Institution
St Thomas' Hospital
Healthcare•London, United Kingdom•
About: St Thomas' Hospital is a healthcare organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Pregnancy. The organization has 12105 authors who have published 15596 publications receiving 624309 citations. The organization is also known as: St Thomas's Hospital & St. Thomas's.
Papers published on a yearly basis
Papers
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TL;DR: It is reported that mice lacking β3Integrins or both β3 and β5 integrins not only support tumorigenesis, but have enhanced tumor growth as well and the tumors in these integrin-deficient mice display enhanced angiogenesis, strongly suggesting that neither β3 nor β5integrins are essential for neovascularization.
Abstract: Enhanced pathological angiogenesis in mice lacking β 3 integrin or β 3 and β 5 integrins
615 citations
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TL;DR: To assess the efficacy and safety of anifrolumab, a type I interferon (IFN) receptor antagonist, in a phase IIb, randomized, double‐blind, placebo‐controlled study of adults with moderate‐to‐severe systemic lupus erythematosus (SLE).
Abstract: Objective
To assess the efficacy and safety of anifrolumab, a type I interferon (IFN) receptor antagonist, in a phase IIb, randomized, double-blind, placebo-controlled study of adults with moderate-to-severe systemic lupus erythematosus (SLE).
Methods
Patients (n = 305) were randomized to receive intravenous anifrolumab (300 mg or 1,000 mg) or placebo, in addition to standard therapy, every 4 weeks for 48 weeks. Randomization was stratified by SLE Disease Activity Index 2000 score (<10 or ≥10), oral corticosteroid dosage (<10 or ≥10 mg/day), and type I IFN gene signature test status (high or low) based on a 4-gene expression assay. The primary end point was the percentage of patients achieving an SLE Responder Index (SRI[4]) response at week 24 with sustained reduction of oral corticosteroids (<10 mg/day and less than or equal to the dose at week 1 from week 12 through 24). Other end points (including SRI[4], British Isles Lupus Assessment Group [BILAG]–based Composite Lupus Assessment [BICLA], modified SRI[6], and major clinical response) were assessed at week 52. The primary end point was analyzed in the modified intent-to-treat (ITT) population and type I IFN–high subpopulation. The study result was considered positive if the primary end point was met in either of the 2 study populations. The Type I error rate was controlled at 0.10 (2-sided), within each of the 2 study populations for the primary end point analysis.
Results
The primary end point was met by more patients treated with anifrolumab (34.3% of 99 for 300 mg and 28.8% of 104 for 1,000 mg) than placebo (17.6% of 102) (P = 0.014 for 300 mg and P = 0.063 for 1,000 mg, versus placebo), with greater effect size in patients with a high IFN signature at baseline (13.2% in placebo-treated patients versus 36.0% [P = 0.004] and 28.2% [P = 0.029]) in patients treated with anifrolumab 300 mg and 1,000 mg, respectively. At week 52, patients treated with anifrolumab achieved greater responses in SRI(4) (40.2% versus 62.6% [P < 0.001] and 53.8% [P = 0.043] with placebo, anifrolumab 300 mg, and anifrolumab 1,000 mg, respectively), BICLA (25.7% versus 53.5% [P < 0.001] and 41.2% [P = 0.018], respectively), modified SRI(6) (28.4% versus 49.5% [P = 0.002] and 44.7% [P = 0.015], respectively), major clinical response (BILAG 2004 C or better in all organ domains from week 24 through week 52) (6.9% versus 19.2% [P = 0.012] and 17.3% [P = 0.025], respectively), and several other global and organ-specific end points. Herpes zoster was more frequent in the anifrolumab-treated patients (2.0% with placebo treatment versus 5.1% and 9.5% with anifrolumab 300 mg and 1,000 mg, respectively), as were cases reported as influenza (2.0% versus 6.1% and 7.6%, respectively), in the anifrolumab treatment groups. Incidence of serious adverse events was similar between groups (18.8% versus 16.2% and 17.1%, respectively).
Conclusion
Anifrolumab substantially reduced disease activity compared with placebo across multiple clinical end points in the patients with moderate-to-severe SLE.
614 citations
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Charité1, Odense University Hospital2, Autonomous University of Barcelona3, University of Montpellier4, University of Southampton5, Norfolk and Norwich University Hospital6, St Thomas' Hospital7, Hiroshima University8, Medical University of South Carolina9, Johns Hopkins University School of Medicine10, Peking University11
TL;DR: A GA2LEN task force report concluded that chronic spontaneous urticaria is a “hidden epidemic” that needs to be addressed to address the unmet clinical needs of patients.
Abstract: Chronic spontaneous urticaria, formerly also known as chronic idiopathic urticaria and chronic urticaria (CU), is more common than previously thought. At any time, 0.5-1% of the population suffers from the disease (point prevalence). Although all age groups can be affected, the peak incidence is seen between 20 and 40 years of age. The duration of the disease is generally 1-5 years but is likely to be longer in more severe cases, cases with concurrent angioedema, in combination with physical urticaria or with a positive autologous serum skin test (autoreactivity). Chronic spontaneous urticaria has major detrimental effects on quality of life, with sleep deprivation and psychiatric comorbidity being frequent. It also has a large impact on society in terms of direct and indirect health care costs as well as reduced performance at work and in private life. In the majority of patients, an underlying cause cannot be identified making a causal and/or curative treatment difficult. Nonsedating H₁-antihistamines are the mainstay of symptomatic therapy, but treatment with licensed doses relieves symptoms effectively in < 50% of patients. Although guideline-recommended updosing up to fourfold increases symptom control in many patients, a substantial number of patients have only little benefit from H₁ -antihistamines. Consequently, there is a great need for new therapeutic strategies.
613 citations
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TL;DR: Important differences in innate and adaptive immunity in immature versus adult brain are highlighted, which support the notion that the consequences of inflammation will be entirely different depending on context and stage of CNS development.
Abstract: Neuroinflammation during critical phases of brain development can increase the risk of neurological and neuropsychiatric disorders, even in adulthood. In this Review, Hagberg et al. review the mechanisms through which inflammation can exacerbate perinatal brain injury, and outline how understanding the interplay between inflammation and brain injury can aid the identification of new strategies to alleviate neurological and neuropsychiatric morbidity. Inflammation is increasingly recognized as being a critical contributor to both normal development and injury outcome in the immature brain. The focus of this Review is to highlight important differences in innate and adaptive immunity in immature versus adult brain, which support the notion that the consequences of inflammation will be entirely different depending on context and stage of CNS development. Perinatal brain injury can result from neonatal encephalopathy and perinatal arterial ischaemic stroke, usually at term, but also in preterm infants. Inflammation occurs before, during and after brain injury at term, and modulates vulnerability to and development of brain injury. Preterm birth, on the other hand, is often a result of exposure to inflammation at a very early developmental phase, which affects the brain not only during fetal life, but also over a protracted period of postnatal life in a neonatal intensive care setting, influencing critical phases of myelination and cortical plasticity. Neuroinflammation during the perinatal period can increase the risk of neurological and neuropsychiatric disease throughout childhood and adulthood, and is, therefore, of concern to the broader group of physicians who care for these individuals.
612 citations
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TL;DR: A sharper focus on intervention before conception is needed to improve maternal and child health and reduce the growing burden of non-communicable diseases, and health professionals should be alerted to ways of identifying women who are planning a pregnancy.
611 citations
Authors
Showing all 12132 results
Name | H-index | Papers | Citations |
---|---|---|---|
David J. Hunter | 213 | 1836 | 207050 |
Rory Collins | 162 | 489 | 193407 |
Steven Williams | 144 | 1375 | 86712 |
Geoffrey Burnstock | 141 | 1488 | 99525 |
Nick C. Fox | 139 | 748 | 93036 |
Christopher D.M. Fletcher | 138 | 674 | 82484 |
David A. Jackson | 136 | 1095 | 68352 |
Paul Harrison | 133 | 1400 | 80539 |
Roberto Ferrari | 133 | 1654 | 103824 |
David Taylor | 131 | 2469 | 93220 |
Keith Hawton | 125 | 657 | 55138 |
Nicole Soranzo | 124 | 316 | 74494 |
Roger Williams | 122 | 1455 | 72416 |
John C. Chambers | 122 | 645 | 71028 |
Derek M. Yellon | 122 | 638 | 54319 |