Epidemiological Profile Of 175 Patients With Crohn's Disease Submitted To Biological Therapy

Introduction: There is currently an increasing use of biological agents in the management of Crohn's disease (CD). There is lack of data regarding the epidemiological profile of patients on infliximab (IFX) and adalimumab (ADA) for CD in Brazil. Objective: To identify the epidemiological characteristics of patients with CD who underwent biological therapy. Method: Retrospective multicenter study, with CD patients on biological therapy. Analyzed variables: gender, age at treatment initiation, Montreal classification, concomitant perianal disease and smoking status. Results: 175 patients without previous exposure to biological agents were included, 93 (53%) were male. The mean age at treatment initiation was 35.5 (2-79) years old an the mean disease duration was 46.9 (0-480) months. Overall, 117 (66.9%) patients used IFX and 58 (33.1%), ADA. Montreal classification: age at diagnosis - A1 (n=21; 12%), A2 (n=102; 58.3%), and A3 (n=52; 29.7%). CD location - L1 (n=42; 24%), L2 (n=51; 29.1%), L3 (n=81; 46.3%), and L4 (n=1, 0.6%). Phenotype -B1 (n=59; 33.7%), B2 (n=46; 26.3%), and B3 (n=70; 40%). Perianal disease was found in 89 (50.9%) patients. Conclusions: The epidemiological profile of patients was similar to the literature. 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A g316a polymorphism in the ornithine decarboxylase gene promoter modulates mycn\u2010driven childhood neuroblastoma

Ornithine decarboxylase (ODC1), a critical regulatory enzyme in polyamine biosynthesis, is a direct transcriptional target of MYCN, amplification of which is a powerful marker of aggressive neuroblastoma. A single nucleotide polymorphism (SNP), G316A, within the first intron of ODC1, results in genotypes wildtype GG, and variants AG/AA. CRISPR\u2010cas9 technology was used to investigate the effects of AG clones from wildtype MYCN\u2010amplified SK\u2010N\u2010BE(2)\u2010C cells and the effect of the SNP on MYCN binding, and promoter activity was investigated using EMSA and luciferase assays. AG clones exhibited decreased ODC1 expression, growth rates, and histone acetylation and increased sensitivity to ODC1 inhibition. MYCN was a stronger transcriptional regulator of the ODC1 promoter containing the G allele, and preferentially bound the G allele over the A. Two neu-roblastoma cohorts were used to investigate the clinical impact of the SNP. In the study cohort, the minor AA genotype was associated with improved survival, while poor prognosis was associated with the GG genotype and AG/GG genotypes in MYCN\u2010amplified and non\u2010amplified patients, re-spectively. These effects were lost in the GWAS cohort. We have demonstrated that the ODC1 G316A polymorphism has functional significance in neuroblastoma and is subject to allele\u2010specific regulation by the MYCN oncoprotein

Mortality from esophagectomy for esophageal cancer across low, middle, and high-income countries: An international cohort study.

BACKGROUND No evidence currently exists characterising global outcomes following major cancer surgery, including esophageal cancer. Therefore, this study aimed to characterise impact of high income countries (HIC) versus low and middle income countries (LMIC) on the outcomes following esophagectomy for esophageal cancer. METHOD This international multi-center prospective study across 137 hospitals in 41 countries included patients who underwent an esophagectomy for esophageal cancer, with 90-day follow-up. The main explanatory variable was country income, defined according to the World Bank Data classification. The primary outcome was 90-day postoperative mortality, and secondary outcomes were composite leaks (anastomotic leak or conduit necrosis) and major complications (Clavien-Dindo Grade III - V). Multivariable generalized estimating equation models were used to produce adjusted odds ratios (ORs) and 95% confidence intervals (CI). RESULTS Between April 2018 to December 2018, 2247 patients were included. Patients from HIC were more significantly older, with higher ASA grade, and more advanced tumors. Patients from LMIC had almost three-fold increase in 90-day mortality, compared to HIC (9.4% vs 3.7%, p < 0.001). On adjusted analysis, LMIC were independently associated with higher 90-day mortality (OR: 2.31, CI: 1.17-4.55, p = 0.015). However, LMIC were not independently associated with higher rates of anastomotic leaks (OR: 1.06, CI: 0.57-1.99, p = 0.9) or major complications (OR: 0.85, CI: 0.54-1.32, p = 0.5), compared to HIC. CONCLUSION Resections in LMIC were independently associated with higher 90-day postoperative mortality, likely reflecting a failure to rescue of these patients following esophagectomy, despite similar composite anastomotic leaks and major complication rates to HIC. These findings warrant further research, to identify potential issues and solutions to improve global outcomes following esophagectomy for cancer