netherlands.
    Kjaer, Maj-Brit N.
    Rigshospitalet, Denmark.
    Klepstad, Pal
    St Olavs Univ Hosp, Norway.
    Krag, Mette
    Holbaek Cent Hosp, Denmark.
    Kvåle, Reidar
    Haukeland Hosp, Norway.
    Malbrain, Manu L. N. G.
    Med Univ Lublin, Poland.
    Meyhoff, Christian S.
    Copenhagen Univ Hosp Bispebjerg & Frederiksberg, Denmark.
    Morgan, Matt
    Royal Perth Hosp, Australia.
    Moller, Anders
    Copenhagen Univ Hosp Bispebjerg & Frederiksberg, Denmark.
    Pfortmueller, Carmen A.
    Bern Univ Hosp, Switzerland.
    Poulsen, Lone M.
    Zealand Univ Hosp, Denmark.
    Robertson, Andrew C.
    Baerum Hosp, Norway.
    Schefold, Joerg C.
    Univ Bern, Switzerland.
    Schjorring, Olav L.
    Aalborg Univ Hosp, Denmark.
    Siegemund, Martin
    Univ Hosp Basel, Switzerland.
    Sigurdsson, Martin I.
    Landspitali Natl Univ Hosp Iceland, Iceland.
    Sjövall, Fredrik
    Skane Univ Hosp, Sweden.
    Strand, Kristian
    Stavanger Univ Hosp, Norway.
    Stueber, Thomas
    Hannover Med Sch, Germany.
    Szczeklik, Wojciech
    Jagiellonian Univ Med Coll, Poland.
    Wahlin, Rebecka R.
    Karolinska Inst, Sweden; Karolinska Inst, Sweden.
    Wangberg, Helge L.
    Volda Hosp, Norway.
    Wian, Karl-Andre
    Vestfold Hosp Trust, Norway.
    Wichmann, Sine
    Copenhagen Univ Hosp North Zealand, Denmark.
    Hofso, Kristin
    Oslo Univ Hosp, Norway.
    Moller, Morten H.
    Rigshospitalet, Denmark.
    Perner, Anders
    Rigshospitalet, Denmark.
    Rasmussen, Bodil S.
    Aalborg Univ Hosp, Denmark.
    Laake, Jon H.
    Oslo Univ Hosp, Norway.
    SVALBARD Investigators,
    A survey of preferences for respiratory support in the intensive care unit for patients with acute hypoxaemic respiratory failure2023In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 67, no 10, p. 1383-1394Article in journal (Refereed)
    Abstract [en]

    BackgroundWhen caring for mechanically ventilated adults with acute hypoxaemic respiratory failure (AHRF), clinicians are faced with an uncertain choice between ventilator modes allowing for spontaneous breaths or ventilation fully controlled by the ventilator. The preferences of clinicians managing such patients, and what motivates their choice of ventilator mode, are largely unknown. To better understand how clinicians preferences may impact the choice of ventilatory support for patients with AHRF, we issued a survey to an international network of intensive care unit (ICU) researchers.MethodsWe distributed an online survey with 32 broadly similar and interlinked questions on how clinicians prioritise spontaneous or controlled ventilation in invasively ventilated patients with AHRF of different severity, and which factors determine their choice.ResultsThe survey was distributed to 1337 recipients in 12 countries. Of these, 415 (31%) completed the survey either fully (52%) or partially (48%). Most respondents were identified as medical specialists (87%) or physicians in training (11%). Modes allowing for spontaneous ventilation were considered preferable in mild AHRF, with controlled ventilation considered as progressively more important in moderate and severe AHRF. Among respondents there was strong support (90%) for a randomised clinical trial comparing spontaneous with controlled ventilation in patients with moderate AHRF.ConclusionsThe responses from this international survey suggest that there is clinical equipoise for the preferred ventilator mode in patients with AHRF of moderate severity. We found strong support for a randomised trial comparing modes of ventilation in patients with moderate AHRF.

  • 16.
    Asp, Marie
    et al.
    Lund Univ, Sweden; Psychiat Clin Lund, Sweden.
    Ambrus, Livia
    Lund Univ, Sweden; Psychiat Clin Lund, Sweden.
    Reis, Margareta
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences.
    Manninen, Sofie
    Lund Univ, Sweden.
    Fernström, Johan
    Lund Univ, Sweden; Psychiat Clin Lund, Sweden.
    Lindqvist, Daniel
    Lund Univ, Sweden; Psychiat Res Skane, Sweden.
    Westrin, Åsa
    Lund Univ, Sweden; Psychiat Res Skane, Sweden.
    Differences in antipsychotic treatment between depressive patients with and without a suicide attempt2021In: Comprehensive Psychiatry, ISSN 0010-440X, E-ISSN 1532-8384, Vol. 109, article id 152264Article in journal (Refereed)
    Abstract [en]

    Background: Depressed suicide attempters are, according to some earlier studies, treated more often with antipsychotics than depressive non-suicide attempters. Cluster B personality disorders, especially borderline personality disorder, are associated with a high suicide risk, and antipsychotics are commonly used for the reduction of symptoms. However, no previous study has taken comorbid personality disorders into account when assessing the use of antipsychotics in patients with unipolar depression. Therefore, the aim of this study was to investigate the clinical selection of pharmacotherapy in unipolar depression with and without a previous suicide attempt, taking into account potential confounders such as cluster B personality disorders. Methods: The study sample consisted of 247 patients with unipolar depression. The study was approved by the Regional Ethical Review Board in Lund, Sweden. Study participants were recruited from 4 different secondary psychiatric care clinics in Sweden and were diagnosed according to the DSM-IV-TR with the MINI and SCID II. Previous and ongoing psychiatric treatments were investigated in detail and medical records were assessed. Results: Thirty percent of the patients had made previous suicide attempts. Depressed suicide attempters underwent both lifetime treatment with antipsychotics and an ongoing antipsychotic treatment significantly more often than non-attempters. Significances remained after a regression analysis, adjusting for cluster B personality disorders, symptom severity, age at the onset of depression, and lifetime psychotic symptoms. Conclusions: This is the first study to consider the effect of comorbidity with cluster B personality disorders when comparing treatment of depressive suicide and non-suicide attempters. Our findings suggest that suicide attempters are more frequently treated with antipsychotics compared to non-suicide attempters, regardless of cluster B personality disorder comorbidity. These findings are important for clinicians to consider and would also be relevant to future studies evaluating reduction of suicide risk with antipsychotics in patients with psychiatric comorbidity and a history of attempted suicide.

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  • 17.
    Atanasova, Diana
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences.
    Mirgorodskaya, Ekaterina
    Proteomics Core Facility, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Moparthi, Lavanya
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Koch, Stefan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Haarhaus, Mathias
    Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Narisawa, Sonoko
    Sanford Children’s Health Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, United States.
    Millán, José Luis
    Sanford Children’s Health Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, United States.
    Landberg, Eva
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Magnusson, Per
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Glycoproteomic profile of human tissue-nonspecific alkaline phosphatase expressed in osteoblasts2024In: JBMR Plus, E-ISSN 2473-4039, Vol. 8, no 2, article id ziae006Article in journal (Refereed)
    Abstract [en]

    Tissue-nonspecific alkaline phosphatase (TNALP) is a glycoprotein expressed by osteoblasts that promotes bone mineralization. TNALP catalyzes the hydrolysis of the mineralization inhibitor inorganic pyrophosphate and ATP to provide inorganic phosphate, thus controlling the inorganic pyrophosphate/inorganic phosphate ratio to enable the growth of hydroxyapatite crystals. N-linked glycosylation of TNALP is essential for protein stability and enzymatic activity and is responsible for the presence of different bone isoforms of TNALP associated with functional and clinical differences. The site-specific glycosylation profiles of TNALP are, however, elusive. TNALP has 5 potential N-glycosylation sites located at the asparagine (N) residues 140, 230, 271, 303, and 430. The objective of this study was to reveal the presence and structure of site-specific glycosylation in TNALP expressed in osteoblasts. Calvarial osteoblasts derived from Alpl+/− expressing SV40 Large T antigen were transfected with soluble epitope-tagged human TNALP. Purified TNALP was analyzed with a lectin microarray, matrix-assisted laser desorption/ionization-time of flight mass spectrometry, and liquid chromatography with tandem mass spectrometry. The results showed that all sites (n = 5) were fully occupied predominantly with complex-type N-glycans. High abundance of galactosylated biantennary N-glycans with various degrees of sialylation was observed on all sites, as well as glycans with no terminal galactose and sialic acid. Furthermore, all sites had core fucosylation except site N271. Modelling of TNALP, with the protein structure prediction software ColabFold, showed possible steric hindrance by the adjacent side chain of W270, which could explain the absence of core fucosylation at N271. These novel findings provide evidence for N-linked glycosylation on all 5 sites of TNALP, as well as core fucosylation on 4 out of 5 sites. We anticipate that this new knowledge can aid in the development of functional and clinical assays specific for the TNALP bone isoforms.

  • 18.
    Augustsson, Cecilia
    et al.
    Univ & Reg Labs Reg Skane, Sweden.
    Taxbro, Knut
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Cty Hosp, Sweden.
    Strandberg, Karin
    Univ & Reg Labs Reg Skane, Sweden.
    Zetterberg, Eva
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    A nonneutralizing antibody as cause of prothrombin deficiency in a patient with follicular lymphoma2024In: Clinical Case Reports, E-ISSN 2050-0904, Vol. 12, no 1, article id e8400Article in journal (Refereed)
    Abstract [en]

    Acquired inhibitors of blood coagulation are rare but of clinical importance. Prothrombin is a vitamin K-dependent protein, and acquired antibodies toward prothrombin are often associated with the presence of lupus anticoagulant. We describe a previously healthy 70-year-old man presenting with both hemorrhage and thrombosis as well as a prolonged prothrombin time. At arrival at the hospital, he was diagnosed with deep venous thrombosis, and an enlarged lymph node in the left groin was noted (revealed as follicular lymphoma grade 1 by biopsy). Prothrombin activity and antibody titer were followed for 5 months with 15 sampling time points to monitor the treatment outcome of the patient. Diagnostic work-up identified prothrombin deficiency as cause of bleeding. A nonneutralizing calcium-dependent antiprothrombin antibody was found, suspected to increase the clearance of prothrombin, which has previously only occasionally been reported. Lupus anticoagulant was ruled out and thrombosis was judged to be caused by a combination of malignant disease and stagnant venous flow following enlarged lymph nodes in the groin. This report illustrates how investigation of prolonged global coagulation tests, triggered the diagnosis of a rare but critical condition, immune-mediated prothrombin deficiency. The diagnosis is challenging and involves proper differential diagnosis. image

  • 19.
    Axelsson, Magnus A. B.
    et al.
    Sahlgrens Univ Hosp, Sweden; Univ Gothenburg, Sweden.
    Lovgren, Hanna
    Sahlgrens Univ Hosp, Sweden.
    Kronstrand, Robert
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linkoping, Sweden.
    Green, Henrik
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linkoping, Sweden.
    Bergstrom, Moa Andresen
    Sahlgrens Univ Hosp, Sweden; Univ Gothenburg, Sweden.
    Retrospective identification of new psychoactive substances in patient samples submitted for clinical drug analysis2022In: Basic & Clinical Pharmacology & Toxicology, ISSN 1742-7835, E-ISSN 1742-7843, Vol. 131, no 5, p. 420-434Article in journal (Refereed)
    Abstract [en]

    New psychoactive substances (NPS) are life threatening through unpredictable toxicity and limited analytical options for clinicians. We present the retrospective identification of NPS in raw data from a liquid chromatography-high resolution mass spectrometry (LC-HRMS)-based multidrug panel analysis on 14 367 clinical oral fluid samples requested during 2019 mainly by psychiatric and addiction care clinics. Retrospectively analysed NPS included 48 notified originally in 2019 by the European Union Early Warning System (EU EWS) and 28 frequently reported in Sweden. Of 88 included NPS, 34 (mitragynine, flualprazolam, 3F/4F-alpha-P(i)HP, etizolam, 4F-MDMB-BINACA, cyproheptadine, 5F-MDMB-PICA, isotonitazene, isohexedrone, MDPEP, N-ethylpentedrone, tianeptine, flubromazolam, 4 -methylhexedrone, alpha-P(i)HP, eutylone, mephedrone, N-ethylhexedrone, 5F-MDMB-PINACA, ADB-BUTINACA, 3-methoxy PCP, 4F-furanylfentanyl, 4F-isobuturylfentanyl, acrylfentanyl, furanylfentanyl, clonazolam, norfludiazepam, 3F-phenmetrazine, 3-MMC, 4-methylpentedrone, BMDP, ethylphenidate, methylone and alpha-PVP) were identified as 219 findings in 84 patients. Eight NPS notified in 2019 were identified, five before EWS release. NPS occurred in 1.20% of all samples and 1.53% of samples containing traditional drugs, and in 1.87% of all patients and 2.88% of patients using traditional drugs. NPS use was more common in men and polydrug users. Legal (not scheduled) NPS were more used than comparable illegal ones. Retrospective identification could be useful when prioritizing NPS for clinical routine analysis and when studying NPS epidemiology.

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  • 20.
    Babarro, Izaro
    et al.
    Faculty of Psychology, University of the Basque Country, UPV/EHU, Donostia/San Sebastian, Spain;Biodonostia Health Research Institute, Group of Environmental Epidemiology and Child Development, Donostia/San Sebastian, Spain.
    Ibarluzea, Jesus
    Faculty of Psychology, University of the Basque Country, UPV/EHU, Donostia/San Sebastian, Spain;Biodonostia Health Research Institute, Group of Environmental Epidemiology and Child Development, Donostia/San Sebastian, Spain;Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain;Health Department of Basque Government, Public Health of Gipuzkoa, Donostia/San Sebastian, Spain.
    Theodorsson, Elvar
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Fano, Eduardo
    Faculty of Psychology, University of the Basque Country, UPV/EHU, Donostia/San Sebastian, Spain;Biodonostia Health Research Institute, Group of Environmental Epidemiology and Child Development, Donostia/San Sebastian, Spain.
    Lebeña, Andrea
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Faculty of Psychology, University of the Basque Country, UPV/EHU, Donostia/San Sebastian, Spain.
    Guxens, Monica
    Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain;Department of Experimental and Health Sciences, Barcelona Institute for Global Health (ISGlobal), Barcelona, Spain;Department of Experimental and Health Sciences, University of Pompeu Fabra (UPF), Barcelona, Spain;Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC University Medical Centre, Roterdam, The Netherlands.
    Sunyer, Jordi
    Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain;Department of Experimental and Health Sciences, Barcelona Institute for Global Health (ISGlobal), Barcelona, Spain;Department of Experimental and Health Sciences, University of Pompeu Fabra (UPF), Barcelona, Spain;Municipal Institute of Medical Research (IMIM-Hospital del Mar), Barcelona, Spain.
    Andiarena, Ainara
    Faculty of Psychology, University of the Basque Country, UPV/EHU, Donostia/San Sebastian, Spain;Biodonostia Health Research Institute, Group of Environmental Epidemiology and Child Development, Donostia/San Sebastian, Spain.
    Hair cortisol as a biomarker of chronic stress in preadolescents: influence of school context and bullying2022In: Child Neuropsychology, ISSN 0929-7049, E-ISSN 1744-4136, Vol. 29, no 5, p. 742-759Article in journal (Refereed)
    Abstract [en]

    Bullying has been identified as the most common form of aggression and a major source of stress among children and adolescents. The main objective of this study was to analyze the association that school context in general and bullying in particular might have with hair cortisol concentration (HCC), examining the effect of executive function and sex on this association. The study included 659 11-year-old preadolescents from the cohorts of Gipuzkoa and Sabadell of the INMA (INfancia y Medio Ambiente-Children and Environment) project. We gathered information about school-related factors (bullying, school environment, problems with peers and academic performance) and executive function (risky decision-making). Hair samples were collected to measure cortisol concentrations and Structural Equation Modeling was used to examine associations between school-related factors, executive function and HCC. Results showed that being involved as a bully/victim was related to higher HCC and, higher HCC was associated with poorer executive function. This study may contribute to a better understanding of the consequences that chronic exposure to a stressful factors may have on preadolescents' health and developmental outcomes. Besides, our results are relevant for designing programs for prevention and intervention, which could modify individual physiological responses to stress and reduce the effects of stress on the health.

  • 21.
    Backberg, Matilda
    et al.
    RISE Res Inst Sweden, Sweden.
    Vikingsson, Svante
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, SE-58758 Linkoping, Sweden; RTI Int, NC 27709 USA.
    Strandberg, Joakim
    Publ Hlth Agcy Sweden, Sweden.
    Wall, Sara
    Publ Hlth Agcy Sweden, Sweden.
    Åstrand, Anna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences.
    Karlsson, Hanna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Persson, Mattias
    Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, SE-58758 Linkoping, Sweden.
    Kronstrand, Robert
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, SE-58758 Linkoping, Sweden.
    Green, Henrik
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, SE-58758 Linkoping, Sweden.
    Using in vitro receptor activity studies of synthetic cannabinoids to support the risk assessment of new psychoactive substances-A Swedish strategy to protect public health from harm2023In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 348, article id 111691Article in journal (Refereed)
    Abstract [en]

    In the past 15 years, close to 1000 of new psychoactive substances (NPS) have been reported in Europe and globally. At the time of identification, data on safety, toxicity and carcinogenic potential of many NPS are not available or very limited. To work more efficiently, a strategy and collaboration between the Public Health Agency of Sweden (PHAS) and the National Board of Forensic Medicine was established involving in vitro receptor activity assays to demonstrate neurological activity of NPS. This report summarizes the first results on the synthetic cannabinoid receptor agonists (SCRAs), and subsequent actions taken by PHAS. A total of 18 potential SCRAs were selected by PHAS for in vitro pharmacological characterization. 17 compounds could be acquired and investigated for their activity on the human cannabinoid-1 (CB1) receptors expressed together with the AequoScreen system in CHO-K1 cells. Dose-response curves were established using eight different concentrations in triplicates at three occasions with JWH-018 as reference. For the MDMB-4enPINACA, MMB-022, ACHMINACA, ADB-BUTINACA, 5F-CUMYL-PeGACLONE, 5C-AKB48, NM-2201, 5FCUMYL-PINACA, JWH-022, 5Cl-AB-PINACA, MPhP-2201, 5F-AKB57 the half maximal effective concentration values ranged from 2.2 nM (5F-CUMYL-PINACA) to 171 nM (MMB-022). EG-018 and 3,5-AB-CHMFUPPYCA were none-active. The results contributed to 14 of these compounds being scheduled as narcotics in Sweden. In conclusion, many of the emerging SCRAs are potent activators of the CB1 receptor in vitro, although some lack activity or are partial agonists. The new strategy proved useful when data on psychoactive effects of the SCRAs under investigation were not available or limited. (c) 2023 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).

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  • 22.
    Backlund, Nils
    et al.
    Umea Univ, Sweden.
    Brattsand, Göran
    Umea Univ, Sweden.
    Lundstedt, Staffan
    Umea Univ, Sweden.
    Aardal-Eriksson, Elisabeth
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Arts and Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences.
    Bartuseviciene, Inga
    Karolinska Univ Hosp, Sweden.
    Berinder, Katarina
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Hoybye, Charlotte
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Burman, Pia
    Skane Univ Hosp, Sweden.
    Eden Engström, Britt
    Uppsala Univ, Sweden; Uppsala Univ Hosp, Sweden.
    Isaksson, Anders
    Lund Univ, Sweden.
    Blomgren, Anders
    Lund Univ, Sweden.
    Ragnarsson, Oskar
    Univ Gothenburg, Sweden; Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Ruetschi, Ulrika
    Sahlgrens Univ Hosp, Sweden.
    Wahlberg, Jeanette
    Orebro Univ, Sweden; Orebro Univ Hosp, Sweden.
    Olsson, Tommy
    Umea Univ, Sweden.
    Dahlqvist, Per
    Umea Univ, Sweden.
    Salivary cortisol and cortisone in diagnosis of Cushings syndrome - a comparison of six different analytical methods2023In: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 61, no 10, p. 1780-1791Article in journal (Refereed)
    Abstract [en]

    Objectives: Salivary cortisol and cortisone at late night and after dexamethasone suppression test (DST) are increasingly used for screening of Cushings syndrome (CS). We aimed to establish reference intervals for salivary cortisol and cortisone with three liquid chromatography-tandem mass spectrometry (LC-MS/MS) techniques and for salivary cortisol with three immunoassays (IAs), and evaluate their diagnostic accuracy for CS.Methods: Salivary samples at 08:00 h, 23:00 h and 08:00 h after a 1-mg DST were collected from a reference population (n=155) and patients with CS (n=22). Sample aliquots were analyzed by three LC-MS/MS and three IA methods. After establishing reference intervals, the upper reference limit (URL) for each method was used to calculate sensitivity and specificity for CS. Diagnostic accuracy was evaluated by comparing ROC curves.Results: URLs for salivary cortisol at 23:00 h were similar for the LC-MS/MS methods (3.4-3.9 nmol/L), but varied between IAs: Roche (5.8 nmol/L), Salimetrics (4.3 nmol/L), Cisbio (21.6 nmol/L). Corresponding URLs after DST were 0.7-1.0, and 2.4, 4.0 and 5.4 nmol/L, respectively. Salivary cortisone URLs were 13.5-16.6 nmol/L at 23:00 h and 3.0-3.5 nmol/L at 08:00 h after DST. All methods had ROC AUCs =0.96.Conclusions: We present robust reference intervals for salivary cortisol and cortisone at 08:00 h, 23:00 h and 08:00 h after DST for several clinically used methods. The similarities between LC-MS/MS methods allows for direct comparison of absolute values. Diagnostic accuracy for CS was high for all salivary cortisol and cortisone LC-MS/MS methods and salivary cortisol IAs evaluated.

  • 23.
    Baginski, Steven R.
    et al.
    Univ Dundee, Scotland.
    Rautio, Tobias
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Nisbet, Lorna A.
    Univ Dundee, Scotland.
    Lindbom, Karin
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences.
    Wu, Xiongyu
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Dahlén, Johan
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Mckenzie, Craig
    Univ Dundee, Scotland; Chiron AS, Norway.
    Green, Henrik
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Artillerigatan 12, S-58758 Linkoping, Sweden.
    The metabolic profile of the synthetic cannabinoid receptor agonist ADB-HEXINACA using human hepatocytes, LC-QTOF-MS and synthesized reference standards2023In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 47, no 9, p. 826-834Article in journal (Refereed)
    Abstract [en]

    Synthetic cannabinoid receptor agonists (SCRAs) remain a major public health concern, with their use implicated in intoxications and drug-related deaths worldwide. Increasing our systematic understanding of SCRA metabolism supports clinical and forensic toxicology casework, facilitating the timely identification of analytical targets for toxicological screening procedures and confirmatory analysis. This is particularly important as new SCRAs continue to emerge on the illicit drug market. In this work, the metabolism of ADB-HEXINACA (ADB-HINACA, N-[1-amino-3,3-dimethyl-1-oxobutan-2-yl]-1-hexyl-1H-indazole-3-carboxamide), which has increased in prevalence in the United Kingdom and other jurisdictions, was investigated using in vitro techniques. The (S)-enantiomer of ADB-HEXINACA was incubated with pooled human hepatocytes over 3 hours to identify unique and abundant metabolites using liquid chromatography-quadrupole time-of-flight mass spectrometry. In total, 16 metabolites were identified, resulting from mono-hydroxylation, di-hydroxylation, ketone formation (mono-hydroxylation then dehydrogenation), carboxylic acid formation, terminal amide hydrolysis, dihydrodiol formation, glucuronidation and combinations thereof. The majority of metabolism took place on the hexyl tail, forming ketone and mono-hydroxylated products. The major metabolite was the 5-oxo-hexyl product (M9), while the most significant mono-hydroxylation product was the 4-hydroxy-hexyl product (M8), both of which were confirmed by comparison to in-house synthesized reference standards. The 5-hydroxy-hexyl (M6) and 6-hydroxy-hexyl (M7) metabolites were not chromatographically resolved, and the 5-hydroxy-hexyl product was the second largest mono-hydroxylated metabolite. The structures of the terminal amide hydrolysis products without (M16, third largest metabolite) and with the 5-positioned ketone (M13) were also confirmed by comparison to synthesized reference standards, along with the 4-oxo-hexyl metabolite (M11). The 5-oxo-hexyl and 4-hydroxy-hexyl metabolites are suggested as biomarkers for ADB-HEXINACA consumption.

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  • 24.
    Bahlmann, Hans
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, ANOPIVA US.
    Werner-Möller, Per
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, ANOPIVA US.
    Clinical Use of Lactate Measurements: Comment2021In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 135, no 4, p. 766-766Article in journal (Other academic)
  • 25.
    Baldimtsi, Evangelia
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine and Geriatrics.
    Whiss, Per A
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology.
    Wahlberg, Jeanette
    Department of Medicine, Örebro University Hospital, Örebro, Sweden; Faculty of Medical Sciences, Örebro University, Örebro, Sweden.
    Systemic biomarkers of microvascular alterations in type 1 diabetes associated neuropathy and nephropathy - A prospective long-term follow-up study2023In: Journal of diabetes and its complications, ISSN 1056-8727, E-ISSN 1873-460X, Vol. 37, no 12, article id 108635Article in journal (Refereed)
    Abstract [en]

    Introduction

    This study aimed to investigate circulating biomarkers associated with the risk of developing diabetic peripheral neuropathy (DPN) and nephropathy in type 1 diabetes (T1D).

    Materials and methods

    Patients with childhood-onset T1D (n = 49, age 38.3 ± 3.8 yrs.) followed prospectively were evaluated after 30 years of diabetes duration. DPN was defined as an abnormality in nerve conduction tests. Matrix metalloproteinase-9 (MMP-9) and its tissue inhibitor TIMP-1, neutrophil gelatinase-associated lipocalin-2 (NGAL), soluble P-selectin (sP-selectin), estimated GFR (eGFR), micro/macroalbuminuria and routine biochemistry were assessed. For comparison, control subjects were included (n = 30, age 37.9 ± 5.5 yrs.).

    Results

    In all, twenty-five patients (51 %) were diagnosed with DPN, and nine patients (18 %) had nephropathy (five microalbuminuria and four macroalbuminuria). Patients with DPN had higher levels of TIMP-1 (p = 0.036) and sP-selectin (p = 0.005) than controls. Patients with DPN also displayed higher levels of TIMP-1 compared to patients without DPN (p = 0.035). Patients with macroalbuminuria had kidney disease stage 3 with lower eGFR, higher levels of TIMP-1 (p = 0.038), and NGAL (p = 0.002). In all patients, we found only weak negative correlations between eGFR and TIMP-1 (rho = −0.304, p = 0.040) and NGAL (rho = −0.277, p = 0.062, ns), respectively. MMP-9 was higher in patients with microalbuminuria (p = 0.021) compared with normoalbuminuric patients.

    Conclusions

    Our findings indicate that TIMP-1 and MMP-9, as well as sP-selectin and NGAL, are involved in microvascular complications in T1D. Monitoring and targeting these biomarkers may be a potential strategy for treating diabetic nephropathy and neuropathy.

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  • 26.
    Balla, Hajnal Zsuzsanna
    et al.
    Orebro Univ, Sweden.
    Cao, Yang
    Orebro Univ, Sweden; Karolinska Inst, Sweden.
    Ström, Jakob O.
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Orebro Univ, Sweden.
    Effect of Beta-Blockers on Stroke Outcome: A Meta-Analysis2021In: Clinical Epidemiology, ISSN 1179-1349, E-ISSN 1179-1349, Vol. 13, p. 225-236Article, review/survey (Refereed)
    Abstract [en]

    Introduction: Cardiovascular events and infections are common in the acute phase after stroke. It has been suggested that these complications may be associated with excessive sympathetic activation due to the stroke, and that beta-adrenergic antagonists (beta-blockers) therefore may be beneficial. Aim: The aim of the current meta-analysis was to investigate the association between beta-blocker treatment in acute stroke and the three outcomes: mortality, functional outcome and post-stroke infections. Methods: A literature search was performed using the keywords stroke, cerebrovascular disorders, adrenergic beta-antagonists, treatment outcome and mortality. Randomized clinical trials and observational studies were eligible for data extraction. Heterogeneity was investigated using I-2 statistics. Random effect model was used when heterogeneity presented among studies; otherwise, a fixed-effect model was used. Publication bias was assessed using Eggers test and by visually inspecting funnel plots. Results: A total of 20 studies were eligible for at least one of the three outcomes. Two of the included studies were randomized controlled trials and 18 were observational studies. Quality assessments indicated that the risk of bias was moderate. The meta-analysis found no significant association between treatment with beta-blockers and any of the three outcomes. The studies analyzed for the outcomes mortality and infection were heterogeneous, while studies analyzed for functional outcome were homogeneous. The articles analyzed for mortality showed signs of publication bias. Conclusion: The lack of significant effects in the current meta-analysis, comprising more than 100,000 patients, does not support the proposed beneficial effects of beta-blockers in the acute phase of stroke.

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  • 27.
    Bartha, Erzsebet
    et al.
    Karolinska Univ Hosp, Sweden.
    Ahlstrand, Rebecca
    Orebro Univ, Sweden.
    Bell, Max
    Karolinska Univ Hosp, Sweden.
    Björne, Håkan
    Karolinska Univ Hosp, Sweden.
    Brattström, Olof
    Karolinska Univ Hosp, Sweden.
    Helleberg, Johan
    Karolinska Univ Hosp, Sweden.
    Nilsson, Lena
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, ANOPIVA US.
    Semenas, Egidijus
    Uppsala Univ Hosp, Sweden.
    Kalman, Sigridur
    Karolinska Univ Hosp, Sweden.
    ASA classification and surgical severity grading used to identify a high-risk population, a multicenter prospective cohort study in Swedish tertiary hospitals2021In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 65, no 9, p. 1168-1177Article in journal (Refereed)
    Abstract [en]

    Background Identification of surgical populations at high risk for negative outcomes is needed for clinical and research purposes. We hypothesized that combining two classification systems, ASA (American Society of Anesthesiology physical status) and surgical severity, we could identify a high-risk population before surgery. We aimed to describe postoperative outcomes in a population selected by these two classifications system. Methods Data were collected in a Swedish multicentre, time-interrupted prospective, consecutive cohort study. Eligibility criteria were age &gt;= 18 years, ASA &gt;= 3, elective or emergent, major to Xmajor/complex (Specialist Procedure Codes used in United Kingdom), gastrointestinal, urogenital or orthopaedic procedures. Postoperative morbidity was identified by the Postoperative Morbidity Survey on postoperative days 3 +/- 1, 7 +/- 1, 10 + 5 and graded for severity by the Clavien-Dindo system. Mortality was assessed at 30, 180 and 360 days. Results Postoperative morbidity was 78/48/47 per cent on postoperative days 3/7/10. Majority of morbidities (67.5 per cent) were graded as &gt;1 by Clavien-Dindo. Any type of postoperative morbidity graded &gt;1 was associated with increased risk for death up to one year. The mortality was 5.7 per cent (61/1063) at 30 days, 13.3 per cent (142/1063) at 6 months and 19.1 per cent (160/1063) at 12 months. Conclusion Severity classification as major to Xmajor/complex and ASA &gt;= 3 could be used to identify a high-risk surgical population concerning postoperative morbidity and mortality before surgery. Combining the two systems future electronic data extraction is possible of a high-risk population in tertiary hospitals.

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  • 28.
    Befekadu, Rahel
    et al.
    Orebro Univ Hosp, Sweden; Orebro Univ, Sweden.
    Grenegård, Magnus
    Orebro Univ, Sweden.
    Larsson, Anders
    Uppsala Univ, Sweden.
    Christensen, Kjeld
    Karlstad Cent Hosp, Sweden.
    Ramström, Sofia
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Orebro Univ, Sweden.
    Dynamic Changes in Pentraxin-3 and Neprilysin in ST Segment Elevation Myocardial Infarction2022In: Biomedicines, E-ISSN 2227-9059, Vol. 10, no 2, article id 275Article in journal (Refereed)
    Abstract [en]

    Pentraxin-3 (PTX3) and neprilysin have been associated with increased morbidity and mortality in chronic inflammatory disease and heart failure, but these biomarkers have been studied less in patients with ST segment elevation myocardial infarction (STEMI). We investigated the dynamic changes in these biomarkers, as well as the well-known C-reactive protein (CRP), in STEMI patients. PTX3, neprilysin and CRP were measured in samples from 165 STEMI patients, collected at the acute stage, 1-3 days after and 3 months after percutaneous coronary intervention (PCI), and from 40 healthy donors. Patient survival was followed for approximately 8 years after the PCI. As compared with samples from healthy donors, plasma levels of CRP and PTX3 were significantly increased in the acute samples and 1-3 days after PCI, but not at 3 months. CRP levels peaked at 1-3 days, while PTX3 was similarly high in both acute and 1-3 days samples. For neprilysin, no significant differences were observed at the group level. We found no significant differences when comparing patients with patent versus occluded culprit vessels or between patients having a thrombus aspiration or not. However, we found a significant reduction in survival for individuals with PTX3 above the median, both for samples collected at the acute stage and 1-3 days after PCI (p = 0.0001 and p = 0.0008, respectively). For CRP, no significant differences were observed using this approach, but patients above the reference range for healthy donors in the acute samples showed significantly lower survival (p = 0.0476). Conclusions: Survival analysis suggests that PTX3 might be a promising marker to predict mortality in this patient population.

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  • 29.
    Befekadu, Rahel
    et al.
    Orebro Univ Hosp, Sweden; Orebro Univ, Sweden.
    Grenegård, Magnus
    Orebro Univ, Sweden.
    Larsson, Anders
    Uppsala Univ, Sweden.
    Christensen, Kjeld
    Karlstad Cent Hosp, Sweden; Orebro Univ Hosp, Sweden.
    Ramström, Sofia
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Orebro Univ, Sweden.
    Levels of soluble tumor necrosis factor receptor 1 and 2 are associated with survival after ST segment elevation myocardial infarction2022In: Scientific Reports, E-ISSN 2045-2322, Vol. 12, no 1, article id 14762Article in journal (Refereed)
    Abstract [en]

    The soluble tumor necrosis factor receptors (sTNFR1 and sTNFR2) are suggested to play dual roles on physiological and pathophysiological actions of TNF-alpha. The aim of this study was to investigate the dynamic changes of these biomarkers in patients with ST-segment elevation myocardial infarction (STEMI). Blood was collected from 165 STEMI patients at admission, 1-3 days and 3 months after percutaneous coronary intervention (PCI) and from 40 healthy blood donors. sTNFR1 and sTNFR2 were measured with ELISA. The plasma levels of both sTNFR1 and sTNFR2 were significantly higher than in healthy donors at all three time points. We found no significant differences in sTNFR1 or sTNFR2 when comparing patients with patent versus occluded culprit vessels, or between patients having a thrombus aspiration or not. Survival analysis was performed comparing patients with levels of biomarkers above and below the median values at that time point. We found significant differences in survival for sTNFR2 in acute samples (p = 0.0151) and for both sTNFR1 and sTNFR2 in samples 1-3 days after PCI (p = 0.0054 and p = 0.0003, respectively). Survival analyses suggest that sTNFR1 or sTNFR2 could be promising markers to predict mortality in STEMI patients after PCI.

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  • 30.
    Bengtsson, Finn
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology.
    Neuropsykofarmakologi2021In: Psykisk ohälsa: ett biopsykosocialt perspektiv / [ed] Ali Sarkohi, Gerhard Andersson, Lund: Studentlitteratur AB, 2021, Vol. Sidorna 381-430, p. 381-430Chapter in book (Other academic)
    Abstract [sv]

    Människans hjärna, centrala nervsystem (CNS), består av ett antal mycket olika strukturer, men naturligtvis med vissa gemensamma drag på till exempel cellulär nivå, strukturer som på grund av både olikheter men också vissa likheter trots allt inte sällan har mycket specialiserade CNS-funktioner. I praktisk biologi och sjukvård skiljer man därför gärna mellan neurologi, psykiatri (inklusive psykologi) och neuropsykiatriska tillstånd. Typiskt för neuropsykiatrisk sjukdom är kroniskt kognitiva störningar på vävnadsstrukturell grund, det vill säga olika typer av demensutveckling som kan hanteras både inom neurologin och psykiatrin men vanligen inom geriatriken.

  • 31.
    Bergemalm, Daniel
    et al.
    Department of Medicine, Faculty of Medicine and Health, Örebro University, Örebro.
    Ramström, Sofia
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Örebro University, Örebro.
    Kardeby, Caroline
    Cardiovascular Research Centre, School of Medical Sciences, Örebro University, Örebro.
    Hultenby, Kjell
    Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm.
    Eremo, Anna Göthlin
    Department of Clinical Research Laboratory, Faculty of Medicine and Health, Örebro University, Örebro.
    Sihlbom, Carina
    Proteomics Core Facility, University of Gothenburg, Gothenburg.
    Bergström, Jörgen
    Proteomics Core Facility, University of Gothenburg, Gothenburg.
    Palmblad, Jan
    Departments of Medicine and Hematology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm.
    Åström, Maria
    Department of Medicine, Faculty of Medicine and Health, Örebro University, Örebro.
    Platelet proteome and function in X-linked thrombocytopenia with thalassemia and in silico comparisons with gray platelet syndrome2021In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 106, no 11, p. 2947-2959Article in journal (Refereed)
    Abstract [en]

    In X-linked thrombocytopenia with thalassemia (XLTT; OMIM 314050), caused by the mutation p.R216Q in exon 4 of the GATA1 gene, male hemizygous patients display macrothrombocytopenia, bleeding diathesis and a ß-thalassemia trait. Herein, we describe findings in two unrelated Swedish XLTT families with a bleeding tendency exceeding what is expected from the thrombocytopenia. Blood tests revealed low P-PAI-1 and P-factor 5, and elevated S-thrombopoietin levels. Transmission electron microscopy showed diminished numbers of platelet a- and dense granules. The proteomes of isolated blood platelets from 5 male XLTT patients, compared to 5 gender- and age matched controls, were explored. Quantitative mass spectrometry showed alterations of 83 proteins (fold change =±1.2, q&lt; .05). Of 46 downregulated proteins, 39 were previously reported to be associated with platelet granules. Reduced protein levels of PTGS1 and SLC35D3 were validated in megakaryocytes of XLTT bone marrow biopsies by immunohistochemistry. Platelet function testing by flow cytometry revealed low dense- and a-granule release and fibrinogen binding in response to ligation of receptors for ADP, the thrombin receptor PAR4 and the collagen receptor GPVI. Significant reductions of a number of a-granule proteins overlapped with a previous platelet proteomics investigation in the inherited macrothrombocytopenia gray platelet syndrome (GPS). In contrast, Ca2+ transporter proteins that facilitate dense granule release were downregulated in XLTT but upregulated in GPS. Ingenuity Pathway Analysis showed altered Coagulation System and Protein Ubiquitination pathways in the XLTT platelets. Collectively, the results revealed protein and functional alterations affecting platelet a- and dense granules in XLTT, probably contributing to bleeding.

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  • 32.
    Berggren, Daniel Moreno
    et al.
    Uppsala Univ, Sweden.
    Garelius, Hege
    Sahlgrens Univ Hosp, Sweden.
    Willner Hjelm, Petter
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Nilsson, Lars
    Skane Univ Hosp, Sweden.
    Rasmussen, Bengt
    Orebro Univ, Sweden.
    Weibull, Caroline E.
    Karolinska Inst, Sweden.
    Lambe, Mats
    Karolinska Inst, Sweden; Reg Canc Ctr Cent Sweden, Sweden.
    Lehmann, Soren
    Uppsala Univ, Sweden; Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Hellstrom-Lindberg, Eva
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Jadersten, Martin
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Ejerblad, Elisabeth
    Uppsala Univ, Sweden.
    Therapy-related MDS dissected based on primary disease and treatment-a nationwide perspective2023In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 37, p. 1103-1112Article in journal (Refereed)
    Abstract [en]

    In this population-based study, we aimed to characterize and compare subgroups of therapy-related Myelodysplastic syndromes (t-MDS) and define the implications of type of previous treatment and primary disease. We combined data from MDS patients, diagnosed between 2009 and 2017 (n = 2705), in the nationwide Swedish MDS register, with several health registers. Furthermore, using matched population controls, we investigated the prevalence of antecedent malignancies in MDS patients in comparison with the general population. This first ever nationwide study on t-MDS confirms a shorter median survival for t-MDS compared to de novo MDS (15.8 months vs 31.1 months, p &lt; 0.001). T-MDS patients previously treated with radiation only had disease characteristics with a striking resemblance to de novo-MDS, in sharp contrast to patients treated with chemotherapy who had a significantly higher risk profile. IPSS-R and the WHO classification differentiated t-MDS into different risk groups. As compared with controls, MDS patients had a six-fold increased prevalence of a previous hematological malignancy but only a 34% increased prevalence of a previous solid tumor. T-MDS patients with a previous hematological malignancy had a dismal prognosis, due both to mortality related to their primary disease and to high-risk MDS.

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  • 33.
    Bergstrom, Anna
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Norrköping.
    Lipcsey, Miklos
    Uppsala Univ, Sweden; Uppsala Univ, Sweden.
    Larsson, Anders
    Uppsala Univ, Sweden.
    Yang, Bei
    Uppsala Univ, Sweden.
    Engblom, David
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Chew, Michelle
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, ANOPIVA US.
    Elander, Louise
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Norrköping. Nykopings Lasarett, Sweden.
    Acetaminophen Attenuates Pulmonary Vascular Resistance and Pulmonary Arterial Pressure and Inhibits Cardiovascular Collapse in a Porcine Model of Endotoxemia2023In: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 59, no 3, p. 442-448Article in journal (Refereed)
    Abstract [en]

    Acetaminophen (paracetamol) is often used in critically ill patients with fever and pain; however, little is known about the effects of acetaminophen on cardiovascular function during systemic inflammation. Here, we investigated the effect of acetaminophen on changes in the systemic and pulmonary circulation induced by endotoxin (0.5 mu g/kg per hour) in anesthetized pigs. Endotoxin infusion led to a rapid increase in pulmonary artery pressure and pulmonary vascular resistance index. Acetaminophen delayed and attenuated this increase. Furthermore, acetaminophen reduced tachycardia and decreased stroke volume, accompanied by systemic inflammation, without affecting inflammatory parameters such as white blood cell count and TNF-alpha in blood. As a proof of concept, we injected a high dose of endotoxin (100 mu g), which induced rapid cardiovascular collapse in pigs. Pigs treated with acetaminophen survived with no obvious hemodynamic instability during the 50-min observation period. In conclusion, acetaminophen attenuates the effects of endotoxin on pulmonary circulation in anesthetized pigs. This may play a role in severe systemic inflammation.

  • 34.
    Bian, Li
    et al.
    Sahlgrenska universitetssjukhuset, Göteborg, Sverige.
    Baghaei, Fariba
    Sahlgrenska universitetssjukhuset, Göteborg, Sverige.
    Antovic, Jovan
    Karolinska universitetssjukhuset, Stockholm, Sverige.
    Fagerberg Blixter, Inger
    Sahlgrenska universitetssjukhuset, Göteborg, Sverige.
    Hillarp, Andreas
    Klinikk for laboratorie­medisin, Sekjson for hemostase og trombose, Oslo Universitetssykehus, Norge.
    Strandberg, Karin
    Laboratorie­medicin, Medicinsk service, Region Skåne, Sverige.
    Willman, David
    Norrlands universitetssjukhus, Umeå, Sverige.
    Lindahl, Tomas
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology.
    Rutinmässig screening med APTT är inte indicerad före operation: [Routine screening with APTT is not indicated before surgery2022In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 119, article id 21240Article, review/survey (Refereed)
    Abstract [en]

    Activated partial thromboplastin time (APTT) is widely practiced in preoperative screening. The value of using this test to predict the risk of perioperative bleeding is not well documented in Sweden. In this article, a literature review is performed to determine whether unselected APTT testing can predict abnormal perioperative bleeding. The current literature does not support coagulation screening with APTT in routine perioperative bleeding assessment, as preoperative screening with APTT has a low sensitivity for detection of clinically significant bleeding disorder. While a comprehensive bleeding history is crucial, the APTT test should only be performed on patients with a history of increased bleeding tendency. The conclusion of this literature review is that patients with a negative bleeding history do not require routine screening with APTT prior to surgery, which, if implemented, would lead to a more cost-effective perioperative routine.

  • 35.
    Björn, Niclas
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences.
    Jakobsen, Ingrid
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Orebro Univ Hosp, Sweden.
    Udagawa, Chihiro
    Natl Canc Ctr, Japan.
    Brandén, Eva
    Gavle Cent Hosp, Sweden; Uppsala Univ, Sweden.
    Koyi, Hirsh
    Gavle Cent Hosp, Sweden; Uppsala Univ, Sweden.
    Lewensohn, Rolf
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    De Petris, Luigi
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Zembutsu, Hitoshi
    Natl Canc Ctr, Japan.
    Green, Henrik
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linkoping, Sweden.
    The association of four genetic variants with myelosuppression in gemcitabine-treated Japanese is not evident in gemcitabine/carboplatin-treated Swedes2022In: Basic & Clinical Pharmacology & Toxicology, ISSN 1742-7835, E-ISSN 1742-7843, Vol. 130, no 4, p. 513-521Article in journal (Refereed)
    Abstract [en]

    Gemcitabine/carboplatin-induced myelosuppressive adverse drug reactions (ADRs) are clinical problems leading to patient suffering and dose alterations. There is a need for personalised medicine to improve treatment effects and patients well-being. We tested four genetic variants, rs11141915, rs1901440, rs12046844 and rs11719165, previously suggested as potential biomarkers for gemcitabine-induced leukopenia/neutropenia in Japanese patients, in 213 Swedish gemcitabine/carboplatin-treated non-small cell lung cancer (NSCLC) patients. DNA was genotyped using TaqMan probes and real-time PCR. The relationships between the risk alleles and low toxicity (non-ADR: Common Terminology Criteria for Adverse Events [CTCAE] grades 0) or high toxicity (ADR: CTCAE grades 3-4) of platelets, leukocytes and neutrophils were evaluated using Fishers exact test. The risk alleles did not correlate with myelosuppression, and the strongest borderline significance (not withstanding adjustment for multiple testing) was for rs1901440 (neutropenia, p = 0.043) and rs11719165 (leukopenia, p = 0.049) where the risk alleles trended towards lower toxicity, contrasting with previous study findings. Risk alleles and higher risk scores were more common among our patients. We conclude that the genetic variants do not apply to Swedish patients treated with gemcitabine/carboplatin. However, they can still be important in other populations and cohorts, especially in a gemcitabine monotherapy setting, where the causal genetic variation might influence myelosuppressive ADRs.

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  • 36.
    Björnqvist, Anton
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Regionledningskontoret, Center for Disaster Medicine and Traumatology.
    Friberg, Marc
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Regionledningskontoret, Center for Disaster Medicine and Traumatology.
    Jonson, Carl-Oscar
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Regionledningskontoret, Center for Disaster Medicine and Traumatology.
    Pettersson, Jenny
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Regionledningskontoret, Center for Disaster Medicine and Traumatology.
    Berggren, Peter
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Regionledningskontoret, Center for Disaster Medicine and Traumatology.
    An Analysis of a Swedish Medical Command and Control System’s Situation Reports from the COVID-19 Pandemic2022In: ISCRAM 2022 Conference Proceedings – 19th International Conference on Information Systems for Crisis Response and Management / [ed] Rob Grace; Hossein Baharmand, 2022, p. 334-348Conference paper (Refereed)
    Abstract [en]

    This paper presents an analysis of situation reports used and created by a crisis management team within the Swedish healthcare sector during the early phase of the COVID-19 pandemic. The analysis was conducted through a deductive content analysis, where categories were identified based on the concepts of common operational pictures, sensemaking, and situation awareness. In the analysis, support for all identified categories was found. Based on the analysis and the concepts, future recommendations regarding what type of information that ought to be included in situation reports were created. These recommendations include, amongst others, the categories of consequences, how it is perceived by the public, objectives, status and implications of information, future scenarios, actions, resources, and work procedures.

  • 37.
    Blixt, Cornelia
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences. 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.
    Johansson, Elin
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. 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.
    Forsner, Maria
    Umea Univ, Sweden; Karolinska Inst, Sweden.
    Angelhoff, Charlotte
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Nursing Sciences and Reproductive 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.
    Compassion fatigue and compassion satisfaction in pediatric and neonatal care nurses during the COVID-19 pandemic in Sweden2023In: Journal of Pediatric Nursing: Nursing Care of Children and Families, ISSN 0882-5963, E-ISSN 1532-8449, Vol. 73, p. e646-e651Article in journal (Refereed)
    Abstract [en]

    Purpose: Quality of care and the mental and physical health of nurses are interlinked. The COVID-19 pandemic has imposed an extremely high burden on health care. This study aimed to: 1) describe professional quality of life of registered nurses (RN) working in the pediatric and neonatal care units during the COVID-19 pandemic in Sweden, 2) compare professional quality of life between RNs with and without a Master's degree in specialist nursing pediatric care (MSc), and 3) compare differences in professional quality of life associated with the nursing experience (years). Design and methods: This study adopted a cross-sectional survey design. The PROQoL (R)-5-questionnaire was administered as a web survey to 160 RNs at four pediatric wards and two neonatal units of two hospitals in Sweden. Results: Seventy-one RNs responded to the survey. Overall, they reported a sufficient professional quality of life. RNs with an MSc suffered significantly lower secondary traumatic stress levels. Experienced RNs reported significantly higher compassion satisfaction and lower occupational burnout. Conclusion: Higher education and longer experience are beneficial for nurses' professional quality of life when working in pediatric care units. Practical implications: Results from this study highlights the importance of offering RN education in pediatric care at master level and supporting novice nurses, to prevent negative professional well-being outcomes in pediatric care, because the health of nurses is of utterly importance when crisis such as a pandemic hits the world. The findings also suggest that the conditions for professional quality of life could improve through activities such as self-care, time for reflection, better working hours, competence-adjusted salary, and educational opportunities. (c) 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).

  • 38.
    Blixt Johansson, Patrik
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, ANOPIVA US. Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology.
    Chew, Michelle
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, ANOPIVA US.
    Åhman, Rasmus
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, ANOPIVA US.
    de Geer, Lina
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, ANOPIVA US.
    Blomqwist, Lill
    Skane Univ Hosp, Sweden.
    Åström, Meriam
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart Center, Department of Clinical Physiology in Linköping.
    Engvall, Jan
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Andersson, Henrik
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, ANOPIVA US.
    Left ventricular longitudinal wall fractional shortening accurately predicts longitudinal strain in critically ill patients with septic shock2021In: Annals of Intensive Care, ISSN 2110-5820, E-ISSN 2110-5820, Vol. 11, no 1, article id 52Article in journal (Refereed)
    Abstract [en]

    Background Left ventricular longitudinal strain (LVLS) may be a sensitive indicator of left ventricular (LV) systolic function in patients with sepsis, but is dependent on high image quality and analysis software. Mitral annular plane systolic excursion (MAPSE) and the novel left ventricular longitudinal wall fractional shortening (LV-LWFS) are bedside echocardiographic indicators of LV systolic function that are less dependent on image quality. Both are sparsely investigated in the critically ill population, and may potentially be used as surrogates for LVLS. We assessed if LVLS may be predicted by LV-LWFS and MAPSE in patients with septic shock. We also assessed the repeatability and inter-rater agreement of LVLS, LV-LWFS and MAPSE measurements. Results 122 TTE studies from 3 echocardiographic data repositories of patients admitted to ICU with septic shock were retrospectively assessed, of which 73 were suitable for LVLS analysis using speckle tracking. The correlations between LVLS vs. LV-LWFS and LVLS vs. MAPSE were 0.89 (p &lt; 0.001) and 0.81 (p &lt; 0.001) with mean squared errors of 5.8% and 9.1%, respectively. Using the generated regression equation, LV-LWFS predicted LVLS with a high degree of accuracy and precision, with bias and limits of agreement of -0.044 +/- 4.7% and mean squared prediction error of 5.8%. Interobserver repeatability was good, with high intraclass correlation coefficients (0.96-0.97), small bias and tight limits of agreement (&lt;= 4.1% for all analyses) between observers for all measurements. Conclusions LV-LWFS may be used to estimate LVLS in patients with septic shock. MAPSE also performed well, but was slightly inferior compared to LV-LWFS in estimating LVLS. Feasibility of MAPSE and LV-LWFS was excellent, as was interobserver repeatability.

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  • 39.
    Blomstrand, Hakon
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology.
    Olsson, Hans
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology.
    Green, Henrik
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Dept Forens Genet & Forens Toxicol, Natl Board Forens Med, Linkoping, Sweden.
    Björnsson, Bergthor
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Elander, Nils
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Clatterbridge Canc Ctr NHS FT, England.
    Impact of resection margins and para-aortic lymph node metastases on recurrence patterns and prognosis in resectable pancreatic cancer - a long-term population-based cohort study2023In: HPB, ISSN 1365-182X, E-ISSN 1477-2574, Vol. 25, no 12, p. 1531-1544Article in journal (Refereed)
    Abstract [en]

    Background: Pancreatic cancer remains a leading cause of cancer-related death. To individualise management and improve survival, more accurate prognostic models are needed.Methods: All patients resected for pancreatic ductal adenocarcinoma in a tertiary Swedish centre during 2009-2019 were thoroughly analysed with regards to pathological and clinical parameters including tumour grade, resection margin status, para-aortic lymph node engagement (node station 16), and systemic treatment.Results: The study cohort included 275 patients. Overall median survival was 21.2 months (95% CI 17.5-24.8). Year of resection, margin status (R1 subdivided into R1(1mm)/R1(ink)), perineural invasion, differentiation grade, TNM stage, and adjuvant therapy were independent factors with significant impact on survival. Margin status also significantly affected recurrence-free survival and relapse patterns, with local and peritoneal relapses being associated with R1-status (p &lt; 0.001 and p = 0.007). Presence of paraaortic lymph node metastases was associated with shorter recurrence-free survival as compared to N1 status only.Conclusion: Survival in resected pancreatic cancer is improving over time. Resection margin status is a key factor affecting recurrence patterns and prognosis. Given the poor recurrence-free survival in node station 16 metastasised patients, the rational for resection remains in doubt, and improved treatment strategies for this patient group is necessary.

  • 40.
    Boknäs, Niklas
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Laine, Cia
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Department of Health, Medicine and Caring Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine and Geriatrics.
    Hillarp, Andreas
    Oslo Univ Hosp, Norway.
    Macwan, Ankit
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences.
    Gustafsson, Kerstin
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Lindahl, Tomas
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Holmström, Margareta
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine and Geriatrics.
    Associations between hemostatic markers and mortality in COVID-19-Compounding effects of D-dimer, antithrombin and PAP complex2022In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 213, p. 97-104Article in journal (Refereed)
    Abstract [en]

    In this single-center cohort study, we applied a panel of laboratory markers to characterize hemostatic function in 217 consecutive patients that underwent testing for COVID-19 as they were admitted to Linkoping ¨ University Hospital between April and June 2020. In the 96 patients that tested positive for SARS-CoV-2 (COVID-19+), the cumulative incidences of death and venous thromboembolism were 24.0% and 19.8% as compared to 12.4% (p = 0.031) and 11.6% (p = 0.13) in the 121 patients that tested negative (COVID-19− ). In COVID-19+ patients, we found pronounced increases in plasma levels of von Willebrand factor (vWF) and fibrinogen. Excess mortality was observed in COVID-19+ patients with the following aberrations in hemostatic markers: high D-dimer, low antithrombin or low plasmin-antiplasmin complex (PAP) formation, with Odds Ratios (OR) for death of 4.7 (95% confidence interval (CI95) 1.7–12.9; p = 0.003) for D-dimer >0.5 mg/L, 5.9 (CI95 1.8–19.7; p = 0.004) for antithrombin (AT) ˂0.85 kIU/l and 4.9 (CI95 1.3–18.3; p = 0.019) for PAP < 1000 μg/L. Compounding increases in mortality was observed in COVID-19+ patients with combined defects in markers of fibrinolysis and coagulation, with ORs for death of 15.7 (CI95 4.3–57; p < 0.001) for patients with PAP <1000 μg/L and D-dimer >0.5 mg/L and 15.5 (CI95 2.8–87, p = 0.002) for patients with PAP <1000 μg/L and AT ˂0.85 kIU/L. We observed an elevated fraction of incompletely degraded D-dimer fragments in COVID-19+ patients with low PAP, indicating impaired fibrinolytic breakdown of cross-linked fibrin. 

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  • 41.
    Borendal Wodlin, Ninnie
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, 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.
    Oliv, Emelie
    Department of Obstetrics and Gynecology, Värnamo Hospital, Värnamo, Sweden.
    Kjölhede, Preben
    Linköping University, Department of Biomedical and Clinical Sciences, 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.
    Nilsson, Lena
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, ANOPIVA US. Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology.
    Influence of Regional Analgesia on Self-Reported Quality of Sleep After Gynecological Abdominal Surgery: A Secondary Analysis of a Randomized Trial2024In: Journal of Obstetrics and Gynaecology Canada, ISSN 1701-2163, Vol. 46, no 1, article id 102228Article in journal (Refereed)
    Abstract [en]

    Objectives: To determine whether intrathecal morphine (ITM) analgesia in abdominal surgery for presumed gynecological malignancy was associated with better self-reported sleep quality postoperatively compared with epidural analgesia (EDA), and to evaluate risk factors for bad sleep quality. Methods: A secondary analysis of a randomized open controlled trial, comparing ITM and EDA as postoperative analgesia in 80 women undergoing laparotomy under general anaesthesia in an enhanced recovery after surgery framework. A total of 38 women allocated to ITM and 39 to EDA completed the study. The Swedish Postoperative Symptoms Questionnaire assessed symptoms and sleep quality during the first postoperative week. Multiple logistic regression models evaluated risk factors. The results are presented as adjusted odds ratios with 95% CIs. Results: The sleep quality night-by-night did not differ significantly between the women who had ITM or EDA. Risk factors for bad sleep quality for night 1 were age (0.91; 0.84–0.99), operation time (1.02; 1.00–1.03), and opioid consumption (0.96; 0.91–0.99). For night 2, regular use of hypnotics preoperatively (15.81; 1.52–164.27) and opioid consumption (1.07; 1.00–1.14) were independent risk factors for bad sleep. After the second night, no risk factors were disclosed. Conclusions: ITM and EDA did not appear to affect the sleep quality postoperatively differently in women undergoing laparotomy for presumed gynecological malignancy. Risk factors for self-reported bad sleep quality varied during the first 3 days after surgery. Younger age, longer operation time, and preoperative use of hypnotics were associated with bad sleep quality, whereas the effect of opioid consumption on sleep quality varied depending on the time since surgery. These findings merit further studies. © 2023 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada

  • 42.
    Braenden, Astrid
    et al.
    Oslo Univ Hosp, Norway; Oslo Univ Hosp, Norway.
    Lebena, Andrea
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Olsen Faresjö, Åshild
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Society and Health. Linköping University, Faculty of Medicine and Health Sciences.
    Theodorsson, Elvar
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Coldevin, Marit
    Lovisenberg Diaconal Hosp, Norway.
    Stubberud, Jan
    Lovisenberg Diaconal Hosp, Norway; Univ Oslo, Norway.
    Zeiner, Pal
    Oslo Univ Hosp, Norway; Univ Oslo, Norway.
    Melinder, Annika
    Oslo Univ Hosp, Norway; Univ Oslo, Norway.
    Excessive hair cortisol concentration as an indicator of psychological disorders in children2023In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 157, article id 106363Article in journal (Refereed)
    Abstract [en]

    Cortisol in hair is a new biomarker assessing long-term hypothalamic-pituitary-adrenal (HPA) axis activity, which is related to emotion regulation. We compare hair cortisol concentrations (HCC), in clinically referred children with disruptive mood dysregulation disorder (DMDD) (n = 19), children with other types of psychological disorders (n = 48), and healthy subjects (n = 36). We also investigate the association between HCC and irritability, age, and sex. Our results show that children with DMDD or other types of psychological disorders have higher HCC than healthy subjects, p &lt; .001, ?(2)(p) = .39. No difference between children with DMDD and those with other types of psychological disorders was found, p = .91, nor an association between HCC and irritability in the clinical sample, p = .32. We found a significant negative correlation between HCC and age in those with DMDD, r = -0.54, p &lt; .05, but not in the normative sample, r = -0.20, p = .25. No differences in HCC between girls and boys were found in the normative sample, p = .49. Children in need of psychological treatment, including those with DMDD, seem to have dysregulated HPA-axis activity over time. Excessive accumulated cortisol concentrations in hair could be an indicator of a psychological disorder in children.

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  • 43.
    Brandon, Andrew M.
    et al.
    Univ Dundee, Scotland; Newcastle Univ, England.
    Baginski, Steven R.
    Univ Dundee, Scotland.
    Peet, Caroline
    Univ Dundee, Scotland; Debiopharm, Switzerland.
    Dugard, Pat
    Univ Dundee, Scotland.
    Green, Henrik
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linkoping, Sweden.
    Sutcliffe, Oliver B.
    Manchester Metropolitan Univ, England.
    Daeid, Niamh Nic
    Univ Dundee, Scotland.
    Nisbet, Lorna A.
    Univ Dundee, Scotland; Newcastle Univ, England.
    Read, Kevin D.
    Univ Dundee, Scotland.
    McKenzie, Craig
    Univ Dundee, Scotland; Chiron AS, Norway.
    Log D7.4 and plasma protein binding of synthetic cannabinoid receptor agonists and a comparison of experimental and predicted lipophilicity2023In: Drug Testing and Analysis, ISSN 1942-7603, E-ISSN 1942-7611Article in journal (Refereed)
    Abstract [en]

    The emergence of new synthetic cannabinoid receptor agonists (SCRAs) onto the illicit drugs market continues to cause harm, and the overall availability of physicochemical and pharmacokinetic data for new psychoactive substances is lacking. The lipophilicity of 23 SCRAs and the plasma protein binding (PPB) of 11 SCRAs was determined. Lipophilicity was determined using a validated chromatographic hydrophobicity index (CHI) log D method; tested SCRAs showed moderate to high lipophilicity, with experimental log D-7.4 ranging from 2.48 (AB-FUBINACA) to 4.95 (4F-ABUTINACA). These results were also compared to in silico predictions generated using seven commercially available software packages and online tools (Canvas; ChemDraw; Gastroplus; MoKa; PreADMET; SwissADME; and XlogP). Licenced, dedicated software packages provided more accurate lipophilicity predictions than those which were free or had prediction as a secondary function; however, the latter still provided competitive estimates in most cases. PPB of tested SCRAs, as determined by equilibrium dialysis, was in the upper range of the lipophilicity scale, ranging from 90.8% (ADB-BUTINACA) to 99.9% (BZO-HEXOXIZID). The high PPB of these drugs may contribute to reduced rate of clearance and extended durations of pharmacological effects compared to lesser-bound SCRAs. The presented data improve understanding of the behaviour of these drugs in the body. Ultimately, similar data and predictions may be used in the prediction of the structure and properties of drugs yet to emerge on the illicit market.

  • 44.
    Bransky, Avishay
    et al.
    PixCell Med Technol Ltd, Israel.
    Larsson, Anders
    Uppsala Univ, Sweden.
    Aardal, Elisabeth
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Ben-Yosef, Yaara
    PixCell Med Technol Ltd, Israel.
    Christenson, Robert H.
    Univ Maryland, MD 21201 USA.
    A Novel Approach to Hematology Testing at the Point of Care2021In: JOURNAL OF APPLIED LABORATORY MEDICINE, ISSN 2576-9456, Vol. 6, no 2, p. 532-542Article in journal (Refereed)
    Abstract [en]

    Background: The need for rapid point-of-care (POC) diagnostics is now becoming more evident due to the increasing need for timely results and improvement in healthcare service. With the recent COVID-19 pandemic outbreak, POC has become critical in managing the spread of disease. Applicable diagnostics should be readily deployable, easy to use, portable, and accurate so that they fit mobile laboratories, pop-up treatment centers, field hospitals, secluded wards within hospitals, or remote regions, and can be operated by staff with minimal training. Complete blood count (CBC), however, has not been available at the POC in a simple-to-use device until recently. The HemoScreen, which was recently cleared by the FDA for POC use, is a miniature, easy-to-use instrument that uses disposable cartridges and may fill this gap. Content: The HemoScreens analysis method, in contrast to standard laboratory analyzers, is based on machine vision (image-based analysis) and artificial intelligence (AI). We discuss the different methods currently used and compare their results to the vision-based one. The HemoScreen is found to correlate well to laser and impedance-based methods while emphasis is given to mean cell volume (MCV), mean cell hemoglobin (MCH), and platelets (PLT) that demonstrate better correlation when the vision-based method is compared to itself due to the essential differences between the underlying technologies. Summary: The HemoScreen analyzer demonstrates lab equivalent performance, tested at different clinical settings and sample characteristics, and might outperform standard techniques in the presence of certain interferences. This new approach to hematology testing has great potential to improve quality of care in a variety of settings.

  • 45.
    Bruder, Nicolas
    et al.
    Aix Marseille Univ, France.
    Chew, Michelle
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, ANOPIVA US.
    Guidelines on postoperative delirium: Where do we go from here?2024In: European Journal of Anaesthesiology, ISSN 0265-0215, E-ISSN 1365-2346, Vol. 41, no 2, p. 79-80Article in journal (Other academic)
  • 46.
    Bruno, Raphael Romano
    et al.
    Heinrich Heine Univ Duesseldorf, Germany.
    Wernly, Bernhard
    Paracelsus Med Private Univ, Austria; Paracelsus Med Univ, Austria.
    Bagshaw, Sean M.
    Univ Alberta, Canada; Alberta Hlth Serv, Canada.
    van den Boogaard, Mark
    Radboud Univ Nijmegen, Netherlands.
    Darvall, Jai N.
    Royal Melbourne Hosp, Australia.
    de Geer, Lina
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, ANOPIVA US.
    Miguelena, Pablo Ruiz de Gopegui
    Hosp Univ Miguel Servet, Spain.
    Heyland, Daren K.
    Queens Univ, Canada.
    Hewitt, David
    Glasgow Royal Infirm Intens Care Unit, Scotland.
    Hope, Aluko A.
    Oregon Hlth & Sci Univ, OR USA.
    Langlais, Emilie
    Univ Rennes 1, France.
    Le Maguet, Pascale
    CHU Rennes, France; CH Quimper, France.
    Montgomery, Carmel L.
    Univ Alberta, Canada; Alberta Hlth Serv, Canada.
    Papageorgiou, Dimitrios
    Univ West Attica UWA Athens, Greece.
    Seguin, Philippe
    Univ Rennes 1, France.
    Geense, Wytske W.
    Radboud Univ Nijmegen, Netherlands.
    Silva-Obregon, J. Alberto
    Hosp Univ Guadalajara, Spain.
    Wolff, Georg
    Heinrich Heine Univ Duesseldorf, Germany.
    Polzin, Amin
    Heinrich Heine Univ Duesseldorf, Germany.
    Dannenberg, Lisa
    Heinrich Heine Univ Duesseldorf, Germany.
    Kelm, Malte
    Heinrich Heine Univ Duesseldorf, Germany; Univ Hosp Dusseldorf, Germany.
    Flaatten, Hans
    Univ Bergen, Norway.
    Beil, Michael
    Hebrew Univ Jerusalem, Israel.
    Franz, Marcus
    Friedrich Schiller Univ, Germany.
    Sviri, Sigal
    Hebrew Univ Jerusalem, Israel.
    Leaver, Susannah
    St Georges Univ Hosp NHS Fdn Trust, England.
    Guidet, Bertrand
    UPMC Univ Paris 06, France; Hop St Antoine, France.
    Boumendil, Ariane
    UPMC Univ Paris 06, France; Hop St Antoine, France.
    Jung, Christian
    Heinrich Heine Univ Duesseldorf, Germany.
    The Clinical Frailty Scale for mortality prediction of old acutely admitted intensive care patients: a meta-analysis of individual patient-level data2023In: Annals of Intensive Care, ISSN 2110-5820, E-ISSN 2110-5820, Vol. 13, no 1, article id 37Article in journal (Refereed)
    Abstract [en]

    Background This large-scale analysis pools individual data about the Clinical Frailty Scale (CFS) to predict outcome in the intensive care unit (ICU). Methods A systematic search identified all clinical trials that used the CFS in the ICU (PubMed searched until 24th June 2020). All patients who were electively admitted were excluded. The primary outcome was ICU mortality. Regression models were estimated on the complete data set, and for missing data, multiple imputations were utilised. Cox models were adjusted for age, sex, and illness acuity score (SOFA, SAPS II or APACHE II). Results 12 studies from 30 countries with anonymised individualised patient data were included (n = 23,989 patients). In the univariate analysis for all patients, being frail (CFS &gt;= 5) was associated with an increased risk of ICU mortality, but not after adjustment. In older patients (&gt;= 65 years) there was an independent association with ICU mortality both in the complete case analysis (HR 1.34 (95% CI 1.25-1.44), p &lt; 0.0001) and in the multiple imputation analysis (HR 1.35 (95% CI 1.26-1.45), p &lt; 0.0001, adjusted for SOFA). In older patients, being vulnerable (CFS 4) alone did not significantly differ from being frail. After adjustment, a CFS of 4-5, 6, and &gt;= 7 was associated with a significantly worse outcome compared to CFS of 1-3. Conclusions Being frail is associated with a significantly increased risk for ICU mortality in older patients, while being vulnerable alone did not significantly differ. New Frailty categories might reflect its "continuum" better and predict ICU outcome more accurately.

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  • 47.
    Buesker, Soeren
    et al.
    Univ Cologne, Germany; Univ Cologne, Germany.
    Jones, A Wayne
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences.
    Hahn, Robert G.
    Sodertalje Hosp, Sweden; Karolinska Inst, Sweden.
    Taubert, Max
    Univ Cologne, Germany; Univ Cologne, Germany.
    Klotz, Ulrich
    Dr Margarete Fischer Bosch Inst Clin Pharmacol, Germany.
    Schwab, Matthias
    Dr Margarete Fischer Bosch Inst Clin Pharmacol, Germany; Univ Hosp Tubingen, Germany; Univ Hosp Tubingen, Germany.
    Fuhr, Uwe
    Univ Cologne, Germany; Univ Cologne, Germany.
    Population Pharmacokinetics as a Tool to Reevaluate the Complex Disposition of Ethanol in the Fed and Fasted States2023In: Journal of clinical pharmacology, ISSN 0091-2700, E-ISSN 1552-4604, Vol. 63, p. 681-694Article in journal (Refereed)
    Abstract [en]

    The pharmacokinetics (PK) of ethanol are important in pharmacology and therapeutics because of potential drug-alcohol interactions as well as in forensic science when alcohol-related crimes are investigated. The PK of ethanol have been extensively studied since the 1930s, although some issues remain unresolved, such as the significance of first-pass metabolism, whether zero-order kinetics apply, and the effects of food on bioavailability. We took advantage of nonlinear mixed-effects modeling to describe blood-alcohol concentration (BAC) profiles derived from 3 published clinical studies involving oral, intraduodenal, and intravenous administration of ethanol with and without food. The overall data set included 1510 BACs derived from 72 healthy subjects (60 men, 12 women) aged between 20 and 60 years. Two-compartment models with first-order absorption and Michaelis-Menten elimination kinetics adequately described the BAC profiles. Food intake had 2 separate effects: It reduced the absorption rate constant and accelerated the maximum elimination rate. Estimates of the maximum elimination rate (fasted) and the food effect (as a factor) were 6.31 g/h (95%CI, 6.04-6.59 g/h) and 1.39-fold (95%CI, 1.33-1.46-fold), respectively. Simulations showed that the area under the BAC-time curve (AUC) was smaller with lower input rate of ethanol, irrespective of any first-pass metabolism. The AUC from time 0 to 10 hours for a 75-kg subject was 2.34 g center dot h/L (fed) and 3.83 g center dot h/L (fasted) after an oral dose of 45 g ethanol. This difference was mainly attributable to the food effect on ethanol elimination and depended less on the absorption rate. Our new approach to explain the complex human PK of ethanol may help when BAC predictions are made in clinical pharmacology and forensic medicine.

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  • 48.
    Buse, Giovanna Lurati
    et al.
    Univ Hosp Dusseldorf, Germany.
    Pinto, Bernardo Bollen
    Geneva Univ Hosp HUG, Switzerland.
    Abelha, Fernando
    Ctr Hosp Univ Sao Joao, Portugal; Univ Porto, Portugal.
    Abbott, Tom E. F.
    Queen Mary Univ London, England.
    Ackland, Gareth
    Queen Mary Univ London, England; Barts Hlth NHS Trust, England.
    Afshari, Arash
    Univ Copenhagen, Denmark.
    De Hert, Stefan
    Univ Ghent, Belgium.
    Fellahi, Jean-Luc
    Hop Univ Louis Pradel, France.
    Giossi, Laure
    Geneva Univ Hosp HUG, Switzerland.
    Kavsak, Peter
    McMaster Univ, Canada.
    Longrois, Dan
    Univ Paris, France.
    MPembele, Rene
    Univ Hosp Dusseldorf, Germany.
    Nucaro, Anthony
    Univ Hosp Dusseldorf, Germany.
    Popova, Ekaterine
    Inst Invest Biomed St Pau IIB ST PAU, Spain; Ctr Cochrane Iberoamer, Spain.
    Puelacher, Christian
    Univ Basel, Switzerland.
    Richards, Toby
    Univ Western Australia, Australia; UCL, England.
    Roth, Sebastian
    Univ Hosp Dusseldorf, Germany.
    Sheka, Mootii
    Geneva Univ Hosp HUG, Switzerland.
    Szczeklik, Wojciech
    Jagiellonian Univ Med Coll, Poland.
    van Waes, Judith
    Univ Utrecht, Netherlands.
    Walder, Bernhard
    Geneva Univ Hosp HUG, Switzerland.
    Chew, Michelle
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, ANOPIVA US.
    ESAIC focused guideline for the use of cardiac biomarkers in perioperative risk evaluation2023In: European Journal of Anaesthesiology, ISSN 0265-0215, E-ISSN 1365-2346, Vol. 40, no 12, p. 888-927Article in journal (Refereed)
    Abstract [en]

    BACKGROUNDIn recent years, there has been increasing focus on the use of cardiac biomarkers in patients undergoing noncardiac surgery.AIMSThe aim of this focused guideline was to provide updated guidance regarding the pre-, post- and combined pre-and postoperative use of cardiac troponin and B-type natriuretic peptides in adult patients undergoing noncardiac surgery.METHODSThe guidelines were prepared using Grading of Recommendations Assessment Development and Evaluation (GRADE) methodology. This included the definition of critical outcomes, a systematic literature search, appraisal of certainty of evidence, evaluation of biomarker measurement in terms of the balance of desirable and undesirable effects including clinical outcomes, resource use, health inequality, stakeholder acceptance, and implementation. The panel differentiated between three different scopes of applications: cardiac biomarkers as prognostic factors, as tools for risk prediction, and for biomarker-enhanced management strategies.RESULTSIn a modified Delphi process, the task force defined 12 critical outcomes. The systematic literature search resulted in over 25,000 hits, of which 115 full-text articles formed the body of evidence for recommendations. The evidence appraisal indicated heterogeneity in the certainty of evidence across critical outcomes. Further, there was relevant gradient in the certainty of evidence across the three scopes of application. Recommendations were issued and if this was not possible due to limited evidence, clinical practice statements were produced.CONCLUSIONThe ESAIC focused guidelines provide guidance on the perioperative use of cardiac troponin and B-type natriuretic peptides in patients undergoing noncardiac surgery, for three different scopes of application.

  • 49.
    Carlstedt, A.
    et al.
    Karlstad Cent Hosp, Sweden.
    Bringman, S.
    Sodertalje Hosp, Sweden; Karolinska Inst, Sweden.
    Egberth, M.
    Mora Hosp, Sweden.
    Emanuelsson, P.
    Karolinska Inst, Sweden.
    Olsson, A.
    Karolinska Inst, Sweden; Capio CFTK, Sweden.
    Petersson, U.
    Lund Univ, Sweden.
    Palstedt, J.
    Karolinska Inst, Sweden; Ersta Hosp, Sweden.
    Sandblom, G.
    Karolinska Inst, Sweden; Soder Sjukhuset, Sweden.
    Sjödahl, Rune
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Stark, B.
    Karolinska Inst, Sweden.
    Strigard, K.
    Umea Univ, Sweden.
    Tall, J.
    Karolinska Inst, Sweden; Ersta Hosp, Sweden.
    Theodorsson, Elvar
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology.
    Management of Diastasis of the Rectus Abdominis Muscles: Recommendations for Swedish National Guidelines2021In: Scandinavian Journal of Surgery, ISSN 1457-4969, E-ISSN 1799-7267, Vol. 110, no 3, p. 452-459Article in journal (Refereed)
    Abstract [en]

    Background: Diastasis of the rectus abdominis muscle is a common condition. There are no generally accepted criteria for diagnosis or treatment of diastasis of the rectus abdominis muscle, which causes uncertainty for the patient and healthcare providers alike. Methods: The consensus document was created by a group of Swedish surgeons and based on a structured literature review and practical experience. Results: The proposed criteria for diagnosis and treatment of diastasis of the rectus abdominis muscle are as follows: (1) Diastasis diagnosed at clinical examination using a caliper or ruler for measurement. Diagnostic imaging by ultrasound or other imaging modality, should be performed when concurrent umbilical or epigastric hernia or other cause of the patients symptoms cannot be excluded. (2) Physiotherapy is the firsthand treatment for diastasis of the rectus abdominis muscle. Surgery should only be considered in diastasis of the rectus abdominis muscle patients with functional impairment, and not until the patient has undergone a standardized 6-month abdominal core training program. (3) The largest width of the diastasis should be at least 5 cm before surgical treatment is considered. In case of pronounced abdominal bulging or concomitant ventral hernia, surgery may be considered in patients with a smaller diastasis. (4) When surgery is undertaken, at least 2 years should have elapsed since last childbirth and future pregnancy should not be planned. (5) Plication of the linea alba is the firsthand surgical technique. Other techniques may be used but have not been found superior. Discussion: The level of evidence behind these statements varies, but they are intended to lay down a standard strategy for treatment of diastasis of the rectus abdominis muscle and to enable uniformity of management.

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  • 50.
    Castiglione, Fabio
    et al.
    Univ Coll London Hosp, England; UCL, England; IRCCS Osped San Raffaele, Italy.
    Albersen, Maarten
    Univ Leuven, Belgium.
    Fiorenzo, Salvatore
    Univ Palermo, Italy.
    Hedlund, Petter
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Lund Univ, Sweden.
    Cakir, Omer Onur
    Univ Coll London Hosp, England.
    Pavone, Carlo
    Univ Palermo, Italy.
    Alnajjar, Hussain M.
    Univ Coll London Hosp, England.
    Joniau, Steven
    Univ Leuven, Belgium.
    Muneer, Asif
    Univ Coll London Hosp, England; UCL, England; Univ Coll London Hosp, England; Univ Coll London Hosp, England.
    Long-term consequences of bilateral cavernous crush injury in normal and diabetic rats: a functional study2022In: International journal of impotence research, ISSN 0955-9930, E-ISSN 1476-5489, Vol. 34, no 8, p. 781-785Article in journal (Refereed)
    Abstract [en]

    A recent statement from the European-Society-for-Sexual-Medicine has highlighted the limitations of using the rat model for nerve-sparing prostatectomy. The use of young rats with no comorbidities and the early evaluation of the erectile function (EF) are deemed a source of bias. Our aim was to evaluate the long-term consequences in EF of bilateral nerve cavernous crush- injury (BNCI) in type 1 diabetic (DM) rats 30-male/12-week-old rats were divided into four groups: Sham, BNCI, DM, and BNCI + DM. Sham group underwent an intraperitoneal injection (IP) of saline solution and after 1 month underwent a sham laparotomy. BNCI underwent an IP of saline solution and after 1 month to BNCI. DM underwent an IP of 60 mg/kg-1-streptozotocin (STZ) and after 1 month to a sham laparotomy. BNCI + DM underwent an IP of 60 mg/kg-1-STZ and after 1 month to BNCI. After 5 months from the induction of diabetes, all rats underwent measurement of intracorporeal pressure (ICP) and mean arterial pressure (MAP) during CN-electrostimulation. Multiple groups were compared using Kruskal-Wallis one-way analysis of variance followed by Mann-Whitney U test for post hoc comparisons. Blood glucose-level was higher (p &lt; 0.05) in the groups with DM and BNCI + DM. After 5-months, DM and BNCI + DM also showed a lower weight compared to other groups (p &lt; 0.05). No differences were noted in ICP/MAP between the sham and BNCI. BNCI + DM showed lower ICP/MAP compared to all the groups (p &lt; 0.05). DM Showed lower ICP/MAP compared to Sham and BNCI (p &lt; 0.05). BNCI in rats without comorbidities did not induce long-term erectile dysfunction (ED) suggesting a spontaneous EF recovery. BNCI in DM induced long-term ED. The results of previous short-term studies can only provide evidence on the time to recovery of spontaneous EF as to the actual EF recovery rate.

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