Comparative Analysis of Short-Term Outcomes of Patients With Heart Failure With a Mid-Range Ejection Fraction After Acute Decompensation.

To determine short-term outcomes after an episode of acute heart failure in patients with mid-range ejection fraction (40%-49%; HFmrEF) compared with patients with reduced (<40%) and preserved (>49%) ejection fractions (HFrEF and HFpEF, respectively) and according to their final destination after emergency department (ED) care. This is an exploratory, secondary analysis of the Epidemiology of Acute Heart Failure in the Emergency departments Registry, which includes consecutive acute heart failure patients diagnosed in 41 Spanish EDs. Patients with echocardiography data were included and divided into HFrEF, HFmrEF, and HFpEF. The primary outcome was 30-day all-cause mortality, and secondary outcomes were in-hospital all-cause mortality, hospital length of stay >10 days, and 30-day postdischarge ED revisit due to AHF and combined end point (ED revisit and/or death). We included 6,856 patients (age 79 [10]; 52.1% women): 21.6% had HFrEF, 14.3% HFmrEF, and 64.1% HFpEF. The main destinations for the 982 HFmrEF patients after ED management were internal medicine (293, 29.8%), cardiology (194, 19.9%) and not hospitalized (241, 24.5%), whereas the remaining 254 patients were admitted to other departments, including geriatric wards, short-stay units and intensive care units. Outcomes for HFmrEF did not differ compared with either HFrEF or HFpEF. Compared with HFmrEF admitted to cardiology, internal medicine admission or direct ED discharge increased the 30-day postdischarge ED revisit (hazard ratio [HR] 1.713, 95% confidence interval [CI] 1.042 to 2.816; and HR 1.683, 95% CI 1.046 to 2.708, respectively) and the 30-day postdischarge combined end point (HR 1.732, 95% CI 1.070 to 2.803; and HR 1.727, 95% CI 1.083 to 2.756, respectively). In conclusion, patients in the newly created HFmrEF category suffering from an acute decompensation have similar short-term outcomes as those in the classical HFrEF and HFpEF categories; nonetheless, HFmrEF patients handled in cardiology wards during decompensation obtain better outcomes, and reasons for these differences have to be unmasked and corrected.

Embryonic Cerebrospinal Fluid Increases Neurogenic Activity in the Brain Ventricular-Subventricular Zone of Adult Mice.

Neurogenesis is a very intensive process during early embryonic brain development, becoming dramatically restricted in the adult brain in terms of extension and intensity. We have previously demonstrated the key role of embryonic cerebrospinal fluid (CSF) in developing brain neurogenic activity. We also showed that cultured adult brain neural stem cells (NSCs) remain competent when responding to the neurogenic influence of embryonic CSF. However, adult CSF loses its neurogenic inductive properties. Here, by means of an organotypic culture of adult mouse brain sections, we show that local administration of embryonic CSF in the subventricular zone (SVZ) niche is able to trigger a neurogenic program in NSCs. This leads to a significant increase in the number of non-differentiated NSCs, and also in the number of new neurons which show normal migration, differentiation and maturation. These new data reveal that embryonic CSF activates adult brain NSCs, supporting the previous idea that it contains key instructive components which could be useful in adult brain neuroregenerative strategies.

Embryonic cerebrospinal fluid collaborates with the isthmic organizer to regulate mesencephalic gene expression.

Early in development, the behavior of neuroepithelial cells is controlled by several factors acting in a developmentally regulated manner. Recently it has been shown that diffusible factors contained within embryonic cerebrospinal fluid (CSF) promote neuroepithelial cell survival, proliferation, and neurogenesis in mesencephalic explants lacking any known organizing center. In this paper, we show that mesencephalic and mesencephalic+isthmic organizer explants cultured only with basal medium do not express the typically expressed mesencephalic or isthmic organizer genes analyzed (otx2 and fgf8, respectively) and that mesencephalic explants cultured with embryonic CSF-supplemented medium do effect such expression, although they exhibit an altered pattern of gene expression, including ectopic shh expression domains. Other trophic sources that are able to maintain normal neuroepithelial cell behavior, i.e., fibroblast growth factor-2, fail to activate this ectopic shh expression. Conversely, the expression pattern of the analyzed genes in mesencephalic+isthmic organizer explants cultured with embryonic cerebrospinal fluid-supplemented medium mimics the pattern for control embryos developed in ovo. We demonstrate that embryonic CSF collaborates with the isthmic organizer in regulation of the expression pattern of some characteristic neuroectodermal genes during early stages of central nervous system (CNS) development, and we suggest that this collaboration is not restricted to the maintenance of neuroepithelial cell survival. Data reported in this paper corroborate the hypothesis that factors contained within embryonic CSF contribute to the patterning of the CNS during early embryonic development.