Guy's and St Thomas' NHS Foundation Trust

About: Guy's and St Thomas' NHS Foundation Trust is a healthcare organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Medicine. The organization has 7686 authors who have published 9631 publications receiving 399353 citations. The organization is also known as: Guy's and St Thomas' National Health Service Foundation Trust & Guy's and St Thomas' National Health Service Trust.

The pathogenesis and management of the coagulopathy of acute promyelocytic leukaemia

Abstract: Coagulopathy occurs in most patients with (APML) and is life-threatening; therefore prompt diagnosis and recognition of any coagulation defect is imperative. Unfortunately haemorrhage remains a major cause of early death, preventing some from reaching treatment. The coagulopathy is caused directly or indirectly by the leukaemic cells through expression of activators of coagulation and fibrinolysis, proteases and cytokine generation, compounded by failure of platelet production due to marrow invasion. At presentation the predominant feature is usually hyperfibrinolysis. Since the introduction of all-trans retinoic acid (ATRA), patient outcome has dramatically improved; yet, haemorrhagic complications remain the most frequent cause of mortality. Thrombotic complications occur but are less well recognized and potentially underreported. Supportive measures and prompt initiation of ATRA currently represent the mainstay of treatment of the coagulopathy in patients with suspected APML, but unanswered questions remain as to the optimal approach to further decrease the associated haemorrhagic and thrombotic risks. In particular, it is unclear how to best predict and monitor the coagulopathy; whether there is a role for the early use of antifibrinolytics; the most appropriate trigger for giving fibrinogen replacement and the value of low-dose anticoagulation to suppress coagulation activation once fibrinolysis has been suppressed.

Development and implementation of centralized simulation training: evaluation of feasibility, acceptability and construct validity

Abstract: What's known on the subject? and What does the study add? A competent urologist should not only have effective technical skills, but also other attributes that would make him/her a complete surgeon. These include team-working, communication and decision-making skills. Although evidence for effectiveness of simulation exists for individual simulators, there is a paucity of evidence for utility and effectiveness of these simulators in training programmes that aims to combine technical and non-technical skills training. This article explains the process of development and validation of a centrally coordinated simulation program (Participants – South-East Region Specialist Registrars) under the umbrella of the British Association for Urological Surgeons (BAUS) and the London Deanery. This program incorporated training of both technical (synthetic, animal and virtual reality models) and non-technical skills (simulated operating theatres). Objectives To establish the feasibility and acceptability of a centralized, simulation-based training-programme. Simulation is increasingly establishing its role in urological training, with two areas that are relevant to urologists: (i) technical skills and (ii) non-technical skills. Materials and Methods For this London Deanery supported pilot Simulation and Technology enhanced Learning Initiative (STeLI) project, we developed a structured multimodal simulation training programme. The programme incorporated: (i) technical skills training using virtual-reality simulators (Uro-mentor and Perc-mentor [Symbionix, Cleveland, OH, USA], Procedicus MIST-Nephrectomy [Mentice, Gothenburg, Sweden] and SEP Robotic simulator [Sim Surgery, Oslo, Norway]); bench-top models (synthetic models for cystocopy, transurethral resection of the prostate, transurethral resection of bladder tumour, ureteroscopy); and a European (Aalborg, Denmark) wet-lab training facility; as well as (ii) non-technical skills/crisis resource management (CRM), using SimMan (Laerdal Medical Ltd, Orpington, UK) to teach team-working, decision-making and communication skills. The feasibility, acceptability and construct validity of these training modules were assessed using validated questionnaires, as well as global and procedure/task-specific rating scales. Results In total 33, three specialist registrars of different grades and five urological nurses participated in the present study. Construct-validity between junior and senior trainees was significant. Of the participants, 90% rated the training models as being realistic and easy to use. In total 95% of the participants recommended the use of simulation during surgical training, 95% approved the format of the teaching by the faculty and 90% rated the sessions as well organized. A significant number of trainees (60%) would like to have easy access to a simulation facility to allow more practice and enhancement of their skills. Conclusions A centralized simulation programme that provides training in both technical and non-technical skills is feasible. It is expected to improve the performance of future surgeons in a simulated environment and thus improve patient safety.

Molecular and Phenotypic Characterisation of Paediatric Glioma Cell Lines as Models for Preclinical Drug Development

Abstract: Background: Although paediatric high grade gliomas resemble their adult counterparts in many ways, there appear to be distinct clinical and biological differences. One important factor hampering the development of new targeted therapies is the relative lack of cell lines derived from childhood glioma patients, as it is unclear whether the well-established adult lines commonly used are representative of the underlying molecular genetics of childhood tumours. We have carried out a detailed molecular and phenotypic characterisation of a series of paediatric high grade glioma cell lines in comparison to routinely used adult lines. Principal Findings: All lines proliferate as adherent monolayers and express glial markers. Copy number profiling revealed complex genomes including amplification and deletions of genes known to be pivotal in core glioblastoma signalling pathways. Expression profiling identified 93 differentially expressed genes which were able to distinguish between the adult and paediatric high grade cell lines, including a number of kinases and co-ordinated sets of genes associated with DNA integrity and the immune response. Significance: These data demonstrate that glioma cell lines derived from paediatric patients show key molecular differences to those from adults, some of which are well known, whilst others may provide novel targets for evaluation in primary tumours. We thus provide the rationale and demonstrate the practicability of using paediatric glioma cell lines for preclinical and mechanistic studies.

Comprehensive microRNA profiling in acetaminophen toxicity identifies novel circulating biomarkers for human liver and kidney injury

Abstract: Our objective was to identify microRNA (miRNA) biomarkers of drug-induced liver and kidney injury by profiling the circulating miRNome in patients with acetaminophen overdose. Plasma miRNAs were quantified in age- and sex-matched overdose patients with (N = 27) and without (N = 27) organ injury (APAP-TOX and APAP-no TOX, respectively). Classifier miRNAs were tested in a separate cohort (N = 81). miRNA specificity was determined in non-acetaminophen liver injury and murine models. Sensitivity was tested by stratification of patients at hospital presentation (N = 67). From 1809 miRNAs, 75 were 3-fold or more increased and 46 were 3-fold or more decreased with APAP-TOX. A 16 miRNA classifier model accurately diagnosed APAP-TOX in the test cohort. In humans, the miRNAs with the largest increase (miR-122-5p, miR-885-5p, miR-151a-3p) and the highest rank in the classifier model (miR-382-5p) accurately reported non-acetaminophen liver injury and were unaffected by kidney injury. miR-122-5p was more sensitive than ALT for reporting liver injury at hospital presentation, especially combined with miR-483-3p. A miRNA panel was associated with human kidney dysfunction. In mice, miR-122-5p, miR-151a-3p and miR-382-5p specifically reported APAP toxicity - being unaffected by drug-induced kidney injury. Profiling of acetaminophen toxicity identified multiple miRNAs that report acute liver injury and potential biomarkers of drug-induced kidney injury.