Prise en charge des patients porteurs de stimulateurs cardiaques ou défibrillateurs automatiques implantables traités par irradiation

An increasing number of patients with cardiac implantable electronic devices benefit from radiotherapy, warranting specific collaborative management between both radiation oncologists and cardiologists. Interactions between electromagnetic fields, secondary particles and cardiac implantable electronic devices may result in transient and reversible malfunctions with significant consequences depending on the underlying cardiac pathology and the level of patient's cardiac implantable electronic devices dependency. Numerous international guidelines on patients’ management have been proposed and all agree on a total cumulated dose limit at the battery of 5 Gy and on the need for an initial as well as repeated evaluation over time, up to 6 months after the last radiation. The analysis of the published data revealed relatively rare incidence of significant adverse events. The most recent international guidelines underline the feasibility and safety of radiotherapy for cardiac implantable electronic devices holders, with the need for systematic local protocol in all radiotherapy centers.     

Her2 a paradigm for targeted therapy

Fifteen percent of breast cancers overexpress Her2, a tyrosin-kinase receptor. Because of its prognosis and its incidence, several efforts have been done in the last years to better understand mechanisms of Her2 action. This led to the development of targeted therapies such as trastuzumab, monoclonal antibody directed against the Her2 extra-cellular domain. Trastuzumab provides significant clinical benefit in women with Her2-positive breast cancers. However, many women will either not respond or progress despite this treatment. The aim of this article is to summarize mechanisms of action of Her2 and of trastuzumab, and to better understand pathways activated in resistant tumors in order to identify ways to overcome them.     

Safety and immunogenicity of a Sf9 insect cell-derived respiratory syncytial virus fusion protein nanoparticle vaccine

Objective

We performed a Phase 1 randomized, observer-blinded, placebo-controlled trial to evaluate the safety and immunogenicity of a recombinant respiratory syncytial virus (RSV) fusion (F) protein nanoparticle vaccine.

Methods

Six formulations with (5, 15, 30 and 60 μg) and without (30 and 60 μg) aluminum phosphate (AdjuPhos) were administered intramuscularly on day 0 and 30 in a dose escalating fashion to healthy adults 18–49 years of age. Solicited and unsolicited events were collected through day 210. Immunogenicity measures taken at day 0, 30 and 60 included RSV A and B microneutralization, anti-F IgG, antigenic site II peptide and palivizumab competitive antibodies.

Results

The vaccine was well-tolerated, with no evident dose-related toxicity or attributable SAEs. At day 60 both RSV A and B microneutralization was significantly increased in vaccinees versus placebo. Across all vaccinees there was a 7- to 19-fold increase in the anti-F IgG and a 7- to 24-fold increase in the antigenic site II binding and palivizumab competitive antibodies.

Conclusions

The RSV F nanoparticle vaccine candidate was well tolerated without dose-related increases in adverse events. Measures of immunity indicate that neutralization, anti-RSV F IgG titers and palivizumab competing antibodies were induced at levels that have been associated with decreased risk of hospitalization.NCT01290419.     

Fractional Anisotropy in Three Variants of Primary Progressive Aphasia

Objective: Our aim was to report diffusion tensor imaging (DTI) patterns in three patients, each with a different primary progressive aphasia (PPA) variant. Design: One agrammatic PPA, one semantic PPA, and one logopenic PPA subject underwent a magnetic resonance imaging examination including DTI sequences. The fractional anisotropy (FA) value was calculated in regions of interest (ROIs) involved in these three variants (perisylvian region, temporal pole, and parietotemporal junction) for each patient. Left-right FA ratios in each ROI were compared between PPA subjects and a group of three amnestic mild cognitive impairment patients with a cerebrospinal fluid biomarker profile of the Alzheimer type. Results: The FA values were lower in the left hemisphere (p = 0.03). The lowest FA values were observed in the left perisylvian region for the non-fluent/agrammatic subtype PPA patient, in the left anterior temporal lobe for the semantic subtype PPA patient, and in the left parietotemporal junction for the logopenic patient (p = 0.028). The left-right FA ratio in these specific ROIs for each PPA variant was significantly lower than in the amnestic mild cognitive impairment group (p = 0.009). Conclusion: DTI patterns could be an effective new tool for diagnosing PPA and classifying the three variants.