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Background: Hereditary angioedema (HAE), caused by deficiency in C1-inhibitor (C1-INH), leads to unpredictable edema of subcutaneous tissues with potentially fatal complications. As surgery can be a trigger for edema episodes, current guidelines recommend preoperative prophylaxis with C1-INH or attenuated androgens in patients with HAE undergoing surgery. However, the risk of an HAE attack in patients without prophylaxis has not been quantified.
Objectives: This analysis examined rates of perioperative edema in patients with HAE not receiving prophylaxis.
Methods: This was a retrospective analysis of records of randomly selected patients with HAE type I or II treated at the Frankfurt Comprehensive Care Centre. These were examined for information about surgical procedures and the presence of perioperative angioedema.
Results: A total of 331 patients were included; 247 underwent 700 invasive procedures. Of these procedures, 335 were conducted in 144 patients who had not received prophylaxis at the time of surgery. Categories representing significant numbers of procedures were abdominal (n = 113), ENT (n = 71), and gynecological (n = 58) procedures. The rate of documented angioedema without prophylaxis across all procedures was 5.7%; in 24.8% of procedures, the presence of perioperative angioedema could not be excluded, leading to a maximum potential risk of 30.5%. Predictors of perioperative angioedema could not be identified.
Conclusion: The risk of perioperative angioedema in patients with HAE type I or II without prophylaxis undergoing surgical procedures ranged from 5.7% to 30.5% (CI 3.5–35.7%). The unpredictability of HAE episodes supports current international treatment recommendations to consider short-term prophylaxis for all HAE patients undergoing surgery.
Mobilized blood has supplanted bone marrow (BM) as the primary source of hematopoietic stem cells for autologous and allogeneic stem cell transplantation. Pharmacologically enforced egress of hematopoietic stem cells from BM, or mobilization, has been achieved by directly or indirectly targeting the CXCL12/CXCR4 axis. Shortcomings of the standard mobilizing agent, granulocyte colony-stimulating factor (G-CSF), administered alone or in combination with the only approved CXCR4 antagonist, Plerixafor, continue to fuel the quest for new mobilizing agents. Using Protein Epitope Mimetics technology, a novel peptidic CXCR4 antagonist, POL5551, was developed. In vitro data presented herein indicate high affinity to and specificity for CXCR4. POL5551 exhibited rapid mobilization kinetics and unprecedented efficiency in C57BL/6 mice, exceeding that of Plerixafor and at higher doses also of G-CSF. POL5551-mobilized stem cells demonstrated adequate transplantation properties. In contrast to G-CSF, POL5551 did not induce major morphological changes in the BM of mice. Moreover, we provide evidence of direct POL5551 binding to hematopoietic stem and progenitor cells (HSPCs) in vivo, strengthening the hypothesis that CXCR4 antagonists mediate mobilization by direct targeting of HSPCs. In summary, POL5551 is a potent mobilizing agent for HSPCs in mice with promising therapeutic potential if these data can be orroborated in humans.
The role of the mRNA-binding protein human antigen R (HuR) in stabilization and translation of AU-rich elements (ARE) containing mRNAs is well established. However, the trafficking of HuR and bound mRNA cargo, which comprises a fundamental requirement for the aforementioned HuR functions is only poorly understood. By administering different cytoskeletal inhibitors, we found that the protein kinase Cδ (PKCδ)-triggered accumulation of cytoplasmic HuR by Angiotensin II (AngII) is an actin-myosin driven process functionally relevant for stabilization of ARE-bearing mRNAs. Furthermore, we show that the AngII-induced recruitment of HuR and its bound mRNA from ribonucleoprotein particles to free and cytoskeleton bound polysomes strongly depended on an intact actomyosin cytoskeleton. In addition, HuR allocation to free and cytoskeletal bound polysomes is highly sensitive toward RNase and PPtase and structurally depends on serine 318 (S318) located within the C-terminal RNA recognition motif (RRM3). Conversely, the trafficking of the phosphomimetic HuRS318D, mimicking HuR phosphorylation at S318 by the PKCδ remained PPtase resistant. Co-immunoprecipitation experiments with truncated HuR proteins revealed that the stimulus-induced association of HuR with myosin IIA is strictly RNA dependent and mediated via the RRM3. Our data implicate a microfilament dependent transport of HuR, which is relevant for stimulus-induced targeting of ARE-bearing mRNAs from translational inactive ribonucleoprotein particles to polysomes.
Background: Patients suffering from acute type A aortic dissection undergo replacement of the ascending aorta, the proximal hemiarch or complete aortic arch, depending on the extent of the individual pathology. In a subset of these treated patients, secondary pathologies of the distal anastomosis or the remaining distal part of the aorta occur. The treatment of these pathologies is challenging, requiring major surgical re-do procedures with aortic arch replacement under extracorporeal circulation and hypothermic circulatory arrest.
Methods: We report our experience of five patients with complex aortic pathologies after previous aortic surgery treated with a single stage re-do hybrid procedure, consisting of bypass grafting of the supraaortic branches off-pump, stent graft placement for endovascular aortic repair (TEVAR) and surgical debranching of the aortic arch.
Results: In all patients the surgical vascular grafts and stent grafts were deployed successfully, there were no intraoperative deaths. Four out of five patients were discharged from hospital in good clinical condition. One patient died postoperatively due to cardiac tamponade. In one patient a type I endoleak persisted leading to occlusion of a bypass branch requiring surgical revision at one year after debranching.
Conclusion: We discuss the prerequisites, all steps and potential pitfalls of this hybrid aortic arch replacement. The current procedure avoids cardiopulmonary bypass and circulatory arrest, which may benefit early patient outcome; however, patient and device selection plays a key role for immediate success and midterm outcomes. In addition, precise procedural planning and development of customized stents may help to develop this procedure into a true alternative for conventional aortic arch replacement.
System size dependence of hadron production properties is discussed within the Wounded Nucleon Model and the Statistical Model in the grand canonical, canonical and micro-canonical formulations. Similarities and differences between predictions of the models related to the treatment of conservation laws are exposed. A need for models which would combine a hydrodynamicallike expansion with conservation laws obeyed in individual collisions is stressed.
Bislang war in deutschen Städten das Wohnen im Eigentum – entweder im Eigenheim oder in der Eigentumswohnung – die Ausnahme. Insbesondere in Großstädten dominierte das Wohnen zur Miete. Gegenwärtig ändert sich dies: Großstädte wie Frankfurt, Berlin, Hamburg, Köln und München sind gegenwärtig geprägt von einer Kauflust privater und institutioneller Investoren. Zugleich hat in vielen Städten ein Ausverkauf und/oder Vermarktlichung des öffentlichen Wohnungsbestandes stattgefunden. Dies hat dazu beigetragen, dass die Preise sehr stark angestiegen sind. In dem Beitrag wird die aktuelle Entwicklung auf städtischen Wohnungsmärkten in Deutschland als Folge einer Finanzialisierung von Immobilien sowie einer Responsibilisierung im Bereich der Wohnversorgung analysiert. Es wird gefragt, welche Folgen dies in Städten hat.
Im Zuge des Bildungsstreiks 2009 besetzten Studierende der Johann Wolfgang Goethe-Universität (JWGU) in Frankfurt das „Casino“, ein zentrales Gebäude auf dem neuen IG-Farben-Campus im Westend. Während frühere Besetzungen von Universitätsgebäuden auf dem alten Campus in Bockenheim von der Universitätsleitung zwar auch nicht gerade begrüßt, aber doch toleriert worden sind, ließ das Präsidium im jüngsten Fall 176 Studierende nach nur drei Tagen polizeilich räumen. Um diesen repressiven Wandel im Umgang mit studentischem Protest zu verstehen, rekonstruieren wir im Folgenden die Art und Weise, wie die JWGU als Teil des Staatsapparates Universität zu unterschiedlichen Zeiten zwei Campus als konkrete Orte (places) hervorgebracht hat, die jeweils als Ausdruck und Verdichtung der nationalen und lokalen gesellschaftlichen Kräfteverhältnisse im Fordismus bzw. Neoliberalismus zu interpretieren sind.
BACKGROUND: The AGO-ETC trial compared 5-year relapse-free survival of intense dose-dense (IDD) sequential chemotherapy with epirubicin (E), paclitaxel (T), and cyclophosphamide (C) (IDD-ETC) every 2 weeks vs conventional scheduled epirubicin/cyclophosphamide followed by paclitaxel (EC→T) (every 3 weeks) as adjuvant treatment in high-risk breast cancer patients. The objective of this study was to evaluate the safety and efficacy of epoetin alfa in a second randomization of the intense dose-dense arm.
METHODS: One thousand two hundred eighty-four patients were enrolled; 658 patients were randomly assigned to the IDD-ETC treatment group. Within the IDD-ETC group, 324 patients were further randomly assigned to the epoetin alfa group, and 319 were randomly assigned to the non-erythropoiesis-stimulating agent (ESA) control group. Primary efficacy endpoints included change in hemoglobin level from baseline to Cycle 9 and the percentage of subjects requiring red blood cell transfusion. Relapse-free survival, overall survival, and intramammary relapse were secondary endpoints estimated with Kaplan-Meier and Cox regression methods. Except for the primary hypothesis, all statistical tests were two-sided.
RESULTS: Epoetin alfa avoided the decrease in hemoglobin level (no decrease in the epoetin alfa group vs -2.20g/dL change for the control group; P < .001) and statistically significantly reduced the percentage of subjects requiring red blood cell transfusion (12.8% vs 28.1%; P < .0001). The incidence of thrombotic events was 7% in the epoetin alfa arm vs 3% in the control arm. After a median follow-up of 62 months, epoetin alfa treatment did not affect overall survival, relapse-free survival, or intramammary relapse.
CONCLUSIONS: Epoetin alfa resulted in improved hemoglobin levels and decreased transfusions without an impact on relapse-free or overall survival. However, epoetin alfa had an adverse effect, resulting in increased thrombosis.
BACKGROUND: To report the clinical outcome of high dose rate brachytherapy as sole treatment for clinically localised prostate cancer.
METHODS: Between March 2004 and January 2008, a total of 351 consecutive patients with clinically localised prostate cancer were treated with transrectal ultrasound guided high dose rate brachytherapy. The prescribed dose was 38.0 Gy in four fractions (two implants of two fractions each of 9.5 Gy with an interval of 14 days between the implants) delivered to an intraoperative transrectal ultrasound real-time defined planning treatment volume. Biochemical failure was defined according to the Phoenix Consensus and toxicity evaluated using the Common Toxicity Criteria for Adverse Events version 3.
RESULTS: The median follow-up time was 59.3 months. The 36 and 60 month biochemical control and metastasis-free survival rates were respectively 98%, 94% and 99%, 98%. Toxicity was scored per event with 4.8% acute Grade 3 genitourinary and no acute Grade 3 gastrointestinal toxicity. Late Grade 3 genitourinary and gastrointestinal toxicity were respectively 3.4% and 1.4%. No instances of Grade 4 or greater acute or late adverse events were reported.
CONCLUSIONS: Our results confirm high dose rate brachytherapy as safe and effective monotherapy for clinically organ-confined prostate cancer.