Publications
392 results found
Robbins AJ, Che Bakri NA, Toke-Bjolgerud E, et al., 2023, The effect of TRV027 on coagulation in COVID 19: A pilot randomized, placebo-controlled controlled trial, British Journal of Clinical Pharmacology, Vol: 89, Pages: 1495-1501, ISSN: 0306-5251
COVID-19 causes significant thrombosis and coagulopathy, with elevated D-dimer a predictor of adverse outcome. The precise mechanism of this coagulopathy remains unclear, one hypothesis is that loss of Angiotensin Converting Enzyme 2 activity during viral endocytosis leads to pro-inflammatory angiotensin II accumulation, loss of angiotensin-1-7 and subsequent vascular endothelial activation. We undertook a double blind randomised, placebo controlled experimental medicine study to assess the effect of TRV027, a synthetic angiotensin-1-7 analogue on D-dimer in 30 patients admitted to hospital with COVID-19 (REC ref. 20/HRA/3414), Clinical Trial No. NCT04419610.The study showed a similar rate of adverse events in TRV027 and control groups. There was a numerical decrease in D-dimer in the TRV027 group and increase in D-dimer in the placebo group, however, this did not reach statistical significance (p=0.15). A Bayesian analysis demonstrated there was a 92% probability that this change represented a true drug effect.
Dominy K, Salmon M, Szydlo R, et al., 2022, Digital Droplet (dd) Polymerase Chain Reaction (PCR) Assays Offer Limited Advantages over Conventional Reverse-Transcriptase Quantitative PCR (RT-qPCR) for the Prediction of Molecular Recurrence after Treatment Discontinuation in Chronic Myeloid Leukemia (CML): Results from the Destiny Study, Publisher: AMER SOC HEMATOLOGY, Pages: 9631-9632, ISSN: 0006-4971
Vladescu C, Hart ACJ, Paul D, et al., 2022, Cognitive Impairment in Patients with Immune Thrombocytopenia, 64th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH), Publisher: AMER SOC HEMATOLOGY, Pages: 5553-5554, ISSN: 0006-4971
Hederih J, Charania A, Waldman A, et al., 2022, Total Body Irradiation Is Associated with Higher Prevalence of Cerebral Microbleeds in Haematopoietic Stem Cell Transplant Survivors, Publisher: AMER SOC HEMATOLOGY, Pages: 12910-12912, ISSN: 0006-4971
Hart ACJ, Cabrera AM, Vladescu C, et al., 2022, Do Children with Immune Thrombocytopenia Have Cerebral Microbleeds?, 64th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH), Publisher: AMER SOC HEMATOLOGY, ISSN: 0006-4971
Stefani S, Saputil RC, Tan MM, et al., 2022, Safety and Efficacy of SARS-CoV-2 Vaccination in Patients with Immune Thrombocytopaenia: a Multi-Centre Review, 64th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH), Publisher: AMER SOC HEMATOLOGY, Pages: 5546-5548, ISSN: 0006-4971
Dexter D, O'Boyle F, Loaiza S, et al., 2022, Thiotepa and suppression of endogenous haemopoiesis with hydroxycarbamide and hypertransfusions abrogates risk of graft failure in haploidentical ric hct for paediatric patients with scd, 48th Annual Meeting of the European-Society-for-Blood-and-Marrow-Transplantation (EBMT), Publisher: SPRINGERNATURE, Pages: 244-245, ISSN: 0268-3369
Ros-Soto J, Matthews NC, Burton C, et al., 2022, Association between vitamin d and GVHD biomarkers with response to immunosuppression and survival in acute GVHD: An exploratory study, 48th Annual Meeting of the European-Society-for-Blood-and-Marrow-Transplantation (EBMT), Publisher: SPRINGERNATURE, Pages: 216-216, ISSN: 0268-3369
Bekono-Nessah I, Rosenburg A, Bowles CT, et al., 2022, Bleeding and thrombotic complications and their impact on mortality in patients supported with left ventricular assist device for cardiogenic shock, PERFUSION-UK, ISSN: 0267-6591
Roufosse C, Cook H, Dominy K, et al., 2022, Diagnostic application of transcripts associated with antibody-mediated rejection in kidney transplant biopsies, Nephrology Dialysis Transplantation, Vol: 37, Pages: 1576-1584, ISSN: 0931-0509
BackgroundThe diagnosis of antibody-mediated rejection (AMR) is reached using the Banff Classification for Allograft Pathology, which now includes gene expression analysis. In this study, we investigate the application of “Increased Expression Of Thoroughly Validated Gene Transcripts/Classifiers Strongly Associated With AMR” as a diagnostic criteria.MethodWe used qRT-PCR for 10 genes associated with AMR in a retrospective cohort of 297 transplant biopsies, including biopsies that met the full diagnostic criteria for AMR, even without molecular data (AMR, n = 27); biopsies that showed features of AMR, but that would only meet criteria for AMR with increased transcripts (AMRsusp, n = 49) and biopsies that would never meet criteria for AMR (No-AMR, n = 221).ResultsA 10-gene AMR score trained by a receiver-operating characteristic to identify AMR found 16 cases with a high score amongst the AMRsusp cases (AMRsusp-high) that had significantly worse graft survival than those with a low score (AMRsusp-low) (n = 33). In both univariate and multivariate Cox regression analysis, the AMR 10-gene score was significantly associated with an increased hazard ratio for graft loss in the AMRsusp group (HR 1.109, p = 0.004 and HR 1.138, p = 0.012), but not in the whole cohort. Net reclassification index and integrated discrimination improvement analyses demonstrated improved risk classification and superior discrimination respectively for graft loss when considering the gene score in addition to histological and serological data, but only in the AMRsusp group, not the whole cohort.ConclusionsThis study provides evidence that a gene score strongly associated with AMR helps identify cases at higher risk of graft loss in biopsies that are suspicious for AMR but don’t meet full criteria.
Lomax-Browne HJ, Medjeral-Thomas NR, Barbour SJ, et al., 2022, Association of Histologic Parameters with Outcome in C3 Glomerulopathy and Idiopathic Immunoglobulin-Associated Membranoproliferative Glomerulonephritis, CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, Vol: 17, Pages: 994-1007, ISSN: 1555-9041
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- Citations: 3
Medjeral-Thomas N, Barbour S, Gisby J, et al., 2022, Histological predictors of outcome in C3 glomerulopathy and idiopathic immunoglobulin-associated membranoproliferative glomerulonephritis, Clinical Journal of the American Society of Nephrology, ISSN: 1555-9041
Background and objectivesC3 glomerulopathy and idiopathic immunoglobulin-associated membranoproliferative glomerulonephritis (Ig-MPGN) are kidney diseases characterised by abnormal glomerular complement C3 deposition. These conditions are heterogeneous in outcome, but approximately 50% of patients reach end stage kidney disease within 10 years. Design, setting, participants and measurementsTo improve identification of patients with poor prognosis we performed a detailed analysis of percutaneous kidney biopsies in a large cohort of patients. Using a validated histological scoring system, we analysed 156 native diagnostic kidney biopsies from a retrospective cohort of 123 patients with C3 glomerulopathy and 33 patients with Ig-MPGN. We used linear regression, survival analysis and Cox proportional hazards models to assess the relationship between histological and clinical parameters with outcome. ResultsFrequent biopsy features were mesangial expansion and hypercellularity, glomerular basement membrane (GBM) double contours and endocapillary hypercellularity. Multivariable analysis showed negative associations between estimated glomerular filtration rate (eGFR) and crescents, interstitial inflammation, and interstitial fibrosis and tubular atrophy (IFTA). Proteinuria positively associated with endocapillary hypercellularity and GBM double contours. Analysis of second native biopsies did not demonstrate associations between immunosuppression treatment and improvement in histology. Using a composite outcome, risk of progression to kidney failure associated with eGFR and proteinuria at time of biopsy, and cellular/fibrocellular crescents, segmental sclerosis and IFTA scores. ConclusionsOur detailed assessment of kidney biopsy data indicated that cellular/fibrocellular crescents and IFTA scores were significant determinants of deterioration in kidney function.
Little C, Odho Z, Szydlo R, et al., 2022, Impact of aspirin on bleeding and blood product usage in off-pump and on-pump coronary artery bypass graft surgery., EJHaem, Vol: 3, Pages: 317-325
Major bleeding is linked to poorer outcomes following cardiac surgery. Current guidelines recommend continuation of aspirin prior to coronary artery by-pass graft (CABG) but the effect of continuing aspirin in patients with prior indication for aspirin, in particular during off-pump CABG (OPCABG), has not been systematically assessed. In this study, we analysed the effect of continuing aspirin prior to OPCABG and on-pump CABG with respect to bleeding and blood product usage. We compared propensity-matched cohorts of patients who continued aspirin until the day of OPCABG or CABG to controls (no antiplatelet) and to patients discontinuing aspirin 5-7 days prior. Length of hospital stay, 30-day mortality and thromboembolism rates were similar for both OPCABG and CABG. During OPCABG, aspirin-continued patients received more intraoperative red cell units compared to controls without difference in bleeding. Aspirin-continued patients received more blood products perioperatively and bled more than aspirin-discontinued patients undergoing OPCABG. The only difference during CABG was a small increase in the volume of cells salvaged among aspirin-continued patients compared to controls. Current guidelines on the continuation of aspirin prior to CABG and OPCABG are safe. Continuation of aspirin prior to OPCABG may result in more bleeding and blood product usage.
Trasanidis N, Katsarou A, Ponnusamy K, et al., 2022, Systems medicine dissection of chr1q-amp reveals a novel PBX1-FOXM1 axis for targeted therapy in multiple myeloma, BLOOD, Vol: 139, Pages: 1939-1953, ISSN: 0006-4971
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- Citations: 6
Ros-Soto J, Snowden JA, Szydlo R, et al., 2022, Outcomes After Donor Lymphocyte Infusion in Patients With Hematological Malignancies: Donor Characteristics Matter, TRANSPLANTATION AND CELLULAR THERAPY, Vol: 28, ISSN: 2666-6375
Dominy KM, Claudiani S, O'Hare M, et al., 2022, Assessment of quantitative polymerase chain reaction for BCR-ABL1 transcripts in chronic myeloid leukaemia: Are improved outcomes in patients with e14a2 transcripts an artefact of technology?, BRITISH JOURNAL OF HAEMATOLOGY, Vol: 197, Pages: 52-62, ISSN: 0007-1048
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- Citations: 2
Trasanidis N, Katsarou A, Ponnusamy K, et al., 2021, Systems medicine dissection of chromosome 1q amplification reveals oncogenic regulatory circuits and informs targeted therapy in cancer
<jats:title>Abstract</jats:title><jats:p>Understanding the biological and clinical impact of copy number aberrations (CNA) in cancer remains an unmet challenge. Genetic amplification of chromosome 1q (chr1q-amp) is a major CNA conferring adverse prognosis in several cancers, including the blood cancer, multiple myeloma (MM). Although several chr1q genes portend high-risk MM disease, the underpinning molecular aetiology remains elusive. Here we integrate patient multi-omics datasets with genetic variables to identify 103 adverse prognosis genes in chr1q-amp MM. Amongst these, the transcription factor PBX1 is ectopically expressed by genetic amplification and epigenetic activation of its own preserved 3D regulatory domain. By binding to reprogrammed super-enhancers, PBX1 directly regulates critical oncogenic pathways, whilst in co-operation with FOXM1, activates a proliferative gene signature which predicts adverse prognosis across multiple cancers. Notably, pharmacological disruption of the PBX1-FOXM1 axis, including with a novel PBX1 inhibitor is selectively toxic against chr1q-amp cancer cells. Overall, our systems medicine approach successfully identifies CNA-driven oncogenic circuitries, links them to clinical phenotypes and proposes novel CNA-targeted therapy strategies in cancer.</jats:p><jats:sec><jats:title>Significance</jats:title><jats:p>We provide a comprehensive systems medicine strategy to unveil oncogenic circuitries and inform novel precision therapy decisions against CNA in cancer. This first clinical multi-omic analysis of chr1q-amp in MM identifies a central PBX1-FOXM1 regulatory axis driving high-risk prognosis, as a novel therapeutic target against chr1q-amp in cancer.</jats:p></jats:sec>
Arachchillage DJ, Rajakaruna I, Scott I, et al., 2021, Impact of major bleeding and thrombosis on 180-day survival in patients with severe COVID-19 supported with veno-venous extracorporeal membrane oxygenation in the United Kingdom: a multicentre observational study, BRITISH JOURNAL OF HAEMATOLOGY, Vol: 196, Pages: 566-576, ISSN: 0007-1048
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- Citations: 12
Arachchillage DJ, Rajakaruna I, Odho Z, et al., 2021, Clinical outcomes and the impact of prior oral anticoagulant use in patients with coronavirus disease 2019 admitted to hospitals in the UK - a multicentre observational study, BRITISH JOURNAL OF HAEMATOLOGY, Vol: 196, Pages: 79-94, ISSN: 0007-1048
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- Citations: 4
Iskander D, Wang G, Heuston EF, et al., 2021, Single-cell profiling of human bone marrow progenitors reveals mechanisms of failing erythropoiesis in Diamond-Blackfan anemia, SCIENCE TRANSLATIONAL MEDICINE, Vol: 13, ISSN: 1946-6234
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- Citations: 9
Innes AJ, Mullish BH, Ghani R, et al., 2021, Fecal microbiota transplant mitigates adverse outcomes in patients colonized with multidrug-resistant organisms undergoing allogeneic hematopoietic cell transplantation, Frontiers in Cellular and Infection Microbiology, Vol: 11, Pages: 1-8, ISSN: 2235-2988
The gut microbiome can be adversely affected by chemotherapy and antibiotics prior to hematopoietic cell transplantation (HCT).This affects graft success and increases susceptibility to multidrug-resistant organism (MDRO) colonization and infection. Weperformed an initial retrospective analysis of our use of fecal microbiota transplantation (FMT) from healthy donors as therapy forMDRO-colonized patients with hematological malignancy. FMT was performed on eight MDRO-colonized patients pre-HCT (FMT-MDROgroup), and outcomes compared with 11 MDRO colonized HCT patients from the same period. At 12 months, survival wassignificantly higher in the FMT-MDRO group (70% versus 36% p = 0.044). Post-HCT, fewer FMT-MDRO patients required intensivecare (0% versus 46%, P = 0.045) or experienced fever (0.29 versus 0.11 days, P = 0.027). Intestinal MDRO decolonization occurred in25% of FMT-MDRO patients versus 11% non-FMT MDRO patients. Despite the significant difference and statistically comparablepatient/transplant characteristics, as the sample size was small, a matched-pair analysis to non-MDRO colonized control cohorts(2:1 matching) was performed. At 12 months, the MDRO group who did not have an FMT had significantly lower survival (36.4%versus 61.9% respectively, p=0.012), and higher non relapse mortality (NRM; 60.2% versus 16.7% respectively, p=0.009) than theirpaired non-colonized cohort. There was no difference in survival (70% versus 43.4%, p=0.14) or NRM (12.5% versus 31.2%respectively, p=0.24) between the FMT-MDRO group and their paired cohort. Negative outcomes, including mortality associatedwith MDRO colonization, may be ameliorated by pre-HCT FMT, despite lack of intestinal decolonization. Further work is needed toexplore the observed benefit.
Toulza F, Dominy K, Beadle J, et al., 2021, GENE EXPRESSION ANALYSIS USING QRT-PCR IN THE DIAGNOSIS OF ANTIBODY-MEDIATED REJECTION IN RENAL TRANSPLANT BIOPSIES, Publisher: WILEY, Pages: 290-290, ISSN: 0934-0874
Zhang S, Asquith B, Szydlo R, et al., 2021, Peripheral T cell lymphopenia in COVID-19: potential mechanisms and impact, Immunotherapy Advances, Vol: 1, Pages: 1-18, ISSN: 2732-4303
Immunopathogenesis involving T lymphocytes, which play a key role in defence against viral infection, could contribute to the spectrum of COVID-19 disease and provide an avenue for treatment. To address this question, are view of clinical observational studies and autopsy data in English and Chinese languages was conducted with a search of registered clinical trials. Peripheral lymphopenia affecting CD4 and CD8 T cells was a striking feature of severe COVID-19 compared with non-severe disease. Autopsy data demonstrated infiltration of T cells into organs, particularly the lung. 74 clinical trials are on-going that could target T cell-related pathogenesis, particularly IL-6 pathways. SARS-CoV-2 infection interrupts T cell circulation in patients with severe COVID-19. This could be due to redistribution of T cells into infected organs, activation induced exhaustion, apoptosis or pyroptosis. Measuring T cell dynamics during COVID-19 will inform clinical risk-stratification of hospitalised patients and could identify those who would benefit most from 66treatments that target T cells
Geva M, Pryce A, Shouval R, et al., 2021, High lactate dehydrogenase at time of admission for allogeneic hematopoietic transplantation associates to poor survival in acute myeloid leukemia and non-Hodgkin lymphoma, BONE MARROW TRANSPLANTATION, Vol: 56, Pages: 2690-2696, ISSN: 0268-3369
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- Citations: 1
Pryce A, Zoubek E, O'Leary A, et al., 2021, The Impact of Covid-19 on Unrelated And Donor Cord Provision To UK Transplant Centres During The 1st Wave of The Pandemic: UK Aligned Registry Study, Publisher: SPRINGERNATURE, Pages: 175-175, ISSN: 0268-3369
Mullish BH, Innes AJ, Ghani R, et al., 2021, FECAL MICROBIOTA TRANSPLANT PRIOR TO ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANT IN PATIENTS COLONIZED WITH MULTI-DRUG RESISTANT ORGANISMS IS ASSOCIATED WITH IMPROVED SURVIVAL, Society-for-Surgery-of-the-Alimentary-Tract Annual Meeting at Digestive Disease Week (DDW), Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S168-S169, ISSN: 0016-5085
Ghani R, Mullish B, Innes A, et al., 2021, Faecal microbiota transplant (FMT) prior to allogeneic haematopoietic cell transplantation (HCT) in patients colonised with multidrug-resistant organisms (MDRO) results in improved survival, ECCMID
Salisbury RA, Curto-Garcia N, OSullivan J, et al., 2021, Results of a national UK physician reported survey of COVID-19 infection in patients with a myeloproliferative neoplasm, Leukemia, Vol: 35, Pages: 2424-2430, ISSN: 0887-6924
Bedwani NARH, Kelada M, Smart N, et al., 2021, Glue versus mechanical mesh fixation in laparoscopic inguinal hernia repair: meta-analysis and trial sequential analysis of randomized clinical trials, BRITISH JOURNAL OF SURGERY, Vol: 108, Pages: 14-23, ISSN: 0007-1323
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- Citations: 4
Claudiani S, Apperley JF, Szydlo R, et al., 2020, TKI dose reduction can effectively maintain major molecular remission in patients with chronic myeloid leukaemia, BRITISH JOURNAL OF HAEMATOLOGY, Vol: 193, Pages: 346-355, ISSN: 0007-1048
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- Citations: 7
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