Time- and dose-dependent volume decreases in subcortical grey matter structures of glioma patients after radio(chemo)therapy.

Background and purpose: Radiotherapy (RT) is an adjuvant treatment option for glioma patients. Side effects include tissue atrophy, which might be a contributing factor to neurocognitive decline after treatment. The goal of this study was to determine potential atrophy of the hippocampus, amygdala, thalamus, putamen, pallidum and caudate nucleus in glioma patients having undergone magnetic resonance imaging (MRI) before and after RT. Materials and methods: Subcortical volumes were measured using T1-weighted MRI from patients before RT (N = 91) and from longitudinal follow-ups acquired in three-monthly intervals (N = 349). The volumes were normalized to the baseline values, while excluding structures touching the clinical target volume (CTV) or abnormal tissue seen on FLAIR imaging. A multivariate linear effects model was used to determine if time after RT and mean RT dose delivered to the corresponding structures were significant predictors of tissue atrophy. Results: The hippocampus, amygdala, thalamus, putamen, and pallidum showed significant atrophy after RT as function of both time after RT and mean RT dose delivered to the corresponding structure. Only the caudate showed no dose or time dependant atrophy. Conversely, the hippocampus was the structure with the highest atrophy rate of 5.2 % after one year and assuming a mean dose of 30 Gy. Conclusion: The hippocampus showed the highest atrophy rates followed by the thalamus and the amygdala. The subcortical structures here found to decrease in volume indicative of radiosensitivity should be the focus of future studies investigating the relationship between neurocognitive decline and RT.

Overestimation of grey matter atrophy in glioblastoma patients following radio(chemo)therapy.

OBJECTIVE: Brain atrophy has the potential to become a biomarker for severity of radiation-induced side-effects. Particularly brain tumour patients can show great MRI signal changes over time caused by e.g. oedema, tumour progress or necrosis. The goal of this study was to investigate if such changes affect the segmentation accuracy of normal appearing brain and thus influence longitudinal volumetric measurements. MATERIALS AND METHODS: T1-weighted MR images of 52 glioblastoma patients with unilateral tumours acquired before and three months after the end of radio(chemo)therapy were analysed. GM and WM volumes in the contralateral hemisphere were compared between segmenting the whole brain (full) and the contralateral hemisphere only (cl) with SPM and FSL. Relative GM and WM volumes were compared using paired t tests and correlated with the corresponding mean dose in GM and WM, respectively. RESULTS: Mean GM atrophy was significantly higher for full segmentation compared to cl segmentation when using SPM (mean ± std: ΔVGM,full = - 3.1% ± 3.7%, ΔVGM,cl = - 1.6% ± 2.7%; p < 0.001, d = 0.62). GM atrophy was significantly correlated with the mean GM dose with the SPM cl segmentation (r = - 0.4, p = 0.004), FSL full segmentation (r = - 0.4, p = 0.004) and FSL cl segmentation (r = -0.35, p = 0.012) but not with the SPM full segmentation (r = - 0.23, p = 0.1). CONCLUSIONS: For accurate normal tissue volume measurements in brain tumour patients using SPM, abnormal tissue needs to be masked prior to segmentation, however, this is not necessary when using FSL.

Reduced diffusion in white matter after radiotherapy with photons and protons.

BACKGROUND AND PURPOSE: Radio(chemo)therapy is standard in the adjuvant treatment of glioblastoma. Inevitably, brain tissue surrounding the target volume is also irradiated, potentially causing acute and late side-effects. Diffusion imaging has been shown to be a sensitive method to detect early changes in the cerebral white matter (WM) after radiation. The aim of this work was to assess possible changes in the mean diffusivity (MD) of WM after radio(chemo)therapy using Diffusion-weighted imaging (DWI) and to compare these effects between patients treated with proton and photon irradiation. MATERIALS AND METHODS: 70 patients with glioblastoma underwent adjuvant radio(chemo)therapy with protons (n = 20) or photons (n = 50) at the University Hospital Dresden. MRI follow-ups were performed at three-monthly intervals and in this study were evaluated until 33 months after the end of therapy. Relative white matter MD changes between baseline and all follow-up visits were calculated in different dose regions. RESULTS: We observed a significant decrease of MD (p < 0.05) in WM regions receiving more than 20 Gy. MD reduction was progressive with dose and time after radio(chemo)therapy (maximum: -7.9 ± 1.2% after 24 months, ≥50 Gy). In patients treated with photons, significant reductions of MD in the entire WM (p < 0.05) were seen at all time points. Conversely, in proton patients, whole brain MD did not change significantly. CONCLUSIONS: Irradiation leads to measurable MD reduction in white matter, progressing with both increasing dose and time. Treatment with protons reduces this effect most likely due to a lower total dose in the surrounding white matter. Further investigations are needed to assess whether those MD changes correlate with known radiation induced side-effects.

[Cognitive deficits following brain tumor radiation therapy]. / Kognitive Defizite nach Strahlentherapie von Hirntumoren.

Brain radiation is an important treatment option for malignant and benign brain diseases. The possible acute or chronic impact of radiation therapy on cognitive performance is important for daily functioning and quality of life. A detailed evaluation of cognitive impairment is important in the context of how to control disease progression. The susceptibility of the hippocampus to radiation-induced neuronal damage and its important role in memory highlight that therapeutic strategies require precision medicine.

Glioblastoma multiforme: emerging treatments and stratification markers beyond new drugs.

Glioblastoma multiforme (GBM) is the most common primary brain tumour in adults. The standard therapy for GBM is maximal surgical resection followed by radiotherapy with concurrent and adjuvant temozolomide (TMZ). In spite of the extensive treatment, the disease is associated with poor clinical outcome. Further intensification of the standard treatment is limited by the infiltrating growth of the GBM in normal brain areas, the expected neurological toxicities with radiation doses >60 Gy and the dose-limiting toxicities induced by systemic therapy. To improve the outcome of patients with GBM, alternative treatment modalities which add low or no additional toxicities to the standard treatment are needed. Many Phase II trials on new chemotherapeutics or targeted drugs have indicated potential efficacy but failed to improve the overall or progression-free survival in Phase III clinical trials. In this review, we will discuss contemporary issues related to recent technical developments and new metabolic strategies for patients with GBM including MR (spectroscopy) imaging, (amino acid) positron emission tomography (PET), amino acid PET, surgery, radiogenomics, particle therapy, radioimmunotherapy and diets.

[Microbiologic diagnosis of selected skin infections]. / Mikrobiologische Diagnostik ausgewählter bakterieller Hautinfektionen.

Using as examples either common or important but less frequent bacterial skin diseases, detailed practice-oriented information is provided on microbiologic diagnostic procedures. Despite the availability of many advanced techniques, often the simplest measures can provide the correct diagnosis and help guide therapy. The practicing physician must also know what is required for more advanced diagnostic procedures; if they are used improperly, unnecessary costs accumulate. Conversely, the decision process and technical methods must be understandable for those without special background in microbiology. The value of all methods is discussed from the perspective of dermatology with emphasis on appropriate sampling and handling of specimens.

Pruritic urticarial papules and plaques of pregnancy (PUPPP)--a case report.

Pruritic urticarial papules and plaques of pregnancy (PUPPP) is a rare dermatosis of unknown etiology that is most frequently seen in primiparas and twin/multiple pregnancies. The prognosis is favorable. We report a case of PUPPP in a primipara and review the clinical signs, differential diagnosis, possible etiologic factors, diagnosis, and therapy.

Modern management instruments--control of a water resources management association by means of an agreement on targets (balanced scorecard).

Since the matter of water supply and sewage disposal is safeguarded in Germany, public concern would no longer appear to be directed at questions of disposal reliability, but almost exclusively to economic efficiency. The requirements with respect to sewage disposal are dominated not only by growing environmental regulations and technical challenges, but also to a major extent by a discussion on the costs arising. In order to ensure a viable and at the same time economic water supply and sewage disposal despite this, it is necessary to have a holistic corporate control system. As a counterpart to the river basin management approach adopted at the Wupperverband there is, on the business management side, the agreement on targets (balanced scorecard) as a management and controlling approach. This incorporates purely financial variables as well as non-financial variables in the economic valuation of corporate success. The starting point is the formulation of strategic goals, while including customer-oriented, in-company and forward-looking perspectives, taking into account at the same time the interactions between them. A major perspective of such balanced scorecards is customer satisfaction. By means of an intensive dialogue with members, licensing and supervisory authorities of the Wupperverband within the framework of a holistic corporate control, it has been possible not only to improve corporate success, but also, and more importantly, to achieve an appreciable increase in confidence.

[Generalized allergic reaction to chloralhydrate]. / Generalisierte allergische Reaktion gegenüber Chloralhydrat

It is casuistically reported on a severe drug allergy of the immediate type compared with chloral hydrate. The unusually manifold allergic symptomatology allows a classification into the feature of the allergic mononucleosis.