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  • 1
    In: The Lancet Haematology, Elsevier BV, Vol. 9, No. 11 ( 2022-11), p. e833-e843
    Type of Medium: Online Resource
    ISSN: 2352-3026
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
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  • 2
    In: The Lancet, Elsevier BV, Vol. 396, No. 10266 ( 2020-12), p. 1885-1894
    Type of Medium: Online Resource
    ISSN: 0140-6736
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
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  • 3
    In: BJS Open, Oxford University Press (OUP), Vol. 3, No. 3 ( 2019-06), p. 403-414
    Type of Medium: Online Resource
    ISSN: 2474-9842 , 2474-9842
    URL: Issue
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
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  • 4
    In: British Journal of Surgery, Oxford University Press (OUP), Vol. 106, No. 2 ( 2019-01-08), p. e103-e112
    Abstract: The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89·6 per cent) compared with that in countries with a middle (753 of 1242, 60·6 per cent; odds ratio (OR) 0·17, 95 per cent c.i. 0·14 to 0·21, P & lt; 0·001) or low (363 of 860, 42·2 per cent; OR 0·08, 0·07 to 0·10, P & lt; 0·001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference −9·4 (95 per cent c.i. −11·9 to −6·9) per cent; P & lt; 0·001), but the relationship was reversed in low-HDI countries (+12·1 (+7·0 to +17·3) per cent; P & lt; 0·001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0·60, 0·50 to 0·73; P & lt; 0·001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.
    Type of Medium: Online Resource
    ISSN: 0007-1323 , 1365-2168
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
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  • 5
    In: HemaSphere, Ovid Technologies (Wolters Kluwer Health), Vol. 7, No. S3 ( 2023-08), p. e998506d-
    Type of Medium: Online Resource
    ISSN: 2572-9241
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
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  • 6
    In: Blood, American Society of Hematology, Vol. 106, No. 11 ( 2005-11-16), p. 2588-2588
    Abstract: Budd-Chiari Syndrome (BCS) is a group of disorders resulting from obstruction to hepatic venous outflow; myeloproliferative disorder (MPD) accounts for 10–40% of cases. A number of BCS cases labelled as ‘idiopathic’ do not fulfil the accepted diagnostic criteria for MPD but have features suggestive of a latent form of MPD based on hyperplastic bone marrow and spontaneous erythroid colony progenitor cell culture studies; these cases may subsequently develop overt MPD. A clonal mutation in JAK2 tyrosine kinase (JAK2V617F) occurs in a high proportion of patients with MPD and is of potential use in the characterization of latent MPD in BCS. We studied 44 patients with BCS (female n=27, mean age 36.1 years, SD 13) presenting between 1985 and 2005. Genomic DNA obtained from archived bone marrow films was screened by allele-specific PCR for the JAK2V617F tyrosine kinase mutation. JAK2V617F was detected in 27/44 (61.4%) subjects. Fulminant hepatic failure was the presenting feature in 86.4%. 3/38 subjects had previously diagnosed Polycythemia Vera and all of these were JAK2V617F positive. Analysis for hereditary thrombophilia in 32/44 cases showed Factor V Leiden (FVL) heterozygosity (n=2) and Protein C deficiency (n=1); JAK2V617F was detected in one of the FVL cases. Screening for antiphospholipid antibodies and paroxysmal nocturnal hemoglobinuria in 31 and 30 out of 44 cases respectively proved negative. 22/44 cases had splenomegaly of which 72.2% had JAK2V617F detected. Mean hemoglobin concentration was higher in patients with JAK2V617F (12.4 g/dL, SD 2.8) compared to the wild-type allele (10.2 g/dL, SD 2.1)(p=0.005). Mean neutrophil count was similar (p=0.26) in both groups (JAK2V617F 7.8 x109/L, SD 5.5; wild-type 6.1 x109/L, SD 4.5). Mean platelet count was higher (p=0.01) in subjects with JAK2V617F (289 x109/L, SD 192) compared to wild-type (180 x109/L, SD 158). The bone marrow (BM) was hyperplastic in all lineages in 19/44 subjects of which 15 (78.9%) contained the JAK2V617F mutation. Importantly, in 25/44 subjects without hyperplastic BM, 48% had JAK2V617F detected. Clonal cytogenetic abnormalities occurred in 6/44 subjects all of which carried JAK2V617F. In 35 evaluable subjects, 10/35 (28.6%) showed endogenous erythroid colony (EEC) formation (8/10 JAK2V617F positive), and the remainder (25/35) showed no EEC formation (14/25 JAK2V617F positive). Treatment of BCS included anticoagulation (n=44), porto-systemic shunt insertion (n=26) and orthotopic liver transplantation (OLT) (n=15). Overall survival was 81.8% (median 32.5 months, range 2 days-240 months). In the 8 non-survivors, JAK2V617F was detected in 50%. 15/44 subjects underwent OLT (11/15 JAK2V617F positive) of which 14/15 are alive at a median of 36 months post transplant (1–240 months). 14/44 subjects were treated with cytoreductive treatment following diagnosis of BCS and in 92.9% of these JAK2V617F was detected. 5/15 subjects went on to receive cytoreductive treatment following OLT of which all were JAK2V617F positive. We have found a high prevalence of JAK2V617F in patients with BCS. Latent MPD was missed in 12/25 subjects on BM morphology and 14/25 subjects on BM progenitor culture. We suggest that JAK2V617F analysis should be performed in all new cases of BCS. Given their age, these patients are possible candidates for JAK2 targeted therapy.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2005
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  • 7
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 4158-4158
    Abstract: Abstract 4158 Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative procedure for patients of high-risk acute myeloid leukaemia (AML) and Myelodysplastic syndromes (MDS). The development of reduced intensity protocols (RIC) has expanded this treatment modality to older patients and to those with comorbidities. The development of the HCT-CI has been an important advance in attempting to more effectively assess patient′s fitness and likely non-relapse mortality (NRM); however its prognosis significance in a population of elderly patients remains uncertain. We evaluated the impact of HCT-CI and other factors that may enhance risk stratification in patients of advanced age receiving a RIC HSCT with alemtuzumab T-cell depletion. 85 consecutive patients aged 〉 60 years who received a RIC HSCT for MDS and AML between January 2002 and December 2010 were retrospectively analysed, All patients received an FBC conditioning regimen (fludarabine 150mg/m2 iv, busulphan 8mg/kg oral or 6.4 mg/kg iv, alemtuzumab 100mg iv) followed by HSCT from an HLA identical sibling (n=19) or volunteer unrelated donors (n=66). Median age was 64 years (range 60–72), with 57/28 male/female. Diagnoses included AML with trilineage dysplasia (AML-TLD n=47), RAEB I/II (n=17), CMML (n=8) and RCMD (n=13),cytogenetics (high risk n= 22), IPSS risk divided patients in Low/Intermediate 1 risk (n=13), Intermediate 2 (n=11), High risk (n=6), AML (n=47). A survival analysis for NRM, overall survival (OS), disease free survival (DFS) was performed including pre-transplant HCT-CI (HCT-CI 0 n=20, HCT-CI 1–2 n=21 and HCT-CI 〉 =3 n=43), ferritin level ( 〈 1500 mg n=43, 〉 1500 n=42), number of courses of high dose chemotherapy (= 〈 2 courses n=49, 〉 2 courses n=33), disease status pre-transplant (CR n=75, no CR n=10), CRP level ( 〈 10 n=34, 〉 10 n=25), age 〉 = 65 ( 〈 65 n=53, 〉 65 n= 32), albumin median (albumin median = 42g/L), median Inmunoglobulin G (IgG, median = 9,85g/L) and median Inmunoglobulin M (IgM, median = 0,79g/L). At last follow up 60/85 patient had died (NRM, n=25, relapse n=35; median follow-up, 3.5 years, range 0.3–9.5). HCT-CI score showed no statistically significant impact on 2-year NRM (27 %, 40% and 42% in patients having an HCI-CI score of 0, 1–2 and 〉 =3 respectively, p=0.522, Figure) and 3-year NRM (27%, 52% and 49% respectively) or on 2-year OS (40 %, 39% and 29% in patients having an HCI-CI score of 0, 1–2 and 〉 =3 respectively, p=0.577). Ferritin level, number of courses of high dose chemotherapy, CRP level, age 〉 = 65, albumin level and IgM had not statistically significant impact on NRM or OS, while there was a trend of better outcome for patients with higher IgG level (2 and 3-year NRM 26% and 35% vs 53% and 61%, p=0,090, Figure 1). Of note -and as expected- patients in CR at the time of transplant had a better outcome (2 year OS of 38% vs 0%, p=0,008), and high risk cytogenetics was associated with poorer 2-year OS (41% vs 15% (p=0,006). In summary HCT-CI does not best identify patients at higher risk of NRM in patients older than 60 years receiving an alemtuzumab T-cell depleted RIC allo HSCT for AML or MDS while there is a trend toward worse NRM in patients with lower IgG level; this suggests that poorer humoral immunity before transplant might reflect higher risk of NRM although the underlying mechanism remains to be further investigated. Figure 1. Figure 1. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
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  • 8
    In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-16), p. 3790-3790
    Abstract: The clinical severity of sickle cell disease (SCD) is dependent on genetic and environmental variables. The impact of environmental factors on disease is a major public health issue and air pollution has been consistently correlated with poor health outcomes. Environmental factors in SCD have been poorly studied. We have retrospectively studied the numbers of daily admissions with vaso-occlusive sickle cell pain to King’s College Hospital, London, in relation to local daily air quality measurements. We analysed 1047 patient episodes over 1400 days (1st January 1998 to 31st October 2001). Statistical time series analysis was performed using cross-correlation function (CCF), where the observations of one series are correlated with the observations of another series at various lags and leads, values 〉 0.05 being significant. This showed a significant association between increased numbers of admissions and low levels of nitric oxide (NO) (CCF=0.063), low levels of carbon monoxide (CO) (CCF=0.064) and high levels of ozone (O3) (CCF=0.067). There was no association with sulphur dioxide (SO2), nitric dioxide (NO2) or dust. The significant results were further examined using quartile analysis. This confirmed that increased numbers of hospital admissions were associated with high levels of O3 (oneway ANOVA p=0.039) and low levels of CO (oneway ANOVA p=0.042). Low NO levels were also associated with increased admissions, not however reaching statistical significance on quartile analysis (oneway ANOVA p=0.158). O3 levels show marked seasonal variation, with high levels occurring in summer months in the UK. We have previously shown a trend towards increased admissions in the summer months with acute sickle related pain, whereas other groups, which are primarily based in rural tropical climates, found increased admissions in cold, rainy months. The adverse effect of high O3 levels may explain this difference. There is no direct evidence to explain the mechanism by which high O3 levels leads to vaso-occlusion in SCD but high levels of O3 have been linked to reduced respiratory function, which may in turn precipitate vaso-occlusion. Independent studies have shown high CO levels are linked to increased respiratory and cardiovascular admissions. Paradoxically we found that high CO levels were linked to decreased admission numbers and may be protective against acute pain in SCD. CO may confer benefit by forming carboxyhaemoglobin that cannot polymerise resulting in decreased sickling. Previous studies have shown prolonged red cell survival in vivo following administration of CO to patients with SCD. Our study also suggests higher levels of atmospheric NO are linked to fewer admissions. NO is known to be central in the pathophysiology of vaso-occlusion and sickle cell patients are thought to have functional deficiency of NO. Many groups have reported inhaled NO as beneficial in the treatment of sickle pain. Our study suggests air quality has a significant effect on acute pain in SCD and that patients should be counselled accordingly. Based on these findings it would be appropriate to warn patients that high O3 levels might precipitate complications of SCD. The potential beneficial effect of CO and NO is intriguing and requires further investigation.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2006
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  • 9
    Online Resource
    Online Resource
    American Society of Hematology ; 2010
    In:  Blood Vol. 116, No. 21 ( 2010-11-19), p. 915-915
    In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 915-915
    Abstract: Abstract 915 In this study we put forward a novel approach to investigate the T cell compartment of chronic lymphocytic leukaemia (CLL). The role of T cells in the pathobiology of CLL has become the subject of much research due to compelling evidence that CLL is derived from antigen experienced B cells that are subject to ongoing activation. The malignant proliferation occurs particularly within the pseudofollicles of lymph nodes where the CLL cells are in close proximity with T cells and stromal cells of the microenvironment. Our group has previously shown, by multi-parameter confocal microscopy of paraffin embedded CLL lymph node biopsy sections, that almost all proliferating CLL cells are in close contact with CD4+ CD25+ FOXP3- T cells. In order to gain access to this T cell compartment and gain further insight into the phenotype and role of these T cells we have utilized the technique of lymph node fine needle aspiration (LN-FNA). Patients with a diagnosis of CLL and who have lymphadenopathy accessible to LN-FNA were invited to participate in the study. A total of 21 LN-FNAs were collected from 18 patients. The median cell yield obtained was 4.1 x106 (range 1–13×106). Multi-colour flow cytometry using antibody panels of up to 7 flurochrome combinations was performed using a BD FACSCanto II (BD Biosciences) and analyzed with FlowJo (Treestar) and GraphPad Prism (GraphPad Software Inc.). Uniquely we have been able to compare the phenotype of the T cells derived from the LN-FNA with cells from the peripheral blood (PB) of the same patient taken at the same time. A panel consisting of CD3 (APC-Cy7), CD4 (PerCp-Cy5.5), CD8 (Pacific Blue), CD25 (FITC), CD40L (PE), CTLA-4 (Pe-Cy7), PD-1 (APC) was designed to investigate T cell subsets and activation markers. We found a statistically significant higher number of CD3+ T cells in the lymphocyte gate of CLL LN-FNAs (20.75% +/−13.80) compared to PB (6.25% +/− 4.06); p=0.0152. Additionally, of the CD3+ cells, there were more CD4+ cells in the LN-FNA (72.25% +/− 8.10) compared to PB (59.38% +/− 15.73); p=0.005, and conversely less CD8+ cells in the LN-FNA (17.43% +/− 6.50) compared to PB (27.43% +/− 14.18); p=0.03. The percentage of CD4+ and CD8+ cells expressing CD25, CD40L and CTLA-4 was not found to be significantly different. A further panel consisting of CD4 (PerCP-Cy5.5), CD8 (Pacific Blue), CD45RA (Pe-Cy7), CD62L (APC-Cy7), CCR7 (PE), CD28 (APC) and CD25 (FITC) was used to differentiate between effector memory, central memory and naive T cells. In the LN-FNA CD4+ cells there was a trend towards an increased effector memory phenotype compared to the peripheral blood (60%+/− 20 vs. 29%+/−13). One of the most striking observations in this study was the significantly increased mean fluorescence intensity of the exhaustion marker PD-1 on the CD4+ LN-FNA cells (1041+/− 1130) compared to PB (415.9+/− 487); p=0.0002. This was also mirrored in the CD8+ cells, LN-FNA (1342+/− 1219) compared to PB (465.8+/− 658.7); p=0.0015. Additionally significantly less PD-1 expression was observed in both CD4+ and CD8+ T cells from age matched normal controls confirming the relevance of these findings. Importantly, we have reproduced these observations using multi-parameter immunofluorescence microscopy on paraffin embedded CLL and normal lymph node biopsy samples. Lymph node sections were antigen retrieved and fluorescently labelled with combinations of CD4, CD23, Ki67 as well as PD-1 and then visualised using a Zeiss Axiovert LSM 510 microscope. Our results support the hypothesis that T cells in CLL are chronically stimulated by antigen within the lymph node. In addition, the results from the PB imply that either PD-1 expression is down-regulated on these cells or that the T cell pools derived from LN-FNA and PB are distinct from one another. To investigate this further we are currently examining the T cell receptor repertoires from these two compartments. In addition, it is known that expression levels of PD-L1, a ligand of PD-1, correlates with poor prognosis in many solid tumours and we are therefore investigating the role of this ligand pairing in CLL. In order to understand how this disease persists and progresses it is necessary to unravel the complex network of signals that mediate the survival and proliferation of the CLL cells. Our data suggest that T cells are part of this complex cellular crosstalk and blocking receptor ligand interactions, such as PD-1 and PD-L1, may offer potential future therapeutic targets. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2010
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  • 10
    Online Resource
    Online Resource
    Elsevier BV ; 2011
    In:  Clinical Lymphoma Myeloma and Leukemia Vol. 11 ( 2011-10), p. S191-S192
    In: Clinical Lymphoma Myeloma and Leukemia, Elsevier BV, Vol. 11 ( 2011-10), p. S191-S192
    Type of Medium: Online Resource
    ISSN: 2152-2650
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2011
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    detail.hit.zdb_id: 2193618-3
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