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Perings C.,Ruhr University Bochum | Rudolf Bauer W.,University of Wrzburg | Bondke H.-J.,Charit Universittsmedizin Berlin | Mewis C.,Saarland University | And 8 more authors.
Europace | Year: 2011

Aims Intracardiac electrograms (IEGMs) recorded by implantable cardioverter-defibrillators (ICDs) are essential for arrhythmia diagnosis and ICD therapy assessment. Short IEGM snapshots showing 310 s before arrhythmia detection were added to the Biotronik Home Monitoring system in 2005 as the first-generation IEGM Online. The RIONI study tested the primary hypothesis that experts' ratings regarding the appropriateness of ICD therapy based on IEGM Online and on standard 30 s IEGM differ in <10 of arrhythmia events. Methods and results A total of 619 ICD patients were enrolled and followed for 1 year. According to a predefined procedure, 210 events recorded by the ICDs were selected for evaluation. Three expert board members rated the appropriateness of ICD therapy and classified the underlying arrhythmia using coded IEGM Online and standard IEGM to avoid bias. The average duration of IEGM Online was 4.4 ± 1.5 s. According to standard IEGM, the underlying arrhythmia was ventricular in 135 episodes (64.3), supraventricular in 53 episodes (25.2), oversensing in 17 episodes (8.1), and uncertain in 5 episodes (2.4). The expert boards rating diverged between determinable IEGM Online tracings and standard IEGM in 4.6 of episodes regarding the appropriateness of ICD therapy (95 CI up to 8.0) and in 6.6 of episodes regarding arrhythmia classification (95 CI up to 10.5). Conclusion By enabling accurate evaluation of the appropriateness of ICD therapy and the underlying arrhythmia, the first-generation IEGM Online provided a clinically effective basis for timely interventions and for optimized patient management schemes, which was comparable with current IEGM recordings. © 2010 The Author.


Lip G.Y.H.,University of Birmingham | Ponikowski P.,Wroclaw Medical University | Andreotti F.,Catholic University Hospital | Anker S.D.,Charit Universittsmedizin Berlin | And 7 more authors.
European Journal of Heart Failure | Year: 2012

Chronic heart failure (HF) with either reduced or preserved ejection fraction is common and remains an extremely serious disorder with a high mortality and morbidity. Many complications related to HF can be related to thrombosis. Epidemiological and pathophysiological data also link HF to an increased risk of thrombosis, leading to the clinical consequences of sudden death, stroke, systemic thrombo-embolism, and/or venous thrombo-embolism. This consensus document of the Heart Failure Association (EHFA) of the European Society of Cardiology (ESC) and the ESC Working Group on Thrombosis reviews the published evidence and summarizes 'best practice', and puts forward consensus statements that may help to define evidence gaps and assist management decisions in everyday clinical practice. In HF patients with atrial fibrillation, oral anticoagulation is recommended, and the CHA 2DS 2-VASc and HAS-BLED scores should be used to determine the likely riskbenefit ratio (thrombo-embolism prevention vs. risk of bleeding) of oral anticoagulation. In HF patients with reduced left ventricular ejection fraction who are in sinus rhythm there is no evidence of an overall benefit of vitamin K antagonists (e.g. warfarin) on mortality, with risk of major bleeding. Despite the potential for a reduction in ischaemic stroke, there is currently no compelling reason to use warfarin routinely for these patients. Risk factors associated with increased risk of thrombo-embolic events should be identified and decisions regarding use of anticoagulation individualized. Patient values and preferences are important determinants when balancing the risk of thrombo-embolism against bleeding risk. New oral anticoagulants that offer a different riskbenefit profile compared with warfarin may appear as an attractive therapeutic option, but this would need to be confirmed in clinical trials. © 2012 The Author.


Gutzwiller F.S.,University of Basel | Schwenkglenks M.,University of Basel | Schwenkglenks M.,University Zrich | Blank P.R.,University of Basel | And 8 more authors.
European Journal of Heart Failure | Year: 2012

Aims The purpose of this study was to evaluate the cost-effectiveness of iron repletion using intravenous (i.v.) ferric carboxymaltose (FCM) in chronic heart failure (CHF) patients with iron deficiency with or without anaemia. Cost-effectiveness was studied from the perspective of the National Health Service in the UK. Methods and Results A model-based cost-effectiveness analysis was used to compare iron repletion with FCM with no iron treatment. Using data from the FAIR-HF trial and publicly available sources and publications, per patient costs and clinical effectiveness of FCM were estimated compared with placebo. Cost assessment was based on study drug and administration costs, cost of CHF treatment, and hospital length of stay. The incremental cost-effectiveness ratio (ICER) of FCM use was expressed as cost per quality-adjusted life year (QALY) gained, and sensitivity analyses were performed on the base case. The time horizon of the analysis was 24 weeks. Mean QALYs were higher in the FCM arm (difference 0.037 QALYs; bootstrap-based 95 confidence interval 0.0170.060). The ICER of FCM compared with placebo was €4414 per QALY gained for the FAIR-HF dosing regimen. Sensitivity analyses confirmed the base case result to be robust. Conclusion From the UK payers' perspective, managing iron deficiency in CHF patients using i.v. FCM was cost-effective in this analysis. The base case ICER was clearly below the threshold of €22 200€33 300/QALY gained (£20 000£30 000) typically used by the UK National Institute for Health and Clinical Excellence and proved to be robust in sensitivity analysis. Improved symptoms and better quality of life contributed to this result. © 2012 The Author.


Schaefers A.T.U.,Bielefeld University | Grafen K.,Bielefeld University | Teuchert-Noodt G.,Bielefeld University | Winter Y.,Bielefeld University | And 2 more authors.
Neural Plasticity | Year: 2010

Hippocampal cell proliferation is strongly increased and synaptic turnover decreased after rearing under social and physical deprivation in gerbils (Meriones unguiculatus). We examined if a similar epigenetic effect of rearing environment on adult neuroplastic responses can be found in mice (Mus musculus). We examined synaptic turnover rates in the dentate gyrus, CA3, CA1, subiculum, and entorhinal cortex. No direct effects of deprived rearing on rates of synaptic turnover were found in any of the studied regions. However, adult wheel running had the effect of leveling layer-specific differences in synaptic remodeling in the dentate gyrus, CA3, and CA1, but not in the entorhinal cortex and subiculum of animals of both rearing treatments. Epigenetic effects during juvenile development affected adult neural plasticity in mice, but seemed to be less pronounced than in gerbils. Copyright © 2010 Andrea T. U. Schaefers et al.


Hamdan A.,Deutsches Herzzentrum Berlin | Hamdan A.,Tel Aviv University | Asbach P.,Charit Universittsmedizin Berlin | Wellnhofer E.,Deutsches Herzzentrum Berlin | And 6 more authors.
JACC: Cardiovascular Imaging | Year: 2011

Objectives: The purpose of the present study was to directly compare the diagnostic accuracy of magnetic resonance imaging (MRI) and multislice computed tomography (CT) for the detection of coronary artery stenosis. Background Both imaging modalities have emerged as potential noninvasive coronary imaging modalities; however, CTunlike MRIexposes patients to radiation and iodinated contrast agent. Methods One hundred twenty consecutive patients with suspected or known coronary artery disease prospectively underwent 32-channel 3.0-T MRI and 64-slice CT before elective X-ray angiography. The diagnostic accuracy of the 2 modalities for detecting significant coronary stenosis (<50% luminal diameter stenosis) in segments <1.5 mm diameter was compared with quantitative invasive coronary angiography as the reference standard. Results In the patient-based analysis MRI and CT angiography showed similar diagnostic accuracy of 83% (95% confidence interval [CI]: 75 to 87) versus 87% (95% CI: 80 to 92), p = 0.38; sensitivity of 87% (95% CI: 76 to 93) versus 90% (95% CI: 80 to 95), p = 0.16; and specificity of 77% (95% CI: 63 to 87) versus 83% (95% CI: 70 to 91), p = 0.06, respectively. All cases of left main or 3-vessel disease were correctly diagnosed by MRI and CT angiography. In the patient-based analysis MRI and CT angiography were similar in their ability to identify patients who subsequently underwent revascularization: the area under the receiver-operator characteristic curve was 0.78 (95% CI: 0.69 to 0.87) for MRI and 0.82 (95% CI: 0.74 to 0.90) for CT angiography. Conclusions Thirty-two channel 3.0-T MRI and 64-slice CT angiography similarly identify significant coronary stenosis in patients with suspected or known coronary artery disease scheduled for elective coronary angiography. However, CT angiography showed a favorable trend toward higher diagnostic performance. © 2011 American College of Cardiology Foundation.


Beinder E.,Charit Universittsmedizin Berlin
Zeitschrift fur Geburtshilfe und Neonatologie | Year: 2011

The incidence of premature births is not decreasing in developed countries, but rather shows a tendency to increase. This rise is primarily due to an increase in the number iatrogenic late preterm births at a gestational age between 34+0 and 36+6 weeks. Late preterm births account for up to 80% of all preterm births and these newborns have higher morbidity and mortality rates and a higher rate in neurodevelopmental long-term impairment in comparison to term infants. In order to reduce iatrogenic preterm birth, it is necessary to apply standardised treatment algorithms especially in cases of mild preeclampsia and intrauterine growth restriction. © Georg Thieme Verlag KG Stuttgart New York.


Budde K.,Charit Universittsmedizin Berlin | Gaedeke J.,Charit Universittsmedizin Berlin
American Journal of Kidney Diseases | Year: 2012

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder promoting the development of benign tumors in multiple organ systems, including the skin, brain, and kidneys. In contrast to asymptomatic spontaneous angiomyolipomas, angiomyolipomas in patients with TSC are mostly bilateral and are accompanied by other typical clinical features of TSC. Kidney angiomyolipomas are benign tumors composed of blood vessels, adipose tissue, and smooth muscle and are associated with spontaneous bleeding and potential life-threatening hemorrhage if >4 cm. Current treatment options for angiomyolipoma are focused on conserving kidney function and limiting potentially fatal hemorrhage. TSC is caused by mutations in either TSC1 or TSC2 suppressor genes, resulting in increased mammalian target of rapamycin (mTOR) activity. Preclinical studies have shown the efficacy of mTOR inhibitors in inhibiting the growth of patient-derived cell lines and suppressing tumors in animal models of TSC. In the clinical setting, mTOR inhibitors have shown promising efficacy in patients with TSC-associated angiomyolipomas and subependymal giant cell astrocytomas. This review explores the diagnosis and current management of TSC-associated angiomyolipomas, the relevance of the mTOR pathway in the pathogenesis of TSC, and the potential promise of mTOR-inhibitor therapy as a systemic therapeutic approach to treat the underlying cause of TSC. © 2012 National Kidney Foundation, Inc.


Khnen P.,Charit Universittsmedizin Berlin | Marquard J.,University Childrens Hospital | Ernert A.,Charit Universittsmedizin Berlin | Meissner T.,University Childrens Hospital | And 3 more authors.
Hormone Research in Paediatrics | Year: 2012

Background: Medical treatment is a substantial therapeutic measure to achieve glycemic control and prevent hypoglycemic brain damage without surgery in patients with congenital hyperinsulinism (CHI). However, only few drugs are available and even fewer are approved as a medical therapy to maintain normal blood glucose levels. The established therapies are demanding for caregivers and complicated by different side effects such as gastrointestinal symptoms, hypertrichosis, and obesity. Therefore, it is important to develop new strategies to improve blood glucose control. Methods: We report the use of the very-long-acting somatostatin analogue lanreotide autogel in 6 patients with CHI over a mean duration of 40.8 months. Blood glucose levels before and after the start and dosage titration of lanreotide in these patients are compared. Results: In 3 of 6 patients, switching to lanreotide raised mean blood glucose levels and reduced individually as well as overall the risk for hypoglycemic episodes (odds ratio 0.38) significantly. Conclusion: Lanreotide autogel can be used as an alternative pharmacological treatment and may be beneficial in conservatively treated patients with CHI. Copyright © 2012 S. Karger AG, Basel.


Meisel A.,Neurocure Clinical Research Center | Meisel C.,Charit Universittsmedizin Berlin | Harms H.,Neurocure Clinical Research Center | Hartmann O.,Thermo Fisher Scientific | Ulm L.,Neurocure Clinical Research Center
Cerebrovascular Diseases | Year: 2012

About one third of early deaths and poor outcomes after acute stroke are caused by potentially preventable stroke-associated complications, especially infections. Early identification of patients at high risk of infections and poor prognosis with biomarkers might help to initiate adequate therapies and guide treatment decisions. Acute injury of the central nervous system, including stroke, disturbs the normally well-balanced interplay between the sympathetic nervous system and the immune system, thereby impairing the antibacterial immune response in stroke patients. Changes in immune and stress markers, for example a reduction in HLA-DR expression on monocytes or an increase in serum catecholamine levels, occur very early after stroke onset, explain the high susceptibility of stroke patients to bacterial infections, and are predictive of infectious complications occurring up to 2 weeks after stroke. Outcome prediction is of utmost importance for decision-making in stroke units as well as in neurological intensive care units. However, to date the accuracy of outcome prediction by physicians and clinical scoring systems is only moderate. So far, only two blood-based biomarkers have been identified as independent predictors of outcome and mortality after stroke: the stress marker copeptin and midregional pro-atrial natriuretic peptide. Careful evaluation of prognostic markers is needed to prevent the occurrence of self-fulfilling prophecy. © 2012 S. Karger AG, Basel.


Scheurig-Muenkler C.,Charit Universittsmedizin Berlin | Wagner M.,Charit Universittsmedizin Berlin | Franiel T.,Charit Universittsmedizin Berlin | Hamm B.,Charit Universittsmedizin Berlin | Kroencke T.J.,Charit Universittsmedizin Berlin
Journal of Vascular and Interventional Radiology | Year: 2010

Purpose: To document immediate and short-term changes in uterine perfusion after uterine artery embolization (UAE). Materials and Methods: Fifteen patients (median age, 42 years) underwent UAE with tris-acryl gelatin microspheres and a limited embolization protocol. Contrast-enhanced magnetic resonance imaging was performed before therapy and 1 hour (immediate), 4872 hours (subacute), and a median of 5 months (short-term follow-up) after UAE to determine uterine and leiomyoma perfusion. Leiomyomas with a minimum diameter of 10 mm were included. Changes in regional (ie, fundus/body/cervix), zonal (ie, endometrium/inner/ middle and outer myometrial layer), and leiomyoma perfusion were documented. Results: UAE was technically successful in all patients. Immediate contrast-enhanced MR imaging revealed ischemia of the uterine body and fundus. The endometrium and inner myometrial layer was involved in all 15 patients; the middle layer was also involved in 13. Ischemic defects were seen in the outer layer in one patient but never in the cervix. Subacute follow-up showed reperfusion of the myometrium in 73% of patients. Ischemic defects occurred in the endometrial and junctional zone in four patients and in the middle zone in one. Five-month follow-up showed perfusion of all uterine layers in all patients. Ten patients had complete infarction of all leiomyomas; five presented with 11 partially perfused leiomyomas. Conclusions: Limited bilateral UAE leads to transient uterine ischemia, particularly involving the endometrium and inner and middle zone of the myometrium of the uterine body and fundus. The cervix and subserosal layer are spared. Complete reperfusion of myometrial tissue is observed within 4872 hours in most cases, whereas ischemic leiomyomas undergo irreversible infarction. © 2010 SIR.

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