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1004 Publications visible to you, out of a total of 1004
Lifestyle intervention in BRCA1/2 mutation carriers: study protocol for a prospective, randomized, controlled clinical feasibility trial (LIBRE-1 study)
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Abstract (Expand)

BACKGROUND Women with highly penetrant BRCA mutations have a 55-60% lifetime risk for breast cancer and a 16-59% lifetime risk for ovarian cancer. However, penetrance differs interindividually, indicating …g that environmental and behavioral factors may modify this risk. These include lifestyle factors such as physical activity status, dietary habits, and body weight. The modification of penetrance by changing lifestyle factors has not thus far been investigated in a randomized trial in BRCA mutation carriers. METHODS Therefore, we intend to enroll 60 BRCA1/2 mutation carriers in a pilot feasibility study (Lifestyle Intervention Study in Women with Hereditary Breast and Ovarian Cancer (LIBRE) pilot). This multi-center, prospective, controlled trial aims to randomize (1:1) participants into a (1) multi-factorial lifestyle intervention group (IG) versus (2) the control group with usual care (CG). The primary endpoint is feasibility and acceptance of a structured interdisciplinary lifestyle intervention program over 12 months (at least 70% of the patients to complete the 1-year intervention). Furthermore, the effects on physical fitness, BMI, quality of life, and stress coping capacity will be investigated. During the first 3 months, women in the IG will receive structured, individualized and mainly supervised endurance training of \geq18 MET*h/week (MET = metabolic equivalent task) and personal nutritional counseling based on the Mediterranean diet. During the subsequent 9 months, the IG will receive monthly group training sessions and regular telephone contacts for motivation, whereas the CG will only receive usual care (one general counseling on healthy nutrition and benefits of regular physical activity on health status). At randomization and subsequent time points (3, 6, 12 months), cardiopulmonary fitness will be assessed by spiroergometry and nutritional and psychological status by validated questionnaires. DISCUSSION This pilot study will investigate the optimal strategy to improve physical fitness, nutritional habits, and psychological factors in women at high risk for developing breast or ovarian cancer. The results of this pilot feasibility study will be the basis for a larger prospective randomized trial including clinical events (LIBRE). TRIAL REGISTRATION ClinicalTrials.gov, NCT02087592.

Authors: Marion Kiechle, Christoph Engel, Anika Berling, Katrin Hebestreit, Stephan Bischoff, Ricarda Dukatz, Wolf-Dieter Gerber, Michael Siniatchkin, Katharina Pfeifer, Sabine Grill, Maryam Yahiaoui-Doktor, Ellen Kirsch, Uwe Niederberger, Nicole Marter, Ute Enders, Markus Löffler, Alfons Meindl, Kerstin Rhiem, Rita Schmutzler, Nicole Erickson, Martin Halle

Date Published: 1st Dec 2016

Publication Type: Journal article

Human Diseases: hereditary breast ovarian cancer syndrome

PROGRESS - prospective observational study on hospitalized community acquired pneumonia
Genetical Statistics and Systems Biology

Abstract (Expand)

BACKGROUND Community acquired pneumonia (CAP) is a high incidence disease resulting in about 260,000 hospital admissions per year in Germany, more than myocardial infarction or stroke. Worldwide, CAP …P is the most frequent infectious disease with high lethality ranging from 1.2 % in those 20-29 years old to over 10 % in patients older than 70 years, even in industrial nations. CAP poses numerous medical challenges, which the PROGRESS (Pneumonia Research Network on Genetic Resistance and Susceptibility for the Evolution of Severe Sepsis) network aims to tackle: Operationalization of disease severity throughout the course of disease, outcome prediction for hospitalized patients and prediction of transitions from uncomplicated CAP to severe CAP, and finally, to CAP with sepsis and organ failure as a life-threatening condition. It is a major aim of PROGRESS to understand and predict patient heterogeneity regarding outcome in the hospital and to develop novel treatment concepts. METHODS PROGRESS was designed as a clinical, observational, multi-center study of patients with CAP requiring hospitalization. More than 1600 patients selected for low burden of co-morbidities have been enrolled, aiming at a total of 3000. Course of disease, along with therapy, was closely monitored by daily assessments and long-term follow-up. Daily blood samples allow in depth molecular-genetic characterization of patients. We established a well-organized workflow for sample logistics and a comprehensive data management system to collect and manage data from more than 50 study centers in Germany and Austria. Samples are stored in a central biobank and clinical data are stored in a central data base which also integrates all data from molecular assessments. DISCUSSION With the PROGRESS study, we established a comprehensive data base of high quality clinical and molecular data allowing investigation of pressing research questions regarding CAP. In-depth molecular characterization will contribute to the discovery of disease mechanisms and establishment of diagnostic and predictive biomarkers. A strength of PROGRESS is the focus on younger patients with low burden of co-morbidities, allowing a more direct look at host biology with less confounding. As a resulting limitation, insights from PROGRESS will require validation in representative patient cohorts to assess clinical utility. TRIAL REGISTRATION The PROGRESS study was retrospectively registered on May 24(th), 2016 with ClinicalTrials.gov: NCT02782013.

Authors: Peter Ahnert, Petra Creutz, Markus Scholz, Hartwig Schütte, Christoph Engel, Hamid Hossain, Trinad Chakraborty, Michael Bauer, Michael Kiehntopf, Uwe Völker, Sven Hammerschmidt, Markus Loeffler, Norbert Suttorp

Date Published: 1st Dec 2016

Publication Type: Journal article

Comparing performance of modern genotype imputation methods in different ethnicities
Genetical Statistics and Systems Biology

Abstract (Expand)

A variety of modern software packages are available for genotype imputation relying on advanced concepts such as pre-phasing of the target dataset or utilization of admixed reference panels. In this … study, we performed a comprehensive evaluation of the accuracy of modern imputation methods on the basis of the publicly available POPRES samples. Good quality genotypes were masked and re-imputed by different imputation frameworks: namely MaCH, IMPUTE2, MaCH-Minimac, SHAPEIT-IMPUTE2 and MaCH-Admix. Results were compared to evaluate the relative merit of pre-phasing and the usage of admixed references. We showed that the pre-phasing framework SHAPEIT-IMPUTE2 can overestimate the certainty of genotype distributions resulting in the lowest percentage of correctly imputed genotypes in our case. MaCH-Minimac performed better than SHAPEIT-IMPUTE2. Pre-phasing always reduced imputation accuracy. IMPUTE2 and MaCH-Admix, both relying on admixed-reference panels, showed comparable results. MaCH showed superior results if well-matched references were available (Nei’s GST ≤ 0.010). For small to medium datasets, frameworks using genetically closest reference panel are recommended if the genetic distance between target and reference data set is small. Our results are valid for small to medium data sets. As shown on a larger data set of population based German samples, the disadvantage of pre-phasing decreases for larger sample sizes.

Authors: Nab Raj Roshyara, Katrin Horn, Holger Kirsten, Peter Ahnert, Markus Scholz

Date Published: 1st Dec 2016

Publication Type: Journal article

Sevoflurane and Isoflurane-Pharmacokinetics, Hemodynamic Stability, and Cardioprotective Effects During Cardiopulmonary Bypass
Genetical Statistics and Systems Biology

Abstract (Expand)

OBJECTIVES This study aimed to evaluate the pharmacokinetic profiles of sevoflurane and isoflurane during use of minimized extracorporeal circulation to perform coronary artery bypass graft surgery. …. Furthermore, cardiovascular stability during bypass and the postoperative release of troponins were evaluated. DESIGN Prospective, randomized study. SETTING University hospital. PARTICIPANTS The study comprised 31 adult patients undergoing coronary artery bypass grafting. INTERVENTIONS The pharmacokinetic measurements of the concentration of the volatile anesthetics in the arterial and venous blood, air inlet, air outlet, and gas exhaust of the extracorporeal circulation were recorded. Secondary end-points were cardiovascular stability during bypass, amount of postoperative release of troponin, time to extubation, time to discharge from the intensive care unit and the hospital, and 30-day mortality. MEASUREMENTS AND MAIN RESULTS Thirty patients completed the protocol. The pharmacokinetics of isoflurane and sevoflurane were almost identical, with a rapid wash-in (time to reach 50% of arterial steady state) concentration of 0.87\pm0.97 minutes and 1.14\pm0.35 minutes for isoflurane and sevoflurane, respectively, and a biphasic venous elimination with a terminal half-life of approximately 10 minutes for both compounds. There was a correlation between the gas inlet and the gas exhaust of the extracorporeal circulation. No difference in cardiovascular stability was found. High-sensitivity troponin concentrations on the first postoperative morning were 0.355\pm0.312 µg/mL and 0.225\pm0.111 µg/mL in the isoflurane and sevoflurane groups, respectively (p = 0.147). CONCLUSIONS The study found similar pharmacokinetics regarding wash-in and wash-out for sevoflurane and isoflurane. In addition, no difference in cardiovascular stability was found. The markers of cardiac damage were not different between the two anesthetics. Based on these data, sevoflurane and isoflurane might be used equivalently in patients undergoing coronary artery bypass graft surgery with extracorporeal circulation.

Authors: David Freiermuth, Berend Mets, Daniel Bolliger, Oliver Reuthebuch, Thomas Doebele, Markus Scholz, Michael Gregor, Matthias Haschke, Manfred Daniel Seeberger, Jens Fassl

Date Published: 1st Dec 2016

Publication Type: Journal article

Predicting early signs of dyslexia at a preliterate age by combining behavioral assessment with structural MRI
Genetical Statistics and Systems Biology

Abstract (Expand)

BACKGROUND Recent studies suggest that neurobiological anomalies are already detectable in pre-school children with a family history of developmental dyslexia (DD). However, there is a lack of longitudinal …l studies showing a direct link between those differences at a preliterate age and the subsequent literacy difficulties seen in school. It is also not clear whether the prediction of DD in pre-school children can be significantly improved when considering neurobiological predictors, compared to models based on behavioral literacy precursors only. METHODS We recruited 53 pre-reading children either with (N=25) or without a family risk of DD (N=28). Quantitative T1 MNI data and literacy precursor abilities were assessed at kindergarten age. A subsample of 35 children was tested for literacy skills either one or two years later, that is, either in first or second grade. RESULTS The group comparison of quantitative T1 measures revealed significantly higher T1 intensities in the left anterior arcuate fascicle (AF), suggesting reduced myelin concentration in preliterate children at risk of DD. A logistic regression showed that DD can be predicted significantly better (p=.024) when neuroanatomical differences between groups are used as predictors (80%) compared to a model based on behavioral predictors only (63%). The Wald statistic confirmed that the T1 intensity of the left AF is a statistically significant predictor of DD (p\textless.05). CONCLUSIONS Our longitudinal results provide evidence for the hypothesis that neuroanatomical anomalies in children with a family risk of DD are related to subsequent problems in acquiring literacy. Particularly, solid white matter organization in the left anterior arcuate fascicle seems to play a pivotal role.

Authors: Indra Kraft, Jan Schreiber, Riccardo Cafiero, Riccardo Metere, Gesa Schaadt, Jens Brauer, Nicole E. Neef, Bent Müller, Holger Kirsten, Arndt Wilcke, Johannes Boltze, Angela D. Friederici, Michael A. Skeide

Date Published: 1st Dec 2016

Publication Type: Journal article

Obesity is Associated with White Matter Changes and Cognitions among Healthy Elderly
LIFE - Leipzig Research Center for Civilization Diseases

Abstract (Expand)

Midlife obesity has often been associated with accelerated cognitive decline during aging. Obesity leads to changes in multiple physiological factors that could impact neuronal tissue. Numerous studies … have linked obesity and higher body mass index (BMI) with differences in cognitive functions and brain structure, including total brain volume, regional gray matter volume and white matter (WM) microstructure. However, regarding to WM, the available neuroimaging studies incorporated mainly small sample sizes that yielded less conclusive results. Thus, we investigated the association of obesity, measured using BMI and waist to hip ratio (WHR), with changes in WM microstructure, as well as variance in cognitive test scores in a large cohort of community-dwelling healthy individuals older than 60 years.

Authors: Rui Zhang, L. Lampe, Frauke Beyer, Sebastian Huhn, S. K. Masouleh, T. Luck, S. G. Riedel-Heller, Markus Löffler, M. L. Schroeter

Date Published: 28th Nov 2016

Publication Type: Not specified

Human Diseases: obesity

[Adverse drug reactions in elderly people : First data from the Leipzig Research Center for Civilization Diseases (LIFE)].
LIFE Adult

Abstract (Expand)

BACKGROUND: Few data exist on adverse drug reactions (ADR) in elderly people. In this group, pharmacotherapy represents a challenge with regard to comorbidities, drug interactions and compliance. … OBJECTIVE: The aim of this article is to highlight the characteristics of ADR in elderly patients. METHODS: In addition to a literature review we present the first data from the Leipzig Research Center for Civilization Diseases (LIFE). Between 2011 and 2015 a total of 9537 subjects aged 40-79 years were randomly included in this population-based, age and sex standardized investigation in the inhabitants of Leipzig, Germany and special emphasis was placed on allergies including questions with regard to ADR. RESULTS: Of the 9537 subjects, data on allergies were available from 8979 subjects. Female gender, comorbidities and the use of multiple drugs were significantly associated with an increased risk of ADR. Women also reported ADR significantly more frequently than men. Of the subjects 22% reported suffering from some form of ADR as a result of medications, while in 2.3% this reaction had occurred within the previous 12 months. Less than 15% of LIFE patients with ADR were in possession of a document giving details of the ADR. DISCUSSION: The occurrence of ADR significantly contributes to morbidity in elderly patients. For prevention of ADR knowledge of patient-related factors, underlying diseases, drug characteristics and drug interactions are necessary.

Authors: R. Treudler, F. Walther, P. Ahnert, J. C. Simon

Date Published: 23rd Nov 2016

Publication Type: Journal article

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