Evaluation of automated multiclass fluid segmentation in optical coherence tomography images using the Pegasus fluid segmentation algorithms

Purpose: To evaluate the performance of the Pegasus-OCT (Visulytix Ltd) multiclass automated fluid segmentation algorithms on independent spectral domain optical coherence tomography data sets. Methods: The Pegasus automated fluid segmentation algorithms were applied to three data sets with edematous pathology, comprising 750, 600, and 110 b-scans, respectively. Intraretinal fluid (IRF), sub-retinal fluid (SRF), and pigment epithelial detachment (PED) were automatically segmented by Pegasus-OCT for each b-scan where ground truth from data set owners was available. Detection performance was assessed by calculating sensitivities and specificities, while Dice coefficients were used to assess agreement between the segmentation methods. Results: For two data sets, IRF detection yielded promising sensitivities (0.98 and 0.94, respectively) and specificities (1.00 and 0.98) but less consistent agreement with the ground truth (dice coefficients 0.81 and 0.59); likewise, SRF detection showed high sensitivity (0.86 and 0.98) and specificity (0.83 and 0.89) but less consistent agreement (0.59 and 0.78). PED detection on the first data set showed moderate agreement (0.66) with high sensitivity (0.97) and specificity (0.98). IRF detection in a third data set yielded less favorable agreement (0.46–0.57) and sensitivity (0.59–0.68), attributed to image quality and ground truth grader discordance. Conclusions: The Pegasus automated fluid segmentation algorithms were able to detect IRF, SRF, and PED in SD-OCT b-scans acquired across multiple independent data sets. Dice coefficients and sensitivity and specificity values indicate the potential for application to automated detection and monitoring of retinal diseases such as age-related macular degeneration and diabetic macular edema. Translational Relevance: The potential of Pegasus-OCT for automated fluid quantification and differentiation of IRF, SRF, and PED in OCT images has application to both clinical practice and research

A simulation tool for better management of retinal services

Background: Advances in the management of retinal diseases have been fast-paced as new treatments become available, resulting in increasing numbers of patients receiving treatment in hospital retinal services. These patients require frequent and long-term follow-up and repeated treatments, resulting in increased pressure on clinical workloads. Due to limited clinic capacity, many National Health Service (NHS) clinics are failing to maintain recommended follow-up intervals for patients receiving care. As such, clear and robust, long term retinal service models are required to assess and respond to the needs of local populations, both currently and in the future. Methods: A discrete event simulation (DES) tool was developed to facilitate the improvement of retinal services by identifying efficiencies and cost savings within the pathway of care. For a mid-size hospital in England serving a population of over 500,000, we used 36 months of patient level data in conjunction with statistical forecasting and simulation to predict the impact of making changes within the service. Results: A simulation of increased demand and a potential solution of the 'Treat and Extend' (T&E) regimen which is reported to result in better outcomes, in combination with virtual clinics which improve quality, effectiveness and productivity and thus increase capacity is presented. Without the virtual clinic, where T&E is implemented along with the current service, we notice a sharp increase in the number of follow-ups, number of Anti-VEGF injections, and utilisation of resources. In the case of combining T&E with virtual clinics, there is a negligible (almost 0%) impact on utilisation of resources. Conclusions: Expansion of services to accommodate increasing number of patients seen and treated in retinal services is feasible with service re-organisation. It is inevitable that some form of initial investment is required to implement service expansion through T&E and virtual clinics. However, modelling with DES indicates that such investment is outweighed by cost reductions in the long term as more patients receive optimal treatment and retain vision with better outcomes. The model also shows that the service will experience an average of 10% increase in surplus capacity.Peer reviewedFinal Published versio

Interleukin-6 gene amplification and shortened survival in glioblastoma patients

Interleukin-6 (IL-6) is known to promote tumour growth and survival. We evaluated IL-6 gene amplification in tumours from 53 glioma patients using fluorescence in situ hybridisation. Amplification events were detected only in glioblastomas (15 out of 36 cases), the most malignant tumours, and were significantly associated with decreased patient survival

The relationship between the preoperative systemic inflammatory response and cancer-specific survival in patients undergoing potentially curative resection for renal clear cell cancer

The relationship between tumour stage, grade (Fuhrman), performance status (ECOG), a combined score (UCLA Integrated Staging System, UISS), systemic inflammatory response (elevated C-reactive protein concentration), and cancer-specific survival was examined in patients undergoing potentially curative resection for renal clear cell cancer (n=100). On univariate survival analysis, sex (P=0.050), tumour stage (P=0.001), Fuhrman grade (P<0.001), UISS (P<0.001), C-reactive protein (P=0.002) were significant predictors of survival. On multivariate analysis with sex, UISS and C-reactive protein entered as covariates, only UISS (HR 2.70, 95% CI 1.00–7.30, P=0.050) and C-reactive protein (HR 4.00, 95% CI 1.21–13.31, P=0.024) were significant independent predictors of survival. The presence of a preoperative systemic inflammatory response predicts poor cancer-specific survival in patients who have undergone potentially curative resection for renal clear cell cancer

A human, compact, fully functional anti-ErbB2 antibody as a novel antitumour agent

A new human, compact antibody was engineered by fusion of a human, antitumour ErbB2-directed scFv with a human IgG1 Fc domain. Overexpression of the ErbB2 receptor is related to tumour aggressiveness and poor prognosis. This new immunoagent meets all criteria for a potential anticancer drug: it is human, hence poorly or not immunogenic; it binds selectively and with high affinity to target cells, on which it exerts an effective and selective antiproliferative action, including both antibody-dependent and complement-dependent cytotoxicity; it effectively inhibits tumour growth in vivo. Its compact molecular size should provide for an efficient tissue penetration, yet suitable to a prolonged serum half-life

Strategies to inhibit tumour associated integrin receptors: rationale for dual and multi-antagonists

YesThe integrins are a family of 24 heterodimeric transmembrane cell surface receptors. Involvement in cell attachment to the extracellular matrix, motility, and proliferation identifies integrins as therapeutic targets in cancer and associated conditions; thrombosis, angiogenesis and osteoporosis. The most reported strategy for drug development is synthesis of an agent that is highly selective for a single integrin receptor. However, the ability of cancer cells to change their integrin repertoire in response to drug treatment renders this approach vulnerable to the development of resistance and paradoxical promotion of tumor growth. Here, we review progress towards development of antagonists targeting two or more members of the RGD-binding integrins, notably αvβ3, αvβ5, αvβ6, αvβ8, α5β1, and αIIbβ3, as anticancer therapeutics

Early administration of IL-6RA does not prevent radiation-induced lung injury in mice

<p>Abstract</p> <p>Background</p> <p>Radiation pneumonia and subsequent radiation lung fibrosis are major dose-limiting complications for patients undergoing thoracic radiotherapy. Interleukin-6 (IL-6) is a pleiotropic cytokine and plays important roles in the regulation of immune response and inflammation. The purpose of this study was to investigate whether anti-IL-6 monoclonal receptor antibody (IL-6RA) could ameliorate radiation-induced lung injury in mice.</p> <p>Methods</p> <p>BALB/cAnNCrj mice having received thoracic irradiation of 21 Gy were injected intraperitoneally with IL-6RA (MR16-1) or control rat IgG twice, immediately and seven days after irradiation. Enzyme-linked immunosorbent assay was used to examine the plasma level of IL-6 and serum amyloid A (SAA). Lung injury was assessed by histological staining with haematoxylin and eosin or Azan, measuring lung weight, and hydroxyproline.</p> <p>Results</p> <p>The mice treated with IL-6RA did not survive significantly longer than the rat IgG control. We observed marked up-regulation of IL-6 in mice treated with IL-6RA 150 days after irradiation, whereas IL-6RA temporarily suppressed early radiation-induced increase in the IL-6 release level. Histopathologic assessment showed no differences in lung section or lung weight between mice treated with IL-6RA and control.</p> <p>Conclusions</p> <p>Our findings suggest that early treatment with IL-6RA after irradiation alone does not protect against radiation-induced lung injury.</p