Complement activation products in acute heart failure: Potential role in pathophysiology, responses to treatment and impacts on long-term survival

Previous studies have indicated a correlation between heart failure, inflammation and poorer outcome. However, the pathogenesis and role of inflammation in acute heart failure (AHF) is incompletely studied and understood. The aim of our study was to explore the potential role of innate immunity - quantified by complement activation products (CAPs) - in pathophysiology, responses to treatment and impacts on long-term survival in AHF.; In a prospective study enrolling 179 unselected patients with AHF, plasma concentrations of C4d, C3a and sC5b-9 were measured in a blinded fashion on the first day of hospitalisation and prior to discharge. The final diagnosis, including the AHF phenotype, was adjudicated by two independent cardiologists. Long-term follow-up was obtained. Findings in AHF were compared to that obtained in 75 healthy blood donors (control group).; Overall, concentrations of all three CAPs were significantly higher in patients with AHF than in healthy controls (all p < 0.001). In an age-adjusted subgroup analysis, significant differences could be confirmed for concentrations of C4d and sC5b-9, and these parameters further increased after 6 days of in-hospital treatment ( p < 0.001). In contrast, C3a levels in AHF patients did not differ from those of the control group in the age-adjusted subgroup analysis and remained constant during hospitalisation. Concentrations of C4d, C3a and sC5b-9 were significantly higher when AHF was triggered by an infection as compared to other triggers ( p < 0.001). In addition, CAP levels significantly correlated with each other ( r = 0.64-0.76), but did not predict death within 2 years.; Activation of complement with increased plasma levels of C4d and sC5b-9 at admission and increasing levels during AHF treatment seems to be associated with AHF, particularly when AHF was triggered by an infection. However, CAPs do not have a prognostic value in AHF

Meeting Report: Aging Research and Drug Discovery

Aging is the single largest risk factor for most chronic diseases, and thus possesses large socioeconomic interest to continuously aging societies. Consequently, the field of aging research is expanding alongside a growing focus from the industry and investors in aging research. This year's 8th Annual Aging Research and Drug Discovery ARDD) meeting was organized as a hybrid meeting from August 30th to September 3rd 2021 with more than 130 attendees participating on-site at the Ceremonial Hall at University of Copenhagen, Denmark, and 1800 engaging online. The conference comprised of presentations from 75 speakers focusing on new research in topics including mechanisms of aging and how these can be modulated as well as the use of AI and new standards of practices within aging research. This year, a longevity workshop was included to build stronger connections with the clinical community

Interpretation of special findings in laboratory medicine and medical responsibility

Die Befundung individueller Fallkonstellationen bei geeigneten Parameterkonstellationen und Fragestellungen ist ein zentraler Bestandteil der medizinischen Aufgabenstellung des Fachgebietes Laboratoriumsmedizin. Um den labormedizinischen Anteil der medizinischen Diagnostik umfassend zu unterstützen, sollte unabhängig vom Einsatz wissensbasierter Systeme die labormedizinische Spezialbefundung generell bei entsprechenden Fragestellungen und Kenngrößenkonstellationen sowie bei Verfügbarkeit der jeweils geeigneten Methodik, bei Vorhandensein der entsprechenden Krankheitsprävalenzen und der entsprechenden labormedizinischen Kenntnisse durchgeführt werden. Dieser Notwendigkeit wird aber oft wegen des Aufwandes der individuellen fallbezogenen Befunderstellung nicht im erforderlichen Umfang entsprochen. Bei richtigem Einsatz wissensbasierter Systeme kann die labormedizinische Spezialbefundung effizient unterstützt und auf hohem Niveau optimiert und, soweit sinnvoll, standardisiert werden. Dies ist eine der wesentlichen Zielsetzungen der Pro.M.D.-Entwicklung (Prologsystem zur Unterstützung Medizinischer Diagnostik). Weitere zum Teil ebenfalls bereits zu einem großen Teil erreichte Ziele bei der Pro.M.D.-Entwicklung sind die Schaffung einer gemeinsamen Notationsebene für das bei der labormedizinischen Spezialbefundung formalisierbare Wissen und die dadurch erreichbare Verbesserung des fallbezogenen Erfahrungsaustausches.special findings based on suitable parameter constellations and clinical questions is one central task. To support the part of laboratory medicine in diagnostics, special interpretation should be carried out for clinical questions and parameterc onstellations generally, if appropriate methods/prevalence Information and laboratory-medical knowledge are available, regardless of whether knowledge-based Systems are in use. Frequently this necessity is not considered, due to the expenditure of creating individual reports on special findings. By the correct use of knowledge based-systems, Interpretation of special findings can be supported efficiently, be optimised at a high level and äs far äs sensible be standardised. This is one main aim in the development of Pro.M.D.

Ten Year's Experiences with a Microscopic-Microchemical Method for Analysis of Components of Urinary Calculi

Um eine gezielte Prophylaxe und Therapie der Urolithiasis zu ermöglichen und um die Rezidivrate zu senken, ist die genaue Kenntnis der Steinzusammensetzung erforderlich. Wegen des hohen Beschaffungspreises sind Röntgendiffraktion und Infrarotspektroskopie nur wenigen Laboratorien vorbehalten, andererseits sollten unspezifisch-chemische Steinanalysenmethoden wegen deren geringeren Sensitivität und Spezifität heute nicht mehr angewendet werden. In dieser Arbeit wird eine unter dem Mikroskop durchführbare Harnsteinkomponentenanalysenmethode (Harzalith) beschrieben. Es handelt sich um eine mikroskopisch-mikrochemische Harnsteinanalysenmethode. Sie basiert auf der Auswertung mikroskopisch typischer, leicht einprägsamer Farbmuster, die sich je nach Steinzusammensetzung in charakteristischer Weise nach Zugabe des Steinmaterials zum Reagenz innerhalb von Sekunden entwickeln. Eine Bewertung der mikroskopisch-mikrochemischen Harnsteinkomponentenanalyse gegenüber Röntgendiffraktion, Infrarotspektroskopie und unspezifisch-chemischen Methoden erfolgt anhand von Ergebnissen aus über 10jähriger eigener Anwendungserfahrung. Folgende Vorteile werden kurz dargestellt: 1. Es werden Steinkomponenten und nicht nur Ionen erfaßt. 2. Es können geringste Steinprobenmengen analysiert werden. 3. Die Ergebnisse der Methode hinsichtlich Richtigkeit, Sensitivität und Spezifität sind in gleicher Größenordnung wie die von Infrarotspektroskopie und Röntgendiffraktion. 4. Die Methode ist einfach zu erlernen, schnell, genau und von leichter Handhabung. Sie ist damit eine echte Alternative gegenüber den anderen apparativ-aufwendigen Harnsteinanalysenverfahren.Accurate knowledge of the composition of urinary calculi is necessary for purposeful prophylaxis and therapy of urolithiasis, and in order to reduce the rate of relapses. On account of the high acquisition price of X-ray diffraction and infrared spectroscopy, only few laboratories can use these techniques. On the other hand, unspecific chemical procedures for the analysis of urinary calculi are obsolet and should no longer be used because of their Iow sensitivity and specificity. In this publication we refer once more to a method of analysis urinary calculi undera microscop. The procedure is a microscopical one. It is based on the evaluation of microscopically typical, easily remembered colour patterns which - depending on the composition of the calculi - result within one minute affer the addition of parts of the calculi to the reagent. A comparison of the microscopical microchemical analysis of urinary calculi versus X-ray diffraction, infrared spectroscopy and unspecific chemical methods is made by means of the results obtained from over 10 years of our own application experience and by contrasting the result&of precision tests (i. e. 'Ringversuche') from the past ten years. The following advantages are particularly indicated: 1. Calculi constituents and not just ions are registered. 2. Minute quantities of calculi samples can be used. 3. The results of the method show the same degree.of correctness, sensitivity and specificity äs those of infrared spectroscopy and X-ray diffraction. 4. The method is simple to learn rapid, accurate and easily managed. It thus represents a genuine alternative to the methods of analysing urinary calculi which require more apparatus

Integrated Risk Assessment of Suicidal Ideation and Behavior in Drug Development

Suicide is a major public health concern with emerging understanding of its neuropharmacological basis. Treatment-related suicidal ideation and behavior (SIB) as adverse events of psychiatric and non-psychiatric drugs are under increasing public, legal and regulatory scrutiny. Prospective assessment of SIB is emerging as a challenging safety requirement by health authorities worldwide for the development of certain drugs while the underlying risk factors remain ill defined. To help with the understanding and harmoniation of risk factors that trigger a prospective assessment of SIB in clinical trials, Bristol-Meyers-Squibb, Eli Lilly, Novartis, Pfizer and Roche/Genentech present a consensus framework for risk assessment and decision making of SIB during drug development. Application of this strategy is based on chemical and pharmacological similarities of compounds with clinical evidence of suicidal intent, target/indication classes associated with high incidence of SIB, in vitro neuropharmacological activity profile, in vivo ADME properties, the patient population of the underlying indication and regulatory precedents