Spontaneous Extradural Hematoma in a Sickle Cell Anemia Patient with Hyperinflammation and Thrombotic Microangiopathy Successfully Treated with Eculizumab: A Case Report and Review of the Literature.

BACKGROUND: The event of extradural hematoma in the absence of head trauma is a rare central nervous system complication of sickle cell disease. We report here a case of spontaneous extradural hematoma in a patient being treated for sickle cell vasoocclusive crisis complicated by hyperinflammation and thrombotic microangiopathy. The significance of inflammation as an integral component of the pathomechanism of vasoocclusive crisis in patients with sickle cell disease and the role of heme in activating the complement system's alternative pathway are highlighted in this case report. CASE PRESENTATION: A teenage patient with sickle cell disease developed a spontaneous right parietal extradural hematoma while receiving treatment for sickle cell vasoocclusive crisis. The concurrent events of hyperinflammation, disseminated intravascular coagulation, hyperhemolysis syndrome, thrombotic microangiopathy, and refractory postoperative bleeding complicated this patient's clinical course after surgical evacuation of extradural hematoma. This patient was subsequently treated with eculizumab and improved in the days following. CONCLUSION: Treatment with the anti-C5 monoclonal antibody eculizumab, which targets and inhibits terminal complement system activation, reversed the deleterious cascade of events in this patient with sickle cell disease.

The utility of plasma circulating cell-free messenger RNA as a biomarker of glioma: a pilot study.

BACKGROUND: Research into the potential utility of plasma-derived circulating cell-free nucleic acids as non-invasive adjuncts to radiological imaging have been occasioned by the invasive nature of brain tumour biopsy. The objective of this study was to determine whether significant differences exist in the plasma transcriptomic profile of glioma patients relative to differences in their tumour characteristics, and also whether any observed differences were representative of synchronously obtained glioma samples and TCGA glioma-derived RNA. METHODS: Blood samples were collected from twenty glioma patients prior to tumour resection. Plasma ccfmRNAs and glioma-derived RNA were extracted and profiled. RESULTS: BCL2L1, GZMB, HLA-A, IRF1, MYD88, TLR2, and TP53 genes were significantly over-expressed in glioma patients (p < 0.001, versus control). GZMB and HLA-A genes were significantly over-expressed in high-grade glioma patients (p < 0.001, versus low-grade glioma patients). Moreover, the fold change of the BCL2L1 gene was observed to be higher in patients with high-grade glioma (p = 0.022, versus low-grade glioma patients). There was positive correlation between the magnitude of fold change of differentially expressed genes in plasma- and glioma-derived RNA (Spearman r = 0.6344, n = 14, p = 0.017), and with the mean FPKM in TCGA glioma-derived RNA samples (Spearman r = 0.4614, n = 19, p < 0.05). There was positive correlation between glioma radiographic tumour burden and the magnitude of fold change of the CSF3 gene (r = 0.9813, n = 20, p < 0.001). CONCLUSION: We identified significant differential expression of genes involved in cancer inflammation and immunity crosstalk among patients with different glioma grades, and there was positive correlation between their transcriptomic profile in plasma and tumour samples, and with TCGA glioma-derived RNA.

Plasma circulating cell free messenger RNA as a potential biomarker of melanoma.

BACKGROUND: Blood borne cell free nucleic acids are increasingly emerging as significant non-invasive adjuncts to current methods of disease status evaluation in cancer patients. In this study, we sought to examine whether significant differences exist in the plasma transcriptomic profile of advanced melanoma patients with a high disease burden compared to patients with a low disease burden or therapeutic response. METHODS: Pathway focussed gene expression analysis was performed using cDNA derived from the plasma circulating cell free messenger ribonucleic acid (ccfmRNA) samples of twenty-two patients with advanced melanoma. Patients were assessed with paired blood sample collection and CT scan assessments at baseline and at 3 months follow up. RESULTS: We identified several genes which were significantly over-expressed in patients with a low disease burden or therapeutic response; BCL2L1, CXCL9, IDO1, IL13, MIF, MYD88 and TLR4 (p ≤ 0.001, versus high disease burden). There was an increase in the magnitude of fold change (2^ (-dd CT)) of BCL2L1 (p = 0.031), CCL4 (p = 0.001), CCL5 (p = 0.043), CXCL9 (p = 0.012), GZMB (p = 0.023) and TNFSF10 (p = 0.039) genes in patients with therapeutic response at 3 months follow up assessment relative to baseline assessment. Moreover, in stage IV melanoma patients with brain metastases, CCL18, CCR1, CCR4, CD274, CSF2, EGF, and PTGS2 genes were significantly over-expressed (p < 0.001, versus patients without melanoma brain metastasis). CONCLUSION: Significant differences were observed in the plasma transcriptomic profile between the various melanoma patient groups, and we postulate that these differences may be exploited to identify novel therapeutic targets or biomarkers relevant to melanoma.