60 research outputs found

    Factors associated with early outcomes following standardised therapy in children with ulcerative colitis (PROTECT): a multicentre inception cohort study

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    Background Previous retrospective studies of paediatric ulcerative colitis have had limited ability to describe disease progression and identify predictors of treatment response. In this study, we aimed to identify characteristics associated with outcomes following standardised therapy after initial diagnosis. Methods The PROTECT multicentre inception cohort study was based at 29 centres in the USA and Canada and included paediatric patients aged 4?17 years who were newly diagnosed with ulcerative colitis. Guided by the Pediatric Ulcerative Colitis Activity Index (PUCAI), patients received initial standardised treatment with mesalazine (PUCAI 10?30) oral corticosteroids (PUCAI 35?60), or intravenous corticosteroids (PUCAI ò65). The key outcomes for this analysis were week 12 corticosteroid-free remission, defined as PUCAI less than 10 and taking only mesalazine, and treatment escalation during the 12 study weeks to anti-tumour necrosis factor à (TNFà) agents, immunomodulators, or colectomy among those initially treated with intravenous corticosteroids. We identified independent predictors of outcome through multivariable logistic regression using a per-protocol approach. This study is registered with ClinicalTrials.gov, number NCT01536535. Findings Patients were recruited between July 10, 2012, and April 21, 2015. 428 children initiated mesalazine (n=136), oral corticosteroids (n=144), or intravenous corticosteroids (n=148). Initial mean PUCAI was 31ú1 (SD 13ú3) in children initiating with mesalazine, 50ú4 (13ú8) in those initiating oral corticosteroids, and 66ú9 (13ú7) in those initiating intravenous corticosteroids (p<0ú0001 for between-group comparison). Week 12 outcome data were available for 132 patients who initiated with mesalazine, 141 with oral corticosteroids, and 143 with intravenous corticosteroids. Corticosteroid-free remission with the patient receiving mesalazine treatment only at 12 weeks was achieved by 64 (48%) patients in the mesalazine group, 47 (33%) in the oral corticosteroid group, and 30 (21%) in the intravenous corticosteroid group (p<0ú0001). Treatment escalation was required by nine (7%) patients in the mesalazine group, 21 (15%) in the oral corticosteroid group, and 52 (36%) in the intravenous corticosteroid group (p<0ú0001). Eight patients, all of whom were initially treated with intravenous corticosteroids, underwent colectomy. Predictors of week 12 corticosteroid-free remission were baseline PUCAI less than 35 (odds ratio 2ú44, 95% CI 1ú41?4ú22; p=0ú0015), higher baseline albumin by 1 g/dL increments among children younger than 12 years (4ú05, 1ú90?8ú64; p=0ú00030), and week 4 remission (6ú26, 3ú79?10ú35; p<0ú0001). Predictors of treatment escalation by week 12 in patients initially treated with intravenous corticosteroids included baseline total Mayo score of 11 or higher (2ú59, 0ú93?7ú21; p=0ú068 [retained in model due to clinical relevance]), rectal biopsy eosinophil count less than or equal to 32 cells per high power field (4ú55, 1ú62?12ú78; p=0ú0040), rectal biopsy surface villiform changes (3ú05, 1ú09?8ú56; p=0ú034), and not achieving week 4 remission (30ú28, 6ú36?144ú20; p<0ú0001). Interpretation Our findings provide guidelines to assess the response of children newly diagnosed with ulcerative colitis to standardised initial therapy and identify predictors of treatment response and failure. These data suggest that additional therapeutic interventions might be warranted to improve early outcomes, especially in patients presenting with severe disease and requiring intravenous corticosteroids. Funding National Institutes of Health

    Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma

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    Genome-wide association studies (GWAS) have transformed our understanding of susceptibility to multiple myeloma (MM), but much of the heritability remains unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry. Collectively, these data provide evidence for six new MM risk loci, bringing the total number to 23. Integration of information from gene expression, epigenetic profiling and in situ Hi-C data for the 23 risk loci implicate disruption of developmental transcriptional regulators as a basis of MM susceptibility, compatible with altered B-cell differentiation as a key mechanism. Dysregulation of autophagy/apoptosis and cell cycle signalling feature as recurrently perturbed pathways. Our findings provide further insight

    Why do dairy cows have reproductive problems? How can we solve those reproductive problems?

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    The 1989 Annual KSU Dairy Day is known as Dairy Day, 1989Except for very low producing herds, management of reproduction does not seem to have much effect on the herd's level of production. To counter this statement, we must ask the question: "If they did not manage reproduction, what would their production level be?" Dairy cows develop reproductive problems from three major categories of causes: man-made, biological, and environmental
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