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  • Journal article
    Ali A-R, Li J, Yang G, O'Shea SJet al., 2020,

    A machine learning approach to automatic detection of irregularity in skin lesion border using dermoscopic images

    , PEERJ COMPUTER SCIENCE, ISSN: 2376-5992
  • Journal article
    McAdoo S, Prendecki M, Tanna A, Bhatt T, Bhangal G, McDaid J, masuda E, Cook H, Tam F, Pusey Cet al., 2020,

    Spleen tyrosine kinase inhibition is an effective treatment for established vasculitis in a pre-clinical model

    , Kidney International, Vol: 97, Pages: 1196-1207, ISSN: 0085-2538

    The anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV) are a group of life-threatening multi-system diseases characterized by necrotising inflammation of small blood vessels and crescentic glomerulonephritis. ANCA are thought to play a direct pathogenic role. Previous studies have shown that spleen tyrosine kinase (SYK) is phosphorylated during ANCA-induced neutrophil activation in vitro. However, the role of SKY in vivo is unknown. Here, we studied its role in the pathogenesis of experimental autoimmune vasculitis, a pre-clinical model of myeloperoxidase-ANCA-induced pauci-immune systemic vasculitis in the Wistar Kyoto rat. Up-regulation of SYK expression in inflamed renal and pulmonary tissue during early autoimmune vasculitis was confirmed by immunohistochemical and transcript analysis. R406, the active metabolite of fostamatinib, a small molecule kinase inhibitor with high selectivity for SYK, inhibited ANCA-induced pro-inflammatory responses in rat leucocytes in vitro. In an in vivo study, treatment with fostamatinib for 14 days after disease onset resulted in rapid resolution of urinary abnormalities, significantly improved renal and pulmonary pathology, and preserved renal function. Short-term exposure to fostamatinib did not significantly affect circulating myeloperoxidase-ANCA levels, suggesting inhibition of ANCA-induced inflammatory mechanisms in vivo. Finally, SYK expression was demonstrated within inflammatory glomerular lesions in ANCA-associated glomerulonephritis in patients, particularly within CD68+ve monocytes/macrophages. Thus, our data indicate that SYK inhibition warrants clinical investigation in the treatment of AAV.
  • Journal article
    Tarkin JM, Wall C, Gopalan D, Aloj L, Manavaki R, Fryer TD, Aboagye EO, Bennett MR, Peters JE, Rudd JHF, Mason JCet al., 2020,

    Novel approach to imaging active takayasu arteritis using somatostatin receptor positron emission tomography/magnetic resonance imaging.

    , Circulation: Cardiovascular Imaging, Vol: 13, Pages: 1-3, ISSN: 1941-9651

    Although 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) is an important diagnostic test for Takayasu arteritis (TAK),118F-FDG lacks inflammatory cell selectivity and cannot accurately distinguish arteritis from metabolically active vascular remodeling.2 This observation has led to the search for more sensitive and specific PET tracers for TAK. Macrophage activation antigen SST2 (somatostatin receptor subtype-2) PET represents a potential alternative imaging biomarker for defining disease activity in TAK, as macrophages are a major feature of the inflammatory infiltrate. We aimed to determine the ability of SST2 PET/magnetic resonance imaging (MRI) to detect arteritis in 2 patients with clinically active TAK.
  • Journal article
    Yang G, Chen J, Gao Z, Li S, Ni H, Angelini E, Wong T, Mohiaddin R, Nyktari E, Wage R, Xu L, Zhang Y, Du X, Zhang H, Firmin D, Keegan Jet al., 2020,

    Simultaneous left atrium anatomy and scar segmentations via deep learning in multiview information with attention

    , Future Generation Computer Systems: the international journal of grid computing: theory, methods and applications, Vol: 107, Pages: 215-228, ISSN: 0167-739X

    Three-dimensional late gadolinium enhanced (LGE) cardiac MR (CMR) of left atrial scar in patients with atrial fibrillation (AF) has recently emerged as a promising technique to stratify patients, to guide ablation therapy and to predict treatment success. This requires a segmentation of the high intensity scar tissue and also a segmentation of the left atrium (LA) anatomy, the latter usually being derived from a separate bright-blood acquisition. Performing both segmentations automatically from a single 3D LGE CMR acquisition would eliminate the need for an additional acquisition and avoid subsequent registration issues. In this paper, we propose a joint segmentation method based on multiview two-task (MVTT) recursive attention model working directly on 3D LGE CMR images to segment the LA (and proximal pulmonary veins) and to delineate the scar on the same dataset. Using our MVTT recursive attention model, both the LA anatomy and scar can be segmented accurately (mean Dice score of 93% for the LA anatomy and 87% for the scar segmentations) and efficiently (0.27 s to simultaneously segment the LA anatomy and scars directly from the 3D LGE CMR dataset with 60–68 2D slices). Compared to conventional unsupervised learning and other state-of-the-art deep learning based methods, the proposed MVTT model achieved excellent results, leading to an automatic generation of a patient-specific anatomical model combined with scar segmentation for patients in AF.
  • Journal article
    Li M, Wang C, Zhang H, Yang Get al., 2020,

    MV-RAN: Multiview recurrent aggregation network for echocardiographic sequences segmentation and full cardiac cycle analysis

    , Computers in Biology and Medicine, Vol: 120, ISSN: 0010-4825

    Multiview based learning has generally returned dividends in performance because additional information can be extracted for the representation of the diversity of different views. The advantage of multiview based learning fits the purpose of segmenting cardiac anatomy from multiview echocardiography, which is a non-invasive, low-cost and low-risk imaging modality. Nevertheless, it is still challenging because of limited training data, a poor signal-to-noise ratio of the echocardiographic data, and large variances across views for a joint learning. In addition, for a better interpretation of pathophysiological processes, clinical decision-making and prognosis, such cardiac anatomy segmentation and quantitative analysis of various clinical indices should ideally be performed for the data covering the full cardiac cycle. To tackle these challenges, a multiview recurrent aggregation network (MV-RAN) has been developed for the echocardiographic sequences segmentation with the full cardiac cycle analysis. Experiments have been carried out on multicentre and multi-scanner clinical studies consisting of spatio-temporal (2D + t) datasets. Compared to other state-of-the-art deep learning based methods, the MV-RAN method has achieved significantly superior results (0.92 ± 0.04 Dice scores) for the segmentation of the left ventricle on the independent testing datasets. For the estimation of clinical indices, our MV-RAN method has also demonstrated great promise and will undoubtedly propel forward the understanding of pathophysiological processes, computer-aided diagnosis and personalised prognosis using echocardiography.
  • Journal article
    Porter A, Youngstein T, Tombetti E, Mason Jet al., 2020,

    Biologic therapy in supra-aortic Takayasu arteritis can improve symptoms of cerebral ischaemia without surgical intervention

    , Rheumatology, Vol: 59, Pages: iii28-iii32, ISSN: 0080-2727

    Background: Takayasu arteritis typically results in severe arterial injury with stenoses, occlusions and occasionally aneurysms. Involvement of the supra-aortic arteries is common, and in its most severe form may compromise cerebral blood supply, resulting in signs of cerebral ischaemia including visual impairment, dysphasia, hemiparesis, loss of consciousness and stroke. In addition to combination immunosuppression, the management paradigm for symptomatic cerebral ischaemia includes revascularisation. The invasive nature of this surgery, the risk of complications and the relatively high rate of re-stenosis is of concern to patients and physicians alike.The aim of this study was to determine whether combined immunosuppression with early escalation to biologic therapy improved outcomes and reduced the need for high risk surgical intervention Methods: A retrospective review of 145 Takayasu arteritis patients attending Imperial College Healthcare between 2010-2018 was conducted to identify those with cerebral ischaemia secondary to supra-aortic disease and to analyse their treatment and outcomes. Results: Eight patients (5.5%) were identified. Seven received long-term combined immunosuppressive therapy and six were prescribed biologics. The data revealed a higher than expected comprehensive response to therapy, with significant falls in disease activity, cerebral ischaemia score and prednisolone dose required, over a median follow-up of 37 months. Serial imaging analysis detected no arterial disease progression after the initiation of optimal therapy. Only one patient required surgical intervention for persistent neurological symptoms. Conclusion: Early use of biologic therapy in those with supra-aortic Takayasu arteritis presenting with cerebral ischaemia may reduce the numbers of patients requiring surgical intervention and improve outcomes.
  • Journal article
    Weiner M, Goh SM, Mohammad AJ, Hrušková Z, Tanna A, Sharp P, Kang A, Bruchfeld A, Selga D, Chocová Z, Westman K, Eriksson P, Harper L, Pusey CD, Tesaŕ V, Salama AD, Segelmark Met al., 2020,

    Impact of treatment on damage and hospitalization in elderly patients with microscopic polyangiitis and granulomatosis with polyangiitis

    , J Rheumatol, Vol: 47, Pages: 580-588, ISSN: 0315-162X

    OBJECTIVE: Age is a risk factor for organ damage, adverse events, and mortality in microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). However, the relationship between treatment and damage, hospitalizations, and causes of death in elderly patients is largely unknown. METHODS: Consecutive patients from Sweden, England, and the Czech Republic diagnosed between 1997 and 2013 were included. Inclusion criteria were a diagnosis of MPA or GPA and age 75 years or more at diagnosis. Treatment with cyclophosphamide, rituximab, and corticosteroids the first three months was registered. Outcomes up to two years from diagnosis included vasculitis damage index (VDI), hospitalization, and cause of death. RESULTS: Treatment data was available for 167 of 202 patients. At two years, 4% had no items of damage. There was a positive association between VDI score at two years and Birmingham Vasculitis Activity Score at onset, and a negative association with treatment using cyclophosphamide or rituximab. Intravenous methylprednisolone dose was associated with treatment-related damage. During the first year, 69% of patients were readmitted to hospital. MPO-ANCA positivity and lower creatinine levels decreased the odds for readmission. The most common cause of death was infection, and this was associated with cumulative oral prednisolone dose. CONCLUSION: Immunosuppressive treatment with cyclophosphamide or rituximab in elderly patients with MPA and GPA was associated with development of less permanent organ damage and was not associated with hospitalization. However, higher doses of corticosteroids during the first three months was associated with treatment-related damage and fatal infections.
  • Journal article
    Dufton NP, Peghaire CR, Osuna-Almagro L, Raimondi C, Kalna V, Chauhan A, Webb G, Yang Y, Birdsey GM, Lalor P, Mason JC, Adams DH, Randi AMet al., 2020,

    Dynamic regulation of canonical TGF beta signalling by endothelial transcription factor ERG protects from liver fibrogenesis (vol 31, pg 450, 2017)

    , Nature Communications, Vol: 11, Pages: 1-1, ISSN: 2041-1723
  • Journal article
    Gao Z, Zhang H, Dong S, Sun S, Wang X, Yang G, Wu W, Li S, de Albuquerque VHCet al., 2020,

    Salient Object Detection in the Distributed Cloud-Edge Intelligent Network

    , IEEE NETWORK, Vol: 34, Pages: 216-224, ISSN: 0890-8044
  • Journal article
    Walsh M, Merkel PA, Peh C-A, Szpirt WM, Puechal X, Fujimoto S, Hawley CM, Khalidi N, Flossmann O, Wald R, Girard LP, Levin A, Gregorini G, Harper L, Clark WF, Pagnoux C, Specks U, Smyth L, Tesar V, Ito-Ihara T, de Zoysa JR, Szczeklik W, Flores-Suarez LF, Carette S, Guillevin L, Pusey CD, Casian AL, Brezina B, Mazzetti A, McAlear CA, Broadhurst E, Reidlinger D, Mehta S, Ives N, Jayne DRWet al., 2020,

    Plasma Exchange and Glucocorticoids in Severe ANCA-Associated Vasculitis

    , NEW ENGLAND JOURNAL OF MEDICINE, Vol: 382, Pages: 622-631, ISSN: 0028-4793

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