EPZ011989, A Potent,Orally-Available EZH2 Inhibitor with Robust in Vivo Activity

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Comparison of 18FDG-PET/CT and conventional follow-up methods in colorectal cancer: A randomised prospective study

BackgroundA surveillance program was performed in colorectal cancer (CRC) patients after surgery, to diagnose asymptomatic recurrence.AimsTo assess whether 18-FDG positron emission tomography/CT (PET/CT) improved the detection of recurrence during a 3-year follow-up.MethodsA multicentre, two-arm randomised prospective trial comparing different 36-month follow-up strategies. Complete colonoscopy was performed at baseline and after 3 years and clinical exams with imaging every 3 months. The conventional arm (A) received carcinoembryonic antigen, liver echography, and alternated between lung radiography and computed tomography (CT) scans. The experimental arm (B) received PET/CT.ResultsA total of 365 patients with colon (79.4%) or rectal cancer (20.6%), stages II (48.2%) or III (50.8%), were enroled in this study. At 36 months, intention-to-treat analysis revealed recurrence in 31 (17.2%) patients in arm A and 47 (25.4%) in arm B (p = 0.063). At 3 years, 7 of 31 relapses (22.5%) in arm A were surgically treated with curative intent, compared to 17 of 47 (36.2%) in arm B (p = 0.25). The rates of recurrence and new cancers were higher in arm B than arm A (p = 0.038).ConclusionsPET/CT follow-up every 6 months did not increase the rate of recurrence at 3 years or the rate of surgically treated recurrence compared with conventional follow-up.     

Cutaneous microvascular blood flow and reactivity in patients with homozygous sickle cell anaemia

Homozygous sickle cell anaemia (SS disease) involves a high prevalence of skin ulcerations, and background experience concerning the cutaneous microcirculatory flux and reactivity in this disease is very limited. We investigated, by laser-Doppler velocimetry, the microcirculatory cutaneous blood flow and vasoreactivity in 17 patients with SS disease but no cutaneous trophic changes, vs. the corresponding values in 18 normal matched controls. The laser-Doppler probe was placed on the foot dorsum, and recordings were made in the supine and dependent positions, and after post-ischaemic hyperaemia. The venoarteriolar reflex was calculated as the difference between the fluxes in the supine and dependent positions. In both positions, patients with SS disease exhibited clear vasodilation, with larger cutaneous fluxes than those of the controls (P=0.024 and 0.0009, respectively). The venoarteriolar reflex, expressed as a percentage of the resting supine flux, was lower in the patients (P=0.0004). These impairments of the microcirculatory fluxes, which combine a vasodilated state with abnormal vasoreactivity, resemble those observed in patients with chronic venous insufficiency and might be crucial in determining the pathogenesis of the skin ulcerations that occur in SS disease. Laser-Doppler velocimetry seems a suitable non-invasive technique for investigating such cutaneous microangiopathy.     

Acculturation and Nutritional Health of Immigrants in Canada: A Scoping Review

Although recent immigrants to Canada are healthier than Canadian born (i.e., the Healthy Immigrant Effect), they experience a deterioration in their health status which is partly due to transitions in dietary habits. Since pathways to these transitions are under-documented, this scoping review aims to identify knowledge gaps and research priorities related to immigrant nutritional health. A total of 49 articles were retrieved and reviewed using electronic databases and a stakeholder consultation was undertaken to consolidate findings. Overall, research tends to confirm the Healthy Immigrant Effect and suggests that significant knowledge gaps in nutritional health persist, thereby creating a barrier to the advancement of health promotion and the achievement of maximum health equity. Five research priorities were identified including (1) risks and benefits associated with traditional/ethnic foods; (2) access and outreach to immigrants; (3) mechanisms and coping strategies for food security; (4) mechanisms of food choice in immigrant families; and (5) health promotion strategies that work for immigrant populations.     

Breast-specific gamma imaging is a cost effective and efficacious imaging modality when compared with MRI

Background

Both MRI and breast-specific gamma imaging are tools for surgical planning in newly diagnosed breast cancer. Breast-specific gamma imaging (BSGI) is used less frequently although it is of similar utility and lower cost. We compared the diagnostic and cost efficacy of BSGI with MRI.

Methods

Retrospective review of 1,480 BSGIs was performed in a community breast health center, 539 had a new diagnosis of cancer, 75 patients having both MRI and BSGI performed within 2 months of each other. Institutional charges for BSGI ($850) and MRI ($3,381) were noted.

Results

BSGI had a sensitivity of 92%, specificity of 73%, positive predictive value of 78%, and negative predictive value of 90%. This compared favorably with MRI that had sensitivity of 89%, specificity 54%, positive predictive value 67%, and negative predictive value 83%. The accuracy of BSGI was higher at 82% vs MRI at 72%. Total cost of MRI imaging was $253,575 vs BSGI at $63,750.

Conclusions

BSGI is a cost-effective and accurate imaging study for further evaluation of dense breast tissue and new diagnosis of cancer.     

Automated Quantitative Pupillometry for the Prognostication of Coma After Cardiac Arrest

Background

Sedation and therapeutic hypothermia (TH) delay neurological responses and might reduce the accuracy of clinical examination to predict outcome after cardiac arrest (CA). We examined the accuracy of quantitative pupillary light reactivity (PLR), using an automated infrared pupillometry, to predict outcome of post-CA coma in comparison to standard PLR, EEG, and somato-sensory evoked potentials (SSEP).

Methods

We prospectively studied over a 1-year period (June 2012–June 2013) 50 consecutive comatose CA patients treated with TH (33 °C, 24 h). Quantitative PLR (expressed as the % of pupillary response to a calibrated light stimulus) and standard PLR were measured at day 1 (TH and sedation; on average 16 h after CA) and day 2 (normothermia, off sedation: on average 46 h after CA). Neurological outcome was assessed at 90 days with Cerebral Performance Categories (CPC), dichotomized as good (CPC 1–2) versus poor (CPC 3–5). Predictive performance was analyzed using area under the ROC curves (AUC).

Results

Patients with good outcome [n = 23 (46 %)] had higher quantitative PLR than those with poor outcome [n = 27; 16 (range 9–23) vs. 10 (1–30) % at day 1, and 20 (13–39) vs. 11 (1–55) % at day 2, both p < 0.001]. Best cut-off for outcome prediction of quantitative PLR was <13 %. The AUC to predict poor outcome was higher for quantitative than for standard PLR at both time points (day 1, 0.79 vs. 0.56, p = 0.005; day 2, 0.81 vs. 0.64, p = 0.006). Prognostic accuracy of quantitative PLR was comparable to that of EEG and SSEP (0.81 vs. 0.80 and 0.73, respectively, both p > 0.20).

Conclusions

Quantitative PLR is more accurate than standard PLR in predicting outcome of post-anoxic coma, irrespective of temperature and sedation, and has comparable prognostic accuracy than EEG and SSEP.     

Sustained neural activity to gaze and emotion perception in dynamic social scenes

To understand social interactions, we must decode dynamic social cues from seen faces. Here, we used magnetoencephalography (MEG) to study the neural responses underlying the perception of emotional expressions and gaze direction changes as depicted in an interaction between two agents. Subjects viewed displays of paired faces that first established a social scenario of gazing at each other (mutual attention) or gazing laterally together (deviated group attention) and then dynamically displayed either an angry or happy facial expression. The initial gaze change elicited a significantly larger M170 under the deviated than the mutual attention scenario. At around 400 ms after the dynamic emotion onset, responses at posterior MEG sensors differentiated between emotions, and between 1000 and 2200 ms, left posterior sensors were additionally modulated by social scenario. Moreover, activity on right anterior sensors showed both an early and prolonged interaction between emotion and social scenario. These results suggest that activity in right anterior sensors reflects an early integration of emotion and social attention, while posterior activity first differentiated between emotions only, supporting the view of a dual route for emotion processing. Altogether, our data demonstrate that both transient and sustained neurophysiological responses underlie social processing when observing interactions between others.