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228 Publications visible to you, out of a total of 228
Limited role for extended maintenance temozolomide for newly diagnosed glioblastoma.
GGN - German Glioma Network

Abstract (Expand)

OBJECTIVE: To explore an association with survival of modifying the current standard of care for patients with newly diagnosed glioblastoma of surgery followed by radiotherapy plus concurrent and 6 … cycles of maintenance temozolomide chemotherapy (TMZ/RT --> TMZ) by extending TMZ beyond 6 cycles. METHODS: The German Glioma Network cohort was screened for patients with newly diagnosed glioblastoma who received TMZ/RT --> TMZ and completed >/=6 cycles of maintenance chemotherapy without progression. Associations of clinical patient characteristics, molecular markers, and residual tumor determined by magnetic resonance imaging after 6 cycles of TMZ with progression-free survival (PFS) and overall survival (OS) were analyzed with the log-rank test. Multivariate analyses using the Cox proportional hazards model were performed to assess associations of prolonged TMZ use with outcome. RESULTS: Sixty-one of 142 identified patients received at least 7 maintenance TMZ cycles (median 11, range 7-20). Patients with extended maintenance TMZ treatment had better PFS (20.5 months, 95% confidence interval [CI] 17.7-23.3, vs 17.2 months, 95% CI 10.2-24.2, p = 0.035) but not OS (32.6 months, 95% CI 28.9-36.4, vs 33.2 months, 95% CI 25.3-41.0, p = 0.126). However, there was no significant association of prolonged TMZ chemotherapy with PFS (hazard ratio [HR] = 0.8, 95% CI 0.4-1.6, p = 0.559) or OS (HR = 1.6, 95% CI 0.8-3.3, p = 0.218) adjusted for age, extent of resection, Karnofsky performance score, presence of residual tumor, O(6)-methylguanine DNA methyltransferase (MGMT) promoter methylation status, or isocitrate dehydrogenase (IDH) mutation status. CONCLUSION: These data may not support the practice of prolonging maintenance TMZ chemotherapy beyond 6 cycles. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that in patients with newly diagnosed glioblastoma, prolonged TMZ chemotherapy does not significantly increase PFS or OS.

Authors: D. Gramatzki, P. Kickingereder, B. Hentschel, J. Felsberg, U. Herrlinger, G. Schackert, J. C. Tonn, M. Westphal, M. Sabel, U. Schlegel, W. Wick, T. Pietsch, G. Reifenberger, M. Loeffler, M. Bendszus, M. Weller

Date Published: 11th Apr 2017

Publication Type: Journal article

Human Diseases: brain glioblastoma multiforme

Secular trends in the incidence of dementia in high-income countries: a protocol of a systematic review and a planned meta-analysis.
LIFE Adult

Abstract (Expand)

INTRODUCTION: A global dementia epidemic is projected for the year 2050 with an ever-rising number of individuals living with the syndrome worldwide. However, increasingly, studies are emerging from … high-income countries (HIC) that show a positive trend towards a possible decrease in dementia occurrence. Therefore, we aim to systematically summarise evidence regarding secular trends in the incidence of dementia in HIC. METHODS AND ANALYSIS: We will conduct a systematic review of the literature on secular trends in dementia incidence in HIC according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and the Meta-analysis of Observational Studies in Epidemiology (MOOSE) statements. To do so, we will search the databases MEDLINE (PubMed interface), EMBASE (Ovid interface) and Web of Science (Web of Science interface), as well as the grey literature on unpublished studies. To be eligible, studies must have been published in English or German since 1990 and provide sufficient information on prespecified eligibility criteria regarding outcome measurement and methodological approach. Study selection, data extraction and risk of bias assessment will be performed independently by 2 reviewers. Disagreement will be resolved by discussion and/or the involvement of a third researcher. Data abstraction will include study and participant characteristics, outcomes and methodological aspects. Results will be described and discussed regarding methodology. Depending on the number of studies found and the heterogeneity between the studies, we plan to combine outcome data through meta-analysis in order to get pooled incidence measures. ETHICS AND DISSEMINATION: No primary data will be collected; thus, ethical approval is not required. The results will be disseminated through a peer-reviewed publication and conference presentations. PROSPERO REGISTRATION NUMBER: CRD42016043232.

Authors: S. Roehr, A. Pabst, T. Luck, S. G. Riedel-Heller

Date Published: 7th Apr 2017

Publication Type: Journal article

Human Diseases: dementia, Alzheimer's disease

Predicting behavioral variant frontotemporal dementia with pattern classification in multi-center structural MRI data.
LIFE Adult

Abstract (Expand)

PURPOSE: Frontotemporal lobar degeneration (FTLD) is a common cause of early onset dementia. Behavioral variant frontotemporal dementia (bvFTD), its most common subtype, is characterized by deep … alterations in behavior and personality. In 2011, new diagnostic criteria were suggested that incorporate imaging criteria into diagnostic algorithms. The study aimed at validating the potential of imaging criteria to individually predict diagnosis with machine learning algorithms. MATERIALS & METHODS: Brain atrophy was measured with structural magnetic resonance imaging (MRI) at 3 Tesla in a multi-centric cohort of 52 bvFTD patients and 52 healthy control subjects from the German FTLD Consortium's Study. Beside group comparisons, diagnosis bvFTD vs. controls was individually predicted in each subject with support vector machine classification in MRI data across the whole brain or in frontotemporal, insular regions, and basal ganglia known to be mainly affected based on recent meta-analyses. Multi-center effects were controlled for with a new method, "leave one center out" conjunction analyses, i.e. repeatedly excluding subjects from each center from the analysis. RESULTS: Group comparisons revealed atrophy in, most consistently, the frontal lobe in bvFTD beside alterations in the insula, basal ganglia and temporal lobe. Most remarkably, support vector machine classification enabled predicting diagnosis in single patients with a high accuracy of up to 84.6%, where accuracy was highest in a region-of-interest approach focusing on frontotemporal, insular regions, and basal ganglia in comparison with the whole brain approach. CONCLUSION: Our study demonstrates that MRI, a widespread imaging technology, can individually identify bvFTD with high accuracy in multi-center imaging data, paving the road to personalized diagnostic approaches in the future.

Authors: S. Meyer, K. Mueller, K. Stuke, S. Bisenius, J. Diehl-Schmid, F. Jessen, J. Kassubek, J. Kornhuber, A. C. Ludolph, J. Prudlo, A. Schneider, K. Schuemberg, I. Yakushev, M. Otto, M. L. Schroeter

Date Published: 29th Mar 2017

Publication Type: Journal article

Human Diseases: frontotemporal dementia

Predicting brain-age from multimodal imaging data captures cognitive impairment.
LIFE Adult

Abstract (Expand)

The disparity between the chronological age of an individual and their brain-age measured based on biological information has the potential to offer clinically relevant biomarkers of neurological … syndromes that emerge late in the lifespan. While prior brain-age prediction studies have relied exclusively on either structural or functional brain data, here we investigate how multimodal brain-imaging data improves age prediction. Using cortical anatomy and whole-brain functional connectivity on a large adult lifespan sample (N=2354, age 19-82), we found that multimodal data improves brain-based age prediction, resulting in a mean absolute prediction error of 4.29 years. Furthermore, we found that the discrepancy between predicted age and chronological age captures cognitive impairment. Importantly, the brain-age measure was robust to confounding effects: head motion did not drive brain-based age prediction and our models generalized reasonably to an independent dataset acquired at a different site (N=475). Generalization performance was increased by training models on a larger and more heterogeneous dataset. The robustness of multimodal brain-age prediction to confounds, generalizability across sites, and sensitivity to clinically-relevant impairments, suggests promising future application to the early prediction of neurocognitive disorders.

Authors: F. Liem, G. Varoquaux, J. Kynast, F. Beyer, S. Kharabian Masouleh, J. M. Huntenburg, L. Lampe, M. Rahim, A. Abraham, R. C. Craddock, S. Riedel-Heller, T. Luck, M. Loeffler, M. L. Schroeter, A. V. Witte, A. Villringer, D. S. Margulies

Date Published: 1st Mar 2017

Publication Type: Journal article

Sleep quality in the general population: psychometric properties of the Pittsburgh Sleep Quality Index, derived from a German community sample of 9284 people.
LIFE Adult

Abstract (Expand)

BACKGROUND: The Pittsburgh Sleep Quality Index (PSQI) is frequently used to assess sleep problems in patients. The aim of this study was to provide reference values for this questionnaire, to test … psychometric properties, and to analyze associations with psychological, sociodemographic, and behavioral factors. METHODS: A German community sample comprising 9284 adult residents (aged 18-80 years) was surveyed using the PSQI and several other questionnaires. RESULTS: According to the generally accepted cut-off (PSQI > 5), 36% of the general population slept badly. Females reported significantly more sleep problems than males (mean scores: M = 5.5 vs. M = 4.4, respectively; effect size d = 0.35), but there was no linear association between age and sleep quality. Sleep problems were correlated with fatigue, quality of life (physical as well as mental), physical complaints, anxiety, and lack of optimism. Sleep quality was also strongly associated with socioeconomic status, professional situation (poorest sleep quality in unemployed people), and obesity. In addition to the results of the PSQI total score, mean scores of specific components of sleep quality were presented (sleep latency, sleep duration, and use of sleep medication). CONCLUSION: The PSQI proved to be a suitable instrument for measuring sleep quality. Gender differences, psychological factors, and obesity should be taken into account when groups of patients are compared with respect to sleep problems.

Authors: A. Hinz, H. Glaesmer, E. Brahler, M. Loffler, C. Engel, C. Enzenbach, U. Hegerl, C. Sander

Date Published: 21st Feb 2017

Publication Type: Journal article

Alteration of Multiple Leukocyte Gene Expression Networks is Linked with Magnetic Resonance Markers of Prognosis After Acute ST-Elevation Myocardial Infarction.
LIFE Heart

Abstract (Expand)

Prognostic relevant pathways of leukocyte involvement in human myocardial ischemic-reperfusion injury are largely unknown. We enrolled 136 patients with ST-elevation myocardial infarction (STEMI) after … primary angioplasty within 12 h after onset of symptoms. Following reperfusion, whole blood was collected within a median time interval of 20 h (interquartile range: 15-25 h) for genome-wide gene expression analysis. Subsequent CMR scans were performed using a standard protocol to determine infarct size (IS), area at risk (AAR), myocardial salvage index (MSI) and the extent of late microvascular obstruction (lateMO). We found 398 genes associated with lateMO and two genes with IS. Neither AAR, nor MSI showed significant correlations with gene expression. Genes correlating with lateMO were strongly related to several canonical pathways, including positive regulation of T-cell activation (p = 3.44 x 10(-5)), and regulation of inflammatory response (p = 1.86 x 10(-3)). Network analysis of multiple gene expression alterations associated with larger lateMO identified the following functional consequences: facilitated utilisation and decreased concentration of free fatty acid, repressed cell differentiation, enhanced phagocyte movement, increased cell death, vascular disease and compensatory vasculogenesis. In conclusion, the extent of lateMO after acute, reperfused STEMI correlated with altered activation of multiple genes related to fatty acid utilisation, lymphocyte differentiation, phagocyte mobilisation, cell survival, and vascular dysfunction.

Authors: A. Teren, H. Kirsten, F. Beutner, M. Scholz, L. M. Holdt, D. Teupser, M. Gutberlet, J. Thiery, G. Schuler, I. Eitel

Date Published: 3rd Feb 2017

Publication Type: Journal article

Human Diseases: myocardial infarction

Research in Progress on Integrating Health and Environmental Data in Epidemiological Studies
LIFE - Leipzig Research Center for Civilization Diseases

Abstract (Expand)

Epidemiological studies analyze and monitor the health state of a population. They typically use different methods and techniques to capture and to integrate data of interest before they can be analyzed. … As new technologies and, thus, devices are available for data capturing, such as wearables, new requirements arise for current data integration approaches. In this paper, we review current techniques and approaches as well as new trends in data capturing and the resulting requirement for its integration.

Authors: T. Kirsten, J. Bumberger, G. Ivanova, P. Dietrich, C. Engel, M. Loeffler, W. Kiess

Date Published: 2017

Publication Type: InBook

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