Search

Objective To compare the convenience and effectiveness of the existing lumbosacral orthoses (LSO) (classic LSO and Cybertech) and a newly developed LSO (V-LSO) by analyzing postoperative data.Methods This prospective cohort study was performed from May 2019 to November 2019 and enrolled and analyzed 88 patients with degenerative lumbar spine disease scheduled for elective lumbar surgery. Three types of LSO that were provided according to the time of patient registration were applied for 6 weeks. Patients were randomized into the classic LSO group (n=31), Cybertech group (n=26), and V-LSO group (n=31). All patients were assessed using the Oswestry Disability Index (ODI) preoperatively and underwent plain lumbar radiography (anteroposterior and lateral views) 10 days postoperatively. Lumbar lordosis (LS angle) and frontal imbalance were measured with and without LSO. At the sixth postoperative week, a follow-up assessment with the ODI and orthosis questionnaire was conducted.Results No significant differences were found among the three groups in terms of the LS angle, frontal imbalance, ODI, and orthosis questionnaire results. When the change in the LS angle and frontal imbalance toward the reference value was defined as a positive change with and without LSO, the rate of positive change was significantly different in the V-LSO group (LS angle: 41.94% vs. 61.54% vs. 83.87%; p=0.003).Conclusion The newly developed LSO showed no difference regarding its effectiveness and compliance when compared with the existing LSO, but it was more effective in correcting lumbar lordosis.

Magnetic tunneling junction (MTJ) materials such as CoFeB, Co, Pt, MgO, and the hard mask material such as W and TiN were etched with a reactive ion beam etching (RIBE) system using H2/NH3. By using gas mixtures of H2 and NH3, especially with the H2/NH3( 2:1) ratio, higher etch rates of MTJ related materials and higher etch selectivities over mask materials (>30) could be observed compared to those etching using pure H2( no etching) and NH3. In addition, no significant chemical and physical damages were observed on etched magnetic materials surfaces and, for CoPt and MTJ nanoscale patterns etched by the H2/NH3( 2:1) ion beam, highly anisotropic etch profiles >83° with no sidewall redeposition could be observed. The higher etch rates of magnetic materials such as CoFeB by the H2/NH3( 2:1) ion beam compared to those by H2 ion beam or NH3 ion beam are believed to be related to the formation of volatile metal hydrides (MH, M = Co, Fe, etc) through the reduction of M-NHx( x = 1 ∼ 3) formed in the CoFeB surface by the exposure to NH3 ion beam. It is believed that the H2/NH3 RIBE is a suitable technique in the etching of MTJ materials for the next generation nanoscale spin transfer torque magnetic random access memory (STT-MRAM) devices.

Background: FMS-like tyrosine kinase 3 (FLT3), a member of the class III receptor tyrosine kinase family, plays a pivotal role in regulating cell growth and differentiation of hematopoietic cells. FLT3 is mutated in approximately 30% of AML patients either by internal tandem duplication (ITD) within the juxtamembrane portion or by point-mutations in the kinase domain (TKD). Thus, FLT3 inhibitors including quizartinib (AC220), midostaurin (PKC412) and gilteritinib (ASP2215) have been developed and undergone clinical testing for the treatment of AML. However, patients frequently relapse due to intrinsic and extrinsic resistance to these FLT3 inhibitors in spite of the initial clinical efficacy. We have developed a potent third-generation FLT3 inhibitor, PHI-101, capable of overcoming some of these mechanisms of resistance. Methods: Biochemical kinase assays for PHI-101 have been performed on 9 different FLT3 mutants and wild type FLT3. Cellular potencies of PHI-101 have also been assessed using various patient-derived AML cells as well as MV4-11, MOLM14 and BaF3 cell lines transformed with human FLT3 mutants including single mutations [FLT3(ITD), FLT3(D835Y)], double or triple mutations [FLT3(ITD/D835Y), FLT3(ITD/F691L), FLT3(ITD/F691L/D835Y)]. In order to evaluate in vivo efficacies of oral administration of PHI-101, xenograft mouse models and in vivo bioluminescence imaging have been utilized. Results: PHI-101 possessed excellent enzymatic potencies against FLT3 potential resistant mutants such as ITD/D835V and the gatekeeper ITD/F691L mutation, as well as against FLT3 single activating mutants that include ITD, D835V, D835H, and D835Y. PHI-101 inhibited the phosphorylation of FLT3 and downstream STAT5 and ERK1/2 more effectively than quizartinib and gilteritinib at equivalent doses. Moreover, oral administration of PHI-101 induced tumor regression in the xenograft mouse models developed by injection of BaF3 cells transformed with FLT3-ITD, FLT3-TKD or FLT3-ITD/TKD mutants in a dose-dependent fashion with no appreciable toxicities. In luciferase-bearing blood circulating mouse models with FLT3-double mutants (ITD/D835Y and ITD/F691L) or triple mutants (ITD/D835Y/F691L), oral administration (30 mpk, QD) of PHI-101 diminished more than 89% of bioluminescent intensity and reduced leukemic burden. PHI-101 also showed increased efficacy in extending the lifespan of xenograft mice compared to quizartinib. PHI-101 strongly suppressed proliferation and induced apoptosis in primary AML samples harboring FLT3/ITD and FLT3/TKD mutations with little effect on wild-type FLT3 samples. Conclusion: PHI-101, an orally bioavailable novel small molecule, is a potent third-generation FLT3 inhibitor able to overcome resistance to several resistance mutations based on in vitro and in vivo experiments. PHI-101 possesses excellent in vitro and in vivo activities against not only FLT3 single activating mutations (ITD or TKD mutants) but also FLT3 double (ITD/D835Y or ITD/F691L) and triple (ITD/D835Y/F691L) resistant mutations with no pronounced toxicities. Preclinical evaluation of PHI-101 showed clear evidence of antileukemic activity and improved efficacy in both in vitro and in vivo models. PHI-101 is currently under investigation in first-in-human clinical trials with relapsed or refractory AML patients. Disclosures Nam: Pharos I&BT Co., Ltd.: Current equity holder in private company. Im:Pharos I&BT Co., Ltd.: Current Employment. Han:Pharos I&BT Co., Ltd.: Current equity holder in private company. Kim:Pharos I&BT Co., Ltd.: Current Employment. Yoon:Pharos I&BT Co., Ltd.: Current equity holder in private company. Cho:Pharos I&BT Co., Ltd.: Research Funding. Choi:Pharos I&BT Co., Ltd.: Research Funding. Young:Pharos I&BT Co., Ltd.: Research Funding. Nguyen:Pharos I&BT Co., Ltd.: Research Funding. Zhu:Pharos I&BT Co., Ltd.: Research Funding. Li:Pharos I&BT Co., Ltd.: Research Funding. Small:Pharos I&BT Co., Ltd.: Consultancy, Research Funding. Sim:Pharos I&BT Co., Ltd.: Research Funding.