Publications by authors named "Friedrich Erhart"

16 Publications

  • Page 1 of 1

Heme Biosynthesis mRNA Expression Signature: Towards a Novel Prognostic Biomarker in Patients with Diffusely Infiltrating Gliomas.

Cancers (Basel) 2021 Feb 7;13(4). Epub 2021 Feb 7.

Department of Neurosurgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.

Diffusely infiltrating gliomas are characterized by a variable clinical course, and thus novel prognostic biomarkers are needed. The heme biosynthesis cycle constitutes a fundamental metabolic pathway and might play a crucial role in glioma biology. The aim of this study was thus to investigate the role of the heme biosynthesis mRNA expression signature on prognosis in a large glioma patient cohort. Glioma patients with available sequencing data on heme biosynthesis expression were retrieved from The Cancer Genome Atlas (TCGA). In each patient, the heme biosynthesis mRNA expression signature was calculated and categorized into low, medium, and high expression subgroups. Differences in progression-free and overall survival between these subgroups were investigated including a multivariate analysis correcting for WHO grade, tumor subtype, and patient age and sex. In a total of 693 patients, progression-free and overall survival showed a strictly monotonical decrease with increasing mRNA expression signature subgroups. In detail, median overall survival was 134.2 months in the low, 79.9 months in the intermediate, and 16.5 months in the high mRNA expression signature subgroups, respectively. The impact of mRNA expression signature on progression-free and overall survival was independent of the other analyzed prognostic factors. Our data indicate that the heme biosynthesis mRNA expression signature might serve as an additional novel prognostic marker in patients with diffusely infiltrating gliomas to optimize postoperative management.
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http://dx.doi.org/10.3390/cancers13040662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916021PMC
February 2021

Combined proteomics/miRNomics of dendritic cell immunotherapy-treated glioblastoma patients as a screening for survival-associated factors.

NPJ Vaccines 2020 Jan 16;5(1). Epub 2020 Jan 16.

Activartis Biotech GmbH, Vienna, Austria.

Glioblastoma is the most prevalent and aggressive brain cancer. With a median overall survival of ~15-20 months under standard therapy, novel treatment approaches are desperately needed. A recent phase II clinical trial with a personalized immunotherapy based on tumor lysate-charged dendritic cell (DC) vaccination, however, failed to prolong survival. Here, we investigated tumor tissue from trial patients to explore glioblastoma survival-related factors. We followed an innovative approach of combining mass spectrometry-based quantitative proteomics (n = 36) with microRNA sequencing plus RT-qPCR (n = 38). Protein quantification identified, e.g., huntingtin interacting protein 1 (HIP1), retinol-binding protein 1 (RBP1), ferritin heavy chain (FTH1) and focal adhesion kinase 2 (FAK2) as factor candidates correlated with a dismal prognosis. MicroRNA analysis identified miR-216b, miR-216a, miR-708 and let-7i as molecules potentially associated with favorable tissue characteristics as they were enriched in patients with a comparably longer survival. To illustrate the utility of integrated miRNomics and proteomics findings, focal adhesion was studied further as one example for a pathway of potential general interest.Taken together, we here mapped possible drivers of glioblastoma outcome under immunotherapy in one of the largest DC vaccination tissue analysis cohorts so far-demonstrating usefulness and feasibility of combined proteomics/miRNomics approaches. Future research should investigate agents that sensitize glioblastoma to (immuno)therapy-potentially building on insights generated here.
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http://dx.doi.org/10.1038/s41541-019-0149-xDOI Listing
January 2020

Precision Medicine for the Management of Therapy Refractory Colorectal Cancer.

J Pers Med 2020 Dec 11;10(4). Epub 2020 Dec 11.

Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna, 1090 Vienna, Austria.

In this analysis, we examined the efficacy, feasibility, and limitations of molecular-based targeted therapies in heavily pretreated metastatic colorectal cancer (mCRC) patients after failure of all standard treatments. In this single-center, real-world retrospective analysis of our platform for precision medicine, we mapped the molecular profiles of 60 mCRC patients. Tumor samples of the patients were analyzed using next-generation sequencing panels of mutation hotspots, microsatellite instability testing, and immunohistochemistry. All profiles were reviewed by a multidisciplinary team to provide a targeted treatment recommendation after consensus discussion. In total, we detected 166 mutations in 53 patients. The five most frequently found mutations were and . In 28 cases (47% of all patients), a molecularly targeted therapy could be recommended. Eventually, 12 patients (20%) received the recommended therapy. Six patients (10%) had a clinical benefit. The median time to treatment failure was 3.1 months. Our study demonstrates the feasibility and applicability of using targeted therapies in daily clinical practice for heavily pretreated mCRC patients. This could be used as a targeted treatment option in half of the patients.
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http://dx.doi.org/10.3390/jpm10040272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768503PMC
December 2020

TCGA mRNA Expression Analysis of the Heme Biosynthesis Pathway in Diffusely Infiltrating Gliomas: A Comparison of Typically 5-ALA Fluorescent and Non-Fluorescent Gliomas.

Cancers (Basel) 2020 Jul 24;12(8). Epub 2020 Jul 24.

Department of Neurosurgery, Medical University Vienna, 1090 Vienna, Austria.

5-Aminolevulinic acid (5-ALA) is a fluorescent dye that after metabolization to Protoporphyrin IX (PpIX) by the heme biosynthesis pathway typically leads to visible fluorescence in WHO grade IV but not grade II gliomas. The exact mechanism for high PpIX levels in WHO grade IV gliomas and low PpIX levels in WHO grade II gliomas is not fully clarified. To detect relevant changes in mRNA expression, we performed an in-silico analysis of WHO grade II and IV glioma sequencing datasets provided by The Cancer Genome Atlas (TCGA) to investigate mRNA expression levels of relevant heme biosynthesis genes: Solute Carrier Family 15 Member 1 and 2 (SLC15A1 and SLC15A2), Aminolevulinate-Dehydratase (ALAD), Hydroxymethylbilane-Synthase (HMBS), Uroporphyrinogen-III-Synthase (UROS), Uroporphyrinogen-Decarboxylase (UROD), Coproporphyrinogen-Oxidase (CPOX), Protoporphyrinogen-Oxidase (PPOX), ATP-binding Cassette Subfamily B Member 6 (ABCB6)/G Member 2 (ABCG2) and Ferrochelatase (FECH). Altogether, 258 WHO grade II and 166 WHO grade IV samples were investigated. The mRNA expression levels showed significant differences in 8 of 11 examined genes between WHO grade II and IV gliomas. Significant differences in mRNA expression included increases of HMBS, UROD, FECH and PPOX as well as decreases of SLC15A2, ALAD, UROS and ABCB6 in WHO IV gliomas. Since the majority of changes was found in directions that might actually impair PpIX accumulation in WHO grade IV gliomas, additional studies are needed to analyze the corresponding factors of the heme biosynthesis also on protein level.
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http://dx.doi.org/10.3390/cancers12082043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7466145PMC
July 2020

Combined proteomics/miRNomics of dendritic cell immunotherapy-treated glioblastoma patients as a screening for survival-associated factors.

NPJ Vaccines 2020 16;5. Epub 2020 Jan 16.

Activartis Biotech GmbH, Vienna, Austria.

Glioblastoma is the most prevalent and aggressive brain cancer. With a median overall survival of ~15-20 months under standard therapy, novel treatment approaches are desperately needed. A recent phase II clinical trial with a personalized immunotherapy based on tumor lysate-charged dendritic cell (DC) vaccination, however, failed to prolong survival. Here, we investigated tumor tissue from trial patients to explore glioblastoma survival-related factors. We followed an innovative approach of combining mass spectrometry-based quantitative proteomics ( = 36) with microRNA sequencing plus RT-qPCR ( = 38). Protein quantification identified, e.g., huntingtin interacting protein 1 (HIP1), retinol-binding protein 1 (RBP1), ferritin heavy chain (FTH1) and focal adhesion kinase 2 (FAK2) as factor candidates correlated with a dismal prognosis. MicroRNA analysis identified miR-216b, miR-216a, miR-708 and let-7i as molecules potentially associated with favorable tissue characteristics as they were enriched in patients with a comparably longer survival. To illustrate the utility of integrated miRNomics and proteomics findings, focal adhesion was studied further as one example for a pathway of potential general interest. Taken together, we here mapped possible drivers of glioblastoma outcome under immunotherapy in one of the largest DC vaccination tissue analysis cohorts so far-demonstrating usefulness and feasibility of combined proteomics/miRNomics approaches. Future research should investigate agents that sensitize glioblastoma to (immuno)therapy-potentially building on insights generated here.
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http://dx.doi.org/10.1038/s41541-019-0149-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6965118PMC
January 2020

Low molecular weight heparin versus unfractioned heparin for anticoagulation during perioperative extracorporeal membrane oxygenation: A single center experience in 102 lung transplant patients.

Artif Organs 2020 Jun 18;44(6):638-646. Epub 2020 Feb 18.

Department of Anesthesiology, Intensive Care and Pain Medicine, Medical University of Vienna, Vienna, Austria.

Extracorporeal membrane oxygenation (ECMO) is gaining importance in the perioperative management of lung transplant patients. To date, the ideal substance for anticoagulation of ECMO patients is still a matter of debate. In this study, we describe our experience with the use of low molecular weight heparin (LMWH) in comparison with unfractioned heparin (UFH) in lung transplant patients undergoing perioperative ECMO support. We retrospectively analyzed data from all lung transplant patients who underwent perioperative ECMO support at our institution between 2013 and 2017. Bleeding events served as primary outcome parameter. Secondary outcome parameters consisted of thromboembolic events. 102 patients were included in this study, of which 22 (21.6%) received UFH for anticoagulation, and 80 (78.4%) received LMWH. There was no difference between the two groups in regard to serious bleeding events (22.7% in the UFH group vs 12.5% in the LMWH group, P = .31). However, the proportion of patients experiencing thromboembolic events was significantly higher in the UFH group than in the LMWH group (50% vs 20%, P = .01). After adjusting for baseline differences between the two groups, we still observed a difference with respect to thromboembolic events. These data remain to be validated in future prospective, randomized trials.
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http://dx.doi.org/10.1111/aor.13642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317732PMC
June 2020

Spheroid glioblastoma culture conditions as antigen source for dendritic cell-based immunotherapy: spheroid proteins are survival-relevant targets but can impair immunogenic interferon γ production.

Cytotherapy 2019 06 8;21(6):643-658. Epub 2019 Apr 8.

Activartis Biotech GmbH, Vienna, Austria.

Background: Glioblastoma is the most aggressive type of brain cancer. Dendritic cell (DC)-based immunotherapy against glioblastoma depends on the effectiveness of loaded antigens. Sphere-inducing culture conditions are being studied by many as a potential antigen source. Here, we investigated two different in vitro conditions (spheroid culture versus adherent culture) in relation to DC immunotherapy: (1) We studied the specific spheroid-culture proteome and assessed the clinical importance of spheroid proteins. (2) We evaluated the immunogenicity of spheroid lysate - both compared to adherent conditions.

Methods: We used seven spheroid culture systems, three of them patient-derived. Stemness-related markers were studied in those three via immunofluorescence. Spheroid-specific protein expression was measured via quantitative proteomics. The Cancer Genome Atlas (TCGA) survival data was used to investigate the clinical impact of spheroid proteins. Immunogenicity of spheroid versus adherent cell lysate was explored in autologous ELISPOT systems (DCs and T cells from the three patients).

Results: (1) The differential proteome of spheroid versus adherent glioblastoma culture conditions could successfully be established. The top 10 identified spheroid-specific proteins were associated with significantly decreased overall survival (TCGA MIT/Harvard cohort; n = 350, P = 0.014). (2) In exploratory experiments, immunogenicity of spheroid lysate vis-á-vis interferon (IFN)γ production was lower than that of adherent cell lysate (IFNγ ELISPOT; P = 0.034).

Conclusions: Spheroid culture proteins seem to represent survival-relevant targets, supporting the use of spheroid culture conditions as an antigen source for DC immunotherapy. However, immunogenicity enhancement should be considered for future research. Transferability of our findings in terms of clinical impact and regarding different spheroid-generation techniques needs further validation.
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http://dx.doi.org/10.1016/j.jcyt.2019.03.002DOI Listing
June 2019

Immunological analysis of phase II glioblastoma dendritic cell vaccine (Audencel) trial: immune system characteristics influence outcome and Audencel up-regulates Th1-related immunovariables.

Acta Neuropathol Commun 2018 12 5;6(1):135. Epub 2018 Dec 5.

Activartis Biotech GmbH, Wilhelminenstraße 91/IIf, 1160, Vienna, Austria.

Audencel is a dendritic cell (DC)-based cellular cancer immunotherapy against glioblastoma multiforme (GBM). It is characterized by loading of DCs with autologous whole tumor lysate and in vitro maturation via "danger signals". The recent phase II "GBM-Vax" trial showed no clinical efficacy for Audencel as assessed with progression-free and overall survival in all patients. Here we present immunological research accompanying the trial with a focus on immune system factors related to outcome and Audencel's effect on the immune system. Methodologically, peripheral blood samples (from apheresis before Audencel or venipuncture during Audencel) were subjected to functional characterization via enzyme-linked immunospot (ELISPOT) assays connected with cytokine bead assays (CBAs) as well as phenotypical characterization via flow cytometry and mRNA quantification. GBM tissue samples (from surgery) were subjected to T cell receptor sequencing and immunohistochemistry. As results we found: Patients with favorable pre-existing anti-tumor characteristics lived longer under Audencel than Audencel patients without them. Pre-vaccination blood CD8+ T cell count and ELISPOT Granzyme B production capacity in vitro upon tumor antigen exposure were significantly correlated with overall survival. Despite Audencel's general failure to induce a significant clinical response, it nevertheless seemed to have an effect on the immune system. For instance, Audencel led to a significant up-regulation of the Th1-related immunovariables ELISPOT IFNγ, the transcription factor T-bet in the blood and ELISPOT IL-2 in a dose-dependent manner upon vaccination. Post-vaccination levels of ELISPOT IFNγ and CD8+ cells in the blood were indicative of a significantly better survival. In summary, Audencel failed to reach an improvement of survival in the recent phase II clinical trial. No clinical efficacy was registered. Our concomitant immunological work presented here indicates that outcome under Audencel was influenced by the state of the immune system. On the other hand, Audencel also seemed to have stimulated the immune system. Overall, these immunological considerations suggest that DC immunotherapy against glioblastoma should be studied further - with the goal of translating an apparent immunological response into a clinical response. Future research should concentrate on investigating augmentation of immune reactions through combination therapies or on developing meaningful biomarkers.
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http://dx.doi.org/10.1186/s40478-018-0621-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6280511PMC
December 2018

Gliomasphere marker combinatorics: multidimensional flow cytometry detects CD44+/CD133+/ITGA6+/CD36+ signature.

J Cell Mol Med 2019 01 22;23(1):281-292. Epub 2018 Nov 22.

Department of Tumor Immunology, St. Anna Kinderkrebsforschung Children's Cancer Research Institute, Vienna, Austria.

Glioblastoma is the most dangerous brain cancer. One reason for glioblastoma's aggressiveness are glioblastoma stem-like cells. To target them, a number of markers have been proposed (CD133, CD44, CD15, A2B5, CD36, CXCR4, IL6R, L1CAM, and ITGA6). A comprehensive study of co-expression patterns of them has, however, not been performed so far. Here, we mapped the multidimensional co-expression profile of these stemness-associated molecules. Gliomaspheres - an established model of glioblastoma stem-like cells - were used. Seven different gliomasphere systems were subjected to multicolor flow cytometry measuring the nine markers CD133, CD44, CD15, A2B5, CD36, CXCR4, IL6R, L1CAM, and ITGA6 all simultaneously based on a novel 9-marker multicolor panel developed for this study. The viSNE dimensionality reduction algorithm was applied for analysis. All gliomaspheres were found to express at least five different glioblastoma stem-like cell markers. Multi-dimensional analysis showed that all studied gliomaspheres consistently harbored a cell population positive for the molecular signature CD44+/CD133+/ITGA6+/CD36+. Glioblastoma patients with an enrichment of this combination had a significantly worse survival outcome when analyzing the two largest available The Cancer Genome Atlas datasets (MIT/Harvard Affymetrix: P = 0.0015, University of North Carolina Agilent: P = 0.0322). In sum, we detected a previously unknown marker combination - demonstrating feasibility, usefulness, and importance of high-dimensional gliomasphere marker combinatorics.
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http://dx.doi.org/10.1111/jcmm.13927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6307809PMC
January 2019

Audencel Immunotherapy Based on Dendritic Cells Has No Effect on Overall and Progression-Free Survival in Newly Diagnosed Glioblastoma: A Phase II Randomized Trial.

Cancers (Basel) 2018 Oct 5;10(10). Epub 2018 Oct 5.

Clinical Division of Medical Oncology, Department for Internal Medicine I, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.

Dendritic cells (DCs) are antigen-presenting cells that are capable of priming anti-tumor immune responses, thus serving as attractive tools to generate tumor vaccines. In this multicentric randomized open-label phase II study, we investigated the efficacy of vaccination with tumor lysate-charged autologous DCs (Audencel) in newly diagnosed glioblastoma multiforme (GBM). Patients aged 18 to 70 years with histologically proven primary GBM and resection of at least 70% were randomized 1:1 to standard of care (SOC) or SOC plus vaccination (weekly intranodal application in weeks seven to 10, followed by monthly intervals). The primary endpoint was progression-free survival at 12 months. Secondary endpoints were overall survival, safety, and toxicity. Seventy-six adult patients were analyzed in this study. Vaccinations were given for seven (3⁻20) months on average. No severe toxicity was attributable to vaccination. Seven patients showed flu-like symptoms, and six patients developed local skin reactions. Progression-free survival at 12 months did not differ significantly between the control and vaccine groups (28.4% versus 24.5%, = 0.9975). Median overall survival was similar with 18.3 months (vaccine: 564 days, 95% CI: 436⁻671 versus control: 568 days, 95% CI: 349⁻680; = 0.89, harzard ratio (HR) 0.99). Hence, in this trial, the clinical outcomes of patients with primary GBM could not be improved by the addition of Audencel to SOC.
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http://dx.doi.org/10.3390/cancers10100372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6210090PMC
October 2018

IFN-γ and tumor gangliosides: Implications for the tumor microenvironment.

Cell Immunol 2018 03 2;325:33-40. Epub 2018 Feb 2.

Tumor Immunology, Children's Cancer Research Institute, St. Anna Kinderkrebsforschung e.V., Zimmermannplatz 10, Vienna, Austria. Electronic address:

Gangliosides shed by tumors into their microenvironment (TME) are immunoinhibitory. Interferon-γ (IFN-γ) may boost antitumor immune responses. Thus we wondered whether IFN-γ would counteract tumor ganglioside-mediated immune suppression. To test this hypothesis, we exposed human monocyte-derived LPS-activated dendritic cells (DC) to IFN-γ and to a highly purified ganglioside, GD1a. DC ganglioside exposure decreased TLR-dependent p38 signaling, explaining the previously observed ganglioside-induced down-modulation of pro-inflammatory surface markers and cytokines. Strikingly, while increasing LPS-dependent DC responses, IFN-γ unexpectedly did not counteract the inhibitory effects of GD1a. Rather, induction of indoleamine 2,3-dioxygenase (IDO1), and expression of STAT1/IRF-1 and programmed cell death ligand (PD-L1), indicated that the immunoinhibitory, not an immune stimulatory, IFN-γ-signaling axis, was active. The combination, IFN-γ and DC ganglioside enrichment, markedly impaired DC stimulatory potential of CD8 T-cells. We suggest that gangliosides and IFN-γ may act in concert as immunosuppressive mediators in the TME, possibly promoting tumor progression.
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http://dx.doi.org/10.1016/j.cellimm.2018.01.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5826801PMC
March 2018

Mast Cells Are Abundant in Primary Cutaneous T-Cell Lymphomas: Results from a Computer-Aided Quantitative Immunohistological Study.

PLoS One 2016 28;11(11):e0163661. Epub 2016 Nov 28.

Department of Dermatology and Venereology, Karl Landsteiner University of Health Sciences, St. Pölten, Austria.

Background: Mast cells (MC) are bone marrow derived haematopoetic cells playing a crucial role not only in immune response but also in the tumor microenvironment with protumorigenic and antitumorigenic functions. The role of MC in primary cutaneous T-cell lymphomas (CTCL), a heterogeneous group of non-Hodgkin lymphomas with initial presentation in the skin, is largely unknown.

Objective: To gain more accurate information about presence, number, distribution and state of activation (degranulated vs. non-degranulated) of MC in CTCL variants and clinical stages.

Materials And Methods: We established a novel computer-aided tissue analysis method on digitized skin sections. Immunohistochemistry with an anti-MC tryptase antibody was performed on 34 biopsies of different CTCL subtypes and on control skin samples. An algorithm for the automatic detection of the epidermis and of cell density based CTCL areas was developed. Cells were stratified as being within the CTCL infiltrate, in P1 (a surrounding area 0-30 μm away from CTCL), or in P2 (30-60 μm away from CTCL) area.

Results: We found high MC counts within CTCL infiltrates and P1 and a decreased MC number in the surrounding dermis P2. Higher MC numbers were found in MF compared to all other CTCL subgroups. Regarding different stages of MF, we found significantly higher mast cell counts in stages IA and IB than in stages IIA and IIB. Regarding MC densities, we found a higher density of MC in MF compared to all other CTCL subgroups. More MC were non-degranulated than degranulated.

Conclusion: Here for the first time an automated method for MC analysis on tissue sections and its use in CTCL is described. Eliminating error from investigator bias, the method allows for precise cell identification and counting. Our results provide new insights on MC distribution in CTCL reappraising their role in the pathophysiology of CTCL.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0163661PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5125565PMC
June 2017

Illness Perception in Primary Cutaneous T-cell Lymphomas: What Patients Believe About Their Disease.

Acta Derm Venereol 2016 Mar;96(3):381-5

Department of Dermatology and Venereology, Karl Landsteiner University of Health Sciences, 3100 St. Poelten, Austria.

There is currently no information available on illness perception in primary cutaneous T-cell lymphomas (CTCL). The aim of this study was therefore to gather initial information on disease understanding and interpretation in patients with CTCL. Consecutive patients from a hospital-based primary cutaneous lymphoma ward completed the Revised Illness Perception Questionnaire (IPQ-R) on 2 consecutive visits. A total of 24 patients with different variants of CTCL were included in the study. Patients experienced their condition as being long-lasting, but not fundamentally affecting their lives. Patients had poor belief in personal control, but strong belief in treatment control. They did not show a good understanding of their disease, and had a moderately negative emotional response to their illness. In conclusion, the IPQ-R provides a feasible and reproducible tool for measurement and better understanding of illness perception in patients with CTCL. Knowledge of patients' attitudes towards their disease should enable optimization of the patient-physician relationship and patient care.
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http://dx.doi.org/10.2340/00015555-2245DOI Listing
March 2016

Benefit of immediate beta-blocker therapy on mortality in patients with ST-segment elevation myocardial infarction.

Crit Care Med 2013 Jun;41(6):1396-404

Department of Internal Medicine, Landesklinikum Waldviertel Zwettl, Austria.

Objectives: Despite the recommendations to initiate β-blockade to all patients with an ST-segment elevation myocardial infarction, data concerning the timing of the administration of β-blockers are controversially discussed. In view of these controversies, we analyzed the effect of immediate vs. delayed β-blockade on all-cause mortality of patients with ST-segment elevation myocardial infarction in the Lower Austrian Myocardial Infarction Network.

Design: Nonrandomized, prospective observational cohort study.

Setting: Myocardial infarction network including the out-of-hospital emergency services, five primary-care hospitals and a percutaneous coronary intervention-capable hospital in the western part of Lower Austria.

Patients: The data of all patients with ST-segment elevation myocardial infarction defined according to the American Heart Association criteria and treated according to the treatment protocol of the network were consecutively collected. For the purpose of survival analyses, the baseline survival time was set to 48 hours after the first electrocardiogram, and in all patients with recurrent MI within the observational period, only the first MI was regarded.

Interventions: The treatment protocol recommended either the immediate oral administration of 2.5 mg bisoprolol (within 30 min after the first electrocardiogram) or 24 hours after acute myocardial infarction (delayed β-blockade).

Measurements And Main Results: In total, out of the 664 patients with ST-segment elevation myocardial infarction, 343 (n = 52%) received immediate β-blockade and 321 (48%) received delayed β-blockade. The probability of any death (baseline survival time: 48 hours after first electrocardiogram; 640 patients) was 19.2% in the delayed treatment group and 10.7% in the immediate treatment group (p = 0.0022). Also the probability of cardiovascular mortality was significantly lower in the immediate β-blocker treatment group (immediate treatment group: 9 (5.2%); delayed treatment group: 30 (13.4%); p = 0.0002). Multivariable Cox regression analysis identified immediate β-blocker therapy to be independently protective against death of any cause (odds ratio: 0.55, p = 0.033).

Conclusion: Immediate β-blocker administration in the emergency setting is associated with a reduction of all-cause and cardiovascular mortality in patients with ST-segment elevation myocardial infarction and seems to be superior to a delayed β-blockade in our patient cohort.
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http://dx.doi.org/10.1097/CCM.0b013e31827caa64DOI Listing
June 2013

Outbreak of leptospirosis among triathlon participants in Langau, Austria, 2010.

Wien Klin Wochenschr 2011 Dec 24;123(23-24):751-5. Epub 2011 Nov 24.

Austrian Agency for Health and Food Safety, Vienna, Austria.

We report on the first documented outbreak of leptospirosis in Austria. In July 2010, four cases of serologically confirmed leptospirosis occurred in athletes after a triathlon held in Langau. Heavy rains preceded the triathlon (rainfall: 22 mm). The index case (Patient A) was a 41-year-old previously healthy male, who was admitted to hospital A on July 8 with a four-day history of fever up to 40°C that began 14 days after attending the triathlon event. On July 7, patient B, a 42-year-old male, was admitted to the same hospital, with signs and symptoms of kidney failure. Hemodialysis was performed every other day for 3 weeks. While the serum drawn on the day of admission was negative for antibodies against Leptospira, a specimen from July 28 tested positive with Leptospira interrogans. On July 11, patient C, a 40-year-old male, was admitted to hospital B for nephritis. On July 14, patient D, a 44-year-old male, was admitted to hospital C with a ten days history of intermittent fever, mild dry cough and headache. Our report underlines that in Austria recreational users of bodies of freshwater must be aware of an existing risk of contracting leptospirosis, particularly after heavy rains. The suppressive influence of a triathlon on the immune system is well documented and therefore an outbreak in this population group can be seen as a sensitive indicator concerning possible risk for the general population.
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http://dx.doi.org/10.1007/s00508-011-0100-2DOI Listing
December 2011

Prehospital treatment of patients with acute myocardial infarction with bivalirudin.

Am J Emerg Med 2012 Jan 23;30(1):12-7. Epub 2010 Oct 23.

3rd Medical Department, Landesklinikum St. Pölten, A-3100 St. Pölten, Austria.

Objectives: Patients with acute myocardial infarction are at high risk of dying within the first hours after onset of coronary ischemia. Therefore, pharmacological intervention should be started in the prehospital setting. This study investigates the effect of the prehospital administration of bivalirudin on short-term morbidity and mortality compared to heparin plus abciximab in patients with ST-segment-elevation myocardial infarction (STEMI).

Methods: One hundred ninety-eight patients with STEMI treated with bivalirudin in the prehospital setting were prospectively collected. Coronary angiography was performed to identify the infarct-related artery. In case of a percutaneous coronary intervention, bivalirudin was given according to the guidelines. The historic control group consisted of 171 consecutive patients from the same myocardial infarction network treated with unfractioned heparin and abciximab administration before the admission to the emergency department of the percutaneous coronary intervention center. The primary outcome parameter was the incidence of major adverse cardiac events (recurrent myocardial infarction, stroke, death, target vessel revascularization for ischemia) within 30 days after the primary event.

Results: The overall rate of major adverse cardiac events was significantly lower in the bivalirudin group compared to the abciximab group (7.6% vs 14.6%; P = .04). The number of major bleedings was significantly higher in the abciximab group compared to the bivalirudin group (11.8% vs 3.8%; P = .03).

Conclusions: The use of bivalirudin in the prehospital setting leads to a reduced rate of major cardiovascular events compared to a standard treatment with abciximab plus heparin. Bivalirudin is a reasonable choice of treatment in the prehospital setting for patients with STEMI.
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http://dx.doi.org/10.1016/j.ajem.2010.09.010DOI Listing
January 2012