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Background and Purpose: Post-traumatic cardiac dysfunction often occurs in multiply injured patients (ISS ≥ 16). Next to direct cardiac injury, post-traumatic cardiac dysfunction is mostly induced by the release of inflammatory biomarkers. One of these is the heparin-binding factor Midkine, which is elevated in humans after fracture, burn injury and traumatic spinal cord injury. Midkine is associated with cardiac pathologies but the exact role of Midkine in the development of those diseases is ambiguous. The systemic profile of Midkine after multiple trauma, its effects on cardiomyocytes and the association with post-traumatic cardiac dysfunction, remain unknown. Experimental Approach: Midkine levels were investigated in blood plasma of multiply injured humans and pigs. Furthermore, human cardiomyocytes (iPS) were cultured in presence/absence of Midkine and analyzed regarding viability, apoptosis, calcium handling,metabolic alterations, and oxidative stress. Finally, theMidkine filtration capacity of the therapeutic blood absorption column CytoSorb ®300 was tested with recombinant Midkine or plasma from multiply injured patients. Key Results: Midkine levels were significantly increased in blood plasma of multiply injured humans and pigs. Midkine acts on human cardiomyocytes, altering their mitochondrial respiration and calcium handling in vitro. CytoSorb®300 filtration reduced Midkine concentration ex vivo and in vitro depending on the dosage. Conclusion and Implications: Midkine is elevated in human and porcine plasma after multiple trauma, affecting the functionality and metabolism of human cardiomyocytes in vitro. Further examinations are required to determine whether the application of CytoSorb®300 filtration in patients after multiple trauma is a promising therapeutic approach to prevent post-traumatic cardiac disfunction., publishedVersion

The seventh "Future of the Allergists and Specific Immunotherapy (FASIT)" workshop held in 2019 provided a platform for global experts from academia, allergy clinics, regulatory authorities and industry to review current developments in the field of allergen immunotherapy (AIT). Key domains of the meeting included the following: (a) Biomarkers for AIT and allergic asthma; (b) visions for the future of AIT; (c) progress and data for AIT in asthma and the updates of GINA and EAACI Asthma Guidelines (separated for house dust mite SCIT, SLIT tablets and SLIT drops; patient populations) including a review of clinically relevant endpoints in AIT studies in asthma; (d) regulatory prerequisites such as the "Therapy Allergen Ordinance" in Germany; (e) optimization of trial design in AIT clinical research; (f) challenges planning and conducting phase III (field) studies and the future role of Allergen Exposure Chambers (AEC) in AIT product development from the regulatory point of view. We report a summary of panel discussions of all six domains and highlight unmet needs and possible solutions for the future. ispartof: ALLERGY vol:74 pages:3-25 ispartof: location:Denmark status: published

The relevance of azathioprine and 6-mercaptopurine therapy in inflammatory bowel disease, Crohn's disease, and ulcerative colitis, has been challenged in recent publications. In this article, a panel of experts gives advice, based on the relevant literature, on indications and practical use of azathioprine/6-mercaptopurine, prevention, and management of drug adverse reactions and special situations such as vaccination, pregnancy, and lactation.

Background: The treatment of severe full-thickness skin defects represents a significant and common clinical problem worldwide. A bio-engineered autologous skin substitute would significantly reduce the problems observed with today's gold standard. Methods: Within 15 years of research, the Tissue Biology Research Unit of the University Children's Hospital Zurich has developed autologous tissue-engineered skin grafts based on collagen type I hydrogels. Those products are considered as advanced therapy medicinal products (ATMPs) and are routinely produced for clinical trials in a clean room facility following the guidelines for good manufacturing practice (GMP). This article focuses on hurdles observed for the translation of ATMPs from research into the GMP environment and clinical application. Results and Conclusion: Personalized medicine in the field of rare diseases has great potential. However, ATMPs are mainly developed and promoted by academia, hospitals, and small companies, which face many obstacles such as high financial burdens.

Nahrungsmittelunvertraglichkeiten sind deutlich seltener objektiv nachweisbar als subjektiv empfunden. Insbesondere zum wissenschaftlichen Kenntnisstand nichtallergischer Uberempfindlichkeitsreaktionen bestehen grose Defizite. Ein Beispiel ist die Histamin-unvertraglichkeit, die. aufgrund der starken Thematisierung in den Medien und im Internet von Betroffenen oftmals als Ausloser ihrer Gesundheitsbeschwerden vermutet wird. Die wissen-schaftliehe Evidenz fur die postulierten Zusammen-hange ist begrenzt, eine verlassliche Labarbestirnmung zur definitiven Diagnose nicht vorhanden. Obwohl wissen-schaftliche Untersuchungen zur Unvertraglichkeit gegenuber exogen zugefuhrtem Histamin bisher ausschlieslich bei Erwachsenen durchgefuhrt wurden, wird die Diagnose auch bei Kindern und Jugendlichen gestellt, mit oftmals ein-schneidenden Konsequenzen fur den Speiseplan der Betroffenen. Die vorliegende Leitlinie der Arbeitsgruppe Nahrungsmittelallergie der Deutschen Gesellschaft fur Allergologie und klinische Immunologie (DGAKI) in Zusammenarbeit mit dem Arzteverband Deutscher Allergologen (ADA) und der Gesellschaft fur Padiatrisehe Allergologie und Umweltmedizin (GPA) fasst wichtige Aspekte zur Histaminunvertraglichkeit und deren Konsequenzen fur die Diagnostik und Therapie zusammen.