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265 Publications visible to you, out of a total of 265
Biomarker candidates for the detection of an infectious etiology of febrile neutropenia
SepNet - German Competence Network Sepsis

Abstract (Expand)

PURPOSE Infections and subsequent septicemia are major complications in neutropenic patients with hematological malignancies. Here, we identify biomarker candidates for the early detection of an …n infectious origin, and monitoring of febrile neutropenia (FN). METHODS Proteome, metabolome, and conventional biomarkers from 20 patients with febrile neutropenia without proven infection (FNPI) were compared to 28 patients with proven infection, including 17 patients with bacteremia. RESULTS Three peptides (mass to charge ratio 1017.4-1057.3; p-values 0.011-0.024), six proteins (mass to charge ratio 6881-17,215; p-values 0.002-0.004), and six phosphatidylcholines (p-values 0.007-0.037) were identified that differed in FNPI patients compared to patients with infection or bacteremia. Seven of these marker candidates discriminated FNPI from infection at fever onset with higher sensitivity and specificity (ROC-AUC 0.688-0.824) than conventional biomarkers i.e., procalcitonin, C-reactive protein, or interleukin-6 (ROC-AUC 0.535-0.672). In a post hoc analysis, monitoring the time course of four lysophosphatidylcholines, threonine, and tryptophan allowed for discrimination of patients with or without resolution of FN (ROC-AUC 0.648-0.919) with higher accuracy compared to conventional markers (ROC-AUC 0.514-0.871). CONCLUSIONS Twenty-one promising biomarker candidates for the early detection of an infectious origin or for monitoring the course of FN were found which might overcome known shortcomings of conventional markers.

Authors: Martin E. Richter, Sophie Neugebauer, Falco Engelmann, Stefan Hagel, Katrin Ludewig, Paul La Rosée, Herbert G. Sayer, Andreas Hochhaus, Marie von Lilienfeld-Toal, Tom Bretschneider, Christine Pausch, Christoph Engel, Frank M. Brunkhorst, Michael Kiehntopf

Date Published: 1st Apr 2016

Publication Type: Journal article

Human Diseases: disease by infectious agent

Tobacco use is associated with reduced amplitude and intensity dependence of the cortical auditory evoked N1-P2 component.
LIFE Adult

Abstract (Expand)

RATIONALE: Tobacco use is linked to cerebral atrophy and reduced cognitive performance in later life. However, smoking-related long-term effects on brain function remain largely uncertain. Previous … studies suggest that nicotine affects serotonergic signaling, and the intensity dependence (alias loudness dependence) of the auditory evoked N1-P2 potential has been proposed as a marker of serotonergic neurotransmission. OBJECTIVE: In the present study, we assesed the effects of chronic smoking on amplitude and intensity dependence of the auditory evoked N1-P2 potential. METHODS: Subjects underwent a 15-min intensity dependence of auditory evoked potentials (IAEP) paradigm. From N = 1739 eligible subjects (40-79 years), we systematically matched current smokers, ex-smokers, and never-smokers by sex, age, alcohol and caffeine consumption, and socioeconomic status. Between-group differences and potential dose-dependencies were evaluated. RESULTS: Analyses revealed higher N1-P2 amplitudes and intensity dependencies in never-smokers relative to ex- and current smokers, with ex-smokers exhibiting intermediate intensity dependencies. Moreover, we observed pack years and number of cigarettes consumed per day to be inversely correlated with amplitudes in current smokers. CONCLUSIONS: According to the IAEP serotonin hypothesis, our results suggest serotonin activity to be highest in current smokers, intermediate in ex-smokers, and lowest in never-smokers. To our knowledge, the present study is the first providing evidence for a dose-dependent reduction in N1-P2 amplitudes. Further, we extend prior research by showing reduced amplitudes and intensity dependencies in ex-smokers even 25 years, on average, after cessation. While we can rule out several smoking-related confounders to bias observed associations, causal inferences remain to be established by future longitudinal studies.

Authors: P. Jawinski, N. Mauche, C. Ulke, J. Huang, J. Spada, C. Enzenbach, C. Sander, U. Hegerl, T. Hensch

Date Published: 18th Mar 2016

Publication Type: Not specified

Relationship Between Determinants of Arterial Stiffness Assessed by Diastolic and Suprasystolic Pulse Oscillometry: Comparison of Vicorder and Vascular Explorer.
Genetical Statistics and Systems Biology, LIFE Heart

Abstract (Expand)

Pulse wave velocity (PWV) and augmentation index (AI) are independent predictors of cardiovascular health. However, the comparability of multiple oscillometric modalities currently available for their … assessment was not studied in detail. In the present study, we aimed to evaluate the relationship between indices of arterial stiffness assessed by diastolic and suprasystolic oscillometry.In total, 56 volunteers from the general population (23 males; median age 70 years [interquartile range: 65-72 years]) were recruited into observational feasibility study to evaluate the carotid-femoral/aortic PWV (cf/aoPWV), brachial-ankle PWV (baPWV), and AI assessed by 2 devices: Vicorder (VI) applying diastolic, right-sided oscillometry for the determination of all 3 indices, and Vascular explorer (VE) implementing single-point, suprasystolic brachial oscillometry (SSBO) pulse wave analysis for the assessment of cfPWV and AI. Within- and between-device correlations of measured parameters were analyzed. Furthermore, agreement of repeated measurements, intra- and inter-observer concordances were determined and compared for both devices.In VI, both baPWV and cfPWV inter-correlated well and showed good level of agreement with bilateral baPWV measured by VE (baPWV[VI]-baPWV[VE]R: overall concordance correlation coefficient [OCCC] = 0.484, mean difference = 1.94 m/s; cfPWV[VI]-baPWV[VE]R: OCCC = 0.493, mean difference = 1.0 m/s). In contrast, SSBO-derived aortic PWA (cf/aoPWA[VE]) displayed only weak correlation with cfPWV(VI) (r = 0.196; P = 0.04) and ipsilateral baPWV (cf/aoPWV[VE]R-baPWV[VE]R: r = 0.166; P = 0.08). cf/aoPWA(VE) correlated strongly with AI(VE) (right-sided: r = 0.725, P < 0.001). AI exhibited marginal between-device agreement (right-sided: OCCC = 0.298, mean difference: 6.12%). All considered parameters showed good-to-excellent repeatability giving OCCC > 0.9 for 2-point-PWV modes and right-sided AI(VE). Intra- and inter-observer concordances were similarly high except for AI yielding a trend toward better reproducibility in VE (interobserver-OCCC[VI] vs [VE] = 0.774 vs 0.844; intraobserver-OCCC[VI] vs [VE] = 0.613 vs 0.769).Both diastolic oscillometry-derived PWV modes, and AI measured either with VI or VE, are comparable and reliable alternatives for the assessment of arterial stiffness. Aortic PWV assessed by SSBO in VE is not related to the corresponding indices determined by traditional diastolic oscillometry.

Authors: A. Teren, F. Beutner, K. Wirkner, M. Loffler, M. Scholz

Date Published: 11th Mar 2016

Publication Type: Journal article

Serum S100B Is Related to Illness Duration and Clinical Symptoms in Schizophrenia-A Meta-Regression Analysis.
LIFE Adult

Abstract (Expand)

S100B has been linked to glial pathology in several psychiatric disorders. Previous studies found higher S100B serum levels in patients with schizophrenia compared to healthy controls, and a number of … covariates influencing the size of this effect have been proposed in the literature. Here, we conducted a meta-analysis and meta-regression analysis on alterations of serum S100B in schizophrenia in comparison with healthy control subjects. The meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement to guarantee a high quality and reproducibility. With strict inclusion criteria 19 original studies could be included in the quantitative meta-analysis, comprising a total of 766 patients and 607 healthy control subjects. The meta-analysis confirmed higher values of the glial serum marker S100B in schizophrenia if compared with control subjects. Meta-regression analyses revealed significant effects of illness duration and clinical symptomatology, in particular the total score of the Positive and Negative Syndrome Scale (PANSS), on serum S100B levels in schizophrenia. In sum, results confirm glial pathology in schizophrenia that is modulated by illness duration and related to clinical symptomatology. Further studies are needed to investigate mechanisms and mediating factors related to these findings.

Authors: K. Schumberg, M. Polyakova, J. Steiner, M. L. Schroeter

Date Published: 5th Mar 2016

Publication Type: Journal article

Human Diseases: schizophrenia

Prevalence of BRCA1/2 germline mutations in 21 401 families with breast and ovarian cancer.
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Abstract (Expand)

PURPOSE: To characterise the prevalence of pathogenic germline mutations in BRCA1 and BRCA2 in families with breast cancer (BC) and ovarian cancer (OC) history. PATIENTS AND METHODS: Data from 21 401 … families were gathered between 1996 and 2014 in a clinical setting in the German Consortium for Hereditary Breast and Ovarian Cancer, comprising full pedigrees with cancer status of all individual members at the time of first counselling, and BRCA1/2 mutation status of the index patient. RESULTS: The overall BRCA1/2 mutation prevalence was 24.0% (95% CI 23.4% to 24.6%). Highest mutation frequencies were observed in families with at least two OCs (41.9%, 95% CI 36.1% to 48.0%) and families with at least one breast and one OC (41.6%, 95% CI 40.3% to 43.0%), followed by male BC with at least one female BC or OC (35.8%; 95% CI 32.2% to 39.6%). In families with a single case of early BC (<36 years), mutations were found in 13.7% (95% CI 11.9% to 15.7%). Postmenopausal unilateral or bilateral BC did not increase the probability of mutation detection. Occurrence of premenopausal BC and OC in the same woman led to higher mutation frequencies compared with the occurrence of these two cancers in different individuals (49.0%; 95% CI 41.0% to 57.0% vs 31.5%; 95% CI 28.0% to 35.2%). CONCLUSIONS: Our data provide guidance for healthcare professionals and decision-makers to identify individuals who should undergo genetic testing for hereditary breast and ovarian cancer. Moreover, it supports informed decision-making of counselees on the uptake of genetic testing.

Authors: K. Kast, K. Rhiem, B. Wappenschmidt, E. Hahnen, J. Hauke, B. Bluemcke, V. Zarghooni, N. Herold, N. Ditsch, M. Kiechle, M. Braun, C. Fischer, N. Dikow, S. Schott, N. Rahner, D. Niederacher, T. Fehm, A. Gehrig, C. Mueller-Reible, N. Arnold, N. Maass, G. Borck, N. de Gregorio, C. Scholz, B. Auber, R. Varon-Manteeva, D. Speiser, J. Horvath, N. Lichey, P. Wimberger, S. Stark, U. Faust, B. H. Weber, G. Emons, S. Zachariae, A. Meindl, R. K. Schmutzler, C. Engel

Date Published: 2nd Mar 2016

Publication Type: Journal article

Human Diseases: breast cancer, ovarian cancer

Compression of dementia morbidity by higher education
LIFE - Leipzig Research Center for Civilization Diseases

Abstract (Expand)

Objectives: The concept of compression of morbidity suggests that compressing cognitive morbidity into a shorter lifetime period would result in a better cumulative lifetime cognitive functioning. Some … lifestyle factors, like higher education, that are known to protect cognitive functioning in old age and lower dementia risk, could compress cognitive morbidity. Therefore the aim of our study was to investigate whether higher education leads to a better cumulative lifetime cognitive functioning and, hence, the compression of cognitive morbidity. Methods: Data were derived from the population-based Leipzig longitudinal study of the aged (LEILA75+). From 1998-2005, individuals aged 75 years and older underwent up to seven assessments at a 1.5-year interval and a long-term follow-up assessment after 15 years (2013). Analyses on the impact of higher education on compression of cognitive morbidity were carried out via multilevel logistic mixed-models and tobit analyses using the participants’ age as time scale (n=742). Results: The results revealed that more years of education were significantly associated with a better cognitive functioning but not with the age at dementia onset or the age at death. Computation of cumulative lifetime cognitive functioning was weighted for survival probability and indicated a gain of 21 MMSE points during the lifetime period 75 through 100 years of age by having more than 12 years of education compared to having less than 9 years of education. Conclusion: Overall, the findings suggest a compression of cognitive morbidity by higher education prior to dementia onset. More years of education could therefore contribute to a better cognitive functioning even under consideration of survival probability. Hence, efforts to ensure access to higher education for as many people in a population as possible might compress disease burden due to cognitive morbidity.

Authors: F. S. Then, T. Luck, H. Matschinger, M. C. Angermeyer, S. G. Riedel-Heller

Date Published: 1st Mar 2016

Publication Type: Not specified

Human Diseases: dementia

Validating new diagnostic imaging criteria for primary progressive aphasia via anatomical likelihood estimation meta-analyses.
LIFE Adult

Abstract (Expand)

Recently, diagnostic clinical and imaging criteria for primary progressive aphasia (PPA) have been revised by an international consortium (Gorno-Tempini et al. Neurology 2011;76:1006-14). The aim of … this study was to validate the specificity of the new imaging criteria and investigate whether different imaging modalities [magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET)] require different diagnostic subtype-specific imaging criteria. Anatomical likelihood estimation meta-analyses were conducted for PPA subtypes across a large cohort of 396 patients: firstly, across MRI studies for each of the three PPA subtypes followed by conjunction and subtraction analyses to investigate the specificity, and, secondly, by comparing results across MRI vs. FDG-PET studies in semantic dementia and progressive nonfluent aphasia. Semantic dementia showed atrophy in temporal, fusiform, parahippocampal gyri, hippocampus, and amygdala, progressive nonfluent aphasia in left putamen, insula, middle/superior temporal, precentral, and frontal gyri, logopenic progressive aphasia in middle/superior temporal, supramarginal, and dorsal posterior cingulate gyri. Results of the disease-specific meta-analyses across MRI studies were disjunct. Similarly, atrophic and hypometabolic brain networks were regionally dissociated in both semantic dementia and progressive nonfluent aphasia. In conclusion, meta-analyses support the specificity of new diagnostic imaging criteria for PPA and suggest that they should be specified for each imaging modality separately.

Authors: S. Bisenius, J. Neumann, M. L. Schroeter

Date Published: 23rd Feb 2016

Publication Type: Not specified

Human Diseases: aphasia

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