A combination of hemolysis, elevated liver enzymes, and low platelets-the HELLP syndrome-is one of the most severe forms of preeclampsia and one for which no definitive treatment is available. The use of corticosteroids has been proposed because of their ability to reduce platelet adhesion, limit platelet removal by the spleen, activate platelets, and exert a direct effect on the endothelium.In this prospective, randomized, double-blind, placebo-controlled trial,105 women with HELLP syndrome in the postpartum period were assigned to receive either 10 mg of dexamethasone or placebo solution by intravenous injection every 12 hours over 4 days. In addition, all patients received magnesium sulfate to prevent or treat eclamptic convulsions, and captopril to control hypertensive peaks exceeding 180 mm Hg systolic and/or 120 mm Hg diastolic.Baseline characteristics were similar in the 56 women given dexamethasone and the 49 receiving placebo. Complication rates also were similar in the 2 groups. Oliguria was the most frequent complication, followed by hemorrhage at a variety of sites. Acute renal failure occurred in 16% of steroid-treated women and 24.5% of the control group. The respective figures for acute pulmonary edema were 3.6% and 10.2%. No significant differences in either maternal morbidity or mortality were observed. Two steroid-treated patients (3.6%) and 2 placebo recipients (4.1%) died. The groups also were comparable with respect to time in hospital and the need for blood products. There were no significant group differences in the pattern of platelet recovery, levels of aspartate aminotransferase or lactate dehydrogenase, hemoglobin, or diuresis.The investigators conclude that these findings fail to support the routine use of dexamethasone following childbirth in women with HELLP syndrome.
The epigenome offers an additional facet of cancer that can help categorize patients into those at risk of disease, recurrence, or treatment failure. We conducted a retrospective, nested, case-control study of advanced and recurrent high-grade serous ovarian cancer (HGSOC) patients in which we assessed epigenome-wide association using Illumina methylationEPIC arrays to characterize DNA methylation status and RNAseq to evaluate gene expression. Comparing HGSOC tumors with normal fallopian tube tissues we observe global hypomethylation but with skewing towards hypermethylation when interrogating gene promoters. In total, 5,852 gene interrogating probes revealed significantly different methylation. Within HGSOC, 57 probes highlighting 17 genes displayed significant differential DNA methylation between primary and recurrent disease. Between optimal vs suboptimal surgical outcomes 99 probes displayed significantly different methylation but only 29 genes showed an inverse correlation between methylation status and gene expression. Overall, differentially methylated genes point to several pathways including RAS as well as hippo signaling in normal vs primary HGSOC; valine, leucine, and isoleucine degradation and endocytosis in primary vs recurrent HGSOC; and pathways containing immune driver genes in optimal vs suboptimal surgical outcomes. Thus, differential DNA methylation identified numerous genes that could serve as potential biomarkers and/or therapeutic targets in HGSOC.
Background-Chemoresistance and metastasis are the main reasons for the failure of current treatments with sarcoma patients. Novel biomarkers are required to predict metastasis and response to treatment. The oncogene MTDH/AEG1 and the long noncoding RNA (lincRNA) HOTAIR are two novel factors involved in drug resistance and metastasis in various types of solid tumors. However, the correlation between MTDH/AEG-1 and HOTAIR expression with metastasis and drug resistance in sarcoma is unknown.
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