Background— The adaptive growth of blood vessels is an important protective mechanism in cardiovascular disease. However, the underlying regulatory mechanisms of this process are only partly understood. Recently, small endogenous RNAs (microRNAs [miRNAs]) were found to play an important role in embryonic and postnatal vascular development. Here, we used miRNA transcriptome analysis after induction of hind-limb ischemia in mice to screen for miRNAs involved in adaptive blood vessel growth following arterial occlusion. Methods and Results— Using miRNA arrays, we explored the miRNA expression profile during adaptive neovascularization. We describe specific changes in miRNA expression patterns and show that miRNA-100 is significantly downregulated after induction of hind-limb ischemia in mice. Our data demonstrate that miR-100 modulates proliferation, tube formation, and sprouting activity of endothelial cells and migration of vascular smooth muscle cells and functions as an endogenous repressor of the serine/threonine protein kinase mammalian target of rapamycin (mTOR). Whereas miR-100 inhibition increased mTOR levels in endothelial cells, overexpression of miR-100 reduced mTOR expression and consequently attenuated cellular proliferation. Supporting this notion, overexpression of an mTOR construct lacking the miRNA binding site rescued the inhibitory effect of miR-100 on cell proliferation. Accordingly, miR-100 inhibition by specific antagomirs in vivo stimulated angiogenesis and resulted in functional improvement of perfusion after femoral artery occlusion in mice. In contrast, treatment with the mTOR inhibitor rapamycin had the opposite effect. Conclusions— Our data demonstrate that miR-100 has an antiangiogenic function and represses mTOR signaling in endothelial and vascular smooth muscle cells. Inhibition of miR-100 could be a novel approach for the modulation of blood vessel growth and other mTOR-dependent processes.

Forkhead box (Fox) transcription factors are important regulators of cardiovascular development and several Fox-proteins have recently been shown to modulate embryonic and post-natal angiogenesis. However, the role of the FoxP subfamily, which is highly expressed in cardiovascular tissue, has not been investigated so far. Here, we show that the transcription factor FoxP1 is the highest expressed FoxP-protein in endothelial cells and that it is upregulated at the site of neovascularization during hindlimb ischemia in mice. Silencing of FoxP1 results in a strong inhibition of proliferation, tube formation and migration of cultured endothelial cells. Accordingly, knockdown of FoxP1 in zebrafish was followed by a disruption of intersomitic vascular formation. Using gene expression profiling, we show that FoxP1 induces a specific change of the endothelial transcriptome and functions as a suppressor of semaphorin 5B, which has previously been described as a neuronal inhibitory factor. Our findings now demonstrate that semaphorin 5B also acts as a FoxP1- dependent suppressor of endothelial cell proliferation, migration and sprouting, mediating the effects of FoxP1. In summary, our data indicate that the transcription factor FoxP1 is essential for the angiogenic function of endothelial cells and functions as a suppressor of the inhibitory guidance cue semaphorin 5B, suggesting an important function of FoxP1 in the regulation of neovascularization.

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Zusammenfassung Hintergrund Das neue, pandemische Coronavirus SARS-CoV-2 und die damit einhergehende Erkrankung COVID-19 (Coronavirus Disease 2019) stellt die medizinischen Versorgungssysteme vor große Herausforderungen. Die vorliegende Arbeit fasst die Strategie, Organisation und Maßnahmen der COVID-Taskforce des Universitätsklinikums Freiburg zusammen und berichtet über Erfahrungen und Behandlungsergebnisse von der Versorgung der ersten 115 COVID-19-Patienten. Methoden Retrospektive, narrative Prozessbeschreibung und -analyse des Zeitraums Ende Januar bis Anfang April 2020, durchgeführt unter Mitwirken der beteiligten Departments, Kliniken und Institute des Universitätsklinikums Freiburg. Ergänzend erfolgte eine retrospektive Beobachtungsstudie mit deskriptiver statistischer Auswertung der epidemiologischen und klinischen Daten aller bis 31. März 2020 hospitalisierten COVID-19-Patienten. Ergebnisse Durch eine interdisziplinär zusammengesetzte Taskforce Coronavirus wurden Maßnahmen in den Bereichen ambulante Testung und Beratung, Separierung der Patientenströme sowie Eskalation der Versorgungskapazitäten auf Normal- und Intensivstationen im Sinne eines dynamischen Stufenmodells angeregt und umgesetzt. Die Versorgung der ersten 115 Patienten gelang somit ohne Entstehung von Engpässen. Diskussion Durch Zusammenwirken sämtlicher Disziplinen und Abteilungen des Universitätsklinikums Freiburg konnte eine adäquate Versorgung von COVID-19-Patienten sichergestellt und die Handlungsfähigkeit des Klinikums in der aktuellen Ausbruchsituation erhalten werden.

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Background In this retrospective routine data analysis, we investigate the number of emergency department (ED) consultations during the COVID-19 pandemic of 2020 in Germany compared to the previous year with a special focus on numbers of myocardial infarction and acute heart failure. Methods Aggregated case numbers for the two consecutive years 2019 and 2020 were obtained from 24 university hospitals and 9 non-university hospitals in Germany and assessed by age, gender, triage scores, disposition, care level and by ICD-10 codes including the tracer diagnoses myocardial infarction (I21) and heart failure (I50). Results A total of 2,216,627 ED consultations were analyzed, of which 1,178,470 occurred in 2019 and 1,038,157 in 2020. The median deviation in case numbers between 2019 and 2020 was − 14% [CI (− 11)–(− 16)]. After a marked drop in all cases in the first COVID-19 wave in spring 2020, case numbers normalized during the summer. Thereafter starting in calendar week 39 case numbers constantly declined until the end of the year 2020. The decline in case numbers predominantly concerned younger [− 16%; CI (− 13)–(− 19)], less urgent [− 18%; CI (− 12)–(− 22)] and non-admitted cases [− 17%; CI (− 13)–(− 20)] in particular during the second wave. During the entire observation period admissions for chest pain [− 13%; CI (− 21)–2], myocardial infarction [− 2%; CI (− 9)–11] and heart failure [− 2%; CI (− 10)–6] were less affected and remained comparable to the previous year. Conclusions ED visits were noticeably reduced during both SARS-CoV-2 pandemic waves in Germany but cardiovascular diagnoses were less affected and no refractory increase was noted. However, long-term effects cannot be ruled out and need to be analysed in future studies. Graphical abstract

Background Musculoskeletal conditions are among the main contributors to the global burden of disease. International guidelines consider patient education and movement exercises as the preferred therapeutic option for unspecific and degenerative musculoskeletal conditions. Innovative and decentralized therapeutic means are required to provide access to and availability of such care to meet the increasing therapeutic demand for this spectrum of conditions. Objective This retrospective observational study of preliminary use and outcome data explores the clinical outcomes of Vivira (hereafter referred to as “program”), a smartphone-based program for unspecific and degenerative pain in the back, hip, and knee before it received regulatory approval for use in the German statutory health insurance system. Methods An incomplete matched block design was employed to assess pain score changes over the intended 12-week duration of the program. Post hoc analyses were performed. In addition, a matched comparison of self-reported functional scores and adherence rates is presented. Results A total of 2517 participants met the inclusion criteria and provided sufficient data to be included in the analyses. Overall, initial self-reported pain scores decreased significantly from an average of 5.19 out of 10 (SD 1.96) to an average of 3.35 out of 10 (SD 2.38) after 12 weeks. Post hoc analyses indicate a particularly emphasized pain score reduction over the early use phases. Additionally, participants with back pain showed significant improvements in strength and mobility scores, whereas participants with hip or knee pain demonstrated significant improvements in their coordination scores. Across all pain areas and pain durations, a high yet expected attrition rate could be observed. Conclusions This observational study provides the first insights into the clinical outcomes of an exercise program for unspecific and degenerative back, hip, and knee pain. Furthermore, it demonstrates a potential secondary benefit of improved functionality (ie, strength, mobility, coordination). However, as this study lacks confirmatory power, further research is required to substantiate the clinical outcomes of the program assessed. Trial Registration German Clinical Trials Register DRKS00021785; https://drks.de/search/en/trial/DRKS00021785

BackgroundThe incidence of overweight and obesity has been steadily on the rise and has reached epidemic proportions in various countries and this represents a well-known major health problem. Nevertheless, current guidelines for resuscitation do not include special sequences of action in this subset of patients. The aim of this letter is to bring this controversy into focus and to suggest alterations of the known standard cardiopulmonary resuscitation in the obese.Case presentationAn obese patient weighing 272 kg fell to the floor, afterwards being unable to get up again. Thus, emergency services were called for assistance. There were no signs or symptoms signifying that the person had been harmed in consequence of the fall. Only when brought into a supine position the patient suffered an immediate cardiac arrest. Cardiopulmonary resuscitation was performed but there was no return of a stable spontaneous circulation until the patient was brought into a full lateral position. In spite of immediate emergency care the patient ultimately suffered a lethal hypoxic brain damage.ConclusionA full lateral position should be considered in obese patients having a cardiac arrest as it might help to re-establish stable circulatory conditions.