| 1. |
- Gyllenberg, A, et al.
(författare)
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Variability in the CIITA gene interacts with HLA in multiple sclerosis.
- 2014
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Ingår i: Genes and immunity. - Stockholm : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- The human leukocyte antigen (HLA) is the main genetic determinant of multiple sclerosis (MS) risk. Within the HLA, the class II HLA-DRB1*15:01 allele exerts a disease-promoting effect, whereas the class I HLA-A*02 allele is protective. The CIITA gene is crucial for expression of class II HLA molecules and has previously been found to associate with several autoimmune diseases, including MS and type 1 diabetes. We here performed association analyses with CIITA in 2000 MS cases and up to 6900 controls as well as interaction analysis with HLA. We find that the previously investigated single-nucleotide polymorphism rs4774 is associated with MS risk in cases carrying the HLA-DRB1*15 allele (P=0.01, odds ratio (OR): 1.21, 95% confidence interval (CI): 1.04-1.40) or the HLA-A*02 allele (P=0.01, OR: 1.33, 95% CI: 1.07-1.64) and that these associations are independent of the adjacent confirmed MS susceptibility gene CLEC16A. We also confirm interaction between rs4774 and HLA-DRB1*15:01 such that individuals carrying the risk allele for rs4774 and HLA-DRB1*15:01 have a higher than expected risk for MS. In conclusion, our findings support previous data that variability in the CIITA gene affects MS risk, but also that the effect is modulated by MS-associated HLA haplotypes. These findings further underscore the biological importance of HLA for MS risk.Genes and Immunity advance online publication, 16 January 2014; doi:10.1038/gene.2013.71.
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| 2. |
- Paulsson, J., et al.
(författare)
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High expression of stromal PDGFR beta is associated with reduced benefit of tamoxifen in breast cancer
- 2017
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Ingår i: Journal of Pathology Clinical Research. - : Wiley. - 2056-4538. ; 3:1, s. 38-43
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Tidskriftsartikel (refereegranskat)abstract
- Cancer-associated fibroblasts (CAFs) regulate tumour growth, metastasis and response to treatment. Recent studies indicate the existence of functionally distinct CAF subsets. Suggested mechanisms whereby CAFs can impact on treatment response include paracrine signalling affecting cancer cell drug sensitivity and effects on tumour drug uptake. PDGFR beta is an important regulator of fibroblasts. Experimental studies have linked PDGFR beta-positive fibroblasts to metastasis and also to reduced tumour drug uptake. This study has investigated the potential role of PDGFR beta-positive fibroblasts in response to adjuvant tamoxifen treatment of breast cancer. Analyses of two breast cancer collections from randomised studies analysing adjuvant tamoxifen treatment in early breast cancer demonstrated significant benefit of tamoxifen in the group with low stromal PDGFR beta, which was not observed in the group with high stromal PDGFR beta. In general terms these findings provide novel evidence, derived from analyses of randomised clinical studies, of response-predictive capacity of a marker-defined subset of CAFs and, more specifically, identify stromal PDGFR beta as a marker related to tamoxifen benefit in early breast cancer.
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| 3. |
- Svensson, M.K, 1965, et al.
(författare)
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The risk for diabetic nephropathy is low in young adults in a 17-year follow-up from the Diabetes Incidence Study in Sweden (DISS). Older age and higher BMI at diabetes onset can be important risk factors
- 2015
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Ingår i: Diabetes-Metabolism Research and Reviews. - : Wiley. - 1520-7560 .- 1520-7552. ; 31:2, s. 138-146
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Tidskriftsartikel (refereegranskat)abstract
- AimsThe main objective of this study was to estimate the occurrence of diabetic nephropathy in a population-based cohort of patients diagnosed with diabetes as young adults (15-34years). MethodsAll 794 patients registered 1987-1988 in the Diabetes Incidence Study in Sweden (DISS) were invited to a follow-up study 15-19years after diagnosis, and 468 (58%) participated. Analysis of islet antibodies was used to classify type of diabetes. ResultsAfter median 17years of diabetes, 15% of all patients, 14% T1DM and 25% T2DM, were diagnosed with diabetic nephropathy. Ninety-one percent had microalbuminuria and 8.6% macroalbuminuria. Older age at diagnosis (HR 1.05; 95% CI 1.01-1.10 per year) was an independent and a higher BMI at diabetes diagnosis (HR 1.04; 95% CI 1.00-1.09 per 1kg/m(2)), a near-significant predictor of development of diabetic nephropathy. Age at onset of diabetes (p=0.041), BMI (p=0.012) and HbA1c (p<0.001) were significant predictors of developing diabetic nephropathy between 9 and 17years of diabetes. At 17years of diabetes duration, a high HbA1c level (OR 1.06; 95% CI 1.03-1.08 per 1mmol/mol increase) and systolic blood pressure (OR 1.08; 95% CI 1.051.12 per 1mmHg increase) were associated with DN. ConclusionsPatients with T2DM diagnosed as young adults seem to have an increased risk to develop diabetic nephropathy compared with those with T1DM. Older age and higher BMI at diagnosis of diabetes were risk markers for development of diabetic nephropathy. In addition, poor glycaemic control but not systolic blood pressure at 9years of follow-up was a risk marker for later development of diabetic nephropathy. Copyright (c) 2014 John Wiley & Sons, Ltd.
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| 4. |
- Gronhaug, K. M. L., et al.
(författare)
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Subsequent ipsi- and contralateral femoral fractures after intramedullary nailing of a trochanteric or subtrochanteric fracture: a cohort study on 2012 patients
- 2022
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Ingår i: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Background The literature is inconclusive as to whether an intramedullary nail changes the distribution of a subsequent ipsi- or contralateral fracture of the femur. We have compared the incidence, localisation, and fracture pattern of subsequent femoral fractures after intramedullary nailing of trochanteric or subtrochanteric fractures in patients without previous implants in either femur at the time of surgery. Methods Retrospective analysis was performed of a two-centre cohort of 2012 patients treated with a short or long intramedullary nail for the management of trochanteric or subtrochanteric fracture between January 2005 and December 2018. Subsequent presentations with ipsi- and contralateral femoral fractures were documented. Only patients with no previous femoral surgery performed, other than the index nailing were followed. Odds ratios (ORs) for subsequent femoral fracture were calculated using robust variance estimates in logistic regression. Results The mean age of the cohort was 82.4 years and 72.1% were female. The total number of patients presenting with subsequent femoral fractures was 299 (14.9%). The number of patients presenting with subsequent ipsilateral and contralateral femoral fractures was 51 (2.5%) and 248 (12.3%) respectively (OR 5.0; CI 3.7-6.9). Twenty-six (8.7%) of all subsequent femoral fractures occured in the ipsilateral shaft, 14 (4.7%) in the ipsilateral metaphyseal area, one (0.33%) in the contralateral shaft, and three (1.0%) in the contralateral metaphysis (OR 10; CI 3.6-29). Conclusion An intramedullary nail significantly changes the fracture pattern in the event of a second low-energy trauma, reducing the risk of subsequent proximal ipsilateral femoral fractures and increasing the risk of subsequent ipsilateral femoral fractures in the shaft and distal metaphyseal area compared with the native contralateral femur.
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| 5. |
- Javidgonbadi, Davood, 1964, et al.
(författare)
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Short atrioventricular delay pacing therapy in young and old patients with hypertrophic obstructive cardiomyopathy: good long-term results and a low need for reinterventions
- 2018
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Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 20:10, s. 1683-1691
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Examination of long-term results following different treatments in hypertrophic obstructive cardiomyopathy (HOCM) in a complete geographical cohort. Methods and results: HOCM patients attending during 2002-13 in all 10 hospitals in the West Gotaland Region, Sweden, were identified (n = 251), follow-up 14.4 (+/-8.9) years (mean +/- SD), 121 managed medically, 42 treated with myectomy and 88 with short atrioventricular (AV) delay pacing as first interventional procedure. Post-intervention follow-up was 12.9 +/- 8.7 years and 12.2 +/- 5.0 years, respectively. Both intervention treatments improved New York Heart Association (NYHA) class and outflow gradients significantly. Patients treated with pacing were older (median age 64 vs. 43 years, P < 0.001). Freedom from disease-related death post-procedure at 5, 10, and 20 years were 93%, 80%, 56% vs. 93%, 93%, 57% in pacing and myectomy groups, respectively (log-rank P = 0.43). Survival after diagnosis was not different in patients just treated conservatively (P = 0.51 pacing/conservative; P = 0.39 myectomy/conservative). Reintervention for outflow gradients in patients >/=18 years at procedure occurred in 3.5% in pacing group and 15.6% in myectomy group (P = 0.007). Pacing therapy was equally effective in patients aged 13-64 years (n = 44), as in patients >/=65 years (n = 44): resting gradient pre-procedure and at last follow-up were median (IQR) 65 (71) and 12 (20) mmHg for <65 year-olds (P < 0.001), and 75 (64) and 14 (38) mmHg, respectively, for >/=65 year-olds (P < 0.001). New York Heart Association class improved significantly in both age ranges to 1.6 +/- 0.6 and 1.8 +/- 0.7, respectively (P < 0.001; P < 0.001). Conclusion: Short AV delay pacing provided lasting satisfactory relief of symptoms and outflow obstruction in the majority of patients, with low risk of requiring reintervention. Our findings support the view that pacing therapy should be considered a valid option to treat patients with HOCM.
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| 6. |
- Tobin, N. P., et al.
(författare)
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An Endothelial Gene Signature Score Predicts Poor Outcome in Patients with Endocrine-Treated, Low Genomic Grade Breast Tumors
- 2016
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Ingår i: Clinical Cancer Research. - : American Association for Cancer Research (AACR). - 1078-0432 .- 1557-3265. ; 22:10, s. 2417-2426
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The ability of vascular genes to provide treatment predictive information in breast cancer patients remains unclear. As such, we assessed the expression of genes representative of normal endothelial microvasculature (MV) in relation to treatment-specific patient subgroups. Experimental Design: We used expression data from 993 breast tumors to assess 57 MV genes (summarized to yield an MV score) as well as the genomic grade index (GGI) and PAM50 signatures. MV score was compared with CD31 staining by correlation and gene ontology (GO) analysis, along with clinicopathologic characteristics and PAM50 subtypes. Uni-, multivariate, and/or t-test analyses were performed in all and treatment-specific subgroups, along with a clinical trial cohort of patients with metastatic breast cancer, seven of whom received antiangiogenic therapy. Results: MV score did not correlate with microvessel density (correlation = 0.096), but displayed enrichment for angiogenic GO terms, and was lower in Luminal B tumors. In endocrine-treated patients, a high MV score was associated with decreased risk of metastasis [HR 0.58; 95% confidence interval (CI), 0.38-0.89], even after adjusting for histologic grade, but not GGI or PAM50. Subgroup analysis showed the prognostic strength of the MV score resided in low genomic grade tumors and MV score was significantly increased in metastatic breast tumors after treatment with sunitinib + docetaxel (P = 0.031). Conclusions: MV score identifies two groups of better and worse survival in low-risk endocrine-treated breast cancer patients. We also show normalization of tumor vasculature on a transcriptional level in response to an angiogenic inhibitor in human breast cancer samples. (C) 2016 AACR.
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