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Incidence of severe sepsis and septic shock in German intensive care units: the prospective, multicentre INSEP study.
German Competence Network Sepsis (SepNet)

Abstract (Expand)

PURPOSE: To estimate the incidence density, point prevalence and outcome of severe sepsis and septic shock in German intensive care units (ICUs). METHODS: In a prospective, multicentre, longitudinal …servational study, all patients already on the ICU at 0:00 on 4 November 2013 and all patients admitted to a participating ICU between 0:00 on 4 November 2013 and 2359 hours on 1 December 2013 were included. The patients were followed up for the occurrence of severe sepsis or septic shock (SEPSIS-1 definitions) during their ICU stay. RESULTS: A total of 11,883 patients from 133 ICUs at 95 German hospitals were included in the study, of whom 1503 (12.6 %) were diagnosed with severe sepsis or septic shock. In 860 cases (57.2 %) the infections were of nosocomial origin. The point prevalence was 17.9 % (95 % CI 16.3-19.7).The calculated incidence rate of severe sepsis or septic shock was 11.64 (95 % CI 10.51-12.86) per 1000 ICU days. ICU mortality in patients with severe sepsis/septic shock was 34.3 %, compared with 6 % in those without sepsis. Total hospital mortality of patients with severe sepsis or septic shock was 40.4 %. Classification of the septic shock patients using the new SEPSIS-3 definitions showed higher ICU and hospital mortality (44.3 and 50.9 %). CONCLUSIONS: Severe sepsis and septic shock continue to be a frequent syndrome associated with high hospital mortality. Nosocomial infections play a major role in the development of sepsis. This study presents a pragmatic, affordable and feasible method for the surveillance of sepsis epidemiology. Implementation of the new SEPSIS-3 definitions may have a major effect on future epidemiological data.

Editor:

Date Published: No date defined

Publication Type: Not specified

Human Diseases: disease by infectious agent

Automated macrophage counting in DLBCL tissue samples: a ROF filter based approach
Molecular Mechanisms in Malignant Lymphomas - Demonstrators of Personalized Medicine

Abstract (Expand)

We describe a Rudin-Osher-Fatemi (ROF) filter based segmentation approach for whole tissue samples, combining floating intensity thresholding and rule-based feature detection. Method is validated against … manual counts and compared with two commercial software kits (Tissue Studio 64, Definiens AG, and Halo, Indica Labs) and a straightforward machine-learning approach in a set of 50 test images. Further, the novel method and both commercial packages are applied to a set of 44 whole tissue sections. Outputs are compared with gene expression data available for the same tissue samples. Finally, the ROF based method is applied to 44 expert-specified tumor subregions for testing selection and subsampling strategies. Our method is deterministic, fully automated, externally repeatable, independent on training data and -- in difference to most commercial software kits -- completely documented. Among all tested methods, the novel approach is best correlated with manual count (0.9297). Automated detection of evaluation subregions proved to be fully reliable. Subsampling within tumor subregions is possible with results almost identical to full sampling. Comparison with gene expression data obtained for the same tissue samples reveals only moderate to low correlation levels, thus indicating that image morphometry constitutes an independent source of information about antibody-polarized macrophage occurence and distribution.

Authors: Marcus Wagner, René Hänsel, Sarah Reinke, Julia Richter, Michael Altenbuchinger, Ulf-Dietrich Braumann, Rainer Spang, Markus Löffler, Wolfram Klapper

Date Published: No date defined

Publication Type: Not specified

Human Diseases: diffuse large B-cell lymphoma

An image dataset related to automated macrophage detection in immunostained lymphoma tissue samples
Molecular Mechanisms in Malignant Lymphomas - Demonstrators of Personalized Medicine

Abstract (Expand)

A large set of IHC stained DLBCL specimens is provided together with segmentation masks for different cell populations generated by a reference method for automated image analysis, thus featuring … considerable reuse potential. Provided image data comprise a) fluorescence microscopy images of 44 multiple immunohistostained DLBCL tumor subregions, captured at four channels corresponding to CD14, CD163, Pax5 and DAPI; b) cartoon-filtered versions of these images, generated by Rudin-Osher-Fatemi (ROF) denoising; c) an automatically generated mask of the evaluation subregion, based on information from the DAPI channel, and d) automatically generated segmentation masks for macrophages, B-cells and the total of cell nuclei, using information from CD14, CD163, Pax5 and DAPI channels, respectively.

Authors: Marcus Wagner, Sarah Reinke, René Hänsel, Wolfram Klapper, Ulf-Dietrich Braumann

Date Published: No date defined

Publication Type: Not specified

Human Diseases: diffuse large B-cell lymphoma

On the Cooperation between Epigenetics and Transcription Factor Networks in the Specification of Tissue Stem Cells
Leipzig Health Atlas

Abstract (Expand)

It is generally accepted that epigenetic modifications, such as DNA and histone methylations, affect transcription and that a gene’s transcription feeds back on its epigenetic profile. Depending on the … epigenetic modification, positive and negative feedback loops have been described. Here, we study whether such interrelation are mandatory and how transcription factor networks affect it. We apply self-organizing map machine learning to a published data set on the specification and differentiation of murine intestinal stem cells in order to provide an integrative view of gene transcription and DNA, as well as histone methylation during this process. We show that, although gain/loss of H3K4me3 at a gene promoter is generally considered to be associated with its increased/decreased transcriptional activity, such an interrelation is not mandatory, i.e., changes of the modification level do not necessarily affect transcription. Similar considerations hold for H3K27me3. In addition, even strong changes in the transcription of a gene do not necessarily affect its H3K4me3 and H3K27me3 modification profile. We provide a mechanistic explanation of these phenomena that is based on a model of epigenetic regulation of transcription. Thereby, the analyzed data suggest a broad variance in gene specific regulation of histone methylation and support the assumption of an independent regulation of transcription by histone methylation and transcription factor networks. The results provide insights into basic principles of the specification of tissue stem cells and highlight open questions about a mechanistic modeling of this process.

Authors: T. Thalheim, Lydia Hopp, Hans Binder, G. Aust, J. Galle

Date Published: No date defined

Publication Type: Not specified

Genome-wide analysis of carotid plaque burden suggests a role of IL5 in men.
Genetical Statistics and Systems Biology

Abstract (Expand)

BACKGROUND: Carotid artery plaque is an established marker of subclinical atherosclerosis with pronounced sex-dimorphism. Here, we aimed to identify genetic variants associated with carotid plaque … burden (CPB) and to examine potential sex-specific genetic effects on plaque sizes. METHODS AND RESULTS: We defined six operationalizations of CPB considering plaques in common carotid arteries, carotid bulb, and internal carotid arteries. We performed sex-specific genome-wide association analyses for all traits in the LIFE-Adult cohort (n = 727 men and n = 550 women) and tested significantly associated loci for sex-specific effects. In order to identify causal genes, we analyzed candidate gene expression data for correlation with CPB traits and corresponding sex-specific effects. Further, we tested if previously reported SNP associations with CAD and plaque prevalence are also associated with CBP. We found seven loci with suggestive significance for CPB (p<3.33x10-7), explaining together between 6 and 13% of the CPB variance. Sex-specific analysis showed a genome-wide significant hit for men at 5q31.1 (rs201629990, beta = -0.401, p = 5.22x10-9), which was not associated in women (beta = -0.127, p = 0.093) with a significant difference in effect size (p = 0.008). Analyses of gene expression data suggested IL5 as the most plausible candidate, as it reflected the same sex-specific association with CPBs (p = 0.037). Known plaque prevalence or CAD loci showed no enrichment in the association with CPB. CONCLUSIONS: We showed that CPB is a complementary trait in analyzing genetics of subclinical atherosclerosis. We detected a novel locus for plaque size in men only suggesting a role of IL5. Several estrogen response elements in this locus point towards a functional explanation of the observed sex-specific effect.

Authors: J. Pott, F. Beutner, K. Horn, H. Kirsten, K. Olischer, K. Wirkner, M. Loeffler, M. Scholz

Date Published: 30th May 2020

Publication Type: Journal

Human Diseases: cardiovascular system disease, atherosclerosis

The aging human body shape.
LIFE Adult

Abstract (Expand)

Body shape and composition are heterogeneous among humans with possible impact for health. Anthropometric methods and data are needed to better describe the diversity of the human body in human … populations, its age dependence, and associations with health risk. We applied whole-body laser scanning to a cohort of 8499 women and men of age 40-80 years within the frame of the LIFE (Leipzig Research Center for Civilization Diseases) study aimed at discovering health risk in a middle European urban population. Body scanning delivers multidimensional anthropometric data, which were further processed by machine learning to stratify the participants into body types. We here applied this body typing concept to describe the diversity of body shapes in an aging population and its association with physical activity and selected health and lifestyle factors. We find that aging results in similar reshaping of female and male bodies despite the large diversity of body types observed in the study. Slim body shapes remain slim and partly tend to become even more lean and fragile, while obese body shapes remain obese. Female body shapes change more strongly than male ones. The incidence of the different body types changes with characteristic Life Course trajectories. Physical activity is inversely related to the body mass index and decreases with age, while self-reported incidence for myocardial infarction shows overall the inverse trend. We discuss health risks factors in the context of body shape and its relation to obesity. Body typing opens options for personalized anthropometry to better estimate health risk in epidemiological research and future clinical applications.

Authors: A. Frenzel, H. Binder, N. Walter, K. Wirkner, M. Loeffler, H. Loeffler-Wirth

Date Published: 29th Mar 2020

Publication Type: Not specified

Ontological Modelling and Reasoning of Phenotypes
Leipzig Health Atlas, Onto-Med Research Group, SMITH

Abstract (Expand)

The successful determination and analysis of phenotypes plays a key role in the diagnostic process, the evaluation of risk factors and the recruitment of participants for clinical and epidemiological … studies. The development of computable phenotype algorithms to solve these tasks is a challenging problem, caused by various reasons. Firstly, the term ‘phenotype’ has no generally agreed definition and its meaning depends on context. Secondly, the phenotypes are most commonly specified as non-computable descriptive documents. Recent attempts have shown that ontologies are a suitable way to handle phenotypes and that they can support clinical research and decision making. The SMITH Consortium is dedicated to rapidly establish an integrative medical informatics framework to provide physicians with the best available data and knowledge and enable innovative use of healthcare data for research and treatment optimization. In the context of a methodological use case “phenotype pipeline” (PheP), a technology to automatically generate phenotype classifications and annotations based on electronic health records (EHR) is developed. A large series of phenotype algorithms will be implemented. This implies that for each algorithm a classification scheme and its input variables have to be defined. Furthermore, a phenotype engine is required to evaluate and execute developed algorithms. In this article we present a Core Ontology of Phenotypes (COP) and a software Phenotype Manager (PhenoMan), which implements a novel ontology-based method to model and calculate phenotypes. Our solution includes an enhanced iterative reasoning process combining classification tasks with mathematical calculations at runtime. The ontology as well as the reasoning method were successfully evaluated based on different phenotypes (including SOFA score, socioeconomic status, body surface area and WHO BMI classification) and several data sets.

Authors: Alexandr Uciteli, Christoph Beger, Toralf Kirsten, Frank A. Meineke, Heinrich Herre

Date Published: 20th Dec 2019

Publication Type: Proceedings

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