Kiessling M.K.,UniversityHospital Zurich |
Rogler G.,UniversityHospital Zurich
Swiss Medical Weekly | Year: 2015
Targeting of oncogenic driver mutations with small-molecule inhibitors resulted in powerful treatment options for cancer patients in recent years. The RAS (rat sarcoma) pathway is among the most frequently mutated pathways in human cancer. Whereas targeting mutant Kirsten RAS (KRAS) remains difficult, mutant B rapidly accelerated fibrosarcoma (BRAF) kinase is an established drug target in cancer. Now data show that neuroblastoma RAS (NRAS) and even Harvey RAS (HRAS) mutations could be predictive markers for treatment with mitogen-activated protein kinase (MEK) inhibitors. This review discusses recent preclinical and clinical studies of MEK inhibitors in BRAF and RAS mutant cancer. © 2015, EMH Swiss Medical Publishers Ltd. All rights reserved.
Schu tzler L.,Charité - Medical University of Berlin |
Witt C.M.,Charité - Medical University of Berlin |
Witt C.M.,UniversityHospital Zurich
BMC Complementary and Alternative Medicine | Year: 2014
Background: Complementary and alternative medicine (CAM) is widely used in Germany, with some treatments eligible for health insurance reimbursements. CAM encourages patients to play an active role in their healing process. The belief that a person's own behavior influences health is assessed as the internal health locus of control (IHLOC). Studies on the association between IHLOC and CAM use yield inconsistent results. Using various indicators of CAM use, we evaluated whether there were differences in IHLOC between different groups of CAM users.Methods: A cross-sectional online survey was conducted. IHLOC was compared between participants with high and low appraisal of CAM, between participants who used different types of medications (none, CAM, conventional, both), and who consulted with different health care professionals (none, CAM, conventional, both). Independent samples t-tests and ANOVAs were conducted for the total group and for subgroups of chronically ill and healthy participants. Post-hoc, we conducted a multivariate linear regression evaluating which indicators of CAM use or other characteristics showed the strongest association with IHLOC.Results: A total of 1,054 undergraduate students completed the survey. Participants with high CAM appraisal showed higher IHLOC than those with low CAM appraisal, regardless of whether they were chronically ill (p < .001). Participants without chronic conditions showed higher IHLOC when only using CAM medications than when using either conventional medications alone or both conventional and CAM medications (p < .05). All participants showed higher IHLOC when visiting only CAM practitioners than when visiting either only conventional or both conventional and CAM practitioners (p < .05). CAM appraisal was associated the strongest with IHLOC in the linear regression model.Conclusions: Generally, participants using CAM more or exclusively, and participants with higher appraisal of CAM showed higher IHLOC than those with less CAM use or lower CAM appraisal. Because of the cross-sectional design, it is not possible to determine whether differences in IHLOC are reasons for or consequences of CAM use. Research using a longitudinal design is needed. The sample, though more representative than most student samples, might not represent the general population. Studies evaluating clinical populations might add to the findings. © 2014 Schu¨tzler and Witt; licensee BioMed Central Ltd.
Toteberg-Harms M.,UniversityHospital Zurich |
Sturm V.,UniversityHospital Zurich |
Sel S.,Martin Luther University of Halle Wittenberg |
Sasse A.,Eye Laser Center Halle |
Landau K.,UniversityHospital Zurich
Klinische Monatsblatter fur Augenheilkunde | Year: 2011
Background: Retinal astrocytomas are exceedingly rare benign tumours of the retina. Their occurrence can be solitary or multiple, uni- or bilateral, isolated or in association with a phakomatosis such as tuberous sclerosis or neurofibromatosis type 1. Patients and Methods: We report the long-term follow-up in three patients with retinal astrocytomas. Results: Over many years of follow-up all astrocytomas showed very little progression and no deterioration of visual function. Subtle changes occurred inside the lesions. Conclusions: Even after long-term follow-up the natural course of retinal astrocytic hamartomas seems to be favourable, with visual loss and significant growth being unlikely to occur. A thorough ophthalmological and general evaluation, in order to rule out an underlying systemic disease and to document the ocular status, are needed initially. Thereafter eye examinations can be scheduled in long intervals. © Georg Thieme Verlag KG Stuttgart - New York.
Gessat M.,University of Zürich |
Gessat M.,ETH Zurich |
Hopf R.,ETH Zurich |
Pollok T.,TU Berlin |
And 7 more authors.
IEEE Transactions on Biomedical Engineering | Year: 2014
An approach for extracting the radial force load on an implanted stent from medical images is proposed. To exemplify the approach, a system is presented which computes a radial force estimation from computer tomography images acquired from patients who underwent transcatheter aortic valve implantation (TAVI). The deformed shape of the implanted valve prosthesis' Nitinol frame is extracted from the images. A set of displacement vectors is computed that parameterizes the observed deformation. An iterative relaxation algorithm is employed to adapt the information extracted from the images to a finite-element model of the stent, and the radial components of the interaction forces between the stent and the tissue are extracted. For the evaluation of the method, tests were run using the clinical data from 21 patients. Stent modeling and extraction of the radial forces were successful in 18 cases. Synthetic test cases were generated, in addition, for assessing the sensitivity to the measurement errors. In a sensitivity analysis, the geometric error of the stent reconstruction was below 0.3 mm, which is below the image resolution. The distribution of the radial forces was qualitatively and quantitatively reasonable. An uncertainty remains in the quantitative evaluation of the radial forces due to the uncertainty in defining a radial direction on the deformed stent. With our approach, the mechanical situation of TAVI stents after the implantation can be studied in vivo, which may help to understand the mechanisms that lead to the complications and improve stent design. © 1964-2012 IEEE.
Toteberg-Harms M.,Massachusetts Eye and Ear Infirmary |
Toteberg-Harms M.,UniversityHospital Zurich |
Hanson J.V.,UniversityHospital Zurich |
Funk J.,UniversityHospital Zurich
BMC Ophthalmology | Year: 2013
Background: Cataract surgery combined with excimer laser trabeculotomy (phaco-ELT) can reduce intraocular pressure (IOP). The aim of this study was to evaluate the effect of phaco-ELT on IOP in patients as a function of preoperative IOP. Methods. Patients with open-angle glacuoma or ocular hypertension who received phaco-ELT between 01/2008 and 10/2009 were included. Patients were assigned based on preoperative IOP either to the study group (≤21 mmHg) or control group (>21 mmHg) in this IRB-approved, prospective, consecutive case series. Visual Acuity, IOP, and number of anti-glaucoma drugs (AGD) were recorded at baseline and 12 months after phaco-ELT. Any postoperative complications were also recorded. Results: 64 eyes of 64 patients (76.5 ± 9.4 years) were included. Baseline IOP was 19.8 ± 5.3 mmHg (AGD 2.4 ± 1.1) for all eyes, 16.5 ± 2.9 mmHg (AGD 2.5 ± 1.0) for the study group, and 25.8 ± 2.9 mmHg (AGD 2.2 ± 1.4) for the control group. Across the two groups, IOP was reduced by 4.5 ± 5.9 mmHg (-23.0%, p < 0.001) and AGD by 0.9 ± 1.5 (-38.9%, p < 0.001). For the study group IOP was reduced by 1.9 ± 4.4 mmHg (-11. 5 %, p = 0.012) and AGD by 1.1 ± 1.4 (-42.9%, p < 0.001), and for the control group by 9.5 ± 5.4 mmHg (-36.6%, p < 0.001) and AGD by 0.7 ± 1.6 (-29.5%, p = 0.085). There were no serious postoperative complications such as endophthalmitis, significant hyphema, or a severe fibrinous reaction of the anterior chamber. Conclusions: IOP remained significantly reduced from baseline 12 months after phaco-ELT regardless of preoperative IOP levels, with no major complications. The IOP reduction remained constant over the entire follow-up. Hence, phaco-ELT can be considered in glaucoma and ocular hypertensive patients whenever cataract surgery is performed, in order to further reduce IOP or to reduce the requirement for IOP-reducing medications. © 2013 Töteberg-Harms et al.; licensee BioMed Central Ltd.
Kochendorfer L.,UniversityHospital Zurich |
Bauer P.,Cantonal Hospital Winterthur |
Funk J.,UniversityHospital Zurich |
Toteberg-Harms M.,UniversityHospital Zurich |
Toteberg-Harms M.,Massachusetts Eye and Ear Infirmary
Klinische Monatsblatter fur Augenheilkunde | Year: 2014
Background: The aim of this study was to evaluate the reproducibility of the posterior pole asymmetry analysis (PPAA) in glaucomatous eyes and healthy controls in comparison to retinal nerve fiber layer measurements (RNFL) with spectral domain optical coherence tomography (SD-OCT). Patients and Methods: Prospectively, in a single session by one operator, three measurements were taken of the retinal thickness with the PPAA and three measurements of the RNFL with the eye-tracker function of the Heidelberg Spectralis SD-OCT. Results: The mean intraclass correlation coefficient (ICC) and lower confidence intervals (in parentheses) for PPAA were 0.98 (0.96) in both healthy (36 eyes) and glaucomatous eyes (26 eyes). Global coefficients of variation (COVs) were between 0.0 and 1.1% in healthy controls and between 0.0 and 1.9% in glaucoma eyes. Global ICCs for RNFL were 0.98 (0.96) in healthy controls and 0.98 (0.97) in glaucoma eyes and global COVs were between 0.0 and 6.8% in healthy controls and between 0.0 and 3.0% in glaucoma eyes. Conclusion: Reproducibility of the PPAA was good and exceeds that of established RNFL measurements. Thus, PPAA is an additional useful tool in management of glaucoma. © Georg Thieme Verlag KG · Stuttgart · New York.
PubMed | UniversityHospital Zurich
Type: | Journal: Current opinion in ophthalmology | Year: 2016
Despite a decrease in real average growth rates per capita since 2009, healthcare costs continue to rise worldwide. Numerous patient-related and doctor-related factors have contributed to this rise. Glaucoma is the leading cause of irreversible blindness and requires chronic, usually lifelong treatment. As with other chronic diseases, the adherence to prescribed treatment is often low and maybe influenced by the cost of the therapy. The purpose of this review is to seek potential solutions to best control the escalating costs of glaucoma care.The studies we selected for this review can be divided into four different categories: costs of diagnostic tests; costs of direct comparisons between drugs or laser and conventional surgery; patient-related factors (such as adherence); and general aspects regarding costs: theoretical models and calculations.It is challenging to find reliable studies concerning this subject matter. As patients are under the umbrellas of variously organized healthcare systems which span different cultures, the costs between countries are difficult to compare. However, one common aspect to lower costs in glaucoma care is to improve patient adherence. Theoretical models with actual patient studies could enable cost reductions by comparing multiple diagnostic and therapeutic scenarios. VIDEO ABSTRACT: http://links.lww.com/COOP/A22.
PubMed | University of Zürich, UniversityHospital Zurich and Children's Hospital of Philadelphia
Type: Journal Article | Journal: PloS one | Year: 2016
High-risk neuroblastoma remains lethal in about 50% of patients despite multimodal treatment. Recent attempts to identify molecular targets for specific therapies have shown that Neuroblastoma RAS (NRAS) is significantly mutated in a small number of patients. However, few inhibitors for the potential treatment for NRAS mutant neuroblastoma have been investigated so far. In this in-vitro study, we show that MEK inhibitors AZD6244, MEK162 and PD0325901 block cell growth in NRAS mutant neuroblastoma cell lines but not in NRAS wild-type cell lines. Several studies show that mutant NRAS leads to PI3K pathway activation and combined inhibitors of PI3K/mTOR effectively block cell growth. However, we observed the combination of MEK inhibitors with PI3K or AKT inhibitors did not show synergestic effects on cell growth. Thus, we tested single mTOR inhibitors Everolimus and AZD8055. Interestingly, Everolimus and AZD8055 alone were sufficient to block cell growth in NRAS mutant cell lines but not in wild-type cell lines. We found that Everolimus alone induced apoptosis in NRAS mutant neuroblastoma. Furthermore, the combination of mTOR and MEK inhibitors resulted in synergistic growth inhibition. Taken together, our results show that NRAS mutant neuroblastoma can be targeted by clinically available Everolimus alone or in combination with MEK inhibitors which could impact future clinical studies.
PubMed | UniversityHospital Zurich
Type: | Journal: Swiss medical weekly | Year: 2015
Targeting of oncogenic driver mutations with small-molecule inhibitors resulted in powerful treatment options for cancer patients in recent years. The RAS (rat sarcoma) pathway is among the most frequently mutated pathways in human cancer. Whereas targeting mutant Kirsten RAS (KRAS) remains difficult, mutant B rapidly accelerated fibrosarcoma (BRAF) kinase is an established drug target in cancer. Now data show that neuroblastoma RAS (NRAS) and even Harvey RAS (HRAS) mutations could be predictive markers for treatment with mitogen-activated protein kinase (MEK) inhibitors. This review discusses recent preclinical and clinical studies of MEK inhibitors in BRAF and RAS mutant cancer.
PubMed | Triemli Hospital Zurich and UniversityHospital Zurich
Type: Comparative Study | Journal: Klinische Monatsblatter fur Augenheilkunde | Year: 2014
The aim of the study was to analyse the efficacy of selective laser trabeculoplasty in patients on medical therapy and to evaluate a possible influence of prostaglandin therapy on intraocular pressure reduction.A retrospective chart review was undertaken of patients with ocular hypertension or open angle glaucoma who underwent selective laser trabeculoplasty between 3/2008 and 12/2010. Data were collected preoperatively, on the day of intervention, 1 day, 1 month and then every 3 months post selective laser trabeculoplasty. The main outcome measure was mean intraocular pressure reduction.109 eyes (76 on prostaglandins) were included. Mean preoperative intraocular pressure was 22.3 4.5 mmHg (prostaglandin nave) and 19.2 4.8 mmHg (on prostaglandin) (p=0.003). Up to 1 year follow-up, intraocular pressure was statistically significantly reduced in both groups (p 0.019). Eyes with a higher preoperative intraocular pressure had a greater pressure reduction (Spearman rho=0.387, p=0.002). Eyes nave to prostaglandins initially had a greater reduction in intraocular pressure, although after 1 year of follow-up the difference was no longer statistically significant.Selective laser trabeculoplasty significantly reduces intraocular pressure in patients already on medical therapy. A sustained influence of prostaglandin therapy on the efficacy of selective laser trabeculoplasty was not found.