Gemtuzumab Ozogamicin: Back Again.

Despite the recent onslaught of approved medications in oncology, acute myeloid leukemia (AML) has been a disease state bereft of pharmaceutical development for decades. The long-standing first-line regimen, 7 + 3, was developed in 1973. A group of four physicians at Roswell Park Memorial Institute built upon prior combinations of daunorubicin and cytarabine to find the optimal combination of 7 days of cytarabine and 3 days of daunorubicin (Lichtman, 2013). This regimen has undergone multiple modifications and patient performance status-based stratifications, but has remained the first-line therapy for AML for the past 45 years. In September 2017, gemtuzumab ozogamicin returned to market and shortly thereafter was added to the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for AML, to be administered in combination with 7 + 3, and as monotherapy for both newly diagnosed and relapsed patients with acute myeloid leukemia (NCCN, 2018; US Food & Drug Administration, 2017). Gemtuzumab ozogamicin continues to be explored in various leukemia settings and is a welcomed addition to the currently available treatment options for AML.

A role for cryptochromes in sleep regulation.

BACKGROUND: The cryptochrome 1 and 2 genes (cry1 and cry2) are necessary for the generation of circadian rhythms, as mice lacking both of these genes (cry1,2-/-) lack circadian rhythms. We studied sleep in cry1,2-/- mice under baseline conditions as well as under conditions of constant darkness and enforced wakefulness to determine whether cryptochromes influence sleep regulatory processes. RESULTS: Under all three conditions, cry1,2-/- mice exhibit the hallmarks of high non-REM sleep (NREMS) drive (i.e., increases in NREMS time, NREMS consolidation, and EEG delta power during NREMS). This unexpected phenotype was associated with elevated brain mRNA levels of period 1 and 2 (per1,2), and albumin d-binding protein (dbp), which are known to be transcriptionally inhibited by CRY1,2. To further examine the relationship between circadian genes and sleep homeostasis, we examined wild type mice and rats following sleep deprivation and found increased levels of per1,2 mRNA and decreased levels of dbp mRNA specifically in the cerebral cortex; these changes subsided with recovery sleep. The expression of per3, cry1,2, clock, npas2, bmal1, and casein-kinase-1epsilon did not change with sleep deprivation. CONCLUSIONS: These results indicate that mice lacking cryptochromes are not simply a genetic model of circadian arrhythmicity in rodents and functionally implicate cryptochromes in the homeostatic regulation of sleep.

Activity level during a one-hour labor check evaluation: walking versus bed rest.

PURPOSE: Determine if bed rest or walking during a 1-hour labor check evaluation affects progression to delivery. STUDY DESIGN: Randomized controlled trial. METHODS: Convenience sample of nulliparous full-term, low-risk women with an initial negative exam for active labor (cervical dilatation < 4 cm; intact membranes) were randomly assigned to bed rest or walking for 1 hour prior to reassessment. Cervical dilatation and comfort level were evaluated before and after 1 hour of bed rest or walking. For patients who delivered within 24 hours, time to delivery was documented. Data were analyzed with Student's t-test and c-test. Positive and negative predictive values were calculated for the 1-hour labor check evaluation as a screen for delivery within 24 hours (negative screen = no change in cervical dilatation after 1 hour; positive screen = ≥1 cm change in cervical dilatation after 1 hour). RESULTS: Sixty-three participants were studied before and after a 1-hour period of bed rest (n = 32) or walking (n = 31). No differences were found between the groups in changes of cervical dilatation, time to delivery, number of women delivering within 24 hours, or maternal comfort after the 1-hour labor check evaluation. Predictive values of the 1-hour labor check evaluation to determine delivery within 24 hours were 88.2% (positive predictive value) and 54.3% (negative predictive value). CLINICAL IMPLICATIONS: Cervical dilatation and time to delivery were similar for nulliparous, full-term, low-risk women regardless of activity level during a 1-hour, in-hospital labor check evaluation. The woman's preference can be used to determine activity level during a labor check evaluation. Positive 1-hour labor check evaluations were highly predictive of delivery within 24 hours. A negative 1-hour labor check evaluation, however, was not a good predictor of delivery within 24 hours.