The clinical scenario, which is based on systolic blood pressure (SBP) upon admission, is useful for classifying and determining initial treatment for acute heart failure (HF). However, the ...prognostic significance of SBP following the initial treatment is unclear.The Japanese Heart Failure Syndrome with Preserved Ejection Fraction (JASPER) registry is a nationwide, observational, and prospective registration of consecutive Japanese patients hospitalized with HF with preserved ejection fraction (HFpEF) and left ventricular ejection fraction ≥ 50%. We divided 525 patients into three groups based on their SBP on the day following hospitalization: high (SBP > 140 mmHg, n = 72, 13.7%); normal (100 ≤ SBP ≤ 140 mmHg, n = 379, 72.2%); and low (SBP < 100 mmHg, n = 74, 14.1%) groups. This analysis had two primary endpoints: (1) all-cause death and (2) all-cause death or rehospitalization for HF. In the Kaplan-Meier analysis, both of the endpoints were the highest in the low group (Log-Rank < 0.05, respectively). Compared to the normal and high groups, the low group demonstrated a higher prevalence of atrial fibrillation (67.1%, 63.9%, and 47.8%, P = 0.026) and the lowest left ventricular outflow tract velocity time integral determined by echocardiography (16.4 cm, 19.4 cm, and 23.3 cm, P = 0.001). In the multivariable Cox proportional hazard analysis, low SBP on the day following hospitalization was an independent predictor of all-cause death (hazard ratio 1.868, 95% confidence interval 1.024-3.407, P = 0.042) and the composite endpoint (hazard ratio 1.660, 95% confidence interval 1.103-2.500, P = 0.015).Classification based on SBP on the day following initial treatment predicts post-discharge prognosis in hospitalized patients with HFpEF.
Neuroblastoma (NB) is one of the primary causes of death for pediatric malignancies. Given the high heterogeneity in NB's mutation landscape, optimizing individualized therapies is still challenging. ...In the context of genomic alterations, MYCN amplification is the most correlated event with poor outcomes. MYCN is involved in the regulation of several cellular mechanisms, including cell cycle. Thus, studying the influence of MYCN overexpression in the G1/S transition checkpoint of the cell cycle may unveil novel druggable targets for the development of personalized therapeutical approaches. Here, we show that high expression of E2F3 and MYCN correlate with poor prognosis in NB despite the RB1 mRNA levels. Moreover, we demonstrate through luciferase reporter assays that MYCN bypasses RB function by incrementing E2F3-responsive promoter activity. We showed that MYCN overexpression leads to RB inactivation by inducing RB hyperphosphorylation during the G1 phase through cell cycle synchronization experiments. Moreover, we generated two MYCN-amplified NB cell lines conditionally knockdown (cKD) for the RB1 gene through a CRISPRi approach. Indeed, RB KD did not affect cell proliferation, whereas cell proliferation was strongly influenced when a non-phosphorylatable RB mutant was expressed. This finding revealed the dispensable role of RB in regulating MYCN-amplified NB's cell cycle. The described genetic interaction between MYCN and RB1 provides the rationale for using cyclin/CDK complexes inhibitors in NBs carrying MYCN amplification and relatively high levels of RB1 expression.
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