Sydvestjysk Hospital

Esbjerg, Denmark

Sydvestjysk Hospital

Esbjerg, Denmark
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Green T.M.,University of Southern Denmark | Young K.H.,University of Houston | Visco C.,San Bortolo Hospital | Xu-Monette Z.Y.,University of Houston | And 8 more authors.
Journal of Clinical Oncology | Year: 2012

Purpose: Approximately 5% of diffuse large B-cell lymphomas (DLBCLs) are double-hit lymphomas (DHLs) with translocations of both MYC and BCL2. DHLs are characterized by poor outcome. We tested whether DLBCLs with high expression of MYC protein and BCL2 protein share the clinical features and poor prognosis of DHLs. Patients and Methods: Paraffin-embedded lymphoma samples from 193 patients with de novo DLBCL who were uniformly treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were studied using immunohistochemistry for MYC, BCL2, CD10, BCL6, and MUM1/interferon regulatory factor 4, and fluorescent in situ hybridization (FISH) for MYC and BCL2. Results: FISH analysis identified DHL in 6% of patients, who showed the expected poor overall survival (OS; P = .002). On the basis of immunohistochemical MYC and BCL2 expression, a double-hit score (DHS) was assigned to all patients with DLBCL. The DHS-2 group, defined by high expression of both MYC and BCL2 protein, comprised 29% of the patients. DHS 2 was significantly associated with lower complete response rate (P = .004), shorter OS (P < .001), and shorter progression-free survival (PFS; P < .001). The highly significant correlation with OS and PFS was maintained in multivariate models that controlled for the International Prognostic Index and the cell-of-origin subtype (OS, P < .001; PFS, P < .001). DHS was validated in an independent cohort of 116 patients who were treated with R-CHOP. Conclusion: The immunohistochemical DHS defined a large subset of DLBCLs with double-hit biology and was strongly associated with poor outcome in patients treated with R-CHOP. © 2012 by American Society of Clinical Oncology.

Diederichsen S.Z.,University of Southern Denmark | Gerke O.,University of Southern Denmark | Olsen M.H.,University of Southern Denmark | Lambrechtsen J.,Svendborg Hospital | And 5 more authors.
Journal of Hypertension | Year: 2013

Purpose: To improve risk stratification for development of ischaemic heart disease, several markers have been proposed. Both the presence of coronary artery calcification (CAC) and ECG pattern of left ventricular hypertrophy/strain have been shown to provide independent prognostic information. In this study, we investigated the association between established risk factors, ECG measurements and the presence of coronary artery calcification. Method: A random sample of healthy men and women aged 50 or 60 years were invited to the screening study. Established risk factors were measured. A noncontrast computed tomographic (CT) scan was performed to assess the CAC score. ECG analysis included left ventricular hypertrophy (LVH) using the Sokolow-Lyon criteria and the Cornell voltage x QRS duration product, and strain pattern based on ST segment depression and T-wave abnormalities. The association between the presence of CAC, clinical variables and ECG findings was evaluated by means of multivariate logistic regression. Results: Of 1825 invited individuals, 1226 accepted the screening. The prevalence of hypertension was 50%. Hypertensive patients frequently had LVH and/or strain when compared with nonhypertensive individuals (21 vs. 14%, P < 0.0001) as well as CAC (52 vs. 38%, P < 0.0001). In multiple logistic regressions analyses, there was no association between the ECG abnormalities and the presence of CAC. Conclusion: There appears to be no relationship between CAC and ECG-suspected LVH and/or strain. We propose that these markers identify different individuals at risk and together may have additive prognostic value. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Lindberg S.O.,Roskilde Hospital | la Cour J.L.,Herlev Hospital | Folkestad L.,Sydvestjysk Hospital | Hallas P.,Rigshospitalet | Brabrand M.,Esbjerg Hospital
Danish Medical Bulletin | Year: 2011

Introduction: The emergency departments (EDs) handle approximately 1,000,000 contacts annually. Danish health care is undergoing reorganization that involves the creation of fewer and larger EDs to handle these contacts. There is therefore a need to prioritize the use of resources to optimize treatment. We thus wanted to investigate if Danish EDs are using triage systems and, if so, which systems they are using. Material And Methods: We performed a cross-sectional study on triage at all EDs in the 20 Danish hospitals that have been designated for emergency care. Results: The response rate was 100% (n = 20). We found that triage was used at 75% (n = 15) of the EDs. Adaptive process triage (ADAPT) was the most frequently used validated triage system (25% (n = 5)), while 40% (n = 8) used non-validated systems. Triage was performed by nurses at 73% (n = 11) of the EDs using triage. Conclusion: Triage systems were used in 75% of Danish EDs. ADAPT was the primary triage system in 25% of the EDs, while 40% used non-validated triage systems. An improvement in the quality of health care in Danish EDs may possibly be achieved by implementing validated triage, i.e. ADAPT. Funding: not relevant Trial Registration: not relevant.

PubMed | Hvidovre Hospital, University of Aarhus, Koge Hospital, Helmholtz Center Munich and 10 more.
Type: Journal Article | Journal: PloS one | Year: 2015

The inflammatory bowel diseases (IBD), Crohns disease (CD) and ulcerative colitis (UC), result from the combined effects of susceptibility genes and environmental factors. Previous studies have shown that polymorphisms in the Toll-like receptor (TLR), the apoptosis, the IL-23/IL-17 and the interferon gamma (IFNG) pathways are associated with risk of both CD and UC.Using a candidate gene approach, 21 functional single nucleotide polymorphisms (SNPs) in 15 genes were assessed in a clinical homogeneous group of severely diseased ethnic Danish patients consisting of 624 patients with CD, 411 patients with UC and 795 controls. The results were analysed using logistic regression.The polymorphisms TLR5 (rs5744174) and IL12B (rs6887695) were associated with risk of CD, and TLR1 (rs4833095) and IL18 (rs187238) were associated with risk of both CD and UC (p<0.05). After Bonferroni correction for multiple testing, the homozygous variant genotype of TLR1 743 T>C (rs4833095) was associated with increased risk CD (OR: 3.15, 95% CI: 1.59-6.26, p = 0.02) and CD and UC combined (OR: 2.96, 95% CI: 1.64-5.32, p = 0.005).Our results suggest that genetically determined high activity of TLR1 and TLR5 was associated with increased risk of both CD and UC and CD, respectively. This supports that the host microbial composition or environmental factors in the gut are involved in risk of IBD. Furthermore, genetically determined high activity of the IL-23/IL-17 pathway was associated with increased risk of CD and UC. Overall, our results support that genetically determined high inflammatory response was associated with increased risk of both CD and UC.

PubMed | Hvidovre Hospital, University of Aarhus, Koge Hospital, Helmholtz Center Munich and 10 more.
Type: | Journal: The pharmacogenomics journal | Year: 2017

Anti-tumour necrosis factor- (TNF-) is used for treatment of severe cases of inflammatory bowel diseases (IBD), including Crohns disease (CD) and ulcerative colitis (UC). However, one-third of the patients do not respond to the treatment. A recent study indicated that genetically determined high activity of pro-inflammatory cytokines, including interleukin-1 (IL-1), IL-6 and interferon gamma (IFN-), are associated with non-response to anti-TNF therapy. Using a candidate gene approach, 21 functional single-nucleotide polymorphisms (SNPs) in 14 genes in the Toll-like receptors, the inflammasome and the IFNG pathways were assessed in 482 and 256 prior anti-TNF nave Danish patients with CD and UC, respectively. The results were analysed using logistic regression (adjusted for age and gender). Eight functional SNPs were associated with anti-TNF response either among patients with CD (TLR5 (rs5744174) and IFNGR2 (rs8126756)), UC (IL12B (rs3212217), IL18 (rs1946518), IFNGR1 (rs2234711), TBX21 (rs17250932) and JAK2 (rs12343867)) or in the combined cohort of patient with CD and UC (IBD) (NLRP3 (rs10754558), IL12B (rs3212217) and IFNGR1 (rs2234711)) (P<0.05). Only the association with heterozygous genotype of IL12B (rs3212217) (OR: 0.24, 95% CI: 0.11-0.53, P=0.008) among patients with UC withstood Bonferroni correction for multiple testing. In conclusion, Our results suggest that SNPs associated with genetically determined high activity of TLR5 among patients with CD and genetically determined high IL-12 and IL-18 levels among patients with UC were associated with non-response. Further studies will evaluate whether these genes may help stratifying patients according to the expected response to anti-TNF treatment.The Pharmacogenomics Journal advance online publication, 31 January 2017; doi:10.1038/tpj.2016.84.

Diederichsen A.C.P.,University of Southern Denmark | Mahabadi A.-A.,University of Duisburg - Essen | Gerke O.,University of Southern Denmark | Lehmann N.,University of Duisburg - Essen | And 8 more authors.
Atherosclerosis | Year: 2015

Objectives: The European HeartScore has traditionally differentiated between low and high-risk countries. Until 2012 Germany and Denmark were considered to be high-risk countries but have now been defined as low-risk countries. In this survey we aim to address the consequences of this downgrading. Methods: A screening of 3932 randomly selected (mean age 56 years, 46% male) individuals from Germany and Denmark free of cardiovascular disease was performed. Traditional risk factors were determined, and the HeartScore was measured using both the low-risk and the high-risk country models. A non-contrast Cardiac-CT scan was performed to detect coronary artery calcification (CAC). Results: Agreement of HeartScore risk groups with CAC groups was poor, but higher when applying the algorithm for the low-risk compared to the high-risk country model (agreement rate: 77% versus 63%, and weighted Kappa: 0.22 versus 0.15). However, the number of subjects with severe coronary calcification (CAC score ≥400) increased in the low and intermediate HeartScore risk group from 78 to 147 participants (from 2.7 % to 4.2 %, p=0.001), when estimating the risk based on the algorithm for low-risk countries. Conclusion: As a consequence of the reclassification of Germany and Denmark as low-risk countries more people with severe atherosclerosis will be classified as having a low or intermediate risk of fatal cardiovascular disease. © 2015 Elsevier Ireland Ltd.

PubMed | University of Southern Denmark, Sydvestjysk Hospital and Slagelse Hospital
Type: Journal Article | Journal: Molecular & cellular proteomics : MCP | Year: 2015

Metastasis is the main cause of cancer-related deaths and remains the most significant challenge to management of the disease. Metastases are established through a complex multistep process involving intracellular signaling pathways. To gain insight to proteins central to specific steps in metastasis formation, we used a metastasis cell line model that allows investigation of extravasation and colonization of circulating cancer cells to lungs in mice. Using stable isotopic labeling by amino acids in cell culture and subcellular fractionation, the nuclear, cytosol, and mitochondria proteomes were analyzed by LC-MS/MS, identifying a number of proteins that exhibited altered expression in isogenic metastatic versus nonmetastatic cancer cell lines, including NADH-cytochrome b5 reductase 3 (CYB5R3), l-lactate dehydrogenase A (LDHA), Niemann-pick c1 protein (NPC1), and nucleolar RNA helicase 2 (NRH2). The altered expression levels were validated at the protein and transcriptional levels, and analysis of breast cancer biopsies from two cohorts of patients demonstrated a significant correlation between high CYB5R3 expression and poor disease-free and overall survival in patients with estrogen receptor-negative tumors (DFS: p = .02, OS: p = .04). CYB5R3 gene knock-down using siRNA in metastasizing cells led to significantly decreased tumor burden in lungs when injected intravenously in immunodeficient mice. The cellular effects of CYB5R3 knock-down showed signaling alterations associated with extravasation, TGF and HIF pathways, and apoptosis. The decreased apoptosis of CYB5R3 knock-down metastatic cancer cell lines was confirmed in functional assays. Our study reveals a central role of CYB5R3 in extravasation/colonization of cancer cells and demonstrates the ability of our quantitative, comparative proteomic approach to identify key proteins of specific important biological processes that may also prove useful as potential biomarkers of clinical relevance. MS data are available via ProteomeXchange with identifier PXD001391.

Kampmann U.,Aarhus University Hospital | Mosekilde L.,Aarhus University Hospital | Juhl C.,Sydvestjysk Hospital | Moller N.,Aarhus University Hospital | And 4 more authors.
Metabolism: Clinical and Experimental | Year: 2014

Objectives Vitamin D insufficiency is common in subjects with type 2 diabetes. Observational studies suggest that vitamin D plays a role in the pathogenesis of type 2 diabetes. However, results of intervention studies have been inconsistent. We investigated the effects of improving vitamin D status on insulin sensitivity, insulin secretion, and inflammatory markers in patients with type 2 diabetes. Materials/methods A double blind, randomized, placebo controlled trial was conducted. Sixteen patients with type 2 diabetes and hypovitaminosis D were recruited. Eight patients received colecalciferol and (280 μg daily for 2 weeks, 140 μg daily for 10 weeks) and 8 patients received identical placebo tablets for 12 weeks. Before and after intervention, patients underwent IVGTT, hyperinsulinemic euglycemic clamp, assessment of baseline high-frequency insulin pulsatility, glucose-entrained insulin pulsatility, DXA scans, 24-hour-ambulatory blood pressure monitorings, and fasting blood samples. Results Serum-25(OH) vitamin D and serum-1,25(OH) 2 vitamin D increased significantly after 12 weeks in the intervention group (p = 0.01, p = 0.004). Serum-25(OH) vitamin D was also significantly higher in the vitamin D group compared to the placebo group (p = 0.02) after intervention. Although no significant changes in insulin sensitivity, inflammation, blood pressure, lipid profile, or HbA1c were found, we observed borderline (p between 0.05 and 0.10) improvements of insulin secretion, in terms of c-peptide levels, first phase incremental AUC insulin and insulin secretory burst mass. Conclusions Improvement in vitamin D status does not improve insulin resistance, blood pressure, inflammation or HbA1c, but might increase insulin secretion in patients with established type 2 diabetes. © 2014 Elsevier Inc.

Juhl C.B.,Sydvestjysk Hospital | Juhl C.B.,University of Southern Denmark | Bradley U.,Royal Victoria Hospital | Holst J.J.,Copenhagen University | And 3 more authors.
Diabetic Medicine | Year: 2014

Aims: To explore insulin sensitivity and insulin secretion in people with latent autoimmune diabetes in adulthood (LADA) compared with that in people with Type 2 diabetes. Methods: A total of 12 people with LADA, defined as glutamic acid decarboxylase (GAD) antibody positivity and > 1 year of insulin independency (group A) were age-matched pairwise to people with Type 2 diabetes (group B) and to six people with Type 2 diabetes of similar age and BMI (group C). β-cell function (first-phase insulin secretion and assessment of insulin pulsatility), insulin sensitivity (hyperinsulinemic-euglycemic clamp) and metabolic response during a mixed meal were studied. Results: Both first-phase insulin secretion and insulin release during the meal were greater (P = 0.05 and P = 0.009, respectively) in Type 2 diabetes as compared with LADA; these differences were lost on adjustment for BMI (group C) and could be explained by BMI alone in a multivariate analysis. Neither insulin pulsatility, incretin secretion nor insulin sensitivity differed among the groups. Conclusions: We found no evidence that LADA and Type 2 diabetes were distinct disease entities beyond the differences explained by BMI. © 2014 Diabetes UK.

Bar-Shalom D.,University of Southern Denmark | Poulsen M.K.,University of Southern Denmark | Rasmussen L.M.,University of Southern Denmark | Diederichsen A.C.P.,University of Southern Denmark | And 3 more authors.
Diabetes and Vascular Disease Research | Year: 2014

Recently, copeptin was found associated with cardiovascular disease (CVD) and all-cause mortality in type 2 diabetes mellitus (T2DM) patients treated in primary care. This study aimed to evaluate whether plasma copeptin correlated to CVD in asymptomatic T2DM patients intensively investigated for sub-clinical CVD. A total of 302 T2DM patients referred to the Diabetes Clinic at Odense University Hospital, Denmark, entered the study. None of the patients had known or suspected CVD. As a control group, 30 healthy adults were recruited from the DanRisk study - a random sample of middle-aged Danes. A variety of clinical investigations were performed, including blood pressure measurements, carotid intima media thickness evaluation and myocardial perfusion scintigraphy. Blood sample analyses included copeptin measurements. Median plasma copeptin concentrations were similar in the T2DM group and the control group. However, men had significantly higher copeptin concentrations than women in the T2DM group (p < 0.001), and also, T2DM men had significantly higher copeptin concentrations than men without T2DM (p = 0.038). Copeptin correlated significantly with a number of variables, but the strongest correlation was with creatinine (R = 0.432, p < 0.001), and in multiple regression analysis, only this correlation remained significant. When association with clinical scores were investigated, plasma copeptin remained significantly associated with peripheral arterial disease (PAD) (p = 0.01). We found correlations between creatinine, copeptin levels and PAD in T2DM patients, and if confirmed, plasma copeptin combined with plasma creatinine could be a candidate for PAD screening in T2DM patients. © 2014 The Author(s).

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