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2481. Clinical utility of random anti-tumour necrosis factor drug testing and measurement of anti-drug antibodies on long-term treatment response in rheumatoid arthritis.
作者: Meghna Jani.;Hector Chinoy.;Richard B Warren.;Christopher E M Griffiths.;Darren Plant.;Ann W Morgan.;Anthony G Wilson.;Kimme L Hyrich.;John Isaacs.;Anne Barton.
来源: Lancet. 2015年385 Suppl 1卷S48页
Up to 40% of patients with rheumatoid arthritis treated with anti-tumour necrosis factor (TNF) drugs do not respond because of primary inefficacy or loss of response. Although one explanation is that immunogenicity leads to the development of anti-drug antibodies and low drug concentrations, the clinical usefulness of pharmacological monitoring is debated. Our aim was to assess whether the presence of anti-drug antibodies and non-trough drug concentrations could predict treatment response in patients with rheumatoid arthritis treated with anti-TNF drugs.
2482. Is variation in copy number of the human beta defensin gene cluster associated with preterm birth?
作者: Catherine James.;Razan Abujaber.;Mona Bajaj-Elliott.;Argyro Syngelaki.;Nigel Klein.;Kypros Nicolaides.;Edward Hollox.;Donald Peebles.
来源: Lancet. 2015年385 Suppl 1卷S47页
Increased expression of antimicrobial peptides including human beta defensins (HBD) has been reported in the amniotic fluid and vaginal secretions of women who deliver preterm. We have previously shown that these women have increased first trimester serum HBD2. The gene encoding HBD2, DEFB4A, is part of a defensin beta (DEFB) cluster on chromosome 8 that is variable in copy number. Increased serum HBD2 is associated with increased DEFB copy number. We aimed to test the hypothesis that variation in DEFB copy number is associated with preterm birth.
2483. The active intrathecal B-cell response in LGI1-antibody encephalitis.
作者: Sarosh R Irani.;Klaus Lehmann-Horn.;Michael Geschwind.;Shengzhi Wang.;Angela Vincent.;H-Christian von Büdingen.
来源: Lancet. 2015年385 Suppl 1卷S46页
Leucine-rich glioma inactivated 1 (LGI1) is a component of the voltage-gated potassium channel complex. IgG antibodies against LGI1 are associated with immunotherapy-responsive encephalitis and epilepsies. LGI1-antibody concentrations are 10-100 times greater in serum than in cerebrospinal fluid (CSF). Oligoclonal IgG bands are rarely found in patients with LGI1-antibody encephalitis or epilepsy. These observations raise questions about the sources of the B cells that result in production of LGI1 antibodies and how the IgGs reach the brain. We aimed to investigate the migration and expansions of peripheral and central B cells to the production of LGI1-specific IgG.
2484. Natural killer cell maturation markers in the human liver and expansion of an NKG2C+KIR+ population.
作者: Theresa Hydes.;Mohammed Abuhilal.;Thomas Armstrong.;John Primrose.;Arjun Takhar.;Salim Khakoo.
来源: Lancet. 2015年385 Suppl 1卷S45页
Selected populations of murine natural killer (NK) cells possess memory features to haptens, cytokines, and viruses. Liver-specific adhesion molecules CXCR6 and CD49a have been identified as surface markers in mice. In people, expansion of long-lived terminally differentiated NKG2C+ populations occur in the blood after viral infection. We aimed to compare intrahepatic and blood NK cell receptor expression to determine the existence of CD49a+ and CXCR6+ NK cells in human liver and define the maturation status of NKG2C+ NK cells at this site.
2485. Association of anti-carbamylated protein antibodies with long-term disability and increased disease activity in patients with early inflammatory arthritis: results from the Norfolk Arthritis Register.
作者: Jennifer Humphreys.;Marije Verheul.;Anne Barton.;Bo Fu.;Rene Toes.;Deborah Symmons.;Leendert Trouw.;Suzanne Verstappen.
来源: Lancet. 2015年385 Suppl 1卷S44页
Anti-citrullinated protein antibodies (ACPA) predict increased disease activity and disability in patients with inflammatory arthritis such as rheumatoid arthritis. However, the absence of these antibodies does not confer universally good prognosis. Recently, a new set of antibodies, anti-carbamylated (anti-CarP) antibodies, have been identified in patients with rheumatoid arthritis. This study aimed to investigate the association between anti-CarP antibodies, disability, and disease activity in these patients.
2486. What are important outcomes of bariatric surgery? An in-depth analysis to inform the development of a core outcome set and a comparison between the views of surgeons and other health professionals (the BARIACT study).
作者: James Hopkins.;Noah Howes.;Katy Chalmers.;Katie Whale.;Jelena Savovic.;Karen Coulman.;Alex Nicholson.;James Byrne.;Robert Whistance.;Richard Welbourn.;Robert Andrews.;Jane Blazeby.; .
来源: Lancet. 2015年385 Suppl 1卷S43页
Outcome reporting in bariatric surgery needs uniformity. A core outcome set is an agreed minimum set of outcomes reported in all studies of a particular condition, but members of the bariatric multidisciplinary team might value outcomes differently. The aim of this study was to summarise existing outcome reporting in bariatric surgery, to inform the development of a core outcome set, and to compare outcomes selected as important by type of health professional.
2487. Multidimensional endotypes of asthma: topological data analysis of cross-sectional clinical, pathological, and immunological data.
作者: Timothy Hinks.;Xiaoying Zhou.;Karl Staples.;Borislav Dimitrov.;Alexander Manta.;Tanya Petrossian.;Pek Lum.;Caroline Smith.;Jon Ward.;Peter Howarth.;Andrew Walls.;Stephan D Gadola.;Ratko Djukanović.
来源: Lancet. 2015年385 Suppl 1卷S42页
Incomplete understanding of mechanisms and clinicopathobiological heterogeneity in asthma hinders research progress. Pathogenic roles for T-helper-type 17 (Th17) cells and invariant T cells implied by murine data have yet to be assessed in man. We aimed to investigate the role of Th17 and mucosal associated invariant T (MAIT) cells in airway inflammation; to characterise associations between diverse clinical and immunological features of asthma; and to identify novel multidimensional asthma endotypes.
2488. Emergency department attendance by patients with cancer in the last month of life: a systematic review and meta-analysis.
作者: Lesley Henson.;Wei Gao.;Irene Higginson.;Melinda Smith.;Joanna Davies.;Clare Ellis-Smith.;Barbara Daveson.
来源: Lancet. 2015年385 Suppl 1卷S41页
Emergency department visits towards the end of life by people with cancer are increasing over time. This increase has occurred despite evidence of an association with poor patient outcomes, the majority of patients preferring home-based care, and significant overcrowding and capacity concerns for many emergency departments. We aimed to explore factors associated with emergency department attendance by cancer patients in the last month of life.
2489. Delay to admission to critical care and mortality among deteriorating ward patients in UK hospitals: a multicentre, prospective, observational cohort study.
Annually, more than 11 million patients are admitted to hospital overnight in England, but the UK is ranked 24 of 31 European countries with respect to per head provision of intensive care unit (ICU) beds. This lack of beds places strain on the capacity to admit patients from the ward because of high ICU occupancy. Such delay can cause harm, but the effect of such harm is difficult to measure. Prompt admissions are prompt precisely because these patients are severely unwell. Measured severity is unlikely to completely capture the clinical judgment used to allocate early admission, and therefore risk-adjusted outcomes will be biased against the early admission. We aimed to evaluate the effect of delayed admission to critical care without this treatment selection bias.
2490. Use of a novel floxed mouse to characterise the cellular source of plasma coagulation FXIII-A.
作者: Kathryn Griffin.;Kingsley Simpson.;Cora Beckers.;Jane Brown.;Jean Vacher.;Wilhelm Ouwehand.;Warren Alexander.;Richard Pease.;Peter Grant.
来源: Lancet. 2015年385 Suppl 1卷S39页
Coagulation factor XIII-A has a crucial role in thrombus stabilisation and tissue repair. Factor XIII-A deficiency causes a severe bleeding phenotype and impaired wound healing, but the cellular origin of Factor XIII-A is unknown. To identify the cells that maintain the plasma pool, we generated a mouse floxed in coding exon7 of the factor XIII-A gene (F13A1). These mice were crossed with mice transgenic for Pf4-Cre-recombinase (thrombopoietic deletion) or Cd11b-Cre-recombinase (myeloid deletion). The resultant mice were compared with a Mpl-/- (thrombopoietin receptor knockout) thrombocytopenic murine model.
2491. Choice of a patient-reported outcome measure for patients with anal cancer for use in cancer clinical trials and routine clinical practice: a mixed methods approach.
作者: Alexandra Gilbert.;Elaine O'Connell Francischetto.;Jane Blazeby.;Patricia Holch.;Susan Davidson.;David Sebag-Montefiore.;Galina Velikova.
来源: Lancet. 2015年385 Suppl 1卷S38页
In the USA, more than 7200 new cases of anal cancer were diagnosed in 2014 with incidence rising. Concurrent chemoradiotherapy improves cancer-related outcomes but has led to an increase in acute and late adverse events. Patient-reported outcomes (PRO) are increasingly included in trials as a surrogate measure for reporting of late adverse events. This study aimed to select the most effective PRO to use in clinical research and practice for anal cancer since no questionnaire specific for anal cancer has been developed.
2492. Integrated molecular analysis to investigate the role of microRNAs in pancreatic tumour growth and progression.
作者: Adam E Frampton.;Leandro Castellano.;Teresa Colombo.;Elisa Giovannetti.;Jonathan Krell.;Jimmy Jacob.;Loredana Pellegrino.;Laura Roca-Alonso.;Niccola Funel.;Tamara M H Gall.;Raida Ahmad.;Nagy A Habib.;Thomas Knösel.;Justin Stebbing.;Long R Jiao.
来源: Lancet. 2015年385 Suppl 1卷S37页
MicroRNAs (miRNAs) are small non-coding RNAs involved in the post-transcriptional regulation of mRNAs and are aberrantly expressed in cancer with important roles in tumorigenesis. A broad analysis of the combined effects of altered activities of miRNAs in pancreatic ductal adenocarcinoma (PDAC) has not been done, and how miRNAs might affect tumour progression or patient outcomes is unclear.
2493. The role of metalloproteinases and their tissue inhibitors in adipose tissue remodelling and whole-body lipid distribution: a cross-sectional clinical study.
作者: Matthew Fenech.;Jelena Gavrilovic.;Paul Malcolm.;Andoni Toms.;Jeremy Turner.
来源: Lancet. 2015年385 Suppl 1卷S36页
Metabolically unhealthy obesity is associated with insulin resistance. Dysfunctional adipose tissue remodelling might explain features of this disorder, such as chronic white adipose tissue inflammation, adipocyte hypertrophy, and ectopic lipid deposition. Metalloproteinases and their tissue inhibitors (TIMPs) have been implicated in human adipose tissue remodelling. In a cross-sectional study, we investigated the association of adipose metalloproteinase and TIMP expression with whole-body lipid distribution and insulin resistance.
2494. Effect of tissue inhibitor of metalloproteinases 3 on DLK1 shedding in cultured human pre-adipocytes and implications for adipose tissue remodelling.
Metabolically unhealthy obesity is associated with adipose tissue inflammation and increased risk of type 2 diabetes. Dysfunctional adipose tissue remodelling has been implicated in development of metabolically unhealthy obesity, but the pathogenesis remains poorly characterised. We hypothesised that in health, tissue inhibitor of metalloproteinases 3 (TIMP3) modulates adipose tissue remodelling by regulating extracellular matrix turnover and shedding of the adipogenic regulator DLK1, but that in adipose tissue inflammation it might drive development of metabolically unhealthy obesity.
2495. Presurgical entorhinal cortex volume and postoperative seizure outcome in temporal lobe epilepsy.
作者: Samia Elkommos.;Mark P Richardson.;Jan-Christoph Schoene-Bake.;Anthony Marson.;Christian Elger.;Bernd Weber.;Simon S Keller.
来源: Lancet. 2015年385 Suppl 1卷S34页
Although temporal lobe surgery is an effective treatment for patients with intractable mesial temporal lobe epilepsy (mTLE), a third of patients will continue to experience seizures at 2 years after surgery. The reasons are unknown. One suggestion is that patients with abnormalities of the entorhinal cortex might have a subtype of mTLE that is resistant to surgery. We investigated the association between presurgical entorhinal cortex volume and postoperative outcome in patients with mTLE.
2496. Epidemiology and outcomes of older patients admitted to Scottish intensive care units: a national database linkage study.
作者: Annemarie Docherty.;Nazir Lone.;Niall Anderson.;Timothy Walsh.
来源: Lancet. 2015年385 Suppl 1卷S33页
As the general population ages and life expectancy increases, health-care use by elderly people increases, including intensive care. Rationing and variation of access are ethically and politically challenging. We aimed to characterise the population-based incidence of intensive care unit (ICU) admissions of elderly people in Scotland; compare ICU admission and mortality between elderly and younger populations; and compare treatment intensity between these groups.
2497. One size does not fit all. Management of the laparoscopic adjustable gastric band in pregnancy: a national prospective cohort study.
作者: Katie Cornthwaite.;Amanda Jefferys.;Erik Lenguerrand.;Judith Hyde.;Mary Lynch.;Tim Draycott.;Andrew Johnson.;Dimitrios Siassakos.
来源: Lancet. 2015年385 Suppl 1卷S32页
Pregnancies are increasingly seen in women with a gastric band, but no guidance exists on band management during pregnancy. Although band inflation can prevent excessive gestational weight gain and its associated complications, it might have detrimental effects on fetal growth. We compared maternal and perinatal outcomes according to band management strategy-keeping the band inflated throughout pregnancy versus deflation.
2498. Topical emollient for prevention of infection in preterm infants: a systematic review.
Breakdown of the developmentally immature epidermal barrier in the preterm infant can permit entry of microorganisms leading to invasive infection. Topical emollients might improve skin integrity and barrier function and thereby prevent invasive infection, a major cause of mortality and morbidity in these infants. The aim of this study was to appraise and synthesise the evidence for topical application of emollients in the prevention of invasive infection and mortality in preterm infants.
2499. CD4+CD28- T-cell expansions in ANCA-associated vasculitis and association with arterial stiffness: baseline data from a randomised controlled trial.
作者: Dimitrios Chanouzas.;Lovesh Dyall.;Jessica Dale.;Paul Moss.;Matthew Morgan.;Lorraine Harper.
来源: Lancet. 2015年385 Suppl 1卷S30页
Cardiovascular risk is increased in the anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV). CD4+CD28- T cells are expanded in patients with AAV who are seropositive for cytomegalovirus (CMV), and are associated with increased mortality. CMV seropositivity in other conditions is associated with arterial stiffness, a marker of cardiovascular risk. We assessed whether CD4+CD28- T cells in CMV seropositive patients with AAV are associated with arterial stiffness and whether treatment with valaciclovir reduces this cell population.
2500. Does grandparents' diet affect weight and risk of hypogonadism in subsequent generations?
Worldwide, obesity has doubled since 1980. WHO declares obesity as preventable and attributes the increase in prevalence to high consumption of energy-rich foods and decreased physical activity. Epidemiological and experimental studies suggest that parents' and grandparents' diet could also have a role. We established a model of grandparents' high-fat diet (HFD) to explore potential mechanisms.
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