Background & Aims: Thiopurine-related myelosuppression (most frequently leukopenia) interferes with thiopurine therapy for patients with inflammatory bowel diseases (IBD). We investigated whether pretreatment analyses genetic variants associated with thiopurine-induced leukopenia could be used to effectively identify patients who required dose adjustments.
Methods: We performed a multicenter, prospective study of patients with IBD at 5 tertiary medical centers in Korea, from January 2016 through September 2018. Seventy-two patients were randomly assigned to a group that underwent genotype analysis for the NUDT15 variant (rs116855232) and FTO variant (rs79206939) and 3 common TPMT variants (rs1800460, rs1800462, rs1142345) associated with myelosuppression and 92 patients were assigned to a group that did not undergo genotype analysis (non-genotyping group). Patients heterozygous for any variant received 50 mg azathioprine equivalents, whereas those who were homozygous for any variant received alternative drugs. Patients who did not carry any of the genetic variants and patients in the non-genotyping group received 50 mg azathioprine equivalents followed by dose escalation up to 2-2.5 mg/kg. Myelosuppression was defined as white blood cell counts below 3000/μL, levels of hemoglobin 10 g/dL, or platelet counts below 100 K/μL.
Results: Twelve patients (16.7%) in the genotype analysis group and 33 patients (35.9%) in the non-genotyping group developed myelosuppression (P=.005). A multivariate analysis revealed that body mass indices above 21 kg/m (hazard ratio [HR], 0.43; 95% CI, 0.22-0.81; P = .009), pretreatment genotype analysis (HR, 0.37; 95% CI, 0.18-0.77; P = .008), and the maximum dose of thiopurines (HR, 0.34; 95% CI, 0.19-0.59; P < .001) independently decreased risk of myelosuppression. Pretreatment genotype analysis reduced numbers of outpatient clinic visit and numbers of patients with drug discontinuation or dose reductions.
Conclusions: In a randomized controlled study of patients undergoing thiopurine therapy for IBD, we found that selection of therapy based on genetic variants associated with thiopurine-induced leukopenia significantly reduced the proportion of patients with myelosuppression during treatment. ClinicalTrials.gov no: NCT03719118.
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http://dx.doi.org/10.1016/j.cgh.2019.08.034 | DOI Listing |
Avian Pathol
January 2025
College of Animal Science and Technology, Shandong Agricultural University, Tai'an, Shandong, People's Republic of China.
In the last decade, the emergence of variant strains of avian orthoreovirus (ARV) has caused an enormous economic impact on the poultry industry across China and other countries. This study aimed to evaluate the molecular evolution of the ARV lineages detected in Chinese commercial broiler farms. Firstly, ARV isolation and identification of commercial broiler arthritis cases from different provinces in China from 2016 to 2021 were conducted.
View Article and Find Full Text PDFVet Med Sci
January 2025
Faculty of Veterinary Medicine, Department of Animal Breeding and Husbandry, Ondokuz Mayıs University, Samsun, Turkey.
Background: Ration composition may significantly impact the nutrient absorption, duodenal parameters, intestinal health and feed efficiency of animals.
Objectives: The objective of this study was to analyse the impact of concentrate- and forage-based diets on essential morphological parameters of the duodenum, including villus height, villus width, crypt depth and goblet cell density, in three different lamb breeds.
Methods: Forty-five lambs, aged between 2.
FASEB J
January 2025
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang, China.
Inflammatory bowel disease (IBD) with the two predominant endophenotypes-Crohn's disease (CD) and ulcerative colitis (UC)-represents a group of chronic gastrointestinal inflammatory conditions. Since most genetic associations with IBD are often limited to independent subtypes, we reported a genome-wide association study (GWAS) cross-trait analysis combined with CD and UC to enhance statistical power. Initially, we detected 256 association signals at 54 genomic susceptibility loci and further characterized the functionality of variants within these regions.
View Article and Find Full Text PDFMicrobiol Spectr
January 2025
National Food Virology Reference Center, Bureau of Microbial Hazards, Health Canada, Ottawa, Ontario, Canada.
Human noroviruses are the leading cause of non-bacterial shellfish-associated gastroenteritis. In 2022, a multi-jurisdictional norovirus outbreak associated with contaminated oysters occurred that involved hundreds of illnesses. Here, we conducted genetic analysis on 30 clinical samples associated with this oyster outbreak.
View Article and Find Full Text PDFAppl Environ Microbiol
January 2025
Tohoku Research Center, Forestry and Forest Products Research Institute, Forest Research and Management Organization, Morioka, Japan.
Unlabelled: , a white-colored truffle that is endemic to Japan, is promising for culinary purposes due to its unique aroma. We were able to cultivate in plantations of inoculated seedlings for the first time. Ascocarps were found after 43 months at one site and after 61 months at another.
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