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Related Concept Videos

Inflammatory Bowel Disease V: Surgical Management01:21

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Surgical interventions for inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease, are essential in managing symptoms and addressing complications. The selection of surgical procedures is contingent upon the specific conditions and complications that stem from these illnesses.
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Inflammatory Bowel Disease II: Crohn's Disease01:30

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Introduction
Inflammatory bowel disease, commonly known as IBD, refers to a collection of disorders that lead to persistent inflammation of the gastrointestinal tract. The two types of IBD are ulcerative colitis, which impacts the colon, and Crohn's disease, which can involve any part of the gastrointestinal segment.
Crohn's disease
Crohn's disease is a chronic, systemic inflammatory bowel disease (IBD) that predominantly affects the gastrointestinal tract. It is marked by...
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Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab...
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Crohn's disease is an inflammatory bowel disorder marked by chronic inflammation of the GI tract. Various treatment strategies for Crohn's disease are employed, such as immunomodulatory agents, glucocorticoids, and biologics or anti-TNF therapy. Azathioprine (Imuran), a commonly used immunomodulatory drug for Crohn's disease, is converted in the body to mercaptopurine, which inhibits purine biosynthesis and cell proliferation. Both are utilized in severe cases of Inflammatory Bowel...
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Glucocorticoids, a class of anti-inflammatory drugs, are pivotal in treating moderate to severe Crohn's disease by inducing remission. They exhibit their anti-inflammatory action by inhibiting the production of inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1, and chemokines like IL-8. In addition, they reduce the expression of inflammatory cell adhesion molecules and inhibit gene transcription of nitric oxide synthase, phospholipase A2, cyclooxygenase-2...
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A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
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Novel Genetic Variant Predicts Surgical Recurrence Risk in Crohn's Disease Patients.

Ming-Hsi Wang1,2, Jessica J Friton1, Laura E Raffals1

  • 1Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.

Inflammatory Bowel Diseases
|March 16, 2021
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Summary

A new genetic marker, rs2060886 in TCF4, predicts surgical recurrence risk in Crohn's disease (CD) patients after initial abdominal surgery. Early surgery era also indicates higher recurrence, aiding personalized CD management.

Keywords:
Crohn’s diseasegeneticssurgical recurrence risk

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Area of Science:

  • Genetics and Genomics
  • Gastroenterology
  • Surgical Outcomes

Background:

  • Crohn's disease (CD) patients undergoing abdominal surgery face significant risk of recurrence.
  • Predicting surgical recurrence is crucial for optimizing patient management and surgical strategies.
  • Current models lack comprehensive integration of genetic and clinical risk factors.

Purpose of the Study:

  • To identify a predictive model for surgical recurrence risk in CD patients post-abdominal surgery.
  • To investigate both clinical and genome-wide genetic factors associated with surgical recurrence.
  • To validate a genetic risk profile using independent inflammatory bowel disease (IBD) cohorts.

Main Methods:

  • Utilized two independent IBD cohort studies for derivation and validation.
  • Genotyped 372 CD patients using Illumina Immunochip custom genotyping array.
  • Defined surgical recurrence as second or more abdominal bowel resections post-first surgery.

Main Results:

  • 35.5% of CD patients experienced surgical recurrence after their first abdominal surgery.
  • Immunomodulatory drug history (OR, 3.96) and earlier era of first surgery (OR, 1.12) were significant clinical predictors.
  • A novel genome-wide significant locus, rs2060886 in TCF4 (chr18q21.2), strongly associated with surgical recurrence (OR, 4.10; P=4.58E-08).

Conclusions:

  • The novel genetic locus rs2060886 in TCF4 is significantly associated with surgical recurrence risk in CD patients.
  • Early surgical era for CD predicts a higher risk of subsequent surgical recurrence.
  • Genetic variants, like rs2060886, may guide management strategies for CD patients at high risk of repeated surgeries.