RESUMO
Background: Transcriptional profiling has been performed on biopsies from ulcerative colitis patients. Limitations in prior studies include the variability introduced by inflammation, anatomic site of biopsy, extent of disease, and medications. We sought to more globally understand the variability of gene expression from patients with ulcerative colitis to advance our understanding of its pathogenesis and to guide clinical study design. Methods: We performed transcriptional profiling on 13 subjects, including pediatric and adult patients from 2 hospital sites. For each patient, we collected 6 biopsies from macroscopically inflamed tissue and 4 biopsies from macroscopically healthy-appearing tissue. Isolated RNA was used for microarray gene expression analysis utilizing Affymetrix Human Primeview microarrays. Ingenuity pathway analysis was used to assess over-representation of gene ontology and biological pathways. RNAseq was also performed, and differential analysis was assessed to compare affected vs unaffected samples. Finally, we modeled the minimum number of biopsies required to reliably detect gene expression across different subject numbers. Results: Transcriptional profiles co-clustered independently of the hospital collection site, patient age, sex, and colonic location, which parallels prior gene expression findings. A small set of genes not previously described was identified. Our modeling analysis reveals the number of biopsies and patients per cohort to yield reliable results in clinical studies. Conclusions: Key findings include concordance, including some expansion, of previously published gene expression studies and similarity among different age groups. We also established a reliable statistical model for biopsy collection for future clinical studies.
Assuntos
Colite Ulcerativa/genética , Colo/metabolismo , Mucosa Intestinal/metabolismo , Adolescente , Adulto , Suscetibilidade a Doenças/metabolismo , Feminino , Expressão Gênica , Genoma Humano/genética , Humanos , Íleo/metabolismo , Masculino , Análise em Microsséries , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , RNA/metabolismo , Adulto JovemRESUMO
Background: Patients with inflammatory bowel disease (IBD) have reported use of marijuana to treat symptoms of the disease, yet its classification as a Schedule 1 substance by the federal government has restricted its use. In 2012, Massachusetts legalized medicinal marijuana. We aimed to assess the impact of legalization on use in IBD. Methods: Consecutive patients with IBD, cared for at a tertiary care center in Boston, were surveyed regarding use of marijuana, including its perceived benefits and attitudes. Data were then compared with results of a similar survey study conducted at our center in 2012, before marijuana's legalization. Results: The survey was completed by 302 patients. There was a significant increase in marijuana use overall from 12.3% in 2012 to 22.8% in 2017 (P < 0.001). However, there was no significant increase in medicinal use from 2012 to 2017. On bivariate analysis, severe disease, as assessed by SIBDQ score, prior hospitalization, biologic therapy use, prior surgery, and chronic abdominal pain, was found to be more predictive of medicinal use now than in 2012. Among patients surveyed who have never used marijuana, 39.4% reported being interested in using medicinal marijuana, and 54.3% indicated that legalization did not affect their likelihood of using medicinal marijuana. Conclusions: In an IBD tertiary care center, we identified an overall upward trend in marijuana use but no significant change in medicinal use since its legalization in 2012. Our data suggests that the legalization of medical marijuana has resulted in an insignificant change in medicinal marijuana use in this population. 10.1093/ibd/izy141_video1izy141.video15786500236001.