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.

CD161 expression characterizes a subpopulation of human regulatory T cells that produces IL‐17 in a STAT3‐dependent manner

Abstract: Treg cells are critical for the prevention of autoimmune diseases and are thus prime candidates for cell-based clinical therapy. However, human Treg cells are “plastic”, and are able to produce IL-17 under inflammatory conditions. Here, we identify and characterize the human Treg subpopulation that can be induced to produce IL-17 and identify its mechanisms. We confirm that a subpopulation of human Treg cells produces IL-17 in vitro when activated in the presence of IL-1β, but not IL-6. “IL-17 potential” is restricted to population III (CD4+CD25hiCD127loCD45RA−) Treg cells expressing the natural killer cell marker CD161. We show that these cells are functionally as suppressive and have similar phenotypic/molecular characteristics to other subpopulations of Treg cells and retain their suppressive function following IL-17 induction. Importantly, we find that IL-17 production is STAT3 dependent, with Treg cells from patients with STAT3 mutations unable to make IL-17. Finally, we show that CD161+ population III Treg cells accumulate in inflamed joints of patients with inflammatory arthritis and are the predominant IL-17-producing Treg-cell population at these sites. As IL-17 production from this Treg-cell subpopulation is not accompanied by a loss of regulatory function, in the context of cell therapy, exclusion of these cells from the cell product may not be necessary.

Antidepressant utilisation and incidence of weight gain during 10 years' follow-up: population based cohort study.

Abstract: Objective To evaluate the long term association between antidepressant prescribing and body weight. Design Population based cohort study. Setting General practices contributing to the UK Clinical Practice Research Datalink, 2004-14. Participants 136 762 men and 157 957 women with three or more records for body mass index (BMI). Main outcome measures The main outcomes were antidepressant prescribing, incidence of ≥5% increase in body weight, and transition to overweight or obesity. Adjusted rate ratios were estimated from a Poisson model adjusting for age, sex, depression recording, comorbidity, coprescribing of antiepileptics or antipsychotics, deprivation, smoking, and advice on diet. Results In the year of study entry, 17 803 (13.0%) men and 35 307 (22.4%) women with a mean age of 51.5 years (SD 16.6 years) were prescribed antidepressants. During 1 836 452 person years of follow-up, the incidence of new episodes of ≥5 weight gain in participants not prescribed antidepressants was 8.1 per 100 person years and in participants prescribed antidepressants was 11.2 per 100 person years (adjusted rate ratio 1.21, 95% confidence interval 1.19 to 1.22, P Conclusion Widespread utilisation of antidepressants may be contributing to long term increased risk of weight gain at population level. The potential for weight gain should be considered when antidepressant treatment is indicated.

Status dystonicus: a practice guide

Abstract: Status dystonicus is a rare, but life-threatening movement disorder emergency Urgent assessment is required and management is tailored to patient characteristics and complications The use of dystonia action plans and early recognition of worsening dystonia may potentially facilitate intervention or prevent progression to status dystonicus However, for established status dystonicus, rapidly deployed temporizing measures and different depths of sedation in an intensive care unit or high dependency unit are the most immediate and effective modalities for abating life-threatening spasms, while dystonia-specific treatment takes effect If refractory status dystonicus persists despite orally active anti-dystonia drugs and unsuccessful weaning from sedative or anaesthetic agents, early consideration of intrathecal baclofen or deep brain stimulation is required During status dystonicus, precise documentation of dystonia sites and severity as well as the baseline clinical state, using rating scales and videos is recommended Further published descriptions of the clinical nature, timing of evolution, resolution, and epidemiology of status dystonicus are essential for a better collective understanding of this poorly understood heterogeneous emergency In this review, we provide an overview of the clinical presentation and suggest a management approach for status dystonicus

Lymphoid tumours and breast cancer in ataxia telangiectasia; substantial protective effect of residual ATM kinase activity against childhood tumours

Abstract: Lymphoid tumours and breast cancer in ataxia telangiectasia; substantial protective effect of residual ATM kinase activity against childhood tumours