Hepatitis E Virus infection in HIV-infected patients with elevated serum transaminases levels

Increases in aminotransferases levels are frequently encountered in HIV-positive patients and often remain unexplained. The role in this setting and natural history of hepatitis E in HIV-infected patients are unknown. The aim of the study was to assess HEV infection in HIV-infected patients attending a Parisian hospital, with a current or previous cryptogenic hepatitis.191 plasma samples collected from 108 HIV-infected patients with elevated aminotransferases levels were retrospectively tested for the presence of hepatitis E virus (HEV) infection markers: anti-HEV IgM antibodies, anti-HEV IgG antibodies, anti-HEV IgG avidity index and plasma HEV RNA.One acute infection, documented by positive tests for anti-HEV IgM antibody, low anti-HEV IgG avidity index and plasma HEV RNA (genotype 3e), and three past infections were diagnosed, without any observed case of persistent infection. The acute hepatitis was benign and resolved spontaneously within two weeks. This infection was probably contracted locally. Acute HEV hepatitis can occur in HIV-infected patients but rarely explains cryptogenic hepatitis, at least in an urban HIV population, regardless geographic origin and CD4 counts

DGKI Methylation Status Modulates the Prognostic Value of MGMT in Glioblastoma Patients Treated with Combined Radio-Chemotherapy with Temozolomide

International audienceBackgroundConsistently reported prognostic factors for glioblastoma (GBM) are age, extent of surgery, performance status, IDH1 mutational status, and MGMT promoter methylation status. We aimed to integrate biological and clinical prognostic factors into a nomogram intended to predict the survival time of an individual GBM patient treated with a standard regimen. In a previous study we showed that the methylation status of the DGKI promoter identified patients with MGMT-methylated tumors that responded poorly to the standard regimen. We further evaluated the potential prognostic value of DGKI methylation status.Methods399 patients with newly diagnosed GBM and treated with a standard regimen were retrospectively included in this study. Survival modelling was performed on two patient populations: intention-to-treat population of all included patients (population 1) and MGMT-methylated patients (population 2). Cox proportional hazard models were fitted to identify the main prognostic factors. A nomogram was developed for population 1. The prognostic value of DGKI promoter methylation status was evaluated on population 1 and population 2.ResultsThe nomogram-based stratification of the cohort identified two risk groups (high/low) with significantly different median survival. We validated the prognostic value of DGKI methylation status for MGMT-methylated patients. We also demonstrated that the DGKI methylation status identified 22% of poorly responding patients in the low-risk group defined by the nomogram.ConclusionsOur results improve the conventional MGMT stratification of GBM patients receiving standard treatment. These results could help the interpretation of published or ongoing clinical trial outcomes and refine patient recruitment in the future

Anaplastic oligodendrogliomas with 1p19q codeletion have a proneural gene expression profile

<p>Abstract</p> <p>Background</p> <p>In high grade gliomas, 1p19q codeletion and <it>EGFR </it>amplification are mutually exclusive and predictive of dramatically different outcomes. We performed a microarray gene expression study of four high grade gliomas with 1p19q codeletion and nine with <it>EGFR </it>amplification, identified by CGH-array.</p> <p>Results</p> <p>The two groups of gliomas exhibited very different gene expression profiles and were consistently distinguished by unsupervised clustering analysis. One of the most striking differences was the expression of normal brain genes by oligodendrogliomas with 1p19q codeletion. These gliomas harbored a gene expression profile that partially resembled the gene expression of normal brain samples, whereas gliomas with <it>EGFR </it>amplification expressed many genes in common with glioblastoma cancer stem cells. The differences between the two types of gliomas and the expression of neuronal genes in gliomas with 1p19q codeletion were both validated in an independent series of 16 gliomas using real-time RT-PCR with a set of 22 genes differentiating the two groups of gliomas (<it>AKR1C3</it>, <it>ATOH8</it>, <it>BMP2</it>, <it>C20orf42</it>, <it>CCNB1</it>, <it>CDK2</it>, <it>CHI3L1</it>, <it>CTTNBP2</it>, <it>DCX, EGFR, GALNT13, GBP1, IGFBP2, IQGAP1, L1CAM, NCAM1, NOG, OLIG2, PDPN, PLAT, POSTN, RNF135</it>). Immunohistochemical study of the most differentially expressed neuronal gene, alpha-internexin, clearly differentiated the two groups of gliomas, with 1p19q codeletion gliomas showing specific staining in tumor cells.</p> <p>Conclusion</p> <p>These findings provide evidence for neuronal differentiation in oligodendrogliomas with 1p19q codeletion and support the hypothesis that the cell of origin for gliomas with 1p19q codeletion could be a bi-potential progenitor cell, able to give rise to both neurons and oligodendrocytes.</p

Cumulative incidence and risk factors for radiation induced leukoencephalopathy in high grade glioma long term survivors

The incidence and risk factors associated with radiation-induced leukoencephalopathy (RIL) in long-term survivors of high-grade glioma (HGG) are still poorly investigated. We performed a retrospective research in our institutional database for patients with supratentorial HGG treated with focal radiotherapy, having a progression-free overall survival > 30 months and available germline DNA. We reviewed MRI scans for signs of leukoencephalopathy on T2/FLAIR sequences, and medical records for information on cerebrovascular risk factors and neurological symptoms. We investigated a panel of candidate single nucleotide polymorphisms (SNPs) to assess genetic risk. Eighty-one HGG patients (18 grade IV and 63 grade III, 50M/31F) were included in the study. The median age at the time of radiotherapy was 48 years old (range 18–69). The median follow-up after the completion of radiotherapy was 79 months. A total of 44 patients (44/81, 54.3%) developed RIL during follow-up. Twenty-nine of the 44 patients developed consistent symptoms such as subcortical dementia (n = 28), gait disturbances (n = 12), and urinary incontinence (n = 9). The cumulative incidence of RIL was 21% at 12 months, 42% at 36 months, and 48% at 60 months. Age > 60 years, smoking, and the germline SNP rs2120825 (PPARg locus) were associated with an increased risk of RIL. Our study identified potential risk factors for the development of RIL (age, smoking, and the germline SNP rs2120825) and established the rationale for testing PPARg agonists in the prevention and management of late-delayed radiation-induced neurotoxicity

ASPM-associated stem cell proliferation is involved in malignant progression of gliomas and constitutes an attractive therapeutic target

<p>Abstract</p> <p>Background</p> <p>ASPM (<it>Abnormal Spindle-like Microcephaly associated</it>) over-expression was recently implicated in the development of malignant gliomas.</p> <p>Results</p> <p>To better characterize the involvement of ASPM in gliomas, we investigated the mRNA expression in 175 samples, including 8 WHO Grade II, 75 WHO Grade III and 92 WHO Grade IV tumors. <it>Aspm </it>expression was strongly correlated with tumor grade and increased at recurrence when compared to the initial lesion, whatever the initial grade of the primary tumor. ASPM expression also increased over serial passages in gliomaspheres <it>in vitro </it>and in mouse xenografts <it>in vivo</it>. Lentivirus-mediated shRNA silencing of ASPM resulted in dramatic proliferation arrest and cell death in two different gliomasphere models.</p> <p>Conclusion</p> <p>These data suggest that ASPM is involved in the malignant progression of gliomas, possibly through expansion of a cancer stem cell compartment, and is an attractive therapeutic target in glioblastoma multiforme.</p

Gynecologic oncology patients' satisfaction and symptom severity during palliative chemotherapy

BACKGROUND: Research on quality and satisfaction with care during palliative chemotherapy in oncology patients has been limited. The objective was to assess the association between patient's satisfaction with care and symptom severity and to evaluate test-retest of a satisfaction survey in this study population. METHODS: A prospective cohort of patients with recurrent gynecologic malignancies receiving chemotherapy were enrolled after a diagnosis of recurrent cancer. Patients completed the Quality of End-of-Life care and satisfaction with treatment scale (QUEST) once upon enrollment in an outpatient setting and again a week later. Patients also completed the Mini-Mental Status Exam, the Hospital Anxiety/Depression Scale, a symptom severity scale and a demographic survey. Student's t-test, correlation statistics and percent agreement were used for analysis. RESULTS: Data from 39 patients were analyzed. Mean (SD) quality of care summary score was 41.95 (2.75) for physicians and 42.23 (5.42) for nurses (maximum score was 45; p = 0.76 for difference in score between providers). Mean (SD) satisfaction of care summary score was 29.03 (1.92) for physicians and 29.28 (1.70) for nurses (maximum score was 30; p = 0.49 for difference between providers). Test-retest for 33 patients who completed both QUEST surveys had high percent agreement (74–100%), with the exception of the question regarding the provider arriving late (45 and 53%). There was no correlation between quality and satisfaction of care and symptom severity. Weakness was the most common symptom reported. Symptom severity correlated with depression (r = 0.577 p < 0.01). There was a trend towards a larger proportion of patients reporting pain who had three or more prior chemotherapy regimens (p = 0.075). Prior number of chemotherapy regimens or time since diagnosis was not correlated with symptom severity score. Anxiety and depression were correlated with each other (r = 0.711, p < 0.01). There was no difference in symptom severity score at enrollment between those patients who have since died (n = 19) versus those who are still alive. CONCLUSION: The QUEST Survey has test-retest reliability when used as a written instrument in an outpatient setting. However, there was no correlation between this measure and symptom severity. Patient evaluation of care may be more closely related to the interpersonal aspects of the health care provider relationship than it is to physical symptoms