Wörth an der Isar, Germany
Wörth an der Isar, Germany

Time filter

Source Type

Kleine J.F.,Klinikum Rechts der Isar | Beller E.,Klinikum Rechts der Isar | Zimmer C.,Klinikum Rechts der Isar | Kaesmacher J.,Klinikum Rechts der Isar
Journal of NeuroInterventional Surgery | Year: 2017

Background In stroke due to middle cerebral artery (MCA) occlusion, collaterals may sustain tissue in the peripheral MCA territory, extending the time window for recanalizing therapies. However, MCA occlusions often block some or all of the 'lenticulostriate' (LS) arteries originating from the M1 segment, eliminating blood flow to dependent territories in the striatum, which have no collateral supply. This study examines whether mechanical thrombectomy (MTE) can avert imminent striatal infarction in patients with acute MCA occlusion. Methods 279 patients with isolated MCA occlusion subjected to MTE were included. Actual LS occlusions and infarctions were assigned to predefined 'LS occlusion' and 'LS infarct' patterns derived from known LS vascular anatomy. The predictive performance of LS occlusion patterns regarding ensuing infarction in striatal subterritories was assessed by standard statistical measures. Results LS occlusion patterns predicted infarction in associated striatal subterritories with a positive predictive value (PPV) of 91% and a negative predictive value of 81%. In 15 of the 22 patients who did not develop the predicted striatal infarctions, reassessment of angiographies revealed LS vascular supply variants that explained these 'false positive' LS occlusion patterns, raising the PPV to 96%. Symptom onset to recanalization times were relatively short, but this alone could not account for the false positive LS occlusion patterns in the remaining seven of these patients. Conclusions With currently achievable symptom onset to recanalization times, striatal infarctions are determined by MCA occlusion sites and individual vascular anatomy, and cannot normally be averted by MTE, but there are exceptions. Further study of such exceptional cases may yield important insights into the determinants of infarct growth in the hyperacute phase of infarct evolution. © Published by the BMJ Publishing Group Limited.

News Article | March 1, 2017
Site: www.eurekalert.org

Reston, Va. - In the featured article of the March 2017 issue of "The Journal of Nuclear Medicine," researchers demonstrate that a new positron emission tomography (PET) radiotracer, gallium-68 (Ga-68)-pentixafor, can quickly and non-invasively identify life-threatening atherosclerotic plaques. The tracer binds to the CXCR4 receptor on inflammatory cells present in atherosclerotic plaques--making it possible to find and treat atherosclerosis early. Atherosclerosis represents the main cause of heart attack and stroke. According to the Centers for Disease Control and Prevention, every year about 735,000 Americans have a heart attack and 800,000 have a stroke. Stroke kills more than 130,00 Americans a year, and about 610,000 die from cardiovascular disease. Atherosclerosis develops over decades with the progressive accumulation of lipids, inflammatory cells and connective tissue within the inner layer of arterial walls leading to a local thickening of the vascular wall called atherosclerotic plaque. These plaques can remain asymptomatic for years, but an inflammatory reaction can develop causing the plaques to rupture and stimulate clot formation. If a clot completely blocks an artery, no oxygen can reach the downstream tissue--resulting in the sudden development of heart attack or stroke. The challenge is to identify patients with these dangerous atherosclerotic plaques before a heart attack or stroke occurs. Currently, there is no clinically available non-invasive imaging technique specifically to detect inflammation. F-18-fluorodeoxyglucose (FDG)-PET is being used but has important limitations. It is taken up by many cells other than inflammatory cells, including cardiac and brain cells. The strong signal present in the organs next to the arteries limits the precise analysis of the radiotracer uptake in atherosclerotic plaques. In addition, patients need to fast at least six hours before FDG injection to avoid interferences with blood sugar and muscular uptake of the tracer that impair image quality. "Ga-68-pentixafor binds more specifically to inflammatory cells than FDG and does not require the patient to fast for six hours before imaging," explains Fabien Hyafil, MD, PhD, of Klinikum Rechts der Isar, Munich, Germany, and Bichat University Hospital, Assistance Publique, Hôpitaux de Paris, Paris, France. In the study, the specific binding of Ga-68-pentixafor to inflammatory cells located in atherosclerotic plaques was first validated in an animal model. Seven atherosclerotic rabbits and five controls were imaged on a PET-MRI system after injection of the tracer. Resulting images clearly showed inflammation in plaques in the abdominal aorta and right carotid artery of the atherosclerotic rabbits. The researchers also confirmed with a small number of human patients that the radiotracer detected atherosclerotic plaques located in their carotid arteries. Hyafil emphasizes, "This new radiotracer will strongly facilitate the imaging of inflammation in atherosclerotic plaques with PET and hopefully support the early detection and treatment of atherosclerosis, thus preventing heart attack or stroke." Authors of the article "Imaging the cytokine receptor CXCR4 in atherosclerotic plaques with the radiotracer 68Ga-pentixafor for positron emission tomography" include Fabien Hyafil, Klinikum Rechts der Isar, Munich, Germany, and Bichat University Hospital, Assistance Publique, Hôpitaux de Paris, Paris, France; Jaroslav Pelisek, Iina Laitinen, Miriam Mohring; Michael Kallmayer, Johannes Fischer, Christine Baumgartner, and Hans-Henning Eckstein, of Klinikum Rechts der Isar; Margret Schottelius, Katja Steiger, Andreas Poschenrieder, Johannes Notni, and Hans-Jürgen Wester, Technische Universität München, Garching, Germany; Yvonne Döring and Emiel P.C. van der Vorst, Ludwig-Maximilians-Universität München, Munich, Germany; Christian Weber, Ludwig-Maximilians-Universität München, Technische Universität München, Klinikum Rechts der Isar, DZHK partner site Munich Heart Alliance, and Maastricht University, The Netherlands; Christoph Rischpler, Stephan G. Nekolla, and Markus Schwaiger, Klinikum Rechts der Isar, Bichat University Hospital, Assistance Publique - Hôpitaux de Paris, Technische Universität München, Ludwig-Maximilians-Universität München, DZHK partner site Munich Heart Alliance. This work was supported by the European Research Council Executive Agency through a Multimodal Molecular Imaging Advanced Research Grant (Grant number 294582), the Deutsche Forschungsgemeinschaft (SFB 824-B5 and SFB 1123-A1), and Deutsches Zentrum für Herz-Kreislauf Forschung through a high-risk, high-volume grant. Please visit the SNMMI Media Center to view the PDF of the study, including images, and more information about molecular imaging and personalized medicine. To schedule an interview with the researchers, please contact Laurie Callahan at (703) 652-6773 or lcallahan@snmmi.org. Current and past issues of The Journal of Nuclear Medicine can be found online at http://jnm. . The Society of Nuclear Medicine and Molecular Imaging (SNMMI) is an international scientific and medical organization dedicated to raising public awareness about nuclear medicine and molecular imaging, a vital element of today's medical practice that adds an additional dimension to diagnosis, changing the way common and devastating diseases are understood and treated and helping provide patients with the best health care possible. SNMMI's more than 17,000 members set the standard for molecular imaging and nuclear medicine practice by creating guidelines, sharing information through journals and meetings and leading advocacy on key issues that affect molecular imaging and therapy research and practice. For more information, visit http://www. .

Santoro A.,Instituto Clinico Humanitas IRCCS | Rimassa L.,Instituto Clinico Humanitas IRCCS | Borbath I.,Cliniques Universitaires Saint Luc | Daniele B.,G Rummo Hospital | And 24 more authors.
The Lancet Oncology | Year: 2013

Background: Tivantinib (ARQ 197), a selective oral inhibitor of MET, has shown promising antitumour activity in hepatocellular carcinoma as monotherapy and in combination with sorafenib. We aimed to assess efficacy and safety of tivantinib for second-line treatment of advanced hepatocellular carcinoma. Methods: In this completed, multicentre, randomised, placebo-controlled, double-blind, phase 2 study, we enrolled patients with advanced hepatocellular carcinoma and Child-Pugh A cirrhosis who had progressed on or were unable to tolerate first-line systemic therapy. We randomly allocated patients 2:1 to receive tivantinib (360 mg twice-daily) or placebo until disease progression. The tivantinib dose was amended to 240 mg twice-daily because of high incidence of treatment-emergent grade 3 or worse neutropenia. Randomisation was done centrally by an interactive voice-response system, stratified by Eastern Cooperative Oncology Group performance status and vascular invasion. The primary endpoint was time to progression, according to independent radiological review in the intention-to-treat population. We assessed tumour samples for MET expression with immunohistochemistry (high expression was regarded as ≥2+ in ≥50% of tumour cells). This study is registered with ClinicalTrials.gov, number NCT00988741. Findings: 71 patients were randomly assigned to receive tivantinib (38 at 360 mg twice-daily and 33 at 240 mg twice-daily); 36 patients were randomly assigned to receive placebo. At the time of analysis, 46 (65%) patients in the tivantinib group and 26 (72%) of those in the placebo group had progressive disease. Time to progression was longer for patients treated with tivantinib (1·6 months [95% CI 1·4-2·8]) than placebo (1·4 months [1·4-1·5]; hazard ratio [HR] 0·64, 90% CI 0·43-0·94; p=0·04). For patients with MET-high tumours, median time to progression was longer with tivantinib than for those on placebo (2·7 months [95% CI 1·4-8·5] for 22 MET-high patients on tivantinib vs 1·4 months [1·4-1·6] for 15 MET-high patients on placebo; HR 0·43, 95% CI 0·19-0·97; p=0·03). The most common grade 3 or worse adverse events in the tivantinib group were neutropenia (ten patients [14%] vs none in the placebo group) and anaemia (eight [11%] vs none in the placebo group). Eight patients (21%) in the tivantinib 360 mg group had grade 3 or worse neutropenia compared with two (6%) patients in the 240 mg group. Four deaths related to tivantinib occurred from severe neutropenia. 24 (34%) patients in the tivantinib group and 14 (39%) patients in the placebo group had serious adverse events. Interpretation: Tivantinib could provide an option for second-line treatment of patients with advanced hepatocellular carcinoma and well-compensated liver cirrhosis, particularly for patients with MET-high tumours. Confirmation in a phase 3 trial is needed, with a starting dose of tivantinib 240 mg twice-daily. Funding: ArQule, Daiichi Sankyo (Daiichi Sankyo Group). © 2013 Elsevier Ltd.

Rusai K.,Klinikum Rechts der Isar | Schmaderer C.,Klinikum Rechts der Isar | Hermans J.J.R.,Maastricht University | Lutz J.,Klinikum Rechts der Isar | And 2 more authors.
Transplantation | Year: 2011

BACKGROUND.: Blockade of the renin-angiotensin system (RAS) with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II (Ang II) receptor blockers (ARBs) slow the progression of various chronic kidney diseases and chronic allograft dysfunction. RAS inhibition can be achieved also by directly blocking renin upstream from ACE. However, direct renin inhibition can have additional effects since formation of renoprotective Ang II breakdown products such as angiotensin (Ang) (1-7) that are produced by ACE2 are also inhibited. METHODS.: Using a Fischer-to-Lewis renal transplantation model, the effect of the renin inhibitor aliskiren (10 mg/kg/day) was assessed on the development of chronic allograft dysfunction compared with vehicle treatment and Ang II receptor blockers candesartan. RESULTS.: Aliskiren had no effect on renal function (proteinuria, creatinine clearance) or on renal morphological changes (glomerulosclerosis collagen deposition, myofibroblast accumulation and macrophage infiltration) compared with the vehicle- and candesartan-treated animals determined 24 weeks after transplantation. On the other hand, atrophy of tubular cells was significantly attenuated. Candesartan reduced both proteinuria and structural injury of the kidney. In aliskiren-treated animals reduced serum Ang II and Ang (1-7) levels were detected, whereas the level of urine angiotensinogen was unchanged. CONCLUSIONS.: The renin inhibitor aliskiren does not slow the progression of chronic allograft dysfunction. We suggest that the lack of protection might be due to reduced formation of the protective Ang II breakdown products such as Ang (1-7) or due to unchanged intrarenal RAS activity demonstrated by urinary angiotensinogen levels. Copyright © 2011 by Lippincott Williams & Wilkins.

Shutin D.,University of Graz | Zlobinskaya O.,Klinikum rechts der Isar
Computer Methods and Programs in Biomedicine | Year: 2010

The goal of this contribution is to apply model-based information-theoretic measures to the quantification of relative differences between immunofluorescent signals. Several models for approximating the empirical fluorescence intensity distributions are considered, namely Gaussian, Gamma, Beta, and kernel densities. As a distance measure the Hellinger distance and the Kullback-Leibler divergence are considered. For the Gaussian, Gamma, and Beta models the closed-form expressions for evaluating the distance as a function of the model parameters are obtained. The advantages of the proposed quantification framework as compared to simple mean-based approaches are analyzed with numerical simulations. Two biological experiments are also considered. The first is the functional analysis of the p8 subunit of the TFIIH complex responsible for a rare hereditary multi-system disorder-trichothiodystrophy group A (TTD-A). In the second experiment the proposed methods are applied to assess the UV-induced DNA lesion repair rate. A good agreement between our in vivo results and those obtained with an alternative in vitro measurement is established. We believe that the computational simplicity and the effectiveness of the proposed quantification procedure will make it very attractive for different analysis tasks in functional proteomics, as well as in high-content screening. © 2009 Elsevier Ireland Ltd. All rights reserved.

Meindl A.,Klinikum Rechts der Isar | Ditsch N.,Klinik und Poliklinik fur Gynakologie und Geburtshilfe der LMU | Kast K.,Universitatsklinikum Carl Gustav Carus | Rhiem K.,Universitatsklinikum Cologne | Schmutzler R.K.,Universitatsklinikum Cologne
Deutsches Arzteblatt | Year: 2011

Background: Every year, 60 000 women in Germany are found to have breast cancer, and 9000 to have ovarian cancer. Familial clustering of carcinoma is seen in about 20% of cases. Methods: We selectively review relevant articles published up to December 2010 that were retrieved by a search in PubMed, and we also discuss findings from the experience of the German Consortium for Hereditary Breast and Ovarian Cancer. Results: High risk is conferred by the highly penetrant BRCA1 and BRCA2 genes as well as by other genes such as RAD51C. Genes for breast cancer that were originally designated as moderately penetrant display higher penetrance than previously thought in families with a hereditary predisposition. The role these genes play in DNA repair is thought to explain why tumors associated with them are sensitive to platin derivatives and PARP inhibitors. In carriers of BRCA1 and BRCA2, prophylactic bilateral mastectomy and adnexectomy significantly lowers the incidence of breast and ovarian cancer. Moreover, prophylactic adnexectomy also lowers the breastand-ovarian-cancer- specific mortality, as well as the overall mortality. If a woman bearing a mutation develops cancer in one breast, her risk of developing cancer in the other breast depends on the particular gene that is mutated and on her age at the onset of disease. Conclusion: About half of all monogenically determined carcinomas of the breast and ovary are due to a mutation in one or the other of the highly penetrant BRCA genes (BRCA1 and BRCA2). Women carrying a mutated gene have an 80% to 90% chance of developing breast cancer and a 20% to 50% chance of developing ovarian cancer. Other predisposing genes for breast and ovarian cancer have been identified. Clinicians should develop and implement evidence-based treatments on the basis of these new findings.

Glanzmann M.C.,Orthopadie Obere Extremitaten | Buchmann S.,Orthopadie Obere Extremitaten | Audige L.,Klinikum Rechts der Isar | Kolling C.,Orthopadie Obere Extremitaten | Flury M.,Orthopadie Obere Extremitaten
Archives of Orthopaedic and Trauma Surgery | Year: 2013

Introduction: Persistent horizontal instability after acute acromioclavicular (AC) joint separation may provoke unsatisfactory results of conservative treatment. Hypothesis: the arthroscopically assisted double flip button stabilization of acute horizontally unstable grade III and IV AC joint disruptions results in full functional restoration and stable radiological reposition. Materials: 21 patients treated for an acute grade III or IV AC joint separation were enrolled. Clinical assessment at least 2-year postoperative included the constant score (CS) and the simple shoulder test. A panorama stress view, bilateral axial view and an AC view were obtained for radiographic evaluation. Results: 19 individuals (mean 37 years; 17 men) with 16 Rockwood type III and 3 type IV injuries were available for examination 24-51 months postoperatively. The mean CS was 90.2 points (SD 6.5) with no statistically significant difference between CS and age-adjusted normative values. The mean Simple Shoulder Test scored 11.5 points (range 8-12). Loss of reduction of more than 2 mm in the coronal plane stress views was present in 6 patients (32 %) with no associated loss of functional outcome. Two of four reported complications in four patients were treated surgically (one open revision with graft augmentation for coracoid implant break out, one arthroscopic capsular release for persistent glenohumeral stiffness). Conclusion: Arthroscopically assisted double flip button stabilization for acute grade III and IV AC joint separation restores fully horizontal stability and age-expected shoulder function, resulting in high patient satisfaction, despite a loss of reduction observed radiographically in approximately one-third of patients. Level of evidence: IV. © 2013 Springer-Verlag Berlin Heidelberg.

Glanzmann M.C.,Schulthess Clinic Upper Extremities | Imhoff A.B.,Klinikum Rechts der Isar | Schwyzer H.-K.,Schulthess Clinic Upper Extremities
International Orthopaedics | Year: 2013

Purpose: Musculoskeletal tumours are rare in the daily practice of an orthopaedic surgeon or even a shoulder and elbow specialist. Patient complaints are often related to secondary changes to the underlying disease making the correct diagnosis challenging. The goal of this study is to identify key symptoms and findings which should give rise to suspicion of an osteoid osteoma. Methods: This retrospective study analyses the diagnostic pathway, surgical treatment and clinical outcome of six patients who underwent resection of an osteoid osteoma of the shoulder or elbow joint. Results: Average follow-up was 24 months (range 16-36 months). The neoplasm was often associated with synovitis mimicking a frozen joint causing marked delay in tumour identification. Misdiagnosis led to surgery without addressing the tumour in two cases, making further surgical intervention necessary. Once the tumour was identified and removed the pain resolved rapidly. Conclusions: In cases of chronic shoulder or elbow pain without an adequate clinical history an underlying cause including rarities such as an osteoid osteoma or other musculoskeletal tumours should be taken into consideration. Particularly in young patients, a magnetic resonance imaging (MRI)-proven hot spot of unknown origin should prompt a computed tomography examination to further clarify the source of pain and stiffness. Level of evidence: IV, case series © 2013 Springer-Verlag Berlin Heidelberg.

Jochberger S.,Klinikum Rechts der Isar | Dunser M.W.,Paracelsus Medical University
Wiener Klinische Wochenschrift | Year: 2011

Concomitant hydrocortisone and arginine vasopressin therapy increases arginine vasopressin plasma levels and may improve survival in septic shock. The objective of this post hoc analysis of a prospective study was to determine whether hydrocortisone therapy increases arginine vasopressin plasma levels in patients with septic shock. Forty-five patients were included into the study, of whom 23 (51.1%) received a hydrocortisone infusion because of escalating vasopressor dosages. Median arginine vasopressin plasma levels did not differ between patients treated with and without hydrocortisone therapy [4.2 (2.2-6.2) vs. 4.3 (2.7-6.1) pmol/L] both in a bivariate (p = 0.43, Mann-Whitney U-test) and a logistic regression model adjusted for differences in disease severity (p = 0.38). No association was further detected between hydrocortisone therapy and arginine vasopressin plasma levels in an adjusted linear regression model [β-coefficient, -0.57 (-1.86-0.73), p = 0.39]. We conclude that increased arginine vasopressin plasma levels during concomitant arginine vasopressin and hydrocortisone therapy in septic shock result from reduced arginine vasopressin clearance and not increased arginine vasopressin secretion or interaction of hydrocortisone with the arginine vasopressin assay. © 2011 Springer-Verlag.

Gastroesophageal cancer is the second leading cancer cause of death globally. Despite having improved treatment modalities over the last decade, for most patient's only modest improvements have been seen in overall survival with a median survival below one year. Therefore, in the era of intense translational research and personalized therapy, the identification of novel predictive and diagnostic targets is urgently needed. Patients with Her-2 overexpression or amplification have experienced significant gains in overall survival with the treatment of Trastuzumab in addition to chemotherapy. However, apart from the successful targeting of Her-2 overexpression in gastroesophageal cancer with Trastuzumab, other targeted therapies have fallen short. The molecular targets currently being evaluated in various phase II and III clinical trials include the epidermal derived growth factor receptor (EGFR) with subtypes ERBB-1, ERBB-2 (Her-2/neu), ERBB-3 and ERBB-4, vascular endothelial derived growth factor (VEGF) and its receptor (VEGFR), mammalian target of Rapamycin (mTOR) and antibodies against the tyrosinkinase receptor c-Met.

Loading Klinikum Rechts der Isar collaborators
Loading Klinikum Rechts der Isar collaborators