Schmidbauer W.,Bundeswehrkrankenhaus Berlin |
Genzwurker H.,Hospitals Buchen and Mosbach |
Ahlers O.,Charité - Medical University of Berlin |
Proquitte H.,Charité - Medical University of Berlin |
Kerner T.,Asklepios Klinik Harburg
British Journal of Anaesthesia | Year: 2012
Background. Supraglottic airway devices (SADs) play an increasing role in airway management in clinical anaesthesia and emergency medicine. Until now, no data exist concerning the extent of oesophageal insufflation when oropharyngeal leak pressures are exceeded. Methods. Laryngeal masks LMA-Supreme™ and LMA-ProSeal™, laryngeal tubes LTS-D and LTS II, Combitube™, and I-Gel were inserted into unfixed human cadavers. The oesophagus was connected to a volumeter, while the trachea was closed surgically to simulate complete airway obstruction. Volumes of oesophageal insufflation resulting from pressure-controlled ventilation at inspiratory pressures of 20, 40, and 60 mbar were measured. Results. No oesophageal insufflation could be detected at a ventilation pressure of 20 mbar in any device. Using inspiratory pressures of 40 and 60 mbar, oesophageal insufflation occurred in all devices, with significantly higher volumes of intraoesophageal air for both laryngeal tubes. Conclusions.The use of SADs with inspiratory pressures of 20 mbar appears to be safe regarding the risk of intragastric insufflation. Higher inspiratory pressures should be strictly avoided. © 2012 The Author. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved.
Janne P.A.,Dana-Farber Cancer Institute |
Paz-Ares L.,University of Seville |
Eschbach C.,Asklepios Klinik Harburg |
Hirsh V.,Royal Victoria Hospital |
And 3 more authors.
Journal of Thoracic Oncology | Year: 2014
INTRODUCTION: In this phase II study, patients with stage IIIB/IV non-small-cell lung cancer were randomly assigned (1:1:1) to receive LY293111 (200 mg twice daily [200 LY293111] or 600 mg twice daily [600 LY293111]) or placebo for 7 days, followed by concurrent cisplatin (75 mg/m2; day 1) and gemcitabine (1250 mg/m2; days 1 and 8), every 21 days.The primary endpoint was progression-free survival, (PFS), with 75% power to detect 33% improvement compared with placebo (5 months). METHODS: Of 200 randomized patients, 195 were treated. Demographics were well balanced across treatment arms: 65% of the patients were men; median age was 62 years; 85% had stage IV disease; and patients had an Eastern Cooperative Oncology Group performance status of 0 (36%) or 1 (64%). RESULTS: The most frequent study drug-related toxicities were nausea, vomiting, and fatigue. Response rates were similar across treatment arms (200 LY293111: 20%; 600 LY293111: 25%; placebo: 31%). CONCLUSIONS: Median PFS (95% confidence interval) was not significantly different across treatment arms (200 LY293111: 4.6 months [3.2-5.0]; 600 LY293111: 5.6 months [4.1-6.8]; placebo: 6.0 months [5.2-7.5]). LY293111 combined with gemcitabine-cisplatin did not increase median PFS compared with placebo plus gemcitabine-cisplatin in patients with non-small-cell lung cancer. Copyright © 2013 by the International Association for the Study of Lung Cancer.
O'Byrne K.J.,St James's Hospital |
Gatzemeier U.,Hospital Grosshansdorf |
Bondarenko I.,Dnepropetrovsk State Medical Academy |
Barrios C.,Hospital Sao Lucas |
And 14 more authors.
The Lancet Oncology | Year: 2011
Background: Findings from the phase 3 FLEX study showed that the addition of cetuximab to cisplatin and vinorelbine significantly improved overall survival, compared with cisplatin and vinorelbine alone, in the first-line treatment of EGFR-expressing, advanced non-small-cell lung cancer (NSCLC). We investigated whether candidate biomarkers were predictive for the efficacy of chemotherapy plus cetuximab in this setting. Methods: Genomic DNA extracted from formalin-fixed paraffin-embedded (FFPE) tumour tissue of patients enrolled in the FLEX study was screened for KRAS codon 12 and 13 and EGFR kinase domain mutations with PCR-based assays. In FFPE tissue sections, EGFR copy number was assessed by dual-colour fluorescence in-situ hybridisation and PTEN expression by immunohistochemistry. Treatment outcome was investigated according to biomarker status in all available samples from patients in the intention-to-treat population. The primary endpoint in the FLEX study was overall survival. The FLEX study, which is ongoing but not recruiting participants, is registered with ClinicalTrials.gov, number NCT00148798. Findings: KRAS mutations were detected in 75 of 395 (19%) tumours and activating EGFR mutations in 64 of 436 (15%). EGFR copy number was scored as increased in 102 of 279 (37%) tumours and PTEN expression as negative in 107 of 303 (35%). Comparisons of treatment outcome between the two groups (chemotherapy plus cetuximab vs chemotherapy alone) according to biomarker status provided no indication that these biomarkers were of predictive value. Activating EGFR mutations were identified as indicators of good prognosis, with patients in both treatment groups whose tumours carried such mutations having improved survival compared with those whose tumours did not (chemotherapy plus cetuximab: median 17·5 months [95% CI 11·7-23·4] vs 8·5 months [7·1-10·8], hazard ratio [HR] 0·52 [0·32-0·84], p=0·0063; chemotherapy alone: 23·8 months [15·2-not reached] vs 10·0 months [8·7-11·0], HR 0·35 [0·21-0·59], p<0·0001). Expression of PTEN seemed to be a potential indicator of good prognosis, with patients whose tumours expressed PTEN having improved survival compared with those whose tumours did not, although this finding was not significant (chemotherapy plus cetuximab: median 11·4 months [8·6-13·6] vs 6·8 months [5·9-12·7], HR 0·80 [0·55-1·16], p=0·24; chemotherapy alone: 11·0 months [9·2-12·6] vs 9·3 months [7·6-11·9], HR 0·77 [0·54-1·10], p=0·16). Interpretation: The efficacy of chemotherapy plus cetuximab in the first-line treatment of advanced NSCLC seems to be independent of each of the biomarkers assessed. Funding: Merck KGaA. © 2011 Elsevier Ltd.
Park J.-W.,Asklepios Klinik Harburg |
Bethencourt A.,Hospital Universitario Son Dureta |
Sievert H.,Cardiovascular Center Sankt Katharinen |
Santoro G.,Azienda Ospedaliera Universitaria Careggi |
And 7 more authors.
Catheterization and Cardiovascular Interventions | Year: 2011
Background: In most patients with atrial fibrillation (AF) and stroke, there is thrombotic embolization from the left atrial appendage (LAA). Percutaneous closure of the LAA is a novel alternative for the treatment of patients with AF at a high risk of stroke, in whom long-term anticoagulation therapy is not possible or not desired. This study details the initial experience with the Amplatzer Cardiac Plug (ACP) in humans. Methods: Investigator-initiated retrospective preregistry data collection to evaluate procedural feasibility and safety up to 24 hr after implantation of the ACP, a nitinol device designed for percutaneous trans-septal implantation in LAA of patients with paroxysmal, permanent, or persistent AF. Results: In 137 of 143 patients, LAA occlusion was attempted, and successfully performed in 132 (96%). There were serious complications in 10 (7.0%) patients (three patients with ischemic stroke; two patients experienced device embolization, both percutaneously recaptured; and five patients with clinically significant pericardial effusions). Minor complications were insignificant pericardial effusions in four, transient myocardial ischemia in two, and loss of the implant in the venous system in one patient. Conclusion: The implantation of the ACP device is a feasible method for percutaneous occlusion of the LAA. © 2011 Wiley-Liss, Inc.
Karen T.,University of Duisburg - Essen |
Schlager G.W.,University of Duisburg - Essen |
Bendix I.,University of Duisburg - Essen |
Sifringer M.,Charité - Medical University of Berlin |
And 6 more authors.
PLoS ONE | Year: 2013
Background:Propofol is commonly used as sedative in newborns and children. Recent experimental studies led to contradictory results, revealing neurodegenerative or neuroprotective properties of propofol on the developing brain. We investigated neurodevelopmental short- and long-term effects of neonatal propofol treatment.Methods:6-day-old Wistar rats (P6), randomised in two groups, received repeated intraperitoneal injections (0, 90, 180 min) of 30 mg/kg propofol or normal saline and sacrificed 6, 12 and 24 hrs following the first injection. Cortical and thalamic areas were analysed by Western blot and quantitative real-time PCR (qRT-PCR) for expression of apoptotic and neurotrophin-dependent signalling pathways. Long-term effects were assessed by Open-field and Novel-Object-Recognition at P30 and P120.Results:Western blot analyses revealed a transient increase of activated caspase-3 in cortical, and a reduction of active mitogen-activated protein kinases (ERK1/2, AKT) in cortical and thalamic areas. qRT-PCR analyses showed a down-regulation of neurotrophic factors (BDNF, NGF, NT-3) in cortical and thalamic regions. Minor impairment in locomotive activity was observed in propofol treated adolescent animals at P30. Memory or anxiety were not impaired at any time point.Conclusion:Exposing the neonatal rat brain to propofol induces acute neurotrophic imbalance and neuroapoptosis in a region- and time-specific manner and minor behavioural changes in adolescent animals. © 2013 Karen et al.
Hormann K.,Universitatsklinikum Mannheim |
Verse T.,Asklepios Klinik Harburg
Surgery for Sleep Disordered Breathing | Year: 2010
The treatment of sleep disordered breathing has been enriched by the development of various new and largely surgical techniques. The question of which treatment best suits each individual patient has become a highly sophisticated decision. Among others, the most important factors for selecting the most appropriate treatment modality are the cruelty of the disease, the pathology found within the upper airway, and the sites of obstruction. Therefore, the second edition of this book focuses on both the surgical treatment modalities and the current concepts for treatment decisions. For each procedure, current data (including data for the entirety of 2007) were reanalyzed according to the principles of evidence-based medicine, and are presented in well-arranged tables. Indications, techniques, complications, and specific follow-up treatments in the realm of sleep medicine have been compiled in the form of a primer. New chapters concerning radiofrequency- uvulopalatoplasty and combined soft palate procedures were added. Both authors run prominent otolaryngological sleep laboratories, and perform approximately 1,500 surgical sleep medicine procedures per year. The complete surgical and sleep medicine expertise of the authors, as well as the experience of numerous international courses on sleep surgery, have been incorporated into this volume, making it an indispensable textbook for sleep medicine surgeons. © Springer-Verlag Berlin Heidelberg 2010. All rights are reserved.
Leithauser B.,Asklepios Klinik Harburg |
Jung F.,Research Center GmbH |
Park J.-W.,Asklepios Klinik Harburg
Clinical Hemorheology and Microcirculation | Year: 2010
Atrial fibrillation (AF), as the most common cardiac rhythm disturbance, gains in importance not only for the persons affected, but also for health care and social economy due to thromboembolic events, of which stroke is the most serious, disabling, and life threatening one. Cardiac embolism is due to thrombus formation mainly in the left atrial appendage (LAA). The pathophysiology leading to increased thrombogenicity is complex and requires a remodelling of the LAA structure, decreased LAA blood flow, activation of inflammatory processes, deviations of the hemostatic/fibrinolytic system, and activation/dysfunction of endothelial/endocardial cells. Altogether, a prothrombotic state proposed by Virchow more than 150 years ago. The presence of a LAA thrombus, therefore, is a result of a dynamic process of clot formation and lysis. A comprehensive understanding of this pathophysiology is helpful to optimize the management of patients at high risk of cardioembolic stroke. Especially those with contraindications for oral anticoagulation are in a need of an alternative approach that is not associated with a long-term risk of hemorrhage and other attendant circumstances. The reasonable alternative may be the exclusion of the LAA cavity from circulation by either surgical or percutaneous catheter-based procedures. © 2010 - IOS Press and the authors. All rights reserved.
Muschter R.,Klinik fur Urologie und Kinderurologie |
Bach T.,Asklepios Klinik Harburg |
Seitz M.,Ludwig Maximilians University of Munich
Urologe - Ausgabe A | Year: 2013
Transurethral resection of the prostate (TURP) is the surgical standard which is truly minimally invasive by using a natural orifice and is also of durable efficacy. The use of TURP removes tissue from benign prostatic hyperplasia (BPH) and leads to clinically relevant improvement in symptoms and quality of life as well as in micturition parameters and obstruction. Tissue is removed by high frequency (HF) current with synchronous hemostasis. Many modifications of TURP, such as the use of video, have become generally accepted and improved the standard. Other modifications were developed because the balance between cutting and hemostasis needed improvement in favor of hemostasis. Several modifications of TURP, such as modulation of HF pulses, band loops and bipolar resection and new procedures, such as vaporization and enucleation showed improved hemostasis. These modifications and procedures, however, have not yet replaced standard TURP but have become established as additional options. © 2013 Springer-Verlag Berlin Heidelberg.
Locker L.S.,Asklepios Klinik Harburg |
Lubbe A.S.,Cecilien Klinik
Progress in Palliative Care | Year: 2015
The principal aim of palliative care is to improve patients’ quality of life. This is more complicated than it seems. There is no generally accepted way to assess quality of life. Through an extensive literature research multiple instruments were found. Of these, four were chosen to be examined further (Schedule for the Evaluation of Individual Quality of Life – Direct Weighting (SEIQoL-DW), European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire – Core 15 – of Palliative Care (EORTC QLQ-C15-PAL), Rotterdam Symptom Checklist (RSCL), and Palliative Care Outcome Scale (POS)). These were used with patients in a German palliative care ward. Staff and patients were interviewed on their understanding of quality of life and its assessment. The results of literature research, interviews, and application of the instruments were then collated and critically evaluated. It became obvious that a deliberate choice of an instrument has a great impact on practicability and outcome in a clinical setting. The EORTC QLQ-C15-PAL seems particularly useful for (international) studies; it leads to clear and easily comparable results. For routine use in clinical palliative care, however, it seems too impersonal to represent more than a rough idea of patients’ actual quality of life. Applying the RSCL, the researcher could gain a basic overview of symptoms and psychological condition of his patients – even though it seems too rigid to allow a deeper insight in quality of life. The POS offers additional insight via an open question and a staff questionnaire. This could provide particularly helpful information for clinical routine –provided patients can cope with its more complex format. The SEIQoL-DW seems to be best suited for use in a clinical situation even though its use can be challenging for both researcher and patient. Assessment requires both parties to interact directly, which seems to have a beneficial impact on relationship and communication. It is the most flexible assessment instrument of those analysed here and therefore seems to be best suited to investigate such a complex matter as quality of life. © W. S. Maney & Son Ltd 2015.
Lam Y.-Y.,Chinese University of Hong Kong |
Yan B.P.,Chinese University of Hong Kong |
Doshi S.K.,Saint Johns Heart Center |
Li A.,Lifetech Scientific Corporation |
And 3 more authors.
International Journal of Cardiology | Year: 2013
Objectives The study evaluated the feasibility and safety of a novel left atrial appendage (LAA) occluder (LAmbre™, Lifetech Scientific Corp., China) in canines. Background Transcatheter LAA occlusion is comparable to warfarin in preventing atrial fibrillation-related strokes. Methods Twenty-two healthy dogs (28 ± 3 kg) received LAmbre implants. The device is delivered by an 8-10 French sheath and has full recapture and repositioning capabilities. All dogs received 1-week antibiotics and 4-week aspirin (80 mg daily) after implants and they were sacrificed in groups at Days 1-3 (n = 5), 1- (n = 7), 3- (n = 4) and 6-months (n = 6) for pathological examinations. Transthoracic echocardiography (TTE) was performed immediately after implant, at Day 3 and before sacrifice. Results The LAmbre was successfully implanted, retrieved, repositioned and re-implanted in all dogs. The mean implant size was 24 ± 3 mm and the device chosen was 36 ± 7% larger than the measured landing zone diameter. Improper device selection (only 21% oversizing) resulted in dislodgement and death of 1 dog on Day 3. Post-implant angiography and TTE showed well-positioned device without pericardial effusion or impingement on surrounding structures. Late complications included device-related thrombus at 1 month (n = 1) and clinically insignificant pericardial effusion at Day 3 (n = 1). Complete healing on the atrial facing surface with optimal LAA obliteration was confirmed by gross and microscopic examinations in dogs that have been followed up ≥ 3 months (n = 10). No infarct was detected in major organs. Conclusions Our preliminary data suggested the LAmbre™ device is feasible with high success rate in canines. Further studies are needed to evaluate its safety and efficacy. © 2013 Elsevier Ireland Ltd.