Incidence of Invasive Fungal Infections in Acute Myeloid Leukemia Without Antifungal Prophylaxis.

BACKGROUND: Antifungal prophylaxis during induction for acute myeloid leukemia (AML) varies according to local rates of invasive fungal infections (IFIs). We evaluated fluconazole prophylaxis and no antifungal prophylaxis, as a natural interrupted time-series study to assess survival and infection complications. PATIENTS AND METHODS: We identified patients with AML ≥ 18 years old undergoing induction chemotherapy during 2 time periods: period 1, fluconazole prophylaxis from August 1, 2013 to September 30, 2015, and period 2, no prophylaxis from October 1, 2015 to December 31, 2017. The primary outcome was incidence of proven or probable IFI. Secondary outcomes included types of IFIs and 60-day overall survival (OS). IFI was defined by the 2002 European Organization for Research and Treatment of Cancer/Mycoses Study Group Consensus criteria. RESULTS: One hundred forty-four patients received induction chemotherapy over the 2 time periods. In the prophylaxis versus no-prophylaxis groups, the rate of proven or probable IFIs was 4 (5%) of 87 versus 12 (21%) of 57 (P = .01). The total number of proven IFIs was 3 (3%) of 87 versus 4 (7%) of 57 (P = .44), whereas probable IFIs were 1 (1%) of 87 versus 8 (14%) of 57 (P < .01). No difference was observed in fungemia. Incidence of IFIs was too low to detect resistance patterns. OS at 60 days was improved in with fluconazole prophylaxis compared with no prophylaxis (hazard ratio, 0.329; 95% confidence interval, 0.12-0.89; P = .028). CONCLUSION: Observed rates of proven or probable IFI were lower in the fluconazole prophylaxis group versus the no-prophylaxis group. Sixty-day OS was higher with fluconazole prophylaxis. Further study is required to evaluate how fluconazole may impart the differences in survival seen in this analysis.

Successful Management of Cryptococcal Meningitis and Bone Marrow Infiltration in a Young HIV/AIDS Patient: A Case Report and Review of the Literature.

Bone marrow cryptococcosis has been rarely reported in the literature, and there are no established treatment guidelines specific to this AIDS-related complication. The recommended treatment for AIDS-related invasive fungal treatments include amphotericin B and flucytosine which are associated with an array of complications making optimal treatment recommendations difficult. This case presentation represents an example of a patient with newly diagnosed AIDS and bone marrow cryptococcosis, which was successfully managed with an antifungal regimen adjusted to her comorbidities.

Acute myeloid leukemia in a patient with constitutional 47,XXY karyotype.

Klinefelter syndrome (KS), a 47,XXY chromosomal abnormality, has been shown to be associated with a number of malignancies, but has not been linked to acute leukemias to date. We present a case of a 54-year-old male diagnosed with acute myeloid leukemia (AML) with monocytic differentiation, whose cytogenetic and subsequent FISH analyses revealed a constitutional 47,XXY karyotype. We also review and discuss relevant prior literature.

Neuroprotective and anti-inflammatory properties of a coffee component in the MPTP model of Parkinson's disease.

Consumption of coffee is associated with reduced risk of Parkinson's disease (PD), an effect that has largely been attributed to caffeine. However, coffee contains numerous components that may also be neuroprotective. One of these compounds is eicosanoyl-5-hydroxytryptamide (EHT), which ameliorates the phenotype of α-synuclein transgenic mice associated with decreased protein aggregation and phosphorylation, improved neuronal integrity and reduced neuroinflammation. Here, we sought to investigate if EHT has an effect in the MPTP model of PD. Mice fed a diet containing EHT for four weeks exhibited dose-dependent preservation of nigral dopaminergic neurons following MPTP challenge compared to animals given control feed. Reductions in striatal dopamine and tyrosine hydroxylase content were also less pronounced with EHT treatment. The neuroinflammatory response to MPTP was markedly attenuated, and indices of oxidative stress and JNK activation were significantly prevented with EHT. In cultured primary microglia and astrocytes, EHT had a direct anti-inflammatory effect demonstrated by repression of lipopolysaccharide-induced NFκB activation, iNOS induction, and nitric oxide production. EHT also exhibited a robust anti-oxidant activity in vitro. Additionally, in SH-SY5Y cells, MPP(+)-induced demethylation of phosphoprotein phosphatase 2A (PP2A), the master regulator of the cellular phosphoregulatory network, and cytotoxicity were ameliorated by EHT. These findings indicate that the neuroprotective effect of EHT against MPTP is through several mechanisms including its anti-inflammatory and antioxidant activities as well as its ability to modulate the methylation and hence activity of PP2A. Our data, therefore, reveal a strong beneficial effect of a novel component of coffee in multiple endpoints relevant to PD.