Frauenklinik der Technischen Universität München

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    Altered sleep behavior strengthens face validity in the ArcAβ mouse model for Alzheimer's disease.

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    Demographic changes will expand the number of senior citizens suffering from Alzheimer's disease (AD). Key aspects of AD pathology are sleep impairments, associated with onset and progression of AD. AD mouse models may provide insights into mechanisms of AD-related sleep impairments. Such models may also help to establish new biomarkers predicting AD onset and monitoring AD progression. The present study aimed to establish sleep-related face validity of a widely used mouse model of AD (ArcAβ model) by comprehensively characterizing its baseline sleep/wake behavior. Chronic EEG recordings were performed continuously on four consecutive days in freely behaving mice. Spectral and temporal sleep/wake parameters were assessed and analyzed. EEG recordings showed decreased non-rapid eye movement sleep (NREMS) and increased wakefulness in transgenic mice (TG). Vigilance state transitions were different in TG mice when compared to wildtype littermates (WT). During NREMS, TG mice had lower power between 1 and 5 Hz and increased power between 5 and 30 Hz. Sleep spindle amplitudes in TG mice were lower. Our study strongly provides sleep-linked face validity for the ArcAβ model. These findings extend the potential of the mouse model to investigate mechanisms of AD-related sleep impairments and the impact of sleep impairments on the development of AD

    Incidence of systemic inflammatory response syndrome and patient outcome following transcatheter edge-to-edge mitral valve repair.

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    OBJECTIVES: Systemic inflammatory response syndrome (SIRS) is a common finding after cardiovascular interventions. Data on the incidence of SIRS and its impact on outcome in patients undergoing transcatheter edge-to-edge mitral valve repair (MV-TEER) for mitral regurgitation (MR) is lacking. METHODS: From January 2013 to December 2020, 373 patients with moderate or severe MR undergoing MV-TEER were included. SIRS was defined as at least two of the following criteria within 48 h after the procedure: leucocyte count > 12.0 or  20 breaths per minute or PaCO2 ≤ 4.3 kPa/32 mmHg, heart rate > 90 bpm and temperature > 38.0 °C or < 36.0 °C. The primary endpoint was 3-years all-cause mortality. RESULTS: SIRS was observed in 49.6% (185/373) of patients. Patients who developed SIRS presented more frequently with NYHA III/IV at baseline [SIRS: 82.4% (149/185) vs. no SIRS: 79.0% (147/188); p = 0.029]. Patients who developed SIRS spent more days on ICU (p < 0.001) and overall length of stay was longer (p < 0.001). Relevant residual MR, defined as MR ≥ III in-hospital, was present more often in patients who developed SIRS [SIRS: 11.3% (20/177) vs. no SIRS: 3.93% (7/178), p = 0.036]. At 3 years, all-cause mortality in the entire population was 33.5% (125/373) with an increased all-cause mortality in patients with SIRS compared to patients without SIRS (HR 1.49, [CI 95% 1.04, 2.13]; p = 0.0264). In the multivariate analysis development of SIRS (HR 1.479 [CI 95% 1.016, 2.154]; p = 0.041) was identified as predictor for 3-years all-cause mortality. CONCLUSIONS: SIRS is a common finding after MV-TEER occurring in approximately half of patients. SIRS after MV-TEER was associated with a longer in-hospital stay. In addition, we observed an increased 3-years all-cause mortality in patients with SIRS

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