Bei der Entwicklung dieses Lehrbuchs haben alle Beteiligten gemeinsam das Ziel verfolgt, das neue Standardwerk der deutschsprachigen Geriatrie zu präsentieren. Es beleuchtet die ganze Palette der Erkrankungen im höheren Lebensalter und der geriatrischen Syndrome, darunter Ernährungs- und Stoffwechselstörungen, Mobilitätsstörungen, Infektionskrankheiten, Tumorerkrankungen, Herz-Kreislauf- und Gefäßerkrankungen, neurologische Erkrankungen, die verschiedenen Formen des kognitiven Abbaus sowie Sarkopenie und Frailty. Zu weiteren wesentlichen Themen gehören das funktionelle Assessment, die Polypharmazie sowie die Palliativmedizin des älteren Patienten. Das Buch vermittelt ein Verständnis von Geriatrie als interdisziplinäre und interprofessionelle Komplexitätsmedizin mit dem Anspruch, ältere Patienten bestmöglich zu behandeln und auf diese Weise ihre Lebensqualität zu erhalten oder zu verbessern. Abschließend werden biologische, epidemiologische und politische Aspekte des Alterns reflektiert. Mit einem modernen, systematischen Aufbau, zahlreichen didaktischen Elementen und anschaulichen Abbildungen ist das Werk ideal für den Einsatz in Klinik und Praxis. In über 130 Kapiteln werden Schlüsselkonzepte der Diagnostik und Behandlung sowie alle relevanten Fragen und Problemstellungen behandelt. Dieses Buch wird Freude an der Geriatrie vermitteln, inspirieren und als Nachschlagewerk für die tägliche Arbeit dienen. Die vier Herausgeber wurden von einem Team von Sektionsherausgebern unterstützt, die anerkannte Experten auf dem Fachgebiet der Geriatrie und der Altersmedizin sind. Die mehr als 200 Autorinnen und Autoren wurden aufgrund ihrer wissenschaftlichen Expertise und ihrer praktischen Erfahrung eingebunden. Ohne die Fachvertreter der benachbarten Disziplinen wäre es nicht möglich gewesen, den hohen Ansprüchen dieser Publikation gerecht zu werden. Dieses neue Standardwerk ist an eine umfangreiche Leserschaft gerichtet: Fachärztinnen und -ärzte für Geriatrie, die eine verlässliche Referenz suchen, Ärztinnen und Ärzte in Weiterbildung bis hin zu allen ärztlichen Kolleginnen und Kollegen, die mit der Versorgung älterer Patienten befasst sind.

Abstract: Cortical demyelination is a widely recognized hallmark of multiple sclerosis (MS) and correlate of disease progression and cognitive decline. The pathomechanisms initiating and driving gray matter damage are only incompletely understood. Here, we determined the infiltrating leukocyte subpopulations in 26 cortical demyelinated lesions of biopsied MS patients and assessed their contribution to cortical lesion formation in a newly developed mouse model. We find that conformation-specific anti-myelin antibodies contribute to cortical demyelination even in the absence of the classical complement pathway. T cells and natural killer cells are relevant for intracortical type 2 but dispensable for subpial type 3 lesions, whereas CCR2+ monocytes are required for both. Depleting CCR2+ monocytes in marmoset monkeys with experimental autoimmune encephalomyelitis using a novel humanized CCR2 targeting antibody translates into significantly less cortical demyelination and disease severity. We conclude that biologics depleting CCR2+ monocytes might be attractive candidates for preventing cortical lesion formation and ameliorating disease progression in MS

Abstract: The immune response to mycobacteria is characterized by granuloma formation, which features multinucleated giant cells as a unique macrophage type. We previously found that multinucleated giant cells result from Toll-like receptor-induced DNA damage and cell autonomous cell cycle modifications. However, the giant cell progenitor identity remained unclear. Here, we show that the giant cell-forming potential is a particular trait of monocyte progenitors. Common monocyte progenitors potently produce cytokines in response to mycobacteria and their immune-active molecules. In addition, common monocyte progenitors accumulate cholesterol and lipids, which are prerequisites for giant cell transformation. Inducible monocyte progenitors are so far undescribed circulating common monocyte progenitor descendants with high giant cell-forming potential. Monocyte progenitors are induced in mycobacterial infections and localize to granulomas. Accordingly, they exhibit important immunological functions in mycobacterial infections. Moreover, their signature trait of high cholesterol metabolism may be piggy-backed by mycobacteria to create a permissive niche

Abstract: Aims Macrophages have a critical and dual role in post-ischaemic cardiac repair, as they can foster both tissue healing and damage. Multiple subsets of tissue resident and monocyte-derived macrophages coexist in the infarcted heart, but their precise identity, temporal dynamics, and the mechanisms regulating their acquisition of discrete states are not fully understood. To address this, we used multi-modal single-cell immune profiling, combined with targeted cell depletion and macrophage fate mapping, to precisely map monocyte/macrophage transitions after experimental myocardial infarction. Methods and results We performed single-cell transcriptomic and cell-surface marker profiling of circulating and cardiac immune cells in mice challenged with acute myocardial infarction, and integrated single-cell transcriptomes obtained before and at 1, 3, 5, 7, and 11 days after infarction. Using complementary strategies of CCR2+ monocyte depletion and fate mapping of tissue resident macrophages, we determined the origin of cardiac macrophage populations. The macrophage landscape of the infarcted heart was dominated by monocyte-derived cells comprising two pro-inflammatory populations defined as Isg15hi and MHCII+Il1b+, alongside non-inflammatory Trem2hi cells. Trem2hi macrophages were observed in the ischaemic area, but not in the remote viable myocardium, and comprised two subpopulations sequentially populating the heart defined as Trem2hiSpp1hi monocyte-to-macrophage intermediates, and fully differentiated Trem2hiGdf15hi macrophages. Cardiac Trem2hi macrophages showed similarities to 'lipid-associated macrophages' found in mouse models of metabolic diseases and were observed in the human heart, indicating conserved features of this macrophage state across diseases and species. Ischaemic injury induced a shift of circulating Ly6Chi monocytes towards a Chil3hi state with granulocyte-like features, but the acquisition of the Trem2hi macrophage signature occurred in the ischaemic tissue. In vitro, macrophages acquired features of the Trem2hi signature following apoptotic-cell efferocytosis. Conclusion Our work provides a comprehensive map of monocyte/macrophage transitions in the ischaemic heart, constituting a valuable resource for further investigating how these cells may be harnessed and modulated to promote post-ischaemic heart repair