Risk factors for intracranial hemorrhage in adults with acute leukemia.

BACKGROUND: Intracranial hemorrhage (ICH) is a rare, but serious complication in patients with acute leukemia. Little is known about why some patients experience serious bleeding, including ICH, while others do not. MATERIALS AND METHODS: Adults between 18 and 80 years old with acute leukemia and ICH between January 1, 2009 and December 31, 2016 were included. Matched controls were identified using the propensity score matching method. Clinical and laboratory characteristics and outcome data were collected to identify variables associated with ICH. RESULTS: Of 2578 patients diagnosed with acute leukemia during the study period, 55 cases and 161 matched controls were included. Patients who experienced ICH were older (62 vs. 55 years, p = .004) and more likely to have diabetes mellitus (p = .04). Patients with ICH had a higher baseline white blood cell count (mean 84.5 ± 115.8 vs. 28.7 ± 58.5 × 109 /L, p = .001), peripheral blast count (61.3 ± 96.5 vs. 21.2 ± 50.8 × 109 /L, p = .004), and a longer PT (16.5 ± 2.06 vs. 15.3 ± 3.2 s, p = .002). Neither the platelet count at diagnosis, the platelet nadir, the number of days with a platelet count of less than 10 × 109 /L, or a diagnosis of platelet refractoriness were associated with ICH. CONCLUSIONS: Older age and more proliferative disease appear to be associated with ICH, whereas thrombocytopenia alone does not. In patients with newly diagnosed acute leukemia, aggressive cytoreduction in those with leukocytosis may help mitigate the risk of ICH.

Acute simvastatin increases endothelial nitric oxide synthase phosphorylation via AMP-activated protein kinase and reduces contractility of isolated rat mesenteric resistance arteries.

Statins can have beneficial cholesterol-independent effects on vascular contractility, which may involve increases in the bioavailability of NO (nitric oxide) as a result of phosphorylation of eNOS (endothelial NO synthase). Although this has been attributed to phosphorylation of Akt (also known as protein kinase B), studies in cultured cells have shown that statins can phosphorylate AMPK (AMP-activated protein kinase); it is unknown whether this has functional effects in intact arteries. Thus we investigated the acute effects of simvastatin on resistance arterial contractile function, evaluating the involvement of NO, Akt and AMPK. Isolated rat mesenteric resistance arteries were mounted on a wire myograph. The effects of incubation (1 and 2 h) with simvastatin (0.1 or 1 µM) on contractile responses were examined in the presence and absence of L-NNA (N-nitro-L-arginine; 10 µM) or mevalonate (1 mM). Effects on eNOS, phospho-eNOS (Ser1177), and total and phospho-Akt and -AMPK protein expression were investigated using Western blotting. The effect of AMPK inhibition (compound C, 10 µM) on eNOS phosphorylation and contractile responses were also studied. Simvastatin (1 µM, 2 h) significantly reduced constriction to U46619 and phenylephrine and enhanced dilations to ACh (acetylcholine) in depolarized, but not in U46619-pre-constricted arteries. These effects were completely and partially prevented by L-NNA and mevalonate respectively. Simvastatin increased eNOS and AMPKα phosphorylation, but had no effect on Akt protein expression and phosphorylation after 2 h incubation. Compound C prevented the effects of simvastatin on eNOS phosphorylation and contractility. Thus simvastain can acutely modulate resistance arterial contractile function via mechanisms that involve the AMPK/phospho-eNOS (Ser1177)/NO-dependent pathway.

Socio-Demographic Characteristics and Patterns of Substance Use Disorder in Oman: A retrospective study of the National Registry Surveillance Programme between 2004 and 2018.

OBJECTIVES: Substance use disorder is a global challenge. Therefore, this study aimed to provide an updated view of socio-demographic characteristics and patterns of substance use in Oman. METHODS: This retrospective descriptive study was conducted between 2004 and 2018. Data were retrieved from Oman's National Drug Addict Registry. The data collected included the socio-demographic characteristics of registered cases, the proportion of various psychoactive substances' consumption and their routes of administration, the associated sociodemographic determinants as well as comorbid conditions. RESULTS: A total of 6,453 cases were registered during the study's timeframe. The majority of which were Omani (97.9%), male (98.7%), single (57.9%), unemployed (50.2%), had an education level below university (81.0%) and were adolescents and young adults (77.0%). Opiates were the most common substance used (66.6%) and more than half of the sample were polydrug users (51.0%). Injecting-drug users constituted 53.4% of the total registered cases. The proportion of people with hepatitis virus C, hepatits virus B and HIV among the registered cases were 46.9%, 5.1% and 3.7%, respectively. CONCLUSION: The findings are in favour of rapidly escalating the introduction of a substance use preventive programme at all school levels as well as making opioid substitution therapy and other harm reduction programmes available in Oman.