Entwicklung einer visuell interaktiven Segmentierungskomponente unter Verwendung von OpenCL für das Operationsplanungssystem MOPS 3D

Das neurochirurgische Operationsplanungssystem MOPS 3D wurde am Institut für Medizinische Biometrie und Informatik der Universität Heidelberg entwickelt. Es unterstützt den Chirurgen mit einer Vielzahl von Methoden bei der Operationsplanung und der Durchführung. Dabei hat sich der Funktionsumfang von MOPS 3D im Laufe der Zeit stetig erweitert. Seit neuem gehört hierzu die Möglichkeit der Volumenvisualisierung, diese wurde mit dem Framework Voreen, welches auf OpenGL basiert, realisiert. Eine weiter Neuerung, die für diese Diplomarbeit von maßgeblicher Bedeutung ist, ist die Entwicklung des OpenCLStandards. Durch diesen wird es nicht nur möglich Anwendungen hochgradig parallel auf der Grafikkarte auszuführen, es ist des Weiteren möglich mit OpenCL direkt auf Darstellungen, die durch OpenGL generierten wurden, zu operieren. Hierdurch ergeben sich vielversprechende Perspektiven bei der Entwicklung neuer Werkzeuge für das Planungssystem MOPS 3D. So wird in der nachfolgenden Arbeit eine neue unabhängige Segmentierungskomponente für das Planungssystem MOPS 3D konzipiert und implementiert. Dabei wird auf die Interoperabilität zwischen OpenGL und OpenCL gesetzt, um ein konstantes visuelles Feedback über den Segmentierungsverlauf an den Anwender in Form von 3D-Volumendarstellungen zu gewährleisten

OneArmPhaseTwoStudy: An R Package for Planning, Conducting, and Analysing Single-Arm Phase II Studies

In clinical phase II studies, the efficacy of a promising therapy is tested in patients for the first time. Based on the results, it is decided whether the development programme should be stopped or whether the benefit-risk profile is promising enough to justify the initiation of large phase III studies. In oncology, phase II trials are commonly conducted as single-arm trials with planned interim analyses to allow for an early stopping for futility. The specification of an adequate study design that guarantees control of the type I and II error rates is a key task in the planning stage of such a trial. A variety of statistical methods exists which can be used to optimise the planning and analysis of such studies. However, there are currently neither commercial nor non-commercial software tools available that support the practical application of these methods comprehensively. The R package OneArmPhaseTwoStudy was implemented to fill this gap. The package allows determining an adequate study design for the particular situation at hand as well as monitoring the progress of the study and evaluating the results with valid and efficient analyses methods. This article describes the features of the R package and its application

Severe paraneoplastic hypereosinophilia in metastatic renal cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Renal cell carcinoma can cause various paraneoplastic syndromes including metabolic and hematologic disturbances. Paraneoplastic hypereosinophilia has been reported in a variety of hematologic and solid tumors. We present the first case in the literature of severe paraneoplastic hypereosinophilia in a patient with renal cell carcinoma.</p> <p>Case presentation</p> <p>A 46 year-old patient patient with a history of significant weight loss, reduced general state of health and coughing underwent radical nephrectomy for metastasized renal cell carcinoma. Three weeks after surgery, the patient presented with excessive peripheral hypereosinophilia leading to profound neurological symptoms due to cerebral microinfarction. Systemic treatment with prednisolone, hydroxyurea, vincristine, cytarabine, temsirolimus and sunitinib led to reduction of peripheral eosinophils but could not prevent rapid disease progression of the patient. At time of severe leukocytosis, a considerable increase of cytokines associated with hypereosinophilia was measurable.</p> <p>Conclusions</p> <p>Paraneoplastic hypereosinophilia in patients with renal cell carcinoma might indicate poor prognosis and rapid disease progression. Myelosuppressive therapy is required in symptomatic patients.</p

Clinical evaluation of dengue and identification of risk factors for severe disease: protocol for a multicentre study in 8 countries

Background: The burden of dengue continues to increase globally, with an estimated 100 million clinically apparent infections occurring each year. Although most dengue infections are asymptomatic, patients can present with a wide spectrum of clinical symptoms ranging from mild febrile illness through to severe manifestations of bleeding, organ impairment, and hypovolaemic shock due to a systemic vascular leak syndrome. Clinical diagnosis of dengue and identification of which patients are likely to develop severe disease remain challenging. This study aims to improve diagnosis and clinical management through approaches designed a) to differentiate between dengue and other common febrile illness within 72 h of fever onset, and b) among patients with dengue to identify markers that are predictive of the likelihood of evolving to a more severe disease course. Method/Design: This is a prospective multi-centre observational study aiming to enrol 7–8000 participants aged ≥ 5 years presenting with a febrile illness consistent with dengue to outpatient health facilities in 8 countries across Asia and Latin America. Patients presenting within 72 h of fever onset who do not exhibit signs of severe disease are eligible for the study. A broad range of clinical and laboratory parameters are assessed daily for up to 6 days during the acute illness, and also at a follow up visit 1 week later. Discussion: Data from this large cohort of patients, enrolled early with undifferentiated fever, will be used to develop a practical diagnostic algorithm and a robust clinical case definition for dengue. Additionally, among patients with confirmed dengue we aim to identify simple clinical and laboratory parameters associated with progression to a more severe disease course. We will also investigate early virological and serological correlates of severe disease, and examine genetic associations in this large heterogeneous cohort. In addition the results will be used to assess the new World Health Organization classification scheme for dengue in practice, and to update the guidelines for “Integrated Management of Childhood Illness” used in dengue-endemic countries. Trial registration: NCT01550016. Registration Date: March 7, 201

Adaptive Designs for Two Candidate Primary Time-to-Event Endpoints

<p>In clinical trials, the choice of an adequate primary endpoint is often difficult. Besides its clinical relevance, the endpoint must be measurable within reasonable time and must allow differentiating between the treatments. Often, the most relevant endpoint is ‘’time-to-death,” but if the overall survival prognosis is good, only a few deaths are observed during the study duration. A possible solution is to use surrogate endpoints instead. However, various examples from the literature demonstrate that surrogates do not always perform as intended. Sometimes, the surrogate effect is smaller than for the original endpoint, or the latter shows a higher effect than anticipated so using the surrogate is not reasonable. In this work, different adaptive design strategies for two candidate endpoints are proposed to solve these problems. The idea is to base the efficacy proof on the significance of at least one endpoint. At an interim analysis, both candidates are evaluated. If it is not possible to stop the study early, the sample size is recalculated based on the more promising endpoint. The new methods are illustrated by a clinical study example and compared in terms of power and sample size using Monte Carlo simulations. The software code is provided as supplementary material.</p