Haderslev Hospital

Haderslev, Denmark

Haderslev Hospital

Haderslev, Denmark
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Theilade J.,Copenhagen University | Kanters J.,Copenhagen University | Kanters J.,Gentofte University Hospital | Kanters J.,Aarhus University Hospital | And 10 more authors.
Cardiology (Switzerland) | Year: 2013

Objectives: We assessed the outcome of cascade screening of families with congenital long QT syndrome (LQTS) in Danish heart centers. Methods: Affected family members were identified through systematic family screening. Results: In total, 228 affected relatives were identified from 90 families. A disease-causing mutation useful for presymptomatic genetic testing was found in 82% of probands. Two-thirds of affected relatives fulfilled electrocardiographic criteria for the diagnosis, whereas diagnosis was based on genetic findings in only one-third. The majority of affected relatives were asymptomatic. Symptomatic relatives and probands most often presented with syncope, followed by aborted cardiac arrest and sudden cardiac death. A serious cardiac event (SCE, such as syncope, aborted cardiac arrest or cardiac arrest) was reported by 32% of affected relatives and 87% of probands (p < 0.0001). Fifty-two percent of affected relatives were on β-blockers and 11% had an implantable cardioverter defibrillator (ICD), as compared to 88 and 49% of probands (p < 0.0001). Appropriate ICD therapy was given to 13% of affected relatives and to 27% of probands (p = 0.1). Conclusions: Clinically driven cascade screening of Danish LQTS families identified 2-3 affected relatives per proband. Affected relatives had milder disease courses, but SCEs in a subset strongly support screening. Danish cardiologists have adopted cascade screening of LQTS families according to specific Danish guidelines. © 2013 S. Karger AG, Basel.


Nielsen J.C.,Aarhus University Hospital | Thomsen P.E.B.,Copenhagen University | Hojberg S.,Bispebjerg Hospital | Moller M.,University of Southern Denmark | And 14 more authors.
European Heart Journal | Year: 2011

Aim s In patients with sick sinus syndrome, bradycardia can be treated with a single-lead pacemaker or a dual-chamber pacemaker. Previous trials have revealed that pacing modes preserving atrio-ventricular synchrony are superior to single-lead ventricular pacing, but it remains unclear if there is any difference between single-lead atrial pacing (AAIR) and dual-chamber pacing (DDDR).Methods and resultsWe randomly assigned 1415 patients referred for first pacemaker implantation to AAIR (n 707) or DDDR (n 708) pacing and followed them for a mean of 5.4 ± 2.6 years. The primary outcome was death from any cause. Secondary outcomes included paroxysmal and chronic atrial fibrillation, stroke, heart failure, and need for pacemaker reoperation. In the AAIR group, 209 patients (29.6) died during follow-up vs. 193 patients (27.3) in the DDDR group, hazard ratio (HR) 1.06, 95 confidence interval (CI) 0.881.29, P 0.53. Paroxysmal atrial fibrillation was observed in 201 patients (28.4) in the AAIR group vs. 163 patients (23.0) in the DDDR group, HR 1.27, 95 CI 1.031.56, P 0.024. A total of 240 patients underwent one or more pacemaker reoperations during follow-up, 156 (22.1) in the AAIR group vs. 84 (11.9) in the DDDR group (HR 1.99, 95 CI 1.532.59, P < 0.001). The incidence of chronic atrial fibrillation, stroke, and heart failure did not differ between treatment groups.Conclusion In patients with sick sinus syndrome, there is no statistically significant difference in death from any cause between AAIR pacing and DDDR pacing. AAIR pacing is associated with a higher incidence of paroxysmal atrial fibrillation and a two-fold increased risk of pacemaker reoperation. These findings support the routine use of DDDR pacing in these patients. Clinical Trial Registration: URL http://www.clinicaltrials.gov. Unique identifier: NCT00236158. © 2010 The Author.


Stauffer Larsen T.,University of Southern Denmark | Iversen K.F.,University of Southern Denmark | Mathiasen A.B.,Rigshospitalet | Marcher C.,University of Southern Denmark | And 9 more authors.
Leukemia Research | Year: 2013

Within recent years data has accumulated demonstrating the efficacy of recombinant interferon alpha2 (rIFN-alpha2) in the treatment of chronic myeloproliferative neoplasms (MPNs). We report on clinical and molecular data in the largest cohort of JAK2 V617F mutant MPN Danish patients (n= 102) being treated long-term with rIFN-alpha2 (rIFN-alpha2a and rIFN-alpha2b in a non-clinical trial setting. The median follow-up was 42 months. We substantiate the capacity of rIFN-alpha2 to induce complete hematologic remissions (ET 95%, PV 68%) and molecular response. In total 76 patients (74.5%) had a decline in JAK2 V617F allele burden with a median reduction from baseline of 59% (95% c.i. 50-73%, range 3-99%). A decline in JAK2 V617F allele burden was recorded in both ET (median 24-10% (95% c.i.: 8-16%), and PV (median 59-35% (95% c.i.: 17-33%). Patients with the lowest pre-treatment JAK2 V617F allele burdens tend to achieve the most favourable responses on long term treatment with rIFN-alpha2. Eleven patients (10%) had deep molecular remissions with ≤2% JAK2 V617F mutant DNA. Finally, long term treatment with rIFN-alpha2 was associated with a very low thrombosis rate. Our observations are supportive of the concept of early up-front treatment with rIFN-alpha2. © 2013 Elsevier Ltd.


Nielsen J.C.,Aarhus University Hospital | Thomsen P.E.B.,Copenhagen University | Hojberg S.,Bispebjerg Hospital | Moller M.,University of Southern Denmark | And 14 more authors.
Europace | Year: 2012

Aims: In the recently published DANPACE trial, incidence of atrial fibrillation (AF) was significantly higher with single-lead atrial (AAIR) pacing than with dual-chamber (DDDR) pacing. The present analysis aimed to evaluate the importance of baseline PQ-interval and percentage of ventricular pacing (VP) on AF. Methods and results: We analysed data on AF during follow-up in 1415 patients included in the DANPACE trial. In a subgroup of 650 patients with DDDR pacemaker, we studied whether VP, baseline PQ-interval, and programmed atrio-ventricular interval (AVI) was associated with AF burden measured as time in mode-switch (MS) detected by the pacemaker. In the entire DANPACE study population, the incidence of AF was significantly higher in patients with baseline PQ-interval >180 ms (P< 0.001). Among 650 patients with DDDR pacemaker, telemetry data were available for 1.337 ± 786 days, %VP was 66 ± 33%, AF was detected at planned follow-up in 160 patients (24.6%), MS occurred in 422 patients (64.9%), and AF burden was marginally higher with baseline PQ-interval >180 ms (P = 0.028). No significant association was detected between %VP and %MS (Spearmans ρ 0.056, P = 0.154). %MS was not different between minimal-paced programmed AVI ≤ 100 and >100 ms (median value), respectively (P = 0.60). Conclusions: The present study indicates that a longer baseline PQ-interval is associated with an increased risk of AF in patients with sick sinus syndrome. Atrial fibrillation burden is not associated with the percentage of VP or the length of the programmed AVI. © 2011 The Author.


Riahi S.,University of Aalborg | Nielsen J.C.,Aarhus University Hospital | Hjortshoj S.,University of Aalborg | Thomsen P.E.B.,Copenhagen University | And 14 more authors.
Europace | Year: 2012

AimsPrevious studies indicate that ventricular pacing may precipitate heart failure (HF). We investigated occurrence of HF during long-term follow-up among patients with sick sinus syndrome (SSS) randomized to AAIR or DDDR pacing. Furthermore, we investigated effects of percentage of ventricular pacing (VP) and pacing site in the ventricle.Methods and resultsWe analysed data from 1415 patients randomized to AAIR (n 707) or DDDR pacing (n 708). Ventricular pacing leads were recorded as located in either an apical or a non-apical position. The VP and HF hospitalizations were recorded during follow-up. Patients were classified with new HF, if in New York Heart Association (NYHA) functional class IV or if presence of <2 of: oedema; dyspnoea; NYHA functional class III. Mean follow-up was 5.4 ± 2.4 years. Heart failure hospitalizations did not differ between groups. In the AAIR group, 170 of the 707 (26) patients developed HF vs. 169 of the 708 (26) patients in the DDDR group, hazard rate ratio (HR) 1.00, 95 confidence interval (CI) 0.791.22, P 0.87. In DDDR patients, 146 of the 512 patients (29) with ventricular leads in an apical position developed HF vs. 28 of the 161 patients (17) with the leads in a non-apical position, HR 0.67, CI 0.451.00, P 0.05. After adjustments this difference was non-significant. The incidence of HF was not associated with VP (P 0.57).ConclusionIn patients with SSS, HF was not associated with pacing mode, VP, or ventricular lead localization. This suggests that DDDR pacing is safe in patients with SSS without precipitating HF. © The Author 2012.


Kristensen L.,University of Southern Denmark | Kristensen T.,University of Southern Denmark | Abildgaard N.,University of Southern Denmark | Thomassen M.,University of Southern Denmark | And 3 more authors.
Leukemia Research | Year: 2015

Chronic lymphocytic leukemia (CLL) is the most common leukemia among adults in the Western world. Autophagy is a highly conserved process in eukaryotic cells. In CLL autophagy is involved in mediating the effect of chemotherapy but the role of autophagy in CLL pathogenesis remains unknown.In the present study, we used real-time RT-PCR to analyze expression of the PIK3C3, PIK3R4, and BECN1 genes. These genes encode the components of the PI3K core complex, which is central to initiation of autophagy. A consecutive series of 149 well-characterized CLL cases from Region of Southern Denmark were included in the study. All three genes were observed to be independent markers of prognosis in CLL with high expression being associated with more aggressive disease. With this clear association with outcome in CLL, these genes thereby represent promising candidates for future functional studies on the role of autophagy in CLL, and they may further represent targets of treatment. © 2015 Elsevier Ltd.


PubMed | University of Southern Denmark, Haderslev Hospital and Hospital of Southwestern Jutland
Type: Journal Article | Journal: Leukemia research | Year: 2015

Chronic lymphocytic leukemia (CLL) is the most common leukemia among adults in the Western world. Autophagy is a highly conserved process in eukaryotic cells. In CLL autophagy is involved in mediating the effect of chemotherapy but the role of autophagy in CLL pathogenesis remains unknown. In the present study, we used real-time RT-PCR to analyze expression of the PIK3C3, PIK3R4, and BECN1 genes. These genes encode the components of the PI3K core complex, which is central to initiation of autophagy. A consecutive series of 149 well-characterized CLL cases from Region of Southern Denmark were included in the study. All three genes were observed to be independent markers of prognosis in CLL with high expression being associated with more aggressive disease. With this clear association with outcome in CLL, these genes thereby represent promising candidates for future functional studies on the role of autophagy in CLL, and they may further represent targets of treatment.


PubMed | Haderslev Hospital, Copenhagen University, Roskilde Hospital, Esbjerg Hospital and 5 more.
Type: | Journal: Clinical epidemiology | Year: 2016

The Danish National Lymphoma Registry (LYFO) was established in order to monitor and improve the diagnostic evaluation and the quality of treatment of all lymphoma patients in Denmark.The LYFO database was established in 1982 as a seminational database including all lymphoma patients referred to the departments of hematology. The database became nationwide on January 1, 2000.The main variables include both clinical and paraclinical variables as well as details of treatment and treatment evaluation. Up to four forms are completed for each patient: a primary registration form, a treatment form, a relapse form, and a follow-up form. Variables are used to calculate six result quality indicators (mortality 30 and 180 days after diagnosis, response to first-line treatment, and survival estimates 1, 3, and 5 years after the time of diagnosis), and three process quality indicators (time from diagnosis until the start of treatment, the presence of relevant diagnostic markers, and inclusion rate in clinical protocols).Approximately 23,000 patients were registered in the period 1982-2014 with a median age of 65 years (range: 16-100 years) and a male/female ratio of 1.23:1. Patients can be registered with any of 42 different subtypes according to the World Health Organization classifications.LYFO is a nationwide database for all lymphoma patients in Denmark and includes detailed information. This information is used for both epidemiological research and clinical follow-up as well as for administrative purposes.


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.


Preiss B.S.,University of Southern Denmark | Bergman O.J.,University of Southern Denmark | Bergman O.J.,Esbjerg Hospital | Friis L.S.,University of Southern Denmark | And 8 more authors.
Cancer Genetics and Cytogenetics | Year: 2010

During a 15-year period, 161 adult patients were diagnosed with secondary acute myeloid leukemia (s-AML) in the region of Southern Denmark. In 73 patients, the AML diagnosis was preceded by myelodysplastic syndrome (MDS-AML), in 31 patients by an antecedent hematologic disease, and in 57 patients by treatment with chemotherapy and/or irradiation (t-AML). Cytogenetic analysis was carried out in 93%, of which 61% had clonal chromosome aberrations. MDS-AML correlated to a normal karyotype (P < 0.001). t-AML correlated to abnormal clones with numerical and structural aberrations (P = 0.03), five or more unrelated aberrations (P = 0.03), marker chromosomes (P = 0.006), abnormal mitoses only (P = 0.01), female sex (P < 0.001), and -7 (P = 0.006). Centromeric breakage correlated to a complex karyotype (P = 0.01). The frequencies of aberrations in s-AML patients were compared with an age-matched group of de novo AML patients diagnosed in the same area and period. In this comparison, s-AML only correlated to -7 (P = 0.02). In 42 patients, we found that MDS patients with an abnormal karyotype were more likely to show cytogenetic evolution during progression to AML than MDS patients with a normal karyotype (P = 0.01). We conclude that population-based cytogenetic studies of adult s-AML and age- and sex-matched de novo AML show comparable distributions of chromosome abnormalities. © 2010 Elsevier Inc.

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