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This study investigated the incidence rate and features of vascular adverse events (VAEs) in Japanese patients with chronic myeloid leukemia (CML) who were treated with tyrosine kinase inhibitors (TKIs). The analysis included 369 CML patients in the chronic or accelerated phases, selected from the CML Cooperative Study Group database; 25 events in 23 (6.2%) of these patients were VAEs. At the time of VAE incidence, nine patients were on treatment with imatinib, 12 with nilotinib, three with dasatinib, and one with bosutinib. VAE incidence comprised 13 cases of ischemic heart disease (IHD), eight of cerebral infarction (CI), and four of peripheral arterial occlusive disease (PAOD). IHD incidence rate in the study population was higher than that in the age-matched general population, particularly in nilotinib-treated patients, while CI incidence rate was almost equivalent. Compared with the Suita score, the SCORE chart and the Framingham score risk assessment tools detected more patients with high or very high risk of VAEs. In conclusion, incidence of IHD requires closer monitoring in nilotinib-treated patients. More detailed investigations for determining the most useful tool to predict VAE incidence and long-term analysis of therapy-related VAE cases are needed for improving safety during TKI therapy. [ABSTRACT FROM AUTHOR]

Objective: The use of tyrosine kinase inhibitors led to an improvement in the prognoses of patients with chronic myeloid leukemia (CML). The aims of this study were to investigate the efficacy and safety of dasatinib in Japanese patients and to explore the factors that affect the achievement of molecular responses. Methods: The primary endpoint was a major molecular response (MMR) by 12 months. The halving time for BCR-ABL1 transcripts was calculated using transcript levels. Results: Thirty-two patients with chronic-phase CML (CML-CP) were enrolled and 30 received 100 mg dasatinib once daily. At 24 months of follow-up, 21 (72%) and 24 (83%) patients achieved an MMR by 12 and 24 months, respectively; the rates of a deep molecular response (DMR) by 12 and 24 months were 48 and 59%, respectively. A shorter halving time of BCR-ABL1 transcripts (≤10.6 days) accurately predicted both an MMR and a DMR. The incidence of pleural effusion was 50%. Our study reconfirmed the efficacy and safety of dasatinib treatment in Japanese patients with newly diagnosed CML-CP. In addition, the usefulness of the halving time of BCR-ABL1 transcripts was validated. Conclusion: These data emphasize the significance of an early treatment response in achieving a DMR during dasatinib therapy. [ABSTRACT FROM AUTHOR]

The development of distance learning courses for less commonly taught languages (LCTLs) oftenmeets with instructional challenges, especially for Asian LCTLs with their distinct non-Roman characters and structures. This study documents the implementation of a fully online, elementary Japanese course at Stony Brook University. The curriculum was designed around the American Council on the Teaching of Foreign Languages's (ACTFL)World-Readiness Standards for Learning Languages; performance-driven assessments; and task-supported, technology-enhanced principles. Asynchronous and synchronous tools were incorporated to facilitate task delivery and reduce the virtual isolation of learners. A simulated Oral Proficiency Interview (OPI) was conducted for the online students in order to compare their oral performance with that of the face-to-face (F2F) cohort in the preceding semester. Quantitative results show that online students outperformed their F2F counterparts in most of the Integrated Performance Assessment's scoring criteria, with a statistically significant difference in the criterion "Communication strategies." Survey results indicate students' positive attitudes toward language gains and corroborate the qualitative results gleaned from student learning journals and survey responses: Students' sense of isolation was replaced by a sense of co-presence. We conclude that developing an online LCTL course, though challenging, is feasible and maximizes outcomes through the synergy of multimodal digital platforms, and a standards-based, task-driven curriculum design. [ABSTRACT FROM AUTHOR]

The European Treatment and Outcome Study (EUTOS) long-term survival (ELTS) score predicts disease-specific death in patients with chronic myeloid leukemia (CML) being treated with imatinib during the chronic phase (CP) of the disease. However, it is unclear whether the ELTS score predicts CML-related events or treatment responses. This study evaluated the predictive value of the ELTS score regarding prognosis and treatment response in patients with CML-CP. Clinical data were retrospectively obtained from patients enrolled in the CML Cooperative Study Group (CML-CSG), which included patients diagnosed with CML-CP from April 2001 to January 2016, and treated with any tyrosine kinase inhibitor (TKI) as first-line therapy. Among 342 eligible patients, the ELTS scores indicated low-, intermediate-, and high-risk in 74%, 21%, and 5% of patients, respectively. Patients with high ELTS scores had significantly higher disease-specific mortality and worse event-free survival, progression-free survival, and overall survival. Among four risk scores, including the Sokal, Hasford, EUTOS, and ELTS scores, risk stratification by the ELTS score had the highest predictive value in assessing patient prognosis, and also in treatment responses. In fact, the EUTOS and ELTS scores were able to predict the major molecular response within 12 months. Most importantly, the ELTS score was the only scoring system that predicted deep molecular response at any time, regardless of risk level (65.0%, 43.7%, and 23.5% in low-, intermediate-, and high-risk groups, respectively). Compared to other risk scores, the ELTS score was the most sensitive risk classification tool for the four endpoints of interest in this study, as well as molecular responses in patients with CML-CP., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Catch connective tissue of echinoderms at rest (in the standard state) either stiffens or softens in response to different kinds of stimulation. The energy consumption associated with the changes was estimated by measurement of the oxygen consumption rate (VO(2)) in three types of connective tissues-echinoid catch apparatus (CA), holothuroid body-wall dermis (HD), and asteroid body-wall dermis (AD). Mechanical stimulation by repetitive compression (10%-15% strain), which increased viscosity measured by creep tests, was employed for inducing the stiff state. Noradrenaline (10(-3) mol l(-1)), which decreased viscosity of CA, and static 80% compressive strain, which decreased viscosity of HD, were used to induce the soft state in the respective tissues. The VO(2) (in μl/g/h) values of the standard state were 2.91 (CA), 1.41 (HD), and 0.56 (AD), which were less than 1/4 of the VO(2) of the resting body-wall muscle of the starfish. The VO(2) of the stiff state was about 1.5 times greater than that of the standard state in all types of connective tissues. The VO(2) of the soft state was 3.4 (CA)-9.1 (HD) times greater than that of the standard state. The economical nature of catch connective tissue in posture maintenance is discussed.

Neoplasms putatively originating from precursor and mature natural killer (NK) cells are rare, and their clinical features are unclear. A nationwide survey was performed in Japan to clarify the clinical features of these neoplasms diagnosed between 1994 and 1998, and data for 237 patients who met the criteria for putative NK cell-lineage neoplasms were analyzed. Among them, 11 had myeloid/NK-cell precursor acute leukemia, 15 blastic NK-cell lymphoma, 21 precursor NK-cell acute lymphoblastic leukemia, 22 aggressive NK-cell leukemia/lymphoma, 149 nasal-type NK-cell lymphoma (123 nasal and 26 extranasal) and 19 chronic NK lymphocytosis. The median overall survival time of patients with aggressive NK-cell leukemia/lymphoma was 2 months, which for chronic NK lymphocytosis was more than 8 years, and that for the other types of NK-cell neoplasms was between 6 and 22 months. Nasal NK-cell lymphoma and extranasal NK-cell lymphoma share the same histology. The age of affliction was the same, but the sex was different with males predominantly having nasal NK-cell lymphoma and females extranasal NK-cell lymphoma. Patients with extranasal NK-cell lymphoma had the tendency to exhibit a more advanced state of disease, with significantly higher International Prognostic Index and LDH levels, and significantly lower hemoglobin and platelet levels. The overall survival, however, did not differ significantly. Precursor NK-cell acute lymphoblastic leukemia and blastic NK-cell lymphoma were arbitrarily defined by the presence or absence of 30% or more of blastic cells in the bone marrow or peripheral blood, but there were no significant differences for affected age, gender, involved sites or prognosis. Aggressive NK-cell leukemia/lymphoma and extranasal NK-cell lymphoma were arbitrarily defined by the presence or absence of 30% or more of large granular lymphocytes in the bone marrow or peripheral blood and it is possible that aggressive NK-cell leukemia/lymphoma is a leukemic phase of extranasal NK-cell lymphoma. The incidence of skin involvement, however, was significantly higher for extranasal NK-cell lymphoma, suggesting that the two diseases are different. In nasal NK-cell lymphoma, Epstein-Barr virus in tumor cells was detected in all patients tested, suggesting its causative role.