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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.


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).


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.


Nielsen M.L.,University of Southern Denmark | Pareek M.,University of Southern Denmark | Gerke O.,University of Southern Denmark | Diederichsen S.Z.,University of Southern Denmark | And 7 more authors.
Journal of Human Hypertension | Year: 2015

We conducted a 1:2 matched case-control study in order to evaluate whether the prevalence of coronary artery calcium (CAC) and electrocardiographic left ventricular hypertrophy (LVH) or strain was higher in patients with uncontrolled hypertension than in subjects from the general population, and evaluate the association between CAC and LVH in patients with uncontrolled hypertension. Cases were patients with uncontrolled hypertension, whereas the controls were random individuals from the general population without cardiovascular disease. CAC score was assessed using a non-contrast computed tomographic scan. LVH was evaluated using the Sokolow-Lyon voltage combination and Cornell voltage-duration product, respectively. Associations between CAC, LVH and traditional cardiovascular risk factors were tested by means of ordinal, conditional and classic binary logistic regression models. We found that uncontrolled hypertension was independently associated with both an ordinal CAC score category (odds ratio (OR) 3.9 (95% CI, 1.6-9.1), P=0.002), the presence of CAC score>99 (OR 4.5 (95% CI, 1.4-14.7), P=0.01) and electrocardiographic LVH (OR 10.1 (95% CI, 3.4-30.2), P<0.001) on both univariate and multivariable analyses. There was, however, no correlation between CAC and LVH. The lack of an association between CAC and LVH suggests that they are markers of different complications of hypertension and may have independent predictive values. Patients with both CAC and LVH may be at higher risk than those in whom only one of these markers is present. © 2015 Macmillan Publishers Limited All rights reserved.


Lindberg S.O.,Roskilde Hospital | la Cour J.L.,Herlev Hospital | Folkestad L.,Sydvestjysk Hospital | Hallas P.,Juliane Marie Centret | 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.

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