Radiotherapy in langerhans cell histiocytosis : a rare indication in a rare disease

Introduction: Langerhans Cell Histiocytosis (LCH) represents a rare benign disorder, previously designated as "Histiocytosis X", "Type II Histiocytosis" or "Langerhans Cell Granulomatosis". Clinical presentation includes osteolysis, ulcerations of skin and soft tissues but also involvement of the CNS is described.Because treatment concepts are not well defined the German Cooperative Group on Radiotherapy for Benign Diseases performed a retrospective analysis. Methods and material: Eight closely cooperating centres collected patients' data of the past 45 years. As study endpoints disease free survival, recurrent disease, death and therapy related side effects were defined. Results: A total of 80 patients with histologically proven LCH were irradiated within the past 45 years. According to the LCH classification of Greenberger et al. 37 patients had stage Ia, 21 patients stage Ib, 13 patients stage II and 9 patients stage IIIb and the median age was 29 years. The median Follow up was 54 months (range 9-134 months). A total of 39 patients had a surgical intervention and 23 patients a chemotherapy regimen.Radiation treatment was carried out with a median total dose of 15 Gy (range 3-50.4 Gy). The median single fraction was 2 Gy (range 1.8-3 Gy).Overall, 77% patients achieved a complete remission and 12.5% achieved a partial remission. The long-term control rate reached 80%. Within an actuarial overall 5-year survival of 90% no radiogenic side and late effects ≥EORTC/RTOG II° were observed. Conclusion: In the present study a large collective of irradiated patients was analysed. Radiotherapy (RT) is a very effective and safe treatment option and even low RT doses show sufficient local control

GABAA_A Receptors Containing the α\alpha2 Subunit Are Critical for Direction-Selective Inhibition in the Retina

Far from being a simple sensor, the retina actively participates in processing visual signals. One of the best understood aspects of this processing is the detection of motion direction. Direction-selective (DS) retinal circuits include several subtypes of ganglion cells (GCs) and inhibitory interneurons, such as starburst amacrine cells (SACs). Recent studies demonstrated a surprising complexity in the arrangement of synapses in the DS circuit, i.e. between SACs and DS ganglion cells. Thus, to fully understand retinal DS mechanisms, detailed knowledge of all synaptic elements involved, particularly the nature and localization of neurotransmitter receptors, is needed. Since inhibition from SACs onto DSGCs is crucial for generating retinal direction selectivity, we investigate here the nature of the GABA receptors mediating this interaction. We found that in the inner plexiform layer (IPL) of mouse and rabbit retina, GABA$_A$ receptor subunit $\alpha$2 (GABA$_A$R $\alpha$2) aggregated in synaptic clusters along two bands overlapping the dendritic plexuses of both ON and OFF SACs. On distal dendrites of individually labeled SACs in rabbit, GABA$_A$R $\alpha$2 was aligned with the majority of varicosities, the cell's output structures, and found postsynaptically on DSGC dendrites, both in the ON and OFF portion of the IPL. In GABA$_A$R $\alpha$2 knock-out (KO) mice, light responses of retinal GCs recorded with two-photon calcium imaging revealed a significant impairment of DS responses compared to their wild-type littermates. We observed a dramatic drop in the proportion of cells exhibiting DS phenotype in both the ON and ON-OFF populations, which strongly supports our anatomical findings that $\alpha$2-containing GABA$_A$Rs are critical for mediating retinal DS inhibition. Our study reveals for the first time, to the best of our knowledge, the precise functional localization of a specific receptor subunit in the retinal DS circuit

Radiotherapy in langerhans cell histiocytosis - a rare indication in a rare disease

Introduction: Langerhans Cell Histiocytosis (LCH) represents a rare benign disorder, previously designated as “Histiocytosis X”, “Type II Histiocytosis” or “Langerhans Cell Granulomatosis”. Clinical presentation includes osteolysis, ulcerations of skin and soft tissues but also involvement of the CNS is described. Because treatment concepts are not well defined the German Cooperative Group on Radiotherapy for Benign Diseases performed a retrospective analysis. Methods and material: Eight closely cooperating centres collected patients’ data of the past 45 years. As study endpoints disease free survival, recurrent disease, death and therapy related side effects were defined. Results: A total of 80 patients with histologically proven LCH were irradiated within the past 45 years. According to the LCH classification of Greenberger et al. 37 patients had stage Ia, 21 patients stage Ib, 13 patients stage II and 9 patients stage IIIb and the median age was 29 years. The median Follow up was 54 months (range 9–134 months). A total of 39 patients had a surgical intervention and 23 patients a chemotherapy regimen. Radiation treatment was carried out with a median total dose of 15 Gy (range 3–50.4 Gy). The median single fraction was 2 Gy (range 1.8-3 Gy). Overall, 77% patients achieved a complete remission and 12.5% achieved a partial remission. The long-term control rate reached 80%. Within an actuarial overall 5-year survival of 90% no radiogenic side and late effects ≥EORTC/RTOG II° were observed. Conclusion: In the present study a large collective of irradiated patients was analysed. Radiotherapy (RT) is a very effective and safe treatment option and even low RT doses show sufficient local control.<br

Kreativität des Findens – Figurationen des Zitats

Manche Zitate sucht man nicht, sondern sie werden gefunden, wie man unversehens über einen Stein oder eine Baumwurzel stolpert. Solche Zufälle der Zitation ergeben Figuren des Ein- und Verrückens von Bedeutung, insofern Zitate immer zwischen Aussagekontexten, zwischen Texten stehen. Denn nicht der Urheber, den die Zitation zuschreibt, spricht, sondern der Zitierende, indem er seine eigene Autorschaft einklammert. Von hier aus ist der Titel einer ›Kreativität des Findens‹ gedacht. Theoretische oder systematische Aspekte einer Kreatologie sind weniger intendiert, wenngleich der Ansatz bei der konkreten Figur fürs Grundsätzliche offen ist – zumal bei ›ästhetischen Objekten‹, dem Gegenstandsbereich dieses Bandes. Das was Robert Musil ›induktive Gesinnung‹ nannte, ist hier Voraussetzung der Erschließung, denn ohne Insistenz des Beispiels gegenüber dem Gesetz entfällt die Relevanz des ästhetischen Objekts. – Drei Bereiche strukturieren den Band nach grundständigen Figuren des Zitats, Perspektiven einer Philologie des Zitats mit Blick auf literarische Zitation und nach Randgängen des Zitats mit medienspezifischen Problemstellungen; der Popliterat Thomas Meinecke erläutert seine Kreativität des Findens als literarisches Sampling

Listen to Your Heart: Evaluation of the Cardiologic Ecosystem

Modern implantable cardiologic devices communicate via radio frequency techniques and nearby gateways to a backend server on the internet. Those implanted devices, gateways, and servers form an ecosystem of proprietary hardware and protocols that process sensitive medical data and is often vital for patients’ health. This paper analyzes the security of this Ecosystem, from technical gateway aspects, via the programmer, to configure the implanted device, up to the processing of personal medical data from large cardiological device producers. Based on a real-world attacker model, we evaluated different devices and found several severe vulnerabilities. Furthermore, we could purchase a fully functional programmer for implantable cardiological devices, allowing us to re-program such devices or even induce electric shocks on untampered implanted devices. Additionally, we sent several Art. 15 and Art. 20 GDPR inquiries to manufacturers of implantable cardiologic devices, revealing non-conforming processes and a lack of awareness about patients’ rights and companies’ obligations. This, and the fact that many vulnerabilities are still to be found after many vulnerability disclosures in recent years, present a worrying security state of the whole ecosystem

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Analyzing medical device connectivity and its effect on cyber security in german hospitals

Background!#!Modern healthcare devices can be connected to computer networks and many western healthcare institutions run those devices in networks. At the same time, cyber attacks are on the rise and there is evidence that cybercriminals do not spare critical infrastructure such as major hospitals, even if they endanger patients. Intuitively, the more and closer connected healthcare devices are to public networks, the higher the risk of getting attacked.!##!Methods!#!To asses the current connectivity status of healthcare devices, we surveyed the field of German hospitals and especially University Medical Center UMCs.!##!Results!#!The results show a strong correlation between the networking degree and the number of medical devices. The average number of medical devices is 25.150, with a median of networked medical devices of 3.600. Actual key users of networked medical devices are the departments Radiology, Intensive Care, Radio-Oncology RO, Nuclear Medicine NUC, and Anaesthesiology in the group of UMCs. In the next five years, the usage of networked medical devices will increase significantly in the departments of Surgery, Intensive Care, and Radiology. We detected a strong correlation between the degree of connectivity and the likelihood of being attacked.The survey answers regarding the cyber security status reveal a lack of security basics in some of the inquired hospitals. We did discover successful attacks in hospitals with separated or subsidiary departments. A fusion of competencies on an organizational level facilitates the right behavior here. Most hospitals rated themselves predominantly positively in the self-assessment but also stated the usefulness of IT security insurance.!##!Conclusions!#!Concluding our results, hospitals are already facing the consequences of omitted measures within their growing pool of medical devices. Continuously relying on historically grown structures without adaption and trusting manufactures to solve vectors is a critical behavior that could seriously endanger patients