Right ventricular thrombus detection and multimodality imaging using contrast echocardiography and cardiac magnetic resonance imaging

We present the case of right ventricular thrombus formation associated with a right ventricular infarct secondary to a proximal right coronary artery thrombus, which was not evident on transthoracic echocardiography but detected on both delayed gadolinium enhanced magnetic resonance imaging and microsphere contrast echocardiography. The diagnosis of right ventricular thrombosis altered the decision to place an implantable cardiac defibrillator in this patient. Anticoagulation with warfarin resulted in resolution of the thrombus. This case highlights the utility of multimodality imaging in the detection and follow-up of right ventricular thrombus in the setting of right ventricular myocardial infarction, and the effectiveness of anticoagulation therapy.     

Traumatic brain injury: review of current management strategies

Head injury is a common condition with a high morbidity and mortality. Serious intracranial haematomas require early recognition and evacuation to maximise chances of independent outcomes. Recent organisational changes have promoted the development of trauma units and major trauma centres where patients can go through triage and be managed in an appropriate environment, and the development of management pathways in intensive treatment units has resulted in improvements in the outcome of traumatic brain injuries. Evidence for the treatment of cerebral perfusion pressure, and management of hyperventilation, osmotherapy, tracheostomy, and leakage of cerebrospinal fluid (CSF) has accumulated during the last decade and is important in the management of patients in all clinical settings. Since head injury is commonly associated with maxillofacial injuries, this review will be relevant to all who deal with this aspect of trauma.     

BRAF<Superscript>V600E</Superscript> Mutation is Associated with Decreased Disease-Free Survival in Papillary Thyroid Cancer

Background

The BRAF ^V600E mutation is a recognised molecular marker in papillary thyroid cancer (PTC), reported incidence from 30 to 80 %. BRAF^V600E aberrantly activates the MAPK pathway, a central regulator of cell growth and proliferation. Previous studies have reported conflicting data regarding the impact of BRAF^V600E on clinicopathological features of PTC. The study aims to determine whether BRAF^V600E is useful as a prognostic biomarker in PTC.

Methods

A cohort study of patients undergoing surgery for PTC was undertaken. The primary outcome measure was disease-free survival. Secondary outcome measures were tumour size, nodal positivity and radioactive iodine ablation rate. All cases were re-examined to confirm PTC. Immunohistochemistry for BRAF^V600E was performed on tissue microarrays. A single endocrine pathologist, blinded to clinicopathological data, interpreted staining.

Results

496 patients with PTC were included, and 309 (62 %) were BRAF^V600E positive. Tumour size was similar for BRAF^V600E-positive and -negative tumours (21.3 vs. 23.2 mm, p = 0.23). BRAF^V600E-positive patients were significantly older at first operation (mean age 45 versus 49 years, p = 0.003). BRAF^V600E-positive PTCs had a higher rate of disease recurrence (12.9 vs. 5.6 %, p = 0.004), lymph node metastasis (44 vs. 29.4 %, p = 0.004) and extra-thyroidal extension (44 vs. 22 %, p < 0.001). Five-year disease-free survival was 89.6 % for BRAF^V600E positive and 96.3 % for negative tumours, p < 0.001. There was no difference between groups for vascular invasion or multifocality. The mean follow-up was 57 months for both groups.

Conclusion

BRAF^V600E in PTC predicts an increased risk of lymph node metastasis, extra-thyroidal extension and reduced disease-free survival. It is an additional useful prognostic biomarker.

     

Disrupted muscarinic M1 receptor signaling correlates with loss of protein kinase C activity and glutamatergic deficit in Alzheimer's disease

There are few studies on the clinical and neurochemical correlates of postsynaptic cholinergic dysfunction in Alzheimer's disease (AD). We have previously found that attenuation of guanine nucleotide-binding (G-) protein coupling to muscarinic M(1) receptors in the neocortex was associated with dementia severity. The present study aims to study whether this loss of M(1)/G-protein coupling is related to alterations in signaling kinases and NMDA receptors. Postmortem frontal cortices of 22 AD subjects and 12 elderly controls were obtained to measure M(1) receptors, M(1)/G-protein coupling, NMDA receptors as well as protein kinase C (PKC) and Src kinase activities. We found that the extent of M(1)/G-protein coupling loss was correlated with reductions in PKC activity and NMDA receptor density. In contrast, Src kinase activity was neither altered nor associated with M(1)/G-protein coupling. Given the well established roles of neuronal PKC signaling and NMDA receptor function in cognitive processes, our results lend further insight into the mechanisms by which postsynaptic cholinergic dysfunction may underlie the cognitive features of AD, and suggest alternative therapeutic targets to cholinergic replacement.     

Megavoltage x-ray skin dose variation with an angle using grid carbon fibre couch tops

It is well known that a skin dose from high-energy x-ray radiation varies with the angle of beam incidence or the presence of a radiotherapy linear accelerator couch top material. This note investigates changes produced to the skin dose from a Varian carbon fibre grid couch top at differing angles of incidence for 6 MV x-rays as is often the case clinically. Results have shown that the skin dose can easily be measured using an EBT Gafchromic film whereby the delivered skin dose can be quantified to a high level of spatial resolution, not easily achieved with other skin dose detectors. Results have shown a significant increase in the skin dose specifically at the point of a cross-sectional carbon fibre grid. Values in % of the skin dose increased from approximately 27% (an open area within a 10 cm x 10 cm field) up to 55% (same field size) at the centre of the carbon fibre mesh strip (0 degrees incidence). This is compared to 19% of the skin dose for an open field of a 10 cm x 10 cm beam without the couch material present. At larger angles similar effects occur with values changing from 52% to 75% (60 degrees , 10 cm x 10 cm) in the open area and under the grid, respectively. This produces a wave effect for the skin dose. The average skin dose magnitude increases with the angle of incidence of the beam, ranging from 37.5% to 66% from 0 degrees to 60 degrees (10 x 10 cm), respectively. The symmetric wave nature of the skin dose profile skews to deliver an increased dose on the posterior side of the carbon fibre grid as the angle of incidence increases. Simulated fractional dose delivery on a phantom has shown that over 30 fractions the wave nature of the delivered skin dose is minimized due to the random nature of most patient positioning on the treatment couch. However, some variations are still present as the ratio of the open to grid area is approximately 4:1 and the dose spread is not necessarily completely averaged during a typical fractionated radiotherapy treatment. As such, if the treatment type results in a more rigorously positioned patient on the treatment couch, the wave nature of skin dose delivery may need to be taken into account.     

Cognitive Function and Vascular Risk Factors Among Older African American Adults

To evaluate the association between vascular risk factors and cognitive impairment among older African American (AA) adults in a primary care clinic. Participants included 96 AA adults aged 60 years or older who were evaluated for global and domain-specific cognition. Participants were interviewed using the Computerized Assessment of Memory and Cognitive Impairment (CAMCI). The relationship between CAMCI cognitive domain scores and vascular risk factors were examined using hierarchical regression models. Patients who smoked, those with higher SBP/DBP values had lower accuracy rates on CAMCI cognitive domains (attention, executive, memory).Those with higher BMI had better attention scores. Patients with higher HbA1C values had worse verbal memory. Patients with higher blood pressure were significantly faster in responding to tasks in the executive domain. Primary care providers working with older AA adults with these VRFs could implement cognitive screening earlier into their practice to reduce barriers of seeking treatment.