Publications by authors named "Kevan Jacobson"

102 Publications

Pediatric Endoscopy Quality Improvement Network (PEnQuIN) Pediatric Endoscopy Reporting Elements: A Joint NASPGHAN/ESPGHAN Guideline.

J Pediatr Gastroenterol Nutr 2021 Aug 16. Epub 2021 Aug 16.

Division of Gastroenterology, Hepatology and Nutrition and the Research and Learning Institutes, The Hospital for Sick Children, Department of Paediatrics and the Wilson Centre, University of Toronto, Toronto, Ontario, Canada Division of Gastroenterology and Nutrition, UMass Memorial Children's Medical Center, Department of Pediatrics, University of Massachusetts Medical School, Worcester, MA, USA Section of Pediatric Gastroenterology, Hepatology and Nutrition, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA Pediatric Gastroenterology & Nutrition, Department of Pediatrics, University Children's Hospital Basel, University of Basel, Basel, Switzerland Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA Paediatric Gastroenterology, Hepatology and Nutrition Department, Royal Hospital for Sick Children, Edinburgh, Scotland, United Kingdom Department of Paediatric Gastroenterology, Sheffield Children's Hospital NHS Foundation Trust, Sheffield University, Sheffield, South Yorkshire, United Kingdom Referral Center for Pediatric Gastroenterology and Nutrition, Children's Hospital Zagreb, University of Zagreb Medical School, Zagreb, University J.J. Strossmayer Medical School, Osijek, Croatia Pediatric Gastroenterology and Liver Unit, Maternal and Child Health Department, Umberto I - University Hospital, Sapienza - University of Rome, Rome, Italy Department of Gastroenterology, Hepatology and Nutrition, University Children's Hospital, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia Department of Pediatric Gastroenterology, Providence St. Vincent's Medical Center, Portland, OR, USA Pediatric Gastroenterology and Nutrition, Department of Pediatrics, Stollery Children's Hospital, University of Alberta, Edmonton, Alberta, Canada Division of Pediatric Gastroenterology, Department of Pediatrics, Goryeb Children's Hospital, Icahn School of Medicine at Mount Sinai, Morristown, NJ, USA Division of Gastroenterology, Hepatology and Nutrition, British Columbia's Children's Hospital and British Columbia Children's Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, Canada Division of Pediatrics, Pediatric Gastroenterology Department, Centro Materno Infantil do Norte, Centro Hospitalar Universitário do Porto, ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Porto, Portugal Division of Gastroenterology, Hepatology and Nutrition, Children's National Medical Center, Department of Pediatrics, George Washington University, Washington D.C., USA Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Washington University School of Medicine/St. Louis Children's Hospital, St. Louis, MO, USA Blizard Institute, Barts and the London School of Medicine, Royal London Children's Hospital, Barts Health NHS Trust, Queen Mary University of London, London, United Kingdom Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Eastern Ontario, Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada Division of Gastroenterology & Nutrition, Department of Pediatrics, McMaster Children's Hospital, McMaster University, Department of Paediatrics, William Osler Health System, Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada Division of Gastroenterology and Hepatology, Medicine and Pediatrics, Cedars-Sinai Medical Center, David Geffen School of Medicine at UCLA, Los Angeles, California, USA Division of Pediatrics, Department of Pediatric Gastroenterology, Queen Fabiola Children's University Hospital, ICBAS - Université Libre de Bruxelles, Brussels, Belgium Division of Pediatrics, Pediatric Gastroenterology, Hepatology and Nutrition, Children's of Wisconsin, Medical College of Wisconsin, Milwaukee, WI, USA Pediatric Gastroenterology, Department of Pediatrics, Centro Hospitalar Universitário S. João, Porto, Portugal Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Children's Hospital of Colorado, University of Colorado, Aurora, Colorado, USA Gastroenterology & Nutrition, Department of Pediatrics, IWK Health, Dalhousie University, Halifax, Nova Scotia, Canada Division of Gastroenterology and Hepatology, Seattle Children's Hospital, Department of Pediatrics, University of Washington, Seattle, WA, United States of America Child Health Evaluative Sciences, SickKids Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.

Introduction: High quality procedure reports are a cornerstone of high quality pediatric endoscopy as they ensure the clear communication of procedural events and outcomes, guide patient care and facilitate continuous quality improvement. The aim of this document is to outline standardized reporting elements that achieved international consensus as requirements for high quality pediatric endoscopy procedure reports.

Methods: With support from the North American and European Societies of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN and ESPGHAN), an international working group of the Pediatric Endoscopy Quality Improvement Network (PEnQuIN) used Delphi methodology to identify key elements that should be found in all pediatric endoscopy reports. Item reduction was attained through iterative rounds of anonymized online voting using a 6-point scale. Responses were analyzed after each round and items were excluded from subsequent rounds if ≤50% of panelists rated them as 5 ('agree moderately') or 6 ('agree strongly'). Reporting elements that ≥70% of panelists rated as 'agree moderately' or 'agree strongly' were considered to have achieved consensus.

Results: Twenty-six PEnQuIN group members from 25 centers internationally rated 63 potential reporting elements that were generated from a systematic literature review and the Delphi panelists. The response rates were 100% for all three survey rounds. Thirty reporting elements reached consensus as essential for inclusion within a pediatric endoscopy report.

Discussion: It is recommended that the PEnQuIN Reporting Elements for pediatric endoscopy be universally employed across all endoscopists, procedures and facilities as a foundational means of ensuring high quality endoscopy services, while facilitating quality improvement activities in pediatric endoscopy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MPG.0000000000003266DOI Listing
August 2021

Pediatric Endoscopy Quality Improvement Network (PEnQuIN) Quality Standards and Indicators for Pediatric Endoscopists and Endoscopists in Training: A Joint NASPGHAN/ESPGHAN Guideline.

J Pediatr Gastroenterol Nutr 2021 Aug 16. Epub 2021 Aug 16.

Division of Gastroenterology, Hepatology and Nutrition and the Research and Learning Institutes, The Hospital for Sick Children, Department of Paediatrics and the Wilson Centre, University of Toronto, Toronto, Ontario, Canada Division of Gastroenterology and Nutrition, UMass Memorial Children's Medical Center, Department of Pediatrics, University of Massachusetts Medical School, Worcester, MA, USA Division of Gastroenterology, Hepatology and Nutrition, Children's National Medical Center, Department of Pediatrics, George Washington University, Washington D.C., USA Division of Pediatrics, Pediatric Gastroenterology, Hepatology and Nutrition, Children's of Wisconsin, Medical College of Wisconsin, Milwaukee, WI, USA Division of Gastroenterology and Hepatology, Medicine and Pediatrics, Cedars-Sinai Medical Center, David Geffen School of Medicine at UCLA, Los Angeles, California, USA Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Eastern Ontario, Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA Department of Paediatric Gastroenterology, Sheffield Children's Hospital NHS Foundation Trust, Sheffield, South Yorkshire, United Kingdom Pediatric Gastroenterology and Liver Unit, Maternal and Child Health Department, Umberto I - University Hospital, Sapienza - University of Rome, Rome, Italy Department of Pediatric Gastroenterology, Providence St. Vincent's Medical Center, Portland, OR, USA Division of Pediatric Gastroenterology, Department of Pediatrics, Goryeb Children's Hospital, Icahn School of Medicine at Mount Sinai, Morristown, NJ, USA Division of Pediatrics, Pediatric Gastroenterology Department, Centro Materno Infantil do Norte, Centro Hospitalar Universitário do Porto, ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Porto, Portugal Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Washington University School of Medicine/St. Louis Children's Hospital, St. Louis, MO, USA Pediatric Gastroenterology, Department of Pediatrics, Centro Hospitalar Universitário S. João, Porto, Portugal Division of Pediatrics, Department of Pediatric Gastroenterology, Queen Fabiola Children's University Hospital, ICBAS - Université Libre de Bruxelles, Brussels, Belgium Division of Gastroenterology & Nutrition, Department of Pediatrics, McMaster Children's Hospital, McMaster University, Department of Paediatrics, William Osler Health System, Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada Blizard Institute, Barts and the London School of Medicine, Royal London Children's Hospital, Barts Health NHS Trust, Queen Mary University of London, London, United Kingdom Section of Pediatric Gastroenterology, Hepatology and Nutrition, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA Pediatric Gastroenterology & Nutrition, Department of Pediatrics, University Children's Hospital Basel, University of Basel, Basel, Switzerland Paediatric Gastroenterology, Hepatology and Nutrition Department, Royal Hospital for Sick Children, Edinburgh, Scotland, United Kingdom Referral Center for Pediatric Gastroenterology and Nutrition, Children's Hospital Zagreb, University of Zagreb Medical School, Zagreb, University J.J. Strossmayer Medical School, Osijek, Croatia Department of Gastroenterology, Hepatology and Nutrition, University Children's Hospital, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia Pediatric Gastroenterology and Nutrition, Department of Pediatrics, Stollery Children's Hospital, University of Alberta, Edmonton, Alberta, Canada Division of Gastroenterology, Hepatology and Nutrition, British Columbia's Children's Hospital and British Columbia Children's Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, Canada Division of Gastroenterology and Hepatology, Seattle Children's Hospital, Department of Pediatrics, University of Washington, Seattle, WA, United States of America Gastroenterology & Nutrition, Department of Pediatrics, IWK Health, Dalhousie University, Halifax, Nova Scotia, Canada Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Children's Hospital of Colorado, University of Colorado, Aurora, Colorado, USA Child Health Evaluative Sciences, SickKids Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada Child Health Evaluative Sciences, SickKids Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada Department of Paediatric Gastroenterology, Sheffield Children's Hospital NHS Foundation Trust, Sheffield University, Sheffield, South Yorkshire, United Kingdom.

Introduction: High quality pediatric endoscopy requires reliable performance of procedures by competent individual providers who consistently uphold all standards determined to assure optimal patient outcomes. Establishing consensus expectations for ongoing monitoring and assessment of individual pediatric endoscopists is a method for confirming the highest possible quality of care for such procedures worldwide. We aim to provide guidance to define and measure quality of endoscopic care for children.

Methods: With support from the North American and European Societies of Pediatric Gastroenterology Hepatology and Nutrition (NASPGHAN and ESPGHAN), an international working group of the Pediatric Endoscopy Quality Improvement Network (PEnQuIN) used the methodological strategy of the Appraisal of Guidelines for REsearch and Evaluation (AGREE) II instrument to develop standards and indicators relevant for assessing the quality of endoscopists. Consensus was sought via an iterative online Delphi process and finalized at an in-person conference. The quality of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach.

Results: The PEnQuIN working group achieved consensus on 6 standards that all providers who perform pediatric endoscopy should uphold and 2 standards for pediatric endoscopists in training, with a corresponding 7 indicators that can be used to identify high quality endoscopists. Additionally, these can inform continuous quality improvement at the provider level. Minimum targets for defining high quality pediatric ileocolonoscopy were set for 2 key indicators: cecal intubation rate (≥90%) and terminal ileal intubation rate (≥85%).

Discussion: It is recommended that all individual providers performing or training to perform pediatric endoscopy initiate and engage with these international endoscopist-related standards and indicators developed by PEnQuIN.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MPG.0000000000003265DOI Listing
August 2021

Pediatric Endoscopy Quality Improvement Network (PEnQuIN) Quality Standards and Indicators for Pediatric Endoscopic Procedures: A Joint NASPGHAN/ESPGHAN Guideline.

J Pediatr Gastroenterol Nutr 2021 Aug 16. Epub 2021 Aug 16.

Division of Gastroenterology and Nutrition, UMass Memorial Children's Medical Center, Department of Pediatrics, University of Massachusetts Medical School, Worcester, MA, USA Division of Gastroenterology, Hepatology and Nutrition and the Research and Learning Institutes, The Hospital for Sick Children, Department of Paediatrics and the Wilson Centre, University of Toronto, Toronto, Ontario, Canada Pediatric Gastroenterology and Liver Unit, Maternal and Child Health Department, Umberto I - University Hospital, Sapienza - University of Rome, Rome, Italy Division of Gastroenterology, Hepatology and Nutrition, British Columbia's Children's Hospital and British Columbia Children's Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, Canada Pediatric Gastroenterology and Nutrition, Department of Pediatrics, Stollery Children's Hospital, University of Alberta, Edmonton, Alberta, Canada Department of Gastroenterology, Hepatology and Nutrition, University Children's Hospital, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia Referral Center for Pediatric Gastroenterology and Nutrition, Children's Hospital Zagreb, University of Zagreb Medical School, Zagreb, University J.J. Strossmayer Medical School, Osijek, Croatia Paediatric Gastroenterology, Hepatology and Nutrition Department, Royal Hospital for Sick Children, Edinburgh, Scotland, United Kingdom Pediatric Gastroenterology & Nutrition, Department of Pediatrics, University Children's Hospital Basel, University of Basel, Basel, Switzerland Section of Pediatric Gastroenterology, Hepatology and Nutrition, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA Blizard Institute, Barts and the London School of Medicine, Royal London Children's Hospital, Barts Health NHS Trust, Queen Mary University of London, London, United Kingdom Division of Gastroenterology & Nutrition, Department of Pediatrics, McMaster Children's Hospital, McMaster University, Department of Paediatrics, William Osler Health System, Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada Division of Pediatrics, Department of Pediatric Gastroenterology, Queen Fabiola Children's University Hospital, ICBAS - Université Libre de Bruxelles, Brussels, Belgium Pediatric Gastroenterology, Department of Pediatrics, Centro Hospitalar Universitário S. João, Porto, Portugal Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Washington University School of Medicine/St. Louis Children's Hospital, St. Louis, MO, USA Division of Pediatrics, Pediatric Gastroenterology Department, Centro Materno Infantil do Norte, Centro Hospitalar Universitário do Porto, ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Porto, Portugal Division of Pediatric Gastroenterology, Department of Pediatrics, Goryeb Children's Hospital, Icahn School of Medicine at Mount Sinai, Morristown, NJ, USA Department of Pediatric Gastroenterology, Providence St. Vincent's Medical Center, Portland, OR, USA Department of Paediatric Gastroenterology, Sheffield Children's Hospital NHS Foundation Trust, Sheffield University, Sheffield, South Yorkshire, United Kingdom Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Eastern Ontario, Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada Division of Gastroenterology and Hepatology, Medicine and Pediatrics, Cedars-Sinai Medical Center, David Geffen School of Medicine at UCLA, Los Angeles, California, USA Division of Pediatrics, Pediatric Gastroenterology, Hepatology and Nutrition, Children's of Wisconsin, Medical College of Wisconsin, Milwaukee, WI, USA Division of Gastroenterology, Hepatology and Nutrition, Children's National Medical Center, Department of Pediatrics, George Washington University, Washington D.C., USA Gastroenterology & Nutrition, Department of Pediatrics, IWK Health, Dalhousie University, Halifax, Nova Scotia, Canada Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Children's Hospital of Colorado, University of Colorado, Aurora, Colorado, USA Division of Gastroenterology and Hepatology, Seattle Children's Hospital, Department of Pediatrics, University of Washington, Seattle, WA, United States of America Child Health Evaluative Sciences, SickKids Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.

Introduction: High quality pediatric gastrointestinal procedures are performed when clinically indicated and defined by their successful performance by skilled providers in a safe, comfortable, child-oriented and expeditious manner. The process of pediatric endoscopy begins when a plan to perform the procedure is first made and ends when all appropriate patient follow-up has occurred. Procedure-related standards and indicators developed to date for endoscopy in adults emphasize cancer screening and are thus unsuitable for pediatric medicine.

Methods: With support from the North American and European Societies of Pediatric Gastroenterology Hepatology and Nutrition (NASPGHAN and ESPGHAN), an international working group of the Pediatric Endoscopy Quality Improvement Network (PEnQuIN) used the methodological strategy of the Appraisal of Guidelines for REsearch and Evaluation (AGREE) II instrument to develop standards and indicators relevant for assessing the quality of endoscopic procedures. Consensus was sought via an iterative online Delphi process and finalized at an in-person conference. The quality of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach.

Results: The PEnQuIN working group achieved consensus on 14 standards for pediatric endoscopic procedures, as well as 30 indicators that can be used to identify high quality procedures. These were subcategorized into 3 subdomains: Preprocedural (3 standards, 7 indicators), Intraprocedural (8 standards, 18 indicators) and Postprocedural (3 standards, 5 indicators). A minimum target for the key indicator, 'rate of adequate bowel preparation,' was set at ≥80%.

Discussion: It is recommended that all facilities and individual providers performing pediatric endoscopy worldwide initiate and engage with the procedure-related standards and indicators developed by PEnQuIN to identify gaps in quality and drive improvement.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MPG.0000000000003264DOI Listing
August 2021

Pediatric Endoscopy Quality Improvement Network (PEnQuIN) Quality Standards and Indicators for Pediatric Endoscopy Facilities: A Joint NASPGHAN/ESPGHAN Guideline.

J Pediatr Gastroenterol Nutr 2021 Aug 16. Epub 2021 Aug 16.

Division of Gastroenterology and Nutrition, UMass Memorial Children's Medical Center, Department of Pediatrics, University of Massachusetts Medical School, Worcester, MA, USA Division of Gastroenterology, Hepatology and Nutrition and the Research and Learning Institutes, The Hospital for Sick Children, Department of Paediatrics and the Wilson Centre, University of Toronto, Toronto, Ontario, Canada Department of Paediatric Gastroenterology, Sheffield Children's Hospital NHS Foundation Trust, Sheffield, South Yorkshire, United Kingdom Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Washington University School of Medicine/St. Louis Children's Hospital, St. Louis, MO, USA Division of Pediatrics, Pediatric Gastroenterology Department, Centro Materno Infantil do Norte, Centro Hospitalar Universitário do Porto, ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Porto, Portugal Division of Pediatric Gastroenterology, Department of Pediatrics, Goryeb Children's Hospital, Icahn School of Medicine at Mount Sinai, Morristown, NJ, USA Department of Pediatric Gastroenterology, Providence St. Vincent's Medical Center, Portland, OR, USA Pediatric Gastroenterology and Liver Unit, Maternal and Child Health Department, Umberto I - University Hospital, Sapienza - University of Rome, Rome, Italy Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Eastern Ontario, Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada Division of Gastroenterology and Hepatology, Medicine and Pediatrics, Cedars-Sinai Medical Center, David Geffen School of Medicine at UCLA, Los Angeles, California, USA Division of Pediatrics, Pediatric Gastroenterology, Hepatology and Nutrition, Children's of Wisconsin, Medical College of Wisconsin, Milwaukee, WI, USA Division of Gastroenterology, Hepatology and Nutrition, Children's National Medical Center, Department of Pediatrics, George Washington University, Washington D.C., USA Division of Gastroenterology, Hepatology and Nutrition, British Columbia's Children's Hospital and British Columbia Children's Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, Canada Pediatric Gastroenterology and Nutrition, Department of Pediatrics, Stollery Children's Hospital, University of Alberta, Edmonton, Alberta, Canada Department of Gastroenterology, Hepatology and Nutrition, University Children's Hospital, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia Referral Center for Pediatric Gastroenterology and Nutrition, Children's Hospital Zagreb, University of Zagreb Medical School, Zagreb, University J.J. Strossmayer Medical School, Osijek, Croatia Paediatric Gastroenterology, Hepatology and Nutrition Department, Royal Hospital for Sick Children, Edinburgh, Scotland, United Kingdom Pediatric Gastroenterology & Nutrition, Department of Pediatrics, University Children's Hospital Basel, University of Basel, Basel, Switzerland Section of Pediatric Gastroenterology, Hepatology and Nutrition, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA Blizard Institute, Barts and the London School of Medicine, Royal London Children's Hospital, Barts Health NHS Trust, Queen Mary University of London, London, United Kingdom Division of Gastroenterology & Nutrition, Department of Pediatrics, McMaster Children's Hospital, McMaster University, Department of Paediatrics, William Osler Health System, Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada Division of Pediatrics, Department of Pediatric Gastroenterology, Queen Fabiola Children's University Hospital, ICBAS - Université Libre de Bruxelles, Brussels, Belgium Pediatric Gastroenterology, Department of Pediatrics, Centro Hospitalar Universitário S. João, Porto, Portugal Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Children's Hospital of Colorado, University of Colorado, Aurora, Colorado, USA Division of Gastroenterology and Hepatology, Seattle Children's Hospital, Department of Pediatrics, University of Washington, Seattle, WA, United States of America Gastroenterology & Nutrition, Department of Pediatrics, IWK Health, Dalhousie University, Halifax, Nova Scotia, Canada Child Health Evaluative Sciences, SickKids Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada Child Health Evaluative Sciences, SickKids Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada Department of Paediatric Gastroenterology, Sheffield Children's Hospital NHS Foundation Trust, Sheffield University, Sheffield, South Yorkshire, United Kingdom.

Introduction: There is increasing international recognition of the impact of variability in endoscopy facilities on procedural quality and outcomes. There is also growing precedent for assessing the quality of endoscopy facilities at regional and national levels by using standardized rating scales to identify opportunities for improvement.

Methods: With support from the North American and European Societies of Pediatric Gastroenterology Hepatology and Nutrition (NASPGHAN and ESPGHAN), an international working group of the Pediatric Endoscopy Quality Improvement Network (PEnQuIN) used the methodological strategy of the Appraisal of Guidelines for REsearch and Evaluation (AGREE) II instrument to develop standards and indicators relevant for assessing the quality of facilities where endoscopic care is provided to children. Consensus was reached via an iterative online Delphi process and subsequent in-person meeting. The quality of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development and Evaluation) approach.

Results: The PEnQuIN working group achieved consensus on 27 standards for facilities supporting pediatric endoscopy, as well 10 indicators that can be used to identify high quality endoscopic care in children. These standards were subcategorized into 3 subdomains: Quality of Clinical Operations (15 standards, 5 indicators); Patient and Caregiver Experience (9 standards, 5 indicators); and Workforce (3 standards).

Discussion: The rigorous PEnQuIN process successfully yielded standards and indicators that can be used to universally guide and measure high quality facilities for procedures around the world where endoscopy is performed in children. It also underscores the current paucity of evidence for pediatric endoscopic care processes, and the need for research into this clinical area.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MPG.0000000000003263DOI Listing
August 2021

Overview of the Pediatric Endoscopy Quality Improvement Network (PEnQuIN) Quality Standards and Indicators for Pediatric Endoscopy: A Joint NASPGHAN/ESPGHAN Guideline.

J Pediatr Gastroenterol Nutr 2021 Aug 16. Epub 2021 Aug 16.

Division of Gastroenterology, Hepatology and Nutrition and the Research and Learning Institutes, The Hospital for Sick Children, Department of Paediatrics and the Wilson Centre, University of Toronto, Toronto, Ontario, Canada Division of Gastroenterology and Nutrition, UMass Memorial Children's Medical Center, Department of Pediatrics, University of Massachusetts Medical School, Worcester, MA, USA Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Eastern Ontario, Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada Pediatric Gastroenterology, Department of Pediatrics, Centro Hospitalar Universitário S. João, Porto, Portugal Division of Pediatrics, Department of Pediatric Gastroenterology, Queen Fabiola Children's University Hospital, ICBAS - Université Libre de Bruxelles, Brussels, Belgium Division of Gastroenterology & Nutrition, Department of Pediatrics, McMaster Children's Hospital, McMaster University, Department of Paediatrics, William Osler Health System, Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada Blizard Institute, Barts and the London School of Medicine, Royal London Children's Hospital, Barts Health NHS Trust, Queen Mary University of London, London, United Kingdom Section of Pediatric Gastroenterology, Hepatology and Nutrition, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA Pediatric Gastroenterology & Nutrition, Department of Pediatrics, University Children's Hospital Basel, University of Basel, Basel, Switzerland Paediatric Gastroenterology, Hepatology and Nutrition Department, Royal Hospital for Sick Children, Edinburgh, Scotland, United Kingdom Referral Center for Pediatric Gastroenterology and Nutrition, Children's Hospital Zagreb, University of Zagreb Medical School, Zagreb, University J.J. Strossmayer Medical School, Osijek, Croatia Department of Gastroenterology, Hepatology and Nutrition, University Children's Hospital, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia Pediatric Gastroenterology and Nutrition, Department of Pediatrics, Stollery Children's Hospital, University of Alberta, Edmonton, Alberta, Canada Division of Gastroenterology, Hepatology and Nutrition, British Columbia's Children's Hospital and British Columbia Children's Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, Canada Division of Gastroenterology, Hepatology and Nutrition, Children's National Medical Center, Department of Pediatrics, George Washington University, Washington D.C., USA Division of Pediatrics, Pediatric Gastroenterology, Hepatology and Nutrition, Children's of Wisconsin, Medical College of Wisconsin, Milwaukee, WI, USA Division of Gastroenterology and Hepatology, Medicine and Pediatrics, Cedars-Sinai Medical Center, David Geffen School of Medicine at UCLA, Los Angeles, California, USA Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA Department of Paediatric Gastroenterology, Sheffield Children's Hospital NHS Foundation Trust, Sheffield, South Yorkshire, United Kingdom Pediatric Gastroenterology and Liver Unit, Maternal and Child Health Department, Umberto I - University Hospital, Sapienza - University of Rome, Rome, Italy Department of Pediatric Gastroenterology, Providence St. Vincent's Medical Center, Portland, OR, USA Division of Pediatric Gastroenterology, Department of Pediatrics, Goryeb Children's Hospital, Icahn School of Medicine at Mount Sinai, Morristown, NJ, USA Division of Pediatrics, Pediatric Gastroenterology Department, Centro Materno Infantil do Norte, Centro Hospitalar Universitário do Porto, ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Porto, Portugal Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Washington University School of Medicine/St. Louis Children's Hospital, St. Louis, MO, USA Division of Gastroenterology and Hepatology, Seattle Children's Hospital, Department of Pediatrics, University of Washington, Seattle, WA, United States of America Gastroenterology & Nutrition, Department of Pediatrics, IWK Health, Dalhousie University, Halifax, Nova Scotia, Canada Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Children's Hospital of Colorado, University of Colorado, Aurora, Colorado, USA Child Health Evaluative Sciences, SickKids Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada Child Health Evaluative Sciences, SickKids Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.

Introduction: Pediatric-specific quality standards for endoscopy are needed to define best practices, while measurement of associated indicators is critical to guide quality improvement. The international Pediatric Endoscopy Quality Improvement Network (PEnQuIN) working group was assembled to develop and define quality standards and indicators for pediatric gastrointestinal endoscopic procedures through a rigorous guideline consensus process.

Methods: The Appraisal of Guidelines for REsearch and Evaluation (AGREE) II instrument guided PEnQuIN members, recruited from 31 centers of various practice types representing 11 countries, in generating and refining proposed quality standards and indicators. Consensus was sought via an iterative online Delphi process, and finalized at an in-person conference. Quality of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach.

Results: Forty-nine quality standards and 47 indicators reached consensus, encompassing pediatric endoscopy facilities, procedures, endoscopists and the patient experience. The evidence base for PEnQuIN standards and indicators was largely adult-based and observational, and downgraded for indirectness, imprecision and study limitations to 'very low' quality, resulting in 'conditional' recommendations for most standards (45/49).

Conclusions: The PEnQuIN guideline development process establishes international agreement on clinically meaningful metrics that can be used to promote safety and quality in endoscopic care for children. Through PEnQuIN, pediatric endoscopists and endoscopy services now have a framework for auditing, providing feedback and, ultimately, benchmarking performance. Expansion of evidence and prospective validation of PEnQuIN standards and indicators as predictors of clinically relevant outcomes and high quality pediatric endoscopic care is now a research priority.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MPG.0000000000003262DOI Listing
August 2021

Early Serum Infliximab Levels in Pediatric Ulcerative Colitis.

Front Pediatr 2021 29;9:668978. Epub 2021 Jul 29.

Department of Pediatrics, University of Alberta, Edmonton, AB, Canada.

Data on serum infliximab concentrations during induction in pediatric ulcerative colitis are limited. The study aim is to evaluate the relationship between serum infliximab concentrations during induction and short-term clinical remission in children with ulcerative colitis. We carried out a prospective, multi-center cohort study in pediatric patients with ulcerative colitis. Serum infliximab concentrations were collected at peak dose #1, week 1, trough pre-dose #2, and trough pre-dose #3. Infliximab dosing was left to investigator discretion. Clinical remission was defined by pediatric ulcerative colitis activity index <10 at week 8. Twenty-four of thirty-four subjects (71%) achieved clinical remission at week 8. The median infliximab concentrations were 33.0 μg/mL (interquartile range: 26.5-52.1 μg/mL) pre-dose #2 and 22.5 μg/mL (interquartile range:15.9-32.3 μg/mL) pre-dose #3. Trough pre-dose #2 infliximab concentration yielded area under receiver operator characteristic curve 0.7, 95% CI: 0.5-0.9 in predicting week 8 clinical remission; a cut-off of 33.0 μg/mL yielded 62.5% sensitivity, 66.7% specificity. Trough pre-dose #3 infliximab concentrations were lower for subjects <10 years compared to ≥ 10 years [median 15.9 μg/mL, interquartile range (IQR) 8.5-21.8 μg/mL vs. 27.7 μg/mL, IQR 17.2-46.7 μg/mL, = 0.01] and correlated with baseline weight (Spearman's rank correlation coefficient 0.45, = 0.01). The median half-life following first IFX dose was 6.04 days (IQR 5.3-7.9 days). Infliximab concentrations ≥33 μg/mL prior to the second dose were associated with week 8 clinical remission. As young age and low body weight impact infliximab concentration, prospective studies with proactive adjustment in pediatric patients with ulcerative colitis should be carried out. Clinicians caring for children with UC should diligently adjust and monitor infliximab to optimize response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fped.2021.668978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358797PMC
July 2021

Fasting increases microbiome-based colonization resistance and reduces host inflammatory responses during an enteric bacterial infection.

PLoS Pathog 2021 Aug 5;17(8):e1009719. Epub 2021 Aug 5.

Department of Pediatrics, BC Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada.

Reducing food intake is a common host response to infection, yet it remains unclear whether fasting is detrimental or beneficial to an infected host. Despite the gastrointestinal tract being the primary site of nutrient uptake and a common route for infection, studies have yet to examine how fasting alters the host's response to an enteric infection. To test this, mice were fasted before and during oral infection with the invasive bacterium Salmonella enterica serovar Typhimurium. Fasting dramatically interrupted infection and subsequent gastroenteritis by suppressing Salmonella's SPI-1 virulence program, preventing invasion of the gut epithelium. Virulence suppression depended on the gut microbiota, as Salmonella's invasion of the epithelium proceeded in fasting gnotobiotic mice. Despite Salmonella's restored virulence within the intestines of gnotobiotic mice, fasting downregulated pro-inflammatory signaling, greatly reducing intestinal pathology. Our study highlights how food intake controls the complex relationship between host, pathogen and gut microbiota during an enteric infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.ppat.1009719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8341583PMC
August 2021

Cross-Sectional Analysis of Quality of Life in Pediatric Patients with Inflammatory Bowel Disease in British Columbia, Canada.

J Pediatr 2021 Jul 19. Epub 2021 Jul 19.

Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Faculty of Medicine, British Columbia Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada; British Columbia Children Hospital Research Institute, Vancouver, British Columbia, Canada; Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address:

Objectives: To evaluate quality of life (QoL) in a large cohort of pediatric patients with inflammatory bowel disease (IBD) and to identify the clinical factors that influence QoL.

Study Design: This cross-sectional study analyzes a quality improvement initiative in 351 pediatric patients with IBD in British Columbia, Canada using the self-reported Pediatric Quality of Life Inventory (PedsQL) 4.0 generic scale. The questionnaire was completed at outpatient clinic and biologic infusion appointments. Statistical analysis included the t test, ANOVA, and multilinear regressions to evaluate the relationships between clinical factors and QoL.

Results: Mean (SE) QoL scores (79.95 [0.84]) fell between previously described healthy and chronically ill populations. Disease activity was the most significant predictor of QoL, with patients in remission scoring similar (84.42 [0.87]) to well established healthy norms, and those with moderately or severely active disease having some of the lowest published PedsQL scores (63.13 [3.27]), lower than most other chronic pediatric conditions. Twenty-five patients with moderately or severely active disease at the time of survey completion had follow-up surveys identified 1 year later and had a significant improvement of both their disease activity (P < .005) and their PedsQL scores (follow-up survey mean 76.13 [3.11]). Additional clinical factors independently associated with poor QoL were school nonattendance (15.5% decrease in QoL, P < .001), immune-modulator selection (methotrexate conferring a 9.5% lower mean QoL score than azathioprine, P = .005), and female gender (P = .031).

Conclusion: Pediatric patients with IBD experience a QoL significantly impacted by multiple clinical factors including current severity of IBD symptoms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpeds.2021.07.036DOI Listing
July 2021

Anti-Microbial Antibody Response is Associated With Future Onset of Crohn's Disease Independent of Biomarkers of Altered Gut Barrier Function, Subclinical Inflammation, and Genetic Risk.

Gastroenterology 2021 Jul 20. Epub 2021 Jul 20.

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. Electronic address:

Background And Aims: Altered host immune reactivity to microbial antigens is hypothesized to trigger the onset of Crohn's disease (CD). We aimed to assess whether increased serum anti-microbial antibody response in asymptomatic first-degree relatives (FDRs) of CD patients is an independent risk factor for future CD development.

Methods: We measured host serum antibody response to 6 microbial antigens at enrollment (Prometheus enzyme-linked immunosorbent assay test: anti-Saccharomyces cerevisiae antibodies immunoglobulin A/immunoglobulin G, anti-OmpC, anti-A4-Fla2, anti-FlaX, anti-CBir1) and derived the sum of positive antibodies (AS). We used samples at enrollment of prospectively followed healthy FDRs from a nested case-control cohort of the Crohn's and Colitis Canada Genetics Environment Microbial Project. Those who later developed CD (n = 77) were matched 1:4 by age, sex, follow-up duration, and geographic location with control FDRs remaining healthy (n = 307). To address our research aims, we fitted a multivariable conditional logistic regression model and performed causal mediation analysis.

Results: High baseline AS (≥2) (43% of cases, 11% of controls) was associated with higher risk of developing CD (adjusted odds ratio, 6.5; 95% confidence interval, 3.4-12.7; P < .001). Importantly, this association remained significant when adjusted for markers of gut barrier function, fecal calprotectin, C-reactive protein, and CD-polygenic risk score, and in subjects recruited more than 3 years before diagnosis. Causal mediation analysis showed that the effect of high AS on future CD development is partially mediated (42%) via preclinical gut inflammation.

Conclusions: Our results suggest that increased anti-microbial antibody responses are associated with risk of future development of CD, independent of biomarkers of abnormal gut barrier function, subclinical inflammation, and CD-related genetic risks. This suggests that anti-microbial antibody responses are an early predisease event in the development of CD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.gastro.2021.07.009DOI Listing
July 2021

E-type prostanoid receptor 4 drives resolution of intestinal inflammation by blocking epithelial necroptosis.

Nat Cell Biol 2021 07 8;23(7):796-807. Epub 2021 Jul 8.

Department of Medicine 1, University of Erlangen-Nuremberg, Erlangen, Germany.

Inflammatory bowel diseases present with elevated levels of intestinal epithelial cell (IEC) death, which compromises the gut barrier, activating immune cells and triggering more IEC death. The endogenous signals that prevent IEC death and break this vicious cycle, allowing resolution of intestinal inflammation, remain largely unknown. Here we show that prostaglandin E2 signalling via the E-type prostanoid receptor 4 (EP4) on IECs represses epithelial necroptosis and induces resolution of colitis. We found that EP4 expression correlates with an improved IBD outcome and that EP4 activation induces a transcriptional signature consistent with resolution of intestinal inflammation. We further show that dysregulated necroptosis prevents resolution, and EP4 agonism suppresses necroptosis in human and mouse IECs. Mechanistically, EP4 signalling on IECs converges on receptor-interacting protein kinase 1 to suppress tumour necrosis factor-induced activation and membrane translocation of the necroptosis effector mixed-lineage kinase domain-like pseudokinase. In summary, our study indicates that EP4 promotes the resolution of colitis by suppressing IEC necroptosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41556-021-00708-8DOI Listing
July 2021

Prebiotic Enriched Exclusive Enteral Nutrition Suppresses Colitis via Gut Microbiome Modulation and Expansion of Anti-inflammatory T Cells in a Mouse Model of Colitis.

Cell Mol Gastroenterol Hepatol 2021 Jun 29;12(4):1251-1266. Epub 2021 Jun 29.

BC Children's Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, Canada; Division of Gastroenterology, Hepatology and Nutrition, BC Children's Hospital, Vancouver, Canada. Electronic address:

Background & Aims: Exclusive enteral nutrition (EEN) is used to treat pediatric Crohn's disease (CD), but therapeutic benefits are variable, and EEN can lead to microbial dysbiosis. Because of reported lower efficacy EEN is not routinely used to treat pediatric ulcerative colitis (UC). Inulin-type fructans (IN) beneficially modulate the gut microbiome and promote expansion of anti-inflammatory immune cells. We hypothesized that enriching EEN with IN (EEN IN) would enhance treatment efficacy. To test this, we examined the effects of EEN IN on colitis development, the gut microbiome, and CD4 T cells using an adoptive T-cell transfer model of colitis.

Methods: TCR-β deficient () mice were randomized to 1 of 4 groups: (1) Control, (2) Chow, (3) EEN, and (4) EEN IN, and naive CD4 T cells were adoptively transferred into groups 2-4, after which mice were monitored for 5 weeks before experimental endpoint.

Results: Mice fed EEN IN showed greater colitis protection, with colonic shortening, goblet cell, and crypt density loss reduced compared with EEN fed mice and reduced disease activity and immune cell infiltration compared with chow fed mice, and less crypt hyperplasia and higher survival compared with both groups. EEN IN mice had less deterioration in the colonic mucus layer and had increased levels of Foxp3IL-10 and RorγtIL-22 and reduced levels of TbetIFNγ and TbetTNF CD4 T cells. EEN IN also led to higher butyrate concentrations, Bifidobacterium spp. and Anaerostipes caccae relative abundance, and lower [Clostridium] innocuum group spp. and Escherichia-Shigella spp. relative abundance.

Conclusions: The EEN IN group showed reduced colitis development as compared with the chow and EEN groups. This highlights the potential benefits of EEN IN as a novel induction therapy for pediatric CD and UC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcmgh.2021.06.011DOI Listing
June 2021

Inflammatory bowel disease increases the risk of venous thromboembolism in children: a population-based matched cohort study.

J Crohns Colitis 2021 Jun 27. Epub 2021 Jun 27.

SickKids Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada.

Background And Aims: Although venous thromboembolism (VTE) is a well-known complication of inflammatory bowel disease (IBD) in adults, limited data exist on the risk in children. We report the incidence of VTE among children with and without IBD.

Methods: We conducted a matched cohort study within a distributed network of population-based Canadian provincial health administrative databases. Children diagnosed with IBD <16 years were identified using validated algorithms from administrative data in Alberta, Manitoba, Nova Scotia, Ontario, and Québec and compared to age- and sex-matched children without IBD. Hospitalizations for VTE within five years of IBD diagnosis were identified. Generalized linear mixed-effects models were used to pool province-specific incidence rates and incidence rate ratios (IRR) with 95% confidence intervals (CI). Hazard ratios (HR) from Cox proportional hazards models were pooled with fixed-effects meta-analysis.

Results: The five-year incidence of VTE among 3593 children with IBD was 31.2 (95%CI 23.7-41.0) per 10,000 person-years (PY) compared to 0.8 (95%CI 0.4-1.7) per 10,000 PY among 16,289 children without IBD (unadjusted IRR 38.84, 95%CI 16.59-90.83; adjusted HR 22.91, 95%CI 11.50-45.63). VTE was less common in Crohn's disease than ulcerative colitis (unadjusted IRR 0.47, 95%CI 0.27-0.83; adjusted HR 0.52, 95%CI 0.29-0.94). Findings were similar for deep vein thrombosis (DVT) and pulmonary embolism (PE) when comparing children with and without IBD.

Conclusions: The risk of VTE is much higher in children with IBD than controls without IBD. While the absolute risk is low, we found a higher incidence rate than previously described in the pediatric literature.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ecco-jcc/jjab113DOI Listing
June 2021

Interleukin-37 regulates innate immune signaling in human and mouse colonic organoids.

Sci Rep 2021 Apr 15;11(1):8206. Epub 2021 Apr 15.

Department of Pediatrics, BC Children's Hospital, University of British Columbia, Vancouver, BC, Canada.

Intestinal epithelial cells (IEC) reside in close proximity to the gut microbiota and are hypo-responsive to bacterial products, likely to prevent maladaptive inflammatory responses. This is in part due to their strong expression of Single Ig IL-1 related receptor (SIGIRR), a negative regulator of interleukin (IL)-1 and toll-like receptor signaling. IL-37 is an anti-inflammatory cytokine that inhibits innate signaling in diverse cells by signaling through SIGIRR. Despite the strong expression of SIGIRR by IEC, few studies have examined whether IL-37 can suppress their innate immune signaling. We characterized innate immune responses of human and murine colonoids to bacteria (FliC, LPS) and host (IL-1β) products and the role of IL-37/SIGIRR in regulating these responses. We demonstrated that human colonoids responded only to FliC, but not to LPS or IL-1β. While colonoids derived from different donors displayed significant inter-individual variability in the magnitude of their innate responses to FliC stimulation, all colonoids released a variety of chemokines. Interestingly, IL-37 attenuated these responses through inhibition of p38 and NFκB signaling pathways. We determined that this suppression by IL-37 was SIGIRR dependent, in murine organoids. Along with species-specific differences in IEC innate responses, we show that IL-37 can promote IEC hypo-responsiveness by suppressing inflammatory signaling.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-87592-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050237PMC
April 2021

Harnessing Big Data to Optimize an Algorithm for Rapid Diagnosis of Pulmonary Tuberculosis in a Real-World Setting.

Front Cell Infect Microbiol 2021 18;11:650163. Epub 2021 Mar 18.

Department of Pediatrics, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada.

Background: The prompt diagnosis of pulmonary tuberculosis (PTB) remains a challenge in clinical practice. The present study aimed to optimize an algorithm for rapid diagnosis of PTB in a real-world setting.

Methods: 28,171 adult inpatients suspected of having PTB in China were retrospectively analyzed. Bronchoalveolar lavage fluid (BALF) and/or sputum were used for acid-fast bacilli (AFB) smear, Xpert MTB/RIF (Xpert), and culture. A positive mycobacterial culture was used as the reference standard. Peripheral blood mononuclear cells (PBMC) were used for T-SPOT.. We analyzed specimen types' effect on these assays' performance, determined the number of smears for diagnosing PTB, and evaluated the ability of these assays performed alone, or in combination, to diagnose PTB and nontuberculous mycobacteria (NTM) infections.

Results: Sputum and BALF showed moderate to substantial consistency when they were used for AFB smear or Xpert, with a higher positive detection rate by BALF. 3-4 smears had a higher sensitivity than 1-2 smears. Moreover, simultaneous combination of AFB and Xpert correctly identified 44/51 of AFB/Xpert and 6/7 of AFB/Xpert cases as PTB and NTM, respectively. Lastly, when combined with AFB/Xpert sequentially, T-SPOT showed limited roles in patients that were either AFB or Xpert. However, T-SPOT (manufacturer-defined cut-off) showed a high negative predicative value (99.1%) and suboptimal sensitivity (74.4%), and TBAg/PHA (ratio of -specific antigens to phytohaemagglutinin spot-forming cells, which is a modified method calculating T-SPOT. assay results) ≥0.3 demonstrated a high specificity (95.7%) and a relatively low sensitivity (16.3%) in AFB/Xpert patients.

Conclusions: Concurrently performing AFB smear (at least 3 smears) and Xpert on sputum and/or BALF could aid in rapid diagnosis of PTB and NTM infections in a real-world high-burden setting. If available, BALF is preferred for both AFB smear and Xpert. Expanding this algorithm, PBMC T-SPOT and TBAg/PHA ratios have a supplementary role for PTB diagnosis in AFB/Xpert patients (moderately ruling out PTB and ruling in PTB, respectively). Our findings may also inform policy makers' decisions regarding prevention and control of TB in a high burden setting.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcimb.2021.650163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012509PMC
July 2021

Comparing Health Administrative and Clinical Registry Data: Trends in Incidence and Prevalence of Pediatric Inflammatory Bowel Disease in British Columbia.

Clin Epidemiol 2021 11;13:81-90. Epub 2021 Feb 11.

Department of Pediatrics, BC Children's Hospital, Vancouver, British Columbia, Canada.

Purpose: Canada maintains robust health administrative databases and British Columbia Children's Hospital (BCCH), as the only tertiary care pediatric hospital in British Columbia (BC), maintains a comprehensive clinical inflammatory bowel disease (IBD) registry. To evaluate the strengths and weaknesses of utilizing health administrative and clinical registry data to study the epidemiology of IBD in BC, we conducted a population-based retrospective cohort study of all children <18 years of age who were diagnosed with IBD between 1996 and 2008 in BC.

Methods: IBD cases from health administrative data were identified using a combination of IBD-coded physician encounters and hospitalizations while a separate IBD cohort was identified from the BCCH clinical registry data. Age and gender standardized incidence and prevalence rates were fitted to Poisson regression models.

Results: The overall incidence of pediatric IBD identified in health administrative data increased from 7.1 (95% CI 5.5-9.2) in 1996 to 10.3 (95% CI 8.2-12.7) per 100,000 children in 2008. Similarly, the incidence of the BCCH cohort increased from 4.3 (95% CI 3.0-6.0) to 9.7 (95% CI 7.6-12.1) per 100,000. Children aged 10-17 had the highest rise in incidence in both data sources; however, the administrative data identified significantly more 10-17-year-olds and significantly less 6-9-year-olds (p<0.05) compared to clinical registry data.

Conclusion: While the application of both health administrative and clinical registry data demonstrates that the incidence of IBD is increasing in BC, we identify strengths and limitations to both and suggest that the utilization of either data source requires unique considerations that mitigate misclassification biases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/CLEP.S292546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886108PMC
February 2021

Ulcerative Colitis-associated pathobionts potentiate colitis in susceptible hosts.

Gut Microbes 2020 11 1;12(1):1847976. Epub 2020 Dec 1.

Department of Pediatrics, BC Children's Hospital, University of British Columbia , Vancouver, BC, Canada.

Ulcerative colitis (UC) is a chronic inflammatory condition linked to intestinal microbial dysbiosis, including the expansion of strains related to extra-intestinal pathogenic . These "pathobionts" exhibit pathogenic properties, but their potential to promote UC is unclear due to the lack of relevant animal models. Here, we established a mouse model using a representative UC pathobiont strain (p19A), and mice lacking single immunoglobulin and toll-interleukin 1 receptor domain (SIGIRR), a deficiency increasing susceptibility to gut infections. Strain p19A was found to adhere to the cecal mucosa of -/- mice, causing modest inflammation. Moreover, it dramatically worsened dextran sodium sulfate-induced colitis. This potentiation was attenuated using a p19A strain lacking α-hemolysin genes, or when we targeted pathobiont adherence using a p19A strain lacking the adhesin FimH, or following treatment with FimH antagonists. Thus, UC pathobionts adhere to the intestinal mucosa, and worsen the course of colitis in susceptible hosts.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/19490976.2020.1847976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781664PMC
November 2020

Severe COVID-19 Infection and Pediatric Comorbidities: A Systematic Review and Meta-Analysis.

Int J Infect Dis 2021 Feb 20;103:246-256. Epub 2020 Nov 20.

Department of Pediatrics, BC Children's Hospital, Vancouver, BC, Canada; Division of Gastroenterology, Hepatology and Nutrition, BC Children's Hospital, Vancouver, BC, Canada; BC Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada; Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC, Canada. Electronic address:

Objective: There is limited information on the severity of COVID-19 infection in children with comorbidities. We investigated the effects of pediatric comorbidities on COVID-19 severity by means of a systematic review and meta-analysis of published literature.

Methods: PubMed, Embase, and Medline databases were searched for publications on pediatric COVID-19 infections published January 1 to October 5, 2020. Articles describing at least one child with and without comorbidities, COVID-19 infection, and reported outcomes were included.

Results: 42 studies containing 275,661 children without comorbidities and 9,353 children with comorbidities were included. Severe COVID-19 was present in 5.1% of children with comorbidities, and in 0.2% without comorbidities. Random-effects analysis revealed a higher risk of severe COVID-19 among children with comorbidities than for healthy children; relative risk ratio 1.79 (95% CI 1.27 - 2.51; I = 94%). Children with underlying conditions also had a higher risk of COVID-19-associated mortality; relative risk ratio 2.81 (95% CI 1.31 - 6.02; I = 82%). Children with obesity had a relative risk ratio of 2.87 (95% CI 1.16 - 7.07; I = 36%).

Conclusions: Children with comorbidities have a higher risk of severe COVID-19 and associated mortality than children without underlying disease. Additional studies are required to further evaluate this relationship.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijid.2020.11.163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7679116PMC
February 2021

Fiber and Prebiotic Interventions in Pediatric Inflammatory Bowel Disease: What Role Does the Gut Microbiome Play?

Nutrients 2020 Oct 20;12(10). Epub 2020 Oct 20.

Department of Pediatrics, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.

The etiology of inflammatory bowel disease (IBD) is complex but is thought to be linked to an intricate interaction between the host's immune system, resident gut microbiome and environment, i.e., diet. One dietary component that has a major impact on IBD risk and disease management is fiber. Fiber intakes in pediatric IBD patients are suboptimal and often lower than in children without IBD. Fiber also has a significant impact on beneficially shaping gut microbiota composition and functional capacity. The impact is likely to be particularly important in IBD patients, where various studies have demonstrated that an imbalance in the gut microbiome, referred to as dysbiosis, occurs. Microbiome-targeted therapeutics, such as fiber and prebiotics, have the potential to restore the balance in the gut microbiome and enhance host gut health and clinical outcomes. Indeed, studies in adult IBD patients demonstrate that fiber and prebiotics positively alter the microbiome and improve disease course. To date, no studies have been conducted to evaluate the therapeutic potential of fiber and prebiotics in pediatric IBD patients. Consequently, pediatric IBD specific studies that focus on the benefits of fiber and prebiotics on gut microbiome composition and functional capacity and disease outcomes are required.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu12103204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589214PMC
October 2020

Direct Clinical Evidence Recommending the Use of Proteinase K or Dithiothreitol to Pretreat Sputum for Detection of SARS-CoV-2.

Front Med (Lausanne) 2020 18;7:549860. Epub 2020 Sep 18.

Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

One of the primary tools for diagnosing COVID-19 is the nucleic acid-based real-time reverse transcriptase-polymerase chain reaction (RT-PCR) test performed on respiratory specimens. The detection rate of SARS-CoV-2 in lower respiratory specimens (such as sputum) is higher than that for upper respiratory specimens (such as nasal and pharyngeal swabs). However, sputum specimens are usually quite viscous, requiring a homogenization process prior to nucleic acid (NA) extraction for RT-PCR. Sputum specimens from COVID-19 and non-COVID-19 patients were treated with four commonly used reagents-saline, N-acetyl-L-cysteine (NALC), proteinase K (PK), and dithiothreitol (DTT), prior to NA extraction. These reagents were then compared for their performance in diagnosing COVID-19 in real clinical practice. The detection rate of SARS-CoV-2 in PK- or DTT-treated sputum was comparable, and higher than that in sputum treated with NALC or saline. While there was a 4.8% (1/21) false negative rate for the PK- and DTT-treated sputum, neither treatment showed any false positive cases among patients with non-COVID diseases. Moreover, sputum pretreated with saline, NALC, PK or DTT showed higher detection rates of SARS-CoV-2 as compared to pharyngeal swabs. Taken together, we provide direct evidence recommending the use of PK or DTT to pretreat sputum samples to facilitate SARS-CoV-2 detection by clinical laboratories. Moreover, our methods should help to standardize the procedure of processing sputum specimens and improve the ability to detect SARS-CoV-2 in these samples.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmed.2020.549860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7530184PMC
September 2020

Diagnostic Delay Is Associated With Complicated Disease and Growth Impairment in Paediatric Crohn's Disease.

J Crohns Colitis 2021 Mar;15(3):419-431

SickKids Hospital, University of Toronto, Toronto, ON, Canada.

Background: Paediatric data on the association between diagnostic delay and inflammatory bowel disease [IBD] complications are lacking. We aimed to determine the effect of diagnostic delay on stricturing/fistulising complications, surgery, and growth impairment in a large paediatric cohort, and to identify predictors of diagnostic delay.

Methods: We conducted a national, prospective, multicentre IBD inception cohort study including 1399 children. Diagnostic delay was defined as time from symptom onset to diagnosis >75th percentile. Multivariable proportional hazards [PH] regression was used to examine the association between diagnostic delay and stricturing/fistulising complications and surgery, and multivariable linear regression to examine the association between diagnostic delay and growth. Predictors of diagnostic delay were identified using Cox PH regression.

Results: Overall (64% Crohn's disease [CD]; 36% ulcerative colitis/IBD unclassified [UC/IBD-U]; 57% male]), median time to diagnosis was 4.2 (interquartile range [IQR] 2.0-9.2) months. For the overall cohort, diagnostic delay was >9.2 months; in CD, >10.8 months and in UC/IBD-U, >6.6 months. In CD, diagnostic delay was associated with a 2.5-fold higher rate of strictures/internal fistulae (hazard ratio [HR] 2.53, 95% confidence interval [CI] 1.41-4.56). Every additional month of diagnostic delay was associated with a decrease in height-for-age z-score of 0.013 standard deviations [95% CI 0.005-0.021]. Associations persisted after adjusting for disease location and therapy. No independent association was observed between diagnostic delay and surgery in CD or UC/IBD-U. Diagnostic delay was more common in CD, particularly small bowel CD. Abdominal pain, including isolated abdominal pain in CD, was associated with diagnostic delay.

Conclusions: Diagnostic delay represents a risk factor for stricturing/internal fistulising complications and growth impairment in paediatric CD.

Podcast: This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ecco-jcc/jjaa197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944510PMC
March 2021

Increased Intestinal Permeability Is Associated With Later Development of Crohn's Disease.

Gastroenterology 2020 12 10;159(6):2092-2100.e5. Epub 2020 Aug 10.

Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada; Department of Medicine, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Background & Aims: Increased intestinal permeability has been associated with Crohn's disease (CD), but it is not clear whether it is a cause or result of the disease. We performed a prospective study to determine whether increased intestinal permeability is associated with future development of CD.

Methods: We assessed the intestinal permeability, measured by the urinary fractional excretion of lactulose-to-mannitol ratio (LMR) at recruitment in 1420 asymptomatic first-degree relatives (6-35 years old) of patients with CD (collected from 2008 through 2015). Participants were then followed up for a diagnosis of CD from 2008 to 2017, with a median follow-up time of 7.8 years. We analyzed data from 50 participants who developed CD after a median of 2.7 years during the study period, along with 1370 individuals who remained asymptomatic until October 2017. We used the Cox proportional hazards model to evaluate time-related risk of CD based on the baseline LMR.

Results: An abnormal LMR (>0.03) was associated with a diagnosis of CD during the follow-up period (hazard ratio, 3.03; 95% CI, 1.64-5.63; P = 3.97 × 10). This association remained significant even when the test was performed more than 3 years before the diagnosis of CD (hazard ratio, 1.62; 95% CI, 1.051-2.50; P = .029).

Conclusions: Increased intestinal permeability is associated with later development of CD; these findings support a model in which altered intestinal barrier function contributes to pathogenesis. Abnormal gut barrier function might serve as a biomarker for risk of CD onset.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.gastro.2020.08.005DOI Listing
December 2020

Discontinuation of Immunosuppressive Medications in Children With Inflammatory Bowel Disease on Combination Therapy.

J Pediatr Gastroenterol Nutr 2020 12;71(6):740-743

Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, British Columbia Children's Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.

We determined the frequency and factors associated with the first clinical relapse after immunomodulator (IM) withdrawal in a cohort of children with inflammatory bowel disease on combination therapy. A total of 105 patients (89 with Crohn disease [CD]) in clinical remission were included (91 [86.7%] were on infliximab, 53 [50.5%] with methotrexate, and 52 on azathioprine). The median duration of combination therapy was 2.1 years (interquartile range [IQR] 1.3-2.8). Only 11 (10.5%) patients experienced a clinical relapse over a median duration of follow-up of 12.0 months (IQR 5.0-19.0) after IM discontinuation. The median baseline pediatric CD activity index in those with CD who relapsed after IM discontinuation was 47.5 (IQR: 35.0-55.0) versus those who did not relapse (median 35.0, IQR: 20.0-52.5; P = 0.04). In the patients who did not relapse, the median IFX trough level at IM discontinuation was 6.2 and 3.8 μg/mL in those who relapsed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MPG.0000000000002857DOI Listing
December 2020

High body mass index is not associated with increased treatment failure in infliximab treated pediatric patients with inflammatory bowel disease.

JGH Open 2020 Jun 23;4(3):446-453. Epub 2019 Nov 23.

Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Faculty of Medicine University of British Columbia Vancouver Canada.

Background And Aim: While weight gain during infliximab therapy in inflammatory bowel disease (IBD) is common, there has been limited research evaluating its impact on infliximab efficacy.

Methods: Primary aims of this study were to determine the frequency of excess weight gain (body mass index [BMI] > 25 kg/m) in children with IBD on maintenance infliximab and evaluate the impact on infliximab dosing, serum trough levels, and treatment failure. Secondary aims were to determine differences in weight gain, treatment characteristics, and clinical/biochemical variables between patients with therapeutic and subtherapeutic maintenance therapy trough levels. We performed a retrospective study of 253 pediatric IBD (75.1% Crohn's disease, 23.3% ulcerative colitis, 1.6% IBD-unclassified) patients on infliximab followed at BC Children's Hospital between January 2013 and January 2018.

Results: Median age at infliximab initiation was 13.9 years, median length of follow up was 56.9 months, and 55.7% were males; 10.3% of the cohort demonstrated excess weight gain (7.5% overweight, 2.8% obese). Average mg/kg dosing was not statistically different between groups (normal, overweight, and obese: 6.7, 6.4, and 6.7 mg/kg, respectively, = 0.52). Median BMI of patients with therapeutic and subtherapeutic trough levels was similar at 19.9 kg/m (interquartile range [IQR], 17.3-23.8) and 19.7 kg/m (IQR, 17.4-21.9), respectively. BMI had no effect on secondary loss of response to infliximab, with no significant difference between normal and high BMI subgroups (13.4 vs. 16.7%, = 0.9).

Conclusions: In a subgroup of pediatric IBD patients on maintenance infliximab, excess weight gain was not associated with higher weight-based dosing, lower serum trough levels, or increased risk of treatment failure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jgh3.12277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273726PMC
June 2020

Enteroids Derived From Inflammatory Bowel Disease Patients Display Dysregulated Endoplasmic Reticulum Stress Pathways, Leading to Differential Inflammatory Responses and Dendritic Cell Maturation.

J Crohns Colitis 2020 Jul;14(7):948-961

Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada.

Background And Aims: Endoplasmic reticulum [ER] stress in intestinal epithelial cells [IECs] contributes to the pathogenesis of inflammatory bowel disease [IBD]. We hypothesized that ER stress changes innate signalling in human IECs, augmenting toll-like receptor [TLR] responses and inducing pro-inflammatory changes in underlying dendritic cells [DCs].

Methods: Caco-2 cells and primary human colon-derived enteroid monolayers were exposed to ATP [control stressor] or thapsigargin [Tg] [ER stress inducer], and were stimulated with the TLR5 agonist flagellin. Cytokine release was measured by an enzyme immunoassay. ER stress markers CHOP, GRP78 and XBP1s/u were measured via quantitative PCR and Western blot. Monocyte-derived DCs [moDCs] were cultured with the IEC supernatants and their activation state was measured. Responses from enteroids derived from IBD patients and healthy control participants were compared.

Results: ER stress enhanced flagellin-induced IL-8 release from Caco-2 cells and enteroids. Moreover, conditioned media activated DCs to become pro-inflammatory, with increased expression of CD80, CD86, MHCII, IL-6, IL-15 and IL-12p70 and decreased expression of CD103 and IL-10. Flagellin-induced IL-8 production correlated with DC activation, suggesting a common stress pathway. Moreover, there were distinct differences in cytokine expression and basal ER stress between IBD and healthy subject-derived enteroid monolayers, suggesting a dysregulated ER stress pathway in IBD-derived enteroids.

Conclusions: Cellular stress enhances TLR5 responses in IECs, leading to increased DC activation, indicating a previously unknown mechanistic link between epithelial ER stress and immune activation in IBD. Furthermore, dysregulated ER stress may be propagated from the intestinal epithelial stem cell niche in IBD patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ecco-jcc/jjz194DOI Listing
July 2020

In Reply to (Meta-analysis on obesity and risk of inflammatory bowel disease: re-analysis is needed).

Obes Rev 2020 01 5;21(1):e12956. Epub 2019 Nov 5.

Department of Pediatrics, BC Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/obr.12956DOI Listing
January 2020

Capsule Endoscopy Complements Magnetic Resonance Enterography and Endoscopy in Evaluating Small Bowel Crohn's Disease.

J Can Assoc Gastroenterol 2020 Dec 28;3(6):279-287. Epub 2019 Sep 28.

Department of Paediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, British Columbia Children's Hospital and University of British Columbia, Vancouver, British Columbia, Canada.

Aims: Wireless capsule endoscopy (WCE) and magnetic resonance enterography (MRE) are increasingly utilized to evaluate the small bowel (SB) in Crohn's disease (CD). The primary aims were to compare the ability of WCE and MRE to detect SB inflammation in children with newly diagnosed CD, and in the terminal ileum (TI) to compare them to ileo-colonoscopy. Secondary aims were to compare diagnostic accuracy of WCE and MRE and changes in Paris classification after each study.

Methods: Patients (10 to 17 years of age) requiring ileo-colonoscopy for suspected CD were invited to participate. Only patients with endoscopic/histologic evidence of CD underwent MRE and WCE. SB inflammation and extent were documented and comparative analyses performed.

Results: Of 38 initially recruited subjects, 20 completed the study. WCE and MRE were similarly sensitive in identifying active TI inflammation (16 [80%] versus 12 [60%]) and any SB inflammation (17 [85%] versus 16 [80%]). However, WCE detected more extensive SB disease than MRE with active inflammation throughout the SB in 15 [75%] versus 1 [5%] patient ( < 0.001). Moreover, WCE was more likely to detect proximal SB disease (jejunum and ileum) compared to MRE (85% versus 50%, = 0.04). Overall, the Paris classification changed in 65% and 85% of patients following MRE and WCE, respectively.

Conclusions: WCE is as sensitive as MRE for identifying active TI inflammation, but appears more sensitive in identifying more proximal SB inflammation. In the absence of concern regarding stricturing or extra-luminal disease WCE can be considered for the evaluation of suspected SB CD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jcag/gwz028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678730PMC
December 2020

Suppressive and Gut-Reparative Functions of Human Type 1 T Regulatory Cells.

Gastroenterology 2019 12 10;157(6):1584-1598. Epub 2019 Sep 10.

BC Children's Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, Canada; School of Biomedical Engineering, University of British Columbia, Vancouver, British Columbia, Canada; Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address:

Background & Aims: T-regulatory (Treg) cells suppress the immune response to maintain homeostasis. There are 2 main subsets of Treg cells: FOXP3 (forkhead box protein 3)-positive Treg cells, which do not produce high levels of effector cytokines, and type 1 Treg (Tr1) cells, which are FOXP3-negative and secrete interleukin (IL) 10. IL10 is an anti-inflammatory cytokine, so Tr1 cells might be used in the treatment of inflammatory bowel diseases. We aimed to develop methods to isolate and expand human Tr1 cells and define their functions.

Methods: We obtained blood and colon biopsy samples from patients with Crohn's disease or ulcerative colitis or healthy individuals (controls). CD4 T cells were isolated from blood samples and stimulated with anti-CD3 and anti-CD28 beads, and Tr1 cells were purified by using an IL10 cytokine-capture assay and cell sorting. FOXP3-positive Treg cells were sorted as CD4CD25CD127 cells from unstimulated cells. Tr1 and FOXP3-positive Treg cells were expanded, and phenotypes and gene expression profiles were compared. T cells in peripheral blood mononuclear cells from healthy donors were stimulated with anti-CD3 and anti-CD28 beads, and the suppressive abilities of Tr1 and FOXP3-positive Treg cells were measured. Human colon organoid cultures were established, cultured with supernatants from Tr1 or FOXP3-positive cells, and analyzed by immunofluorescence and flow cytometry. T84 cells (human colon adenocarcinoma epithelial cells) were incubated with supernatants from Tr1 or FOXP3-positive cells, and transepithelial electrical resistance was measured to determine epithelial cell barrier function.

Results: Phenotypes of Tr1 cells isolated from control individuals vs patients with Crohn's disease or ulcerative colitis did not differ significantly after expansion. Tr1 cells and FOXP3-positive Treg cells suppressed proliferation of effector T cells, but only Tr1 cells suppressed secretion of IL1B and tumor necrosis factor from myeloid cells. Tr1 cells, but not FOXP3-positive Treg cells, isolated from healthy individuals and patients with Crohn's disease or ulcerative colitis secreted IL22, which promoted barrier function of human intestinal epithelial cells. Tr1 cell culture supernatants promoted differentiation of mucin-producing goblet cells in intestinal organoid cultures.

Conclusions: Human Tr1 cells suppress proliferation of effector T cells (adaptive immune response) and production of IL1B and TNF by myeloid cells (inmate immune response). They also secrete IL22 to promote barrier function. They might be developed as a cell-based therapy for intestinal inflammatory disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.gastro.2019.09.002DOI Listing
December 2019

Analysis of Genetic Association of Intestinal Permeability in Healthy First-degree Relatives of Patients with Crohn's Disease.

Inflamm Bowel Dis 2019 10;25(11):1796-1804

Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada.

Excessive intestinal permeability or intestinal barrier dysfunction as measured by various assays has been observed in various diseases. However, little is known about the factors contributing to altered gut permeability in these diseases. Our objective was to determine the genetic determinants of altered gut permeability as measured by the lactulose mannitol fractional excretion ratio (LacMan ratio) in 1075 healthy first-degree relatives of patients with Crohn's disease (CD). In a targeted analysis of single nucleotide polymorphisms (SNPs) located in genes associated with intestinal barrier function related or not to inflammatory bowel disease, we did not find a significant association with intestinal permeability. In an untargeted genome-wide association analysis, the top 100 associations were located in 22 genomic loci, although they were not statistically significant after correction for multiple testing (raw P values [1.8 × 10-7 - 1.4 × 10-5]. The lowest P value was obtained for rs9616637 (22q13.33, C22orf34), for which the minor allele A was associated with a decreased LacMan ratio. These results suggest that host genetic background has limited contribution toward intestinal permeability. Despite this, our study is currently the largest of its kind assessing gut permeability in vivo. It remains possible that smaller genetic effect sizes on LacMan ratio are not detectable in this sized cohort. Larger studies are warranted to identify the potential genetic contribution to intestinal permeability.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ibd/izz116DOI Listing
October 2019

Body mass index and risk of inflammatory bowel disease: A systematic review and dose-response meta-analysis of cohort studies of over a million participants.

Obes Rev 2019 09 12;20(9):1312-1320. Epub 2019 Jun 12.

Department of Pediatrics, BC Children's Hospital, University of British Columbia, Vancouver, Canada.

The relationship between body mass index (BMI) and risk of inflammatory bowel disease (IBD) is controversial. We performed a dose-response meta-analysis to investigate the association between BMI and risk of incident ulcerative colitis (UC) and Crohn's disease (CD) using prospective cohort studies. A systematic search was conducted in MEDLINE/PubMed, SCOPUS, Cochrane, and Web of Science databases from inception to January 2019. DerSimonian and Laird random-effects model was used to estimate combined hazard ratios (HRs). Overall, 882 articles were screened, and 42 full-text articles were reviewed for inclusion using the study eligibility criteria. Five studies evaluated the association between BMI and IBD with 1 044 517 participants. Pooled results showed a significant association between participants affected by obesity and risk of CD (HR: 1.42, 95% CI: 1.18-1.71, I : 0.00). There was a significant nonlinear association between BMI and risk of CD (P = .01, coeff = 0.5024). Pooled results did not show any significant association between being underweight and risk of UC (HR: 1.07, 95% CI: 0.96-1.19, I : 0.00) or CD (HR: 1.11, 95% CI: 0.93-1.31, I : 12.8). There was no difference in the risk for UC among participants affected by obesity compared with participants categorized as having normal BMI (HR: 0.96, 95% CI: 0.80-1.14, I : 8.0). This systematic review and meta-analysis identified significant dose-response relationship between being affected by obesity, as a risk factor, and incidence of CD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/obr.12875DOI Listing
September 2019

Consecutive fecal calprotectin measurements for predicting relapse in pediatric Crohn's disease patients.

World J Gastroenterol 2019 Mar;25(10):1266-1277

Division of Gastroenterology, Hepatology and Nutrition, British Columbia Children's Hospital, Vancouver, BC V6H 3V4, Canada.

Background: Asymptomatic children with Crohn's disease (CD) require ongoing monitoring to ensure early recognition of a disease exacerbation.

Aim: In a cohort of pediatric CD patients, we aimed to assess the utility of serial fecal calprotectin measurements to detect intestinal inflammatory activity and predict disease relapse.

Methods: In this prospective longitudinal cohort study, children with CD on infliximab therapy in clinical remission were included. Fecal calprotectin levels were assessed at baseline and at subsequent 2-5 visits. Clinical and biochemical disease activity were assessed using the Pediatric Crohn's Disease Activity Index, C-reactive protein and erythrocyte sedimentation rate at baseline and at visits over the following 18 mo.

Results: 53 children were included and eighteen patients (34%) had a clinical disease relapse during the study. Baseline fecal calprotectin levels were higher in patients that developed symptomatic relapse [median (interquartile range), relapse 723 μg/g (283-1758) 244 μg/g (61-627), = 0.02]. Fecal calprotectin levels > 250 μg/g demonstrated good predictive accuracy of a clinical flare within 3 mo (area under the receiver operator curve was 0.86, 95% confidence limits 0.781 to 0.937).

Conclusion: Routine fecal calprotectin testing in children with CD in clinical remission is useful to predict relapse. Levels > 250 μg/g are a good predictor of relapse in the following 3 mo. This information is important to guide monitoring standards used in this population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3748/wjg.v25.i10.1266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6421242PMC
March 2019
-->