Neue Biomarker zur Diagnosestellung der spontan bakteriellen Peritonitis

Die SBP stellt eine schwere Komplikation bei Patienten mit einer Leberzirrhose dar. Die zugrundeliegenden Pathomechanismen sind bis heute nicht abschließend geklärt. Aufgrund der nach wie vor hohen 1 Jahres-Mortalität der SBP sind neue Biomarker zur früheren Diagnosestellung von großer klinischer Bedeutung. In unserer Untersuchung wurden 190 Aszitesflüssigkeitsproben von insgesamt 128 Patienten mittels ELISA und BCA-Assay analysiert. Die Diagnose einer SBP (PMNs ≥ 250/µl Aszitesflüssigkeit) konnte in 29 Proben gestellt werden. Ein klinisch sehr relevantes Ergebnis unserer Studie ist unser Befund, dass eine entzündliche Aktivität in der Aszitesflüssigkeit bereits bei Zellzahlen von weniger als 250 neutrophilen Granulozyten pro µl Aszitesflüssigkeit nachgewiesen werden kann. Es kann keine Korrelation von IL 6 oder IP-10 mit den Diagnosekriterien oder dem Krankheitsverlauf bei einer SBP dargestellt werden. Trotz einer statistischen Korrelation von IL 8 und IL-10 mit den Diagnosekriterien einer SBP eignen sich die beiden Proteine nicht als Biomarker im Krankheitsbild einer SBP. Die C3a-Konzentration zeigt sich im Falle einer SBP verringert, verglichen mit Proben von Patienten ohne Leberzirrhose. Lactoferrin zeigt keine statistische Korrelation mit den Diagnosekriterien einer SBP, jedoch lassen sich aufgrund der Analyse von Verlaufsproben Abschätzungen zum Krankheitsverlauf einer SBP anstellen. Calprotectin korreliert sowohl mit den Diagnosekriterien als auch mit dem Krankheitsverlauf einer SBP und stellt einen potenziellen Biomarker im Krankheitsbild der SBP dar. Im Rahmen dieser Arbeit gelingt die Erstbeschreibung von S100a12 als neuer Biomarker zur Diagnostik und Beurteilung des klinischen Verlaufes im Krankheitsbild der SBP. Die Entwicklung eines Bedside-Tests, ggf. auch als App, aufgrund der in dieser Arbeit gewonnenen Erkenntnisse ist in Planung

Bacterial Species Associated with Highly Allergenic Plant Pollen Yield a High Level of Endotoxins and Induce Chemokine and Cytokine Release from Human A549 Cells

none10siSensitization to pollen allergens has been increasing in Europe every year. Most studies in this field are related to climate change, phenology, allergens associated with different pollens, and allergic disorders. As a plant microhabitat, pollen is colonized by diverse microorganisms, including endotoxin-producing bacteria which may contribute to pollen allergy (pollinosis). Therefore, bacteria isolated from high allergenic and low allergenic plant pollen, as well as the pollen itself with all microbial inhabitants, were used to assess the effect of the pollen by measuring the endotoxins lipopolysaccharides (LPS) and lipoteichoic acid (LTA) concentrations and their effect on chemokine and cytokine release from transwell cultured epithelial A549 cells as a model of epithelial lung barrier. High allergenic pollen showed a significantly higher level of bacterial endotoxins; interestingly, the endotoxin level found in the bacterial isolates from high allergenic pollen was significantly higher compared to that of bacteria from low allergenic pollen. Moreover, bacterial LPS concentrations across different pollen species positively correlated with the LPS concentration across their corresponding bacterial isolates. Selected bacterial isolates from hazel pollen (HA5, HA13, and HA7) co-cultured with A549 cells induced a potent concentration-dependent release of the chemokine interleukin-8 and monocyte chemotactic protein-1 as well as the cytokine TNF-alpha and interleukin-2 to both apical and basal compartments of the transwell model. This study clearly shows the role of bacteria and bacterial endotoxins in the pollen allergy as well as seasonal allergic rhinitis.Ambika Manirajan, Binoy; Hinrichs, Ann-Kathrin; Ratering, Stefan; Rusch, Volker; Schwiertz, Andreas; Geissler-Plaum, Rita; Eichner, Gerrit; Cardinale, Massimiliano; Kuntz, Sabine; Schnell, SylviaAmbika Manirajan, Binoy; Hinrichs, Ann-Kathrin; Ratering, Stefan; Rusch, Volker; Schwiertz, Andreas; Geissler-Plaum, Rita; Eichner, Gerrit; Cardinale, Massimiliano; Kuntz, Sabine; Schnell, Sylvi

Introduction of innovations in joint arthroplasty: Recommendations from the 'EFORT implant and patient safety initiative'

With the implementation of the new MDR 2017/745 by the European Parliament, more robust clinical and pre-clinical data will be required due to a more stringent approval process. The EFORT Implant and Patient Safety Initiative WG1 ‘Introduction of Innovation’, combined knowledge of orthopaedic surgeons, research institutes, orthopaedic device manufacturers, patient representatives and regulatory authorities to develop a comprehensive set of recommendations for the introduction of innovations in joint arthroplasty within the boundaries of MDR 2017/745. Recommendations have been developed to address key questions about pre-clinical and clinical requirements for the introduction of new implants and implant-related instrumentation with the participation of a steering group, invited by the EFORT Board in dialogue with representatives from European National Societies and Speciality Societies. Different degrees of novelty and innovation were described and agreed on in relation to when surgeons can start, using implants and implant-related instrumentation routinely. Before any clinical phase of a new implant, following the pre-market clinical investigation or the equivalent device PMCF pathway, it is a common understanding that all appropriate pre-clinical testing (regulatory mandatory and evident state of the art) – which has to be considered for a specific device – has been successfully completed. Once manufacturers receive the CE mark for a medical device, it can be used in patients routinely when a clinical investigation has been conducted to demonstrate the conformity of devices according to MDR Article 62 or full equivalence for the technical, biological and clinical characteristics has been demonstrated (MDR, Annex XIV, Part A, 3.) and a PMCF study has been initiated

COgnitive behavioural therapy vs standardised medical care for adults with Dissociative non-Epileptic Seizures (CODES): a multicentre randomised controlled trial protocol

Background The evidence base for the effectiveness of psychological interventions for patients with dissociative non-epileptic seizures (DS) is currently extremely limited, although data from two small pilot randomised controlled trials (RCTs), including from our group, suggest that Cognitive Behavioural Therapy (CBT) may be effective in reducing DS occurrence and may improve aspects of psychological status and psychosocial functioning. Methods/Design The study is a multicentre, pragmatic parallel group RCT to evaluate the clinical and cost-effectiveness of specifically-tailored CBT plus standardised medical care (SMC) vs SMC alone in reducing DS frequency and improving psychological and health-related outcomes. In the initial screening phase, patients with DS will receive their diagnosis from a neurologist/epilepsy specialist. If patients are eligible and interested following the provision of study information and a booklet about DS, they will consent to provide demographic information and fortnightly data about their seizures, and agree to see a psychiatrist three months later. We aim to recruit ~500 patients to this screening stage. After a review three months later by a psychiatrist, those patients who have continued to have DS in the previous eight weeks and who meet further eligibility criteria will be told about the trial comparing CBT + SMC vs SMC alone. If they are interested in participating, they will be given a further booklet on DS and study information. A research worker will see them to obtain their informed consent to take part in the RCT. We aim to randomise 298 people (149 to each arm). In addition to a baseline assessment, data will be collected at 6 and 12 months post randomisation. Our primary outcome is monthly seizure frequency in the preceding month. Secondary outcomes include seizure severity, measures of seizure freedom and reduction, psychological distress and psychosocial functioning, quality of life, health service use, cost effectiveness and adverse events. We will include a nested qualitative study to evaluate participants’ views of the intervention and factors that acted as facilitators and barriers to participation. Discussion This study will be the first adequately powered evaluation of CBT for this patient group and offers the potential to provide an evidence base for treating this patient group. Trial registration Current Controlled Trials ISRCTN05681227 ClinicalTrials.gov NCT0232554

Marine bacterial communities are resistant to elevated carbon dioxide levels

© 2014 Society for Applied Microbiology and John Wiley & Sons Ltd. Summary: It is well established that the release of anthropogenic-derived CO2 into the atmosphere will be mainly absorbed by the oceans, with a concomitant drop in pH, a process termed ocean acidification. As such, there is considerable interest in how changes in increased CO2 and lower pH will affect marine biota, such as bacteria, which play central roles in oceanic biogeochemical processes. Set within an ecological framework, we investigated the direct effects of elevated CO2, contrasted with ambient conditions on the resistance and resilience of marine bacterial communities in a replicated temporal seawater mesocosm experiment. The results of the study strongly indicate that marine bacterial communities are highly resistant to the elevated CO2 and lower pH conditions imposed, as demonstrated from measures of turnover using taxa-time relationships and distance-decay relationships. In addition, no significant differences in community abundance, structure or composition were observed. Our results suggest that there are no direct effects on marine bacterial communities and that the bacterial fraction of microbial plankton holds enough flexibility and evolutionary capacity to withstand predicted future changes from elevated CO2 and subsequent ocean acidification

Phylodynamics and movement of Phycodnaviruses among aquatic environments

Phycodnaviruses have a significant role in modulating the dynamics of phytoplankton, thereby influencing community structure and succession, nutrient cycles and potentially atmospheric composition because phytoplankton fix about half the carbon dioxide (CO2) on the planet, and some algae release dimethylsulphoniopropionate when lysed by viruses. Despite their ecological importance and widespread distribution, relatively little is known about the evolutionary history, phylogenetic relationships and phylodynamics of the Phycodnaviruses from freshwater environments. Herein we provide novel data on Phycodnaviruses from the largest river system on earth—the Amazon Basin—that were compared with samples from different aquatic systems from several places around the world. Based on phylogenetic inference using DNA polymerase (pol) sequences we show the presence of distinct populations of Phycodnaviridae. Preliminary coarse-grained phylodynamics and phylogeographic inferences revealed a complex dynamics characterized by long-term fluctuations in viral population sizes, with a remarkable worldwide reduction of the effective population around 400 thousand years before the present (KYBP), followed by a recovery near to the present time. Moreover, we present evidence for significant viral gene flow between freshwater environments, but crucially almost none between freshwater and marine environments

The German National Registry of Primary Immunodeficiencies (2012-2017)

Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs. Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel. Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1–25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0–88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%—subcutaneous; 29%—intravenous; 1%—unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy. Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment

Marine Microbial Gene Abundance and Community Composition in Response to Ocean Acidification and Elevated Temperature in Two Contrasting Coastal Marine Sediments

Marine ecosystems are exposed to a range of human-induced climate stressors, in particular changing carbonate chemistry and elevated sea surface temperatures as a consequence of climate change. More research effort is needed to reduce uncertainties about the effects of global-scale warming and acidification for benthic microbial communities, which drive sedimentary biogeochemical cycles. In this research, mesocosm experiments were set up using muddy and sandy coastal sediments to investigate the independent and interactive effects of elevated carbon dioxide concentrations (750 ppm CO2) and elevated temperature (ambient +4∘C) on the abundance of taxonomic and functional microbial genes. Specific quantitative PCR primers were used to target archaeal, bacterial, and cyanobacterial/chloroplast 16S rRNA in both sediment types. Nitrogen cycling genes archaeal and bacterial ammonia monooxygenase (amoA) and bacterial nitrite reductase (nirS) were specifically targeted to identify changes in microbial gene abundance and potential impacts on nitrogen cycling. In muddy sediment, microbial gene abundance, including amoA and nirS genes, increased under elevated temperature and reduced under elevated CO2 after 28 days, accompanied by shifts in community composition. In contrast, the combined stressor treatment showed a non-additive effect with lower microbial gene abundance throughout the experiment. The response of microbial communities in the sandy sediment was less pronounced, with the most noticeable response seen in the archaeal gene abundances in response to environmental stressors over time. 16S rRNA genes (amoA and nirS) were lower in abundance in the combined stressor treatments in sandy sediments. Our results indicated that marine benthic microorganisms, especially in muddy sediments, are susceptible to changes in ocean carbonate chemistry and seawater temperature, which ultimately may have an impact upon key benthic biogeochemical cycles

TRY plant trait database – enhanced coverage and open access

Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives