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 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 24th, 2016 with ClinicalTrials.gov: NCT02782013

Anhand der Daten aus der "Multizentrische Allergie Studie" (MAS) wird der natürliche Verlauf allergischer Erkrankungen und die Zusammenhänge unterschiedlicher Expositionen auf die Entwicklung von Allergien zu untersucht, um daraus verbesserte therapeutische und präventive Maßnahmen ableiten zu können. Methode MAS ist eine prospektive multizentrische Geburtskohortenstudie. 1990 wurden in fünf deutschen Städten 1314 Neugeborenen und deren Familien eingeschlossen (499 Atopie-Risikokinder und 815 zufällig ausgewählte Kinder ohne Atopierisiko). Symptome und Erkrankungen, die Lebenssituation der Familie, Risikofaktoren und Labordaten wurden jährlich über 7 Jahre erhoben. Die Datenanalyse erfolgte mittels multivariater Regressionsmodelle. Ergebnisse und Fazit Für das Serum-Gesamt-IgE wurden populationsbasierte Perzentilen für die ersten sechs Lebensjahre berechnet, die als "Normwerte-Tabellen" interpretiert werden können. Eine allergische Sensibilisierung entwickelt sich hauptsächlich während der ersten Lebensjahre. Am frühesten bilden sich Sensibilisierungen gegen Nahrungsmittelallergene aus, nach dem dritten Geburtstag überwiegen Sensibilisierungen gegen Inhalationsallergene mit Prävalenzen von 10% bis 20%. Als signifikante Risikofaktoren für eine Sensibilisierung erwiesen sich die Exposition gegenüber Umwelt(schad)stoffen wie dem Tabakrauch (OR=2,3), latexhaltigen Materialien in Krankenhäusern (OR=2,4) und verschiedenen Allergenen. Der stärkste Zusammenhang zeigte sich zwischen einer Exposition mit Innenraumallergenen und einer Sensibilisierung gegen diese Allergentypen. Weitere Risikofaktoren waren die Bereitschaft des Organismus, sehr früh in den ersten 2 Lebensjahren erhöhte Niveaus von IgE im Serum auszubilden, und eine atopische Prädisposition. Als wichtigste Risikofaktoren für die Entwicklung einer allergischen Rhinitis erwiesen sich das männliche Geschlecht (OR=2,4), keine weiteren Geschwister (OR=2,0), eine Sensibilisierung gegen Nahrungsmittel (OR=3,3), eine atopischen Dermatitis (OR=2,5) und eine atopische Familienanamnese (OR=3,0). Die prädiktive Wertigkeit einzelner Faktoren wurde gegeneinander abgegrenzt und das Atopierisiko bei unterschiedlichem Auftreten einzelner Prädiktoren berechnet. Trotz der guten prädiktiven Eigenschaften der Prädiktoren "hohes spezifisches IgE gegen Hühnerei" oder "dauerhafter Nachweis von IgE gegen Nahrungsmittel im Kleinkindalter" bedeutet die Verwendung dieser Parameter, dass eine Prädiktion frühestens 1-2 Jahre nach Geburt und erst nach wiederholter Bestimmung der IgE-Antikörper möglich ist. Auch wenn weiterhin Forschungsbedarf zur Allergieprävention besteht und die Wirksamkeit von einigen präventiven Maßnahmen noch systematisch evaluiert werden muss, sind auf einzelnen Feldern konkrete Handlungsanweisungen zur Prävention möglich. / Using data from the German Multicenter Allergy Study (MAS), we investigated the natural course of atopic diseases and the relationship of varied exposures to the development of allergies in order to develop more effective therapeutic and preventative treatment strategies. Methods The MAS is a prospective multicenter birth cohort study. In the year 1990, a total of 1314 newborns and their families from five German cities were included in the study, including 499 infants at high risk for atopy and 815 randomly selected infants with no known risk factors for atopy. Over a period of seven years, data was collected annually regarding symptoms, illnesses, family living situation and environment, risk factors, and laboratory tests. For data analysis we used multivariate regression models. Results and Conclusions From birth to the age of six, total serum IgE levels were calculated annually as population-based percentiles, and can thus be interpreted as a table of standard values. Allergic sensitization generally occurred within the first few years of life. Sensitization to food allergens occurred earliest, whereas sensitization to aeroallergens predominated after the age of three (with a prevalence of 10-20%). Significant risk factors for allergic sensitization included exposure to environmental pollutants/substances such as tobacco smoke (OR=2.3) or latex-containing medical products (OR=2.4). With regard to the relationship between exposure and subsequent sensitization to a specific allergen, the strongest correlation was observed with indoor allergens. Other risk factors included the early development of elevated serum IgE levels within the first year of life and an atopic predisposition. The most important risk factor for the development of allergic rhinitis was male gender (OR=2.4), no siblings (OR=2.0), sensitization to a food allergen (OR=3.3), atopic dermatitis (OR=2.5), and a family history of allergic disease (OR=3.0). The predictive value of individual factors was determined and the risk of developing atopic diseases calculated for individual predictors. In spite of the good predictive qualities of the factors " high values of specific IgE to hen's egg" and "long-lasting sensitization to food allergens during infancy", reliable prediction using these parameters can only be made 1-2 years after birth at the earliest and following a repeated measurement of IgE antibodies. There is still need for further research in allergy prevention, and the effectiveness of a number of preventative measures has yet to be evaluated in a systematic manner. Nevertheless, the results of this and other studies can already help physicians develop clearer, evidence-based strategies in the prevention of allergic disease.

Hypokaliämie ist bei Kühen mit Labmagenverlagerung und zusätzlichen Komplikationen eines der klinischen Probleme. Besonders bei Kühen mit rechtsseitiger Labmagenverlagerung werden Beziehungen des Kaliums zum Krankheitsverlauf deutlich. Serum-Kalium-Konzentrationen < 2 mmol/l sind prognostisch infaust. Durch Begleiterkrankungen werden bei Kühen mit Labmagenverlagerung Kalium sowie Cholesterol, Protein, Albumin, Bilirubin und Beta-Hydroxybutyrat zusätzlich negativ beeinfllusst.

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 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 24th, 2016 with ClinicalTrials.gov: NCT02782013