Background: Hetrombopag is a novel thrombopoietin receptor agonist that has shown an additive effect in stimulating platelet production when combined with recombinant human thrombopoietin (rhTPO). However, it remains unclear whether this combination can promote hematopoietic reconstruction after autologous stem cell transplant (ASCT).
Purpose: To compare the effect of rhTPO plus thrombopoietin receptor agonists (TPO-RA) versus rhTPO alone on hematopoietic recovery, adverse events, postoperative complications, and cost-effectiveness in patients with newly diagnosed multiple myeloma (NDMM) undergoing ASCT.
Methods: A total of 67 consecutive NDMM patients who underwent ASCT at our hospital from January 2021 to May 2024 were included. Of these patients, 35 received a combination of rhTPO and the TPO-RA hetrombopag after stem cell reinfusion (observation group), whereas 32 patients received rhTPO alone (control group). Hematopoietic reconstitution between the two groups was compared.
Results: Baseline clinical characteristics were similar between both groups. In the observation group, the median time to platelet recovery was 9 days after stem cell reinfusion, which was significantly shorter than that in the control group (P = .003). The mean number of platelet transfusions in the observation group was significantly lower than that in the control group (1.0 vs. 2.0 units, P = .034). All patients tolerated rhTPO and TPO-RA well, with no thrombotic events observed. Survival analysis showed no reduction in time to progression (TTP) and overall survival (OS) with the addition of TPO-RA. There were no statistical differences in the incidence of adverse events, drug expenses, and hospital stay between two groups (P > 0.05).
Conclusions: Although sample size and study design limit the data from this study, our findings suggest that the combination of TPO-RA (hetrombopag) and rhTPO enhances platelet recovery in comparison with rhTPO alone, without increasing adverse effects.
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http://dx.doi.org/10.1016/j.jtct.2024.12.015 | DOI Listing |
Background: Alzheimer's disease (AD) is the most common cause of dementia worldwide. It is characterized by dysfunction in the U1 small nuclear ribonucleoproteins (snRNPs) complex, which may precede TAU aggregation, enhancing premature polyadenylation, spliceosome dysfunction, and causing cell cycle reentry and death. Thus, we evaluated the effects of a synthetic single-stranded cDNA, called APT20TTMG, in induced pluripotent stem cells (iPSC) derived neurons from healthy and AD donors and in the Senescence Accelerated Mouse-Prone 8 (SAMP8) model.
View Article and Find Full Text PDFBackground: Our previous study identified that Sildenafil (a phosphodiesterase type 5 [PDE5] inhibitor) is a candidate repurposable drug for Alzheimer's Disease (AD) using in silico network medicine approach. However, the clinically meaningful size and mechanism-of-actions of sildenafil in potential prevention and treatment of AD remind unknown.
Method: We conducted new patient data analyses using both the MarketScan® Medicare with Supplemental database (n = 7.
Background: Convergent evidence indicates that deficits in the endosomal recycling pathway underlies pathogenesis of Alzheimer's disease (AD). SORL1 encodes the retromer-associated receptor SORLA that plays an essential role in recycling of AD-associated cargos such as the amyloid precursor protein and the glutamatergic AMPA receptor. Importantly, loss of function pathogenic SORL1 variants are associated with AD.
View Article and Find Full Text PDFBackground: Although investment in biomedical and pharmaceutical research has increased significantly over the past two decades, there are no oral disease-modifying treatments for Alzheimer's disease (AD).
Method: We performed comprehensive human genetic and multi-omics data analyses to test likely causal relationship between EPHX2 (encoding soluble epoxide hydrolase [sEH]) and risk of AD. Next, we tested the effect of the oral administration of EC5026 (a first-in-class, picomolar sEH inhibitor) in a transgenic mouse model of AD-5xFAD and mechanistic pathways of EC5026 in patient induced Pluripotent Stem Cells (iPSC) derived neurons.
Alzheimers Dement
December 2024
Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Background: Genome-wide association studies (GWAS) have identified close to one hundred loci associated with Alzheimer's disease (AD) risk. However, for most of these loci we do not understand the underlying mechanism leading to disease. Crispr genome editing in human induced pluripotent stem cells (hiPSCs) provides a model system to study the effects of these genetic variants in a disease relevant cell type.
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