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Journal articleGulati K, Edwards H, Prendecki M, et al., 2021,
Combination treatment with rituximab, low-dose cyclophosphamide and plasma exchange for severe antineutrophil cytoplasmic antibody-associated vasculitis
, Kidney International, Vol: 100, Pages: 1316-1324, ISSN: 0085-2538Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis can present with life-threatening lung-kidney syndromes. However, many controlled treatment trials excluded patients with diffuse alveolar hemorrhage or severely impaired glomerular filtration rates, and so the optimum treatment in these cases is unclear. In this retrospective cohort study, we report the outcomes of 64 patients with life-threatening disease treated with a combination regimen of rituximab, low-dose intravenous cyclophosphamide, oral glucocorticoids, and plasma exchange. At entry, the median estimated glomerular filtration rate was 9 mL/min, 47% of patients required dialysis, and 52% had diffuse alveolar hemorrhage. All patients received a minimum of seven plasma exchanges, and the median cumulative doses of rituximab, cyclophosphamide, and glucocorticoid were 2, 3, and 2.6 g, respectively, at six months. A total of 94% of patients had achieved disease remission (version 3 Birmingham Vasculitis Activity Score of 0) at this time point, and 67% of patients who required dialysis recovered independent kidney function. During long-term follow-up (median duration 46 months), overall patient survival was 85%, and 69% of patients remained free from end-stage kidney disease, which compares favorably to a historic cohort with severe disease treated with a conventional induction regimen. Combination treatment was associated with prolonged B cell depletion and low rates of relapse; 87% of patients were in continuous remission at month 36. The serious infection rate during total follow-up was 0.28 infections/patient/year, suggesting that combination treatment is not associated with an enduring risk of infection. Thus, we suggest that combination immunosuppressive therapy may permit glucocorticoid avoidance and provide rapid and prolonged disease control in patients with severe ANCA-associated vasculitis.
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Journal articleLong J, Sun D, Zhou X, et al., 2021,
A mathematical model for predicting intracranial pressure based on noninvasively acquired PC-MRI parameters in communicating hydrocephalus
, JOURNAL OF CLINICAL MONITORING AND COMPUTING, Vol: 35, Pages: 1325-1332, ISSN: 1387-1307- Author Web Link
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- Citations: 1
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Journal articleDuncan CF, Youngstein T, Kirrane MD, et al., 2021,
Diagnostic Challenges in Sepsis
, CURRENT INFECTIOUS DISEASE REPORTS, Vol: 23, ISSN: 1523-3847- Author Web Link
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- Citations: 12
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Conference paperCharania AS, Vergis N, Phillips R, et al., 2021,
Multi-Arm Trial of Inflammatory Signal Inhibitors (MATIS) for hospitalised patients with mild or moderate Covid-19 pneumonia: a structured summary of a study protocol for a randomised controlled trial
, 63rd ASH Annual Meeting and Exposition, Publisher: American Society of Hematology, Pages: 4200-4200, ISSN: 0006-4971 -
Journal articleGoulden B, Youngstein T, Giles I, et al., 2021,
Haemophagocytic lymphohistiocytosis in pregnancy
, CLINICAL MEDICINE, Vol: 21, Pages: E682-E683, ISSN: 1470-2118 -
Journal articleSalas A, Kant S, Floyd L, et al., 2021,
ANCA vasculitis induction management during the COVID-19 pandemic
, Kidney International Reports, Vol: 6, Pages: 2903-2907, ISSN: 2468-0249As the severe acute respiratory syndrome coronavirus 2 pandemic evolved and became a global health threat, the safety of immunosuppression in antineutrophil cytoplasmic antibody-associated vasculitis (AAV) became of utmost important for clinicians and patients. Although timely initiation of immunosuppressive therapy is critical to quell the acute inflammation and prevent AAV-associated mortality and morbidity, concerns for increased susceptibility to Coronavirus Disease 2019 (COVID-19), delayed viral clearance, and decreased humoral response to infection led to speculation about modification in induction therapy practices may be deployed by physicians caring for patients with AAV. This international retrospective cohort study investigated the influence of the COVID-19 pandemic on AAV induction therapy and patient outcomes in different parts of the world by studying differences in treatment regimens in the United States, United Kingdom, and Europe.
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Journal articleMoiseev S, Kronbichler A, Makarov E, et al., 2021,
Association of venous thromboembolic events with skin, pulmonary and kidney involvement in ANCA-associated vasculitis: a multinational study
, RHEUMATOLOGY, Vol: 60, Pages: 4654-4661, ISSN: 1462-0324- Author Web Link
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- Citations: 12
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Journal articlePrendecki M, Gulati K, Turner-Stokes T, et al., 2021,
Characterisation of an enhanced preclinical model of experimental MPO-ANCA autoimmune vasculitis
, Journal of Pathology, Vol: 255, Pages: 107-119, ISSN: 0022-3417Experimental autoimmune vasculitis (EAV) is a model of antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) induced by immunisation of susceptible rat strains with myeloperoxidase (MPO). Animals develop circulating MPO-ANCA, pulmonary haemorrhage and glomerulonephritis, although renal injury is mild and recovers spontaneously without treatment. In this study we aimed to augment the severity of glomerulonephritis. Following induction of EAV on day 0, a sub-nephritogenic dose of nephrotoxic serum (NTS) containing heterologous antibodies to glomerular basement membrane was administered on day 14. This resulted in a significant increase in disease severity at day 28 compared to MPO immunisation alone - with more urinary abnormalities, infiltrating glomerular leucocytes, and crescent formation that progressed to glomerular and tubulointerstitial scarring by day 56, recapitulating important features of human disease. Importantly, the glomerulonephritis remained pauci-immune, and was strictly dependent on the presence of autoimmunity to MPO, as there was no evidence of renal disease following administration of sub-nephritogenic NTS alone or after immunisation with a control protein in place of MPO. Detailed phenotyping of glomerular leucocytes identified an early infiltrate of non-classical monocytes following NTS administration that, in the presence of autoimmunity to MPO, may initiate the subsequent influx of classical monocytes which augment glomerular injury. We also showed that this model can be used to test novel therapeutics by using a small molecule kinase inhibitor (fostamatinib) that rapidly attenuated both glomerular and pulmonary injury over a four-day treatment period. We believe that this enhanced model of MPO-AAV will prove useful for the study of glomerular leucocyte behaviour and novel therapeutics in AAV in the future. This article is protected by copyright. All rights reserved.
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Conference paperPorter A, Maughan R, Pericleous C, et al., 2021,
Investigating Adenosine Deaminase 2 Activity in Large Vessel Vasculitis
, Publisher: WILEY, Pages: 3903-3905, ISSN: 2326-5191 -
Conference paperMaughan R, Lang M, Olsson A, et al., 2021,
Endothelial Cells from Patients with DMARD Naive, Active Inflammatory Arthritis Demonstrate Pro-inflammatory Sensitisation That Is Reversed by Therapy Initiation
, Publisher: WILEY, Pages: 74-76, ISSN: 2326-5191
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