373 results found
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., Br J Haematol
Coagulation dysfunction and thrombosis are major complications in patients with coronavirus disease 2019 (COVID-19). Patients on oral anticoagulants (OAC) prior to diagnosis of COVID-19 may therefore have better outcomes. In this multicentre observational study of 5 883 patients (≥18 years) admitted to 26 UK hospitals between 1 April 2020 and 31 July 2020, overall mortality was 29·2%. Incidences of thrombosis, major bleeding (MB) and multiorgan failure (MOF) were 5·4%, 1·7% and 3·3% respectively. The presence of thrombosis, MB, or MOF was associated with a 1·8, 4·5 or 5·9-fold increased risk of dying, respectively. Of the 5 883 patients studied, 83·6% (n = 4 920) were not on OAC and 16·4% (n = 963) were taking OAC at the time of admission. There was no difference in mortality between patients on OAC vs no OAC prior to admission when compared in an adjusted multivariate analysis [hazard ratio (HR) 1·05, 95% confidence interval (CI) 0·93-1·19; P = 0·15] or in an adjusted propensity score analysis (HR 0·92 95% CI 0·58-1·450; P = 0·18). In multivariate and adjusted propensity score analyses, the only significant association of no anticoagulation prior to diagnosis of COVID-19 was admission to the Intensive-Care Unit (ICU) (HR 1·98, 95% CI 1·37-2·85). Thrombosis, MB, and MOF were associated with higher mortality. Our results indicate that patients may have benefit from prior OAC use, especially reduced admission to ICU, without any increase in bleeding.
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., Sci Transl Med, Vol: 13
[Figure: see text].
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, 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
Roufosse C, Cook H, Dominy K, et al., 2021, Diagnostic application of transcripts associated with antibody-mediated rejection in kidney transplant biopsies, Nephrology Dialysis Transplantation, 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.
Zhang S, Asquith B, Szydlo R, et al., 2021, Peripheral T cell lymphopenia in COVID-19: potential mechanisms and impact, Immunotherapy Advances, 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, ISSN: 0268-3369
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, 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
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
Innes AJ, Ghani R, Mullish BH, et al., 2020, O105. Faecal microbiota transplant (FMT) can reduce the high NRM associated with multi-drug resistant organism (MDRO) colonisation prior to allogeneic HCT., The 46th Annual Meeting of the European Society for Blood and Marrow Transplantation, Publisher: Springer Nature [academic journals on nature.com], Pages: 122-122, ISSN: 0268-3369
Soto JR, Snowden JA, Szydlo R, et al., 2020, Donor Factors Influence Outcomes of Patients Receiving Donor Lymphocyte Infusion for Mixed Chimerism after Reduced Intensity Conditioning Allogeneic Stem Cell Transplantation, Publisher: SPRINGERNATURE, Pages: 551-551, ISSN: 0268-3369
Zoubek E, Ros-Soto J, Szydlo R, et al., 2020, Bone Marrow Donor Characteristics: Influence on Harvest Yield and Donor Recovery, Publisher: SPRINGERNATURE, Pages: 694-695, ISSN: 0268-3369
Gallanagh M, Brown A, Pryce A, et al., 2020, Allogeneic Stem Cell Transplant with minimal-intensity Conditioning in Patients with Cutaneous T-cell Lymphoma. A Single Centre Retrospective Review, Publisher: SPRINGERNATURE, Pages: 282-282, ISSN: 0268-3369
Cuadrado MM, Anthias C, Fernando R, et al., 2020, Impact of Donor-Directed HLA Allo-Antibodies on Primary Graft Failure After Unrelated Donor Allogeneic Haematopoietic Cell Transplantation, Publisher: SPRINGERNATURE, Pages: 133-134, ISSN: 0268-3369
Iskander D, Wang G, Heuston EF, et al., 2020, Single-Cell Transcriptional Landscapes of Human Bone Marrow Reveal Distinct Erythroid Phenotypes Underpinned By Genotype in Diamond-Blackfan Anemia, Publisher: AMER SOC HEMATOLOGY, ISSN: 0006-4971
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, 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.
Layton D, Piel F, Telfer P, et al., 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
Little C, Szydlo R, Aw TC, et al., 2020, Effect of direct-acting oral anticoagulants (DOACs) on bleeding and blood product usage in cardiac surgery compared to warfarin and controls, British Journal of Haematology, Vol: 190, Pages: 284-293, ISSN: 0007-1048
In this retrospective, single-centre, observational study, we assessed (i) use of anticoagulant and antiplatelet (AP) therapy, (ii) the duration of direct-acting oral anticoagulant (DOAC) discontinuation, (iii) renal function and (iv) PT and APTT as predictors of bleeding and blood product usage; in adults (>18 years) undergoing major cardiac surgery from 01.01.2015 to 31.12.2018. Comparisons were made between each treatment group (warfarin, DOAC and DOAC + AP) and untreated controls, and between warfarin and DOAC. A total of 2928 patients were included for analysis. Median (range) of DOAC discontinuation prior to surgery was five days (1-22) for DOAC and five days (2-7) for DOAC + AP. There were no differences in bleeding between anticoagulant groups versus control, or DOAC versus warfarin. There were no differences in blood product use between DOAC and warfarin patients. The duration of DOAC discontinuation but not the creatinine clearance influenced bleeding and blood products use. Thrombosis occurred in 0·7% and 3·1% in controls and patients on warfarin respectively (P = 0·099) with none among patients on DOAC or DOAC + AP. The PT/APTT had no predictive value. Median five-day discontinuation of DOAC +/- AP irrespective of renal function prevents an increase in bleeding compared to patients on warfarin or controls with no increase in thrombosis.
Nacheva E, Ahyee T, Addada J, et al., 2020, Absence of damaging effects of stem cell donation in unrelated donors assessed by FISH and gene variance screening, BONE MARROW TRANSPLANTATION, Vol: 55, Pages: 1290-1296, ISSN: 0268-3369
Banerjee R, Killeen N, Toma S, et al., 2020, Reduced Intensity Conditioning with Thiotepa-Fludarabine-Busulphan (TBF) and Post-Transplant Cyclophosphamide (PTC) Results in Rapid Complete Donor T-cell Chimerism in Haploidentical Recipients with Acute Myeloid Leukaemia, 60th Annual Scientific Meeting of the British-Society-for-Haematology (BSH), Publisher: WILEY, Pages: 180-181, ISSN: 0007-1048
Sookramanien S, Szydlo R, Palanicawandar R, et al., 2020, Platelet recovery after the first cycle of DA chemotherapy for AML is an independent predictor of survival, 60th Annual Scientific Meeting of the British-Society-for-Haematology (BSH), Publisher: WILEY, Pages: 185-186, ISSN: 0007-1048
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
Nteliopoulos G, Bazeos A, Claudiani S, et al., 2019, Somatic variants in epigenetic modifiers can predict failure of response to imatinib but not to second-generation tyrosine kinase inhibitors, Haematologica, Vol: 104, Pages: 2400-2409, ISSN: 0390-6078
There are no validated molecular biomarkers to identify newly-diagnosed individuals with chronic-phase chronic myeloid leukaemia likely to respond poorly to imatinib and who might benefit from first-line treatment with a more potent second-generation tyrosine kinase-inhibitor. Our inability to predict these 'high-risk' individuals reflects the poorly understood heterogeneity of the disease. To investigate the potential of genetic variants in epigenetic modifiers as biomarkers at diagnosis, we used Ion Torrent next-generation sequencing of 71 candidate genes for predicting response to tyrosine kinase-inhibitors and probability of disease progression. 124 subjects with newly-diagnosed chronic-phase chronic myeloid leukaemia began with imatinib (n=62) or second-generation tyrosine kinase-inhibitors (n=62) and were classified as responders or non-responders based on the BCRABL1 transcript levels within the first year and the European LeukemiaNet criteria for failure. Somatic variants affecting 21 genes (e.g. ASXL1, IKZF1, DNMT3A, CREBBP) were detected in 30% of subjects, most of whom were non-responders (41% non-responders, 18% responders to imatinib, 38% non-responders, 25% responders to second-generation tyrosine kinase-inhibitors). The presence of variants predicted the rate of achieving a major molecular response, event-free survival, progression-free survival and chronic-myeloid-leukaemia-related survival in the imatinib but not the second-generation tyrosine kinase-inhibitors cohort. Rare germline variants had no prognostic significance irrespective of treatment while some pre-leukaemia variants suggest a multi-step development of chronic myeloid leukaemia. Our data suggest that identification of somatic variants at diagnosis facilitates stratification into imatinib responders/non-responders, thereby allowing earlier use of second-generation tyrosine kinase-inhibitors, which, in turn, may overcome the negative impact of such variants on disease progression.
Soto JR, Zoubek E, Szydlo R, et al., 2019, Age Matters: Younger Unrelated PBSC Donors Experience Less G-CSF-Related Symptoms and Have a Faster Emotional Recovery Than Older Donors, 61st Annual Meeting and Exposition of the American-Society-of-Hematology (ASH), Publisher: AMER SOC HEMATOLOGY, ISSN: 0006-4971
Nacheva EP, Ahyee T, Navarette C, et al., 2019, Absence of Damaging Effects of Stem Cell Donation in Unrelated Donors Assessed By FISH and Gene Variance Screening, 61st Annual Meeting and Exposition of the American-Society-of-Hematology (ASH), Publisher: AMER SOC HEMATOLOGY, ISSN: 0006-4971
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