Search

There are limited data on second stem cell transplantation (SCT2) outcomes with alternative donors for relapsed AML after the first stem cell transplantation (SCT1). We analyzed the outcomes of 52 adult AML patients who received SCT2 from haploidentical donors (HIT, N = 32) and double-cord blood (dCBT, N = 20) between 2008 and 2021. The HIT group received T-cell-replete peripheral blood stem cells after reduced-toxicity conditioning with anti-thymocyte globulin (ATG), while the dCBT group received myeloablative conditioning. For a median follow-up of 64.9 months, the HIT group, compared to the dCBT group, had earlier engraftment, superior 2-year overall survival (OS), disease-free survival (DFS), and non-relapse mortality (NRM) with similar relapse. Multivariate analysis demonstrated that HIT was significantly associated with better OS, DFS, and lower NRM than dCBT. Both longer remission duration after SCT1 and complete remission at SCT2 were significantly associated with a lower relapse rate. In addition, bone marrow WT1 measurable residual disease (MRD) positivity was significantly associated with inferior OS and higher relapse. This study suggests that T-cell-replete HIT with ATG-based GVHD prophylaxis may be preferred over dCBT as SCT2 for relapsed AML and that WT1-MRD negativity may be warranted for better SCT2 outcomes.

Inflammation and loss of cholinergic transmission are involved in neurodegenerative diseases, but possible interactions between them within neurons, astrocytes, and microglia have not yet been investigated. We aimed to compare store-operated Ca2+ entry (SOCE) in neurons, astrocytes, and microglia following cholinergic dysfunction in combination with (or without) an inflammatory stimulus and to investigate the effects of linalyl acetate (LA) on this process. We used the SH-SY5Y, U373, and BV2 cell lines related to neurons, astrocytes, and microglia, respectively. Scopolamine or lipopolysaccharide (LPS) was used to antagonize the muscarinic receptors or induce inflammatory responses, respectively. The concentration of intracellular Ca2+ was measured using Fura-2 AM. Treatment with scopolamine and LPS significantly increased SOCE in the neuron-like cells and microglia but not in the scopolamine-pretreated astrocytes. LA significantly reduced SOCE in the scopolamine-pretreated neuron-like cells and microglia exposed to LPS, which was partially inhibited by the Na+-K+ ATPase inhibitor ouabain and the Na+/Ca2+ exchanger (NCX) inhibitor Ni2+. Notably, SOCE was significantly reduced in the LPS plus scopolamine-pretreated cells mixed with astrocytes and microglia, with a two-fold increase in the applied number of astrocytes. LA may be useful in protecting neurons and microglia by reducing elevated SOCE that is induced by inflammatory responses and inhibiting the muscarinic receptors via Na+-K+ ATPase and the forward mode of NCX. Astrocytes may protect microglia by reducing increased SOCE under the conditions of inflammation and a muscarinic receptor blockade.

The prognostic significance of KIT mutations and optimal thresholds and time points of measurable residual disease (MRD) monitoring for acute myeloid leukemia (AML) with RUNX1-RUNX1T1 remain controversial in the setting of hematopoietic stem cell transplantation (HSCT). We retrospectively evaluated 166 high-risk patients who underwent allogeneic (Allo-HSCT, n = 112) or autologous HSCT (Auto-HSCT, n = 54). D816V KIT mutation, a subtype of exon 17 mutations, was significantly associated with post-transplant relapse and poor survival, while other types of mutations in exons 17 and 8 were not associated with post-transplant relapse. Pre- and post-transplant RUNX1&ndash, RUNX1T1 MRD assessments were useful for predicting post-transplant relapse and poor survival with a higher sensitivity at later time points. Survival analysis for each stratified group by D816V KIT mutation and pre-transplant RUNX1&ndash, RUNX1T1 MRD status demonstrated that Auto-HSCT was superior to Allo-HSCT in MRD-negative patients without D816V KIT mutation, while Allo-HSCT was superior to Auto-HSCT in MRD-negative patients with D816V KIT mutation. Very poor outcomes of pre-transplant MRD-positive patients with D816V KIT mutation suggested that this group should be treated in clinical trials. Risk stratification by both D816V KIT mutation and RUNX1&ndash, RUNX1T1 MRD status will provide a platform for decision-making or risk-adapted therapeutic approaches.

This study aimed to make an empirical analysis of the effects that the selection attributes of subscription services have on purchase intentions and continuous use intentions, based on the perceived value of digital platform-based subscription service users as a medium. A survey was conducted among 434 subscription service users in Korea, with content superiority, system quality, and service differentiation defined as key selection attributes based on a literature review. Upon analysis, content superiority and service differentiation were found to have a positive effect on perceived value, which in turn positively affected purchase intentions and continuous use intentions, which is why the hypothesis was consequently adopted. Service differentiation was also found to positively affect purchase intentions and continuous use intentions using perceived value as a medium. In contrast, system quality was found to have no effect on perceived value, nor did it affect purchase intentions or continuous use intentions using perceived value as a medium, which is why the hypothesis was rejected. In conclusion, among factors impacting decision-making or buying behavior among users of recent digital platform-based subscription services, new, unique, and meaningful content superiority was found to have a bigger impact compared to system-related aspects based on technology usability.

Simple Summary Venetoclax (VEN)-based combination chemotherapy has been a promising option for acute myeloid leukemia (AML) treatment. However, the risk of infections and strategies of prophylaxis are not yet established. This study aimed to evaluate the severe infectious complications of VEN-based chemotherapy and to clarify the evidence for antimicrobial prophylaxis. The incidence of invasive fungal infections (IFIs) and bloodstream infections (BSIs) was 6.6/100 cycles and 12.7/100 cycles respectively. Secondary and therapy-related AML was an independent risk factor for IFIs (odds ratio, 3.859; 95% confidence interval, 1.344–11.048, p = 0.012). Patients with IFIs showed significantly poorer outcomes, but there was no statistically significant difference in patients with BSIs. Mold-active antifungal agents as prophylaxis are generally recommended in high-risk patients with AML who are treated with VEN-based combination chemotherapy. Abstract Although venetoclax (VEN)-based combination chemotherapy in patients with acute myeloid leukemia (AML) results in prolonged and profound neutropenia, data regarding infectious complications and antimicrobial prophylaxis are lacking. We investigated the infectious complications in 122 adult patients with AML under the same standard of care for prevention. The prophylaxis protocol was fluconazole 400 mg/d without antibacterial agents. The incidence of proven or probable invasive fungal infections (IFIs) was 6.6/100 cycles, and 22 patients (18.0%) were diagnosed (median, second cycle; interquartile range, 1–2). All IFIs were caused by Aspergillus and significantly influenced the overall mortality (odds ratio (OR), 2.737; 95% confidence interval (CI), 1.051–7.128; p = 0.034). In the multivariate analysis, secondary or therapy-related AML was an independent risk factor for IFIs (OR, 3.859; 95% CI, 1.344–11.048, p = 0.012). A total of 39 bloodstream infection (BSIs) episodes occurred in 35 patients (28.7%), with an incidence of 12.7/100 cycles. High-dose steroid administration within 90 days was associated with the occurrence of BSIs (OR, 7.474; 95% CI; 1.661–3.631, p = 0.008), although BSIs themselves did not have an impact on the outcomes. Our findings suggest evidence for the need for mold-active antifungal agents as antifungal prophylaxis, rather than fluconazole, especially in patients with secondary or therapy-related AML.

The aim of the study is to evaluate the risk of heart disease in individuals who underwent cholecystectomy. This was a retrospective cohort study using the National Health Insurance Service database of South Korea. A total of 146,928 patients who underwent cholecystectomy and 268,502 age- and sex-matched controls were compared. Multivariate Cox proportional hazard regression analysis was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for heart disease after cholecystectomy. In results, a previous history of cholecystectomy increased the risk of heart disease (congestive heart failure [CHF], myocardial infarction [MI], atrial fibrillation [AF]) (adjusted HR [aHR]: 1.40, 95% CI: [1.36–1.44]). The increased risk was particularly seen for CHF (1.22 [1.16–1.29]) but not for MI and AF (p &gt, 0.05). In the subgroup analyses, cholecystectomy was associated with an increased risk of MI in patients aged &lt, 65 years (1.49 [1.16–1.92] and 1.18 [1.05–1.35] in patients aged 40–49 and 50–64 years, respectively), but not in those aged ≥ 65 years (0.932 [0.838–1.037]). Moreover, the risk of MI was increased in patients without diabetes mellitus (DM) (1.16 [1.06–1.27]), however, it was decreased in patients with DM (0.83 [0.72–0.97]). In contrast, cholecystectomy did not modify the risk of AF in the subgroup analyses (all p &gt, 0.05). In conclusion, a history of cholecystectomy is associated with an increased risk of CHF. Cholecystectomy may increase the risk of MI in the younger population without DM. These findings suggest that the alteration of bile metabolism and homeostasis might be potentially associated with the development of some heart diseases.

This study investigated the influences of acidity, ethanol, and pigment on the optical properties, microhardness, and surface roughness (Ra) of a nanohybrid dental composite resin. A total of 108 disc-shaped specimens were fabricated using a nanohybrid dental composite and allocated into 36 different storage solutions according to the levels of pH (2.0, 3.0, 4.0, and 5.5), ethanol (0%, 20%, and 40%), and anthocyanin pigment (0%, 2.5%, and 12.5%). Measurements of the colorimetric parameter and the amount of color change (&Delta, E), translucency parameter (TP), microhardness, and surface roughness (Ra) were performed at 24 h (baseline), 1-, 2-, 3-, and 4-weeks. Repeated measures of analysis of variance (ANOVA) with a Tukey honestly significant difference test and Pearson correlation analysis were carried out (&alpha, = 0.05). Pigment of 12.5% or 40% ethanol significantly increased the &Delta, E (P &lt, 0.001, P = 0.048, respectively). Pigment of 2.5% or 12.5% significantly decreased the TP (P = 0.001, P &lt, 0.001, respectively). Microhardness of composite resin stored in pH 2.0, 3.0, 4.0 solution was lower than that for pH 5.5 (P &lt, 0.001). Pigment, ethanol, and pH did not influence the Ra. TP change and &Delta, E, and Ra and &Delta, E had a significant positive correlation (P &lt, 0.05). In conclusion, pigment and ethanol levels influenced the optical properties and acidity affected the microhardness of composite resin.