Publications
212 results found
Stefani S, Buti N, Hart ACJ, et al., 2024, Safety and efficacy of SARS-CoV-2 vaccination in patients with immune thrombocytopenia: A two-centre review., Br J Haematol, Vol: 204, Pages: 324-328
Multiple studies have reported immune thrombocytopenia (ITP) relapse following SARS-CoV-2 vaccination, however baseline ITP relapse rate and antibody response to vaccination are not known. Patients with ITP who received at least one of the first three SARS-CoV-2 vaccination doses were included in the study. One hundred and twenty-four patients met the inclusion criteria. Relapse rate was 4.2% following a first vaccine dose, 9.1% after a second and 2.9% after a third; baseline relapse rate was 7.6%. Ninety-four per cent of patients who received three vaccine doses developed a clinical antibody response. SARS-CoV-2 vaccination appears to be safe and effective in patients with ITP.
Ros-Soto J, Pryce A, Zoubek E, et al., 2023, Favorable recovery profiles and good reliability among youngest unrelated stem cell donors supports lowering the minimum donor registration age, JOURNAL OF CLINICAL APHERESIS, Vol: 38, Pages: 562-572, ISSN: 0733-2459
Arachchillage DJ, Weatherill A, Rajakaruna I, et al., 2023, Thrombosis, major bleeding, and survival in COVID-19 supported by VV- ECMO in the first vs second wave- multicentre observational study in the UK, Journal of Thrombosis and Haemostasis, Vol: 21, Pages: 2735-2746, ISSN: 1538-7836
BACKGROUND: Bleeding and thrombosis are major complications of veno-venous extracorporeal membrane (VV-ECMO). OBJECTIVES: To assess thrombosis, major bleeding (MB) and 180-day in patients supported by VV-ECMO between first (1st March-31st May 2020) and second (1st June 2020-30th June 2021) waves of the COVID-19 pandemic. PATIENTS/METHODS: Observational study of 309 consecutive patients (≥18years) with severe COVID-19 supported by VV-ECMO in four nationally commissioned ECMO centres, UK. RESULTS: Median age was 48 (19-75)years and 70.6% were male. Probabilities of survival, thrombosis, and MB at 180 days in the overall cohort were 62.5% (193/309), 39.8%(123/309) and 30%(93/309). In multivariate analysis, age >55 years (HR 2.29 [1.33-3.93],p=0.003) and elevated creatinine (HR 1.91 [1.19-3.08],p=0.008) were associated with increased mortality. Corrected for duration of VV-ECMO support, arterial thrombosis alone (HR 3.0 [95% CI1.5-5.9], P= 0.002) or circuit thrombosis alone (HR 3.9 [95% 2.4-6.3], P<0.001), but not venous thrombosis, increased mortality. MB during ECMO had 3-fold risk (95% CI 2.6-5.8, P<0.001) of mortality. The first wave cohort had more males (76.7% vs 64%, p=0.014), higher 180-day survival (71.1% vs 53.3% p=0.003), more venous thrombosis alone (46.4% vs 29.2%, p=0.02) and lower circuit thrombosis (9.2% vs 28.1%, p<0.001). The second wave cohort received more steroids (121/150 [80.6%] vs 86/159 [54.1%], p<0.0001) and Tocilizumab (20/150 [13.3%] vs 4/159 [2.5%] p=0.005). CONCLUSIONS: MB and thrombosis are frequent complications in patients on VV-ECMO and significantly increase mortality. Arterial thrombosis alone or circuit thrombosis alone increased mortality whilst venous thrombosis alone had no effect. MB during ECMO support increased mortality 3.9-fold.
Thomas B, Palanicawandar R, Whittaker S, et al., 2023, Non-myeloablative allogeneic stem cell transplantation using TSEBT, TLI and ATG for mycosis fungoides and Sezary syndrome: results from a large single centre cohort, Publisher: ELSEVIER SCI LTD, Pages: S23-S23, ISSN: 0959-8049
Simini G, Akor F, Szydlo R, et al., 2023, Safety and Efficacy of Therapeutic Anticoagulation with Subcutaneous Unfractionated Heparin in Patients with Renal Failure, SEMINARS IN THROMBOSIS AND HEMOSTASIS, ISSN: 0094-6176
Szydlo RM, 2023, The presentation of results from studies in clinical haematology, BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY, Vol: 36, ISSN: 1521-6926
Myburgh JK, Szydlo RM, Bain BJ, 2023, The accuracy of haemoglobin A2 measurements in the presence and absence of haemoglobin S, eJHaem, Vol: 4, Pages: 437-441, ISSN: 2688-6146
The quantification of haemoglobin A2 by high-performance liquid chromatography (HPLC) was compared with quantification by capillary electrophoresis for control subjects and patients with sickle cell trait or sickle cell anaemia. Significant differences were found, with estimated values being higher by HPLC for control subjects and higher by capillary electrophoresis for sickle cell trait and sickle cell anaemia patients. There is an ongoing need for improved standardisation and alignment of methods.
Arachchillage DJ, Rajakaruna I, Laffan M, et al., 2023, Outcomes in COVID-19 supported by ECMO in the first vs second wave -multicentre observational study, Publisher: WILEY, Pages: 25-25, ISSN: 0007-1048
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.
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
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.
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: 5
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
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: 10
Arachchillage DJ, Rajakaruna I, Scott I, et al., 2022, 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: 21
Arachchillage DJ, Rajakaruna I, Odho Z, et al., 2022, 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: 6
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>
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: 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: 17
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.
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
Claudiani S, Apperley JF, Szydlo R, et al., 2021, 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: 14
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 <i>versus</i> 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: 7
Layton D, Piel F, Telfer P, 2020, Real-time national survey of COVID-19 in hemoglobinopathy and rare inherited anemia patients, Haematologica: the hematology journal, Vol: 105, Pages: 2651-2654, ISSN: 0390-6078
Cuadrado MM, Szydlo RM, Watts M, et al., 2020, Predictors of recovery following allogeneic CD34+-selected cell infusion without conditioning to correct poor graft function., Haematologica, Vol: 105, Pages: 2639-2646
Poor graft function is a serious complication following allogeneic hematopoietic stem cell transplantation. Infusion of CD34+-selected stem cells without pre-conditioning has been used to correct poor graft function, but predictors of recovery are unclear. We report the outcome of 62 consecutive patients who had primary or secondary poor graft function who underwent a CD34+-selected stem cell infusion from the same donor without further conditioning. Forty-seven of 62 patients showed hematological improvement and became permanently transfusion and growth factor-independent. In multivariate analysis, parameters significantly associated with recovery were shared CMV seronegative status for recipient/donor, the absence of active infection and matched recipient/donor sex. Recovery was similar in patients with mixed and full donor chimerism. Five -year overall survival was 74.4% (95% CI 59-89) in patients demonstrating complete recovery, 16.7% (95% CI 3-46) in patients with partial recovery and 22.2% (CI 95% 5-47) in patients with no response. In patients with count recovery, those with poor graft function in 1-2 lineages had superior 5-year overall survival (93.8%, 95% CI 82-99) than those with tri-lineage failure (53%, 95% CI 34-88). New strategies including cytokine or agonist support, or second transplant need to be investigated in patients who do not recover.
Cuadrado MM, Szydlo RM, Watts M, et al., 2020, Predictors of recovery following allogeneic CD34<SUP>+</SUP>-selected cell infusion without conditioning to correct poor graft function, HAEMATOLOGICA, Vol: 105, Pages: 2639-2646, ISSN: 0390-6078
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- Citations: 13
Bultitude WP, Schellekens J, Szydlo RM, et al., 2020, Presence of donor-encoded centromeric KIR B content increases the risk of infectious mortality in recipients of myeloablative, T-cell deplete, HLA-matched HCT to treat AML, BONE MARROW TRANSPLANTATION, Vol: 55, Pages: 1975-1984, ISSN: 0268-3369
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- Citations: 9
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