Enterlein G.,Universitatsklinikum Frankfurt |
Byhahn C.,Klinik fur Anasthesie
Anaesthesist | Year: 2013
In February 2013 the Committee of the American Society of Anesthesiologists (ASA) Task Force published the amended version of the "Practice guidelines for management of the difficult airway" which replace the recommendations from 2003. The amended version re-evaluated the recommendations from 2003 in 2011, evaluated recently published studies and recommendations and included them in the new practice guidelines. In particular, new technical developments, such as the recently established video-assisted intubation procedure were taken into consideration. Despite the many publications in the field of airway management the evidence resulting from the data obtained from recent publications is so low that the new information does not necessitate any amendments to the existing guidelines. In short, the current guidelines basically correspond to the previous version published 10 years ago but are, however, more than twice as extensive. This article summarizes and comments on the cornerstones of the guidelines. © 2013 Springer-Verlag Berlin Heidelberg.
Vermehren J.,Universitatsklinikum Frankfurt |
Aghemo A.,University of Milan |
Falconer K.,Karolinska University Hospital |
Susser S.,Universitatsklinikum Frankfurt |
And 5 more authors.
Journal of Hepatology | Year: 2014
Background & Aims The duration of current standard dual and protease inhibitor-based triple therapies for chronic hepatitis C is determined by assessment of early viral kinetics. Little is known about differences between HCV RNA assays for the use in response guided therapy. Methods HCV RNA was assessed by two widely used real-time PCR-based assays, Cobas Ampliprep/Cobas TaqMan (CAP), and Real-Time HCV (ART) in 903 samples of hepatitis C genotype 1 patients treated with dual (n = 169) or telaprevir-based triple therapy (n = 164) in three European countries. Results Overall, CAP and ART were in excellent agreement for the determination of HCV-RNA concentrations (mean difference 0.21 log10 IU/ml). For treatment-naïve patients treated with peginterferon-alfa and ribavirin a lower rate of undetectable HCV-RNA at week 4 (RVR) was observed for ART (9%) vs. CAP (16%). Although 11/27 (41%) of patients with shortened treatment (24 weeks) had detectable HCV-RNA <12 IU/ml by ART at week 4 none of these patients experienced virologic relapse after treatment cessation. In patients who received triple therapy, 67% and 37% had undetectable HCV-RNA at week 4 by CAP and ART, respectively. However, 18/31 (58%) eligible patients for shortened treatment based on CAP had detectable HCV-RNA by ART at week 4. Again, relapse was not observed in these patients. Conclusions Lower rates of undetectable HCV-RNA at week 4 were observed with ART compared to CAP in patients treated with dual and triple therapies. For ART, detectable <12 IU/ml HCV-RNA levels at week 4 may be sufficient as part of the criteria used for selecting patients who receive a shortened treatment regimen. © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Waidmann O.,Universitatsklinikum Frankfurt |
Trojan J.,Universitatsklinikum Frankfurt
Expert Opinion on Investigational Drugs | Year: 2015
Introduction: Sorafenib is the only systemic drug approved for the treatment of advanced hepatocellular carcinoma (HCC). Within recent years, several investigational agents mainly targeting angiogenesis failed in late-phase clinical development either due to toxicity or lack of benefit.Areas covered: This review covers recent clinical data on systemic agents and ongoing trials in patients with advanced HCC.Expert opinion: In unselected patients with advanced HCC, disappointing results have been reported from several large trials. However, in two subgroups encouraging results have been achieved. Treatment with the MET inhibitor tivantinib resulted in a substantial survival benefit in the subgroup of MET overexpressing tumors in a randomized Phase II trial. Furthermore, the vascular endothelial growth factor receptor 2 antibody ramucirumab resulted in improved overall survival in patients with baseline α-fetoprotein (AFP) ≥ 400 ng/ml in a Phase III trial. These two agents, and several others, will be further developed in HCC. Moreover, immunotherapeutics such as checkpoint inhibitors, programmed death receptor-1 blocking antibodies and oncolytic viruses are under investigation in advanced HCC. © 2015 Informa UK, Ltd.
Zacharowski K.,Universitatsklinikum Frankfurt
Anasthesiologie Intensivmedizin Notfallmedizin Schmerztherapie | Year: 2016
Within the European Union, medical disciplines also have been organized. At the European level, the Union Européenne des Médecins Spécialistes (UEMS) currently represents the interests of 42 medical disciplines and offers support to doctors to work in any European country. For this purpose, guidelines were adopted already in 2005, which, among others, regulate automatic recognition of professional qualifications. This does not apply to intensive care medicine, since in most European countri in the guidelines as a special competence. For this purpose, a multidisciplinary joint committee of the UEMS formulated the so-called European Training Requirements (ETR), the aim of which was to raise the professional skills of European doctors working in the field of intensive care to a uniformly high level. The ETR are currently in the process of being voted upon. As things stand, additional training in intensive care medicine in Germany as currently practised would meet the conditions and requirements of the ETR.
Finkelmeier F.,Universitatsklinikum Frankfurt |
Kronenberger B.,Universitatsklinikum Frankfurt |
Koberle V.,Universitatsklinikum Frankfurt |
Bojunga J.,Universitatsklinikum Frankfurt |
And 4 more authors.
Alimentary Pharmacology and Therapeutics | Year: 2014
Background Vitamin D is involved in many biological processes. The role of vitamin D in patients with hepatocellular carcinoma (HCC) remains inconclusive, although there is evolving evidence that vitamin D may modulate cancer development and progression. Aim To evaluate serum vitamin D as prognostic parameter in HCC, we performed a prospective cohort study. Methods HCC patients were prospectively recruited and 25-hydroxyvitamin D3 (25(OH)D3) levels were determined. 25(OH)D3 levels were compared to stages of cirrhosis and HCC stages with nonparametric Kruskal-Wallis tests and Spearman correlations in 200 HCC patients. The association of the 25(OH)D3 levels and overall survival (OS) was assessed in uni- and multivariate Cox regression models. Results Two-hundred patients with HCC were included. The mean follow-up time was 322 ± 342 days with a range of 1-1508 days. Nineteen patients underwent liver transplantation and 60 patients died within the observation time. The mean serum 25(OH)D3 concentration was 17 ± 13 ng/mL with a range of 1-72 ng/mL. 25(OH)D3 serum levels negatively correlated with the stage of cirrhosis as well as with stages of HCC. Patients with severe 25(OH)D3 deficiency had the highest mortality risk (hazard ratio 2.225, 95% confidence interval 1.331-3.719, P = 0.002). Furthermore, very low 25(OH)D3 levels were associated with mortality independently from the MELD score and high alpha-Fetoprotein levels (>400 ng/mL) in a multivariate Cox regression model. Conclusions We conclude that 25(OH)D3 deficiency is associated with advanced stages of hepatocellular carcinoma and it is a prognostic indicator for a poor outcome. © 2014 John Wiley & Sons Ltd.
Koch C.,Universitatsklinikum Frankfurt |
Trojan J.,Universitatsklinikum Frankfurt
Digestion | Year: 2015
Background: Gastrointestinal cancers are among the leading causes of cancer-related deaths worldwide. In different tumor types, personalized systemic treatment strategies based upon biomarker-selection were established over the last years. Although there is a flood of targeted agents in clinical development, only a few targeted agents with a predictive biomarker could be established for the treatment of patients with gastrointestinal cancer patients so far. Summary: Currently, predictive biomarkers for gastrointestinal cancers include Her2 overexpression or amplification (gastroesophageal adenocarcinoma), c-Kit overexpression (gastrointestinal stromal tumors) and RAS wild-type (colorectal cancer). Selection of patients based on these biomarkers allows the efficient use of targeted agents. The presence of a BRAF mutation and/or high microsatellite instability is prognostic and rather a predictive marker in CRC. Promising candidate markers in advanced clinical development are MET amplification in gastroesophageal adenocarcinoma, Met overexpression and high AFP serum levels in hepatocellular carcinoma. Key Message: Biomarker-guided systemic treatment is established in a subset of patients with gastrointestinal cancer. Ongoing clinical trials and further advances in high-throughput technologies will hopefully result in more personalized systemic treatment strategies for these patients in the near future. © 2015 S. Karger AG, Basel.
Arencibia J.M.,Universitatsklinikum Frankfurt |
Pastor-Flores D.,Universitatsklinikum Frankfurt |
Bauer A.F.,Universitatsklinikum Frankfurt |
Schulze J.O.,Universitatsklinikum Frankfurt |
Biondi R.M.,Universitatsklinikum Frankfurt
Biochimica et Biophysica Acta - Proteins and Proteomics | Year: 2013
The group of AGC protein kinases includes more than 60 protein kinases in the human genome, classified into 14 families: PDK1, AKT/PKB, SGK, PKA, PKG, PKC, PKN/PRK, RSK, NDR, MAST, YANK, DMPK, GRK and SGK494. This group is also widely represented in other eukaryotes, including causative organisms of human infectious diseases. AGC kinases are involved in diverse cellular functions and are potential targets for the treatment of human diseases such as cancer, diabetes, obesity, neurological disorders, inflammation and viral infections. Small molecule inhibitors of AGC kinases may also have potential as novel therapeutic approaches against infectious organisms. Fundamental in the regulation of many AGC kinases is a regulatory site termed the "PIF-pocket" that serves as a docking site for substrates of PDK1. This site is also essential to the mechanism of activation of AGC kinases by phosphorylation and is involved in the allosteric regulation of N-terminal domains of several AGC kinases, such as PKN/PRKs and atypical PKCs. In addition, the C-terminal tail and its interaction with the PIF-pocket are involved in the dimerization of the DMPK family of kinases and may explain the molecular mechanism of allosteric activation of GRKs by GPCR substrates. In this review, we briefly introduce the AGC kinases and their known roles in physiology and disease and the discovery of the PIF-pocket as a regulatory site in AGC kinases. Finally, we summarize the current status and future therapeutic potential of small molecules directed to the PIF-pocket; these molecules can allosterically activate or inhibit the kinase as well as act as substrate-selective inhibitors. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases (2012). © 2013 Elsevier B.V.
Rader T.,Universitatsklinikum Frankfurt
HNO | Year: 2014
Background: Cochlear implantation with the aim of hearing preservation for combined electric–acoustic stimulation (EAS) is the therapy of choice for patients with residual low-frequency hearing. Preserved residual acoustic hearing has a positive effect on speech intelligibility in difficult noise conditions. Objectives: The goal of this study was to assess speech reception thresholds in various complex noise conditions for patients with EAS in comparison with patients using bilateral cochlear implants (CI). Materials and methods: Speech perception in noise was measured for bilateral CI and EAS patient groups. A total of 22 listeners with normal hearing served as a control group. Speech reception thresholds (SRT) were measured using a closed-set sentence matrix test. Speech was presented with a single source in frontal position; noise was presented in frontal position or in a multisource noise field (MSNF) consisting of a four-loudspeaker array with independent noise sources. Modulated speech-simulating noise and pseudocontinuous noise served respectively as interference signal with different temporal characteristics. Results: The average SRTs in the EAS group were significantly better in all test conditions than those of the group with bilateral CI. Both user groups showed significant improvement in the MSNF condition compared with the frontal noise condition as a result of bilateral interaction. The normal-hearing control group was able to use short temporal gaps in modulated noise to improve speech perception in noise (gap listening). This effect was absent in both implanted user groups. Conclusion: Patients with combined EAS in one ear and a hearing aid in the contralateral ear show significantly improved speech perception in complex noise conditions compared with bilateral CI recipients. © 2014, Springer-Verlag Berlin Heidelberg.
Kahles H.,Universitatsklinikum Frankfurt
Diabetologe | Year: 2016
Objective: Vitamin D is not only essential for bone metabolism, but also has an additional immune-modulating effect on the immune system, which may play a role in the pathogenesis of several endocrine diseases. Aim: In this review, we debate the effects and recommendations of vitamin D supplementation, especially in the context of the nonclassical effects. Results: Evidence from animal model and epidemiological studies supports a role for vitamin D in many endocrine conditions. Vitamin D supplementation may play a role in the prevention of type 1 diabetes mellitus. Conclusions: Although observational studies support a potential role of vitamin D in endocrine disease, high-quality evidence from clinical trials to establish a place for vitamin D supplementation in optimizing endocrine health are lacking. Based on observational studies, vitamin D deficiency should probably be avoided in individuals at high risk of developing type 1 diabetes, specifically in early life. © 2016, Springer-Verlag Berlin Heidelberg.
Welker M.-W.,Universitatsklinikum Frankfurt |
Trojan J.,Universitatsklinikum Frankfurt
Cancer Management and Research | Year: 2013
Hepatocellular carcinoma (HCC) is a severe complication of advanced liver disease with a worldwide incidence of more than 600,000 patients per year. Liver function, clinical performance status, and tumor size are considered in the Barcelona Clinic Liver Cancer (BCLC) system. While curative treatment options are available for early stages, most patients present with intermediate- or advanced-stage HCC, burdened with a poor prognosis, substantially infuenced by the degree of liver-function impairment. Hypervascularization is a major characteristic of HCC, and antiangiogenic treatments are the basis of treatment in noncurative stages, including interventional and pharmacological treatments. Currently, the tyrosine-kinase inhibitor sorafenib is still the only approved drug for HCC. Further improvements in survival in patients with intermediate- and advanced-stage HCC may be anticipated by both multimodal approaches, such as combination of interventional and systemic treatments, and new systemic treatment options. Until now, the Phase III development of other tyrosine-kinase inhibitors in patients with advanced HCC has failed due to minor effcacy and/or increased toxicity compared to sorafenib. However, promising Phase II data have been reported with MET inhibitors in this hard-to-treat population. This review gives a critical overview of antiangiogenic drugs and strategies in intermediate and advanced stage HCC, with a special focus on safety. © 2013 Welker and Trojan. This work is published by Dove Medical Press Ltd.