Motol University Hospital

Prague, Czech Republic

Motol University Hospital

Prague, Czech Republic
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Hammer J.,Albert Ludwigs University of Freiburg | Hammer J.,Motol University Hospital | Hammer J.,Charles University | Pistohl T.,Albert Ludwigs University of Freiburg | And 8 more authors.
Cerebral Cortex | Year: 2016

How neuronal activity of motor cortex is related to movement is a central topic in motor neuroscience. Motor-cortical single neurons are more closely related to hand movement velocity than speed, that is, the magnitude of the (directional) velocity vector. Recently, there is also increasing interest in the representation of movement parameters in neuronal population activity, such as reflected in the intracranial EEG (iEEG). We show that in iEEG, contrasting to what has been previously found on the single neuron level, speed predominates over velocity. The predominant speed representation was present in nearly all iEEG signal features, up to the 600-1000 Hz range. Using a model of motor-cortical signals arising from neuronal populations with realistic single neuron tuning properties, we show how this reversal can be understood as a consequence of increasing population size. Our findings demonstrate that the information profile in large population signals may systematically differ from the single neuron level, a principle that may be helpful in the interpretation of neuronal population signals in general, including, for example, EEG and functional magnetic resonance imaging. Taking advantage of the robust speed population signal may help in developing brain-machine interfaces exploiting population signals. © 2016 The Author. Published by Oxford University Press.

Raudenska J.,Charles University | Javurkova A.,Kralovske Vinohrady University Hospital | Kozak J.,Motol University Hospital
Neuroendocrinology Letters | Year: 2013

Pain-related fear may pose a serious barrier in the management of patients with chronic musculoskeletal pain, resulting in severe functional impairment in many cases. The paper describes the cognitive-behavioural therapy of a patient with a specific phobia (fear of pain and movement). The principal objective of the therapy was to educate the patient in strategies and skills to manage his fear and to verify the effect of the therapy. Both group and individual therapy was used. Group multimodal therapy of pain was provided by an interdisciplinary team of health care providers, specialising in pain management (psychotherapist, doctors and physiotherapists). The programme was based on operant therapy principles and included pacing and graded exercising and walking, relaxation, group education about ergonomics, and fear and pain relapse prevention. Reduction in the fear of pain and movement was achieved, and social bonds and physical and social activities improved after the psychotherapy, while the results were stable for two years. © 2013 Neuroendocrinology Letters.

Granger C.B.,Duke University | Alexander J.H.,Duke University | McMurray J.J.V.,University of Glasgow | Lopes R.D.,Duke University | And 28 more authors.
New England Journal of Medicine | Year: 2011

BACKGROUND: Vitamin K antagonists are highly effective in preventing stroke in patients with atrial fibrillation but have several limitations. Apixaban is a novel oral direct factor Xa inhibitor that has been shown to reduce the risk of stroke in a similar population in comparison with aspirin. METHODS: In this randomized, double-blind trial, we compared apixaban (at a dose of 5 mg twice daily) with warfarin (target international normalized ratio, 2.0 to 3.0) in 18,201 patients with atrial fibrillation and at least one additional risk factor for stroke. The primary outcome was ischemic or hemorrhagic stroke or systemic embolism. The trial was designed to test for noninferiority, with key secondary objectives of testing for superiority with respect to the primary outcome and to the rates of major bleeding and death from any cause. RESULTS: The median duration of follow-up was 1.8 years. The rate of the primary outcome was 1.27% per year in the apixaban group, as compared with 1.60% per year in the warfarin group (hazard ratio with apixaban, 0.79; 95% confidence interval [CI], 0.66 to 0.95; P<0.001 for noninferiority; P = 0.01 for superiority). The rate of major bleeding was 2.13% per year in the apixaban group, as compared with 3.09% per year in the warfarin group (hazard ratio, 0.69; 95% CI, 0.60 to 0.80; P<0.001), and the rates of death from any cause were 3.52% and 3.94%, respectively (hazard ratio, 0.89; 95% CI, 0.80 to 0.99; P = 0.047). The rate of hemorrhagic stroke was 0.24% per year in the apixaban group, as compared with 0.47% per year in the warfarin group (hazard ratio, 0.51; 95% CI, 0.35 to 0.75; P<0.001), and the rate of ischemic or uncertain type of stroke was 0.97% per year in the apixaban group and 1.05% per year in the warfarin group (hazard ratio, 0.92; 95% CI, 0.74 to 1.13; P = 0.42). CONCLUSIONS: In patients with atrial fibrillation, apixaban was superior to warfarin in preventing stroke or systemic embolism, caused less bleeding, and resulted in lower mortality. Copyright © 2011 Massachusetts Medical Society. All rights reserved.

Hylek E.M.,Boston University | Held C.,Uppsala University | Alexander J.H.,Duke University | Lopes R.D.,Duke University | And 9 more authors.
Journal of the American College of Cardiology | Year: 2014

Objectives This study sought to characterize major bleeding on the basis of the components of the major bleeding definition, to explore major bleeding by location, to define 30-day mortality after a major bleeding event, and to identify factors associated with major bleeding. Background Apixaban was shown to reduce the risk of major hemorrhage among patients with atrial fibrillation in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial. Methods All patients who received at least 1 dose of a study drug were included. Major bleeding was defined according to the criteria of the International Society on Thrombosis and Haemostasis. Factors associated with major hemorrhage were identified using a multivariable Cox model. Results The on-treatment safety population included 18,140 patients. The rate of major hemorrhage among patients in the apixaban group was 2.13% per year compared with 3.09% per year in the warfarin group (hazard ratio [HR] 0.69, 95% confidence interval [CI]: 0.60 to 0.80; p < 0.001). Compared with warfarin, major extracranial hemorrhage associated with apixaban led to reduced hospitalization, medical or surgical intervention, transfusion, or change in antithrombotic therapy. Major hemorrhage followed by mortality within 30 days occurred half as often in apixaban-treated patients than in those receiving warfarin (HR 0.50, 95% CI: 0.33 to 0.74; p < 0.001). Older age, prior hemorrhage, prior stroke or transient ischemic attack, diabetes, lower creatinine clearance, decreased hematocrit, aspirin therapy, and nonsteroidal anti-inflammatory drugs were independently associated with an increased risk. Conclusions Apixaban, compared with warfarin, was associated with fewer intracranial hemorrhages, less adverse consequences following extracranial hemorrhage, and a 50% reduction in fatal consequences at 30 days in cases of major hemorrhage. © © 2014 by the American College of Cardiology Foundation Published by Elsevier Inc.

Background-Although erectile dysfunction (ED) is associated with cardiovascular risk factors and atherosclerosis, it is not known whether the presence of ED is predictive of future events in individuals with cardiovascular disease. We evaluated whether ED is predictive of mortality and cardiovascular outcomes, and because inhibition of the renin-angiotensin system in high-risk patients reduces cardiovascular events, we also tested the effects on ED of randomized treatments with telmisartan, ramipril, and the combination of the 2 drugs (ONTARGET), as well as with telmisartan or placebo in patients who were intolerant of angiotensin-converting enzyme inhibitors (TRANSCEND). Methods and Results-In a prespecified substudy, 1549 patients underwent double-blind randomization, with 400 participants assigned to receive ramipril, 395 telmisartan, and 381 the combination thereof (ONTARGET), as well as 171 participants assigned to receive telmisartan and 202 placebo (TRANSCEND). ED was evaluated at baseline, at 2-year follow-up, and at the penultimate visit before closeout. ED was predictive of all-cause death (hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.21 to 2.81, P=0.005) and the composite primary outcome (HR 1.42, 95% CI 1.04 to 1.94, P=0.029), which consisted of cardiovascular death (HR 1.93, 95% CI 1.13 to 3.29, P=0.016), myocardial infarction (HR 2.02, 95% CI 1.13 to 3.58, P=0.017), hospitalization for heart failure (HR 1.2, 95% CI 0.64 to 2.26, P=0.563), and stroke (HR 1.1, 95% CI 0.64 to 1.9, P=0.742). The study medications did not influence the course or development of ED. Conclusions-ED is a potent predictor of all-cause death and the composite of cardiovascular death, myocardial infarction, stroke, and heart failure in men with cardiovascular disease. © 2010 American Heart Association, Inc.

Honek J.,Charles University | Sramek M.,Charles University | Sefc L.,Charles University | Januska J.,Hospital Podlesi | And 7 more authors.
JACC: Cardiovascular Interventions | Year: 2014

Objectives: This study sought to evaluate the effect of catheter-based patent foramen ovale (PFO) closure on the occurrence of arterial bubbles after simulated dives. Background: PFO is a risk factor of decompression sickness in divers due to paradoxical embolization of bubbles. To date, the effectiveness of catheter-based PFO closure in the reduction of arterial bubbles has not been demonstrated. Methods: A total of 47 divers (age 35.4 ± 8.6 years, 81% men) with a PFO (PFO group) or treated with a catheter-based PFO closure (closure group) were enrolled in this case-controlled observational trial. All divers were examined after a simulated dive in a hyperbaric chamber: 34 divers (19 in the PFO group, 15 in the closure group) performed a dive to 18 m for 80 min, and 13 divers (8 in the PFO group, 5 in the closure group) performed a dive to 50 m for 20 min. Within 60 min after surfacing, the presence of venous and arterial bubbles was assessed by transthoracic echocardiography and transcranial color-coded sonography, respectively. Results: After the 18-m dive, venous bubbles were detected in 74% of divers in the PFO group versus 80% in the closure group (p = 1.0), and arterial bubbles were detected in 32% versus 0%, respectively (p = 0.02). After the 50-m dive, venous bubbles were detected in 88% versus 100%, respectively (p = 1.0), and arterial bubbles were detected in 88% versus 0%, respectively (p < 0.01). Conclusions: No difference was observed in the occurrence of venous bubbles between the PFO and closure groups, but the catheter-based PFO closure led to complete elimination of arterial bubbles after simulated dives. (Nitrogen Bubble Detection After Simulated Dives in Divers With PFO and After PFO Closure; NCT01854281). © 2014 by the American College of Cardiology Foundation.

Klukowska A.,Medical University of Warsaw | Komrska V.,Motol University Hospital | Jansen M.,Octapharma | Laguna P.,Medical University of Warsaw
Haemophilia | Year: 2011

For patients with haemophilia A (HA), lifelong replacement therapy with factor VIII (FVIII) concentrates is the treatment of choice. Octanate® is a plasma-derived, human, von Willebrand factor-stabilized FVIII product with demonstrated haemostatic efficacy in patients with HA. The aim of this ongoing study is to assess the immunogenicity of Octanate® in previously untreated patients (PUPs), monitoring for development of FVIII inhibitors. Interim data on 39 PUPs treated for bleeding, prophylactically and for surgical coverage are reported. Two of 39 subjects (5.1%) developed clinically relevant inhibitor titres over the course of the study. Another two displayed inhibitors that disappeared spontaneously without Octanate® dose change. All inhibitors developed under on-demand treatment and before exposure day (ED) 50. Remarkably, no inhibitor was observed in PUPs receiving prophylaxis with Octanate®. Of 39 subjects, 30 had exceeded 50 EDs at the time of this analysis. All inhibitor subjects were found to have large FVIII gene defects, either intron 22-inversions or large deletions. Octanate® was well-tolerated and the adverse event profile was consistent with the population studied. The haemostatic efficacy of Octanate® in prophylaxis and treatment of bleeding were generally rated as 'excellent', and no complication was reported for surgery. Notable FVIII activity was present in blood at 15min postadministration, and levels remained high at 1h. Mean incremental in vivo recovery (IVR) was 2.0 (±0.6) %IU-1kg-1. These interim results indicate Octanate® to be an efficacious, well-tolerated human FVIII product for management of HA in PUPs, associated with a minimal risk of inhibitors. © 2010 Blackwell Publishing Ltd.

Tweedy J.,London School of Hygiene and Tropical Medicine | Spyrou M.A.,London School of Hygiene and Tropical Medicine | Spyrou M.A.,University of Tübingen | Hubacek P.,Motol University Hospital | And 3 more authors.
Journal of General Virology | Year: 2015

Human herpesvirus-6A (HHV-6A) is rarer than HHV-6B in many infant populations. However, they are similarly prevalent as germline, chromosomally integrated genomes (ciHHV-6A/B). This integrated form affects 0.1–1% of the human population, where potentially virus gene expression could be in every cell, although virus relationships and health effects are not clear. In a Czech/ German patient cohort ciHHV-6A was more common and diverse than ciHHV-6B. Quantitative PCR, nucleotide sequencing and telomeric integration site amplification characterized ciHHV-6 in 44 German myocarditis/cardiomyopathy and Czech malignancy/inflammatory disease (MI) patients plus donors. Comparisons were made to sequences from global virus reference strains, and blood DNA from childhood-infections from Zambia (HHV-6A mainly) and Japan (HHV-6B). The MI cohort were 86% (18/21) ciHHV-6A, the cardiac cohort 65% (13/20) ciHHV-6B, suggesting different disease links. Reactivation was supported by findings of 1) recombination between ciHHV-6A and HHV-6B genes in 20% (4/21) of the MI cohort; 2) expression in a patient subset, of early/late transcripts from the inflammatory mediator genes chemokine receptor U51 and chemokine U83, both identical to ciHHV-6A DNA sequences; and 3) superinfection shown by deep sequencing identifying minor virus-variants only in ciHHV-6A, which expressed transcripts, indicating virus infection reactivates latent ciHHV-6A. Half the MI cohort had more than two copies per cell, median 5.2, indicative of reactivation. Remarkably, the integrated genomes encoded the secreted-active form of virus chemokines, rare in virus from childhoodinfections. This shows integrated virus genomes can contribute new human genes with links to inflammatory pathology and supports ciHHV-6A reactivation as a source for emergent infection. © 2015 The Authors.

Veselka J.,Motol University Hospital
International Journal of Angiology | Year: 2015

Hypertrophic cardiomyopathy (HCM) is characterized by the presence of increased thickness of the left ventricular wall that is not solely explained by abnormal loading conditions. Two-thirds of the patients with HCM have an obstruction in the left ventricle after provocation or even while at rest. This obstruction is associated with more symptoms and a worse prognosis. The two main therapeutic approaches for treating a left ventricular obstruction are alcohol septal ablation and surgical myectomy. Both these techniques are discussed in this article. Currently, the final decision concerning the optimal invasive therapy for patients with obstructive HCM must be individualized to each patient depending on his/her wishes and expectations, way of life, age, heart morphology, and hemodynamics, as well as the experience of the treating center. © 2015 by Thieme Medical Publishers, Inc.

Klozar J.,Motol University Hospital | Tachezy R.,Institute of Hematology and Blood Transfusion
Current Opinion in Otolaryngology and Head and Neck Surgery | Year: 2014

PURPOSE OF REVIEW: Human papillomavirus (HPV) status itself is an important and very probably the strongest prognostic factor in head and neck cancer. Because of the prognostic advantage of patients with HPV-positive cancers, the issue of the quality of life of survivors has become increasingly important. The possibility of treatment de-escalation in patients with virally induced tumors is being considered. Many challenges have to be addressed in order to integrate HPV status in the routine decision-making in patients with oropharyngeal cancer. The present review discusses the standardization of detection methods suitable for clinical use and the differences in predictive parameters between patients with HPV-positive and HPV-negative tumors. RECENT FINDINGS: The gold standard for the identification of patients with oropharyngeal tumors etiologically linked to HPV infection is undoubtedly the detection of HPV 16 E6/E7 mRNA. The detection of a surrogate marker of active viral infection, p16ink4a, has a low sensitivity when used alone and must therefore be combined with the detection of HPV DNA or HPV-specific antibodies. The detailed knowledge of the importance of specific prognostic parameters is crucial in the choice of treatment. Nodal staging is probably much less important in HPV-positive cancers. SUMMARY: It is of great importance to implement standardized testing for the identification of patients with HPV-induced oropharyngeal tumors. The treatment decision models in HPV-positive tumors have to take into account the probably different prognostic value of nodal parameters. Before introducing treatment de-escalation in patients with virally induced tumors into clinical practice, more research and clinical studies are needed. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.

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