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1.
  • Siekmann, W, et al. (författare)
  • Surgical and not analgesic technique affects postoperative inflammation following colorectal cancer surgery : a prospective, randomized study
  • Ingår i: Colorectal Disease. - : Wiley-Blackwell. - 1462-8910 .- 1463-1318. ; 19:6, s. 186-195
  • Tidskriftsartikel (refereegranskat)abstract
    • AIM: Epidural analgesia reduces the surgical stress response. However, its effect on pro- and anti-inflammatory cytokines in the genesis of inflammation following major abdominal surgery remains unclear. Our main objective was to elucidate whether perioperative epidural analgesia prevents the inflammatory response following colorectal cancer surgery.METHODS: Ninety-six patients scheduled for open or laparoscopic surgery were randomized to epidural analgesia (group E) or patient-controlled intravenous analgesia (group P). Surgery and anaesthesia were standardized in both groups. Plasma cortisol, insulin and serum cytokines [interleukin 1β (IL-1β), IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, tumour necrosis factor α, interferon γ, granulocyte-macrophage colony-stimulating factor, prostaglandin E2 and vascular endothelial growth factor] were measured preoperatively (T0), 1-6 h postoperatively (T1) and 3-5 days postoperatively (T2). Mixed model analysis was used, after logarithmic transformation when appropriate, for analyses of cytokines and stress markers.RESULTS: >There were no significant differences in any serum cytokine concentration between groups P and E at any time point except for IL-10 which was 87% higher in group P [median and range 4.1 (2.3-9.2) pg/ml] compared to group E [2.6 (1.3-4.7) pg/ml] (P = 0.002) at T1. There was no difference in plasma cortisol and insulin between the groups at any time point after surgery. A significant difference in median serum cytokine concentration was found between open and laparoscopic surgery with higher levels of IL-6, IL-8 and IL-10 at T1 in patients undergoing open surgery compared to laparoscopic surgery. No difference in serum cytokine concentration was detected between the groups or between the surgical technique at T2.CONCLUSIONS: Open surgery, compared to laparoscopic surgery, has greater impact on these inflammatory mediators than epidural analgesia vs intravenous analgesia.
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2.
  • Andersen, M. R., et al. (författare)
  • Comparative genomics of citric-acid-producing Aspergillus niger ATCC 1015 versus enzyme-producing CBS 513.88
  • 2011
  • Ingår i: Genome Research. - 1088-9051 .- 1549-5469. ; 21:6, s. 885-897
  • Tidskriftsartikel (refereegranskat)abstract
    • The filamentous fungus Aspergillus niger exhibits great diversity in its phenotype. It is found globally, both as marine and terrestrial strains, produces both organic acids and hydrolytic enzymes in high amounts, and some isolates exhibit pathogenicity. Although the genome of an industrial enzyme-producing A. niger strain (CBS 513.88) has already been sequenced, the versatility and diversity of this species compel additional exploration. We therefore undertook wholegenome sequencing of the acidogenic A. niger wild-type strain (ATCC 1015) and produced a genome sequence of very high quality. Only 15 gaps are present in the sequence, and half the telomeric regions have been elucidated. Moreover, sequence information from ATCC 1015 was used to improve the genome sequence of CBS 513.88. Chromosome-level comparisons uncovered several genome rearrangements, deletions, a clear case of strain-specific horizontal gene transfer, and identification of 0.8 Mb of novel sequence. Single nucleotide polymorphisms per kilobase (SNPs/kb) between the two strains were found to be exceptionally high (average: 7.8, maximum: 160 SNPs/kb). High variation within the species was confirmed with exo-metabolite profiling and phylogenetics. Detailed lists of alleles were generated, and genotypic differences were observed to accumulate in metabolic pathways essential to acid production and protein synthesis. A transcriptome analysis supported up-regulation of genes associated with biosynthesis of amino acids that are abundant in glucoamylase A, tRNA-synthases, and protein transporters in the protein producing CBS 513.88 strain. Our results and data sets from this integrative systems biology analysis resulted in a snapshot of fungal evolution and will support further optimization of cell factories based on filamentous fungi
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3.
  • Sjoberg, M., et al. (författare)
  • Infliximab as rescue therapy in hospitalised patients with steroid-refractory acute ulcerative colitis: a long-term follow-up of 211 Swedish patients
  • 2013
  • Ingår i: Alimentary pharmacology & therapeutics. - : Wiley-Blackwell. - 0269-2813 .- 1365-2036. ; 38:4, s. 377-387
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundRescue therapy with infliximab (IFX) has been proven effective in a steroid-refractory attack of ulcerative colitis (UC). The long-term efficacy is not well described. AimTo present a retrospective study of IFX as rescue therapy in UC. Primary end points were colectomy-free survival at 3 and 12months. MethodsIn this multicentre study, 211 adult patients hospitalised between 1999 and 2010 received IFX 5mg/kg as rescue therapy due to a steroid-refractory, moderate-to-severe attack of UC. Exclusion criteria were duration of current flare for >12weeks, corticosteroid treatment for >8weeks before hospitalisation, previous IFX therapy or Crohn's disease. ResultsProbability of colectomy-free survival at 3months was 0.71 (95% CI, 0.64-0.77), at 12months 0.64 (95% CI, 0.57-0.70), at 3years 0.59 (95% CI, 0.52-0.66) and at 5years 0.53 (95% CI, 0.44-0.61). Steroid-free, clinical remission was achieved in 105/211 (50%) and 112/209 (54%) patients at 3 and 12months respectively. Of 75 colectomies during the first year, 48 (64%) were carried out during the first 14days, 13 (17%) on days 15-90 and 14 (19%) between 3 and 12months. There were three (1.4%) deaths during the first 3months. ConclusionsInfliximab is an effective rescue treatment, both short- and long-term, in a steroid-refractory attack of UC. Most IFX failures underwent surgery during the first 14days, which calls for studies on how to optimise induction treatment with IFX. Serious complications, including mortality, were rare.
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4.
  • Bjorkenheim, A., et al. (författare)
  • Rhythm Control and Its Relation to Symptoms during the First Two Years after Radiofrequency Ablation for Atrial Fibrillation
  • 2016
  • Ingår i: Pace-Pacing and Clinical Electrophysiology. - Hoboken, USA : Wiley-Blackwell Publishing Inc.. - 0147-8389 .- 1540-8159. ; 39:9, s. 914-925
  • Tidskriftsartikel (refereegranskat)abstract
    • Clinical Trial RegistrationURL:. Unique Identifier: NCT00697359. ObjectivesTo evaluate rhythm control up to two years after atrial fibrillation (AF) ablation and its relation to reported symptoms. BackgroundThe implantable loop recorder (ILR) continuously records the electrocardiogram (ECG), has an automatic AF detection algorithm, and has a possibility for patients to activate an ECG recording during symptoms. MethodsFifty-seven patients (mean age 57 9 years, 60% male, 88% paroxysmal AF) underwent AF ablation following ILR implantation. Device data were downloaded at the ablation and three, six, 12, 18, and 24 months after ablation. ResultsFifty-four patients completed the two-year follow-up. Thirteen (24%) patients had no AF episodes detected by ILR during follow-up. Ten of 41 patients (24%) with AF recurrence were only detected by ILR and AF recurrences were detected earlier by ILR (P < 0.001). The median AF burden in patients with AF recurrence was 5.7% (interquartile range 0.4-14.4) and was even lower in patients with AF only detected by ILR (P = 0.001). Forty-eight % of the patients indicated symptoms via the patient activator but 33% of those recordings were not due to AF. Early AF recurrence (within 3 months) was highly associated with later AF recurrence (P < 0.001). AF burden >0.5% and longest AF episode >6 hours before the ablation were independent predictors of AF recurrence during intermittent but not continuous monitoring. ConclusionsAfter AF ablation, the AF burden was low throughout the 24 months follow-up. Nevertheless, symptoms were commonly indicated but one-third of patient-activated recordings did not show AF. Continuous monitoring was superior to intermittent follow-up in detecting AF episodes and assessing the AF burden.
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5.
  • Björkenheim, A., et al. (författare)
  • Patient-reported outcomes in relation to continuously monitored rhythm before and during 2 years after atrial fibrillation ablation using a disease-specific and a generic instrument
  • 2018
  • Ingår i: Journal of the American Heart Association. - : Wiley-Blackwell Publishing Inc.. - 2047-9980. ; 7:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Background--Atrial fibrillation (AF) ablation improves patient-reported outcomes, irrespective of mode of intermittent rhythm monitoring. We evaluated the use of an AF-specific and a generic patient-reported outcomes instrument during continuous rhythm monitoring 2 years after AF ablation. Methods and Results--Fifty-four patients completed the generic 36-Item Short-Form Health Survey and the AF-specific AF6 questionnaires before and 6, 12, and 24 months after AF ablation. All patients underwent continuous ECG monitoring via an implantable loop recorder. The generic patient-reported outcomes scores were compared with those of a Swedish age- and sexmatched population. After ablation, both summary scores reached normative levels at 24 months, while role-physical and vitality remained lower than norms. Responders to ablation (AF burden < 0.5%) reached the norms in all individual 36-Item Short-Form Health Survey domains, while nonresponders (AF burden > 0.5%) reached norms only in social functioning and mental component summary. All AF6 items and the sum score showed moderate to large improvement in both responders and nonresponders, although responders showed significantly greater improvement in all items except item 1 from before to 24 months after ablation. Higher AF burden was independently associated with poorer physical component summary and AF6 sum score. Conclusions--The AF-specific AF6 questionnaire was more sensitive to changes related to AF burden than the generic 36-Item Short-Form Health Survey. Patients improved as documented by both instruments, but a higher AF burden after ablation was associated with poorer AF-specific patient-reported outcomes and poorer generic physical but not mental health. Our results support the use of an AF-specific instrument, alone or in combination with a generic instrument, to assess the effect of ablation. © 2018 The Authors.
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6.
  • Carstens, Adam, et al. (författare)
  • Differential clustering of fecal and mucosa-associated microbiota in 'healthy' individuals
  • 2018
  • Ingår i: Journal of Digestive Diseases. - 1751-2972 .- 1751-2980. ; 19:12, s. 745-752
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective Fecal samples are often used to characterize gut microbiota. However, whether or not fecal microbiota differs from mucosa-associated microbiota remains largely unknown. This may be specifically relevant in conditions that are characterized by complex mucosal microbe-host interactions, such as Crohn's disease. We aimed to determine the degree of agreement between fecal and mucosal microbiota profiles in 'healthy' individuals, using two commonly used collection procedures. Methods The gut microbiota composition of fecal samples (sent at ambient temperature before storage at -70 degrees C) and of colonic biopsies (obtained at endoscopy and immediately stored at -70 degrees C) was determined by sequencing the 16S rRNA gene. Altogether 31 randomly selected 'healthy' individuals from the population-based colonoscopy (Popcol) study were included. Results The fecal samples were characterized by a reduced degree of richness (P < 0.0001) and diversity (P = 0.016), and also differences in several phyla, including a lower relative abundance of Proteobacteria (P < 0.0001) and Verrucomicrobia (P = 0.008) than in biopsies. Only three of 30 individuals had a similar fecal and mucosal microbiota profile, based on weighted UniFrac analysis. A difference in Crohn's disease dysbiosis-associated bacteria was observed, including a lower relative abundance of Faecalibacterium (P = 0.004) and a higher relative abundance of Ruminococcus (P = 0.001) in feces than in biopsies. Conclusions The observed differences between fecal samples, transported at ambient temperature, and the colonic mucosa-associated microbiota have implications for the interpretation of the previous literature, and may be specifically relevant to studies on Crohn's disease.
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7.
  • Fadl, H., et al. (författare)
  • Changing diagnostic criteria for gestational diabetes in Sweden-a stepped wedge national cluster randomised controlled trial-the CDC4G study protocol
  • 2019
  • Ingår i: Bmc Pregnancy and Childbirth. - : BioMed Central (BMC). - 1471-2393. ; 19:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The optimal criteria to diagnose gestational diabetes mellitus (GDM) remain contested. The Swedish National Board of Health introduced the 2013 WHO criteria in 2015 as a recommendation for initiation of treatment for hyperglycaemia during pregnancy. With variation in GDM screening and diagnostic practice across the country, it was agreed that the shift to new guidelines should be in a scientific and structured way. The aim of the Changing Diagnostic Criteria for Gestational Diabetes (CDC4G) in Sweden () is to evaluate the clinical and health economic impacts of changing diagnostic criteria for GDM in Sweden and to create a prospective cohort to compare the many long-term outcomes in mother and baby under the old and new diagnostic approaches. Methods This is a stepped wedge cluster randomised controlled trial, comparing pregnancy outcomes before and after the switch in GDM criteria across 11 centres in a randomised manner. The trial includes all pregnant women screened for GDM across the participating centres during January-December 2018, approximately two thirds of all pregnancies in Sweden in a year. Women with pre-existing diabetes will be excluded. Data will be collected through the national Swedish Pregnancy register and for follow up studies other health registers will be included. Discussion The stepped wedge RCT was chosen to be the best study design for evaluating the shift from old to new diagnostic criteria of GDM in Sweden. The national quality registers provide data on the whole pregnant population and gives a possibility for follow up studies of both mother and child. The health economic analysis from the study will give a solid evidence base for future changes in order to improve immediate pregnancy, as well as long term, outcomes for mother and child.
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8.
  • Gustavsson, A, et al. (författare)
  • Clinical trial : colectomy after resue therapy in ulcerative colitis-3-year follow-up of the Swedish-Danish controlled infliximab study
  • 2010
  • Ingår i: Alimentary Pharmacology and Therapeutics. - : Blackwell Publishing Ltd. - 0269-2813 .- 1365-2036. ; 32:8, s. 984-989
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The long-term efficacy of infliximab as rescue therapy in steroid-refractory ulcerative colitis is not well described. AIM: To examine the long-term efficacy of infliximab as a rescue therapy through a 3-year follow-up of a previous placebo-controlled trial of infliximab in acute steroid-refractory ulcerative colitis. METHOD: In the original study, 45 patients were randomized to a single infusion of infliximab 5 mg/kg or placebo, and at 3 months, 7/24 patients given infliximab were operated vs. 14/21 patients given placebo. Three years or later, patients were asked to participate in a clinical follow-up. RESULTS: Another seven patients underwent colectomy during follow-up: five in the infliximab group and two in the placebo group. After 3 years, a total of 12/24 (50%) patients given infliximab and 16/21 (76%) given placebo (P = 0.012) had a colectomy. None of eight patients in endoscopic remission at 3 months later had a colectomy compared with 7/14 (50%) patients who were not in remission (P=0.02). There was no mortality. CONCLUSION: The benefit of rescue therapy with infliximab in steroid-refractory acute ulcerative colitis remained after 3 years. The main advantage of infliximab treatment occurred during the first 3 months, whereas subsequent colectomy rates were similar in the two groups. Mucosal healing at 3 months influenced later risk of colectomy.
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9.
  • Sundh, Josefin, 1972-, et al. (författare)
  • Beta-blockeRs tO patieNts with CHronIc Obstructive puLmonary diseasE (BRONCHIOLE) - Study protocol from a randomized controlled trial
  • 2020
  • Ingår i: ; 21:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Observational studies indicate that beta-blockers are associated with a reduced risk of exacerbation and mortality in patients with chronic obstructive pulmonary disease (COPD) even without overt cardiovascular disease, but data from randomized controlled trials (RCT) are lacking. The aim of this RCT is to investigate whether beta-blocker therapy in patients with COPD without diagnosed cardiovascular disease is associated with a decreased 1-year risk of the composite endpoint of death, exacerbations, or cardiovascular events.Methods: The Beta-blockeRs tO patieNts with CHronIc Obstructive puLmonary diseasE (BRONCHIOLE) study is an open-label, multicentre, prospective RCT. A total of 1700 patients with COPD will be randomly assigned to either standard COPD care and metoprolol at a target dose of 100 mg per day or to standard COPD care only. The primary endpoint is a composite of death, COPD exacerbations, and cardiovascular events. Major exclusion criteria are ischemic heart disease, left-sided heart failure, cerebrovascular disease, critical limb ischemia, and atrial fibrillation/flutter. Study visits are an inclusion visit, a metoprolol titration visit at 1 month, follow-up by telephone at 6 months, and a final study visit after 1 year. Outcome data are obtained from medical history and record review during study visits, as well as from national registries.Discussion: BRONCHIOLE is a pragmatic randomized trial addressing the potential of beta-blockers in patients with COPD. The trial is expected to provide relevant clinical data on the efficacy of this treatment on patient-related outcomes in patients with COPD.
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10.
  • Fransén, Karin, 1973-, et al. (författare)
  • Polymorphism in the retinoic acid metabolizing enzyme CYP26B1 and the development of Crohn's disease
  • 2013
  • Ingår i: ; 8:8, s. e72739-
  • Tidskriftsartikel (refereegranskat)abstract
    • Several studies suggest that Vitamin A may be involved in the pathogenesis of inflammatory bowel disease (IBD), but the mechanism is still unknown. Cytochrome P450 26 B1 (CYP26B1) is involved in the degradation of retinoic acid and the polymorphism rs2241057 has an elevated catabolic function of retinoic acid, why we hypothesized that the rs2241057 polymorphism may affect the risk of Crohn's disease (CD) and Ulcerative Colitis (UC). DNA from 1378 IBD patients, divided into 871 patients with CD and 507 with UC, and 1205 healthy controls collected at Örebro University Hospital and Karolinska University Hospital were analyzed for the CYP26B1 rs2241057 polymorphism with TaqMan® SNP Genotyping Assay followed by allelic discrimination analysis. A higher frequency of patients homozygous for the major (T) allele was associated with CD but not UC compared to the frequency found in healthy controls. A significant association between the major allele and non-stricturing, non-penetrating phenotype was evident for CD. However, the observed associations reached borderline significance only, after correcting for multiple testing. We suggest that homozygous carriers of the major (T) allele, relative to homozygous carriers of the minor (C) allele, of the CYP26B1 polymorphism rs2241057 may have an increased risk for the development of CD, which possibly may be due to elevated levels of retinoic acid. Our data may support the role of Vitamin A in the pathophysiology of CD, but the exact mechanisms remain to be elucidated.
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