Novel oral transforming growth factor‐β signaling inhibitor EW‐7197 eradicates CML‐initiating cells

Recent strategies for treating CML patients have focused on investigating new combinations of tyrosine kinase inhibitors (TKIs) as well as identifying novel translational research agents that can eradicate CML leukemia‐initiating cells (CML‐LICs). However, little is known about the therapeutic benefits such CML‐LIC targeting therapies might bring to CML patients. In this study, we investigated the therapeutic potential of EW‐7197, an orally bioavailable transforming growth factor‐β signaling inhibitor which has recently been approved as an Investigational New Drug (NIH, USA), to suppress CML‐LICs in vivo. Compared to TKI treatment alone, administration of TKI plus EW‐7197 to CML‐affected mice significantly delayed disease relapse and prolonged survival. Notably, combined treatment with EW‐7197 plus TKI was effective in eliminating CML‐LICs even if they expressed the TKI‐resistant T315I mutant BCR‐ABL1 oncogene. Collectively, these results indicate that EW‐7197 may be a promising candidate for a new therapeutic that can greatly benefit CML patients by working in combination with TKIs to eradicate CML‐LICs.     

Combined Effect of Metastasis-Related MicroRNA,miR-34 and miR-124 Family,Methylation on Prognosis of Non–Small-Cell Lung Cancer

Background

Many patients with non–small-cell lung cancer (NSCLC) still develop tumor metastasis and recurrence after pulmonary resection and are the primary causes of lung cancer treatment failure and death. MicroRNAs (miRs) have central roles during tumor metastasis and many miR genes are potentially subjected to control by DNA methylation in multiple tumor types. Recently, miR-34 and miR-124 have been demonstrated as potential regulators of the metastasis process in several cancer types.

Hepatic sinusoidal obstruction syndrome after allogeneic hematopoietic stem cell transplantation in adult patients with idiopathic aplastic anemia

We retrospectively investigated the incidence, risk factors, and outcomes of SOS (sinusoidal obstruction syndrome; previously veno-occlusive disease [VOD]) after allogeneic hematopoietic stem cell transplantation (alloHSCT) in aplastic anemia. Two hundred and sixty patients were included in the analysis. SOS developed in 7.3% (n = 19/260) of patients. Classical Cy (200 mg/m²)-ATG was the most common conditioning regimen (84.2%) in the SOS group. The SOS mortality rate was 4/19 (21.1%). Univariate analyses revealed that Cy 200 mg/m² conditioning (p = 0.035), classical Cy-ATG conditioning (p = 0.007), and horse ATG conditioning (p < 0.001) were significant risk factors for developing SOS. Multivariate analysis revealed that only horse ATG conditioning was a poor prognostic factor (HR = 3.484; 95% CI 1.226–9.904; p = 0.002). Rabbit ATG (HR 12.719; 95% CI 2.332–69.373; p = 0.003) and weight gain > 10% (HR 35.655; 95% CI 2.208–575.805; p = 0.012) were risk factors in the overall SOS group. Both rabbit ATG conditioning and weight gain of more than 10% were associated with poor overall survival with a median of 1.2 months (5Y survival rate, any risk factor vs. none: 74.6% vs. 0.0%; p < 0.001; Fig. 2) in the SOS group.     

The serpentine pattern on MRI as an early prognostic factor after fusion for lumbar spinal stenosis

This study aimed to determine the relationship between the serpentine pattern nerve roots (SNR) and prognosis after lumbar fusion for lumbar spinal stenosis (LSS) by comparing clinical outcomes in patients with or without a serpentine pattern. LSS patients with neurological symptoms often present with SNRs. Several studies have shown that LLS symptoms are worse in patients with SNRs. However, the relationship between SNR and outcome after spinal fusion surgery has not yet been established. A total of 332 patients who underwent spinal fusion surgery between January 1, 2010, and December 31, 2019, were enrolled. Patients were divided into those with a serpentine pattern (S group) and those without a serpentine pattern (N group). The prognosis of the 2 groups was compared using visual analog scale (VAS), Oswestry disability index, claudication distance, medication dose for leg dysesthesia, and glucose tolerance. A total of 113 patients had a serpentine pattern, while the remaining 219 did not. Symptom duration and presence of diabetes mellitus were significantly different between the 2 groups (N = 25.4, S = 32.6, P < .05). Changes in the VAS score for lower extremity pain between the 2 groups at 1 year after surgery showed that patients without a serpentine pattern had significantly better outcomes than those with a serpentine pattern (N: 2.7 ± 1.1 vs S: 4.1 ± 1.3; P < .001), despite the score change at 1 month showing no difference (N: 3.5 ± 0.9 vs S: 3.8 ± 1.0; P = .09). SNRs on MRI are more prevalent in diabetic patients and are a negative prognostic factor in lumbar fusion surgery for LSS. Our insights may help physicians decide the optimal surgical plan and predict the postoperative prognosis of patients with LSS.     

Influence of Tempering Temperature and Time on Microstructure and Mechanical Properties of Additively Manufactured H13 Tool Steel

Among various processes for manufacturing complex-shaped metal parts, additive manufacturing is highlighted as a process capable of reducing the wastage of materials without requiring a post-process, such as machining and finishing. In particular, it is a suitable new manufacturing technology for producing AISI H13 tool steel for hot-worked molds with complex cooling channels. In this study, we manufactured AISI H13 tool steel using the laser power bed fusion (LPBF) process and investigated the effects of tempering temperature and holding time on its microstructure and mechanical properties. The mechanical properties of the sub-grain cell microstructure of the AISI H13 tool steel manufactured using the LPBF process were superior to that of the H13 tool steel manufactured using the conventional method. These sub-grain cells decomposed and disappeared during the austenitizing process; however, the mechanical properties could be restored at a tempering temperature of 500 °C or higher owing to the secondary hardening and distribution of carbides. Furthermore, the mechanical properties deteriorated because of the decomposition of the martensite phase and the accumulation and coarsening of carbides when over-tempering occurred at 500 °C for 5 h and 550 °C for 3 h.     

Characteristics of COVID-19 outbreaks and risk factors for transmission at an army training center in South Korea from June to August 2021

ObjectivesIt is crucial to establish the characteristics of coronavirus disease 2019 (COVID-19) outbreaks at army training centers to develop preventive measures. Therefore, this study aimed to determine the COVID-19 transmission patterns and risk factors in a sequence of outbreaks at an army training center from June to August 2021.Methods This study included 1,324 trainees at an army training center where outbreaks occurred from June to August 2021. The outbreak was qualitatively analyzed according to the period, attack rate, demographic characteristics, vaccination history, and living areas. An aerodynamic experiment was performed to evaluate aerosol transmission in living areas.Results Three outbreaks occurred at the army training center from June to August 2021. The first, second, and third outbreaks lasted for 32, 17, and 24 days, and the attack rates were 12.8%, 18.1%, and 8.9%, respectively. Confirmed cases were distributed in all age groups. Recruits and the unvaccinated were at higher risk for COVID-19. The aerodynamic experiment verified the possibility of aerosol transmission within the same living area.Conclusion COVID-19 transmission at army training centers should be minimized through quarantine and post-admission testing during the latency period as part of integrated measures that include facility ventilation, vaccination, indoor mask-wearing, and social distancing.     

Annual Case Volume and One-Year Mortality for Endovascular Treatment in Acute Ischemic Stroke

BackgroundThe association between endovascular treatment (EVT) case volume per hospital and clinical outcomes has been reported, but the exact volume threshold has not been determined. This study aimed to examine the case volume threshold in this context.MethodsNational audit data on the quality of acute stroke care in patients admitted via emergency department, within 7 days of onset, in hospitals that treated ≥ 10 stroke cases during the audit period were analyzed. Ischemic stroke cases treated with EVT during the last three audits (2013, 2014, and 2016) were selected for the analysis. Annual EVT case volume per hospital was estimated and analyzed as a continuous and a categorical variable (in quartiles). The primary outcome measure was 1-year mortality as a surrogate of 3-month functional outcome. As post-hoc sensitivity analysis, replication of the study results was examined using the 2018 audit data.ResultsWe analyzed 1,746 ischemic stroke cases treated with EVT in 120 acute care hospitals. The median annual EVT case volume was 12.0 cases per hospital, and mortality rates at 1 month, 3 months, and 1 year were 12.7%, 16.6%, and 23.3%, respectively. Q3 and Q4 had 33% lower odds of 1-year mortality than Q1. Adjustments were made for predetermined confounders. Annual EVT case volume cut-off value for 1-year mortality was 15 cases per year (P < 0.02). The same cut-off value was replicated in the sensitivity analysis.ConclusionAnnual EVT case volume was associated with 1-year mortality. The volume threshold per hospital was 15 cases per year.     

Antiangiogenic activity of lupeol from Bombax ceiba

In the search for antiangiogenic agents from medicinal plants used in Vietnam, a methanol extract of the stem barks of Bombax ceiba was found to exhibit a significant antiangiogenic activity on in vitro tube formation of human umbilical venous endothelial cells (HUVEC). Bioactivity-guided fractionation and isolation carried out on this extract afforded lupeol as an active principle. At 50 and 30 microg/mL lupeol showed a marked inhibitory activity on HUVEC tube formation while it did not affect the growth of tumor cell lines such as SK-MEL-2, A549, and B16-F10 melanoma.