The CONFIRM trial protocol: the utility of prostate-specific membrane antigen positron emission tomography/computed tomography in active surveillance for prostate cancer.

OBJECTIVES: Primary objectives: To determine the additive value of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) in the risk stratification of men with newly diagnosed prostate cancer (PCa) who would have otherwise been deemed suitable for active surveillance (AS). Specifically, we aim to determine if PSMA PET/CT can detect a cohort of men on AS that are in fact high risk and likely to experience unfavourable outcomes should they remain on their current treatment pathway. SECONDARY OBJECTIVES: to determine the additive value of PSMA PET/CT to repeat multiparametric magnetic resonance imaging (mpMRI) of the prostate and explore whether a confirmatory biopsy may be avoided in men with a negative PSMA PET/CT and a negative repeat mpMRI of the prostate (Prostate Imaging-Reporting and Data System score of <3). Furthermore, to develop a nomogram combining clinical, imaging and biomarker data to predict the likelihood of failure on AS in men with high-risk features. Also, a blood sample will be taken to perform a Prostate Health Index test at the time of confirmatory biopsy. Furthermore, a portion of this blood will be stored at a biobank for up to 5 years if a follow-up study on molecular biomarkers and genetic assays in this cohort of men is indicated, based on the results from the CONFIRM trial. PATIENTS AND METHODS: The CONFIRM trial is a prospective, multicentre, pre-test/post-test, cohort study across Victoria, Australia, involving men with newly diagnosed low-risk PCa with high-risk features, considered suitable for AS and undergoing confirmatory biopsy. The trial's goal is to provide high-quality evidence to establish whether PSMA PET/CT has a role in risk-stratifying men deemed suitable for AS despite having high-risk feature(s). RESULTS: The CONFIRM trial will measure the proportion of men deemed unsuitable for ongoing AS based on pathological upgrading and multidisciplinary team recommendation due to PSMA PET/CT scan and PSMA-targeted confirmatory biopsy. Additionally, the positive and negative predictive values, sensitivity, and specificity of PSMA PET/CT will be calculated in isolation and combined with repeat mpMRI of the prostate. CONCLUSIONS: This trial will provide robust prospective data to determine if PSMA-PET/CT and standard of care (prostate biopsy ± repeat mpMRI) can improve diagnostic certainty in men undergoing confirmatory biopsy for low-grade PCa with high-risk features.

Magnetic resonance characterization of the 'dot sign' in colloid cysts of the third ventricle.

PURPOSE: To determine the incidence of the 'dot sign' in patients with colloid cysts of the third ventricle and to characterise its MRI appearances. MATERIALS AND METHODS: Single institution retrospective analysis between January 2007 and October 2016 of all patients with either an imaging or imaging and histology-confirmed diagnosis of colloid cysts of the 3rd ventricle was undertaken. For all cases, MRI signal intensities of the cyst fluid component were graded by two independent radiologists relative to brain parenchyma. Presence of a dot, and if present, its size and relative position within the cyst were recorded. Signal intensities of the dot were then similarly assessed. RESULTS: 37 cases of colloid cyst were identified. Of these 37.8% (n = 14) demonstrated the dot sign. The majority (11 of 14) were observed inferiorly within the cyst; two cases were anteroinferior, and one other was posterior. All identified intracystic nodules displayed low signal intensity with respect to cyst fluid on T2 weighted sequences, and only two nodules were hypointense to fluid on T1-weighted imaging, with the remainder either iso- or hyperintense. CONCLUSIONS: An intracystic low T2 'dot' is a common MRI feature of colloid cysts of the third ventricle, and to our knowledge not previously systematically described. Presence of such a dot should not only not dissuade from a diagnosis of colloid cyst being made, but should in fact be used to strengthen the imaging diagnosis.

Endovascular clot retrieval in acute stroke with large ischaemic core is not always associated with poor outcomes.

BACKGROUND: The benefits of endovascular clot retrieval (ECR) for anterior circulation stroke with large ischaemic cores remain uncertain. In spite of recent pooled analysis of randomised controlled studies, conclusions regarding the fate of large ischaemic cores cannot be reached given the small number of included patients. AIM: To evaluate outcomes of ECR in acute stroke with large ischaemic core. METHODS: This was a single centre retrospective study of patients treated with ECR in the period 2012-2017. The inclusion criteria were anterior circulation stroke with symptom onset less than 6 h, baseline computed tomography perfusion and a 90-day clinical follow up defined by the modified Rankin score. RESULTS: Two hundred and sixty-one patients were included. Median age of 72 (interquartile range: 61-78) and 59% were male. The mean ischaemic core volume was 27.6 mL (SD: 34.9 mL). There were 235 patients with an ischaemic core volume of <70 mL and 26 patients with an ischaemic core volume of ≥70 mL. There was no statistically significant difference; however, in a 90-day functional independence with 66% (154/235) in the <70 mL core group and 54% (14/26) in the ≥70 mL core group reaching a 90-day modified Rankin score ≤2. CONCLUSIONS: We found that patients selected for ECR with ischaemic core size ≥70 mL had clinical outcomes not significantly different compared with those with smaller ischaemic cores. We recommend that large ischaemic core size alone does not necessarily constitute an absolute contraindication for ECR. Randomised controlled studies are needed to define better the benefits for this group of patients.

XANAP: A real-world, prospective, observational study of patients treated with rivaroxaban for stroke prevention in atrial fibrillation in Asia.

BACKGROUND: ROCKET AF and its East Asian subanalysis demonstrated that rivaroxaban was non-inferior to warfarin for stroke/systemic embolism (SE) prevention in patients with non-valvular atrial fibrillation (NVAF), with a favorable benefit-risk profile. XANAP investigated the safety and effectiveness of rivaroxaban in routine care in Asia-Pacific. METHODS: XANAP was a prospective, real-world, observational study in patients with NVAF newly starting rivaroxaban. Patients were followed at ~3-month intervals for 1 year, or for ≥30 days after permanent discontinuation. Primary outcomes were major bleeding events, adverse events (AEs), serious AEs and all-cause mortality; secondary outcomes included stroke/SE. Major outcomes were adjudicated centrally. RESULTS: XANAP enrolled 2273 patients from 10 countries: mean age was 70.5 years and 58.1% were male. 49.8% of patients received rivaroxaban 20 mg once daily (od), 43.8% 15 mg od and 5.9% 10 mg od. Mean treatment duration was 296 days, and 72.8% of patients had received prior anticoagulation therapy. Co-morbidities included heart failure (20.1%), hypertension (73.6%), diabetes mellitus (26.6%), prior stroke/non-central nervous system SE/transient ischemic attack (32.8%) and myocardial infarction (3.8%). Mean CHADS2, CHA2DS2-VASc and HAS-BLED scores were 2.3, 3.7 and 2.1, respectively. The rates (events/100 patient-years [95% confidence interval]) of treatment-emergent major bleeding, stroke and all-cause mortality were 1.5 (1.0-2.1), 1.7 (1.2-2.5) and 2.0 (1.4-2.7), respectively. Persistence was 66.2% at the study end. CONCLUSIONS: The real-world XANAP study demonstrated low rates of stroke and bleeding in rivaroxaban-treated patients with NVAF from Asia-Pacific. The results were consistent with the real-world XANTUS study and ROCKET AF.

Four cases of spinal epidural angiolipoma.

Spinal angiolipomas are uncommon benign tumours composed of mature fatty tissue and abnormal vascular elements, most commonly found within the posterior spinal epidural space. Most tumours are located within the mid-thoracic spine; in contrast thoracolumbar junction and purely lumbar angiolipomas are rare. We report a case series of four spinal angiolipomas, including a thoracolumbar junction and a purely lumbar tumour.

Pathological hypertrophy reverses ß2-adrenergic receptor-induced angiogenesis in mouse heart.

ß-adrenergic activation and angiogenesis are pivotal for myocardial function but the link between both events remains unclear. The aim of this study was to explore the cardiac angiogenesis profile in a mouse model with cardiomyocyte-restricted overexpression of ß2-adrenoceptors (ß2-TG), and the effect of cardiac pressure overload. ß2-TG mice had heightened cardiac angiogenesis, which was essential for maintenance of the hypercontractile phenotype seen in this model. Relative to controls, cardiomyocytes of ß2-TGs showed upregulated expression of vascular endothelial growth factor (VEGF), heightened phosphorylation of cAMP-responsive-element-binding protein (CREB), and increased recruitment of phospho-CREB, CREB-binding protein (CBP), and p300 to the VEGF promoter. However, when hearts were subjected to pressure overload by transverse aortic constriction (TAC), angiogenic signaling in ß2-TGs was inhibited within 1 week after TAC. ß2-TG hearts, but not controls, exposed to pressure overload for 1-2 weeks showed significant increases from baseline in phosphorylation of Ca(2+)/calmodulin-dependent kinase II (CaMKIIδ) and protein expression of p53, reduction in CREB phosphorylation, and reduced abundance of phospho-CREB, p300 and CBP recruited to the CREB-responsive element (CRE) site of VEGF promoter. These changes were associated with reduction in both VEGF expression and capillary density. While non-TG mice with TAC developed compensatory hypertrophy, (2-TGs exhibited exaggerated hypertrophic growth at week-1 post-TAC, followed by LV dilatation and reduced fractional shortening measured by serial echocardiography. In conclusion, angiogenesis was enhanced by the cardiomyocyte (2AR/CREB/VEGF signaling pathway. Pressure overload rapidly inhibited this signaling, likely as a consequence of activated CaMKII and p53, leading to impaired angiogenesis and functional decompensation.

Intracranial aneurysms with perianeurysmal edema: long-term outcomes post-endovascular treatment.

BACKGROUND AND PURPOSE: Perianeurysmal edema is rare and is associated with expansion of intracranial aneurysms despite adequate endovascular treatment. The natural history of this condition is poorly understood. We present a case series of perianeurysmal edema to investigate the incidence, natural history and management of these aneurysms. MATERIALS AND METHODS: Retrospective analysis of endovascularly treated aneurysms from January 2001 to December 2012 was performed. Perianeurysmal edema either pre- or post-treatment as detected on MRI was used to identify cases. RESULTS: Ten of the 838 patients demonstrated perianeurysmal edema. The median age was 51.5 (interquartile range 48 to 59). Of the 10 subjects, 50% (5/10) were male. Perianeurysmal edema was detected after the initial presentation and treatment in 70% (7/10) of the patients, with one patient developing headache after endovascular coiling, while the remaining 6 were found on routine follow-up imaging. Only 4 of the patients were ever symptomatic in the setting of perianeurysmal edema, with 3 of these patients improved clinically following treatment of the aneurysm. Radiological follow-up showed expanding neck remnants leading to a second endovascular coiling procedure in 50% (5/10) of the patients and a third procedure in 20% (2/10) of the patients to attenuate aneurysm growth. CONCLUSION: Ten of the aneurysms treated with endovascular therapy in our case series demonstrated perianeurysmal edema. They are mostly asymptomatic, with no cases of re-bleeding identified, however perianeurysmal edema is associated with aneurysm re-expansion despite initial endovascular treatment.