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FLT3 tyrosine kinase inhibitors (TKIs) have clinical efficacy for patients with FLT3-mutated AML (acute myeloid leukemia), but their impact is limited by resistance in the setting of monotherapy and by tolerability problems when used in combination therapies. FF-10101 is a novel compound that covalently binds to a cysteine residue near the active site of FLT3, irreversibly inhibiting receptor signaling. It is effective against most FLT3 activating mutations, and, unlike other inhibitors, is minimally vulnerable to resistance induced by FLT3 ligand. We conducted a phase 1 dose escalation study of oral FF-10101 in patients with relapsed and/or refractory AML, the majority of whom harbored FLT3-activating mutations and/or had prior exposure to FLT3 inhibitors. Fifty-four participants enrolled in cohorts receiving doses ranging from 10 to 225 mg per day and 50 to 100 mg twice daily (BID). The dose limiting toxicities were diarrhea and QT prolongation. Among 40 response-evaluable participants, the composite complete response rate was 10%, and the overall response rate (including partial responses) was 12.5%, including patients who had progressed on gilteritinib. Overall, 56% of participants had prior exposure to FLT3 inhibitors. The recommended phase 2 dose was 75 mg BID. FF-10101 potentially represents a next-generation advance in the management of FLT3-mutated AML. This trial was registered at www.ClinicalTrials.gov as #NCT03194685.

To examine the association between demographic characteristics (i.e., gender, race, age, and years of experience), burnout, and nurses' intent to leave their jobs during the first wave of COVID‐19 in New Jersey. COVID‐19 has exacerbated burnout and intent to leave among acute care nurses. Nonetheless, little is known about demographic factors contributing to nurses' desire to leave their jobs. A cross‐sectional survey of actively licensed registered nurses who provided direct patient care in an acute care hospital in New Jersey during COVID‐19. Among 2760 nurses, those who reported burnout were 4.78 times more likely to report intent to leave their job within 1 year as compared to nurses who did not report burnout. Black RNs were 2.06 times more likely to report intent to leave as compared to White RNs. Older nurses (aged 40–49) were 36% less likely to report intent to leave as compared to younger nurses (aged 21–29). RNs with 30 years of experience or more were 58% less likely to report intent to leave as compared to RNs with less than 5 years of experience. In addition, Black RNs with 6–12 years of experience were 2.07 times more likely to report intent to leave as compared to White RNs with less than 5 years of experience. Nurses' intent to leave during the first wave of the pandemic was influenced by burnout, race, age, and years of experience. Based on the results of the current study, Black nurses were more likely to report intent to leave their job within 1 year as compared to White RNs. Nurses' intention to leave is one of the most important global issues facing the healthcare system. Findings of the current study demonstrate that burnout, race, age, and years of experience are significant predictors of nurses' intent to leave their jobs. Therefore, organizations should prioritize strategies to reduce burnout and create diverse and inclusive work environments. [ABSTRACT FROM AUTHOR]

Aim: To develop a framework for understanding the stress appraisal process among acute care nurses during the COVID‐19 pandemic. Design: A secondary analysis of open‐ended responses from a cross‐sectional survey of 3030 frontline, acute care nurses in New Jersey and the effect of burnout during the COVID‐19 pandemic. Methods: Lazarus and Folkman's transactional model of stress and coping guided the study. Thematic analysis was used to analyse 1607 open‐ended responses. Results: Nine themes emerged during the secondary appraisal of stress. Five themes contributed to distress and burnout including (1) high patient acuity with scarce resources, (2) constantly changing policies with inconsistent messaging, (3) insufficient PPE, (4) unprepared pandemic planning and (5) feeling undervalued. Four themes led to eustress and contributed to post‐traumatic growth including (1) team nursing to ensure sufficient resource allocation, (2) open channels of communication, (3) sense‐ of‐duty and (4) personal strength from new possibilities. Conclusion: The COVID‐19 pandemic was a traumatic event for patients and the nursing workforce. Internal and external demands placed on acute care nurses increased burnout, however, a subset of nurses with adequate support experienced personal growth. Implications for the Profession and/or Patient Care: Beyond mental health interventions for acute care nurses, organizational interventions such as reevaluation of emergency action plans to optimize resource allocation, and work environment strategies such as improved communication and decision‐making transparency are necessary. Impact: To better understand how frontline acute care nurses experienced stress during COVID‐19, a data‐informed framework was developed that included a primary and secondary appraisal of stress. Themes contributing to distress and burnout were identified, and themes leading to eustress and post‐traumatic growth were also identified. These findings can assist nurse leaders in optimizing strategies to reduce burnout and promote post‐traumatic growth in the post‐COVID years. Reporting Method: No patient or public contribution. [ABSTRACT FROM AUTHOR]

This author is an avid consumer of history and has a desire to open students to the endless supply of the riveting stories of men and women struggling to cope with a changing world. The fascination toward the people of the past is enthralling history, and students need to feel that same sense of wonder and love of history. To accomplish this goal, the author developed and used assignments that helped students to understand how history affects and is affected by individuals like themselves. These assignments gave students a sense of how social, political, and economic changes affect the individual, how choices made on the individual level can shape history, and how diverse Americans' experiences have been. The author believes that these teaching projects help students to connect the personal, professional, and political decisions that they are making today with the decisions of their forebears, allowing them to understand the consequences of action and inaction. Historical trends are not just impersonal chapter headings in a textbook, but are life-changing forces that have affected students and their families, and that still resonate today. Student assignments help them in understanding how historical forces continue to act upon their own lives and stimulate their curiosity to learn more about the people of the past.

Keywords: autophagy; oleandrin; autophagosome; mitochondria; pancreatic cancer; Nerium oleander; cardiac glycoside 354 Autophagic Cell Death of Human Pancreatic Tumor Cells Mediated by Oleandrin, a Lipid-Soluble Cardiac Glycoside SAGE Publications, Inc.200710.1177/1534735407309623 [...]