The Immuno-Oncology and Genomic Aspects of DNA-Hypomethylating Therapeutics in Acute Myeloid Leukemia.

Hypomethylating agents (HMAs) have been used for decades in the treatment of hematologic neoplasms, and now, have gathered attention again in terms of their combination with potent molecular-targeted agents such as a BCL-6 inhibitor venetoclax and an IDH1 inhibitor ivosidenib, as well as a novel immune-checkpoint inhibitor (anit-CD47 antibody) megrolimab. Several studies have shown that leukemic cells have a distinct immunological microenvironment, which is at least partially due to genetic alterations such as the TP53 mutation and epigenetic dysregulation. HMAs possibly improve intrinsic anti-leukemic immunity and sensitivity to immune therapies such as PD-1/PD-L1 inhibitors and anti-CD47 agents. This review describes the immuno-oncological backgrounds of the leukemic microenvironment and the therapeutic mechanisms of HMAs, as well as current clinical trials of HMAs and/or venetoclax-based combination therapies.

[Combined intrathecal morphine and bupivacaine for elective post-caesarean pain].

BACKGROUND: Intrathecal morphine is widely used for analgesia following cesarean section in Europe and North America. In Japan analgesic method of intrathecal morphine was admitted to the insurance adjustment and it is necessary to study optimal dose of the morphine. METHODS: We examined 72 parturients undergoing elective cesarean section under spinal anesthesia. Patients were randomly assigned to receive, in a double-blind fashion, either morphine 0.05 mg, morphine 0.1 mg, morphine 0.2 mg, or saline in 0.1 ml (control group) mixed with the bupivacaine for cesarean section. A patient-controlled analgesia (PCA) device for intravenous morphine provided free access to additional analgesics for 24 hr. RESULTS: Total amount of morphine during postoperative first 24 hrs using PCA was significantly higher in the control group than in 0.1 and 0.2 mg groups. There were no significant differences between the control group and the morphine groups with respect to nausea. The incidence of pruritus was significantly higher in 0.1 and 0.2 mg groups than in the control group. In one patient in 0.2 mg group, oxygen saturation decreased below 95% postoperatively, but it was improved by oxygen inhalation. CONCLUSIONS: It is concluded that intrathecal morphine 0.1 mg gives effective analgesia with minimum side effects after cesarean section for the Japanese patients.

[Incidence and onset time of fentanyl-induced cough depends on the dose of IV fentanyl].

BACKGROUND: IV fentanyl en bolus can provoke cough reflex. We evaluated the effects of the IV fentanyl dose on the incidence and onset time of fentanyl-induced cough. METHODS: Tree hundred and eighteen ASA physical status I - II patients scheduled for oral surgery under general anesthesia were randomly assigned to receive 1 microg x kg(-1), 3 microg x kg(-1) or 5 microg x kg(-1) of IV fentanyl (n = 106 for each group). We recorded, in each patient, presence/absence and onset time, if present, of cough reflex for 60 seconds after fentanyl injection. RESULTS: The incidences of fentanyl-induced cough were 6.6%, 22.5%, and 44.3% in the 1 microg x kg(-1), 3 microg x kg(-1), and 5 microg x kg(-1) groups, respectively. The onset times of fentanyl-induced cough were 29.0 +/- 11.8 seconds, 22.5 +/- 7.9 seconds, and 19.5 +/- 7.0 seconds in the 1 microg x kg(-1), 3 microg x kg(-1), and 5 microg x kg(-1) groups, respectively. CONCLUSIONS: The results indicated that the incidence of fentanyl-induced cough increased, and the onset time decreased, with the increasing dose of fentanyl.