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Objectives: Mechanical circulatory support (MCS) is often required to stabilize therapy-refractory cardiogenic shock patients. Left ventricular (LV) unloading by mechanical ventricular support (MVS) via percutaneous devices, such as with Impella® axial pumps, alone or in combination with extracorporeal life support (ECLS, ECMELLA approach), has emerged as a potential clinical breakthrough in the field. While the weaning from MCS is essentially based on the evaluation of circulatory stability of patients, weaning from MVS holds a higher complexity, being dependent on bi-ventricular function and its adaption to load. As a result of this, weaning from MVS is mostly performed in the absence of established algorithms. MVS via Impella is applied in several cardiogenic shock etiologies, such as acute myocardial infarction (support over days) or acute fulminant myocarditis (prolonged support over weeks, PROPELLA). The time point of weaning from Impella in these cohorts of patients remains unclear. We here propose a novel cardiovascular physiology-based weaning algorithm for MVS.Methods: The proposed algorithm is based on the experience gathered at our center undergoing an Impella weaning between 2017 and 2020. Before undertaking a weaning process, patients must had been ECMO-free, afebrile, and euvolemic, with hemodynamic stability guaranteed in the absence of any inotropic support. The algorithm consists of 4 steps according to the acronym TIDE: (i) Transthoracic echocardiography under full Impella-unloading; (ii) Impella rate reduction in single 8–24 h-steps according to patients hemodynamics (blood pressure, heart rate, and ScVO2), including a daily echocardiographic assessment at minimal flow (P2); (iii) Dobutamine stress-echocardiography; (iv) Right heart catheterization at rest and during Exercise-testing via handgrip. We here present clinical and hemodynamic data (including LV conductance data) from paradigmatic weaning protocols of awake patients admitted to our intensive care unit with cardiogenic shock. We discuss the clinical consequences of the TIDE algorithm, leading to either a bridge-to-recovery, or to a bridge-to-permanent LV assist device (LVAD) and/or transplantation. With this protocol we were able to wean 74.2% of the investigated patients successfully. 25.8% showed a permanent weaning failure and became LVAD candidates.Conclusions: The proposed novel cardiovascular physiology-based weaning algorithm is based on the characterization of the extent and sustainment of LV unloading reached during hospitalization in patients with cardiogenic shock undergoing MVS with Impella in our center. Prospective studies are needed to validate the algorithm.

Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is increasingly used in bi-ventricular failure with cardiogenic shock to maintain systemic perfusion. Nonetheless, it tends to increase left ventricular (LV) afterload and myocardial oxygen demand. In order to mitigate these negative effects on the myocardium, an Impella CP® (3.5 L/min Cardiac Output) can be used in conjunction with V-A ECMO (ECMELLA approach). We implemented this strategy in a patient with severe acute myocarditis complicated by cardiogenic shock. Due to a hemolysis crisis, Impella CP® had to be substituted with PulseCath iVAC2L®, which applies pulsatile flow to unload the LV. A subsequent improvement in LV systolic function was noted, with increased LV ejection fraction (LVEF), LV end-diastolic diameter (LVEDD) reduction, and a reduction in plasma free hemoglobin. This case documents the efficacy of iVAC2L in replacing Impella CP as a LV vent during V-A ECMO, with less hemolysis.

Abstract Background Recent clinical trials have shown that pulmonary artery pressure-guided therapy via the CardioMEMS™ system reduces the risk of recurrent hospitalizations in chronic heart failure (HF) patients. The CardioMEMS™ pressure sensor is percutaneously implanted in a branch of the pulmonary artery and allows telemetric pressure monitoring via a receiver. According to the most recent ESC guidelines, this technology has currently a class IIb indication in patients with class III New York Heart Association symptoms and a previous hospitalization for congestive heart failure within the last year, regardless of ejection fraction. Aim of this guided-therapy is multifold, including an early prediction of upcoming decompensation, optimization of patients’ therapy and thereby avoidance of hospital admissions. In addition, it can be used during acute decompensation events as a novel tool to direct intra-hospital therapeutic interventions such as inotropes infusion or left ventricular (LV) assist device monitoring, with the aim of achieving an optimal volume status. Case presentation We present a case series of three end-stage HF patients with reduced ejection fraction (HFrEF) who received a CardioMEMS™ device as an aid in their clinical management. The CardioMEMS™ system enabled a closer non-invasive hemodynamic monitoring of these patients and guided the extent of therapeutic interventions. Patients were free from device- or system-related complications. In addition, no pressure-sensor failure was observed. Two patients received a 24-h infusion of the calcium sensitizer levosimendan. One patient showed a refractory acute decompensation and underwent LV assist device (LVAD) implantation as a bridge to cardiac transplantation. Switching a patient with recurrent hospitalizations to the Angiotensin Receptor Neprilysin Inhibitor (ARNI, Sacubitril-Valsartan) on top of the optimal heart failure-therapy improved its subjective condition and hemodynamics, avoiding further hospitalization. Conclusions Our case series underlines the potential impact of CardioMEMS™ derived data in the daily clinical management of end-stage HF patients. The new concept to combine CardioMEMS™ in the setting of an outpatient levosimendan program as well as a bridge to LVAD-implantation/heart transplantation looks promising but needs further investigations.

The production of the L/T channel blocker ACT-280778 required the enantiomerically pure 5-phenylbicyclo[2.2.2]oct-5-en-2-one (1) as key building block. As the published routes towards 1 are very low yielding (

We present an extension of approximate quasi-interpolation on uniformly distributed nodes, to functions given on a set of nodes close to an uniform, not necessarily cubic, grid.

At present, there is still little information on nitrogen (N) accumulation in forests contrasting with the crucial importance of N in forest ecosystems. This work analyzes the N bioaccumulation in mosses from forested areas from Lower Saxony and North Rhine-Westphalia (two of 16 federal states of Germany), the Weser Ems Region (part of Lower Saxony), and the Euro Region Nissa (covering the Czech Republic, Germany, Poland). The studies involved samples collected from 190 sites between 1998 and 2005. Different spatial scales and regional differences in land use were chosen to assess the factors affecting N bioaccumulation in forested areas. A continuous reduction of N bioaccumulation was found from Lower Saxony (a region where agriculture is most predominant) to North Rhine-Westphalia (mostly urban). The Weser Ems Region (an agricultural region) showed a higher N concentration in mosses than the Euroregion Nissa (a former industrial region). Statistical analyses performed at the different spatial scales revealed that the areas showing greater agricultural and livestock spatial densities favor N bioaccumulation in mosses. N concentration in mosses was moderately correlated with the N concentration in the leaves and needles of the surrounding trees. No significant relationships were found regarding the crown density of forest trees or N deposition estimations from a combination of atmospheric models and deposition measurements.

The regional assessment of global change effects on plant phenology usually relies on local observations that need to be up-scaled. Therefore, methodological difficulties mostly related to data spatial resolution and congruency arise while performing broader-scale evaluations. Geostatiscs could be a useful tool to solve this type of problem, provided that a database with adequate spatial and temporal resolution is available. An assessment of variations in air temperature and plant phenology was carried out at the country level by using two German datasets regarding spring phenological phases of 15 plant species and air temperature. The data were collected from 1961–2002 at 1,279 and 675 sites, respectively. The annual mean air temperature in Germany was found to rise from 8.3°C in the 1961–1990 period to 9.1°C in the 1991–2002 term. The overall 15-species mean for the start of spring was found to be 6 days earlier in the latter period. The geostatistical analysis of the data revealed the suitability of Syringa vulgaris to be used as an indicator species to detect phenological changes in German forests. Moreover, their spatial patterns were found to be related to altitude and latitude. Therefore, geostatistics proved to be a useful tool to overcome some of the methodological problems related to the regional assessments of global change impacts on terrestrial ecosystems.

Environmental planning is an instrument for the operationalisation of the precautionary principle in environmental law and, to this end, must rely on maps depicting the spatial patterns of ecological attributes of aquatic and terrestrial ecosystems and of environmental change effects, respectively. In this context, different mapping techniques are presented by example of three case studies covering terrestrial, coastal and marine environments. The first case study was selected to demonstrate how to compute an ecological land classification of Germany by means of CART. The resulting ecoregions were mapped by GIS. This CARTography enables to regionalise metal bioaccumulation data in terms of 21 ecological land categories and to prove the specifity of emission control measures as being part of environmental policies. The second investigation was chosen to apply for the first time in Germany the regionalisation approach to the research of climate change effects in terms of past, recent and potential future incidences of Anopheles sp. and malaria in Lower Saxony. To investigate whether malaria might be transmitted due to increasing air temperatures, data sets on past and future air temperatures were used to spatially model malaria risk areas. The third example demonstrates the transfer of the CARTography approach presented in the first case study from terrestrial to marine environments. We analysed the statistical relations between data on benthic communities and physical properties of their marine environments by means of CART and applied these rules to geodata which only describe physical characteristics of the benthic habitats. By this, those parts of the sea ground could be predicted where certain benthic communities might occur.

Research that investigates bioaerosol emissions from animal transport vehicles (ATVs) and their importance in the spread of harmful airborne agents while the ATVs travel on roads is limited. To investigate the dynamical behaviour of theoretically released particles from a moving ATV, the open-source computational fluid dynamics (CFD) software OpenFOAM was used to calculate the external and internal air flow fields with passive and forced ventilated openings of a common ATV moving at a speed of 80 km/h. In addition to a computed flow rate of approximately 40,000 m3/h crossing the interior of the ATV, the visualization of the trajectories has demonstrated distinct patterns of the spatial distribution of potentially released bioaerosols in the vicinity of the ATV. Although the front openings show the highest air flow to the outside, the recirculations of air masses between the interior of the ATV and the atmosphere also occur, which complicate the emission and the dispersion characterizations. To specify the future emission rates of ATVs, a database of bioaerosol concentrations within the ATV is necessary in conjunction with high-performance computing resources to simulate the potential dispersion of bioaerosols in the environment.