Predictive factors of human cytomegalovirus reactivation in newly diagnosed glioblastoma patients treated with chemoradiotherapy.

The human cytomegalovirus (HCMV) is a ubiquitous herpes virus which infects 40 to 99% of the population. HCMV reactivation may occur in the context of immunosuppression and can induce significant morbidities. Several cases of HCMV infections or HCMV reactivation have thus been reported in glioblastoma (GBM) patients treated with radio(chemo)therapy. With the aim to identify the main risk factors associated with HCMV reactivation, we reviewed all patients treated for a newly diagnosed GBM in our institution from October 2013 to December 2015. Age, sex, Karnofsky performance status (KPS), absolute lymphocyte count (ALC), serological HCMV status, and steroid doses were recorded at the start and 1 month after the end of radiotherapy (RT). Within the 103 patients analyzed, 34 patients (33%) had an initial negative serology for HCMV, and none of them developed a seroconversion after treatment. Among patients with positive HCMV IgG (n = 69), 16 patients (23%) developed a viremia at one point during treatment. Age (> 60 years), steroid intake, and ALC (< 1500/mm3) before RT were correlated with HCMV reactivation. HCMV viremia was associated with neurological decline 1 month after chemoradiotherapy but progression-free survival was not impacted. A shorter overall survival was seen in these patients when compared with the others, but this could be biased by the older age in this subgroup. HCMV reactivation needs to be sought in case of a neurological decline during RT especially in older patients treated with steroids and low lymphocytes counts.

Feasibility of sub-dermal soft tissue deformation assessment using B-mode ultrasound for pressure ulcer prevention.

Pressure Ulcer (PU) prevention remains a main public health issue. The physio-pathology of this injury is not fully understood, and a satisfactory therapy is currently not available. Recently, several works suggested that mechanical strains are responsible of deformation-induced damage involved in the initiation of Deep Tissue Injury (DTI). A better assessment of the internal behavior could allow to enhance the modeling of the transmission of loads into the different structures composing the buttock. A few studies focused on the experimental in vivo buttock deformation quantification using Magnetic Resonance Imaging (MRI), but its use has important drawbacks. In clinical practice, ultrasound imaging is an accessible, low cost, and real-time technic to study the soft tissue. The objective of the present work was to show the feasibility of using B-mode ultrasound imaging for the quantification of localised soft-tissue strains of buttock tissues during sitting. An original protocol was designed, and the intra-operator reliability of the method was assessed. Digital Image Correlation was used to compute the displacement field of the soft tissue of the buttock during a full realistic loading while sitting. Reference data of the strains in the frontal and sagittal planes under the ischium were reported for a population of 7 healthy subjects. The average of shear strains over the region of interest in the fat layer reached levels up to 117% higher than the damage thresholds previously quantified for the muscular tissue in rats. In addition, the observation of the muscles displacements seems to confirm previous results which already reported the absence of muscular tissue under the ischium in the seated position, questioning the assumption commonly made in Finite Element modeling that deep tissue injury initiates in the muscle underlying the bone.

Neurological adverse events associated with immune checkpoint inhibitors: Review of the literature.

Immune checkpoint inhibitors (ICIs) targeting CTLA4 and PD1 constitute a promising class of cancer treatment but are associated with several immune-related disorders. We here review the literature reporting neurological adverse events (nAEs) associated with ICIs. A systematic search of literature, up to February 2016, mentioning nAEs in patients treated with ICIs was conducted. Eligible studies included case reports and prospective trials. One case seen in our ward was also added. Within the 59 clinical trials (totalling 9208 patients) analysed, the overall incidence of nAEs was 3.8% with anti-CTLA4 antibodies, 6.1% with anti-PD1 antibodies, and 12.0% with the combination of both. The clinical spectrum of neurological disorders was highly heterogeneous. Most of these nAEs were grade 1-2 and consisted of non-specific symptoms such as headache (55%). The incidence of high grade nAEs was below 1% for all types of treatment. Headaches, encephalopathies and meningitis were the most commonly reported (21%, 19% and 15%, respectively). Among the 27 case reports, the most common nAEs were encephalopathies, meningoradiculoneuritis, Guillain-Barré like syndromes and myasthenic syndromes. The median time of nAEs onset was 6 weeks. In most cases, drug interruption and steroids led to neurological recovery, even in conditions where steroids are not usually recommended such as Guillain-Barré syndrome.

Impact of renin-angiotensin system blockade on clinical outcome in glioblastoma.

BACKGROUND AND PURPOSE: Despite surgery, radiotherapy (RT) and temozolomide (TMZ), the prognosis of glioblastoma (GBM) patients remains dismal. Normally prescribed with the aim to lower blood pressure, angiotensin-II (Ang-II) inhibitors were reported to reduce angiogenesis and tumour growth in several tumour models including one glioma. Thus whether treatment with Ang-II inhibitors could be associated with a better clinical outcome in GBM patients was investigated. METHODS: A series of 81 consecutive patients, homogeneously treated with RT and TMZ for a newly diagnosed, supratentorial GBM, were analysed. The objective of this retrospective study was to assess the impact of angiotensin-converting enzyme inhibitors (ACEIs) and Ang-II receptor 1 blockers (ARBs) on functional independence, progression-free survival (PFS) and overall survival (OS). RESULTS: Amongst the 81 GBM patients analysed, 26 were already treated for high blood pressure (seven with ACEIs and 19 with ARBs). The number of patients who remained functionally independent at 6 months after RT was higher in the group of patients treated with Ang-II inhibitors compared to the other patients (85% vs. 56%, P = 0.01). In patients treated with Ang-II inhibitors, PFS was 8.7 months (vs. 7.2 months in the other patients) and OS was 16.7 months (vs. 12.9 months). The use of Ang-II inhibitors was a significant prognostic factor for both PFS (P = 0.04) and OS (P = 0.04) in multivariate analysis. CONCLUSION: Treatment with Ang-II inhibitors in combination with RT and TMZ might improve clinical outcome in GBMs. Prospective trials are needed to test this hypothesis.