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The glitazones or thiazolidinediones are ligands of the peroxisome proliferator-activated receptor ␥ (PPAR␥). The glitazones are used in the treatment of diabetes, regulate adipogenesis, inflammation, cell proliferation, and induce apoptosis in several cancer cell types. High grade astrocytomas are rapidly growing tumors derived from astrocytes, for which new treatments are needed. We determined the effects of two glitazones, ciglitazone and the therapeutic rosiglitazone, on the survival of serum-deprived primary rat astrocytes and glioma cell lines C6 and U251, which were assessed by the methylthiazolyl tetrazolium assay and lactate dehydrogenase release. Rosiglitazone (5-20 M) decreased survival of glioma cells without affecting primary astrocytes, whereas ciglitazone at 20 M was toxic for both cell types. Ciglitazone at 10 M was cytoprotective for primary astrocytes but toxic to glioma cells. Cell death induced by ciglitazone, but not rosiglitazone, presented apoptotic features (Hoechst staining and externalization of phosphatidylserine). Two mechanisms to explain cytotoxicity were investigated: activation of PPAR␥ and production of reactive oxygen species (ROS). PPAR␥ does not seem to be the main mechanism involved, because the order of efficacy for cytotoxicity, ciglitazone > rosiglitazone, was inverse of their reported affinities for activating PPAR␥. In addition, GW9662, an inhibitor of PPAR␥, only slightly attenuated cytotoxicity. However, the rapid increase in ROS production and the marked reduction of cell death with the antioxidants ebselen and N-acetylcysteine, indicate that ROS have a key role in glitazone cytotoxicity. Ciglitazone caused a dose-dependent and rapid loss (in minutes) of mitochondrial membrane potential in glioma cells. Therefore, mitochondria are a likely source of ROS and early targets of glitazone cytotoxicity. Our results highlight the potential of rosiglitazone and related compounds for the treatment of astrogliomas.

CondensationProphylactic use of aspirin in women at high-risk of preeclampsia reduces substantially the length of stay in the neonatal intensive care unit. Short version of article title Secondary analysis of ASPRE trial Implications and ContributionsA. The study was conducted in women at high-risk of preeclampsia to examine the effect of prophylactic use of aspirin during pregnancy on length of stay in the neonatal intensive care unit. B. Prophylactic use of aspirin reduces the length of stay in neonatal intensive care unit by about 70%, mainly due to a decrease in the rate of births at <32 weeks' gestation because of prevention of early-preeclampsia.C. In women at high-risk of preeclampsia prophylactic use of aspirin reduces substantially both the risk of preterm-preeclampsia and length of stay in neonatal intensive care unit.

To evaluate the effectiveness of an integrated emergency department (ED)/hospital at home (HH) medical care model in mild COVID-19 pneumonia and evaluate baseline predictors of major outcomes and potential savings. Retrospective cohort study with patients evaluated for COVID-19 pneumonia in the ED, from March 3 to April 30, 2020. All of them were discharged home and controlled by HH. The main outcomes were ED revisit and the need for deferred hospital admission (protocol failure). Outcome predictors were analyzed by simple logistic regression model (OR; 95% CI). Potential savings of this medical care model were estimated. Of the 377 patients attended in the ED, 109 were identified as having mild pneumonia and were included in the ED/HH medical care model. Median age was 50.0 years, 52.3% were males and 57.8% had Charlson index ≥ 1. The median HH stay was 8 (IQR 3.7–11) days. COVID-19-related ED revisit was 19.2% ( n = 21) within 6 days (IQR 3–12.5) after discharge from ED. Overall protocol failure (deferred hospital admission) was 6.4% ( n = 7), without ICU admission. The ED/HH model provided potential cost savings of 77% compared to traditional stay, due to the costs of home care entails 23% of the expenses generated by a conventional hospital stay. 789 days of hospital stay were avoided by HH, rather than hospital admission. An innovative ED/HH model for selected patients with mild COVID-19 pneumonia is feasible, safe and effective. Less than 6.5% of patients requiring deferred hospital admission and potential savings were generated due to hospitalization. Supplementary Information The online version contains supplementary material available at 10.1007/s11739-021-02661-8.

ObjectiveTo evaluate the diagnostic accuracy of the Fetal Medicine Foundation (FMF) competing risk model (the triple test) for the prediction of preterm pre‐eclampsia (PE) in a Spanish population.MethodsThis was a prospective cohort study performed in eight fetal‐medicine units in five different regions of Spain between September 2017 and December 2019. All pregnant women with singleton pregnancies and non‐malformed live fetuses attending their routine ultrasound examination at 11+0‐13+6 weeks' gestation were invited to participate in the study. We recorded maternal demographic characteristics and medical history and measured MAP, UtA‐PI, and serum PlGF and PAPP‐A following standardized protocols. We also recorded whether the women were treated with aspirin during pregnancy. The raw values of the biomarkers were converted into multiples of the median (MoM), and audits were periodically performed for the operators and laboratories to receive continuous feedback. Risks for term and preterm PE were calculated according to the FMF competing risks model blinded to outcome. The performance of screening for PE, taking account of aspirin, was assessed by calculating the areas under the receiver‐operating‐characteristics curve (AUROC) and detection rates (DRs) with 95% confidence intervals (CI) at different fixed screen‐positive rates (SPRs). Risk calibration was also assessed.ResultsThe study population comprised 10,110 singleton pregnancies, including 72 (0.7%) that developed preterm PE. Compared to those without PE, the median MAP and UtA‐PI were significantly higher in the preterm PE group, and the median serum PlGF and pregnancy‐associated plasma protein A (PAPP‐A) were significantly lower. In the PE group, the deviation in biomarkers from normal was inversely related to the gestational age at delivery. In screening by a combination of maternal characteristics and medical history with MAP, UtA‐PI, and PlGF, at an SPR of 10%, the DR of preterm PE was 72.7 (95% CI, 62.9–82.6). An alternative strategy of replacing PlGF with PAPP‐A in the triple test was associated with poorer screening performance; the DR was 66.5% (95% CI, 55.8–77.2). Calibration plots showed good agreement between predicted and observed cases of preterm PE, with a slope of 0.983 (0.846–1.120) and an intercept of 0.154 (‐0.091 to 0.397). Our DR of preterm PE at 10% SPR by the triple test was lower than that reported by the FMF (72.7% vs. 74.8%).ConclusionsThe FMF model is effective in predicting preterm PE in the Spanish population. This method of screening is feasible and easy to implement in routine clinical practice, but it must be accompanied by a good audit and monitoring system, which helps ensure the quality of the screening.This article is protected by copyright. All rights reserved.