29 results found
Hussain H, Vutipongsatorn K, Jimenez B, et al., 2022, Patient stratification in sepsis: Using metabolomics to detect clinical phenotypes, sub-phenotypes and therapeutic response, Metabolites, ISSN: 2218-1989
Arkell P, Wilson R, Antcliffe DB, et al., 2022, A pilot observational study of CSF vancomycin therapeutic drug monitoring during the treatment of nosocomial ventriculitis., Journal of Infection, ISSN: 0163-4453
Warner B, Harry A, Brett S, et al., 2022, The end is just the beginning: involvement of bereaved next of kin in qualitative research, BMJ Supportive & Palliative Care, Vol: 12, ISSN: 2045-4368
Jones T, Janani L, Gordon A, et al., 2022, A novel role for cytochrome P450 epoxygenase metabolites in septic shock, Critical Care Explorations, Vol: 4, ISSN: 2639-8028
Objectives Oxylipins are oxidative breakdown products of cell membrane fatty acids. Animal models have demonstrated that oxylipins generated by the P450 epoxygenase pathway may be implicated in septic shock pathology. However, these mediators are relatively unexplored in humans with septic shock. We aimed to determine if there were patterns of oxylipins that were associated with 28-day septic shock mortality and organ dysfunction. Design Retrospective analysis of samples collected during the Vasopressin vs. Norepinephrine as Initial Therapy in Septic Shock trial.Setting Intensive Care Units in the United KingdomPatients Adults recruited within six hours of onset of septic shock. Interventions Trial interventions were not considered in this analysis.Measurements and Main Results Oxylipin profiling was performed on 404 serum samples from 152 patients using liquid chromatography-mass spectrometry. Non-survivors were found to have higher levels of 14,15-dihydroxyeicosatrienoic acid at baseline (DHET) than survivors (p=0.02). Patients with 14,15-DHET levels above the lower limit of quantification of the assay were more likely to die than patients with levels below this limit (Hazard Ratio 2.3, 95% CI 1.2-4.5). Patients with measurable 14,15-DHET had higher levels of organ dysfunction and fewer renal failure free days than those in whom it was unmeasurable. Considering samples collected over the first week of intensive care stay, measurable levels of DHET species were associated with higher daily SOFA scores which appeared to be accounted for predominantly by the liver component. Measurable 14,15-DHET showed positive correlation with bilirubin (rs=0.38, p<0.001) and lactate (rs=0.27, p=0.001).Conclusions The P450 epoxygenase-derived DHET species of oxylipins were associated with organ, particularly liver, dysfunction in septic shock and 14,15-DHET was associated with septic shock mortality. These results support further investigation into the role of the P450 epoxygena
Patel BV, Haar S, Handslip R, et al., 2021, Natural history, trajectory, and management of mechanically ventilated COVID-19 patients in the United Kingdom, Intensive Care Medicine, Vol: 47, Pages: 549-565, ISSN: 0342-4642
PurposeThe trajectory of mechanically ventilated patients with coronavirus disease 2019 (COVID-19) is essential for clinical decisions, yet the focus so far has been on admission characteristics without consideration of the dynamic course of the disease in the context of applied therapeutic interventions.MethodsWe included adult patients undergoing invasive mechanical ventilation (IMV) within 48 h of intensive care unit (ICU) admission with complete clinical data until ICU death or discharge. We examined the importance of factors associated with disease progression over the first week, implementation and responsiveness to interventions used in acute respiratory distress syndrome (ARDS), and ICU outcome. We used machine learning (ML) and Explainable Artificial Intelligence (XAI) methods to characterise the evolution of clinical parameters and our ICU data visualisation tool is available as a web-based widget (https://www.CovidUK.ICU).ResultsData for 633 adults with COVID-19 who underwent IMV between 01 March 2020 and 31 August 2020 were analysed. Overall mortality was 43.3% and highest with non-resolution of hypoxaemia [60.4% vs17.6%; P < 0.001; median PaO2/FiO2 on the day of death was 12.3(8.9–18.4) kPa] and non-response to proning (69.5% vs.31.1%; P < 0.001). Two ML models using weeklong data demonstrated an increased predictive accuracy for mortality compared to admission data (74.5% and 76.3% vs 60%, respectively). XAI models highlighted the increasing importance, over the first week, of PaO2/FiO2 in predicting mortality. Prone positioning improved oxygenation only in 45% of patients. A higher peak pressure (OR 1.42[1.06–1.91]; P < 0.05), raised respiratory component (OR 1.71[ 1.17–2.5]; P < 0.01) and cardiovascular component (OR 1.36 [1.04–1.75]; P < 0.05) of the sequential organ failure assessment (SOFA) score and raised lactate (OR 1.33 [0.99–1.79
Patel BV, Haar S, Handslip R, et al., 2020, Natural history, trajectory, and management of mechanically ventilated COVID-19 patients in the United Kingdom, Publisher: Cold Spring Harbor Laboratory
Background To date the description of mechanically ventilated patients with Coronavirus Disease 2019 (COVID-19) has focussed on admission characteristics with no consideration of the dynamic course of the disease. Here, we present a data-driven analysis of granular, daily data from a representative proportion of patients undergoing invasive mechanical ventilation (IMV) within the United Kingdom (UK) to evaluate the complete natural history of COVID-19.Methods We included adult patients undergoing IMV within 48 hours of ICU admission with complete clinical data until death or ICU discharge. We examined factors and trajectories that determined disease progression and responsiveness to ARDS interventions. Our data visualisation tool is available as a web-based widget (https://www.CovidUK.ICU).Findings Data for 623 adults with COVID-19 who were mechanically ventilated between 01 March 2020 and 31 August 2020 were analysed. Mortality, intensity of mechanical ventilation and severity of organ injury increased with severity of hypoxaemia. Median tidal volume per kg across all mandatory breaths was 5.6 [IQR 4.7-6.6] mL/kg based on reported body weight, but 7.0 [IQR 6.0-8.4] mL/kg based on calculated ideal body weight. Non-resolution of hypoxaemia over the first week of IMV was associated with higher ICU mortality (59.4% versus 16.3%; P<0.001). Of patients ventilated in prone position only 44% showed a positive oxygenation response. Non-responders to prone position show higher D-Dimers, troponin, cardiovascular SOFA, and higher ICU mortality (68.9% versus 29.7%; P<0.001). Multivariate analysis showed prone non-responsiveness being independently associated with higher lactate (hazard ratio 1.41, 95% CI 1.03–1.93), respiratory SOFA (hazard ratio 3.59, 95% CI 1.83–7.04); and cardiovascular SOFA score (hazard ratio 1.37, 95% CI 1.05–1.80).Interpretation A sizeable proportion of patients with progressive worsening of hypoxaemia were also refractory to evid
Antcliffe DB, Gordon AC, 2019, Why Understanding Sepsis Endotypes Is Important for Steroid Trials in Septic Shock, Critical Care Medicine, Vol: 47, Pages: 1782-1784, ISSN: 0090-3493
Antcliffe DB, Santhakumaran S, Orme RML, et al., 2019, Levosimendan in septic shock in patients with biochemical evidence of cardiac dysfunction: a subgroup analysis of the LeoPARDS randomised trial, Intensive Care Medicine, Vol: 45, Pages: 1392-1400, ISSN: 0342-4642
PurposeMyocardial dysfunction is common in sepsis but optimal treatment strategies are unclear. The inodilator, levosimendan was suggested as a possible therapy; however, the levosimendan to prevent acute organ dysfunction in Sepsis (LeoPARDS) trial found it to have no benefit in reducing organ dysfunction in septic shock. In this study we evaluated the effects of levosimendan in patients with and without biochemical cardiac dysfunction and examined its non-inotropic effects.MethodsTwo cardiac biomarkers, troponin I (cTnI) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and five inflammatory mediators were measured in plasma from patients recruited to the LeoPARDS trial at baseline and over the first 6 days. Mean total Sequential Organ Failure Assessment (SOFA) score and 28-day mortality were compared between patients with normal and raised cTnI and NT-proBNP values, and between patients above and below median values.ResultsLevosimendan produced no benefit in SOFA score or 28-day mortality in patients with cardiac dysfunction. There was a statistically significant treatment by subgroup interaction (p = 0.04) in patients with NT-proBNP above or below the median value. Those with NT-proBNP values above the median receiving levosimendan had higher SOFA scores than those receiving placebo (mean daily total SOFA score 7.64 (4.41) vs 6.09 (3.88), mean difference 1.55, 95% CI 0.43–2.68). Levosimendan had no effect on the rate of decline of inflammatory biomarkers.ConclusionAdding levosimendan to standard care in septic shock was not associated with less severe organ dysfunction nor lower mortality in patients with biochemical evidence of cardiac dysfunction.
Antcliffe D, Burnham K, Al-Beidh F, et al., 2019, Transcriptomic signatures in sepsis and a differential response to steroids: from the VANISH randomized trial, American Journal of Respiratory and Critical Care Medicine, Vol: 199, Pages: 980-986, ISSN: 1073-449X
Rationale: There remains uncertainty about the role of corticosteroids in sepsis with clear beneficial effects on shock duration but conflicting survival effects. Two transcriptomic sepsis response signatures (SRS) have been identified. SRS1 is relatively immunosuppressed whilst SRS2 is relatively immunocompetent. Objectives: We aimed to categorized patients based on SRS endotypes to determine if these profiles influenced response to either norepinephrine or vasopressin, or to corticosteroids in septic shock. Methods: A post-hoc analysis was performed of a double-blind randomized clinical trial in septic shock (VANISH). Patients were included within 6 hours of onset of shock and were randomized to receive norepinephrine or vasopressin followed by hydrocortisone or placebo. Genome-wide gene expression profiling was performed and SRS endotype was determined using a previously established model using seven discriminant genes. Measurements and Main Results: Samples were available from 176 patients, 83 SRS1 and 93 SRS2. There was no significant interaction between SRS group and vasopressor assignment (p=0·50). However, there was an interaction between assignment to hydrocortisone or placebo, and SRS endotype (p=0·02). Hydrocortisone use was associated with increased mortality in those with an SRS2 phenotype (OR 7·9, 95%CI 1·6-39·9). Conclusions: Transcriptomic profile at onset of septic shock was associated with response to corticosteroids. Those with the immuno-competent SRS2 endotype had significantly higher mortality when given corticosteroids compared to placebo. Clinical trial registration available at www.isrctn.com, ID ISRCTN20769191.
Antcliffe D, Ward J, Marshall T, et al., 2018, Multivariate analysis of cytokines in septic shock predicts outcome, European Society of Intensive Care Medicine Congress, Publisher: SpringerOpen, ISSN: 2197-425X
Antcliffe D, Al-Beidh F, Gordon A, 2018, Metabolic profiles in sepsis evolve over time, European Society of Intensive Care Medicine Congress, Publisher: SpringerOpen, ISSN: 2197-425X
O'Callaghan D, Antcliffe D, 2018, Vasodilators and antihypertensives, Oh's Intensive Care Manual, Editors: Bersten, Handy, Publisher: Elsevier, ISBN: 9780702072215
This bestselling manual covers all aspects of intensive care in sufficient detail for daily practice while keeping you up to date with the latest innovations in the field.
Antcliffe D, Wolfer A, O'Dea K, et al., 2018, Profiling inflammatory markers in patients with pneumonia on intensive care, Scientific Reports, Vol: 8, ISSN: 2045-2322
Clinical investigations lack predictive value when diagnosing pneumonia, especially when patients are ventilated and develop ventilator associated pneumonia (VAP). New tools to aid diagnosis are important to improve outcomes. This pilot study examines the potential for a panel of inflammatory mediators to aid in the diagnosis. Forty-four ventilated patients, 17 with pneumonia and 27 with brain injuries, eight of whom developed VAP, were recruited. 51 inflammatory mediators, including cytokines and oxylipins, were measured in patients’ serum using flow cytometry and mass spectrometry. The mediators could separate patients admitted to ICU with pneumonia compared to brain injury with an area under the receiver operating characteristic curve (AUROC) 0.75 (0.61–0.90). Changes in inflammatory mediators were similar in both groups over the course of ICU stay with 5,6-dihydroxyeicosatrienoic and 8,9-dihydroxyeicosatrienoic acids increasing over time and interleukin-6 decreasing. However, brain injured patients who developed VAP maintained inflammatory profiles similar to those at admission. A multivariate model containing 5,6-dihydroxyeicosatrienoic acid, 8,9-dihydroxyeicosatrienoic acid, intercellular adhesion molecule-1, interleukin-6, and interleukin-8, could differentiate patients with VAP from brain injured patients without infection (AUROC 0.94 (0.80–1.00)). The use of a selected group of markers showed promise to aid the diagnosis of VAP especially when combined with clinical data.
Antcliffe D, Fiorini F, Gordon A, 2018, Lessons from the ICU: choosing the right vasopressor, Hemodynamic Monitoring, Editors: Pinsky, Teboul, Vincent, Publisher: Springer, ISBN: 9783319692692
This book, part of the European Society of Intensive Care Medicine textbook series, teaches readers how to use hemodynamic monitoring, an essential skill for today’s intensivists.
Antcliffe D, Jimenez B, Veselkov K, et al., 2017, Metabolic profiling in patients with pneumonia on intensive care, EBioMedicine, Vol: 18, Pages: 244-253, ISSN: 2352-3964
Clinical features and investigations lack predictive value when diagnosing pneumonia, especially when patients are ventilated and when patients develop ventilator associated pneumonia (VAP). New tools to aid diagnosis are important to improve outcomes. This pilot study examines the potential for metabolic profiling to aid the diagnosis in critical care.In this prospective observational study ventilated patients with brain injuries or pneumonia were recruited in the intensive care unit and serum samples were collected soon after the start of ventilation. Metabolic profiles were produced using 1D 1H NMR spectra. Metabolic data were compared using multivariate statistical techniques including Principal Component Analysis (PCA) and Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA).We recruited 15 patients with pneumonia and 26 with brain injuries, seven of whom went on to develop VAP. Comparison of metabolic profiles using OPLS-DA differentiated those with pneumonia from those with brain injuries (R2Y = 0.91, Q2Y = 0.28, p = 0.02) and those with VAP from those without (R2Y = 0.94, Q2Y = 0.27, p = 0.05). Metabolites that differentiated patients with pneumonia included lipid species, amino acids and glycoproteins.Metabolic profiling shows promise to aid in the diagnosis of pneumonia in ventilated patients and may allow a more timely diagnosis and better use of antibiotics.
Antcliffe D, Gordon AC, 2016, Metabonomics and Intensive Care, Annual Update in Intensive Care and Emergency Medicine 2016, Editors: Vincent, Publisher: Springer, Pages: 353-364, ISBN: 978-3-319-27348-8
Gordon AC, Antcliffe D, 2016, Metabonomics and intensive care, Critical Care, Vol: 20, ISSN: 1364-8535
This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency medicine 2016. Other selected articles can be found online at http://www.biomedcentral.com/collections/annualupdate2016. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901.
Herrmann IK, Bertazzo S, O'Callaghan D, et al., 2015, Differentiating sepsis from non-infectious systemic inflammation based on microvesicle-bacteria aggregation, Nanoscale, Vol: 7, Pages: 13511-13520, ISSN: 2040-3364
Sepsis is a severe medical condition and a leading cause of hospital mortality. Prompt diagnosis and early treatment has a significant, positive impact on patient outcome. However, sepsis is not always easy to diagnose, especially in critically ill patients. Here, we present a conceptionally new approach for the rapid diagnostic differentiation of sepsis from non-septic intensive care unit patients. Using advanced microscopy and spectroscopy techniques, we measure infection-specific changes in the activity of nano-sized cell-derived microvesicles to bind bacteria. We report on the use of a point-of-care-compatible microfluidic chip to measure microvesicle-bacteria aggregation and demonstrate rapid (≤1.5 hour) and reliable diagnostic differentiation of bacterial infection from non-infectious inflammation in a double-blind pilot study. Our study demonstrates the potential of microvesicle activities for sepsis diagnosis and introduces microvesicle-bacteria aggregation as a potentially useful parameter for making early clinical management decisions.
Antcliffe D, Wolfer A, O'Dea KP, et al., 2015, Profiling Of Eicosanoids And Cytokines As An Aid To Diagnosing Pneumonia On Intensive Care, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Antcliffe D, Jimenez B, Veselkov K, et al., 2014, DIAGNOSING PNEUMONIA ON THE INTENSIVE CARE UNIT WITH SERUM H-1 NMR SPECTROSCOPY, 27th Annual Congress of the European-Society-of-Intensive-Care-Medicine (ESICM), Publisher: SPRINGER, Pages: S237-S238, ISSN: 0342-4642
Antcliffe DB, Veselkov K, Pearce JTM, et al., 2013, TRAJECTORY ANALYSIS OF CLINICAL VARIABLES TO IMPROVE DIAGNOSIS OF VENTILATOR ASSOCIATED PNEUMONIA IN PATIENTS Wan BRAIN INJURY, ESICM 26th Annual Congress, Publisher: SPRINGER, Pages: S312-S313, ISSN: 0342-4642
Antcliffe D, Calopez L, Ledbury M, et al., 2009, EFFECT OF IMPLEMENTING ROUTINE OESOPHAGEAL DOPPLER MONITORING IN COLORECTAL AND ORTHOPAEDIC SURGERY, 22nd Annual Congress of the European-Society-of-Intensive-Care-Medicine, Publisher: SPRINGER, Pages: 135-135, ISSN: 0342-4642
Antcliffe D, Nanidis TG, Darzi AW, et al., 2009, A meta-analysis of mini-open versus standard open and laparoscopic living donor nephrectomy, TRANSPLANT INTERNATIONAL, Vol: 22, Pages: 463-474, ISSN: 0934-0874
Nanidis TG, Antcliffe D, Kokkinos C, et al., 2008, Laparoscopic versus open live donor nephrectomy in renal transplantation - A meta-analysis, ANNALS OF SURGERY, Vol: 247, Pages: 58-70, ISSN: 0003-4932
Kokkinos C, Antcliffe D, Nanidis T, et al., 2007, Outcome of kidney transplantation from nonheart-beating versus heart-beating cadaveric donors, TRANSPLANTATION, Vol: 83, Pages: 1193-1199, ISSN: 0041-1337
Kokkinos C, Nanidis T, Antcliffe D, et al., 2007, Comparison of laparoscopic versus hand-assisted live donor nephrectomy, TRANSPLANTATION, Vol: 83, Pages: 41-47, ISSN: 0041-1337
Keelan J, Allen NJ, Antcliffe D, et al., 2001, Quantitative imaging of glutathione in hippocampal neurons and glia in culture using monochlorobimane, JOURNAL OF NEUROSCIENCE RESEARCH, Vol: 66, Pages: 873-884, ISSN: 0360-4012
Cano-Gamez E, Burnham KL, Goh C, et al., An immune dysfunction score for stratification of patients with acute infection based on whole blood gene expression
<jats:title>Abstract</jats:title><jats:p>Dysregulated host responses to infection can lead to organ dysfunction and sepsis, causing millions of deaths globally each year. To alleviate this burden, improved prognostication and biomarkers of response are urgently needed. We investigated the use of whole blood transcriptomics for stratification of patients with severe infection by integrating data from 3,149 samples of sepsis patients and healthy individuals into a gene expression reference map. We used this map to derive a quantitative sepsis response signature (SRSq) score reflective of immune dysfunction and predictive of clinical outcomes, which can be estimated using a 19-gene signature. Finally, we built a machine learning framework, SepstratifieR, to deploy SRSq in sepsis, H1N1 influenza, and COVID-19, demonstrating clinically relevant stratification across diseases and revealing the physiological alterations linking immune dysregulation to mortality. Our method enables early identification of individuals with dysfunctional immune profiles, thus bringing us closer to precision medicine in infection.</jats:p>
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