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.

Aetiology and pathogenesis of IUGR.

Abstract: Intrauterine growth restriction (IUGR) is a major cause of perinatal mortality and morbidity. A complex and dynamic interaction of maternal, placental and fetal environment is involved in ensuring normal fetal growth. An imbalance or lack of coordination in this complex system may lead to IUGR. Animal studies have given us an insight into some aspects of the basic pathophysiology of IUGR, and recent technologies such as Doppler studies of maternal and fetal vessels have added further information. The aetiologies of IUGR are diverse, involving multiple complex mechanisms, which make understanding of the pathophysiology difficult. However, particular focus is placed on the mechanisms involved in uteroplacental insufficiency as a cause of IUGR, as (1) it is common, (2) outcome can be good if timing of delivery is optimal and (3) it may be amenable to therapy in the future. While the research into the pathophysiology of IUGR continues, there have been interesting discoveries related to the genetic contribution to IUGR and the intrauterine programming of adult-onset diseases attributed to IUGR.

Extracutaneous manifestations and complications of inherited epidermolysis bullosa: part II. Other organs.

Abstract: It is well known, primarily via case reports and limited case series, that nonepithelial tissues may become injured in patients with epidermolysis bullosa. Only recently, however, have there been data generated from large, well characterized cohorts. Our objective is to provide dermatologists with a comprehensive review of each of these major extracutaneous complications, with a summary of the pertinent literature and evidence-based recommendations for surveillance, evaluation, and management. Some epidermolysis bullosa subtypes are at risk for severe injury of the bone marrow, musculoskeletal system, heart, kidney, and teeth, and for the development of squamous cell carcinoma, basal cell carcinoma, or malignant melanoma. If untreated, significant morbidity or mortality may result.

Interleukin-17A: a unique pathway in immune-mediated diseases: psoriasis, psoriatic arthritis and rheumatoid arthritis.

Abstract: Experimental evidence points to the importance of the cytokine interleukin-17A (IL-17A) in the pathogenesis of several immunoinflammatory diseases including psoriasis, psoriatic arthritis and rheumatoid arthritis. Although a principal effector of T helper type 17 cells, IL-17A is produced by many other cell types including CD8(+) T cells and γδ T cells, and is found at high levels associated with mast cells and neutrophils at sites of skin and joint disease in humans. IL-17A up-regulates expression of numerous inflammation-related genes in target cells such as keratinocytes and fibroblasts, leading to increased production of chemokines, cytokines, antimicrobial peptides and other mediators that contribute to clinical disease features. Importantly, IL-17A must be considered within the context of the local microenvironment, because it acts synergistically or additively with other pro-inflammatory cytokines, including tumour necrosis factor. Several direct IL-17A inhibitors have shown promising activity in proof of concept and phase 2 clinical studies, thereby providing confirmation of experimental data supporting IL-17A in disease pathogenesis, although levels of response are not predicted by pre-clinical findings. IL-17A inhibitors produced rapid down-regulation of the psoriasis gene signature and high clinical response rates in patients with moderate-to-severe plaque psoriasis, consistent with an important role for IL-17A in psoriasis pathogenesis. Clinical response rates with IL-17A inhibitors in psoriatic arthritis and rheumatoid arthritis, however, were improved to a lesser degree compared with placebo, suggesting that IL-17A is either important in a subset of patients or plays a relatively minor role in inflammatory joint disease. Ongoing phase 3 clinical trials should provide further information on the role of IL-17A in these diseases.

Genome Sequence of a Recently Emerged, Highly Transmissible, Multi-Antibiotic- and Antiseptic-Resistant Variant of Methicillin-Resistant Staphylococcus aureus, Sequence Type 239 (TW)

Abstract: The 3.1-Mb genome of an outbreak methicillin-resistant Staphylococcus aureus (MRSA) strain (TW20) contains evidence of recently acquired DNA, including two large regions (635 kb and 127 kb). The strain is resistant to a wide range of antibiotics, antiseptics, and heavy metals due to resistance genes encoded on mobile genetic elements and also mutations in housekeeping genes.

Tumor Stage After Neoadjuvant Chemotherapy Determines Survival After Surgery for Adenocarcinoma of the Esophagus and Esophagogastric Junction

Abstract: Purpose Neoadjuvant chemotherapy is established in the management of most resectable esophageal and esophagogastric junction adenocarcinomas. However, assessing the downstaging effects of chemotherapy and predicting response to treatment remain challenging, and the relative importance of tumor stage before and after chemotherapy is debatable. Methods We analyzed consecutive resections for esophageal or esophagogastric junction adenocarcinomas performed at two high-volume cancer centers in London between 2000 and 2010. After standard investigations and multidisciplinary team consensus, all patients were allocated a clinical tumor stage before treatment, which was compared with pathologic stage after surgical resection. Survival analysis was conducted using Kaplan-Meier analysis and Cox regression analysis. Results Among 584 included patients, 400 patients (68%) received neoadjuvant chemotherapy. Patients with downstaged tumors after neoadjuvant chemotherapy experienced improved survival compared with patie...