Randomized double-blind sham-controlled trial of thalamic versus GPi stimulation in patients with severe medically refractory Gilles de la Tourette syndrome.

BACKGROUND: There are still no sufficient data regarding the use of deep brain stimulation (DBS) in Gilles de la Tourette syndrome (GTS) and no agreement on optimal target. OBJECTIVE: To compare efficacy and safety of bilateral DBS of thalamus (centromedian-ventro-oral internus, CM-Voi) versus posteroventral lateral globus pallidus internus (pvl GPi)) versus sham stimulation, and baseline in severe medically refractory GTS. METHODS: In this randomized double-blind sham stimulation-controlled trial (RCT), 10 patients (3 women, mean age = 29.4 ± 10.2 SD, range 18-47) underwent three blinded periods each lasting three months including (i) sham, (ii) pvl GPi (on-GPi), and (iii) thalamic stimulation (on-thal) followed by an open uncontrolled long-term follow-up (up to 9 years) with individually determined target and stimulation settings. RESULTS: Nine patients completed the RCT. At group level, on-GPi - but not on-thal - resulted in a significant tic reduction compared to baseline, but had no effect on premonitory urges and psychiatric comorbidities. Direct comparisons of targets resulted in inconsistent or negative (compared to sham) findings. During follow-up, we found no improvement of tics, comorbidities, and quality of life at group level, however, single patients benefitted continuously from thalamic DBS. At last follow-up 89.9 months (mean) after surgery, 50% of patients had discontinued DBS. Hardware infections occurred in 3/10 patients. CONCLUSION: Our data suggest that the initial effect of pvl GPi DBS is superior to thalamic (CM-Voi) DBS. While half of the patients discontinued treatment, single patients benefitted from thalamic DBS even after years. It is likely that outcome is influenced by various factors beyond the mere change in tic severity.

[Diagnosis and treatment of interstitial cystitis (IC/PBS) : S2k guideline of the German Society of Urology]. / Diagnostik und Therapie der interstitiellen Zystitis (IC/BPS) : S2k-Leitlinie der Deutschen Gesellschaft für Urologie.

In this review article, the authors describe all relevant aspects of the new S2k guideline from the German Society of Urology (Deutschen Gesellschaft für Urologie, DGU) for the diagnosis and treatment of IC/PBS (interstitial cystitis/painful bladder syndrome). A list of necessary and optional examinations and the necessity of diagnosis of exclusion are summarized and evaluated. The treatment options listed (ranging from conservative, oral drug, and complementary medicine to interventional surgical procedures) also give the reader a good overview of the contents of the guideline and possible therapeutic approaches. Finally, the recommendations including consensus of the guideline group are also summarized in various information boxes.

Adverse events associated with deep brain stimulation in patients with childhood-onset dystonia.

BACKGROUND: Data on pediatric DBS is still limited because of small numbers in single center series and lack of systematic multi-center trials. OBJECTIVES: We evaluate short- and long-term adverse events (AEs) of patients undergoing deep brain stimulation (DBS) during childhood and adolescence. METHODS: Data collected by the German registry on pediatric DBS (GEPESTIM) were analyzed according to reversible and irreversible AEs and time of occurrence with relation to DBS-surgery: Intraoperative, perioperative (<4 weeks), postoperative (4 weeks < 6 months) and long term AEs (>6 months). RESULTS: 72 patients with childhood-onset dystonia from 10 DBS-centers, who received 173 DBS electrodes and 141 implantable pulse generators (IPG), were included in the registry. Mean time of postoperative follow-up was 4.6 ±â€¯4 years. In total, 184 AEs were documented in 53 patients (73.6%). 52 DBS-related AEs in 26 patients (36.1%) required 45 subsequent surgical interventions 4.7 ±â€¯4.1 years (range 3 months-15 years) after initial implantation. The total risk of an AE requiring surgical intervention was 7.9% per electrode-year. Hardware-related AEs were the most common reason for surgery. There was a tendency of a higher rate of AEs in patients aged 7-9 years beyond 6 months after implantation. DISCUSSION: The intraoperative risk of AEs in pediatric patients with dystonia undergoing DBS is very low, whereas the rate of postoperative hardware-related AEs is a prominent feature with a higher occurrence compared to adults, especially on long-term follow-up. CONCLUSION: Factors leading to such AEs must be identified and patient management has to be focused on risk minimization strategies in order to improve DBS therapy and maximize outcome in pediatric patients.

Indications and Route of Hysterectomy for Benign Diseases. Guideline of the DGGG, OEGGG and SGGG (S3 Level, AWMF Registry No. 015/070, April 2015)

Background: Official guideline "indications and methods of hysterectomy" to assign indications for the different methods published and coordinated by the German Society of Gynecology and Obstetrics (DGGG), the Austrian Society of Gynecology and Obstetrics (OEGGG) and the Swiss Society of Gynecology and Obstetrics (SGGG). Besides vaginal and abdominal hysterectomy, three additional techniques have been implemented due to the introduction of laparoscopy. Organ-sparing alternatives were also integrated. Methods: The guideline group consisted of 26 experts from Germany, Austria and Switzerland. Recommendations were developed using a structured consensus process and independent moderation. A systematic literature search and quality appraisal of benefits and harms of the therapeutic alternatives for symptomatic fibroids, dysfunctional bleeding and adenomyosis was done through MEDLINE up to 6/2014 focusing on systematic reviews and meta-analysis. Results: All types of hysterectomy led in studies to high rates of patient satisfaction. If possible, vaginal instead of abdominal hysterectomy should preferably be done. If a vaginal hysterectomy is not feasible, the possibility of a laparoscopic hysterectomy should be considered. An abdominal hysterectomy should only be done with a special indication. Organ-sparing interventions also led to high patient satisfaction rates, but contain the risk of symptom recurrence. Conclusion: As an aim, patients should be enabled to choose that therapeutic intervention for their benign disease of the uterus that convenes best to them and their personal life situation.

Long-term results of deep brain stimulation in a cohort of eight children with isolated dystonia.

Pallidal deep brain stimulation (DBS) is an established treatment for patients with severe isolated dystonia. However, clinical evidence for the long-term use of DBS in children is limited and controlled trials have not yet been conducted. Here, we provide the long-term results of up to 13 years of pallidal DBS in eight pediatric patients with generalized idiopathic or hereditary isolated dystonia (five males, mean age at surgery 12.5 ± 3.5 years), as assessed by retrospective video rating. Video rating was performed at three time points: pre-operative, 1-year short-term follow-up (1y-FU) and long-term last FU (LT-FU, up to 13 years). Symptom severity and disability were assessed using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). Disability scores were obtained from clinical charts and during the last FU. The mean improvement in BFMDRS motor score was 54.4 ± 8.9 % at 1y-FU and 42.9 ± 11.6 % at LT-FU; the disability scores improved by 59.8 ± 10.3 and 63.3 ± 7.8 %, respectively. Electrode dislocation was noted in one patient and implantable pulse generator dislocation in another, both requiring surgical intervention; no further serious adverse events occurred. Our study presents the first blinded video rating assessment of the short- and long-term effects of pallidal DBS in children with idiopathic or hereditary isolated dystonia. Results confirm that pallidal DBS is a safe and efficacious long-term treatment in children, with overall motor improvement similar to that described in controlled trials in adults.

Advances in the treatment of cutaneous lupus erythematosus.

Lupus erythematosus (LE) is a multifactorial autoimmune disease with clinical manifestations of differing severity which may present with skin manifestations as primary sign of the disease (cutaneous lupus erythematosus, CLE) or as part of a disease spectrum (systemic lupus erythematosus, SLE). To date, no drugs are approved specifically for the treatment of CLE and only single agents have been applied in randomized controlled trials. Therefore, topical and systemic agents are used "off-label", primarily based on open-label studies, case series, retrospective analyses, and expert opinions. In contrast, several agents, such as hydroxychloroquine, chloroquine, cyclophosphamide, azathioprine, and belimumab, are approved for the treatment of SLE. Recent approaches in the understanding of the molecular pathogenesis of LE enabled the development of further new agents, which target molecules such as interleukin 6 (IL-6) and interferon (IFN). Only single trials, however, applied these new agents in patients with cutaneous involvement of the disease and/or included endpoints which evaluated the efficacy of these agents on skin manifestations. This article provides an updated review on new and recent approaches in the treatment of CLE.

Prospective, systematically recorded mycophenolate safety data in Graves' orbitopathy.

CONTEXT: The antiproliferative mechanism of mycophenolate acid (MPA) suggests a beneficial effect in patients with Graves' orbitopathy (GO). OBJECTIVE: To systematically analyze for the first time adverse events (AEs) during MPA treatment in GO. DESIGN: Prospective longitudinal study. SETTING: Academic tertiary referral center with a joint thyroid-eye clinic. PATIENTS: Fifty-three consecutive, unselected patients with clinically active and moderate-to-severe GO. METHODS: MPA 0.720 g was given once daily for 24-weeks in GO patients. AEs were documented and coded according to the standardized medical dictionary for regulatory activities (MedDRA). AE were followed up and seriousness as defined by ICH-guideline E6 was documented. All AEs were analyzed regarding a possible underlying cause and if not, graded as side effect (SE). RESULTS: Fifty GO patients (93 %) had Graves' disease, 37 (70 %) and 29 (54.7 %) were female and smoker, respectively. Thirty-six patients (68 %) reported at least one AE. A total of 88 AEs were documented, most frequent AEs were insomnia (N = 6), fatigue (N = 5) and optic neuropathy (N = 5), while other AEs occurred in up to three patients (5.6 %), only. In 12 (23 %) patients, at least one SE occurred. All 17 reported SE, i.e. mild infections and gastrointestinal intolerance were within the known safety profile of MPA. No patient dropped MPA medication because of drug-induced SE. Most AEs showed a recovered (76 %) or recovering (16 %) outcome. Seven (13 %) patients were hospitalized, five (62 %) due to optic neuropathy, none of these events was graded as SE. CONCLUSIONS: MedDRA-coded data documented the good tolerance of a moderate MPA dose in GO patients.

Actively personalized cancer vaccines--the step into clinical application.

Cancer vaccine development enters a new phase of innovation based on the development of modern sequencing technologies and novel RNA-based synthetic drug formats which enable the analysis and therapeutic targeting of every patient's tumor genome. By applying and combining these innovations, we have brought the concept of "actively personalized cancer vaccines" to clinical testing. Synthetic RNA is used as the drug format, allowing affordable, individual "on demand" manufacturing of tumor-optimized vaccines.

Diagnosis and Therapy of Female Pelvic Organ Prolapse. Guideline of the DGGG, SGGG and OEGGG (S2e-Level, AWMF Registry Number 015/006, April 2016).

Aims: The aim was to establish an official interdisciplinary guideline, published and coordinated by the German Society of Gynecology and Obstetrics (DGGG). The guideline was developed for use in German-speaking countries. In addition to the Germany Society of Gynecology and Obstetrics, the guideline has also been approved by the Swiss Society of Gynecology and Obstetrics (SGGG) and the Austrian Society of Gynecology and Obstetrics (OEGGG). This is a guideline published and coordinated by the DGGG. The aim is to provide evidence-based recommendations obtained by evaluating the relevant literature for the diagnostic, conservative and surgical treatment of women with female pelvic organ prolapse with or without stress incontinence. Methods: We conducted a systematic review together with a synthesis of data and meta-analyses, where feasible. MEDLINE, Embase, Cinahl, Pedro and the Cochrane Register were searched for relevant articles. Reference lists were hand-searched, as were the abstracts of the Annual Meetings of the International Continence Society and the International Urogynecological Association. We included only abstracts of randomized controlled trials that were presented and discussed in podium sessions. We assessed original data on surgical procedures published since 2008 with a minimum follow-up time of at least 12 months. If the studies included descriptions of perioperative complications, this minimum follow-up period did not apply. Recommendations: The guideline encompasses recommendations for the diagnosis and treatment of female pelvic organ prolapse. Recommendations for anterior, posterior and apical pelvic organ prolapse with or without concomitant stress urinary incontinence, uterine preservation options, and the pros and cons of mesh placements during surgery for pelvic organ prolapse are presented. The recommendations are based on an extensive and systematic review and evaluation of the current literature and include the experiences and specific conditions in Germany, Austria and Switzerland.

A multicenter photoprovocation study to identify potential biomarkers by global peptide profiling in cutaneous lupus erythematosus.

Cutaneous lupus erythematosus (CLE) is an inflammatory autoimmune skin disease in which abnormal photosensitivity is an important pathogenetic factor but is difficult to predict, creating a challenge in determining treatment efficacy. Although photosensitivity in CLE patients may change over time, photoprovocation testing with ultraviolet (UV) A and UVB irradiation can be a helpful tool to explore differences between responders and nonresponders during photoprovocation. To identify biomarkers that could substitute for the clinical endpoint lesion development, we performed a global peptidomics profiling analysis of CLE subjects in a controlled photoprovocation study. Plasma and skin biopsy samples were collected before and after UV-irradiation from 13 healthy volunteers and 47 CLE subjects. Twenty-two of the 47 CLE subjects developed skin lesions. The samples were analyzed using a label-free quantitative peptidomics workflow combined with univariate and multivariate statistical analyses. The primary finding was identification of a specific plasma peptide signature separating responders versus nonresponders at baseline. The peptide signature consisted of beta 2-microglobulin (B2MG), human beta-defensin-1, and peptides derived from CD99, polymeric immunoglobulin receptor, and immunoglobulin kappa light chains. In skin, elevated B2MG levels correlated with lesion formation. Our results show that the peptidome is a rich source of potential biomarkers for predicting photosensitivity in CLE.

Ação genotóxica e antiproliferativa de Polygonum punctatum Elliott (Polygonaceae) sobre o ciclo celular de Allium cepa L / Genotoxic and antiproliferative action of Polygonum punctatum Elliott (Polygonaceae) on the cell cycle of Allium cepa L

RESUMO: A espécie Polygonum punctatum Elliott (Polygonaceae) é amplamente utilizada pela população como planta medicinal. O objetivo deste trabalho é o de avaliar o potencial genotóxico e mutagênico de P. punctatum utilizando raízes de bulbos e radículas em sementes germinadas de Allium cepa através do teste in vivo, e realizar comparações da extração do material vegetal por calor (infusões) e extração a frio (extrato). Para isso, foram preparadas dois tipos de soluções, infusões e extratos foliares de P. punctatum, em duas concentrações 0,4 g mL-1 e 2,4 g mL-1. A infusão foi preparada pela adição das folhas secas em água destilada fervente (100ºC), permanecendo por 10 minutos enquanto o extrato foi preparado através da maceração das folhas secas em água destilada fria. Para o teste em A. cepa foram utilizados, para cada tratamento, seis grupos de quatro bulbos e seis caixas gerbox com 50 sementes em cada caixa. Duas lâminas para cada tratamento foram obtidas através da técnica de esmagamento das raízes e coradas com orceína acética 2%. Foram contadas 2000 células por grupo de bulbos e 3000 células por grupo de sementes, observando-se a ocorrência de interrupções em metáfases, alterações cromossômicas estruturais, bem como a inibição ou aumento da divisão celular. Os valores do índice mitótico foram calculados e analisados estatisticamente pelo Teste χ2 (p≤0,05). Os resultados demonstraram que as infusões e os extratos de folhas apresentaram redução nos valores de índices mitóticos nas concentrações utilizadas em relação ao controle em água destilada. Foram identificadas alterações cromossômicas na divisão celular, tais como pontes anafásicas, em todas as concentrações de infusões e extratos indicando assim que P. punctatum possui atividade antiproliferativa e genotóxica.

ABSTRACT: The species Polygonum punctatum Elliott (Polygonaceae) is widely used by the Brazilian population as a medicinal plant. The aims of this study are to evaluate the genotoxic and mutagenic potential of P. punctatum, using its root bulbs and rootlets in germinated seeds of Allium cepa by in vivo testing, and to compare the extraction of plant material by heat (infusions) and cold (extract). Thus, two types of solutions - infusions and leaf extracts - of P. punctatum were prepared at the two concentrations of 0.4 g ml -1 and 2.4 g mL- 1. The infusion was prepared by addition of dry leaves in boiling distilled water (100ºC), remaining for 10 minutes, while the extract was prepared by maceration of dried leaves in cold distilled water. For the A. cepa, we used for each treatment six groups of six bulbs and six seedling boxes with 50 seeds each. Two slides for each treatment were obtained by the technique of crushing the roots, and they were stained with 2 % acetic orcein. For the analysis, 2000 cells per group of bulbs and 3000 cells per group of seeds were counted, and we noted the occurrence of interruptions in the metaphase, chromosomal aberrations, as well as inhibited or increased cell division. The values of the mitotic index were calculated and statistically analyzed by the χ2 test (p ≤ 0.05). The results showed that the infusions and extracts of leaves showed reduced values of mitotic indices in the concentrations used compared to the control in distilled water. Chromosomal alterations were identified in the cell division, in all concentrations of infusions and extracts, thus indicating that P. punctatum has an antiproliferative and genotoxic activity.

Feasibility and quality development of biomaterials in the pretest studies of the German National Cohort.

BACKGROUND: The German National Cohort (GNC) is designed to address research questions concerning a wide range of possible causes of major chronic diseases (e.g. cancer, diabetes, infectious, allergic, neurologic and cardiovascular diseases) as well as to identify risk factors and prognostic biomarkers for early diagnosis and prevention of these diseases. The collection of biomaterials in combination with extensive information from questionnaires and medical examinations represents one of the central study components. OBJECTIVES: In two pretest studies of the German National Cohort conducted between 2011 and 2013, a range of biomaterials from a defined number of participants was collected. Ten study centres were involved in pretest 1 and 18 study centres were involved in pretest 2. Standard operation procedures (SOP) were developed and evaluated to minimize pre-analytical artefacts during biosample collection. Within the pretest studies different aspects concerning feasibility of sample collection/preparation [pretest 1 (a)] and quality control of biomarkers and proteome analyses were investigated [pretest 1 (b), (c)]. Additionally, recruitment of study participants for specific projects and examination procedures of all study centres in a defined time period according to common standards as well as transportation and decentralized storage of biological samples were tested (pretest 2). These analyses will serve as the basis for the biomaterial collection in the main study of the GNC starting in 2014. MATERIALS AND METHODS: Participants, randomly chosen from the population (n = 1000 subjects recruited at ten study sites in pretest 1) were asked to donate blood, urine, saliva and stool samples. Additionally, nasal and oropharyngeal swabs were collected at the study sites and nasal swabs were collected by the participants at home. SOPs for sample collection, preparation, storage and transportation were developed and adopted for pretest 2. In pretest 2, 18 study sites (n = 599 subjects) collected biomaterials mostly identical to pretest 1. Biomarker analyses to test the quality of the biomaterials were performed. RESULTS: In pretest 1 and 2, it was feasible to collect all biomaterials from nearly all invited participants without major problems. The mean response rate of the subjects was 95 %. As one important result we found for example that after blood draw the cellular fraction should be separated from the plasma and serum fractions during the first hour with no significant variation for up to 6 h at 4 ℃ for all analysed biomarkers. Moreover, quality control of samples using a proteomics approach showed no significant clustering of proteins according to different storage conditions. All developed SOPs were validated for use in the main study after some adaptation and modification. Additionally, electronic and paper documentation sheets were developed and tested to record time stamps, volumes, freezing times, and aliquot numbers of the collected biomaterials. DISCUSSION: The collection of the biomaterials was feasible without major problems at all participating study sites. However, the processing times were in some cases too long. To avoid pre-analytical artefacts in sample collection, appropriate standardisation among the study sites is necessary. To achieve this, blood and urine collection will have to be adapted to specific conditions of usage of liquid handling robots, which will be available at all participating study centres in the main study of the GNC. Strict compliance with the SOPs, thorough training of the staff and accurate documentation are mandatory to obtain high sample quality for later analyses. The so obtained biomaterials represent a valuable resource for research on infectious and other common complex diseases in the GNC.

A prospective cohort study on the impact of darbepoetin alfa on quality of life in daily practice following anemia treatment guideline revisions.

OBJECTIVE: This study aimed to evaluate the impact of darbepoetin alfa (DA) on hemoglobin (Hb) levels and quality of life (QoL) in cancer patients with anemia in current daily practice following several revisions of anemia treatment guidelines. METHODS: This was a prospective, multi-center, observational study across Germany in non-myeloid cancer outpatients with chemotherapy-induced anemia treated with DA. Age, sex, cancer type, stage, and therapy, performance status, anemia status and treatment, and Hb concentrations were recorded for up to 18 weeks in a web-based registry. Optional QoL assessments were collected at baseline and at the end of DA treatment. MAIN RESULTS: Of 984 eligible patients, 978 had complete anemia data, 492 also had complete QoL data. In the 978 patients, mean age was 64 (standard deviation, SD 12) years, 62% of patients were women. Breast (26%) and gastrointestinal (22%) cancer were most prevalent. Therapy was palliative in 44% of patients and initiated with curative intent in 29%. Mean baseline Hb was 9.5 (SD 0.9) g/dL, which increased by an average of 1.2 g/dL. In 67% of patients Hb increased either to 10-12 g/dL or by ≥2 g/dL; no Hb response was seen in 219 patients (22%); increases of 0 to 1, >1 to 2, and >2 g/dl were seen in 216 (22%), 265 (27%), and 278 (28%) patients, respectively. Anemia treatment did not result in any significant differences of performance status. However, QoL improvements were significantly greater in Hb responders, although a linear relationship with Hb increments was lacking. None of 47 fatal cases was considered related to treatment with DA. CONCLUSION: Patients treated with DA in routine clinical practice had increases in Hb and reported improvement in QoL. Due to the uncontrolled design, no conclusions can be made regarding causality to treatment and the clinical relevance of the improvement.

Influence of smoking on disease severity and antimalarial therapy in cutaneous lupus erythematosus: analysis of 1002 patients from the EUSCLE database.

BACKGROUND: In recent years it has been controversially discussed in the literature if smoking is associated with the activity of cutaneous lupus erythematosus (CLE) and the efficacy of antimalarial agents. OBJECTIVES: To investigate the influence of smoking on disease severity and antimalarial treatment in patients with CLE using the Core Set Questionnaire of the European Society of Cutaneous Lupus Erythematosus (EUSCLE). METHODS: A total of 1002 patients (768 female, 234 male) with different CLE subtypes were included in this cross-sectional study, which was performed in 14 different countries. Smoking behaviour was assessed by the EUSCLE Core Set Questionnaire in 838 patients and statistically analysed using an SPSS database. The results were correlated with the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) and the efficacy of antimalarial treatment. RESULTS: A high percentage (87·2%) of the 499 patients with CLE, who have ever smoked, had already smoked at the date of their first diagnosis. Patients with intermittent CLE have ever smoked significantly more often than patients with subacute CLE (P < 0·05) and chronic CLE (P < 0·05). The total CLASI activity and damage score of patients with CLE was 6·6 ± 7·1 and 2·6 ± 4·3, respectively, and was higher in patients who have ever smoked than in nonsmokers. Antimalarial treatment was successful in 84·3% of cases, with a significantly higher efficacy in nonsmokers than in patients with CLE who have ever smoked (P < 0·05). CONCLUSIONS: This analysis of a multicentre study population of 838 patients with CLE assessed by the EUSCLE Core Set Questionnaire confirms that smoking negatively influences CLE disease severity and the efficacy of antimalarial treatment.

Venous thrombo-embolism as a complication of cross-sex hormone treatment of male-to-female transsexual subjects: a review.

Administration of cross-sex hormones to male-to-female transsexual subjects, usually oestrogens + often anti-androgens, such as cyproterone acetate, carries a risk of venous thromboembolism (VTE). VTE usually occurs in the first year of oestrogen administration. Ethinyl oestradiol, due to its chemical structure, was in 2003 identified as a major factor in the occurrence of VTE. Most clinics do not prescribe ethinyl oestradiol any longer, but people who take hormones without medical supervision use often oral contraceptives containing ethinyl oestradiol, many times in overdose. Cessation of use of ethinyl oestradiol and peri-operative thrombosis prophylaxis for surgery have reduced prevalence rate of VTE. Other oral oestrogens should not be overdosed, and transdermal oestrogen is to be preferred. Thrombosis prophylaxis for surgery is mandatory. It seems advisable to stop hormone use at least 2 weeks before major surgery, to be resumed only after 3 weeks following full mobilisation.

Initial clinical results of simultaneous 18F-FDG PET/MRI in comparison to 18F-FDG PET/CT in patients with head and neck cancer.

PURPOSE: The aim of this study was to evaluate the diagnostic capability of simultaneous (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/MRI compared to (18)F-FDG PET/CT as well as their single components in head and neck cancer patients. METHODS: In a prospective study 17 patients underwent (18)F-FDG PET/CT for staging or follow-up and an additional (18)F-FDG PET/MRI scan with whole-body imaging and dedicated examination of the neck. MRI, CT and PET images as well as PET/MRI and PET/CT examinations were evaluated independently and in a blinded fashion by two reader groups. Results were compared with the reference standard (final diagnosis determined in consensus using all available data including histology and follow-up). Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated. RESULTS: A total of 23 malignant tumours were found with the reference standard. PET/CT showed a sensitivity of 82.7%, a specificity of 87.3%, a PPV of 73.2% and a NPV of 92.4%. Corresponding values for PET/MRI were 80.5, 88.2, 75.6 and 92.5%. No statistically significant difference in diagnostic capability could be found between PET/CT and PET/MRI. Evaluation of the PET part from PET/CT revealed highest sensitivity of 95.7%, and MRI showed best specificity of 96.4%. There was a high inter-rater agreement in all modalities (Cohen's kappa 0.61-0.82). CONCLUSION: PET/MRI of patients with head and neck cancer yielded good diagnostic capability, similar to PET/CT. Further studies on larger cohorts to prove these first results seem justified.

[Gesundheitsziele.de. Selection of a new health target for Germany]. / Gesundheitsziele.de. Die Auswahl eines neuen Gesundheitsziels für Deutschland.

In 2013, the forum gesundheitsziele.de selected "reduction of alcohol consumption" and "patient safety" as new health targets. Besides the two selected targets, three other topics were considered: health at work, health during pregnancy and childbirth, and health and migration. This paper describes the selection process, which followed several criteria: mortality, morbidity, prevalence, burden of disease, economic impact, potential for improvement, equity in health, empowerment of and priorities of health problems in the population. The analysis particularly focused on the assessment of the feasibility and the readiness of stakeholders to participate in the development and implementation of health targets.

Post-treatment with plant extracts used in Brazilian folk medicine caused a partial reversal of the antiproliferative effect of glyphosate in the Allium cepa test

Species of the genus Psychotria are used for multiple purposes in Brazilian folk medicine, either as water infusions, baths or poultices. This study was aimed to evaluate the genotoxic and antiproliferative effects of infusions of Psychotria brachypoda and P. birotula on the Allium cepa test. Exposure to distilled water was used as a negative control, while exposure to glyphosate was used as a positive control. The interaction of extracts (as a post-treatment) with the effects of glyphosate was also studied. Results showed that glyphosate and the extracts of both P. brachypoda and P. birotula reduced the mitotic index as compared with the negative control (distilled water). Surprisingly, however, both extracts from P. brachypoda and P. birotula caused a partial reversal of the antiproliferative effect of glyphosat e when used as a post-treatment. Glyphosate also induced the highest number of cells with chromosomal alterations, which was followed by that of P. birotula extracts. However, the extracts from P. brachypoda did not show any significant genotoxic effect. Post-treatment of glyphosate-treated samples with distilled water allowed a partial recovery of the genotoxic effect of glyphosate, and some of the Psychotria extracts also did so. Notably, post-treatment of glyphosate-treated samples with P. brachypoda extracts induced a statistically significant apoptotic effect. It is concluded that P. brachypoda extracts show antiproliferative effects and are not genotoxic, while extracts of P. birotula show a less potent antiproliferative effect and may induce chromosomal abnormalities. The finding of a partial reversion of the effects of glyphosate by a post-treatment with extracts from both plants should be followed up.

Cerebellar location may predict an unfavourable prognosis in paediatric high-grade glioma.

BACKGROUND: High-grade glioma (HGG) of the cerebellum accounts for only 5% of paediatric HGG. Since little is known about these tumours, the present study aimed at their further characterisation. METHODS: Twenty-nine paediatric patients with centrally reviewed cerebellar HGG were identified from the HIT-GBM/HIT-HGG database. Clinical and epidemiological data were compared with those of 180 paediatric patients with cortical HGG. RESULTS: Patients with cerebellar tumours were younger (median age of 7.6 vs 11.7 years, P=0.028), but both groups did not differ significantly with regard to gender, tumour predisposing syndromes, secondary HGG, primary metastasis, tumour grading, extent of tumour resection, chemotherapy regimen, or radiotherapy. Except for an increased incidence of anaplastic pilocytic astrocytoma (APA) in the cerebellar subset (20.7% vs 3.3%; P<0.001), histological entities were similarly distributed in both groups. As expected, tumour grading had a prognostic relevance on survival. Compared with cortical HGG, overall survival in the cerebellar location was significantly worse (median overall survival: 0.92 ± 0.02 vs 2.03 ± 0.32 years; P=0.0064), and tumour location in the cerebellum had an independent poor prognostic significance as shown by Cox-regression analysis (P=0.019). CONCLUSION: High-grade glioma represents a group of tumours with an obviously site-specific heterogeneity associated with a worse survival in cerebellar location.