BackgroundHigh tumour stromal content has been found to predict adverse clinical outcome in a range of epithelial tumours. The aim of this study was to assess the prognostic significance of tumour-stroma ratio (TSR) in endometrial adenocarcinomas and investigate its relationship with other clinicopathological parameters.MethodsClinicopathological and 5-year follow-up data were obtained for a retrospective series of endometrial adenocarcinoma patients (n = 400). TSR was measured using a morphometric approach (point counting) on digitised histologic hysterectomy specimens. Inter-observer agreement was determined using Cohen’s Kappa statistic. TSR cut-offs were optimised using log-rank functions and prognostic significance of TSR on overall survival (OS) and disease-free survival (DFS) were determined using Cox Proportional Hazards regression analysis and Kaplan-Meier curves generated. Associations of TSR with other clinicopathological parameters were determined using non-parametric tests followed by Holm-Bonferroni correction for multiple comparisons.ResultsTSR as a continuous variable associated with worse OS (P = 0.034) in univariable Cox-regression analysis. Using the optimal cut-off TSR value of 1.3, TSR-high (i.e. low stroma) was associated with worse OS (HR = 2.51; 95 % CI = 1.22–5.12; P = 0.021) and DFS (HR = 2.19; 95 % CI = 1.15–4.17; P = 0.017) in univariable analysis. However, TSR did not have independent prognostic significance in multivariable analysis, when adjusted for known prognostic variables. A highly significant association was found between TSR and tumour grade (P < 0.001) and lymphovascular space invasion (P < 0.001), both of which had independent prognostic significance in this study population.ConclusionsLow tumour stromal content associates with both poor outcome and with other adverse prognostic indicators in endometrial cancer, although it is not independently prognostic. These findings contrast with studies on many - although not all - cancers and suggest that the biology of tumour-stroma interactions may differ amongst cancer types.

Background: Patient safety is a key priority for healthcare systems. Patient safety huddles have been advocated as a way to improve safety. We explored the feasibility of huddles in general practice. Methods: We invited all general practices in West Yorkshire to complete an online survey and interviewed practice staff. Results: Thirty-four out of 306 practices (11.1%) responded to our survey. Of these, 22 practices (64.7%) reported having breaks for staff to meet and eight (23.5%) reported no longer having breaks in their practices. Seven interviewees identified several barriers to safety huddles including time and current culture; individuals felt meetings or breaks would not be easily integrated into current primary care structure. Discussion: Despite their initial promise, there are major challenges to introducing patient safety huddles within the current context of UK general practice. General practice staff may need more convincing of potential benefits.

Bicuspid aortic valve (BAV) disease presents a unique management challenge both pre- and post-operatively. 4D flow MRI offers multiple tools for the assessment of the thoracic aorta in aortic valve disease. In particular, its assessment of flow patterns and wall shear stress have led to new understandings around the mechanisms of aneurysm development in BAV disease. Novel parameters have now been developed that have the potential to predict pathological aortic dilatation and may help to risk stratify BAV patients in future. This systematic review analyses the current 4D flow MRI literature after aortic valve and/or ascending aortic replacement in bicuspid aortic valve disease. 4D flow MRI has also identified distinct challenges posed by this cohort at the time of valve replacement compared to standard management of tri-leaflet disorders, and may help tailor the type and timing of replacement. Eccentric pathological flow patterns seen after bioprosthetic valve implantation, but not with mechanical prostheses, might be an important future consideration in intervention planning. 4D flow MRI also has promising potential in supporting the development of artificial valve prostheses and aortic conduits with more physiological flow patterns.

Background: Pulmonary vasodilator therapy in Fontan patients can improve exercise tolerance. We aimed to assess the potential for non-invasive testing of acute vasodilator response using four-dimensional (D) flow MRI during oxygen inhalation. Materials and Methods: Six patients with well-functioning Fontan circulations were prospectively recruited and underwent cardiac MRI. Ventricular anatomical imaging and 4D Flow MRI were acquired at baseline and during inhalation of oxygen. Data were compared with six age-matched healthy volunteers with 4D Flow MRI scans acquired at baseline. Results: All six patients tolerated the MRI scan well. The dominant ventricle had a left ventricular morphology in all cases. On 4D Flow MRI assessment, two patients (Patients 2 and 6) showed improved cardiac filling with improved preload during oxygen administration, increased mitral inflow, increased maximum E-wave kinetic energy, and decreased systolic peak kinetic energy. Patient 1 showed improved preload only. Patient 5 showed no change, and patient 3 had equivocal results. Patient 4, however, showed a decrease in preload and cardiac filling/function with oxygen. Discussion: Using oxygen as a pulmonary vasodilator to assess increased pulmonary venous return as a marker for positive acute vasodilator response would provide pre-treatment assessment in a more physiological state – the awake patient. This proof-of-concept study showed that it is well tolerated and has shown changes in some stable patients with a Fontan circulation.

Background Cardiac MRI is an important imaging tool in congenital cardiac disease, but its use has been limited in the neonatal population as general anesthesia has been needed for breath‐holding. Technological advances in four‐dimensional (4D) flow MRI have now made nonsedated free‐breathing acquisition protocols a viable clinical option, but the method requires prospective validation in neonates. Purpose To test the feasibility of compressed sensing (CS) 4D flow MRI in the neonatal population and to compare with standard previously validated two‐dimensional (2D) phase‐contrast (PC) flow MRI. Study type Prospective, cohort, image quality. Population A total of 14 healthy neonates (median [range] age: 2.5 [0–80] days; 8 male). Field Strength and Sequence Noncontrast 2D cine gradient echo sequence with through‐plane velocity encoding (PC) sequence and compressed sensing (CS) three‐dimensional (3D), time‐resolved, cine phase‐contrast MRI with 3D velocity‐encoding (4D flow MRI) at 3 T. Assessment Aortic 2D PC, and aortic, pulmonary trunk and superior vena cava CS 4D flow MRI were acquired using the feed and wrap technique (nonsedated) and quantified using commercially available software. Aortic flow and peak velocity were compared between methods. Internal consistency of 4D flow MRI was determined by comparing mean forward flow of the main pulmonary artery (MPA) vs. the sum of left and right pulmonary artery flows (LPA and RPA) and by comparing mean ascending aorta forward flow (AAo) vs. the sum of superior vena cava (SVC) and descending aorta flows (DAo). Statistical Tests Flow and peak‐velocity comparisons were assessed using paired t‐tests, with P < 0.05 considered significant, and Bland–Altman analysis. Interobserver and intraobserver agreement and internal consistency were analyzed by intraclass correlation co‐efficient (ICC). Results There was no statistically significant difference between ascending aortic forward flow between 2D PC and CS 4D Flow MRI (P = 0.26) with a bias of 0.11 mL (−0.59 to 0.82 mL) nor peak velocity (P = 0.11), with a bias of −5 cm/sec and (−26 to 16 cm/sec). There was excellent interobserver and intraobserver agreement for each vessel (interobserver ICC: AAo 1.00; DAo 0.94, SVC 0.90, MPA 0.99, RPA 0.98, LPA 0.96; intraobserver ICC: AAo 1.00; DAo 0.99, SVC 0.98, MPA 1.00, RPA 1.00, LPA 0.99). Internal consistency measures showed excellent agreement for both mean forward flow of main pulmonary artery vs. the sum of left and right pulmonary arteries (ICC: 0.95) and mean ascending aorta forward flow vs. the sum of superior vena cava and descending aorta flows (ICC: 1.00). Conclusion Sedation‐free neonatal feed and wrap MRI is well tolerated and feasible. CS 4D flow MRI quantification is similar to validated 2D PC free‐breathing imaging with excellent interobserver and intraobserver agreement. Evidence Level 1 Technical Efficacy Stage 2