AudioAbstracts

Host: Esteban Figueroa, MD Exploring the ACE Index in Acute Ulcerative Colitis Rebecca K Grant, Gareth-Rhys Jones, Nikolas Plevris, Ruairi W Lynch, Philip W Jenkinson, Charlie W Lees, Thomas A Manship, Fiona A M Jagger, William M Brindle, Mrithula Shivakumar, Jack Satsangi, Ian D R Arnott Background: Intravenous (IV) steroids remain the first-line treatment for patients with acute ulcerative colitis (UC). However, 30% of patients do not respond to steroids, requiring second-line therapy and/or surgery. There are no existing indices that allow physicians to predict steroid nonresponse at admission. We aimed to determine if admission biochemical and endoscopic values could predict response to IV steroids. Methods: All admissions for acute UC (ICD-10 K51) between November 1, 2011, and October 31, 2016 were identified. Case note review confirmed diagnosis; clinical, endoscopic, and laboratory data were collected. Steroid response was defined as discharge home with no further therapy for active UC. Nonresponse was defined as requirement for second-line therapy or surgery. Univariate and binary logistic regression analyses were employed to identify factors associated with steroid nonresponse. Results: Two hundred and thirty-five acute UC admissions were identified, comprising both acute severe and acute nonsevere UC; 155 of the 235 patients (66.0%) …

Host: Esteban Figueroa, MD Exploring the ACE Index in Acute Ulcerative Colitis Rebecca K Grant, Gareth-Rhys Jones, Nikolas Plevris, Ruairi W Lynch, Philip W Jenkinson, Charlie W Lees, Thomas A Manship, Fiona A M Jagger, William M Brindle, Mrithula Shivakumar, Jack Satsangi, Ian D R Arnott Background: Intravenous (IV) steroids remain the first-line treatment for patients with acute ulcerative colitis (UC). However, 30% of patients do not respond to steroids, requiring second-line therapy and/or surgery. There are no existing indices that allow physicians to predict steroid nonresponse at admission. We aimed to determine if admission biochemical and endoscopic values could predict response to IV steroids. Methods: All admissions for acute UC (ICD-10 K51) between November 1, 2011, and October 31, 2016 were identified. Case note review confirmed diagnosis; clinical, endoscopic, and laboratory data were collected. Steroid response was defined as discharge home with no further therapy for active UC. Nonresponse was defined as requirement for second-line therapy or surgery. Univariate and binary logistic regression analyses were employed to identify factors associated with steroid nonresponse. Results: Two hundred and thirty-five acute UC admissions were identified, comprising both acute severe and acute nonsevere UC; 155 of the 235 patients (66.0%) …

Host: Eric Verdin, MD Here to talk about some of the cellular changes associated with aging, how these changes manifest clinically as we age, and emerging nutritional interventions to target these changes is Dr. Eric Verdin, the President and Chief Executive Officer of the Buck Institute for Research on Aging.

Host: Ewa A. Jankowska, MD, PhD, FESC Hospitalizations due to acute heart failure represent a growing healthcare problem and a large economic burden. Iron deficiency, irrespective of anemia, is prevalent among this population and is associated with a high risk for increased mortality and rehospitalization. Tune in to discover the latest data from the AFFIRM-AHF trial. What does this new information reveal about treatment with intravenous iron in patients with acute heart failure?

Host: John Anderson, MD The outbreak of the COVID-19 pandemic has pushed healthcare professionals to adjust the way they treat patients with chronic conditions like diabetes. Tune in to hear Dr. John Anderson share his experience caring for patients with diabetes amid the pandemic.

Host: John Anderson, MD The outbreak of the COVID-19 pandemic has pushed healthcare professionals to adjust the way they treat patients with chronic conditions like diabetes. Tune in to hear Dr. John Anderson share his experience caring for patients with diabetes amid the pandemic.

Host: Peter Buch, MD, FACG, AGAF, FACP Guest: Douglas Drossman, MD Effective communication is essential to improving the patient-provider relationship. What is the best approach a physician can take when speaking to patients with IBS? Dr. Peter Buch will discuss valuable communication strategies with Dr. Douglas Drossman, president of the Rome Foundation.

Host: Peter Buch, MD, FACG, AGAF, FACP Guest: Douglas Drossman, MD Effective communication is essential to improving the patient-provider relationship. What is the best approach a physician can take when speaking to patients with IBS? Dr. Peter Buch will discuss valuable communication strategies with Dr. Douglas Drossman, president of the Rome Foundation.

Guest: Todd Rice, MD Dive into the DIVINE study with Dr. Todd Rice, a pulmonologist and Associate Professor of Medicine at Vanderbilt University Medical Center. Dr. Rice explores the factors that have prompted a reassessment of macronutrient roles in critical illness and the results from the DIVINE study, which investigated whether a very high protein and lower carbohydrate enteral nutrition formula could facilitate improved glucose control while avoiding worsening hyperglycemia.

Guest: Todd Rice, MD Dive into the DIVINE study with Dr. Todd Rice, a pulmonologist and Associate Professor of Medicine at Vanderbilt University Medical Center. Dr. Rice explores the factors that have prompted a reassessment of macronutrient roles in critical illness and the results from the DIVINE study, which investigated whether a very high protein and lower carbohydrate enteral nutrition formula could facilitate improved glucose control while avoiding worsening hyperglycemia.

Host: Mikhail Kosiborod, MD Despite evidence and guideline recommendations, renin-angiotensin-aldosterone system inhibitor (RAASi) therapy tends to be used suboptimally among patients with heart failure (HF), particularly in patients with chronic kidney disease (CKD). What are the real-world factors that influence RAASi treatment decisions in patients with HF who have or are at risk for hyperkalemia? Hear about how the CARE HK in HF study is being designed to explore the real-world data surrounding this question and its associated impact on outcomes.

Host: Mikhail Kosiborod, MD Despite evidence and guideline recommendations, renin-angiotensin-aldosterone system inhibitor (RAASi) therapy tends to be used suboptimally among patients with heart failure (HF), particularly in patients with chronic kidney disease (CKD). What are the real-world factors that influence RAASi treatment decisions in patients with HF who have or are at risk for hyperkalemia? Hear about how the CARE HK in HF study is being designed to explore the real-world data surrounding this question and its associated impact on outcomes.

Host: Ivy Ka Man Law, PhD A Specific Mutation in Muc2 Determines Early Dysbiosis in Colitis-Prone Winnie Mice Marina Liso, Stefania De Santis, Giulio Verna, Manuela Dicarlo, Maria Calasso, Angelo Santino, Isabella Gigante, Rajaraman Eri, Sathuwarman Raveenthiraraj, Anastasia Sobolewski, Valeria Palmitessa, Antonio Lippolis, Mauro Mastronardi, Raffaele Armentano, Grazia Serino, Maria De Angelis, Marcello Chieppa Background: Inflammatory bowel disease (IBD), including Crohn disease (CD) and ulcerative colitis (UC), is a multifactorial disorder characterized by chronic inflammation and altered gut barrier function. Dysbiosis, a condition defined by dysregulation of the gut microbiome, has been reported in patients with IBD and in experimental models of colitis. Although several factors have been implicated in directly affecting gut microbial composition, the genetic determinants impacting intestinal dysbiosis in IBD remain relatively unknown. Methods: We compared the microbiome of normal, uninflamed wild-type (WT) mice with that of a murine model of UC (ie, Winnie strain). Winnie mice ...

Host: Ivy Ka Man Law, PhD A Specific Mutation in Muc2 Determines Early Dysbiosis in Colitis-Prone Winnie Mice Marina Liso, Stefania De Santis, Giulio Verna, Manuela Dicarlo, Maria Calasso, Angelo Santino, Isabella Gigante, Rajaraman Eri, Sathuwarman Raveenthiraraj, Anastasia Sobolewski, Valeria Palmitessa, Antonio Lippolis, Mauro Mastronardi, Raffaele Armentano, Grazia Serino, Maria De Angelis, Marcello Chieppa Background: Inflammatory bowel disease (IBD), including Crohn disease (CD) and ulcerative colitis (UC), is a multifactorial disorder characterized by chronic inflammation and altered gut barrier function. Dysbiosis, a condition defined by dysregulation of the gut microbiome, has been reported in patients with IBD and in experimental models of colitis. Although several factors have been implicated in directly affecting gut microbial composition, the genetic determinants impacting intestinal dysbiosis in IBD remain relatively unknown. Methods: We compared the microbiome of normal, uninflamed wild-type (WT) mice with that of a murine model of UC (ie, Winnie strain). Winnie mice ...

Guest: Manpreet Mundi, MD Despite the increasing prevalence of home enteral nutrition over the last few decades, there has not been an equal rise in the number of studies being conducted in this population, which makes it difficult to develop guidelines and answer key clinical questions. So to help address this gap, the home enteral nutrition team at Mayo Clinic conducted a retrospective analysis of patients who utilized peptide-based diets, and now, Dr. Manpreet Mundi is here to share the results of that analysis.

Guest: Manpreet Mundi, MD Despite the increasing prevalence of home enteral nutrition over the last few decades, there has not been an equal rise in the number of studies being conducted in this population, which makes it difficult to develop guidelines and answer key clinical questions. So to help address this gap, the home enteral nutrition team at Mayo Clinic conducted a retrospective analysis of patients who utilized peptide-based diets, and now, Dr. Manpreet Mundi is here to share the results of that analysis.

Host: Abdullah Abdussalam, MD Proactive Vs Reactive Therapeutic Drug Monitoring of Infliximab in Crohn’s Diana M Negoescu, Eva A Enns, PhD, Brooke Swanhorst, Bonnie Baumgartner, James P Campbell, Mark T Osterman, MD, Konstantinos Papamichael, PhD, Adam S Cheifetz, MD, Byron P Vaughn, MD Background: Therapeutic drug monitoring (TDM) is increasingly performed for Infliximab (IFX) in patients with Crohn's disease (CD). Reactive TDM is a cost-effective strategy to empiric IFX dose escalation. The cost-effectiveness of proactive TDM is unknown. The aim of this study is to assess the cost-effectiveness of proactive vs reactive TDM in a simulated population of CD patients on IFX. Methods: We developed a stochastic simulation model of CD patients on IFX and evaluated the expected health costs and outcomes of a proactive TDM strategy compared with a reactive strategy. The proactive strategy measured IFX concentration and antibody status every 6 months, or at the time of a flare, and dosed IFX to a therapeutic window. The reactive strategy only did so at the time of a flare.

Host: Abdullah Abdussalam, MD Proactive Vs Reactive Therapeutic Drug Monitoring of Infliximab in Crohn’s Diana M Negoescu, Eva A Enns, PhD, Brooke Swanhorst, Bonnie Baumgartner, James P Campbell, Mark T Osterman, MD, Konstantinos Papamichael, PhD, Adam S Cheifetz, MD, Byron P Vaughn, MD Background: Therapeutic drug monitoring (TDM) is increasingly performed for Infliximab (IFX) in patients with Crohn's disease (CD). Reactive TDM is a cost-effective strategy to empiric IFX dose escalation. The cost-effectiveness of proactive TDM is unknown. The aim of this study is to assess the cost-effectiveness of proactive vs reactive TDM in a simulated population of CD patients on IFX. Methods: We developed a stochastic simulation model of CD patients on IFX and evaluated the expected health costs and outcomes of a proactive TDM strategy compared with a reactive strategy. The proactive strategy measured IFX concentration and antibody status every 6 months, or at the time of a flare, and dosed IFX to a therapeutic window. The reactive strategy only did so at the time of a flare.

Guest: Juan Ochoa, MD Join Dr. Juan Ochoa, Medical Director of Surgical Intensive Care at Oschsner Medical Center, as he reviews a retrospective study that investigated the impacts of high-protein, low-calorie feedings on critically ill patients in the ICU. Dr. Ochoa is a Surgeon, physician scientist, and former Chief Medical Officer of Nestlé Health Science.

Guest: Juan Ochoa, MD Join Dr. Juan Ochoa, Medical Director of Surgical Intensive Care at Oschsner Medical Center, as he reviews a retrospective study that investigated the impacts of high-protein, low-calorie feedings on critically ill patients in the ICU. Dr. Ochoa is a Surgeon, physician scientist, and former Chief Medical Officer of Nestlé Health Science.

Guest: Anish Patel, DO, FACG Real-world Pattern of Biologic Use in Patients With Inflammatory Bowel Disease: Treatment Persistence, Switching, and Importance of Concurrent Immunosuppressive Therapy Chao Chen, PhD, Abraham G Hartzema, PhD, Hong Xiao, PhD, Yu-Jung Wei, PhD, Naueen Chaudhry, MD, Ofor Ewelukwa, MD, Sarah C Glover, DO, Ellen M Zimmermann, MD BACKGROUND AND AIMS:Medication persistence, defined as the time from drug initiation to discontinuation of therapy, has been suggested as a proxy for real-world therapeutic benefit and safety. This study seeks to compare the persistence of biologic drugs among patients with inflammatory bowel disease (IBD). METHODS:Patients with newly diagnosed IBD were included in a retrospective study using Truven MarketScan database. Treatment persistence and switching was compared among biologic medications including infliximab, adalimumab, certolizumab, golimumab, and vedolizumab. Predictors for discontinuation and switching were evaluated using time-dependent proportional hazard regression. RESULTS:In total, 5612 patients with Crohn's disease (CD) and 3533 patients with ulcerative colitis (UC) were included in this analysis. Less than half of the patients continued using their initial biologic treatment after 1 year (48.48% in CD cohort; 44.78% ...

Guest: Anish Patel, DO, FACG Real-world Pattern of Biologic Use in Patients With Inflammatory Bowel Disease: Treatment Persistence, Switching, and Importance of Concurrent Immunosuppressive Therapy Chao Chen, PhD, Abraham G Hartzema, PhD, Hong Xiao, PhD, Yu-Jung Wei, PhD, Naueen Chaudhry, MD, Ofor Ewelukwa, MD, Sarah C Glover, DO, Ellen M Zimmermann, MD BACKGROUND AND AIMS:Medication persistence, defined as the time from drug initiation to discontinuation of therapy, has been suggested as a proxy for real-world therapeutic benefit and safety. This study seeks to compare the persistence of biologic drugs among patients with inflammatory bowel disease (IBD). METHODS:Patients with newly diagnosed IBD were included in a retrospective study using Truven MarketScan database. Treatment persistence and switching was compared among biologic medications including infliximab, adalimumab, certolizumab, golimumab, and vedolizumab. Predictors for discontinuation and switching were evaluated using time-dependent proportional hazard regression. RESULTS:In total, 5612 patients with Crohn's disease (CD) and 3533 patients with ulcerative colitis (UC) were included in this analysis. Less than half of the patients continued using their initial biologic treatment after 1 year (48.48% in CD cohort; 44.78% ...

Guest: Robin Dalal, MD Improving the Quality of Inpatient Ulcerative Colitis Management: Promoting Evidence-Based Practice and Reducing Care Variation With an Inpatient Protocol Sara M Lewin, MD, Ryan A McConnell, MD, Roshan Patel, MD, Suzanne R Sharpton, MD, MAS, Fernando Velayos, MD, MPH, Uma Mahadevan, MD BACKGROUND:Hospitalization for ulcerative colitis is a high-risk period associated with increased risk of Clostridium difficile infection, thromboembolism, and opiate use. The study aim was to develop and implement a quality-improvement intervention for inpatient ulcerative colitis management that standardizes gastroenterology consultant recommendations and improves delivery of evidence-based care. METHODS:All adult patients hospitalized for ulcerative colitis between July 1, 2014, and December 31, 2017, who received intravenous corticosteroids were included. On July 1, 2016, the UCSF Inpatient Ulcerative Colitis Protocol was implemented, featuring standardized core recommendations and a daily checklist for gastroenterology consultant notes, a bundled IBD electronic order set, and an opiate awareness campaign. The composite primary outcome was adherence to all 3 evidence-based care metrics: C. difficile testing performed, pharmacologic venous thromboembolism (VTE) prophylaxis ordered, and opiates avoided. RESULTS:Ninety-three ulcerative colitis hospitalizations occurred, including 36 preintervention and 57 ...

Guest: Robin Dalal, MD Improving the Quality of Inpatient Ulcerative Colitis Management: Promoting Evidence-Based Practice and Reducing Care Variation With an Inpatient Protocol Sara M Lewin, MD, Ryan A McConnell, MD, Roshan Patel, MD, Suzanne R Sharpton, MD, MAS, Fernando Velayos, MD, MPH, Uma Mahadevan, MD BACKGROUND:Hospitalization for ulcerative colitis is a high-risk period associated with increased risk of Clostridium difficile infection, thromboembolism, and opiate use. The study aim was to develop and implement a quality-improvement intervention for inpatient ulcerative colitis management that standardizes gastroenterology consultant recommendations and improves delivery of evidence-based care. METHODS:All adult patients hospitalized for ulcerative colitis between July 1, 2014, and December 31, 2017, who received intravenous corticosteroids were included. On July 1, 2016, the UCSF Inpatient Ulcerative Colitis Protocol was implemented, featuring standardized core recommendations and a daily checklist for gastroenterology consultant notes, a bundled IBD electronic order set, and an opiate awareness campaign. The composite primary outcome was adherence to all 3 evidence-based care metrics: C. difficile testing performed, pharmacologic venous thromboembolism (VTE) prophylaxis ordered, and opiates avoided. RESULTS:Ninety-three ulcerative colitis hospitalizations occurred, including 36 preintervention and 57 ...

Results of an Expert Consensus Survey on the Treatment of Pulmonary Arterial Hypertension with Oral Prostacyclin Pathway Agents Vallerie V McLaughlin, MD, FACC, FCCP; Richard Channick, MD; Teresa De Marco, MD, FACC, FHFSA; Harrison W Farber, MD, FCCP; Sean Gaine, MD, PhD; Nazzareno Galié, MD; Richard A Krasuski, MD; Ioana Preston, MD; Rogerio Souza, MD, PhD; J Gerry Coghlan, MD; Robert P. Frantz, MD; Anna Hemnes, MD; Nick H Kim, MD; Irene M Lang, MD; David Langleben, MD; Mengtao Li, MD; Olivier Sitbon MD, PhD; Victor Tapson, MD; Adaani Frost, MD Funding was provided by Actelion to support the use of independent providers of Delphi methodology expertise and nominal group technique, survey creation, data analysis, medical communication, and meeting management. The authors were not paid an honorarium for their participation. Actelion played no role in the literature search and analysis, development of surveys used to gather consensus, or data analysis; and no Actelion employee was present at the meeting during which consensus statements were finalized. The manuscript was drafted, critically reviewed, and edited solely by the authors with support from an independent professional medical communications agency. Actelion Pharmaceuticals reviewed the final manuscript only to ensure accuracy of UPTRAVI® (selexipag) background ...

Results of an Expert Consensus Survey on the Treatment of Pulmonary Arterial Hypertension with Oral Prostacyclin Pathway Agents Vallerie V McLaughlin, MD, FACC, FCCP; Richard Channick, MD; Teresa De Marco, MD, FACC, FHFSA; Harrison W Farber, MD, FCCP; Sean Gaine, MD, PhD; Nazzareno Galié, MD; Richard A Krasuski, MD; Ioana Preston, MD; Rogerio Souza, MD, PhD; J Gerry Coghlan, MD; Robert P. Frantz, MD; Anna Hemnes, MD; Nick H Kim, MD; Irene M Lang, MD; David Langleben, MD; Mengtao Li, MD; Olivier Sitbon MD, PhD; Victor Tapson, MD; Adaani Frost, MD Funding was provided by Actelion to support the use of independent providers of Delphi methodology expertise and nominal group technique, survey creation, data analysis, medical communication, and meeting management. The authors were not paid an honorarium for their participation. Actelion played no role in the literature search and analysis, development of surveys used to gather consensus, or data analysis; and no Actelion employee was present at the meeting during which consensus statements were finalized. The manuscript was drafted, critically reviewed, and edited solely by the authors with support from an independent professional medical communications agency. Actelion Pharmaceuticals reviewed the final manuscript only to ensure accuracy of UPTRAVI® (selexipag) background ...

Multicenter Clinical Validation of the Molecular-Based BD MAX™ Enteric Viral Panel for the Detection of Enteric Pathogens. William Stokes, MD, Patricia J. Simner, MSc, PhD, Joel Mortensen, PhD, Margret Oethinger, MD, PhD, Kathleen Stellrecht, PhD, Elizabeth Lockamy, PhD, Tricia Lay, MS, Peggy Bouchy, PhD, Dylan Pillai, MD, PhD Background: Conventional methodology for gastrointestinal pathogens remains time-consuming, expensive, and of limited sensitivity. Objective: Performance evaluation of the BD MAX™ Enteric Viral Panel (MAX EVP) assay for identification of viral pathogens in stool specimens from individuals with symptoms of acute gastroenteritis, enteritis, or colitis. Study Design: Prospective and archival stool specimens were collected in Cary-Blair medium or unpreserved containers from adult and pediatric patients with diarrhea. Specimens tested via the MAX EVP (on the BD MAX™ System) were compared to reference method (alternate PCR assays, followed by bi-directional sequencing). Positive percent agreement (PPA) and negative percent agreement (NPA) were calculated. Results: A total of 2,239 specimens were collected, with 2,148 included for analysis. In this population, 39.6% of specimens were from outpatients, 42.1% were from patients < 21 years, and 49.7% were from females. Prevalence rates for prospective specimens were 7.3%, 4.5%, 3.5%, 2.4%, and 1.2% for norovirus, sapovirus, astrovirus, rotavirus, and ...

Host: Alka Goyal, MD Higher Postinduction Infliximab Serum Trough Levels Are Associated With Healing of Fistulizing Perianal Crohn’s Disease in Children. Wael El-Matary, MD, MSc Thomas D Walters, MD Hien Q Huynh, MDJennifer deBruyn, MD David R Mack, MD Kevan Jacobson, MD Mary E Sherlock, MDPeter Church, MD Eytan Wine, MD, PhD Matthew W Carroll, MD, Eric I Benchimol, MD, PhD Sally Lawrence, MD Anne M Griffiths, MD Background: There is some evidence in adults that higher serum infliximab (IFX) levels are needed to adequately treat fistulizing perianal Crohn's disease (CD). However, data in children are lacking. We aimed to determine postinduction serum trough IFX levels that are associated with healing of fistulizing perianal CD (PCD) at week 24. Methods: In a multicenter inception cohort study, consecutive children younger than age 17 years with fistulizing perianal CD treated with IFX between April 2014 and June 2017 who had serum trough IFX titers measured before the fourth infusion were included. Area under the receiver operating characteristic curve (AUROC) was calculated to determine the best cutoff to predict fistula ...

Host: Louis J Cohen, MD Impact of Obesity on Short- and Intermediate-Term Outcomes in Inflammatory Bowel Disease: Pooled Analysis of Placebo Arms of Infliximab Clinical Trials. Siddharth Singh, MD, MS James Proudfoot, MS Ronghui Xu, PhDWilliam J Sandborn, MD Background: To assess whether obesity may affect natural history of inflammatory bowel diseases (IBD), we conducted an individual participant data (IPD) pooled analysis of placebo arms, using data from clinical trials of infliximab in IBD and using the Yale Open Data Access (YODA) Project. Methods: We obtained IPD from 4 placebo-controlled trials of infliximab in adults with IBD (ACCENT-I and ACCENT-II; ACT-1 and ACT-2). Patients were categorized into quartiles based on body mass index (BMI) or weight at time of trial entry. Primary outcome was clinical remission (Crohn’s disease activity index [CDAI]

Host: Alka Goyal, MD Higher Postinduction Infliximab Serum Trough Levels Are Associated With Healing of Fistulizing Perianal Crohn’s Disease in Children. Wael El-Matary, MD, MSc Thomas D Walters, MD Hien Q Huynh, MDJennifer deBruyn, MD David R Mack, MD Kevan Jacobson, MD Mary E Sherlock, MDPeter Church, MD Eytan Wine, MD, PhD Matthew W Carroll, MD, Eric I Benchimol, MD, PhD Sally Lawrence, MD Anne M Griffiths, MD Background: There is some evidence in adults that higher serum infliximab (IFX) levels are needed to adequately treat fistulizing perianal Crohn's disease (CD). However, data in children are lacking. We aimed to determine postinduction serum trough IFX levels that are associated with healing of fistulizing perianal CD (PCD) at week 24. Methods: In a multicenter inception cohort study, consecutive children younger than age 17 years with fistulizing perianal CD treated with IFX between April 2014 and June 2017 who had serum trough IFX titers measured before the fourth infusion were included. Area under the receiver operating characteristic curve (AUROC) was calculated to determine the best cutoff to predict fistula ...

Host: Louis J Cohen, MD Impact of Obesity on Short- and Intermediate-Term Outcomes in Inflammatory Bowel Disease: Pooled Analysis of Placebo Arms of Infliximab Clinical Trials. Siddharth Singh, MD, MS James Proudfoot, MS Ronghui Xu, PhDWilliam J Sandborn, MD Background: To assess whether obesity may affect natural history of inflammatory bowel diseases (IBD), we conducted an individual participant data (IPD) pooled analysis of placebo arms, using data from clinical trials of infliximab in IBD and using the Yale Open Data Access (YODA) Project. Methods: We obtained IPD from 4 placebo-controlled trials of infliximab in adults with IBD (ACCENT-I and ACCENT-II; ACT-1 and ACT-2). Patients were categorized into quartiles based on body mass index (BMI) or weight at time of trial entry. Primary outcome was clinical remission (Crohn’s disease activity index [CDAI]

Host: Damian Maseda, D.M.Sc., PhD Iron Sequestration in Microbiota Biofilms As A Novel Strategy for Treating Inflammatory Bowel Disease. Jean-Paul Motta, PhD Thibault Allain, PhD Luke E Green-Harrison, BScRyan A Groves, MSc Troy Feener, MSc Hena Ramay, PhD Paul L Beck, MD/PhDIan A Lewis, PhD John L Wallace, PhD Andre G Buret, PhD ABSTRACT: Significant alterations of intestinal microbiota and anemia are hallmarks of inflammatory bowel disease (IBD). It is widely accepted that iron is a key nutrient for pathogenic bacteria, but little is known about its impact on microbiota associated with IBD. We used a model device to grow human mucosa-associated microbiota in its physiological anaerobic biofilm phenotype. Compared to microbiota from healthy donors, microbiota from IBD patients generate biofilms ex vivo that were larger in size and cell numbers, contained higher intracellular iron concentrations, and exhibited heightened virulence in a model of human intestinal epithelia in vitro and in the nematode Caenorhabditis elegans. We also describe an unexpected iron-scavenging property for an experimental hydrogen sulfide-releasing derivative of mesalamine. The findings demonstrate that this new drug reduces the virulence of IBD microbiota biofilms through ...

Host: Damian Maseda, D.M.Sc., PhD Iron Sequestration in Microbiota Biofilms As A Novel Strategy for Treating Inflammatory Bowel Disease. Jean-Paul Motta, PhD Thibault Allain, PhD Luke E Green-Harrison, BScRyan A Groves, MSc Troy Feener, MSc Hena Ramay, PhD Paul L Beck, MD/PhDIan A Lewis, PhD John L Wallace, PhD Andre G Buret, PhD ABSTRACT: Significant alterations of intestinal microbiota and anemia are hallmarks of inflammatory bowel disease (IBD). It is widely accepted that iron is a key nutrient for pathogenic bacteria, but little is known about its impact on microbiota associated with IBD. We used a model device to grow human mucosa-associated microbiota in its physiological anaerobic biofilm phenotype. Compared to microbiota from healthy donors, microbiota from IBD patients generate biofilms ex vivo that were larger in size and cell numbers, contained higher intracellular iron concentrations, and exhibited heightened virulence in a model of human intestinal epithelia in vitro and in the nematode Caenorhabditis elegans. We also describe an unexpected iron-scavenging property for an experimental hydrogen sulfide-releasing derivative of mesalamine. The findings demonstrate that this new drug reduces the virulence of IBD microbiota biofilms through ...

Guest: Yash Mittal, MD Reliability of Measuring Ileo-Colonic Disease Activity in Crohn's Disease by Magnetic Resonance Enterography. Vipul Jairath, MD, PhD, Ingrid Ordas, MD, PhD, Guangyong Zou, PhD, Julian Panes, MD, Jaap Stoker, MD, PhD, Stuart A Taylor, MD, Cynthia Santillan, MD, Karin Horsthuis, MD, Mark A Samaan, MD, Lisa M Shackelton, PhD, Larry W Stitt, MSc, Pieter Hindryckx, MD, PhD, Reena Khanna, MD, William J Sandborn, MD ,Geert D'Haens, MD, PhD, Brian G Feagan, MD, Barrett G Levesque, MD, and Jordi Rimola, MD, PhD BACKGROUND: Magnetic resonance enterography is increasingly utilized for assessment of luminal Crohn's disease activity. The Magnetic Resonance Index of Activity and the London Index are the most commonly used outcome measures in clinical trials. We assessed the reliability of these indices and several additional items. METHODS: A consensus process clarified scoring conventions and identified additional items based on face validity. Four experienced radiologists evaluated 50 images in triplicate, in random order, at least 1 month apart, using a central image management system. Intra- and interrater reliability were assessed by calculating and comparing intraclass correlation coefficients. RESULTS: Intrarater intraclass correlation coefficients (95% confidence intervals) for the Magnetic Resonance Index of Activity, London, and London "extended" indices and a visual analogue ...

Guest: Shail Govani, MD, MSc Incidence and Predictors of Success of Adalimumab Dose Escalation and De-escalation in Ulcerative Colitis: a Real-World Belgian Cohort Study. Saartje Van de Vondel, MD, Filip Baert, MD, PhD, Christine Reenaers, MD, PhD, Stijn Vanden Branden, MD, Leila Amininejad, MD, Pieter Dewint, MD, PhD, Wouter Van Moerkercke, MD, Jean-François Rahier, MD, PhD, Pieter Hindryckx, MD, PhD, Peter Bossuyt, MD, Marc Ferrante, MD, PhD, and Belgian IBD Research and Development (BIRD) BACKGROUND: Adalimumab (ADM) has been shown efficacious in ulcerative colitis (UC). In randomized controlled trials, dose escalation from 40 mg ADM every other week to 40 mg every week was required in 20%–25% of patients within 1 year. Real-life data suggest higher escalation rates. Attempts for dose de-escalation have not been studied yet. We assessed the need for, outcome of, and predictors of dose escalation and de-escalation in a large retrospective cohort of UC patients treated with ADM. METHODS: We included 231 consecutive patients from 10 Belgian centers initiating ADM treatment for active UC before September 1, 2015 (follow-up ≥1 year in each patient). We performed detailed chart review to identify variables associated with short-term clinical benefit (based on physician global assessment and absence of rectal bleeding at week 10), success ...

Guest: Yash Mittal, MD Reliability of Measuring Ileo-Colonic Disease Activity in Crohn's Disease by Magnetic Resonance Enterography. Vipul Jairath, MD, PhD, Ingrid Ordas, MD, PhD, Guangyong Zou, PhD, Julian Panes, MD, Jaap Stoker, MD, PhD, Stuart A Taylor, MD, Cynthia Santillan, MD, Karin Horsthuis, MD, Mark A Samaan, MD, Lisa M Shackelton, PhD, Larry W Stitt, MSc, Pieter Hindryckx, MD, PhD, Reena Khanna, MD, William J Sandborn, MD ,Geert D'Haens, MD, PhD, Brian G Feagan, MD, Barrett G Levesque, MD, and Jordi Rimola, MD, PhD BACKGROUND: Magnetic resonance enterography is increasingly utilized for assessment of luminal Crohn's disease activity. The Magnetic Resonance Index of Activity and the London Index are the most commonly used outcome measures in clinical trials. We assessed the reliability of these indices and several additional items. METHODS: A consensus process clarified scoring conventions and identified additional items based on face validity. Four experienced radiologists evaluated 50 images in triplicate, in random order, at least 1 month apart, using a central image management system. Intra- and interrater reliability were assessed by calculating and comparing intraclass correlation coefficients. RESULTS: Intrarater intraclass correlation coefficients (95% confidence intervals) for the Magnetic Resonance Index of Activity, London, and London "extended" indices and a visual analogue ...

Guest: Shail Govani, MD, MSc Incidence and Predictors of Success of Adalimumab Dose Escalation and De-escalation in Ulcerative Colitis: a Real-World Belgian Cohort Study. Saartje Van de Vondel, MD, Filip Baert, MD, PhD, Christine Reenaers, MD, PhD, Stijn Vanden Branden, MD, Leila Amininejad, MD, Pieter Dewint, MD, PhD, Wouter Van Moerkercke, MD, Jean-François Rahier, MD, PhD, Pieter Hindryckx, MD, PhD, Peter Bossuyt, MD, Marc Ferrante, MD, PhD, and Belgian IBD Research and Development (BIRD) BACKGROUND: Adalimumab (ADM) has been shown efficacious in ulcerative colitis (UC). In randomized controlled trials, dose escalation from 40 mg ADM every other week to 40 mg every week was required in 20%–25% of patients within 1 year. Real-life data suggest higher escalation rates. Attempts for dose de-escalation have not been studied yet. We assessed the need for, outcome of, and predictors of dose escalation and de-escalation in a large retrospective cohort of UC patients treated with ADM. METHODS: We included 231 consecutive patients from 10 Belgian centers initiating ADM treatment for active UC before September 1, 2015 (follow-up ≥1 year in each patient). We performed detailed chart review to identify variables associated with short-term clinical benefit (based on physician global assessment and absence of rectal bleeding at week 10), success ...

Guest: Ruchi Gupta, MD, MPH Despite the increasing prevalence of food allergies in children nationwide, accurate and comprehensive statistics regarding its impacts didn’t exist, which is exactly why The Public Health Impact of Parent-Reported Childhood Food Allergies in the United States study was conducted. Here to walk us through its findings is Dr. Ruchi Gupta, Professor of Pediatrics at Northwestern University’s Feinberg School of Medicine and lead author of the study.

Guest: Ruchi Gupta, MD, MPH Despite the increasing prevalence of food allergies in children nationwide, accurate and comprehensive statistics regarding its impacts didn’t exist, which is exactly why The Public Health Impact of Parent-Reported Childhood Food Allergies in the United States study was conducted. Here to walk us through its findings is Dr. Ruchi Gupta, Professor of Pediatrics at Northwestern University’s Feinberg School of Medicine and lead author of the study.

Infliximab Trough Levels at Induction to Predict Treatment Failure During Maintenance. Liefferinckx C1, Minsart C, Toubeau JF, Cremer A, Amininejad L, Quertinmont E, Devière J, Gils A, van Gossum A, Franchimont D. BACKGROUND: Infliximab (IFX) is indicated for the treatment of inflammatory bowel diseases (IBD). Nevertheless, loss of response (LOR) to IFX is reported in up to 10% to 30% of patients within the first year of treatment. Our objective was to evaluate the impact of the pharmacokinetics of IFX at induction on treatment failure. METHODS: This is a longitudinal cohort study on 269 patients with IBD treated with IFX in a single center. A total of 2331 blood samples were prospectively collected from 2007 until March 2015 with a retrospective analysis of clinical data. IFX trough levels (TLs) were measured by enzyme-linked immunosorbent assay. Antibodies to IFX were measured by drug-sensitive bridging assay. RESULTS: During follow-up, patients were defined according to treatment outcome. At week 6, median IFX TL in patients requiring a switch to another treatment due to LOR (LOR switched group) (2.32 μg/mL [0.12-19.93 μg/mL]) was lower than in patients with long-term response (long-term responders) (8.66 μg/mL [0.12-12.09 μg/mL], P = ...

Infliximab Trough Levels at Induction to Predict Treatment Failure During Maintenance. Liefferinckx C1, Minsart C, Toubeau JF, Cremer A, Amininejad L, Quertinmont E, Devière J, Gils A, van Gossum A, Franchimont D. BACKGROUND: Infliximab (IFX) is indicated for the treatment of inflammatory bowel diseases (IBD). Nevertheless, loss of response (LOR) to IFX is reported in up to 10% to 30% of patients within the first year of treatment. Our objective was to evaluate the impact of the pharmacokinetics of IFX at induction on treatment failure. METHODS: This is a longitudinal cohort study on 269 patients with IBD treated with IFX in a single center. A total of 2331 blood samples were prospectively collected from 2007 until March 2015 with a retrospective analysis of clinical data. IFX trough levels (TLs) were measured by enzyme-linked immunosorbent assay. Antibodies to IFX were measured by drug-sensitive bridging assay. RESULTS: During follow-up, patients were defined according to treatment outcome. At week 6, median IFX TL in patients requiring a switch to another treatment due to LOR (LOR switched group) (2.32 μg/mL [0.12-19.93 μg/mL]) was lower than in patients with long-term response (long-term responders) (8.66 μg/mL [0.12-12.09 μg/mL], P = ...

Anti-TNF Treatment for Extraintestinal Manifestations of Inflammatory Bowel Disease in the Swiss IBD Cohort Study. Vavricka SR1, Gubler M, Gantenbein C, Spoerri M, Froehlich F, Seibold F, Protic M, Michetti P, Straumann A, Fournier N, Juillerat P, Biedermann L, Zeitz J, Misselwitz B, Scharl M, Heinrich H, Manser CN, Safroneeva E, Raja Ali RA, Rogler G, Schoepfer AM, Greuter T; Swiss IBD Cohort Study Group. BACKGROUND: Extraintestinal manifestations (EIMs) in patients with inflammatory bowel disease (IBD) are frequently observed. Little is known about the efficacy of anti-tumor necrosis factor (TNF) in EIM management. We assessed the effect of 3 anti-TNF agents (infliximab, adalimumab, and certolizumab pegol) on EIM evolution. METHODS: Data on 1249 patients from the Swiss IBD Cohort Study (SIBDCS) were analyzed. All EIMs were diagnosed by relevant specialists. Response was classified into improvement, stable disease, and clinical worsening based on the physician's interpretation. RESULTS: Of the 366 patients with at least 1 EIM, 213 (58.2%) were ever treated with an anti-TNF. A total of 299 treatments were started for 355 EIMs. Patients with EIM were significantly more often treated with anti-TNF compared with those without EIM (58.2% versus 21.0%, P < 0.001). ...