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1004 Publications visible to you, out of a total of 1004
Parameters of pulse wave velocity: determinants and reference values assessed in the population-based study LIFE-Adult
Genetical Statistics and Systems Biology

Abstract (Expand)

AIMS AND BACKGROUND Parameters of arterial stiffness such as pulse wave velocity (PWV) were recently proposed as independent risk factors of cardiovascular events. We analyse three PWV parameters in …n the large population-based study LIFE-Adult to identify risk factors, normal and reference values. METHODS AND RESULTS Brachial-ankle (ba), brachial-femoral (bf) and carotid-femoral (cf) PWV assessment was performed using Vicorder device. 8509 participants aged 19-80 were analysed. PWV parameters were moderately correlated (r(ba/bf) = 0.6, r(ba/cf) = 0.46, r(bf/cf) = 0.59). Age and blood pressure are the dominant determinants of PWV parameters explaining \textgreater 18% of variability. Sex was only relevant for bfPWV and cfPWV. All further analysed cardiovascular and other risk factors are of minor importance. We provide age-dependent percentiles for the population (reference values) and for the subgroup of normotonic individuals. All percentiles show a strong increase with age. The difference between normotonic and all individuals is small for younger age groups but increases up to 1 m/s for elderly subjects. CONCLUSION Our study confirms and further underpins the strong impact of age and blood pressure on arterial stiffness and the relatively weak contribution of other factors, supporting an independent role of arterial stiffness in cardiovascular disease development. Age-dependent reference and normal values were provided on the basis of the so far largest study sample facilitating the implementation of PWV assessment in clinical practice. Due to better compliance, handling and stronger association with age and blood pressure, baPWV could serve as an alternative to cfPWV. Follow-up data are required to estimate the clinical significance of specified PWV cut-offs.

Authors: Daniel Baier, Andrej Teren, Kerstin Wirkner, Markus Loeffler, Markus Scholz

Date Published: 1st Nov 2018

Publication Type: Journal article

Commentary: Arguing for Adaptive Clinical Trials in Sepsis
SMITH - Smart Medical Information Technology for Healthcare

Abstract

Not specified

Authors: Miriam Kesselmeier, André Scherag

Date Published: 30th Oct 2018

Publication Type: Journal article

Human Diseases: disease by infectious agent

The Influence of Number and Timing of Pregnancies on Breast Cancer Risk for Women With BRCA1 or BRCA2 Mutations
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Abstract (Expand)

Background Full-term pregnancy (FTP) is associated with a reduced breast cancer (BC) risk over time, but women are at increased BC risk in the immediate years following an FTP. No large prospective …e studies, however, have examined whether the number and timing of pregnancies are associated with BC risk for BRCA1 and BRCA2 mutation carriers. Methods Using weighted and time-varying Cox proportional hazards models, we investigated whether reproductive events are associated with BC risk for mutation carriers using a retrospective cohort (5707 BRCA1 and 3525 BRCA2 mutation carriers) and a prospective cohort (2276 BRCA1 and 1610 BRCA2 mutation carriers), separately for each cohort and the combined prospective and retrospective cohort. Results For BRCA1 mutation carriers, there was no overall association with parity compared with nulliparity (combined hazard ratio [HRc] = 0.99, 95% confidence interval [CI] = 0.83 to 1.18). Relative to being uniparous, an increased number of FTPs was associated with decreased BC risk (HRc = 0.79, 95% CI = 0.69 to 0.91; HRc = 0.70, 95% CI = 0.59 to 0.82; HRc = 0.50, 95% CI = 0.40 to 0.63, for 2, 3, and \geq4 FTPs, respectively, Ptrend \textless .0001) and increasing duration of breastfeeding was associated with decreased BC risk (combined cohort Ptrend = .0003). Relative to being nulliparous, uniparous BRCA1 mutation carriers were at increased BC risk in the prospective analysis (prospective hazard ration [HRp] = 1.69, 95% CI = 1.09 to 2.62). For BRCA2 mutation carriers, being parous was associated with a 30% increase in BC risk (HRc = 1.33, 95% CI = 1.05 to 1.69), and there was no apparent decrease in risk associated with multiparity except for having at least 4 FTPs vs. 1 FTP (HRc = 0.72, 95% CI = 0.54 to 0.98). Conclusions These findings suggest differential associations with parity between BRCA1 and BRCA2 mutation carriers with higher risk for uniparous BRCA1 carriers and parous BRCA2 carriers.

Authors: Mary Beth Terry, Yuyan Liao, Karin Kast, Antonis C. Antoniou, Jasmine A. McDonald, Thea M. Mooij, Christoph Engel, Catherine Nogues, Bruno Buecher, Véronique Mari, Jessica Moretta-Serra, Laurence Gladieff, Elisabeth Luporsi, Daniel Barrowdale, Debra Frost, Alex Henderson, Carole Brewer, D. Gareth Evans, Diana Eccles, Jackie Cook, Kai-Ren Ong, Louise Izatt, Munaza Ahmed, Patrick J. Morrison, Charlotte J. Dommering, Jan C. Oosterwijk, Margreet G. E. M. Ausems, Mieke Kriege, Saundra S. Buys, Irene L. Andrulis, Esther M. John, Mary Daly, Michael Friedlander, Sue Anne McLachlan, Ana Osorio, Trinidad Caldes, Anna Jakubowska, Jacques Simard, Christian F. Singer, Yen Tan, Edith Olah, Marie Navratilova, Lenka Foretova, Anne-Marie Gerdes, Marie-José Roos-Blom, Brita Arver, Håkan Olsson, Rita K. Schmutzler, John L. Hopper, Flora E. van Leeuwen, David Goldgar, Roger L. Milne, Douglas F. Easton, Matti A. Rookus, Nadine Andrieu

Date Published: 1st Oct 2018

Publication Type: Journal article

Human Diseases: hereditary breast ovarian cancer syndrome

Longitudinal anthropometry of children and adolescents using 3D-body scanning.
LIFE - Leipzig Research Center for Civilization Diseases, LIFE Child

Abstract (Expand)

3D-body scanning anthropometry is a suitable method for characterization of physiological development of children and adolescents, and for understanding onset and progression of disorders like overweight … and obesity. Here we present a novel body typing approach to describe and to interpret longitudinal 3D-body scanning data of more than 800 children and adolescents measured in up to four follow-ups in intervals of 1 year, referring to an age range between 6 and 18 years. We analyzed transitions between body types assigned to lower-, normal- and overweight participants upon development of children and adolescents. We found a virtually parallel development of the body types with only a few transitions between them. Body types of children and adolescents tend to conserve their weight category. 3D body scanning anthropometry in combination with body typing constitutes a novel option to investigate onset and progression of obesity in children.

Authors: H. Loeffler-Wirth, M. Vogel, T. Kirsten, F. Glock, T. Poulain, A. Korner, M. Loeffler, W. Kiess, H. Binder

Date Published: 14th Sep 2018

Publication Type: Not specified

Human Diseases: obesity

Progression-Free Survival as a Surrogate End Point for Overall Survival in First-Line Diffuse Large B-Cell Lymphoma: An Individual Patient-Level Analysis of Multiple Randomized Trials (SEAL).
GLA - German Lymphoma Alliance

Abstract (Expand)

Purpose Overall survival (OS) is the definitive and best-established primary efficacy end point to evaluate diffuse large B-cell lymphoma (DLBCL) therapies, but it requires prolonged follow-up. An … earlier end point assessed post-treatment would expedite clinical trial conduct and accelerate patient access to effective new therapies. Our objective was to formally evaluate progression-free survival (PFS) and PFS at 24 months (PFS24) as surrogate end points for OS in first-line DLBCL. Patients and Methods Individual patient data were analyzed from 7,507 patients from 13 multicenter randomized controlled trials of active treatment in previously untreated DLBCL, published after 2002, with sufficient PFS data to predict treatment effects on OS. Trial-level surrogacy examining the correlation of treatment effect estimates of PFS/PFS24 and OS was evaluated using both linear regression ( R(2)WLS) and Copula bivariable ( R(2)Copula) models. Prespecified criteria for surrogacy required either R(2)WLS or R(2)Copula >/= 0.80 and neither < 0.7, with lower-bound 95% CI > 0.60. Results Trial-level surrogacy for PFS was strong ( R(2)WLS = 0.83; R(2)Copula = 0.85) and met the predefined criteria for surrogacy. At the patient level, PFS strongly correlated with OS. The surrogate threshold effect had a hazard ratio of 0.89. Surrogacy was consistent across comparisons with or without rituximab and with rituximab maintenance trials. Trial-level surrogacy for PFS24 was relatively strong ( R(2)WLS = 0.77; R(2)Copula = 0.78) but did not meet prespecified criteria. At the patient level, PFS24 significantly correlated with OS. The surrogate threshold effect had an odds ratio of 1.51. Conclusion This large pooled analysis of individual patient data supports PFS as a surrogate end point for OS in future randomized controlled trials evaluating chemoimmunotherapy in DLBCL. Use of this end point may expedite therapeutic development with the intent of bringing novel therapies to this patient population years before OS results are mature.

Authors: Q. Shi, N. Schmitz, F. S. Ou, J. G. Dixon, D. Cunningham, M. Pfreundschuh, J. F. Seymour, U. Jaeger, T. M. Habermann, C. Haioun, H. Tilly, H. Ghesquieres, F. Merli, M. Ziepert, R. Herbrecht, J. Flament, T. Fu, B. Coiffier, C. R. Flowers

Date Published: 1st Sep 2018

Publication Type: Not specified

Human Diseases: diffuse large B-cell lymphoma

Measurement of cerebral biomarkers proving traumatic brain injuries in post-mortem body fluids
Genetical Statistics and Systems Biology

Abstract (Expand)

Until now, it is impossible to identify a fatal traumatic brain injury (TBI) before post-mortem radiological investigations or an autopsy take place. It would be preferable to have an additional … diagnostic tool like post-mortem biochemistry to get greater insight into the pathological pathways and survival times after sustaining TBI. Cerebrospinal fluid (CSF) and serum samples of 84 autopsy cases were collected from forensic autopsies with post-mortem intervals (PMI) of up to 148 h. The cases were categorized into a fatal TBI case group (n=42) and non-TBI controls (n=42). The values of glial fibrillary acidic protein (GFAP), brain-derived neurotrophic factor (BDNF) and neutrophil gelatinase-associated lipocalin (NGAL) were analyzed by means of quantitative chemiluminescent multiplex immunoassays. The main results indicate that the usage of liquid samples with good macroscopic quality is more relevant for meaningful biomarker analyses than the length of the PMI. All three proteins were shown to differentiate TBI fatalities from the controls in CSF. In serum, only GFAP could be shown to be able to identify TBI cases. This study is the first approach to measure the three proteins together in CSF and serum in autopsy cases. Determined threshold values may differentiate between fatal TBI and control cases. The presented results emphasize the possible use of post-mortem biochemistry as a supplemental tool in everyday forensic routine.

Authors: Benjamin Ondruschka, Monique Sieber, Holger Kirsten, Heike Franke, Jan Dressler

Date Published: 1st Sep 2018

Publication Type: Journal article

Footprints of Sepsis Framed Within Community Acquired Pneumonia in the Blood Transcriptome.
CAPSys - Footprints of Sepsis Framed Within Community Acquired Pneumonia in the Blood Transcriptome, oBIG - omics Bioinformatics for Health

Abstract (Expand)

We analyzed the blood transcriptome of sepsis framed within community-acquired pneumonia (CAP) and characterized its molecular and cellular heterogeneity in terms of functional modules of co-regulated … genes with impact for the underlying pathophysiological mechanisms. Our results showed that CAP severity is associated with immune suppression owing to T-cell exhaustion and HLA and chemokine receptor deactivation, endotoxin tolerance, macrophage polarization, and metabolic conversion from oxidative phosphorylation to glycolysis. We also found footprints of host's response to viruses and bacteria, altered levels of mRNA from erythrocytes and platelets indicating coagulopathy that parallel severity of sepsis and survival. Finally, our data demonstrated chromatin re-modeling associated with extensive transcriptional deregulation of chromatin modifying enzymes, which suggests the extensive changes of DNA methylation with potential impact for marker selection and functional characterization. Based on the molecular footprints identified, we propose a novel stratification of CAP cases into six groups differing in the transcriptomic scores of CAP severity, interferon response, and erythrocyte mRNA expression with impact for prognosis. Our analysis increases the resolution of transcriptomic footprints of CAP and reveals opportunities for selecting sets of transcriptomic markers with impact for translation of omics research in terms of patient stratification schemes and sets of signature genes.

Authors: L. Hopp, H. Loeffler-Wirth, L. Nersisyan, A. Arakelyan, H. Binder

Date Published: 2nd Aug 2018

Publication Type: Not specified

Human Diseases: disease by infectious agent, pneumonia

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