{
  "abstract": "Background The PIONIR (Preventing IBD ONset in Individuals at Risk) trial evaluates whether the Tasty&Healthy diet can reduce risk of Crohn’s disease (CD) development in first-degree relatives (FDRs). The optimal preclinical stage of CD for enrolling subjects to prevention trials is unknown.Objectives We aimed to propose a framework for identifying high-risk participants for prevention trials by reporting the outcomes of the pre-PIONIR screening stage.Design Faecal calprotectin was measured in asymptomatic FDRs aged 6–38 years; those with persistent elevation, defined as >70 µg/g in at least two separate tests, were offered panenteric video capsule-endoscopy or ileocolonoscopy.Results Of 950 FDRs approached, 331 (35%) agreed to be screened: 63 (19%) had persistently elevated calprotectin, of whom 42 underwent further evaluation. Nine (2.7%) had endoscopic appearance compatible with presymptomatic CD, 22 (6.6%) had non-specific macroscopic mucosal changes and 11 (3.3%) had normal mucosa despite elevated calprotectin, suggesting probable histological inflammation. The 33 participants in the two latter groups were defined as ‘potential pre-CD’ (17.9% of all screened after adjusting for missing values). Calprotectin >225 µg/g predicted presymptomatic CD (area under the receiver operating characteristic curve 0.97 (95% CI 0.94 to 1.0; p<0.001; sensitivity 89%, specificity 94%). Of those with a single elevated calprotectin value, 22% normalised on repeat testing with significant variability (intraclass correlation coefficient 0.72 (95% CI 0.57 to 0.82)).Conclusion Approximately one in five asymptomatic FDRs had persistently elevated calprotectin, which was able to differentiate those with presymptomatic CD. The findings highlight calprotectin’s utility in identifying at-risk individuals during the potential pre-CD stage for enrolment in prevention trials.",
  "authors": [
    {
      "affiliations": [
        "Institute of Pediatric Gastroenterology, Shaare Zedek Medical Center, Jerusalem, Jerusalem District, Israel",
        "Hebrew University of Jerusalem Faculty of Medicine, Jerusalem, Jerusalem District, Israel"
      ],
      "name": "Dan Turner"
    },
    {
      "affiliations": [
        "Shaare Zedek Medical Center, Jerusalem, Jerusalem District, Israel"
      ],
      "name": "Sarah Kenigsberg"
    },
    {
      "affiliations": [
        "The Juliet Keiden Institute of Pediatric Gastroenterology and Nutrition, Shaare Zedek Medical Center, Jerusalem, Israel"
      ],
      "name": "Gili Focht"
    },
    {
      "affiliations": [
        "Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada",
        "Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada"
      ],
      "name": "Williams Turpin"
    },
    {
      "affiliations": [
        "Paediatric Gastroenterology, Shaare Zedek Medical Center, Jerusalem, Israel",
        "Hebrew University Faculty of Medicine, Jerusalem, Israel"
      ],
      "name": "Oren Ledder"
    },
    {
      "affiliations": [
        "Department of Paediatrics, University of Toronto, Division of Gastroenterology, Hepatology & Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada"
      ],
      "name": "Anne M Griffiths"
    },
    {
      "affiliations": [
        "Michael J. Howorth GEM Project Team, Toronto, Ontario, Canada"
      ],
      "name": "Hien Q Huynh"
    },
    {
      "affiliations": [
        "Shaare Zedek Medical Center Juliet Keidan Institute of Paediatric Gastroenterology and Nutrition, Jerusalem, Israel"
      ],
      "name": "Luba Plotkin"
    },
    {
      "affiliations": [
        "Shaare Zedek Medical Center, Jerusalem, Jerusalem District, Israel"
      ],
      "name": "Yonat Aharoni-Frutkoff"
    },
    {
      "affiliations": [
        "Pediatric Gastroenterology, University of Manitoba, Winnipeg, Manitoba, Canada"
      ],
      "name": "Wael El-Matary"
    },
    {
      "affiliations": [
        "Pediatric Gastroenterology and Nutrition, IWK Health Centre, Halifax, Nova Scotia, Canada"
      ],
      "name": "Anthony R Otley"
    },
    {
      "affiliations": [
        "Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Central, Israel"
      ],
      "name": "Irit Avni-Biron"
    },
    {
      "affiliations": [
        "Pediatrics, British Columbia Children’s Hospital, Vancouver, British Columbia, Canada"
      ],
      "name": "Kevan Jacobson"
    },
    {
      "affiliations": [
        "Medicine, University of Calgary, Calgary, Alberta, Canada"
      ],
      "name": "Remo Panaccione"
    },
    {
      "affiliations": [
        "GI, Mount Sinai School of Medicine, New York City, New York, USA"
      ],
      "name": "Joana Torres"
    },
    {
      "affiliations": [
        "Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada",
        "Division of Gastroenterology & Hepatology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada"
      ],
      "name": "Sun-Ho Lee"
    },
    {
      "affiliations": [
        "Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada",
        "Division of Gastroenterology & Hepatology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada"
      ],
      "name": "Kenneth Croitoru"
    }
  ],
  "title": "Preclinical stages of Crohn’s disease defined by faecal calprotectin in asymptomatic first-degree relatives: screening framework for prevention trials",
  "uid": "277b6b7b-6015-5b57-ad72-83957f821dde"
}