Asklepios Hospital St Georg

St. Georg, Germany

Asklepios Hospital St Georg

St. Georg, Germany
Time filter
Source Type

Bein B.,Asklepios Hospital St Georg | Christ T.,University of Hamburg | Eberhart L.H.J.,University of Marburg
Frontiers in Pharmacology | Year: 2017

A 20:1 combination of cafedrine:theodrenaline (Akrinor®) is widely used in Germany for the treatment of hypotensive states during anesthesia and in emergency medicine. Although this drug formulation has been available since 1963, there are few studies relating to its use and many of the data are only available in German. In this article, we summarize the available data and propose mechanisms for the effects of cafedrine/theodrenaline on cardiac muscle cells and vascular smooth muscle cells. Cafedrine/theodrenaline leads to a rapid increase in mean arterial pressure that is characterized by increased cardiac preload, stroke volume, and cardiac output. Systemic vascular resistance and heart rate remain mostly unchanged. Factors which impact the effects of cafedrine/theodrenaline are gender, high arterial pressure at baseline, use of β-blockers, and heart failure. Importantly, the drug is frequently used in obstetric anesthesia without detrimental effects on umbilical cord pH or APGAR score. © 2017 Bein, Christ and Eberhart.

Stone G.W.,Columbia University | Adams D.H.,Mount Sinai Health System | Abraham W.T.,Ohio State University | Kappetein A.P.,Erasmus Medical Center | And 10 more authors.
Journal of the American College of Cardiology | Year: 2015

Mitral regurgitation (MR) is one of the most prevalent valve disorders and has numerous etiologies, including primary (organic) MR, due to underlying degenerative/structural mitral valve (MV) pathology, and secondary (functional) MR, which is principally caused by global or regional left ventricular remodeling and/or severe left atrial dilation. Diagnosis and optimal management of MR requires integration of valve disease and heart failure specialists, MV cardiac surgeons, interventional cardiologists with expertise in structural heart disease, and imaging experts. The introduction of transcatheter MV therapies has highlighted the need for a consensus approach to pragmatic clinical trial design and uniform endpoint definitions to evaluate outcomes in patients with MR. The Mitral Valve Academic Research Consortium is a collaboration between leading academic research organizations and physician-scientists specializing in MV disease from the United States and Europe. Three in-person meetings were held in Virginia and New York during which 44 heart failure, valve, and imaging experts, MV surgeons and interventional cardiologists, clinical trial specialists and statisticians, and representatives from the U.S. Food and Drug Administration considered all aspects of MV pathophysiology, prognosis, and therapies, culminating in a 2-part document describing consensus recommendations for clinical trial design (Part 1) and endpoint definitions (Part 2) to guide evaluation of transcatheter and surgical therapies for MR. The adoption of these recommendations will afford robustness and consistency in the comparative effectiveness evaluation of new devices and approaches to treat MR. These principles may be useful for regulatory assessment of new transcatheter MV devices, as well as for monitoring local and regional outcomes to guide quality improvement initiatives. © 2015 American College of Cardiology Foundation.

Glass B.,Asklepios Hospital St Georg | Hasenkamp J.,University Medicine Goettingen | Wulf G.,University Medicine Goettingen | Dreger P.,University of Heidelberg | And 10 more authors.
The Lancet Oncology | Year: 2014

Background: Allogeneic stem-cell transplantation has had limited success for patients with refractory and relapsed aggressive B-cell or T-cell lymphoma. We investigated the effect of adding rituximab to standard prophylaxis for graft-versus-host disease after transplantation and estimated overall survival when using a lymphoma-directed myeloablative conditioning regimen. Methods: We did this randomised, open-label, phase 2 study at seven German transplantation centres. We enrolled patients with aggressive B-cell or T-cell lymphoma and primary refractory disease, early relapse (<12 months after first-line treatment), or relapse after autologous transplantation. Conditioning with fludarabine (125 mg/m2), busulfan (12 mg/kg oral or 9·6 mg/kg intravenous), and cyclophosphamide (120 mg/kg) was followed by allogeneic stem-cell transplantation. Patients were randomly assigned (1:1) to receive rituximab (375 mg/m2 on days 21, 28, 35, 42, 175, 182, 189, and 196) or not. Allocation was done with a centralised computer-generated procedure; patients were stratified by histological subtype (B-cell vs T-cell lymphoma) and donor match (HLA-identical vs non-identical). Neither investigators nor patients were masked to allocation. The primary endpoints were the incidence of acute graft-versus-host disease grade 2-4 in each treatment group and overall survival at 1 year in both groups combined. All analyses were done for the intention-to-treat population. The study is registered with, number NCT00785330. Findings: Between June 16, 2004, and March 24, 2009, we screened 86 patients and enrolled 84; 42 were randomly assigned to each group. The cumulative incidence of grade 2-4 acute graft-versus-host disease was 46% (95% CI 32-62) in the rituximab group and 42% (95% CI 29-59) in the no rituximab group (hazard ratio [HR] 0·91, 95% CI 0·52-1·60; p=0·74). Overall survival at 1 year for the whole study population was 52% (95% CI 41-62). Grade 4 haematological toxic effects and grade 3 alopecia occurred in all patients. The most common non-haematological grade 5 toxic effects were pneumonia (nine in the no rituximab group vs ten in the rituximab group) and other infections (seven vs four). Interpretation: The lymphoma-directed myeloablative conditioning regimen developed here is promising for patients with refractory and relapsed aggressive B-cell and T-cell lymphomas. However, the addition of rituximab did not affect the incidence of graft-versus-host disease or overall survival. Funding: Hoffmann-La Roche, Amgen, Astellas Pharma. © 2014 Elsevier Ltd.

Schmitz N.,Asklepios Hospital St Georg | Nickelsen M.,Asklepios Hospital St Georg | Ziepert M.,University of Leipzig | Haenel M.,Municipal Hospital Chemnitz | And 13 more authors.
The Lancet Oncology | Year: 2012

Background: High-dose therapy (HDT) followed by transplantation of autologous haemopoietic stem cells is frequently done as part of first-line therapy in young patients with high-risk aggressive B-cell lymphoma. We investigated whether HDT with cytotoxic agents identical to those used for conventional therapy followed by autologous stem-cell transplantation (ASCT) improved survival outcome compared with conventional chemotherapy when rituximab was added to both modalities. Methods: We did an open-label, randomised trial comparing conventional chemotherapy (cyclophosphamide, doxorubicin, vincristine, etoposide, prednisone) and rituximab (R-CHOEP-14) with dose-escalated sequential HDT and rituximab (R-MegaCHOEP) followed by repetitive ASCT in high-risk (age-adjusted International Prognostic Index [IPI] 2 or 3) patients aged 18-60 years with aggressive B-cell lymphoma. Eligible patients received radiotherapy for bulky, extranodal disease, or both. Randomisation (1:1) used the Pocock minimisation algorithm; patients were stratified by age-adjusted IPI factors, bulky disease, and centre. The primary endpoint was event-free survival. All analyses were done on the intention-to-treat population. This trial is registered with, number NCT00129090. Findings: 136 patients were randomly assigned to R-CHOEP-14 and 139 to R-MegaCHOEP. 130 patients in the R-CHOEP-14 group and 132 in the R-MegaCHOEP group were included in the intention-to-treat population. After a median of 42 months (IQR 29-59), 3-year event-free survival was 69·5% (95% CI 61·3-77·7) in the R-CHOEP-14 group and 61·4% (52·8-70·0) in the R-MegaCHOEP group (p=0·14; hazard ratio 1·3, 95% CI 0·9-2·0). All 128 evaluable patients treated with R-MegaCHOEP had grade 4 leucopenia, as did 48 (58·5%) of 82 patients with documented blood counts in the R-CHOEP-14 group. All 128 evaluable patients in the R-MegaCHOEP group had grade 3-4 thrombocytopenia, as did 26 (33·8%) of 77 patients in the R-CHOEP-14 group with documented blood counts. The most important non-haematological grade 3 or 4 adverse event was infection, which occurred in 96 (75·0%) of 128 patients treated with R-MegaCHOEP and in 40 (31·3%) of 128 patients treated with R-CHOEP-14. Interpretation: In young patients with high-risk aggressive B-cell lymphoma, R-MegaCHOEP was not superior to conventional R-CHOEP therapy and was associated with significantly more toxic effects. R-CHOEP-14 with or without radiotherapy remains a treatment option for these patients, with encouraging efficacy. Funding: Deutsche Krebshilfe. © 2012 Elsevier Ltd.

Schmitz N.,Asklepios Hospital St Georg | Trumper L.,University of Gottingen | Ziepert M.,University of Leipzig | Nickelsen M.,Asklepios Hospital St Georg | And 6 more authors.
Blood | Year: 2010

To evaluate outcome and prognosis of patients with T-cell lymphoma we analyzed 343 patients treated within trials of the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). Two hundred eighty-nine patients belonged to 1 of the 4 major T-cell lymphoma subtypes: anaplastic large cell lymphoma (ALCL), anaplastic large cell lymphoma kinase (ALK)-positive (n = 78); ALCL, ALK-negative (n = 113); peripheral T-cell lymphoma, unspecified (PTCLU; n = 70); and angioimmunoblastic T-cell lymphoma (AITL; n = 28). Treatment consisted of 6-8 courses of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone/prednisolone) or etoposide plus (CHOEP). Three-year event-free survival (EFS) and overall survival were 75.8% and 89.8% (ALK-positive ALCL), 50.0% and 67.5% (AITL), 45.7% and 62.1% (ALK-negative ALCL), and 41.1% and 53.9% (PTCLU), respectively. The International Prognostic Index (IPI) was effective in defining risk groups with significantly different outcomes. For patients, ≤ 60 years with lactate dehydrogenase ≤ upper normal value (UNV), etoposide improved improved 3-year EFS: 75.4% versus 51.0%, P = .003. In patients > 60 years 6 courses of CHOP administered every 3 weeks remains the standard therapy. Patients with ALK-negative ALCL, PTCLU, or AITL presenting with IPI > 1 have a poor prognosis and should be considered candidates for novel treatment strategies. © 2010 by The American Society of Hematology.

Friedrichs B.,Asklepios Hospital St Georg | Tichelli A.,University of Basel | Bacigalupo A.,Hematologia Oncologia | Russell N.H.,University of Nottingham | And 6 more authors.
The Lancet Oncology | Year: 2010

Background: Most allogeneic haematopoietic stem cell transplants now use peripheral blood progenitor cell transplantation (PBPCT) instead of bone-marrow transplantation (BMT). Long-term data on outcome and late effects of PBPCT compared with BMT are scarce. Here we present long-term data from a randomised study comparing PBPCT with BMT. Methods: Between February, 1995, and September, 1999, 329 patients with leukaemia received either PBPCT (n=163) or BMT (n=166) from HLA-identical sibling donors after central randomisation accounting for stratification criteria. Follow-up data were collected via questionnaires from 87% (176 of 202; 84 PBPCT, 92 BMT) patients who survived for more than 3 years (median of 9·3 years) after transplantation. Efficacy analyses included all patients who received treatment. This study is registered with, number NCT01020175. Findings: 10-year overall survival was 49·1% for patients who underwent PBPCT and 56·5% for patients who underwent BMT (HR 0·83, 95% CI 0·60-1·15; p=0·27). Leukaemia-free survival was 28·3% with BMT versus 13·0% with PBPCT (0·61, CI 0·32-1·16; p=0·12) for acute lymphoblastic leukaemia; 62·3% with BMT versus 47·1% with PBPCT for acute myeloid leukaemia (0·67, 0·39-1·16; p=0·16); and 40·2% with BMT versus 48·5% with PBPCT for chronic myeloid leukaemia (1·12, 0·73-1·74; p=0·60). More patients developed chronic graft-versus-host disease after PBPCT (n=56, 73%) than after BMT (n=46, 56%; p=0·021), with more frequent involvement of skin, liver, and oral mucosa, and more patients who underwent PBPCT needed immunosuppressive treatment 5 years after transplantation (n=20, 26%) than patients who had BMT (n=10, 12%; p=0·024). Nonetheless, there was no difference in performance status, return to work, incidence of bronchiolitis obliterans, and haematopoietic function between the two groups. 14 cases of secondary malignancies occurred (five after BMT, nine after PBPCT), resulting in a cumulative incidence of 3% and 7% after BMT and PBPCT (p=0·17), respectively. Interpretation: More than 9 years after transplantation, overall and leukaemia-free survival remain similar in patients who underwent BMT and PBPCT. Differences in the incidence of chronic graft-versus-host disease and the duration of immunosuppression exist, but do not affect survival, general health status, or late events. Funding: No external funding was received. © 2010 Elsevier Ltd.

Kuck K.-H.,Asklepios Hospital St Georg | Hoffmann B.A.,University of Hamburg | Ernst S.,Asklepios Hospital St Georg | Wegscheider K.,University of Hamburg | And 6 more authors.
Circulation: Arrhythmia and Electrophysiology | Year: 2016

Background-Ablation of atrial fibrillation (AF) is an established treatment option for symptomatic patients. It is not known whether complete pulmonary vein isolation (PVI) is superior to incomplete PVI with regard to the patients' clinical outcome. Methods and Results-Patients with drug-refractory, symptomatic paroxysmal AF were randomly assigned to either incomplete (group A) or complete PVI (group B). In group A, a persistent gap was intentionally left within the circumferential ablation line, whereas in group B, complete PVI without any gaps was intended. At 3 months, all patients underwent invasive reevaluation to assess the rate of persistent PVI. Clinical follow-up was based on daily 30-s transtelephonic ECG transmissions. Primary study end point was the time to first recurrence of (symptomatic or asymptomatic) AF. A total of 233 patients were enrolled (116 in group A and 117 in group B). AF recurrence within 3 months was observed in a total of 161 patients (136 [84.5%] with symptomatic and 25 [15.5%] with asymptomatic AF); AF recurred in 62.2% of group B patients and 79.2% of group A patients (P<0.001), for a difference in favor of complete PVI of 17.1% (95% confidence interval, 5.3%-28.9%). Invasive restudy in 103 group A patients and 93 group B patients revealed conduction gaps in 92 (89.3%) and 65 (69.9%) patients, respectively. Conclusions-This study proves the superiority of complete PVI over incomplete PVI with respect to AF recurrence within 3 months. However, the rate of electric reconduction 3 months after PVI is high in patients with initially isolated PVs. Clinical Trial Registration-URL:; Unique identifier: NCT00293943. © 2016 American Heart Association, Inc.

Schmitz N.,Asklepios Hospital St Georg | Zeynalova S.,University of Leipzig | Glass B.,Asklepios Hospital St Georg | Kaiser U.,St Bernward Hospital | And 6 more authors.
Annals of Oncology | Year: 2012

Background: To describe incidence, risk factors, and influence of treatment on occurrence of central nervous system (CNS) relapse or progression in younger patients with aggressive B-cell lymphoma. Patients and methods: We analyzed 2210 patients with aggressive B-cell lymphoma treated on various studies for CNS relapse/progression. Treatment consisted of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) ± etoposide. Six hundred and twenty patients also received rituximab. CNS prophylaxis was intrathecal methotrexate on High-CHOEP and MegaCHOEP phase III studies if upper neck, head, bone marrow, or testes were involved. Results: Fifty-six of 2196 patients (2.6%) developed CNS disease. It occurred early (median 7.0 months), median survival was 5.0 months. Patients with age-adjusted International Prognostic Index (aaIPI) 0 or 1 treated with rituximab showed a low risk for CNS disease (2-year rates: 0% or 0.5%), and rituximab decreased the risk (relative risk 0.3, 95% confidence interval 0.1-0.9, P = 0.029). Patients with aaIPI 2 or 3 showed a moderate risk (4.2%-9.7%) and no significant reduction of CNS disease with rituximab. CNS prophylaxis was of no significant benefit. Conclusions: In younger patients with aaIPI 0 or 1, CNS relapse/progression is very rare; in patients with aaIPI 2 or 3, the risk is higher (up to 10%) and requires new diagnostic strategies and treatment. © The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Krause K.,Asklepios Hospital St Georg | Schneider C.,Asklepios Hospital St Georg | Kuck K.-H.,Asklepios Hospital St Georg | Jaquet K.,Asklepios Hospital St Georg
Cardiovascular Therapeutics | Year: 2010

Heart insufficiency remains the leading cause of death despite pharmacological and interventional therapy as well as primary and secondary prevention. Laboratory research on cardiac repair implementing stem cells and progenitor cells has raised great expectations as well as controversies. The potential of diverse progenitor cells to repair damaged heart tissue includes replacement (tissue transplant), restoration (activation of resident cardiac progenitor cells, paracrine effects), and regeneration (stem cell engraftment forming new myocytes). Based on promising experimental results clinical trials including several hundreds of patients with ischemic heart disease have been initiated using mostly bone marrow-derived cells. Probably, due to a lack of standardization of cell isolation and delivery methods these trials showed controverse results regarding effectiveness. However, significant therapeutic regeneration of human myocardium could not be proven until now. Several issues are at debate concerning the translation of the experimental data into the clinic discussing the adequate cell type, dosing, timing, and delivery mode of myocardial stem cell therapy. This review focusses on the potential and clinical translation of cell based therapies in cardiovascular disease. © 2010 Blackwell Publishing Ltd.

Schmitz N.,Asklepios Hospital St Georg | Wu H.-S.,Asklepios Hospital St Georg | Glass B.,Asklepios Hospital St Georg
Seminars in Hematology | Year: 2014

Except for ALK-positive anaplastic large cell lymphoma (ALCL) and patients with limited disease, mature T- and natural killer (NK) cell lymphomas are disorders with a poor prognosis. Patients with relapsed or refractory ALK-negative ALCL, angioimmunoblastic T-cell lymphoma (AITL), or peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) after allogeneic transplantation of hematopoietic stem cells (alloSCT) achieve long-term survival in 35%-50% of cases. Survival in patients with less frequent subtypes (NK/T-cell lymphoma, cutaneous T-cell lymphomas, acute T-cell leukemia/lymphoma, or hepatosplenic T-cell lymphoma) also seems promising. These results are significantly better than those of any other treatment modality, including the new drugs. Therefore, alloSCT should be considered in patients with relapsed/ refractory T-cell lymphoma. Because of low patient numbers and lack of comparative studies, the optimum conditioning regimen prior to transplantation as well as other details of the transplant procedure remain unknown and await further study. Studies investigating the role of alloSCT as part of first-line therapy in poor-risk T-cell lymphomas are ongoing. At present, data are not sufficient to recommend alloSCT outside of clinical trials. © 2014.

Loading Asklepios Hospital St Georg collaborators
Loading Asklepios Hospital St Georg collaborators