76 results found
Mahomed AS, Burke-Gaffney A, Moledina S, et al., 2019, THE EFFECTS OF BMPRII LOSS ON ENDOTHELIAL SHEAR ADAPTATION IN THE PULMONARY VASCULAR ENDOTHELIUM, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A61-A61, ISSN: 0040-6376
Patel S, Burke-Gaffney A, 2019, The value of mobile tablet computers (iPads) in the undergraduate medical curriculum: an Imperial College medical student view reply, Advances in Medical Education and Practice, Vol: 9, Pages: 769-769, ISSN: 1179-7258
Mahomed A, Burke-Gaffney A, Moledina S, et al., 2019, Late Breaking Abstract - The effects of BMPRII loss on endothelial shear adaptation in the pulmonary vascular endothelium, International Congress of the European-Respiratory-Society (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Nikolakopoulou Z, Hector LR, Creagh-Brown BC, et al., 2019, Plasma S100A8/A9 heterodimer is an early prognostic marker of acute kidney injury associated with cardiac surgery, Biomarkers in Medicine, Vol: 13, Pages: 205-218, ISSN: 1752-0363
We investigated whether plasma levels of the inflammation marker S100A8/A9, could predict acutekidney injury (AKI) onset in patients undergoing cardiac surgery necessitating cardiopulmonary bypass(CPB). Patients & methods: Plasma levels of S100A8/A9 and other neutrophil cytosolic proteins were measured in 39 patients pre- and immediately post-CPB. Results: All markers increased significantly post-CPBwith S100A8/A9, S100A12 and myeloperoxidase levels significantly higher in patients who developed AKIwithin 7 days. S100A8/A9 had good prognostic utility for AKI, with an area under the receiver operating characteristic curve of 0.81 (95% CI: 0.676–0.949) and a cut-off value of 10.6 μg/ml (85.7% sensitivityand 75% specificity) irrespective of age. Conclusion: Plasma S100A8/A9 levels immediately after cardiacsurgery, can predict onset of AKI, irrespective of age.
Mohiaddin H, Wong TDFK, Burke-Gaffney A, et al., 2018, Drug-coated balloon-only percutaneous coronary intervention for the treatment of De novo coronary artery disease: a systematic review, Cardiology and Therapy, Vol: 7, Pages: 127-149, ISSN: 2193-6544
Percutaneous coronary intervention (PCI) with a drug coated balloon (DCB) is a novel treatment which seeks to acutely dilate a coronary stenosis and deliver an anti-proliferative drug to the vessel wall (reducing the risk of re-stenosis), without implanting a drug eluting stent (DES). In this study, we performed a systematic review of stentless DCB-only angioplasty in de novo coronary artery disease. We identified 41 studies examining the effects of DCB-only PCI in a variety of clinical scenarios including small vessels, bifurcations, calcified lesions, and primary PCI. DCB-only PCI appears to be associated with comparable clinical outcomes to DESs and superior angiographic outcomes to plain-old balloon angioplasty. Although current data are promising, there is still a need for further long-term randomized control trial data comparing a DCB-only approach specifically against a second- or third-generation DES. A 4-week period of dual antiplatelet therapy provides a real advantage for the DCB-only PCI approach, which is not possible with most DESs. Since rates of adverse clinical outcomes are very low for all PCI procedures attention should be turned to the development of robust endpoints with which to compare DCB-only PCI approaches to the standard treatment with a DES.
Patel S, Burke-Gaffney A, 2018, The value of mobile tablet computers (iPads) in the undergraduate medical curriculum, Advances in Medical Education and Practice, Vol: 9, Pages: 567-570, ISSN: 1179-7258
The deployment of mobile tablet computers in medical teaching and learning is viewed with mounting interest. Medical educators are embracing insights from technological advancements to ensure that students are equipped with the necessary tools to flourish as physicians. Here we reflect on the benefits and challenges of the tablet learning experience within undergraduate medicine and how students may make the best use of it.
Patel S, Svermova T, Burke-Gaffney A, et al., 2018, Drug-eluting balloons with provisional bail-out or adjunctive stenting in de novo coronary artery lesions-a systematic review and meta-analysis, CARDIOVASCULAR DIAGNOSIS AND THERAPY, Vol: 8, Pages: 121-136, ISSN: 2223-3652
Background: Efficacy of drug-eluting balloons (DEB) for treatment of de novo coronary lesions remains controversial. The present systematic review and meta-analysis of randomised controlled trials assessed DEB with bare-metal stents (BMS) and also DEB with provisional bail-out stents (‘DEB-only’ strategy), to other conventional options: plain-old balloon angioplasty (POBA), BMS and drug-eluting stents (DES).Methods: A systematic literature search from January 2000 until May 2017 was conducted. Primary outcome measure, late lumen loss (LLL); and secondary outcomes; binary restenosis, major adverse cardiac events (MACE), target lesion revascularization (TLR), myocardial infarction (MI), cardiovascular death and stent thrombosis were analysed.Results: Seventeen RCTs were included with 2,616 patients. Several comparative groups showed significant differences. DEB with BMS were inferior to DES for LLL [mean difference (MD) =0.12 mm; 95% confidence interval (CI), 0.03 to 0.22; P=0.01]; and binary restenosis [risk ratio (RR) =1.89; (CI, 1.13 to 3.18); P=0.02]. DEB with BMS was superior to BMS for LLL [MD =−0.27 mm; (−0.45 to −0.10); P=0.002]; and MACE [RR =0.64; (0.46 to 0.90); P=0.010]. Finally, DEB alone was superior to POBA for LLL [MD =−0.39 mm; (−0.67 to −0.11); P=0.006] and binary restenosis [RR =0.20; (0.05 to 0.85); P=0.03] in bifurcation lesions.Conclusions: The results of this meta-analysis showed that whilst DEB with BMS is superior to BMS alone, the combination is inferior to DES for treatment of de novo coronary lesions. Thus, DEB + BMS should not be applied in de novo lesions unless in patients who have absolute contraindications to DES. DEB alone, however, should be considered for relative contraindications to DES such as small vessel disease and bifurcation lesions.
Rasiah MG, Michaeloudes C, Svermova T, et al., 2016, PLASMA SYNDECAN-1 LEVEL AS A PREDICTIVE MARKER OF VASOPLEGIA ASSOCIATED WITH SURGERY REQUIRING CARDIOPULMONARY BYPASS AND POSSIBLE INVOLVEMENT OF OXIDATIVE STRESS, British Thoracic Society Winter Meeting 2016, Publisher: BMJ PUBLISHING GROUP, Pages: A9-A9, ISSN: 0040-6376
Nikolakopoulou Z, Svermova T, Chowdhury J, et al., 2016, Roundabout (Robo) receptors on pulmonary artery endothelial cells: Implications for pulmonary arterial hypertension, ERS, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Burke-Gaffney A, Creagh-Brown BC, 2015, Clinical solutions: not always what they seem?, Critical Care, Vol: 19, ISSN: 1364-8535
Chowdhury J, Ramakrishnan L, Svermova T, et al., 2014, ROBO1/4-SLIT2 EXPRESSION IN PULMONARY VASCULAR CELLS: IMPLICATIONS FOR PAH?, Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A85-A85, ISSN: 0040-6376
Burke-Gaffney A, Svermova T, Mumby S, et al., 2014, Raised Plasma Robo4 and Cardiac Surgery-Associated Acute Kidney Injury, PLOS One, Vol: 9, ISSN: 1932-6203
Objective: Endothelial dysfunction associated with systemic inflammation can contribute to organ injury/failure followingcardiac surgery requiring cardiopulmonary bypass (CPB). Roundabout protein 4 (Robo4), an endothelial-expressedtransmembrane receptor and regulator of cell activation, is an important inhibitor of endothelial hyper-permeability. Weinvestigated the hypothesis that plasma levels of Robo4 are indicative of organ injury, in particular acute kidney injury (AKI),after cardiac surgery.Methods: Patients (n = 32) undergoing elective cardiac surgery with CPB were enrolled, prospectively. Plasma Robo4concentrations were measured pre-, 2 and 24 h post-operatively, using a commercially available ELISA. Plasma andendothelial markers of inflammation [interleukin (IL) -6, -8, -10: von Willibrand factor (vWF) and angiopoeitin-2 (Ang-2)] andthe AKI marker, neutrophil gelatinase-associated lipocalin (NGAL), were also measured by ELISA.Results: Plasma Robo4 increased significantly (p,0.001) from pre-operative levels of 25156904 pg/ml to 447361915 pg/ml, 2 h after surgery; and returned to basal levels (26826979 pg/ml) by 24 h. Plasma cytokines, vWF and NGAL alsoincreased 2 h post-operatively and remained elevated at 24 h. Ang-2 increased 24 h post-operatively, only. There was apositive, significant correlation (r = 0.385, p = 0.0298) between Robo-4 and IL-10, but not other cytokines, 2 h postoperatively.Whilst raised Robo4 did not correlate with indices of lung dysfunction or other biomarkers of endothelialactivation; there was a positive, significant correlation between raised (2 h) plasma NGAL and Robo4 (r = 0.4322, p = 0.0135).When patients were classed as AKI or non-AKI either using NGAL cut-off of 150 ng/ml, or the AKI Network (AKIN) clinicalclassification; plasma Robo4 was significantly higher (p = 0.0073 and 0.003, respectively) in AKI vs. non-AKI patients (NGALcut-off: 535062191 ng/ml, n = 16 vs. 359561068 pg/ml, n = 16; AKIN: 6546 pg/ml, IQR 5025–8079, n
Nikolakopoulou Z, Smith M, Hector LR, et al., 2013, S100A12 AS A BIOMARKER FOR NEUTROPHIL MEDIATED INFLAMMATION IN PATIENTS UNDERGOING CARDIAC SURGERY NECESSITATING CARDIOPULMONARY BYPASS, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A141-A141, ISSN: 0040-6376
Creagh-Brown BC, Quinlan GJ, Hector LR, et al., 2013, Association between preoperative plasma sRAGE levels and recovery from cardiac surgery, Mediators of Inflammation, Vol: 2013, Pages: 1-7, ISSN: 0962-9351
Background. The receptor for advanced glycation end products (RAGE) is an inflammation-perpetuating receptor, and solubleRAGE (sRAGE) is a marker of cellular RAGE expression. This study investigated whether raised plasma levels prior to surgery ofsRAGE or S100A8/A9 (a RAGE ligand) were associated with longer duration of hospital care in patients undergoing cardiac surgerynecessitating cardiopulmonary bypass. Methods. Patients (𝑛 = 130) undergoing elective cardiac surgery were enrolled prospectively.Plasma sRAGE and S100A8/A9 concentrations were measured before and 2 h after surgery. Results. Preoperative plasma sRAGEincreased significantly (𝑃 < 0.0001) from 1.06 ng/mL (IQR, 0.72–1.76) to 1.93 ng/mL (IQR, 1.14–2.63) 2 h postoperatively. PlasmaS100A8/9 was also significantly (𝑃 < 0.0001) higher 2 h postoperatively (2.37 𝜇g/mL, IQR, 1.81–3.05) compared to pre-operativelevels (0.41 𝜇g/mL, IQR, 0.2–0.65). Preoperative sRAGE, but not S100A8/A9, was positively and significantly correlated withduration of critical illness (𝑟 = 0.3, 𝑃 = 0.0007) and length of hospital stay (LOS; 𝑟 = 0.31, 𝑃 < 0.0005). Multivariate binarylogistic regression showed preoperative sRAGE to be, statistically, an independent predictor of greater than median duration ofcritical illness (odds ratio 16.6, 𝑃 = 0.014) and to be, statistically, the strongest independent predictor of hospital LOS. Conclusion.Higher preoperative plasma sRAGE levels were associated with prolonged duration of care in adults undergoing cardiac surgeryrequiring cardiopulmonary bypass.
Nikolakopoulou Z, Creagh-Brown B, Burke-Gaffney A, et al., 2013, Decreased expression of receptor for advanced glycation end-products (RAGE) on neutrophils following surgery necessitating cardiopulmonary bypass (snCPB), 100th Annual Meeting of the American-Association-of-Immunologists, Publisher: AMER ASSOC IMMUNOLOGISTS, ISSN: 0022-1767
Mongardon N, Lemiale V, Borderie D, et al., 2013, Plasma thioredoxin levels during post-cardiac arrest syndrome: relationship with severity and outcome, CRITICAL CARE, Vol: 17, ISSN: 1466-609X
Patel M, Svermova T, Ramakrishnan L, et al., 2012, RAGE ACTIVATION AND ENDOTHELIAL CELL INJURY ASSOCIATED WITH CARDIOPULMONARY BYPASS, Winter Meeting of the British-Thoracic-Society 2012, Publisher: BMJ PUBLISHING GROUP, Pages: A36-A37, ISSN: 0040-6376
Finney SJ, Leaver SK, Evans TW, et al., 2012, Differences in lipopolysaccharide- and lipoteichoic acid-induced cytokine/chemokine expression, Intensive Care Medicine, Vol: 38, Pages: 324-332, ISSN: 1432-1238
Purpose: To investigatedifferences in cytokine/chemokinerelease in response to lipoteichoicacid (LTA) or lipopolysaccharide(LPS) and contributing cellularmechanisms, in order to improveunderstanding of the pathogenesis ofsepsis. Methods: Levels of cytokines/chemokineswere measured inplasma and peritoneal lavage fluid of10-week-old male mice (C57/B16)following intraperitoneal injection ofLTA or LPS (250 lg), and in supernatantsof murine J774.2 cells,immortalised blood monocytes, orisolated human monocytes treatedwith LTA or LPS (0–10 lg/ml). Therole of cytokine/chemokine messengerRNA (mRNA) stability versusnuclear factor-kappaB (NF-jB) andactivator protein-1 (AP-1) in mediatingcytokine/chemokine release inJ774 cells was also assessed.Results: In mice, plasma levels ofkeratinocyte-derived chemokine(KC), macrophage inflammatoryprotein (MIP)-2, interleukin (IL)-10,interferon (IFN)-c and tumour necrosisfactor-alpha (TNF-a) andperitoneal lavage fluid levels of KC, MIP-2 and TNF-a increased signifi-cantly 1 h after LPS. Only KC andMIP-2 levels increased 1 h after LTA.LPS-treated (10 lg/ml) J774 cellsreleased MIP-2, IL-10, IFN-c andTNF-a but not KC (24 h), whereascells treated with 10 lg/ml LTAreleased only MIP-2. LPS-stimulatedhuman monocytes released IL-10 andIL-8 (24 h); by contrast, LTA-treatedcells released only IL-8. LPS andLTA activated NF-jB and AP-1 inJ774 cells. The protein synthesisinhibitor cycloheximide abolishedLPS-induced IL-10 mRNA expressionand increased LTA- and LPSinducedmRNA for MIP-2 in J774cells. Conclusion: LTA and LPS, atclinically relevant concentrations,induced differential cytokine/chemokinerelease in vitro and in vivo, viaeffects distal to activation of NF-jB/AP-1 that might include chromatinremodelling or mRNA stability.
Burke-Gaffney A, Evans TW, 2012, Lest we forget the endothelial glycocalyx in sepsis, CRITICAL CARE, Vol: 16, ISSN: 1466-609X
Zhang J, Creagh-Brown BC, Mumby S, et al., 2011, INCREASED PLASMA LEVELS OF SYNDECAN-1 AND sFLT-1 DURING CARDIOPULMONARY BYPASS SURGERY: ASSOCIATIONS WITH sRAGE, Winter Meeting of the British-Thoracic-Society, Publisher: B M J PUBLISHING GROUP, Pages: A36-A36, ISSN: 0040-6376
Creagh-Brown BC, Burke-Gaffney A, Evans TW, 2011, sRAGE: A useful biomarker in acute lung injury?, CRITICAL CARE MEDICINE, Vol: 39, Pages: 589-590, ISSN: 0090-3493
Leaver SK, Quinlan GJ, Evans TW, et al., 2010, THIOREDOXIN MODIFIES MIF RELEASE FROM HUMAN MONOCYTES FOLLOWING STIMULATION WITH LTA AND LPS, British-Thoracic-Society-Winter-Meeting 2010, Publisher: B M J PUBLISHING GROUP, Pages: A25-A26, ISSN: 0040-6376
Kaneshamoorthy M, Creagh-Brown BC, Burke-Gaffney A, 2010, RAGE-MEDIATED CYTOKINE RELEASE FROM LEUKOCYTES: IMPLICATIONS FOR SYSTEMIC INFLAMMATION, British-Thoracic-Society-Winter-Meeting 2010, Publisher: B M J PUBLISHING GROUP, Pages: A23-A24, ISSN: 0040-6376
Creagh-Brown BC, Quinlan GJ, Evans TW, et al., 2010, The RAGE axis in systemic inflammation, acute lung injury and myocardial dysfunction: an important therapeutic target?, INTENSIVE CARE MEDICINE, Vol: 36, Pages: 1644-1656, ISSN: 0342-4642
Leaver SK, MacCallum NS, Pingle V, et al., 2010, Increased plasma thioredoxin levels in patients with sepsis: positive association with macrophage migration inhibitory factor., Intensive Care Med, Vol: 36, Pages: 336-341, ISSN: 1432-1238
PURPOSE: To establish the relationship between plasma levels of thioredoxin (Trx) and macrophage migration inhibitory factor (MIF) in systemic inflammatory stress syndrome (SIRS)/sepsis. METHODS: Enzyme-linked immunosorbent assay measurements of Trx, MIF, IL-6, -8, and -10 and enzyme-linked fluorescent assay determination of procalcitonin (PCT) in plasma from patients with SIRS/sepsis, neutropenic sepsis, healthy volunteers and pre-oesophagectomy patients. RESULTS: Thioredoxin was significantly higher in SIRS/sepsis patients [101.3 ng ml(-1), interquartile range (IQR) 68.7-155.6, n = 32] compared with that in healthy controls (49.5 ng ml(-1), IQR 31.4-71.1, P < 0.001, n = 17) or pre-oesophagectomy patients (40.5 ng ml(-1), IQR 36.9-63.2, P < 0.01, n = 7), but was not raised in neutropenics (n = 5). MIF levels were also significantly higher in SIRS/sepsis patients (12.1 ng ml(-1), IQR 9.5-15.5, n = 35), but not in the neutropenic group, when compared with healthy controls (9.3 ng ml(-1), IQR 7.3-10.7, P < 0.01, n = 20). Trx levels correlated, positively, with MIF levels and APACHE II scores. Plasma levels of IL-6, -8 and -10 and PCT increased significantly in patients with SIRS/sepsis (P < 0.001) and with neutropenic sepsis, but did not correlate with Trx or MIF levels. CONCLUSION: Plasma levels of Trx, MIF, IL-6, -8, -10 and PCT were raised in patients with SIRS/sepsis. Comparisons between mediators suggest a unique correlation of Trx with MIF. Moreover, Trx and MIF differed from cytokines and PCT in that levels were significantly lower in patients with neutropenia compared with the main SIRS/sepsis group. By contrast, IL-8 and PCT levels were significantly greater in the neutropenic patient group. The link between MIF and Trx highlighted in this study has implications for future investigations into the pathogenesis of SIRS/sepsis.
Creagh-Brown BC, Quinlan G, Evans TW, et al., 2010, Advanced Glycation End-Products, Release Of Their Soluble Receptors (es And SRAGE) And Relationship To CRP After Surgery Necessitating Cardiopulmonary Bypass, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 181, ISSN: 1073-449X
Creagh-Brown BC, Quinlan G, Evans TW, et al., 2010, The RAGE Ligand S100B Induces IL-8 Release From Whole Blood And Isolated Neutrophils, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 181, ISSN: 1073-449X
Burke-Gaffney A, Evans TW, Quinlan GJ, 2009, Thioredoxin in sepsis: Just another biomarker or a plausible therapeutic target?, CRITICAL CARE MEDICINE, Vol: 37, Pages: 2304-2305, ISSN: 0090-3493
Creagh-Brown BC, Hector L, Lagan A, et al., 2009, The Role of sRAGE in the Development of ALI after Surgery Necessitating Cardiopulmonary Bypass., AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 179, ISSN: 1073-449X
Creagh-Brown BC, Hector L, Lagan A, et al., 2009, RAGE Ligands Are Implicated in the Development of SIRS after Surgery Necessitating Cardiopulmonary Bypass, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 179, ISSN: 1073-449X
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