Alstonmarsh6906

Improving treatment outcomes with biological therapy is a demanding current need for patients with inflammatory bowel disease. Discovery of pretreatment prognostic indicators of response may facilitate patient selection and increase long-term remission rates. We aimed to identify baseline mucosal gene expression profiles with predictive value for subsequent response to or failure of treatment with the monoclonal antibody against integrin α4β7, vedolizumab, in patients with active ulcerative colitis (UC).

Mucosal expression of 84 immunological and inflammatory genes was quantified in RNA extracted from colonic biopsies before vedolizumab commencement and compared between patients with or without response to treatment. Significantly differentiated genes were further validated in a larger patient cohort and within available public data sets, and their functional profiles were studied accordingly.

In the discovery cohort, we identified 21 genes with a statistically significant differential expression betweeammatory pathways. Baseline mucosal and/or systemic molecular profiling may help in the optimal stratification of patients to receive vedolizumab for active UC.

Janus kinase (JAK) inhibition shows promise for treatment of patients with moderate to severe Crohn's disease. We aimed to provide mechanistic insights into the JAK1-selective inhibitor upadacitinib through a transcriptomics substudy on biopsies from patients with Crohn's disease from CELEST.

Seventy-four patients consented to this optional substudy. Ileal and colonic biopsies were collected during endoscopy at screening and week 12 or 16. RNA isolated from 226 samples was analyzed by RNAseq, with additional qPCR analysis. Additional biopsies from patients with Crohn's disease receiving anti-tumor necrosis factor (anti-TNF; n = 34) and healthy controls (n = 10) were used for qPCR. Single-cell RNAseq public profiles were used to evaluate treatment effects on specific cellular subsets, associations with endoscopic improvement, and indirect comparisons with the anti-TNF-treated cohort.

In involved areas of mucosa with endoscopic remission after upadacitinib treatment, 1156 and 76 protein-coding genes were TNF-refractory Crohn's disease, including inflammatory fibroblast and interferon-γ-expressing cytotoxic T cell compartments. This substudy is the first to describe the molecular response to JAK1 inhibition in inflammatory bowel disease and differential effects relative to anti-TNF treatment. (Clinical trial identifier NCT02365649).

Celiac disease (CD) is a genetically complex autoimmune disease which is triggered by dietary gluten. Human leukocyte antigen (HLA) class II genes are known to act as high-risk markers for CD, where >95% of CD patients carry (HLA), DQ2 and/or DQ8 alleles. DNA Repair inhibitor Therefore, the present study was conducted to investigate the distribution of HLA haplotypes among Saudi CD patients and healthy controls by using the tag single nucleotide polymorphisms (SNP).

HLA-tag SNPs showing strong linkage value (r2>0.99) were used to predict the HLA DQ2 and DQ8 genotypes in 101 Saudi CD patients and in 103 healthy controls by using real-time polymerase chain reaction technique. Genotype calls were further validated by Sanger sequencing method.

A total of 63.7% of CD cases and of 60.2% of controls were predicted to carry HLA-DQ2 and DQ8 heterodimers, either in the homozygous or heterozygous states. The prevalence of DQ8 in our CD patients was predicted to be higher than the patients from other ethnic populations (35.6%). More than 32% of the CD patients were found to be non-carriers of HLA risk haplotypes as predicted by the tag SNPs.

The present study highlights that the Caucasian specific HLA-tag SNPs would be of limited value to accurately predict CD specific HLA haplotypes in Saudi population, when compared with the Caucasian groups. Prediction of risk haplotypes by tag SNPs in ethnic groups is a good alternate approach as long as the tag SNPs were identified from the local population genetic variant databases.

The present study highlights that the Caucasian specific HLA-tag SNPs would be of limited value to accurately predict CD specific HLA haplotypes in Saudi population, when compared with the Caucasian groups. Prediction of risk haplotypes by tag SNPs in ethnic groups is a good alternate approach as long as the tag SNPs were identified from the local population genetic variant databases.The decision to use adjuvant chemotherapy (ACT) after surgical resection for stage II colon cancer remains an area of clinical uncertainty. Many patients diagnosed with stage II colon cancer receive ACT, despite inconclusive evidence of long-term clinical benefit. This study investigates patient experiences and perceptions of treatment decision-making and shared decision making (SDM) for ACT among patients diagnosed with stage II colon cancer. Stage II colon cancer patients engaged in treatment or follow-up care aged >18 years were recruited from two large NYC health systems. Patients participated in 30-60-min semi-structured interviews. All interviews were transcribed, translated, coded, and analyzed using a thematic analysis approach. We interviewed 31 patients, of which 42% received ACT. Overall, patient perspectives indicate provider inconsistency in communicating ACT harms, benefits, and uncertainties, and poor elicitation of patient preferences and values. Patients reported varying perceptions and understanding of personal risk and clinical benefits of ACT. For many patients, receiving a clear treatment recommendation from the provider limited their participation in the decision-making process, whether it aligned with their decisional support preferences or not. Findings advance understanding of perceived roles and preferences of patients in SDM processes for cancer treatment under heightened clinical uncertainty, and indicate a notable gap in understanding for decisions made using SDM models in the context of clinical uncertainty. Educational and communication strategies and training are needed to support providers in communicating uncertainty, risk, treatment options, and implementing clinical guidelines to support patient awareness and informed decisions.