Critical care wardCritical care involves the care of the sickest patients in the hospital. Critically ill patients have usually been through a significant insult to their body (such as trauma, infection, burn) and have developed organ failure and require life-support. Critical Care is the largest theme bringing together clinicians and scientists from diverse backgrounds and includes collaborative research from hospitals throughout north-west London. Investigations range from evaluating biological mechanisms of organ failure through to the development of innovative technologies which allow the short-term and long-term support and recovery of organs. 

Many people are exposed to the environment of an Intensive care unit (ICU) either personally or through a family member. It is often a life-changing event and our work aims to reduce this impact facilitating post-ICU recovery.

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  • Journal article
    Parnia S, Yang J, Nguyen R, Ahn A, Zhu J, Inigo-Santiago L, Nasir A, Golder K, Ravishankar S, Bartlett P, Xu J, Pogson D, Cooke S, Walker C, Spearpoint K, Kitson D, Melody T, Chilwan M, Schoenfeld E, Richman P, Mills B, Wichtendahl N, Nolan J, Singer A, Brett S, Perkins GD, Deakin CDet al., 2016,

    Cerebral oximetry during cardiac arrest: a multicenter study of neurologic outcomes and survival

    , Critical Care Medicine, Vol: 44, Pages: 1663-1674, ISSN: 0090-3493

    OBJECTIVES: Cardiac arrest is associated with morbidity and mortality because of cerebral ischemia. Therefore, we tested the hypothesis that higher regional cerebral oxygenation during resuscitation is associated with improved return of spontaneous circulation, survival, and neurologic outcomes at hospital discharge. We further examined the validity of regional cerebral oxygenation as a test to predict these outcomes. DESIGN: Multicenter prospective study of in-hospital cardiac arrest. SETTING: Five medical centers in the United States and the United Kingdom. PATIENTS: Inclusion criteria are as follows: in-hospital cardiac arrest, age 18 years old or older, and prolonged cardiopulmonary resuscitation greater than or equal to 5 minutes. Patients were recruited consecutively during working hours between August 2011 and September 2014. Survival with a favorable neurologic outcome was defined as a cerebral performance category 1-2. INTERVENTIONS: Cerebral oximetry monitoring. MEASUREMENTS AND MAIN RESULTS: Among 504 in-hospital cardiac arrest events, 183 (36%) met inclusion criteria. Overall, 62 of 183 (33.9%) achieved return of spontaneous circulation, whereas 13 of 183 (7.1%) achieved cerebral performance category 1-2 at discharge. Higher mean ± SD regional cerebral oxygenation was associated with return of spontaneous circulation versus no return of spontaneous circulation (51.8% ± 11.2% vs 40.9% ± 12.3%) and cerebral performance category 1-2 versus cerebral performance category 3-5 (56.1% ± 10.0% vs 43.8% ± 12.8%) (both p < 0.001). Mean regional cerebral oxygenation during the last 5 minutes of cardiopulmonary resuscitation best predicted the return of spontaneous circulation (area under the curve, 0.76; 95% CI, 0.69-0.83); regional cerebral oxygenation greater than or equal to 25% provided 100% sensitivity (95% CI, 94-100) and 100% negative predictive value (95% CI, 79-100); regional cerebral oxygenation greater than or equal t

  • Journal article
    Zhao H, Mitchell S, Koumpa S, Cui YT, Lian Q, Hagberg H, Johnson M, Takata M, Ma Det al., 2016,

    Heme Oxygenase-1 mediates neuro-protection conferred by argon in combination with hypothermia in neonatal hypoxia-ischemia brain injury

    , Anesthesiology, Vol: 125, Pages: 180-192, ISSN: 1528-1175

    Argon–hypothermia treatment reduced both neuronal death in an in vitro neuronal culture model and brain infarct size in an in vivo rat model of neonatal asphyxia. The protective effects of argon–hypothermia involve both inhibition of apoptosis and neuroinflammation mechanisms and activation of cell survival pathways.

  • Journal article
    Fotopoulou C, Jones BP, Savvatis K, Campbell J, Kyrgiou M, Farthing A, Brett S, Roux R, Hall M, Rustin G, Gabra H, Jiao L, Stumpfle Ret al., 2016,

    Maximal effort cytoreductive surgery for disseminated ovarian cancer in a UK setting: challenges and possibilities

    , Gynecologic Oncology, ISSN: 1095-6859

    OBJECTIVE: To assess surgical morbidity and mortality of maximal effort cytoreductive surgery for disseminated epithelial ovarian cancer (EOC) in a UK tertiary center. METHODS/MATERIALS: A monocentric prospective analysis of surgical morbidity and mortality was performed for all consecutive EOC patients who underwent extensive cytoreductive surgery between 01/2013 and 12/2014. Surgical complexity was assessed by the Mayo clinic surgical complexity score (SCS). Only patients with high SCS ≥5 were included in the analysis. RESULTS: We evaluated 118 stage IIIC/IV patients, with a median age of 63 years (range 19-91); 47.5 % had ascites and 29 % a pleural effusion. Median duration of surgery was 247 min (range 100-540 min). Median surgical complexity score was 10 (range 5-15) consisting of bowel resection (71 %), stoma formation (13.6 %), diaphragmatic stripping/resection (67 %), liver/liver capsule resection (39 %), splenectomy (20 %), resection stomach/lesser sac (26.3 %), pleurectomy (17 %), coeliac trunk/subdiaphragmatic lymphadenectomy (8 %). Total macroscopic tumor clearance rate was 89 %. Major surgical complication rate was 18.6 % (n = 22), with a 28-day and 3-month mortality of 1.7 and 3.4 %, respectively. The anastomotic leak rate was 0.8 %; fistula/bowel perforation 3.4 %; thromboembolism 3.4 % and reoperation 4.2 %. Median intensive care unit and hospital stay were 1.7 (range 0-104) and 8 days (range 4-118), respectively. Four patients (3.3 %) failed to receive chemotherapy within the first 8 postoperative weeks. CONCLUSIONS: Maximal effort cytoreductive surgery for EOC is feasible within a UK setting with acceptable morbidity, low intestinal stoma rates and without clinically relevant delays to postoperative chemotherapy. Careful patient selection, and coordinated multidisciplinary effort appear to be the key for good outcome. Future ev

  • Conference paper
    Patel A, Jhanji S, Pavlu J, Laffan M, Ethell M, Bradshaw A, Olavarria E, Harrington K, Apperley J, Brett Set al., 2016,

    Mesenchymal stromal stem cell (MSC) immunotherapy for experimental septic shock: systematic review and meta-analysis with trial sequential analysis of mortality

    , 42nd Annual Meeting of the European Society for Blood and Marrow Transplantation, Publisher: Nature Publishing Group, Pages: S129-S129, ISSN: 1476-5365
  • Journal article
    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.

  • Journal article
    Shepherd SJ, Newman R, Brett SJ, Griffith DM, Enhancing Rehabilitation After Critical Illness Programme Study Investigatorset al., 2016,

    Pharmacological Therapy for the Prevention and Treatment of Weakness After Critical Illness: A Systematic Review.

    , Critical Care Medicine, Vol: 44, Pages: 1198-1205, ISSN: 1530-0293

    OBJECTIVES: ICU-acquired weakness is a common complication of critical illness and can have significant effects upon functional status and quality of life. As part of preliminary work to inform the design of a randomized trial of a complex intervention to improve recovery from critical illness, we sought to identify pharmacological interventions that may play a role in this area. DATA SOURCES: We systematically reviewed the published literature relating to pharmacological intervention for the treatment and prevention of ICU-acquired weakness. STUDY SELECTION: We searched MEDLINE, EMBASE, CINAHL+, Web of Science, and both U.S. and European trial registries up to July 2014 alongside reviews and reference lists from populations with no age or language restrictions. We included studies that reported a measure of muscle structure or physical function as an outcome measure. DATA EXTRACTION: We estimated pooled odds ratios and 95% CI using data extracted from published articles or where available, original data provided by the authors. Assessment of bias was performed using the Cochrane Collaboration's risk of bias tool. DATA SYNTHESIS: Ten studies met the inclusion criteria. The current body of evidence does not support the use of any pharmacological agent in this setting, although maintaining euglycemia may reduce the prevalence of critical illness polyneuropathy. CONCLUSIONS: At present, no pharmacological intervention can be recommended to prevent or treat ICU-acquired weakness. Further research is required into this field to include more novel agents such as myostatin inhibitors. Challenges in the conduct of research in this area are highlighted.

  • Journal article
    Davenport EE, Burnham KL, Radhakrishnan J, Humburg P, Hutton P, Mills TC, Rautanen A, Gordon AC, Garrard C, Hill AVS, Hinds CJ, Knight JCet al., 2016,

    Genomic landscape of the individual host response and outcomes in sepsis: a prospective cohort study

    , Lancet Respiratory Medicine, Vol: 4, Pages: 259-271, ISSN: 2213-2619

    BackgroundEffective targeted therapy for sepsis requires an understanding of the heterogeneity in the individual host response to infection. We investigated this heterogeneity by defining interindividual variation in the transcriptome of patients with sepsis and related this to outcome and genetic diversity.MethodsWe assayed peripheral blood leucocyte global gene expression for a prospective discovery cohort of 265 adult patients admitted to UK intensive care units with sepsis due to community-acquired pneumonia and evidence of organ dysfunction. We then validated our findings in a replication cohort consisting of a further 106 patients. We mapped genomic determinants of variation in gene transcription between patients as expression quantitative trait loci (eQTL).FindingsWe discovered that following admission to intensive care, transcriptomic analysis of peripheral blood leucocytes defines two distinct sepsis response signatures (SRS1 and SRS2). The presence of SRS1 (detected in 108 [41%] patients in discovery cohort) identifies individuals with an immunosuppressed phenotype that included features of endotoxin tolerance, T-cell exhaustion, and downregulation of human leucocyte antigen (HLA) class II. SRS1 was associated with higher 14 day mortality than was SRS2 (discovery cohort hazard ratio (HR) 2·4, 95% CI 1·3–4·5, p=0·005; validation cohort HR 2·8, 95% CI 1·5–5·1, p=0·0007). We found that a predictive set of seven genes enabled the classification of patients as SRS1 or SRS2. We identified cis-acting and trans-acting eQTL for key immune and metabolic response genes and sepsis response networks. Sepsis eQTL were enriched in endotoxin-induced epigenetic marks and modulated the individual host response to sepsis, including effects specific to SRS group. We identified regulatory genetic variants involving key mediators of gene networks implicated in the hypoxic response and the switch to glycolysis t

  • Journal article
    Corner E, Handy JM, Brett SJ, 2016,

    eLearning to facilitate the education and implementation of The Chelsea Critical Care Physical Assessment: a novel measure of function in critical illness.

    , BMJ Open, Vol: 6, ISSN: 2044-6055

    Objective: To evaluate the efficacy of eLearning in the widespread standardized teaching,distribution and implementation of The Chelsea Critical Care Physical Assessment tool (CPAx): avalidated tool to assess physical function in critically ill patients.Design: Prospective educational study. An eLearning module was developed through aconceptual framework, using the four-stage technique for skills teaching to teach clinicians howto use the CPAx. Example and test video case studies of CPAx assessments were embeddedwithin the module. The CPAx scores for the test case studies and demographic data wererecorded in a secure area of the website. Data were analyzed for inter-rater reliability usingintraclass correlation coefficients (ICC) to see if an eLearning educational package facilitatedconsistent use of the tool. A utility and content validity questionnaire was distributed after oneyear to eLearning module registrants (n= 971). This was to evaluate uptake of the CPAx inclinical practice and content validity of the CPAx from the perspective of clinical users.Setting: The module was distributed for use via professional forums (n=2) and direct contacts(n=95)Participants: Critical care cliniciansPrimary outcome measure: Intraclass correlation co-efficient of the test case studies.Results: Between July and October 2014, 421 candidates from fifteen countries registered forthe eLearning module. The ICC for case one was 0.996 (95% CI 0.990-0.999; n=207). The ICC for case two was .988 (0.996-1.000; n=184). The CPAx has a strong total scale content validityindex (s-CVI) of 0.94 and is well utilized.Conclusions: eLearning is a useful and reliable way of teaching psychomotor skills, such as theCPAx. The CPAx is a well-utilized measure with high content validity rated by clinicians.

  • Conference paper
    Tirlapur N, O'Dea KP, Takata M, 2016,

    Human Neutrophil-Derived Microvesicles Activate Pulmonary Endothelial Cells In An In Vitro Model Of Pulmonary Microvascular Inflammation

    , International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
  • Journal article
    Perkins GD, Jacobs IG, Nadkarni VM, Berg RA, Bhanji F, Biarent D, Bossaert LL, Brett SJ, Chamberlain D, de Caen AR, Deakin CD, Finn JC, Graesner J-T, Hazinski MF, Iwami T, Koster RW, Lim SH, Ma MH-M, McNally BF, Morley PT, Morrison LJ, Monsieurs KG, Montgomery W, Nichol G, Okada K, Ong MEH, Travers AH, Nolan JPet al., 2015,

    Cardiac Arrest and Cardiopulmonary Resuscitation Outcome Reports: Update of the Utstein Resuscitation Registry Templates for Out-of-Hospital Cardiac Arrest A Statement for Healthcare Professionals From a Task Force of the International Liaison Committee on Resuscitation (American Heart Association, European Resuscitation Council, Australian and New Zealand Council on Resuscitation, Heart and Stroke Foundation of Canada, InterAmerican Heart Foundation, Resuscitation Council of Southern Africa, Resuscitation Council of Asia); and the American Heart Association Emergency Cardiovascular Care Committee and the Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation

    , CIRCULATION, Vol: 132, Pages: 1286-1300, ISSN: 0009-7322

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