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Geschlechtsspezifische Faktoren, die die intrazelluläre Infektion menschlicher primärer Makrophagen durch viszerale Leishmania spp. beeinflussen
No full textLeishmaniasis is one of the most important neglected tropical diseases and is caused by protozoan parasites of the genus Leishmania. Depending on infecting parasite species and host immune status, the disease can manifest itself as self-healing skin ulcers, severe mucosal necrosis, or disseminated, often lethal, visceral infections of haematopoietic organs. To date, there are no licensed vaccines available and treatment options are limited and often accompanied by severe adverse effects.
Many parasitic diseases occur with a sex bias in terms of incidence, morbidity and mortality towards male individuals. Leishmaniasis is such an example as it presents with higher numbers of clinical cases in male patients in various endemic areas. The reasons for this observed sex-specific difference are highly multifactorial and can include biological differences such as variances in chromosomes and hormones, as well as sociocultural disparities that can alter the susceptibility towards an infection and influence the outcome of the disease.
Within the mammalian host, Leishmania parasites proliferate mainly in macrophages, while suppressing effective elimination by the host. In order to better understand the biological sex differences in leishmaniasis, the present project aimed to analyse the influence of donor sex on the infection of macrophages with Leishmania species at the cellular and transcriptional level. For the first time, using an in vitro infection model based on primary human macrophages with L. infantum and a high-throughput analysis, higher infection rates and parasite loads were detected in male macrophages than in female macrophages. These differences were most pronounced in later phases of infection (from 28 hours post infection).
Due to their high plasticity in response to external stimuli, macrophages can polarise into pro-inflammatory M1 and anti-inflammatory M2 macrophages, which are distinguished by their different morphological and phenotypic characteristics. In this study, the polarisation during infection with L. infantum was investigated using microscopy- and flow cytometry-based methods. L. infantum-infected macrophages showed increased M1 polarisation and decreases in M2-like macrophages in both sexes, especially at early stages of infection, with a higher tendency towards M1 polarisation observed in female cells.
Quantitative RNA sequencing of infected macrophages and corresponding controls of both sexes showed the most pronounced changes in mRNA levels at early time points of infection, but also more differentially expressed genes (DEGs) in female than in male macrophages. Over time (6, 28 and 52 hours after infection), the number of DEGs decreased in infected cells of both sexes. Genes that were similarly upregulated in both sexes were genes associated with important immunological signalling pathways, including TNF signalling, NF-B signalling, HIF-1 signalling, IL-17 signalling and FoxO signalling, mineral absorption, macrophage cytoskeletal remodelling and cytokine response. Specifically upregulated genes in female macrophages were associated with a more strongly induced interferon signalling pathway and proteasomal activities, while genes associated with interleukin response and Leishmania survival were preferentially upregulated in male macrophages. These results suggest that female macrophages exhibit increased transcriptomic activation and an enhanced anti-parasitic immune response, possibly leading to more effective elimination of the parasites in female-derived macrophages.
The influence of sex hormones on L. infantum infection was investigated by pre-treating macrophages with androgens or estrogens prior to infection. While the administration of testosterone demonstrated no impact on infection rate or parasite burden, estradiol treatment correlated weakly with reduced parasite burden in infected female macrophages.
Taken together, this project identified several biological factors that may contribute to the divergent susceptibilities of sexes towards Leishmania infections. These factors include variances in macrophage polarisation, disparities in the expression of immunity-related genes, and the influence of sex hormones. These findings serve as a foundational framework for subsequent experiments which may identify therapeutic targets
Shape optimization approaches towards scalable algorithms allowing large deformations
No full textFormoptimierung ist ein Bereich, der darauf abzielt, das Design eines Objekts in Bezug auf einen gegebene physikalischen Größe zu verbessern, die durch eine Zielfunktion ausgedrückt wird. In den meisten nicht-trivialen Anwendungen erfordert die Zielfunktion die Lösung einer partiellen Differentialgleichung (englisch: partial differential equation, PDE). Es existieren empirische Techniken zur Verbesserung bestehender Designs. Allerdings haben neue Entwicklungen in der mathematischen Theorie, die zur Formulierung dieser Art von Problemen verwendet wird, neue Forschung in diesem Bereich ausgelöst. Darüber hinaus hat die Entwicklung von zunehmend schnelleren Computern zu Anwendungen geführt, die eine sehr große Anzahl von Freiheitsgraden (englisch: degrees of freedom, DoFs) umfassen.
Das Ziel dieser Arbeit besteht darin, hochmoderne Techniken in der Formoptimierung zu untersuchen, zu entwickeln und umzusetzen. Das Hauptinteressengebiet liegt in Anwendungen, die große Verformungen erfordern, um eine gegebene Domäne zu optimieren. Hier wird das Problem in einem kontinuierlichen Rahmen formuliert und anschließend durch die Methode der finiten Elemente (FEM) diskretisiert. Dieser diskrete Rahmen beschreibt die Geometrie, die durch die Anwendung einer Reihe von Deformationsfeldern über die Knoten des Gitters optimiert werden soll. Während dieses Prozesses können die diskreten Elemente möglicherweise Qualitätsverluste im Gitter erleiden. Daher ist diese Arbeit Teil des fortwährenden Interesses der Forschung an Techniken, die große Verformungen ermöglichen und gleichzeitig die Gitterqualität erhalten.
Im Kontext der Finite-Elemente-Analyse erfordern komplexe Geometrien normalerweise hochfeine Berechnungsgitter, um genaue Ergebnisse zu liefern. Daher konzentrieren wir uns hier auch auf die Implementierung von Fallstudien mit einer sehr großen Anzahl von DoFs. Zu diesem Zweck werden die vorgeschlagenen Algorithmen mit einem parallelisierten Framework, UG4, implementiert. Darüber hinaus werden die Ergebnisse mit massiven verteilten Speichersystemen, d.h. Supercomputern, erzeugt.
Eine auf der Literatur basierende Fallstudie zur Fluiddynamik wird verwendet, um die in dieser Arbeit entwickelten Formoptimierungsmethoden zu benchmarken. Das verwendete Beispiel ist das eines Objekts in der Mitte eines Strömungstunnels, dessen Oberfläche hinsichtlich einer bestimmten Größe wie dem Strömungswiderstand oder dem Auftrieb optimiert werden muss. Für die Studien innerhalb dieser Arbeit ist die Form des Objekts so festgelegt, dass sie geometrische Singularitäten wie Kanten und Ecken enthält, die während der Optimierung entfernt werden sollen. Darüber hinaus ist aus der Literatur bekannt, dass das optimierte Hindernis neu generierte geometrische Singularitäten enthalten muss. Daher handelt es sich um einen guten Benchmark-Fall für Techniken zur Formoptimierung bei großen Verformungen.Shape optimization is an area that aims at improving the design of an object with respect to a given physical quantity expressed by an objective function.
In most meaningful applications the objective function requires the solution to a partial differential equation (PDE).
There are empirical techniques for improving existing designs.
However, recent developments in the mathematical theory used to formulate these kind of problems has triggered new research in this area.
Moreover, the development of progressively faster computers has lead to applications involving very large number of degrees of freedom (DoFs).
The goal of this work is to investigate, develop, and implement state-of-the-art techniques in shape optimization.
The main area of interest is in applications which require large deformations to optimize a given domain.
Here, the formulation of the problem is done in a continuous setting, and its followed by a discretization of the domain via the finite element method (FEM).
This discrete setting describes the geometry which is to be optimized by applying a series of deformation fields across the nodes of the grid.
It is during this process, that the discrete elements might undergo mesh quality losses.
Therefore, this thesis is part of the ongoing interest of the research community on techniques that allow for large deformations, while preserving mesh quality.
In the context of finite element analysis, complex geometries usually require highly refined computational meshes to yield accurate results.
Thus, here we also focus on implementing case studies with a very high number of DoFs.
With this purpose, the proposed algorithms are implemented using the parallel-computing simulation framework UG4.
Additionally, the results are generated using massive distributed-memory systems, i.e. supercomputers.
A literature-based, fluid dynamics case study is used to benchmark the shape optimization methods developed in this thesis.
The used example is that of an object located in the center of a flow tunnel, whose surface must be optimized with respect to a certain quantity such as the drag or lift.
For the studies within this work, the shape of the object is set to include geometric singularities -e.g. edges and corners- which are to be removed during the optimization.
Furthermore, based on the literature, it is known that the optimized obstacle must include newly generated geometric singularities.
Thus, this is a good benchmarking case for large deformation techniques in shape optimization
Swampland Constraints and Non-perturbative String Theory: Towards the boundaries of moduli space in M- and F-theory
No full textIn this thesis we analyse general criteria which consistent theories of quantum gravity must obey according to the so-called Swampland Conjectures, and their interplay with the quantum geometry of non-perturbative string compactifications.
The Swampland Distance Conjecture predicts that infinite-distance limits in the moduli space of a gravitational EFT that can be consistently completed to a theory of quantum gravity are accompanied by an infinite tower of asymptotically massless states, with an exponentially decreasing mass scale in the geodesic distance. The Emergent String Conjecture (ESC) refines this claim by stating that said towers are furnished either by Kaluza-Klein states, signalling a decompactification along the trajectory, or by the excitations of a unique, weakly coupled, asymptotically tensionless critical string, determining the equidimensional duality frame to which we transition at the endpoint of the limit.
We commence by studying the consistency conditions imposed by the ESC on the asymptotic behaviour of quantum gravity under dimensional reduction. Consider an infinite-distance limit in which a (1+2)-dimensional membrane becomes asymptotically tensionless. If its circle reduction leads to a critical string, we show that such a membrane must parametrically decouple from the Kaluza-Klein scale in the original theory. We confirm this censorship against emergent membrane limits, i.e. trajectories in which the membrane sits at the Kaluza-Klein scale, in the hypermultiplet moduli space of Calabi-Yau threefold compactifications of M-theory. While it is possible to find putative membrane limits at the classical level, the quantum corrections to the hypermultiplet moduli space metric arising from M2-instantons obstruct such infinite-distance trajectories, turning them instead into decompactification limits to eleven dimensions.
Next, we turn our attention to the infinite-distance limits in the complex structure moduli space of elliptic Calabi-Yau threefolds. In the context of six-dimensional F-theory, these include infinite-distance trajectories in the non-perturbative open string moduli space. Geometrically, such limits are described as degenerations of elliptic threefolds whose central element exhibits non-minimal elliptic fibers, which do not admit a crepant resolution in the fiber. For this reason, F-theory models presenting codimension-one non-minimal singular elliptic fibers are usually discarded. We set out to understand the geometry and physics of the infinite-distance non-minimal singularities of Calabi-Yau threefolds. Our analysis shows how these non-crepant singularities can be removed by a systematic sequence of blow-ups of the base, leading to a union of log Calabi-Yau spaces glued together along their boundaries. We identify criteria for the blow-ups to give rise to open chains or more complicated trees of components, characterise the base geometry of the resulting log Calabi-Yau spaces, determine the line bundles defined over them and explain how to extract the gauge algebra for F-theory probing such reducible spaces. Focusing on those limits associated with the appearance of non-minimal singularities in the elliptic fiber over genus-zero curves in a Hirzebruch surface base, we determine the asymptotic physics that they lead to. As our main result, we interpret the central fiber of a subclass of these degenerations as endpoints of decompactification limits to theories with six-dimensional defects. The genus-zero single infinite-distance limit degenerations of Hirzebruch models also give rise to emergent string limits, whose endpoints are at global weak coupling. We analyse the geometrical conditions that must be met in order for such global weak coupling to be possible. Our results rely on an adiabatic limit to gain information on the asymptotically massless states from the structure of vanishing cycles. Whenever possible, we employ F-theory/heterotic duality to compare our analysis to the heterotic dual description. Our findings provide further evidence for the Emergent String Conjecture, aligning with general expectations from quantum gravity
Insights into rRNA binding and lncRNAs in Brassicaceae
No full textPlants must quickly adapt to their surroundings due to their sessile nature. Their ability to adjust and thrive in diverse environmental conditions directly impacts their growth and development. This is especially critical for crop plants, where quantity and quality are vital to secure proper global nutrition. Plants have several ways to adapt or respond to external stimuli. One way is through the regulation of their proteome by maintaining the balance between protein synthesis and degradation. Another way is by emitting signaling molecules over short or long distances from affected areas to unaffected areas.
The synthesis of proteins is controlled by ribosomes and their biogenesis is a multistep process that involves the synthesis and maturation of rRNAs with the aid of hundreds of ribosome biogenesis factors (RBFs). Although many RBFs have been identified in plants, a substantial amount remains to be thoroughly studied compared to other organisms. Thus, one of the aims of this work was to characterize the structure and function of the Nucleolar RNA Chaperone-like 1 (NURC1) RBF in A. thaliana. SEC-SAXS results showed that NURC1 is highly flexible and adopts an elongated shape in solution. SEC-MALLS confirmed that NURC1 was a monomer with a molecular weight of ~28 kDa and a Rh of 2.4 nm. The homogeneity of the sample was compromised by the increase of protein concentration as observed through DLS, native electrophoresis and batch SAXS measurements. RNA binding was determined by MST. NURC1 bound the ITS2 RNA of A. thaliana with a Kd of 228 ± 83 nM. Furthermore, NURC1 displayed an RNA chaperone-like activity by FRET. The flexible termini of NURC1 seemed to be essential for structural stability and RNA recognition and/or biding since their truncation led to either increase of the sample polydispersity, decreased the binding affinity towards the ITS2 or reduced the RNA chaperone-like activity.
Long-distance communication is achieved through the phloem. Several classes of RNA have been identified in the phloem sap, including long non-coding RNAs (lncRNAs), which can potentially work as signals. The crop plant B. napus allows to readily collect fair amounts of phloem sap by exudation. Thus far, the population of lncRNAs of B. napus phloem sap remains to be explored. Hence, the second aim of this thesis involved the identification and characterization of lncRNAs in the phloem sap of B. napus by Illumina sequencing. For comparison, leaf samples were also analyzed. Over 3000 putative lncRNAs were identified in phloem and leaf samples. No structural differences were found between leaf and phloem lncRNAs. Differential expression and functional analysis (GO terms) were also performed. Parent genes associated with various molecular functions or pathways were identified, likely due to the diversity of processes that lncRNAs are involved
Entschlüsselung molekularer Subtypen beim fortgeschrittenen Prostatakarzinom mittels Transkriptomuntersuchungen in zirkulierenden Tumorzellen
No full textStandard therapy for prostate cancer is directed against the androgen receptor (AR) signaling pathway. As a result of increased therapeutic pressure from novel hormonal agents, patients are more frequently progressing to AR-independent, aggressive variant prostate cancer (AVPC). The acquisition of neuroendocrine features in a transdifferentiation process leads to the emergence of neuroendocrine prostate cancer (NEPC) and presents one resistance mechanism to AR-targeted therapy. As PSA no longer is a reliable biomarker in AVPC and NEPC, there is an urgent need to identify new biomarkers for AR-independent progression and transdifferentiation. The molecular analysis of circulating tumor cells (CTC) and tumor cell fragments shed into body fluids is known as liquid biopsy (LBx). LBx poses significantly reduced risk to patients, can be performed repeatedly and represents tumor heterogeneity more effectively than a tissue biopsy. Thus, this study aimed to establish a liquid biopsy-based biomarker for the detection and monitoring of patients with NEPC. For this purpose, a transcript panel was selected based on literature review and validated in cell lines and published tumor tissue data sets. The combined workflow of CTC enrichment and transcript detection was validated in spike-in controls. Blood samples were collected from patients with AVPC, NEPC and hormone-sensitive prostate cancer at the University Medical Center Hamburg-Eppendorf. CTC counts were measured by CellSearch. After validation of the enrichment methods, the expression of a 22 gene panel was analyzed in AdnaTestenriched CTCs. Gene expression profiles were evaluated using supervised and unsupervised approaches and correlated to clinical data. Comparison of different enrichment methods showed that CTCs were more frequently detected with EPCAM-based CTC enrichment. The detection of neuroendocrine markers was not improved by Parsortix enrichment compared to AdnaTest. CellSearch analysis revealed significantly increased CTC counts in NEPC and AVPC patients accompanied by a heterogeneous CTC morphology. Gene expression profiles revealed a high degree of heterogeneity between patients with significant deregulation of several individual markers. Unsupervised analysis identified four distinct clusters, which were termed ARhigh, CTClow, amphicrine and pure NEPC. Using a random forest model, HSPC and NEPC samples could be distinguished with an AUC of 95.5 % and an out-of-bag error rate of 15.5 % in cross-validation. In longitudinal samples of single patients, the detection of neuroendocrine markers in CTCs recapitulated the clinical course of therapy response and progression.
In conclusion, AVPC and NEPC patients had a high CTC burden, which facilitated subsequent molecular analyses. The gene expression profiles of the marker panel in CTCs reflected the histology of the tumors and were sufficient to distinguish intrinsic molecular subtypes of advanced prostate cancer. In the future,
the convenient PCR-based analysis pipeline may allow monitoring of advanced prostate cancer patients for earlier adjustment of therapy for NEPC
Die Zelltyp-spezifische Rolle des Amphiregulin in Lupus Nephritis
No full textDer systemische Lupus erythematodes (SLE) ist eine häufige Autoimmunerkrankung, die viele unterschiedliche Organsysteme betreffen kann. Die Lupusnephritis (LN) ist eine der schwersten Manifestationen mit hoher Morbidität. Vor kurzem konnten wir Amphiregulin (AREG), einer der Liganden des epidermalen Wachstumsfaktor-Rezeptors (EGFR), als potenten entzündungshemmenden Mediator der LN identifizieren, der die Aktivierung von pathogenen CD4+ T-Zellen herunterreguliert. Bei der LN wird AREG vor allem von in die Nieren infiltrierenden regulatorischen T-Zellen (Tregs) und Monozyten/Makrophagen (M/M) produziert. Interessanterweise unterscheidet sich seine Funktion je nach dem produzierenden Zelltyp. Ziel dieser Studie war es daher, die Bedeutung der zelltypspezifischen AREG-Sekretion bei der LN zu entschlüsseln. Mit Hilfe von konditionalen Knockout-Mäusen wurde die Rolle von AREG, das von FoxP3+ Tregs und LysM+ myeloischen Zellen sezerniert wird, im Pristane-Modell der chronischen LN untersucht. In vitro wurden die Auswirkungen von AREG auf die Regeneration von Epithelgewebe und die Gefäßheilung untersucht. Mäuse, denen AREG aus Tregs fehlte, zeigten einen schlechteren Verlauf der LN mit erhöhter glomerulärer Zellproliferation und Fibrose des Nierengewebes. Die zellulären und humoralen Immunantworten blieben jedoch unbeeinflusst. Bei Mäusen mit einem M/M- spezifischen Mangel an AREG-Sekretion zeigte sich dagegen keine Veränderung des Verlaufes der LN. In vitro zeigten Scratch-assays an mesangialen und tubulären Zellen der Maus sowie an menschlichen glomerulären Endothelzellen (hGEnC) eine verbesserte Wundheilung nach Inkubation mit rekombinantem AREG. Darüber hinaus untersuchte ich die Auswirkungen von AREG auf das Wachstum und die Formation tubulärer Strukturen von hGEnC, welche durch rekombinantes AREG erheblich gefördert wurden. Insgesamt zeigen meine Daten die wichtige Rolle von Treg-sezerniertem AREG für die Geweberegeneration und den Schutz vor schädlicher Fibrose bei der LN.Systemic Lupus erythematosus (SLE) is an autoimmune disease involving multiple organ systems. Lupus nephritis (LN) is one of the most severe manifestations, with high morbidity. We recently identified Amphiregulin (AREG), one of the Ligands of the epidermal-growth-factor-receptor (EGFR), as a potent anti-inflammatory mediator in LN via downregulation of CD4+ T cell activation. In LN AREG is mainly produced by renal infiltrating regulatory T cells (Tregs) and monocytes/macrophages (M/M). Interestingly, studies by us and others have shown, that its function relevantly differs according to the producing cell type. This study therefore aimed to unravel the relevance of cell-type-specific AREG secretion in LN. Conditional knockout mice were used to investigate the role of AREG secreted by FoxP3+ Tregs and LysM+ myeloid cells in the pristane model of chronic LN. In vitro, AREG effects on epithelial tissue regeneration and vascular healing were studied. Mice lacking Treg- derived AREG showed worse LN outcomes with increased glomerular cell proliferation and renal tissue fibrosis. However, cellular, and humoral immune responses remained unaffected. On the other hand, mice with M/M restricted deficiency of AREG secretion showed no change in LN outcome. In vitro, scratch assays of murine mesangial and tubulus cells, as well as human glomerular endothelial cells (hGEnC) showed improved wound healing after incubation with recombinant AREG. In addition, we explored AREG ́s effects on the growth and tube formation of hGEnC, which was much facilitated by recombinant AREG. Taken together our data show the important role of Treg-derived AREG for tissue regeneration and protection from detrimental fibrosis in LN
High Serum Levels of Wnt Signaling Antagonist Dickkopf-Related Protein 1 Are Associated with Impaired Overall Survival and Recurrence in Esophageal Cancer Patients
No full textEstablishing a local immune tolerance to protect neurons against inflammatory neurodegeneration
No full textRaucherentwöhnung nach einer Krebsdiagnose: Evaluation der Perspektive von Patient:innen sowie des onkologischen Fachpersonals als Grundlage für die Entwicklung eines maßgeschneiderten Raucherentwöhnungsprogramms am Universitären Krebszentrum Hamburg-Eppendorf
No full textIm Rahmen dieses Dissertationsprojektes wurden drei Studien durchgeführt und vier Manuskripte veröffentlicht.
Die PROG-IMP Studie zeigt, dass rauchende Krebspatient:innen ein niedrigeres Risiko für das Gesamtüberleben und ein höheres Risiko das krebsbedingte Sterben haben. Diese Studie unterstreicht die dramatischen Folgen des Weiterrauchens während einer Krebsbehandlung.
Die PreMo-Studie zeigt, dass knapp 8 Prozent aller Krebspatient:innen aktuell rauchen und etwa 50 Prozent aller Krebspatient:innen, die zum Zeitpunkt der Diagnosestellung rauchen, es nicht schaffen, langfristig mit dem Rauchen aufzuhören. Diese Studie unterstreicht die Bedeutung der Patient:innenaufklärung und Motivation sowie des Angebots eines speziell auf Krebspatient:innen zugeschnittenen Tabakentwöhnungsprogramms.
In der QSAC-Pro-Studie wurde besonders deutlich, dass bisher kaum standardisierte Instrumente zur Erfassung des Raucherstatus bei Krebspatient:innen eingesetzt werden und kaum weitere Aufklärung und Motivation stattfindet. Darüber hinaus wird deutlich, dass sich das onkologische Personal bisher nicht ausreichend geschult fühlt, um das Thema Rauchen bei Patient:innen anzusprechen, aufzuklären oder zum Rauchstopp zu motivieren, insbesondere im palliativen Setting.
Das übergeordnete Ziel des Promotionsprojektes war es, einen Beitrag zum bisher geringen Forschungsstand zum Thema "Weiterrauchen nach Krebsdiagnose" zu leisten und das Rauchverhalten von rauchenden Krebspatient:innen in Deutschland aus Sicht der betroffenen rauchenden Krebspatient:innen und ihrer onkologischen Behandler:innen besser zu verstehen. Diese Informationen sollen dazu beitragen, gezieltere Unterstützungsangebote zur Tabakentwöhnung für Krebspatient:innen zu entwickeln
On-pump coronary bypass surgery – Gender-specific differences during 30-day follow-up
No full textDie koronare Herzerkrankung ist die weltweit häufigste Todesursache. Das Beschwerdebild sowie die Baseline-Charakteristika betroffener Patient:innen unterscheiden sich im Geschlechtervergleich, sodass auch eine geschlechtsspezifische Betrachtung der gewählten Therapie sinnvoll erscheint. Eine der etablierten Therapieoptionen der koronaren Herzkrankheit ist die koronare Bypass-Operation mit Zuhilfenahme der Herz-Lungen- Maschine.
In der vorliegenden Arbeit wurde ein Patient:innenkollektiv (nGesamt=1919; n♀= 348; n♂=1571), bei denen eine on-pump Bypass-Operation am Universitären Herzzentrum Hamburg im Zeitraum der Jahre 2012-2018 durchgeführt wurde, mit Hinblick auf geschlechtsspezifische Unterschiede untersucht.
Anhand der hierbei gewonnenen Daten konnte das weibliche Geschlecht nicht als individueller Risikofaktor für eine erhöhte Mortalität im 30-Tages-Verlauf nach einer koronaren Bypass- Operation mit Zuhilfenahme der Herz-Lungen-Maschine identifiziert werden. Es konnte jedoch gezeigt werden, dass die untersuchten Frauen deutlich häufiger Baseline-Charakteristika aufweisen, die mit einer erhöhten 30-Tages-Mortalität vergesellschaftet sind. Dazu gehört ein fortgeschrittenes Alter und ein erhöhtes NYHA-Stadium bei gleichzeitig erhaltener linksventrikulärer Ejektionsfraktion (Konstellation einer HFpEF). Zudem kommt es auch im perioperativen Verlauf bei Frauen deutlich häufiger zu Konstellationen und Ereignissen, die im Zusammenhang mit einer erhöhten 30-Tages-Mortalität stehen. Dies sind eine erhöhte OP- Dringlichkeit, die Konversion eines OPCAB-Eingriffs zur HLM, der Bedarf einer EK- Transfusion, das Auftreten einer sternalen Wundheilungsstörung sowie die Notwendigkeit zur Re-Sternotomie. Gleichwohl konnte kein statistisch signifikanter Geschlechterunterschied in Anbetracht der 30-Tages-Mortalität festgestellt werden. Frauen erlitten jedoch statistisch signifikant häufiger einen intra- bzw. postoperativen Myokardinfarkt und eines zerebro- vaskuläres Ereignis jeweils im 30-Tages-Verlauf.
Bei isolierter Betrachtung der Frauen konnte in der logistischen Regressionsanalyse lediglich für das NYHA-Stadium ≥III und eine Re-Sternotomie ein statistisch signifikanter Effekt auf die Sterblichkeit im 30-Tages-Verlauf festgestellt werden. Bei der Evaluation des Mortalitätsrisikos von Patientinnen sollte somit ein besonderes Augenmerk auf das Auftreten von Herzinsuffizienz-Symptomen gelegt werden.Coronary heart disease is the most frequent cause of death worldwide. The symptoms as well as the baseline characteristics of affected patients differ between genders, therefore a gender-specific examination of the selected therapy appears to bear meaningful insights. One of the established treatment options for coronary heart disease is coronary bypass surgery with heart-lung machine.
In the present study, a patient population (nTotal=1919; n♀= 348; n♂=1571) who underwent on- pump bypass surgery at the University Heart Center Hamburg in the period 2012-2018 was evaluated regarding gender differences.
Based on the data obtained female gender was not an individual risk factor for increased 30- day-mortality after coronary bypass surgery with heart-lung machine. However, women showed significantly more baseline characteristics associated with increased 30-day- mortality. These include older age and a high NYHA classification with simultaneously preserved left ventricular ejection fraction (constellation of a HFpEF). In the perioperative course women had significantly more constellations and events associated with an increased 30-day-mortality such as urgency surgery, conversion from off-pump procedure to on-pump procedure, need for erythrocyte concentrate transfusion, occurrence of sternal wound healing disorder and re-sternotomy.
Nevertheless, no statistically significant gender difference was found in 30-day-mortality. Women were statistically significantly more likely to suffer from intraoperative or postoperative myocardial infarction or cerebrovascular events in 30-day follow-up. Evaluating women ́s outcomes only, NYHA stage ≥III and re-sternotomy were associated with increased 30-day-mortality in the logistic regression analysis. When evaluating the mortality risk of female patients, heart failure symptoms should be in the focus