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UK Center (uk + center)
Selected AbstractsContribution of the novel inflammatory bowel disease gene IL23R to disease susceptibility and phenotypeINFLAMMATORY BOWEL DISEASES, Issue 9 2007J.R. Fraser Cummings MRCP(UK) Abstract Background: A North American genome-wide single nucleotide polymorphism (SNP) association study identified IL23R as a novel inflammatory bowel disease (IBD) susceptibility gene. Association was reported with multiple risk variants in the centromeric portion of IL23R in 3 large independent cohorts. The aims of this study were to replicate the association of IL23R with Crohn's disease (CD), examine subphenotype relationships, and look for evidence of epistasis with the known CD susceptibility gene CARD15 and susceptibility haplotype IBD5 in a large collection of CD patients. We further investigated the relationship between IL23R and ulcerative colitis (UC). Methods: In all, 604 CD and 647 UC patients who had been rigorously phenotyped and who had been recruited from a single UK center were used in this study. Controls were either spouses of patients (141) or were recruited from well-person clinics (993). Eight SNPs were genotyped using MassArray (Sequenom). All 8 SNPs genotyped were significantly associated with CD. Results: The association with the nonsynonymous SNP rs11209026 was confirmed (P = 6.65 × 10,6, odds ratio [OR], 0.43, 95% confidence interval [CI]: 0.29-0.64). The most significant SNP in our study was rs7517847 (P = 4.9 × 10,9, OR 0.65, 0.56,0.75), which is statistically independent of rs11209026. Preliminary evidence suggests an epistatic interaction with the IBD5 risk haplotype. The effects of mutations in this IL23R appear weaker in UC (P = 0.008, OR 0.63, 0.45,0.89 and 0.005 OR, 0.81, 0.71,0.94, respectively). No subphenotype associations were identified. Conclusions: We confirmed the findings that IL23R is a susceptibility gene for IBD with suggestive epistasis with the IBD5 locus in the CD population. (Inflamm Bowel Dis 2007) [source] Confirmation of the role of ATG16l1 as a Crohn's disease susceptibility geneINFLAMMATORY BOWEL DISEASES, Issue 8 2007J.R. Fraser Cummings MRCP(UK) Abstract Background: A German genome-wide nonsynonymous single nucleotide polymorphism (nsSNP) association study identified ATG16L1 as a Crohn's disease (CD) susceptibility gene. The association appeared to be confined to the nsSNP rs2241880 and was confirmed in 2 German independent case-control collections (combined P = 4.0 × 10,8, odds ratio [OR] 1.45; 95% confidence interval [CI]: 1.21-1.74), a CD transmission disequilibrium test (TDT) collection, and an independent UK cohort. A weak statistical interaction with CARD15 was demonstrated. No association with ulcerative colitis (UC) was demonstrated. The aims of the study were to replicate the association with CD, examine subphenotype associations and statistical interactions with CARD15, IL23R, and the IBD5 risk haplotype, as well as explore the association with UC. Methods: The study included 645 CD and 676 UC rigorously phenotyped patients recruited from a single UK center. Unaffected controls comprised either spouses of patients (141) or individuals recruited from well-person clinics (1049). The nsSNP rs2241880 was genotyped using MassArray (Sequenom). Results: A strong association with CD was demonstrated (P = 2.33 × 10,7, OR 1.45 [1.25,1.67]), but no significant association was demonstrated with any subphenotype. We failed to replicate the reported interaction between rs2241880 and the CARD15 low-risk haplotypes dd and Dd. No significant statistical interaction with the 3 known CD susceptibility genes was seen. No association with UC susceptibility (P = 0.37, OR 1.06 [0.93-1.22]), or any UC subphenotype was identified. Conclusions: We confirmed the findings that ATG16L1 is a CD susceptibility gene and found no evidence of interaction with CARD15, IL23R, or IBD5. (Inflamm Bowel Dis 2007) [source] The effect of preoperative weight loss and body mass index on postoperative outcome in patients with esophagogastric carcinomaDISEASES OF THE ESOPHAGUS, Issue 7 2009J. Skipworth SUMMARY Studies have shown that weight loss is associated with adverse outcomes in all treatment modalities for esophagogastric carcinoma. Because of the increased prevalence of obesity and the effectiveness of perioperative nutrition, a number of patients are now obese or have normal body mass index (BMI) at the time of treatment. We investigated the relationship between weight loss, BMI, and outcome of surgery for patients with esophagogastric carcinoma. Data were collected over a 38-month period for all patients diagnosed with operable esophagogastric cancer at two UK centers. All patients underwent resection by a single Consultant Upper Gastrointestinal Surgeon and the use of perioperative jejunal feeding was universal. Ninety-three patients (57 male) underwent esophagogastric resection; 48 had no preoperative weight loss (34 with a BMI > 25 and 14 with a BMI < 25). Forty-five patients had preoperative weight loss (20 with BMI > 25 and 25 with BMI < 25). There was no significant difference in complication rates, median hospital stay, or mortality between the four groups. A significantly higher number of patients displaying preoperative weight loss were found to have stage III disease, but difference in survival of up to 3 years did not reach statistical significance on multivariate analysis. Preoperative weight loss and low BMI did not significantly influence the complication rate, perioperative mortality rate, length of hospital stay, or short-term prognosis. We conclude that preoperative weight loss can not be reliably used as an independent predictor of poor outcome in patients undergoing surgery for esophagogastric carcinoma. However, patients with preoperative weight loss and low BMI are more likely to have advanced disease. [source] Time to Cardiac Death After Withdrawal of Life-Sustaining Treatment in Potential Organ DonorsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2009C. Suntharalingam Organ donation after cardiac death (DCD) is increasing markedly, allowing more patients to benefit from transplantation. The time to cardiac death following withdrawal of life-supporting treatment varies widely and is an important determinant of whether organ donation occurs. A prospective multicenter study of potential DCD donors was undertaken to evaluate the time to death and identify associated factors. One hundred and ninety-one potential adult DCD donors at nine UK centers were studied. Treatment withdrawal comprised stopping ventilator support and inotropes. Demographics and physiological variables at the time of death were recorded. Following treatment withdrawal, all potential donors died, with median time to death of 36 min (range 5 min to 3.3 days). Eighty-three potential donors (43.5%) remained alive 1 h after treatment withdrawal, and 69 (36.1%) and 54 (28.3%) at 2 and 4 h, respectively. Univariate analysis revealed that age, cause of death, ventilation mode, inotrope use, systolic blood pressure, FiO2 and arterial pH at treatment withdrawal were all associated with time to death. Multivariable analysis showed that younger age, higher FiO2 and mode of ventilation were independently associated with shorter time to death. This information may aid planning and resourcing of DCD organ recovery and help maximize DCD donor numbers. [source] | ||||||||||