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  • Ehrstedt, Christoffer, et al. (författare)
  • Clinical characteristics and late effects in CNS tumours of childhood : Do not forget long term follow-up of the low grade tumours
  • 2016
  • Ingår i: European journal of paediatric neurology. - 1090-3798 .- 1532-2130. ; 20:4, s. 580-587
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: To investigate clinical characteristics and late effects of CNS tumours in childhood with a special focus on low-grade tumours, especially low-grade astrocytoma and glib neuronal tumours. Methods: A retrospective population based study was performed at Uppsala University Children's Hospital, a tertiary referral centre for children with CNS tumours. Patients were identified from the National Brain Tumour Registry and the National Epilepsy Surgery Registry. Hospital medical records were analysed for patients with a follow up of >= 5 years after diagnosis. A re-evaluation of the neuro-pathological diagnosis was performed. Results: A total of 193 patients (age 0-17.99 years) during a twelve-year period (1995-2006) were included; 149 survived >= 5 years. Three larger subgroups could be identified: astrocytic, embryonal and glioneuronal tumours. A supratentorial location was found in 52%. Medical late effects were mainly neurological and endocrinological, affecting 81% and 26% of surviving patients. Cognitive late effects were a frequent finding in the whole group but also in low-grade astrocytoma and glioneuronal tumours (53% and 67%). Thirty per cent had some kind of pedagogic support in school. Conclusion: Late effects are common in long-term survivors of CNS tumours in childhood. Low-grade astrocytoma and glioneuronal tumours are no exception, and the findings support the need for long-term follow up.
  • Rasmussen, Gunlög, 1973-, et al. (författare)
  • Long term molecular epidemiology of methicillin-susceptible staphylococcus aureus bacteremia isolates in Sweden
  • 2014
  • Ingår i: PLoS ONE. - San Francisco, USA : Public Library Science. - 1932-6203. ; 9:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Staphylococcus aureus is one of the major pathogens that causes bacteremia; therefore, it is important to understand the long-term molecular epidemiology of S. aureus bacteremia infections. In particular, little is known about the population structure of methicillin-sensitive S. aureus (MSSA) compared to that of methicillin-resistant S. aureus. We investigated potential changes in the MSSA molecular epidemiology in Örebro County, Sweden, from 1980 through 2010. 400 MSSA bacteremia isolates, the first 100 isolated each decade from 1980 through 2010, were retrospectively identified and analyzed regarding assignment to clonal complexes (CCs), presence of virulence genes and antibiotic resistant determinants with DNA microarray-based genotyping. 24 different CCs were identified. Most isolates (80%) belonged to 6 predominant lineages. Of those, the number of isolates assigned to CC5 and CC15 increased, and those assigned to CC8, CC25, and CC30 decreased. The most prevalent clone, CC45, did not show a significant change in prevalence during the study period. A change in prevalence was observed for some of the virulence genes, mainly attributed with their association to certain CCs. With the exception of the common blaZ gene (encoding penicillinase), antibiotic resistance genes were only sporadically detected. In conclusion, the MSSA population structure was genetically diverse. We observed decadal changes in assignments to five predominant clones, and corresponding changes in the prevalence of some virulence genes linked to CC affiliation. In light of the restrictive antibiotics prescriptions and extensive infection control procedures in Sweden, antibiotic resistance genes were rarely detected and their prevalence unaffected during the study period.
  • Rosfors, S, et al. (författare)
  • Venous occlusion plethysmography in patients with post-thrombotic venous claudication
  • 2013
  • Ingår i: Journal of Vascular Surgery. - Elsevier. - 0741-5214. ; 58:3, s. 722-726
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Post-thrombotic venous claudication is a serious condition that may be treated with iliac vein stenting or open surgery, and there is a need for hemodynamic tests in the preoperative evaluation. The purpose of this study was to describe the results of venous occlusion plethysmography in patients with venous claudication and to analyze the outflow curve to find variables that best describe the functional abnormality in this patient group.METHODS: Twenty-nine patients with previous deep venous thrombosis and with clinical evidence of venous claudication were retrospectively identified. The results of venous occlusion plethysmography in these patients were compared with results obtained in a group of 63 healthy control subjects of similar age and sex. Computerized strain-gauge plethysmography was used in a capacitance mode where the occlusion time is determined by an electronic detector allowing the maximal venous volume to be achieved in all limbs. Outflow volumes (OV1, OV4) and outflow fractions (OF1, OF4) were calculated at 1 and 4 seconds after cuff release. Outflow fraction is OV divided by maximal venous volume.RESULTS: Both outflow volumes and outflow fractions were significantly reduced in patients compared with healthy control subjects. Outflow fractions were more sensitive than outflow volumes in identifying patients with venous claudication. The most discriminating variable was OF4 that was reduced below the normal lower limit in 69% of the patients, most severely reduced in patients with severe claudication.CONCLUSIONS: Patients with venous claudication attributable to remaining post-thrombotic iliofemoral obstructive disease are characterized by a functional disturbance shown with venous occlusion plethysmography as a reduced venous outflow during the initial 4 seconds following cuff release in relation to their true maximal venous volume. Our results suggest that venous occlusion plethysmography can be a valuable tool in the preoperative workup for selection of patients with iliofemoral vein obstruction that may benefit from venous intervention.
  • Skoglund, Kristofer, et al. (författare)
  • Decline in Self-reported Health (EQ-5D) over Time after Surgical Reconstruction of the Right Ventricular Outflow Tract: A Longitudinal Cohort Study of 103 Patients
  • 2015
  • Ingår i: Congenital Heart Disease. - Wiley-Blackwell. - 1747-079X. ; 10:2, s. 54-59
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectivePatients with congenital heart disease may be operated with surgical reconstruction of the right ventricular outflow tract (RVOT). Reintervention is common in this group of patients. The aim of this study was to examine longitudinal self-reported health measured by the EQ-5D questionnaire. DesignData were collected from the Swedish Registry of Congenital Heart Disease. EQ-5D, which measures health outcome, was introduced into the registry in 2005. All adult patients with previous surgical reconstruction of the RVOT who had EQ-5D data from their first and latest visit were analyzed. ResultsAmong 103 patients (65 male and 38 female), mean age 31 (range 19-78 years), the diagnoses were: tetralogy of Fallot (n=66); truncus, transpositions, and double outlet right ventricle (n=23); and Ross-operated congenital aortic valve disease (n=14). Time from first to latest visit was 3 years (range 1-7 years). Eighteen patients underwent 26 reinterventions in the observational period from the first to latest visit, including operations, percutaneous interventions, pacemaker implantations, and ablations. Health perception, mean EQ-5D visual analog scale, VAS, declined from 84.4 (standard deviation (SD)=14.6) to 78.6 (SD=18.3) at the latest visit, P=.001. The decline is almost exclusively seen in patients without reinterventions. Low EQ-VAS was associated with symptoms and New York Heart Association class II-IV. Patient-reported problems in the EQ-5D dimension usual activities were more common in the patients having reinterventions (25%) than those without reintervention (7%), P=.04. ConclusionIn this longitudinal cohort study of patients with previous surgical reconstruction of the RVOT, health perception declined over time. The decline was not observed in patients undergoing any additional interventions.
  • Andelin, M., et al. (författare)
  • Assessing the Accuracy of Continuous Glucose Monitoring (CGM) Calibrated With Capillary Values Using Capillary or Venous Glucose Levels as a Reference.
  • 2016
  • Ingår i: Journal of Diabetes Science and Technology. - Diabetes Technology Society. ; 10:4, s. 876-884
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Using the standard venous reference for the evaluation of continuous glucose monitoring (CGM) systems could possibly negatively affect measured CGM accuracy since CGM are generally calibrated with capillary glucose and venous and capillary glucose concentrations differ. We therefore aimed to quantify the effect of using capillary versus venous glucose reference samples on estimated accuracy in capillary calibrated CGM.less thanbr /greater thanMethods: We evaluated 41 individuals with type 1 diabetes mellitus (T1DM) using the Dexcom G4 CGM system over 6 days. Patients calibrated their CGM devices with capillary glucose by means of the HemoCue system. During 2 visits, capillary and venous samples were simultaneously measured by HemoCue and compared to concomitantly obtained CGM readings. The mean absolute relative difference (MARD) was calculated using capillary and venous reference samples.less thanbr /greater thanResults: Venous glucose values were 0.83 mmol/L (15.0 mg/dl) lower than capillary values over all glycemic ranges, P less than .0001. Below 4 mmol/l (72 mg/dl), the difference was 1.25 mmol/l (22.5 mg/dl), P = .0001, at 4-10 mmol/l (72-180 mg/dl), 0.67 mmol/l (12.0 mg/dl), P less than .0001 and above 10 mmol/l (180 mg/dl), 0.95 mmol/l (17.1 mg/dl), P less than .0001. MARD was 11.7% using capillary values as reference compared to 13.7% using venous samples, P = .037. Below 4 mmol/l (72 mg/dl) MARD was 16.6% and 31.8%, P = .048, at 4-10 mmol/l (72-180 mg/dl) 12.1% and 12.6%, P = .32, above 10 mmol/l (180 mg/dl) 8.7% and 9.2%, P = .82.less thanbr /greater thanConclusion: Using capillary glucose concentrations as reference to evaluate the accuracy of CGM calibrated with capillary samples is associated with a lower MARD than using venous glucose as the reference. Capillary glucose concentrations were significantly higher than venous in all glycemic ranges.less thanbr /greater than (© 2016 Diabetes Technology Society.)
  • Cedervall, Jessica, et al. (författare)
  • Pharmacological targeting of peptidylarginine deiminase 4 prevents cancer-associated kidney injury in mice.
  • 2017
  • Ingår i: Oncoimmunology. - 2162-4011 .- 2162-402X. ; 6:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Renal insufficiency is a frequent cancer-associated problem affecting more than half of all cancer patients at the time of diagnosis. To minimize nephrotoxic effects the dosage of anticancer drugs are reduced in these patients, leading to sub-optimal treatment efficacy. Despite the severity of this cancer-associated pathology, the molecular mechanisms, as well as therapeutic options, are still largely lacking. We here show that formation of intravascular tumor-induced neutrophil extracellular traps (NETs) is a cause of kidney injury in tumor-bearing mice. Analysis of clinical biomarkers for kidney function revealed impaired creatinine clearance and elevated total protein levels in urine from tumor-bearing mice. Electron microscopy analysis of the kidneys from mice with cancer showed reversible pathological signs such as mesangial hypercellularity, while permanent damage such as fibrosis or necrosis was not observed. Removal of NETs by treatment with DNase I, or pharmacological inhibition of the enzyme peptidylarginine deiminase 4 (PAD4), was sufficient to restore renal function in mice with cancer. Tumor-induced systemic inflammation and impaired perfusion of peripheral vessels could be reverted by the PAD4 inhibitor. In conclusion, the current study identifies NETosis as a previously unknown cause of cancer-associated renal dysfunction and describes a novel promising approach to prevent renal failure in individuals with cancer.
  • Djureinovic, Dijana, et al. (författare)
  • Profiling cancer testis antigens in non-small-cell lung cancer
  • 2016
  • Ingår i: JCI INSIGHT. - 2379-3708. ; 1:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Cancer testis antigens (CTAs) are of clinical interest as biomarkers and present valuable targets for immunotherapy. To comprehensively characterize the CTA landscape of non-small-cell lung cancer (NSCLC), we compared RNAseq data from 199 NSCLC tissues to the normal transcriptome of 142 samples from 32 different normal organs. Of 232 CTAs currently annotated in the Caner Testis Database (CTdatabase), 96 were confirmed in NSCLC. To obtain an unbiased CTA profile of NSCLC, we applied stringent criteria on our RNAseq data set and defined 90 genes as CTAs, of which 55 genes were not annotated in the CTdatabase, thus representing potential new CTAs. Cluster analysis revealed that CTA expression is histology dependent and concurrent expression is common. IHC confirmed tissue-specific protein expression of selected new CTAs (TKTL1, TGIF2LX, VCX, and CXORF67). Furthermore, methylation was identified as a regulatory mechanism of CTA expression based on independent data from The Cancer Genome Atlas. The proposed prognostic impact of CTAs in lung cancer was not confirmed, neither in our RNAseq cohort nor in an independent meta-analysis of 1,117 NSCLC cases. In summary, we defined a set of 90 reliable CTAs, including information on protein expression, methylation, and survival association. The detailed RNAseq catalog can guide biomarker studies and efforts to identify targets for immunotherapeutic strategies.
  • Hammarsten, Ola, et al. (författare)
  • Evaluation of a Sensitive Copeptin Assay for Clinical Measurement
  • 2012
  • Ingår i: The Open Clinical Chemistry Journal. - 2588-7785. ; 5:1, s. 21-26
  • Tidskriftsartikel (refereegranskat)abstract
    • Abstract: Background: Copeptin, a marker of vasopressin production, has been introduced for earlier diagnosis of acute myocardial infarction and other clinical emergencies. We evaluated the analytical performance of a new generation copeptin assay in an inter-laboratory trial. Methods: Precision, linearity range, carry-over contamination, the limit of blank and an inter-laboratory comparison trial for the copeptin US KRYPTOR assay were performed on the B·R·A·H·M·S KRYPTOR compact PLUS. Results: The intra-assay imprecision (CVs) was 12.6–2.2% and total imprecision over five days was 12.3-4.3% between 3.1 and 18.2 pmol/L. The assay had excellent linearity between 7-222 pmol/L. The limit of blank was 2.5 pmol/L and the limit of detection was 3.2 pmol/L, but was dependent on the analyte-free material used. No significant difference between sample type, such as serum or different types of plasma or reagent lots, was noted. The copeptin results remained unchanged upon five repeated freeze-thaw cycles. A set of patient samples with a mean copeptin concentration of 2.1-61 pmol/L run at two separate sites showed close correlation (r2=0.99, slope=1.01, intercept=0.35), indicating comparable results across laboratories. Conclusion: The new ultrasensitive copeptin KRYPTOR assay shows excellent inter-lab precision, opening up the possibility for international guidelines to exclude acute myocardial infarction.
  • Johannsson, Gudmundur, 1960-, et al. (författare)
  • Serum leptin concentration and insulin sensitivity in men with abdominal obesity.
  • 1998
  • Ingår i: Obesity research. - 1071-7323. ; 6:6, s. 416-21
  • Tidskriftsartikel (refereegranskat)abstract
    • We have examined the association between generalized adiposity, abdominal adiposity, insulin sensitivity, and serum levels of leptin in a cross-sectional study of abdominally obese men.Thirty men, 48 to 66 years of age with a body mass index (BMI) of between 25 kg/m2 and 35 kg/m2 and a waist hip ratio of >0.95, were included in the study. Serum leptin concentration was measured using radioimmunoassay. Total body fat percentage was determined from total body potassium, abdominal adiposity was measured by computed tomography, and the glucose disposal rate (GDR) was measured during an euglycemic, hyperinsulinemic glucose clamp.Significant correlations were found between serum leptin concentration and BMI, percentage body fat, abdominal subcutaneous adipose tissue, serum insulin, GDR, and 24-hour urinary-free cortisol. In a multiple regression analysis, it was shown that abdominal subcutaneous adipose tissue, GDR, and BMI explained 72% of the variability of serum leptin concentration. GDR demonstrated an independent inverse correlation with serum leptin concentration.In abdominally obese men with insulin resistance, it was demonstrated that most of the individual variability in serum leptin concentration was explained by the amount of subcutaneous abdominal adipose tissue, insulin sensitivity, and BMI.
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