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1.
  • Olofsson, P, et al. (författare)
  • Genetic variants of TNFSF4 and risk for carotid artery disease and stroke
  • 2008
  • Ingår i: Journal of Molecular Medicine. - New York : Springer. - 0946-2716 .- 1432-1440. ; 87:4, s. 337-346
  • Tidskriftsartikel (refereegranskat)abstract
    • In two independent human cohorts, the minor allele of SNP rs3850641 in TNFSF4 was significantly more frequent in individuals with myocardial infarction than in controls. In mice, Tnfsf4 expression is associated with increased atherosclerosis. The expression of TNFSF4 in human atherosclerosis and the association between genotype and cerebrovascular disease have not yet been investigated. TNFSF4 messenger RNA (mRNA) levels were significantly higher in human atherosclerotic lesions compared with controls (730 +/- 30 vs 330 +/- 65 arbitrary units, p < 0.01). TNFSF4 was mainly expressed by macrophages in atherosclerotic lesions. In cell culture, endothelial cells upregulated TNFSF4 in response to tumor necrosis factor alpha (TNF-alpha; 460 +/- 110 vs 133 +/- 8 arbitrary units, p < 0.001 after 6 h of stimulation). We analyzed the TNFSF4 gene in 239 patients who had undergone carotid endarterectomy and 138 matching controls from The Biobank of Karolinska Carotid Endarterectomies and Stockholm Heart Epidemiology Program cohorts and 929 patients and 1,382 matching controls from the Sahlgrenska Academy Study on Ischemic Stroke and Case Control Study of Stroke cohorts, limiting inclusion to patients with ischemic stroke. Participants were genotyped for the rs3850641 SNP in TNFSF4. Genotype associations were neither found with TNFSF4 mRNA levels nor with atherosclerosis associated systemic factors or risk for stroke. This study shows that TNFSF4 is expressed on antigen-presenting cells in human carotid atherosclerotic lesions but provides no evidence for an association of TNFSF4 gene variation with the risk for ischemic stroke.
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2.
  • Bock, David, 1976, et al. (författare)
  • Agreement between patient reported outcomes and clinical reports after radical prostatectomy - a prospective longitudinal study
  • 2019
  • Ingår i: Bmc Urology. - : BioMed Central (BMC). - 1471-2490. ; 19
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundIn clinical research information can be retrieved through various sources. The aim is to evaluate the agreement between answers in patient questionnaires and clinical reports in a study of patients after radical prostatectomy and patient characteristics associated with agreement between these two data sources.MethodsIn the prospective non-randomized longitudinal trial LAParoscopic Prostatectomy Robot Open (LAPPRO) 4003 patients undergoing radical prostatectomy at 14 centers in Sweden were followed. Analysis of agreement is made using a variety of methods, including the recently proposed Gwet's AC1, which enables us to handle the limitations of Cohen's Kappa where agreement depends on the underlying prevalence.ResultsThe incidence of postoperative events was consistently reported higher by the patient compared with the clinical reports for all outcomes. Agreement regarding the absence of events (negative agreement) was consistently higher than agreement regarding events (positive agreement) for all outcome variables. Overall impression of agreement depends on which measure used for the assessment. The previously reported desirable properties of Gwet's AC1 as well as the patient characteristics associated with agreement were confirmed.ConclusionThe differences in incidence and agreement across the different variables and time points highlight the importance of carefully assessing which source of information to use in clinical research.
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3.
  • Bock, David, 1976, et al. (författare)
  • Do negative intrusive thoughts at diagnosis predict impaired quality of life, depressed mood and waking up with anxiety 3, 12 and 24 months after radical prostatectomy?–a longitudinal study
  • 2020
  • Ingår i: Scandinavian Journal of Urology. - : Taylor & Francis. - 2168-1805 .- 2168-1813. ; 54:3, s. 220-226
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To evaluate the effect of intrusive thoughts at diagnosis on quality of life, depressed mood and waking up with anxiety up to two years after radical prostatectomy. Method: The Laparoscopic Prostatectomy Robot Open (LAPPRO) trial was a prospective, longitudinal multicenter study of 4003 patients undergoing radical prostatectomy. Questionnaire data were collected preoperatively, at 3, 12 and 24 months after surgery. Results: The group of patients with intrusive thoughts at diagnosis had a statistically significant higher postoperative prevalence of impaired quality of life, depressed mood and waking up with anxiety as compared with the group of patients with no or minor intrusive thoughts. The highest risk increase for impaired QoL, depressed mood and waking up with anxiety ≥1/week was at 12, 3 and 3 months, respectively, where the three outcomes increased by 38% (RR: 1.38; 95%CI: 1.27–1.49)), 136% (RR: 2.36; 95%CI: 1.74–3.19)) and 165% (RR: 2.65; 95%CI: 2.22–3.17)), respectively. Conclusions: The demonstrated link between intrusive thoughts and quality of life, depressed mood and waking up with anxiety deliver is further evidence to the idea that intrusive thoughts has potential as an endpoint for assessing and predicting psychological distress among men with prostate cancer diagnosis. Trial registration number: ISRCTN06393679 (www.isrctn.com). Date of registration: 07/02/2008. Retrospectively registered. © 2020, © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
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4.
  • Bock, David, 1976, et al. (författare)
  • Habits and self-assessed quality of life, negative intrusive thoughts and depressed mood in patients with prostate cancer: a longitudinal study
  • 2017
  • Ingår i: Scandinavian Journal of Urology. - : Taylor & Francis. - 2168-1805 .- 2168-1813. ; 51:5, s. 353-359
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The aim of this study was to evaluate the association of self-assessed preoperative physical activity, alcohol consumption and smoking with self-assessed quality of life, negative intrusive thoughts and depressed mood after radical prostatectomy.Materials and methods: The Laparoscopic Prostatectomy Robot Open (LAPPRO) trial was a prospective, controlled, non-randomized longitudinal trial of patients (n=4003) undergoing radical prostatectomy at 14 centers in Sweden. Validated patient questionnaires were collected at baseline, and 3, 12 and 24 months after surgery.Results: Preoperative medium or high physical activity or low alcohol consumption or non-smoking was associated with a lower risk of depressed mood. High alcohol consumption was associated with increased risk of negative intrusive thoughts. Postoperatively, quality of life and negative intrusive thoughts improved gradually in all groups. Depressed mood appeared to be relatively unaffected.Conclusions: Evaluation of preoperative physical activity, tobacco and alcohol consumption habits can be used to identify patients with a depressed mood in need of psychological support before and immediately after surgery. Quality of life and intrusive thoughts improved postoperatively.
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5.
  • Hagman, A., et al. (författare)
  • Urinary continence recovery and oncological outcomes after surgery for prostate cancer analysed by risk category: results from the LAParoscopic prostatectomy robot and open trial
  • 2021
  • Ingår i: World Journal of Urology. - : Springer. - 0724-4983. ; 39:119, s. 3239-3249
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose To evaluate urinary continence (UC) recovery and oncological outcomes in different risk-groups after robot-assisted radical prostatectomy (RALP) and open retropubic radical prostatectomy (RRP). Patients and methods We analysed 2650 men with prostate cancer from seven open (n = 805) and seven robotic (n = 1845) Swedish centres between 2008 and 2011 in a prospective non-randomised trial, LAPPRO. UC recovery was defined as change of pads less than once in 24 h. Information was collected through validated questionnaires. Rate of positive surgical margins (PSM) and biochemical recurrence (BCR), defined as prostate-specific antigen (PSA) > 0.25 mg/ml, were recorded. We stratified patients into two risk groups (low-intermediate and high risk) based on the D'Amico risk classification system. Result Among men with high-risk prostate cancer, we found significantly higher rates of UC recovery up to 24 months after RRP compared to RALP (66.1% vs 60.5%) RR 0.85 (CI 95% 0.73-0.99) while PSM was more frequent after RRP compared to RALP (46.8% vs 23.5%) RR 1.56 (CI 95% 1.10-2.21). In the same group no significant difference was seen in BCR. Overall, however, BCR was significantly more common after RRP compared to RALP at 24 months (9.8% vs 6.6%) RR 1.43 (Cl 95% 1.08-1.89). The limitations of this study are its non-randomized design and the relatively short time of follow-up. Conclusions Our study indicates that men with high-risk tumour operated with open surgery had better urinary continence recovery but with a higher risk of PSM than after robotic-assisted laparoscopic surgery. No significant difference was seen in biochemical recurrence.
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6.
  • Mansouri, Larry, et al. (författare)
  • Functional loss of IκBε leads to NF-κB deregulation in aggressive chronic lymphocytic leukemia.
  • 2015
  • Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 212:6, s. 833-843
  • Tidskriftsartikel (refereegranskat)abstract
    • NF-κB is constitutively activated in chronic lymphocytic leukemia (CLL); however, the implicated molecular mechanisms remain largely unknown. Thus, we performed targeted deep sequencing of 18 core complex genes within the NF-κB pathway in a discovery and validation CLL cohort totaling 315 cases. The most frequently mutated gene was NFKBIE (21/315 cases; 7%), which encodes IκBε, a negative regulator of NF-κB in normal B cells. Strikingly, 13 of these cases carried an identical 4-bp frameshift deletion, resulting in a truncated protein. Screening of an additional 377 CLL cases revealed that NFKBIE aberrations predominated in poor-prognostic patients and were associated with inferior outcome. Minor subclones and/or clonal evolution were also observed, thus potentially linking this recurrent event to disease progression. Compared with wild-type patients, NFKBIE-deleted cases showed reduced IκBε protein levels and decreased p65 inhibition, along with increased phosphorylation and nuclear translocation of p65. Considering the central role of B cell receptor (BcR) signaling in CLL pathobiology, it is notable that IκBε loss was enriched in aggressive cases with distinctive stereotyped BcR, likely contributing to their poor prognosis, and leading to an altered response to BcR inhibitors. Because NFKBIE deletions were observed in several other B cell lymphomas, our findings suggest a novel common mechanism of NF-κB deregulation during lymphomagenesis.
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7.
  • Nilsson, Andreas E, et al. (författare)
  • Age at surgery, educational level and long-term urinary incontinence after radical prostatectomy.
  • 2011
  • Ingår i: BJU international. - 1464-410X .- 1464-4096.
  • Tidskriftsartikel (refereegranskat)abstract
    • Study Type - Harm (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Several factors including age, body mass index (BMI), prostate size and previous transurethral resection of the prostate have been suggested to play a part in determining the risk of urinary incontinence after radical prostatectomy. Results relating to the importance of each factor have been conflicting, so we need more data to be able to identify the relevant factors. In this consecutive series with information from 1179 patients who had undergone radical prostatectomy, age at the time of surgery, educational level, respiratory disease and salvage radiation therapy predicted the occurrence of long-term urinary incontinence. Increasing age predicted the risk in an exponential manner, and the data indicate a correlation across all educational levels. There was no certain association between previous transurethral resection of the prostate, increased BMI or prostate size and urinary incontinence. OBJECTIVE: • To identify predictors for long-term urinary leakage after radical prostatectomy. PATIENTS AND METHODS: • A consecutive series of 1411 patients who underwent radical prostatectomy (open surgery or robot-assisted laparoscopic surgery) at Karolinska University Hospital between 2002 and 2006 were invited to complete a study-specific questionnaire. • Urinary leakage was defined as use of two or more pads per day. RESULTS: • Questionnaires were received from 1288 (91%) patients with a median follow-up of 2.2 years. Age at surgery predicts in an exponential manner long-term urinary incontinence at follow-up with an estimated relative increase of 6% per year. • Among the oldest patients, 19% had urinary incontinence compared with 6% in the youngest age group, translating to a prevalence ratio of 2.4 (95% confidence interval [CI], 1.5-8.1). • Low educational level, as compared with high, yielded an increased age-adjusted prevalence ratio of 2.5 (95% CI, 1.7-3.9). • Patients who had undergone salvage radiation therapy had an increased prevalence of urinary incontinence (2.5; 95% CI, 1.6-3.8), as did those with respiratory disease (2.4; 95% CI, 1.3-4.4). • Body mass index, prostate weight, presence of diabetes or previous transurethral resection did not appear to influence the prevalence of urinary incontinence. CONCLUSIONS: • In this series, a patient's age at radical prostatectomy influenced, in an exponential manner, his risk of long-term urinary incontinence. • Other predictors are low educational level, salvage radiation therapy and respiratory disease. • Intervention studies are needed to understand if these data are relevant to the prevalence of urinary leakage if a radical prostatectomy is postponed in an active monitoring programme.
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8.
  • Nyberg, M., et al. (författare)
  • Risk of Recurrent Disease 6 Years After Open or Robotic-assisted Radical Prostatectomy in the Prospective Controlled Trial LAPPRO
  • 2020
  • Ingår i: European Urology Open Science. - : Elsevier. - 2666-1691 .- 2666-1683. ; 20, s. 54-61
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Conclusive evidence of superiority in oncological outcome for robotassisted laparoscopic prostatectomy (RALP) over retropubic radical prostatectomy (RRP) is lacking. Objective: To compare RALP and RRP regarding recurrent disease and to report the mortality rate 6 yr after surgery. Design, setting, and participants: A total of 4003 men with localized prostate cancer were enrolled between 2008 and 2011 in Laparoscopic Prostatectomy Robot Open (LAPPRO)- a prospective, controlled, nonrandomized trial performed at 14 Swedish centers. Outcome measurements and statistical analysis: Data were collected at visits and by patient questionnaires at 3, 12, and 24 mo, and through a structured telephone interview at 6 yr. Cause of death was retrieved from the National Cause of Death Register in Sweden. The modified Poisson regression approach was used for analyses. Results and limitations: After adjustment for patient-, tumor-, and surgeon-related confounders, no statistically significant difference was observed between RALP and RRP in biochemical recurrence rate (14 vs 16%, relative risk [RR] 0.77, 95% confidence interval [CI] 0.56-1.06) or in not cured endpoint (22% vs 23%, RR 0.82, 95% CI 0.6-1.11). Stratified by D'Amico risk group, a significant benefit for RALP existed for recurrent disease in high-risk patients (RR 0.47, 95% CI 0.26-0.86, p = 0.02). All-cause mortality was 3% (n = 96). Prostate cancer-specific mortality was 0.6% (n = 21) overall, 0.3% (n = 8) after RALP, and 1.5% (n = 13) after RRP. The nonrandomized design is a limitation. Conclusions: No significant difference was observed for cancer recurrence rate between RALP and RRP 6 yr after surgery. However, in a subgroup analysis, we found a significant benefit for RALP regarding recurrence rate in the high-risk group. Larger studies with longer follow-up are needed to make a firm conclusion and to evaluate a possible survival benefit. Patient summary: In general, the oncological outcome is comparable between robotic and open radical prostatectomy 6 yr after surgery. For high-risk patients, our findings indicate that there is an advantage for robotics, but further studies with longer follow-up time is needed to make a firm conclusion. (c) 2020 Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/).
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9.
  • Nyberg, M., et al. (författare)
  • Surgeon heterogeneity significantly affects functional and oncological outcomes after radical prostatectomy in the Swedish LAPPRO trial
  • 2020
  • Ingår i: BJU International. - : Wiley-Blackwell. - 1464-4096 .- 1464-410X. ; 127:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives To evaluate how surgeon heterogeneity - the variation in outcomes between individual surgeons - influences functional and oncological outcomes after robot-assisted laparoscopic prostatectomy (RALP) and retropubic radical prostatectomy (RRP), and to assess whether surgeon heterogeneity affects the comparison between RALP and RRP. Patients and Methods Laparoscopic Prostatectomy Robot Open (LAPPRO) is a prospective, controlled, non-randomized trial performed at 14 Swedish centres with 68 operating surgeons. A total of 4003 men with localized prostate cancer were enrolled between 2008 and 2011. The endpoints were urinary incontinence, erectile dysfunction (ED) and recurrence at 24 months after surgery. Logistic regression models were built to evaluate surgeon heterogeneity and, secondarily, surgeon-specific factors were added to the models to investigate their influence on heterogeneity and the comparison between RALP and RRP. Results Among surgeons who performed at least 20 surgeries during the study period (n=25), we observed statistically significant heterogeneity for incontinence (P= 0.001), ED (P< 0.001) and rate of recurrent disease (P< 0.001). The significant heterogeneity remained when analysing only experienced surgeons with a stated experience of at least 250 radical prostatectomies (n=12). Among all participating surgeons (n=68), differences in surgeon volume explained 42% of the observed heterogeneity for incontinence (P= 0.003), 11% for ED (P= 0.03) and 19% for recurrence (P= 0.01). Taking surgeon volume into account when comparing RALP and RRP had a significant impact on the results. The effect was greatest for functional outcomes, and the additional adjustments for the surgeons' previous experience changed whether the difference between techniques was statistically significant or not. The surgeons' annual volume had the greatest effect on the recurrence rate. Conclusions There was a large degree of heterogeneity among surgeons regarding both functional and oncological outcomes and this had a significant impact on the results when comparing RALP and RRP. Some of the observed heterogeneity was explained by differences in surgeon volume. Efforts to decrease heterogeneity are warranted and variation among surgeons must be accounted for when conducting comparative analyses between surgical techniques.
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10.
  • Rachakonda, P. Sivaramakrishna, et al. (författare)
  • TERT promoter mutations in bladder cancer affect patient survival and disease recurrence through modification by a common polymorphism
  • 2013
  • Ingår i: Proceedings of the National Academy of Sciences. - : National Acad Sciences. - 1091-6490. ; 110:43, s. 17426-17431
  • Tidskriftsartikel (refereegranskat)abstract
    • The telomerase reverse transcriptase (TERT) promoter, an important element of telomerase expression, has emerged as a target of cancer-specific mutations. Originally described in melanoma, the mutations in TERT promoter have been shown to be common in certain other tumor types that include glioblastoma, hepatocellular carcinoma, and bladder cancer. To fully define the occurrence and effect of the TERT promoter mutations, we investigated tumors from a well-characterized series of 327 patients with urothelial cell carcinoma of bladder. The somatic mutations, mainly at positions - 124 and - 146 bp from ATG start site that create binding motifs for E-twenty six/ternary complex factors (Ets/TCF), affected 65.4% of the tumors, with even distribution across different stages and grades. Our data showed that a common polymorphism rs2853669, within a preexisting Ets2 binding site in the TERT promoter, acts as a modifier of the effect of the mutations on survival and tumor recurrence. The patients with the mutations showed poor survival in the absence [hazard ratio (HR) 2.19, 95% confidence interval (CI) 1.02-4.70] but not in the presence (HR 0.42, 95% CI 0.18-1.01) of the variant allele of the polymorphism. The mutations in the absence of the variant allele were highly associated with the disease recurrence in patients with Tis, Ta, and T1 tumors (HR 1.85, 95% CI 1.11-3.08). The TERT promoter mutations are the most common somatic lesions in bladder cancer with clinical implications. The association of the mutations with patient survival and disease recurrence, subject to modification by a common polymorphism, can be a unique putative marker with individualized prognostic potential.
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