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Myocardial ischemia is one of the leading health problems worldwide. Therapy consists of the restitution of coronary perfusion which is followed by myocardial inflammation. Platelet–neutrophil interaction is a crucial process during inflammation, yet its consequences are not fully understood. Here, we show that platelet–neutrophil complexes (PNCs) are increased in patients with acute myocardial infarction and that this is associated with increased levels of neuronal guidance protein semaphorin 7A (SEMA7A). To investigate this further, we injected WT animals with Sema7a and found increased infarct size with increased numbers of PNCs. Experiments in genetically modified animals identify Sema7a on red blood cells to be crucial for this condition. Further studies revealed that Sema7a interacts with the platelet receptor glycoprotein Ib (GPIb). Treatment with anti-Sema7a antibody protected from myocardial tissue injury. In summary, we show that Sema7a binds to platelet GPIb and enhances platelet thrombo-inflammatory activity, aggravating post-ischemic myocardial tissue injury., Reperfusion injury following myocardial ischemia is aggravated by inflammation and platelet–neutrophil complex formation. Here the authors show that semaphorin 7A binds to platelet GPIb, enhancing platelet–neutrophil interaction and increasing post-ischemic myocardial tissue injury, and that blockage of semaphorin 7A is protective.

Comorbidities are risk factors for development of severe coronavirus disease 2019 (COVID-19). However, the extent to which an underlying comorbidity influences the immune response to severe acute respiratory syndrome coronavirus 2 remains unknown.Our aim was to investigate the complex interrelations of comorbidities, the immune response, and patient outcome in COVID-19.We used high-throughput, high-dimensional, single-cell mapping of peripheral blood leukocytes and algorithm-guided analysis.We discovered characteristic immune signatures associated not only with severe COVID-19 but also with the underlying medical condition. Different factors of the metabolic syndrome (obesity, hypertension, and diabetes) affected distinct immune populations, thereby additively increasing the immunodysregulatory effect when present in a single patient. Patients with disorders affecting the lung or heart, together with factors of metabolic syndrome, were clustered together, whereas immune disorder and chronic kidney disease displayed a distinct immune profile in COVID-19. In particular, severe acute respiratory syndrome coronavirus 2-infected patients with preexisting chronic kidney disease were characterized by the highest number of altered immune signatures of both lymphoid and myeloid immune branches. This overall major immune dysregulation could be the underlying mechanism for the estimated odds ratio of 16.3 for development of severe COVID-19 in this burdened cohort.The combinatorial systematic analysis of the immune signatures, comorbidities, and outcomes of patients with COVID-19 has provided the mechanistic immunologic underpinnings of comorbidity-driven patient risk and uncovered comorbidity-driven immune signatures.

Levosimendan is a calcium sensitizer and opens adenosine triphosphate-dependent potassium channels. Since 20 years, it is approved for acute decompensated heart failure. It has been tested in many clinical trials for treatment of at-risk patients in cardiac surgery, right ventricular failure, pulmonary hypertension, weaning of extracorporeal systems, cardiogenic shock, septic shock, ARDS and others.Levosimendan has diverse positive effects next to positive inotropy. It improves ventriculoarterial coupling, increases peripheral perfusion, increases kidney glomerular filtration rate, coronary blood flow and it reduces preload and afterload as well as pulmonary capillary wedge pressure.Due to the opening of potassium channels, it also acts on mitochondria resulting in organ protection. Levosimendan acts anti-apoptotic. These positive effects were described in many small studies. Although this sounds like a promising drug for a variety of settings, results of several multicentre randomized placebo-controlled studies were frustrating. This review resumes some facts of levosimendan in different diseases.Vasopressoren kommen besonders in kritischen, nicht selten lebensbedrohlichen Situationen der Anästhesie, Notfall- und Intensivmedizin zum Einsatz. Die Wahl der geeigneten Substanz sowie die Erkennung und Beherrschung möglicher Nebenwirkungen sind von großer Bedeutung. Im folgenden Beitrag sollen daher die klinisch wichtigsten Substanzen vorgestellt und deren pharmakologische Charakteristika beleuchtet werden.

Immune profiling of COVID-19 patients has identified numerous alterations in both innate and adaptive immunity. However, whether those changes are specific to SARS-CoV-2 or driven by a general inflammatory response shared across severely ill pneumonia patients remains unknown. Here, we compared the immune profile of severe COVID-19 with non-SARS-CoV-2 pneumonia ICU patients using longitudinal, high-dimensional single-cell spectral cytometry and algorithm-guided analysis. COVID-19 and non-SARS-CoV-2 pneumonia both showed increased emergency myelopoiesis and displayed features of adaptive immune paralysis. However, pathological immune signatures suggestive of T cell exhaustion were exclusive to COVID-19. The integration of single-cell profiling with a predicted binding capacity of SARS-CoV-2-petides to the patients’ HLA profile further linked the COVID-19 immunopathology to impaired virus recognition. Towards clinical translation, circulating NKT cell frequency was identified as a predictive biomarker for patient outcome. Our comparative immune map serves to delineate treatment strategies to interfere with the immunopathologic cascade exclusive to severe COVID-19., Graphical Abstract, The pathogen-specific immune alterations in severe COVID-19 remain unknown. Using longitudinal, high-dimensional single-cell spectral cytometry and algorithm-guided comparison of COVID-19 vs. non-SARS-CoV-2-pneumonia patient samples, Kreutmair et al. identify T and NK cell immune signatures specific to SARS-CoV-2. They furthermore reveal NKT cell frequency as a predictive biomarker for COVID-19 outcome prediction and link impaired virus recognition to HLA genetics.

In recent years, the role of the anesthesiologist has turned tremendously from the "anaesthesia doctor" into a perioperative physician and risk specialist. Patients are older, multimorbid, and are called up for more and more extensive surgery and interventions. Socioeconomic aspects have grown in importance. The anesthesiologist, paving the way for a good outcome, is involved in nearly all perioperative processes: preoperative evaluation, definition and optimization of preoperative and intraoperative conditions, management of modern intraoperative anesthesia as well as postoperative medically indicated, effective and efficient treatment of partially highly complex patients. The individual perioperative process steps in this way are examined in accordance with established guidelines and the increase in current requirements. Finally, a special emphasis is placed on the perception that the perioperative process has not been completed with the end of surgery - postoperative outcome is not least adversely affected by postoperative complications on the normal ward. The risk of death after complications, "failure to rescue", should be identified early and treated promptly.In den letzten Jahren hat sich die Rolle des Anästhesisten vom „Narkosearzt“ zum perioperativen Mediziner und Risikospezialisten enorm gewandelt. Die Patienten sind älter, multimorbide und werden zu immer umfangreicheren Eingriffen und Interventionen aufgeboten. Sozioökonomische Aspekte haben an Bedeutung zugenommen. Der Anästhesist ist als Wegbereiter eines guten Outcomes in nahezu alle perioperativen Prozesse involviert: präoperative Evaluation, Festlegung und Optimierung der prä- und intraoperativen Bedingungen, moderne intraoperative Anästhesieführung sowie eine postoperative, medizinisch indizierte, effektive und effiziente Behandlung der teilweise hochkomplexen Patienten. Die einzelnen perioperativen Prozessschritte auf diesem Weg werden in Anlehnung an etablierte Leitlinien und die Zunahme der gegenwärtigen Anforderungen beleuchtet. Schließlich wird ein besonderer Akzent auf die Erkenntnis gelegt, dass der perioperative Prozess nicht mit dem Operationsende abgeschlossen ist – postoperatives Outcome ist nicht zuletzt von postoperativen Komplikationen auf der Normalstation negativ beeinflusst. Das Risiko für Todesfälle nach Komplikationen, „Failure to rescue“, sollte frühzeitig erkannt und umgehend behandelt werden.