308 results on '"Joel R. Rosh"'
Search Results
2. Targeted Assessment of Mucosal Immune Gene Expression Predicts Clinical Outcomes in Children with Ulcerative Colitis
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Kathryn Clarkston, Rebekah Karns, Anil G Jegga, Mihika Sharma, Sejal Fox, Babajide A Ojo, Phillip Minar, Thomas D Walters, Anne M Griffiths, David R Mack, Brendan Boyle, Neal S LeLeiko, James Markowitz, Joel R Rosh, Ashish S Patel, Sapana Shah, Robert N Baldassano, Marian Pfefferkorn, Cary Sauer, Subra Kugathasan, Yael Haberman, Jeffrey S Hyams, Lee A Denson, and Michael J Rosen
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Adult ,Mucous Membrane ,Adrenal Cortex Hormones ,Gastroenterology ,Humans ,Gene Expression ,Colitis, Ulcerative ,General Medicine ,Original Articles ,Child ,Mesalamine - Abstract
Background and AimsWe aimed to determine whether a targeted gene expression panel could predict clinical outcomes in paediatric ulcerative colitis [UC] and investigated putative pathogenic roles of predictive genes.MethodsIn total, 313 rectal RNA samples from a cohort of newly diagnosed paediatric UC patients (PROTECT) were analysed by a real-time PCR microfluidic array for expression of type 1, 2 and 17 inflammation genes. Associations between expression and clinical outcomes were assessed by logistic regression. Identified prognostic markers were further analysed using existing RNA sequencing (RNA-seq) data sets and tissue immunostaining.ResultsIL13RA2 was associated with a lower likelihood of corticosteroid-free remission (CSFR) on mesalamine at week 52 (p = .002). A model including IL13RA2 and only baseline clinical parameters was as accurate as an established clinical model, which requires week 4 remission status. RORC was associated with a lower likelihood of colectomy by week 52. A model including RORC and PUCAI predicted colectomy by 52 weeks (area under the receiver operating characteristic curve 0.71). Bulk RNA-seq identified IL13RA2 and RORC as hub genes within UC outcome-associated expression networks related to extracellular matrix and innate immune response, and lipid metabolism and microvillus assembly, respectively. Adult UC single-cell RNA-seq data revealed IL13RA2 and RORC co-expressed genes were localized to inflammatory fibroblasts and undifferentiated epithelial cells, respectively, which was supported by protein immunostaining.ConclusionTargeted assessment of rectal mucosal immune gene expression predicts 52-week CSFR in treatment-naïve paediatric UC patients. Further exploration of IL-13Rɑ2 as a therapeutic target in UC and future studies of the epithelial-specific role of RORC in UC pathogenesis are warranted.
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- 2023
3. Pediatric Management of Crohn’s Disease
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Elana B, Mitchel and Joel R, Rosh
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Adult ,Crohn Disease ,Gastroenterology ,Humans ,Child - Abstract
Pediatric Crohn's disease is often more severe, requires higher levels of immunosuppression, and is associated with greater morbidity compared with adult Crohn's disease. Unique considerations in pediatric Crohn's disease include growth impairment, pubertal delay, bone disease, longevity of disease burden, and psychosocial impact. Treatment options are limited, requiring off-label use of therapy in this challenging patient population. Understanding the medications available, the existing evidence supporting their use, and side effects is important. There is tremendous potential for growth and improvement in this field and it is essential that all gastroenterologists have an understanding of this complex and unique patient population.
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- 2022
4. Methotrexate
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Joel R. Rosh
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- 2023
5. Treatment of pouchitis, Crohn's disease, cuffitis, and other inflammatory disorders of the pouch: consensus guidelines from the International Ileal Pouch Consortium
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Mark S. Silverberg, Udayakumar Navaneethan, André D'Hoore, Severine Vermeire, Jason Schairer, Joseph A Picoraro, Sandra El-Hachem, Sunanda V. Kane, Revital Kariv, Ellen Scherl, Samir A. Shah, Bincy Abraham, Gursimran Kochhar, Akira Sugita, Dino Tarabar, Jessica Philpott, Raymond K. Cross, Paulo Gustavo Kotze, Shannon Chang, Stuart Bentley-Hibbert, David A. Schwartz, Darrell S. Pardi, Bo Shen, Xiuli Liu, Maia Kayal, David T. Rubin, Ravi P. Kiran, Francis A Farraye, Rocio Sedano, Jonathan Segal, James McCormick, Philip Fleshner, Joel R. Rosh, Charles N. Bernstein, William J. Sandborn, David H. Bruining, and Priya Sehgal
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medicine.medical_specialty ,Consensus ,medicine.drug_class ,Cutaneous Fistula ,Antibiotics ,Anti-Inflammatory Agents ,Colonic Pouches ,Constriction, Pathologic ,Disease ,Pouchitis ,Gastroenterology ,Inflammatory bowel disease ,Maintenance Chemotherapy ,Crohn Disease ,Gastrointestinal Agents ,Recurrence ,Risk Factors ,Internal medicine ,Intestinal Fistula ,Secondary Prevention ,medicine ,Humans ,Biological Products ,Crohn's disease ,Hepatology ,medicine.diagnostic_test ,Tumor Necrosis Factor-alpha ,business.industry ,Intestinal Polyps ,medicine.disease ,digestive system diseases ,Anti-Bacterial Agents ,Endoscopy ,stomatognathic diseases ,Acute Disease ,Chronic Disease ,Etiology ,Pouch ,business - Abstract
Summary Pouchitis, Crohn's disease of the pouch, cuffitis, polyps, and extraintestinal manifestations of inflammatory bowel disease are common inflammatory disorders of the ileal pouch. Acute pouchitis is treated with oral antibiotics and chronic pouchitis often requires anti-inflammatory therapy, including the use of biologics. Aetiological factors for secondary pouchitis should be evaluated and managed accordingly. Crohn's disease of the pouch is usually treated with biologics and its stricturing and fistulising complications can be treated with endoscopy or surgery. The underlying cause of cuffitis determines treatment strategies. Endoscopic polypectomy is recommended for large, symptomatic inflammatory polyps and polyps in the cuff. The management principles of extraintestinal manifestations of inflammatory bowel disease in patients with pouches are similar to those in patients without pouches.
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- 2022
6. Stratification of risk of progression to colectomy in ulcerative colitis via measured and predicted gene expression
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David R. Mack, Jarod Prince, Susan S. Baker, Brendan M. Boyle, Rebekah Karns, Suresh Venkateswaran, Subra Kugathasan, Talin Haritunians, Dermot P.B. McGovern, Mamta Giri, James Markowitz, Nai Yun Hsu, Melvin B. Heyman, Lee A. Denson, Ling-Shiang Chuang, Mayte Suárez-Fariñas, Greg Gibson, Jeffrey S. Hyams, Neal S. LeLeiko, Andrew Kasarskis, Kyle Gettler, Bruce J. Aronow, Cary G. Sauer, Yael Haberman, Carmen Argmann, Anne M. Griffiths, Joel R. Rosh, Nathan Gotman, Angela Mo, Dalia Arafat, Sapana Shah, Paul A. Rufo, Thomas D. Walters, Marian Pfefferkorn, Ashish S. Patel, Sonia Davis Thomas, Judy H. Cho, Robert N. Baldassano, Emebet Mengesha, Joshua D. Noe, and Sini Nagpal
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Oncology ,Multifactorial Inheritance ,medicine.medical_treatment ,Datasets as Topic ,Ulcerative ,Disease ,Medical and Health Sciences ,cell-type-specific gene expression ,Cohort Studies ,Crohn Disease ,Colectomy ,Genetics (clinical) ,Biological Specimen Banks ,Genetics & Heredity ,Framingham Risk Score ,eQTLs ,Biological Sciences ,Colitis ,Prognosis ,Ulcerative colitis ,transcriptome-wide association studies ,Disease Progression ,Patient Safety ,predicted polygenic transcriptional risk scores ,Biotechnology ,medicine.medical_specialty ,Colon ,Quantitative Trait Loci ,Quantitative trait locus ,Autoimmune Disease ,Risk Assessment ,Article ,Clinical Research ,Internal medicine ,Genetics ,medicine ,Humans ,Genetic association ,business.industry ,Prevention ,Gene Expression Profiling ,Human Genome ,Inflammatory Bowel Disease ,medicine.disease ,United Kingdom ,Gene expression profiling ,transcriptional risk scores ,prediction of disease progression ,Expression quantitative trait loci ,Colitis, Ulcerative ,Generic health relevance ,Digestive Diseases ,Transcriptome ,business ,Genome-Wide Association Study - Abstract
Summary An important goal of clinical genomics is to be able to estimate the risk of adverse disease outcomes. Between 5% and 10% of individuals with ulcerative colitis (UC) require colectomy within 5 years of diagnosis, but polygenic risk scores (PRSs) utilizing findings from genome-wide association studies (GWASs) are unable to provide meaningful prediction of this adverse status. By contrast, in Crohn disease, gene expression profiling of GWAS-significant genes does provide some stratification of risk of progression to complicated disease in the form of a transcriptional risk score (TRS). Here, we demonstrate that a measured TRS based on bulk rectal gene expression in the PROTECT inception cohort study has a positive predictive value approaching 50% for colectomy. Single-cell profiling demonstrates that the genes are active in multiple diverse cell types from both the epithelial and immune compartments. Expression quantitative trait locus (QTL) analysis identifies genes with differential effects at baseline and week 52 follow-up, but for the most part, differential expression associated with colectomy risk is independent of local genetic regulation. Nevertheless, a predicted polygenic transcriptional risk score (PPTRS) derived by summation of transcriptome-wide association study (TWAS) effects identifies UC-affected individuals at 5-fold elevated risk of colectomy with data from the UK Biobank population cohort studies, independently replicated in an NIDDK-IBDGC dataset. Prediction of gene expression from relatively small transcriptome datasets can thus be used in conjunction with TWASs for stratification of risk of disease complications.
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- 2021
7. Early Change in Fecal Calprotectin Predicts One-Year Outcome in Children Newly Diagnosed With Ulcerative Colitis
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Ashwin N. Ananthakrishnan, Cary G. Sauer, Joel R. Rosh, Anne M. Griffiths, Jeffrey S. Hyams, David R. Mack, Lee A. Denson, Neal S. Leleiko, Brendan M. Boyle, Subra Kugathasan, James Markowitz, Erin Bonkowski, Chenthan Krishnakumar, and Thomas D. Walters
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medicine.medical_specialty ,medicine.medical_treatment ,Newly diagnosed ,New diagnosis ,Feces ,Primary outcome ,Internal medicine ,medicine ,Humans ,Child ,Mesalamine ,Colectomy ,business.industry ,Remission Induction ,Gastroenterology ,Clinical course ,medicine.disease ,Ulcerative colitis ,Treatment Outcome ,Pediatrics, Perinatology and Child Health ,Colitis, Ulcerative ,Calprotectin ,business ,Leukocyte L1 Antigen Complex ,Biomarkers - Abstract
While fecal calprotectin (FC) is used to assess disease activity in ulcerative colitis (UC) there are little data concerning the role of serial FC levels at diagnosis in predicting clinical course. We sought to determine whether FC at diagnosis or early change following therapy predicts clinical outcomes in pediatric UC.Methods: Children with newly diagnosed UC were treated with standardized regimens of mesalamine or corticosteroids (CS). CS tapering and escalation to additional therapy or colectomy were by protocol. Patients with baseline or week 4 or week 12 FC levels were included in the analysis. Our primary outcome was CS-free remission on mesalamine at week 52. We compared the prognostic value of a baseline FC as well as a change in FC by week 4 or week 12 in predicting clinical outcomes.The study included 352 children (113 initial mesalamine, 239 initial CS, mean age 12.6 years) with UC. At Week 52, 135 (38.3%), 84 (23.8%), and 19 (5.4%) children achieved CS-free remission, needed anti-tumor necrosis factor therapy or had colectomy respectively. Baseline FC was not associated with CS-free remission at week 52. However, both week 4 (odds ratio [OR] 0.95, 95% confidence interval [CI] 0.901.00) and week 12 FC levels (OR 0.91, 95% CI 0.87-0.96) were associated with outcomes, with the latter having a stronger association with CS-free remission. Patients with a75% decrease by 12 weeks, had a 3-fold increased likelihood of CS-free remission at 1 year.Longitudinal changes in FC may predict 1 year outcomes better than values at diagnosis in children with a new diagnosis of UC.
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- 2021
8. Pediatric Endoscopy Quality Improvement Network Quality Standards and Indicators for Pediatric Endoscopic Procedures: A Joint NASPGHAN/ESPGHAN Guideline
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Hien Q. Huynh, Raoul I. Furlano, Diana G. Lerner, Marta Tavares, Petar Mamula, David R. Mack, Matjaž Homan, Patrick Bontems, Quin Y. Liu, Matthew R Riley, Kevan Jacobson, Douglas S. Fishman, Iva Hojsak, Ian H. Leibowitz, Nicholas M. Croft, Graham McCreath, Veronik Connan, Salvatore Oliva, Herbert Brill, Robert E. Kramer, Mike Thomson, Catharine M. Walsh, Jenifer R. Lightdale, Anthony R. Otley, Peter M. Gillett, Lusine Ambartsumyan, Priya Narula, Jorge Amil-Dias, Joel R. Rosh, and Elizabeth C. Utterson
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Adult ,medicine.medical_specialty ,Consensus ,Quality management ,children ,pediatric endoscopy ,quality indicators ,media_common.quotation_subject ,Delphi method ,MEDLINE ,Endoscopy, Gastrointestinal ,healthcare ,patient care/standards ,patient safety ,pediatric gastroenterology/∗standards ,performance measures ,quality assurance ,Cancer screening ,medicine ,Humans ,Medical physics ,Quality (business) ,Child ,Grading (education) ,Pediatric gastroenterology ,media_common ,business.industry ,Gastroenterology ,Guideline ,Quality Improvement ,Pediatrics, Perinatology and Child Health ,business - Abstract
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 three 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.
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- 2021
9. Clinical and Host Biological Factors Predict Colectomy Risk in Children Newly Diagnosed With Ulcerative Colitis
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Suresh Venkateswaran, Thomas D. Walters, Subra Kugathasan, Cary G. Sauer, Joelynn Dailey, James Markowitz, Marian Pfefferkorn, Neal S. Leleiko, Yael Haberman, Jeffrey S. Hyams, Brendan M. Boyle, Michael Brimacombe, Robert N. Baldassano, Lee A. Denson, David R. Mack, Joel R. Rosh, Angela Mo, Anne M. Griffiths, Greg Gibson, Ashish S. Patel, and Sapana Shah
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medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Gastroenterology ,Cohort Studies ,Biological Factors ,Internal medicine ,medicine ,Humans ,Immunology and Allergy ,Child ,Mesalamine ,Colectomy ,Retrospective Studies ,medicine.diagnostic_test ,business.industry ,Proportional hazards model ,Area under the curve ,Gene signature ,medicine.disease ,Ulcerative colitis ,Infliximab ,Confidence interval ,Treatment Outcome ,Child, Preschool ,Erythrocyte sedimentation rate ,Colitis, Ulcerative ,Leading Off ,business ,medicine.drug - Abstract
Background Develop a clinical and biological predictive model for colectomy risk in children newly diagnosed with ulcerative colitis (UC). Methods This was a multicenter inception cohort study of children (ages 4-17 years) newly diagnosed with UC treated with standardized initial regimens of mesalamine or corticosteroids (CS) depending upon initial disease severity. Therapy escalation to immunomodulators or infliximab was based on predetermined criteria. Patients were phenotyped by clinical activity per the Pediatric Ulcerative Colitis Activity Index (PUCAI), disease extent, endoscopic/histologic severity, and laboratory markers. In addition, RNA sequencing defined pretreatment rectal gene expression and high density DNA genotyping by the Affymetrix UK Biobank Axiom Array. Coprimary outcomes were colectomy over 3 years and time to colectomy. Generalized linear models, Cox proportional hazards multivariate regression modeling, and Kaplan-Meier plots were used. Results Four hundred twenty-eight patients (mean age 13 years) started initial theapy with mesalamine (n = 136), oral CS (n = 144), or intravenous CS (n = 148). Twenty-five (6%) underwent colectomy at ≤1 year, 33 (9%) at ≤2 years, and 35 (13%) at ≤3 years. Further, 32/35 patients who had colectomy failed infliximab. An initial PUCAI ≥ 65 was highly associated with colectomy (P = 0.0001). A logistic regression model predicting colectomy using the PUCAI, hemoglobin, and erythrocyte sedimentation rate had a receiver operating characteristic area under the curve of 0.78 (95% confidence interval [0.73, 0.84]). Addition of a pretreatment rectal gene expression panel reflecting activation of the innate immune system and response to external stimuli and bacteria to the clinical model improved the receiver operating characteristic area under the curve to 0.87 (95% confidence interval [0.82, 0.91]). Conclusions A small group of children newly diagnosed with severe UC still require colectomy despite current therapies. Our gene signature observations suggest additional targets for management of those patients not responding to current medical therapies.
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- 2021
10. Development and Testing of a New Simplified Endoscopic Mucosal Assessment for Crohn’s Disease: The SEMA-CD
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Haley C Neef, Shuemein J Mar, Alka Goyal, Jeremy Adler, Kelly C. Sandberg, George M. Zacur, Kelley Rose French, Shehzad Ahmed Saeed, Joseph A Picoraro, Sally J. Eder, Acham Gebremariam, Jeffery D. Lewis, J. Fernando Del Rosario, Andrew A.M. Singer, Joel R. Rosh, Christopher J. Moran, Jess L. Kaplan, Ila Moncion, Dawn R Ebach, Jonathan Moses, and Lee M. Bass
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0301 basic medicine ,medicine.medical_specialty ,Colon ,Colonoscopy ,Severity of Illness Index ,03 medical and health sciences ,0302 clinical medicine ,Cohen's kappa ,Crohn Disease ,Humans ,Immunology and Allergy ,Medicine ,Child ,Reliability (statistics) ,Crohn's disease ,medicine.diagnostic_test ,business.industry ,Gastroenterology ,Reproducibility of Results ,Intra-rater reliability ,Gold standard (test) ,medicine.disease ,Endoscopy ,Clinical trial ,030104 developmental biology ,030211 gastroenterology & hepatology ,Radiology ,business - Abstract
Objectives Endoscopic mucosal improvement is the gold standard for assessing treatment efficacy in clinical trials of Crohn’s disease. Current endoscopic indices are not routinely used in clinical practice. The lack of endoscopic information in large clinical registries limits their use for research. A quick, easy, and accurate method is needed for assessing mucosal improvement for clinicians in real-world practice. We developed and tested a novel simplified endoscopic mucosal assessment for Crohn’s disease (SEMA-CD). Methods We developed a 5-point scale for ranking endoscopic severity of ileum and colon based on Simple Endoscopic Score for Crohn’s disease (SES-CD). Central readers were trained to perform SES-CD and SEMA-CD. Pediatric patients with Crohn’s disease undergoing colonoscopy were enrolled. Video recordings of colonoscopies were de-identified and randomly assigned to blinded central readers. The SES-CD and SEMA-CD were scored for each video. The SES-CD was considered the validated standard for comparison. Correlation was assessed with Spearman rho, inter- and intrarater reliability with kappa statistics. Results Fifty-seven colonoscopies were read a total of 212 times. Correlation between SEMA-CD and SES-CD was strong (rho = 0.98, P < 0.0001). Inter-rater reliability for SEMA-CD was 0.80, and intrarater reliability was 0.83. Central readers rated SEMA-CD as easier than SES-CD. Conclusion The SEMA-CD accurately and reproducibly correlates with the standard SES-CD. Central readers viewed SEMA-CD as easier than SES-CD. Use of SEMA-CD in practice should enable collecting mucosal improvement information in large populations of patients. This will improve the quality of research that can be conducted in clinical registries. External validation is needed.
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- 2020
11. Guidance for Restarting Inflammatory Bowel Disease Therapy in Patients Who Withheld Immunosuppressant Medications During COVID-19
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Britt Christensen, Gerassimos J. Mantzaris, Scott Chapman, Michael D. Kappelman, Joel R. Rosh, Corey A. Siegel, David A. Wohl, Douglas F Johnson, Ryan C. Ungaro, and Asher Kornbluth
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medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,media_common.quotation_subject ,IBD ,Pneumonia, Viral ,Supplement Articles ,Inflammatory bowel disease ,Asymptomatic ,Risk Assessment ,Drug Administration Schedule ,Betacoronavirus ,Immunocompromised Host ,COVID-19 Testing ,Internal medicine ,Pandemic ,medicine ,Humans ,Clinical significance ,Asymptomatic Infections ,Pandemics ,media_common ,AcademicSubjects/MED00260 ,business.industry ,Clinical Laboratory Techniques ,SARS-CoV-2 ,Convalescence ,Gastroenterology ,COVID-19 ,immunomodulator ,General Medicine ,medicine.disease ,Inflammatory Bowel Diseases ,digestive system diseases ,de-escalation ,Crohn’s ,medicine.symptom ,business ,Risk assessment ,Coronavirus Infections ,biologic ,De-escalation ,Immunosuppressive Agents - Abstract
Patients with inflammatory bowel diseases [IBD] are frequently treated with immunosuppressant medications. During the coronavirus disease 2019 [COVID-19] pandemic, recommendations for IBD management have included that patients should stay on their immunosuppressant medications if they are not infected with the severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2], but to temporarily hold these medications if symptomatic with COVID-19 or asymptomatic but have tested positive for SARS-CoV-2. As more IBD patients are infected globally, it is important to also understand how to manage IBD medications during convalescence while an individual with IBD is recovering from COVID-19. In this review, we address the differences between a test-based versus a symptoms-based strategy as related to COVID-19, and offer recommendations on when it is appropriate to consider restarting IBD therapy in patients testing positive for SARS-CoV-2 or with clinical symptoms consistent with COVID-19. In general, we recommend a symptoms-based approach, due to the current lack of confidence in the accuracy of available testing and the clinical significance of prolonged detection of virus via molecular testing.
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- 2020
12. Overview of the Pediatric Endoscopy Quality Improvement Network Quality Standards and Indicators for Pediatric Endoscopy: A Joint NASPGHAN/ESPGHAN Guideline
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Iva Hojsak, Diana G. Lerner, Petar Mamula, Raoul I. Furlano, Hien Q. Huynh, Douglas S. Fishman, Veronik Connan, Ian H. Leibowitz, Catharine M. Walsh, Graham McCreath, Salvatore Oliva, Jenifer R. Lightdale, Robert E. Kramer, Jorge Amil-Dias, Mike Thomson, Anthony R. Otley, Peter M. Gillett, Priya Narula, Marta Tavares, Patrick Bontems, Kevan Jacobson, Matjaž Homan, Nicholas M. Croft, Herbert Brill, Quin Y. Liu, Elizabeth C. Utterson, Matthew R Riley, Joel R. Rosh, David R. Mack, and Lusine Ambartsumyan
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Adult ,medicine.medical_specialty ,Quality management ,Consensus ,Best practice ,media_common.quotation_subject ,children ,pediatric endoscopy ,quality indicators ,Delphi method ,Audit ,Endoscopy, Gastrointestinal ,Patient experience ,medicine ,Humans ,Medical physics ,Quality (business) ,Child ,media_common ,business.industry ,Gastroenterology ,Guideline ,Benchmarking ,Quality Improvement ,Pediatrics, Perinatology and Child Health ,endoscopy ,gastrointestinal/∗standards ,key performance indicators ,pediatric gastroenterology/∗standards ,practice guidelines as topic/∗standards ,quality assurance ,business - Abstract
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.
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- 2021
13. Pediatric Endoscopy Quality Improvement Network Pediatric Endoscopy Reporting Elements: A Joint NASPGHAN/ESPGHAN Guideline
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Elizabeth C. Utterson, Robert E. Kramer, Veronik Connan, Douglas S. Fishman, Patrick Bontems, Salvatore Oliva, Marta Tavares, Raoul I. Furlano, Graham McCreath, Kevan Jacobson, Herbert Brill, Hien Q. Huynh, Ian H. Leibowitz, Quin Y. Liu, Peter M. Gillett, David R. Mack, Diana G. Lerner, Petar Mamula, Iva Hojsak, Nicholas M. Croft, Priya Narula, Mike Thomson, Matthew R Riley, Catharine M. Walsh, Jenifer R. Lightdale, Anthony R. Otley, Lusine Ambartsumyan, Joel R. Rosh, Jorge Amil-Dias, and Matjaž Homan
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computerized/∗organization & administration ,digestive system/∗statistics & numerical data ,documentation/standards ,electronic health records/∗standards ,endoscopy ,medical record systems ,registries ,medicine.medical_specialty ,Quality management ,Consensus ,medicine.diagnostic_test ,Delphi Technique ,business.industry ,Delphi method ,MEDLINE ,Gastroenterology ,Guideline ,Quality Improvement ,Endoscopy, Gastrointestinal ,Endoscopy ,Systematic review ,Pediatrics, Perinatology and Child Health ,medicine ,Humans ,Medical physics ,business ,Child ,computer ,Pediatric gastroenterology ,Delphi ,computer.programming_language - Abstract
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.
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- 2021
14. Predicting disease course in ulcerative colitis using stool proteins identified through an aptamer-based screen
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Kyung Hyun Lee, Malavika Nidhi, Marwa Kharboutli, Jeffrey S. Hyams, Sanam Soomro, Chandra Mohan, Suresh Venkateswaran, Prashanth Sasidharan, Claudia Pedroza, Joel R. Rosh, Subra Kugathasan, James Markowitz, Ting Zhang, Lee A. Denson, Kamala Vanarsa, and Ramya Susarla
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Proteomics ,0301 basic medicine ,medicine.medical_specialty ,Adolescent ,Science ,General Physics and Astronomy ,Predictive markers ,Fibrinogen ,Severity of Illness Index ,Gastroenterology ,Inflammatory bowel disease ,Article ,General Biochemistry, Genetics and Molecular Biology ,Feces ,03 medical and health sciences ,fluids and secretions ,0302 clinical medicine ,Crohn Disease ,Internal medicine ,medicine ,Humans ,Colitis ,Child ,Gastrointestinal diseases ,Multidisciplinary ,biology ,business.industry ,digestive, oral, and skin physiology ,Haptoglobin ,Proteins ,General Chemistry ,medicine.disease ,Ulcerative colitis ,030104 developmental biology ,Child, Preschool ,biology.protein ,Properdin ,Colitis, Ulcerative ,030211 gastroenterology & hepatology ,Resistin ,Calprotectin ,business ,Leukocyte L1 Antigen Complex ,Aptamers, Peptide ,Biomarkers ,medicine.drug - Abstract
In the search for improved stool biomarkers for inflammatory bowel disease (IBD), an aptamer-based screen of 1129 stool proteins was conducted using stool samples from an IBD cohort. Here we report that of the 20 proteins subsequently validated by ELISA, stool Ferritin, Fibrinogen, Haptoglobin, Hemoglobin, Lipocalin-2, MMP-12, MMP-9, Myeloperoxidase, PGRP-S, Properdin, Resistin, Serpin A4, and TIMP-1 are significantly elevated in both ulcerative colitis (UC) and Crohn’s disease (CD) compared to controls. When tested in a longitudinal cohort of 50 UC patients at 4 time-points, fecal Fibrinogen, MMP-8, PGRP-S, and TIMP-2 show the strongest positive correlation with concurrent PUCAI and PGA scores and are superior to fecal calprotectin. Unlike fecal calprotectin, baseline stool Fibrinogen, MMP-12, PGRP-S, TIMP-1, and TIMP-2 can predict clinical remission at Week-4. Here we show that stool proteins identified using the comprehensive aptamer-based screen are superior to fecal calprotectin alone in disease monitoring and prediction in IBD., Stool biomarkers hold promise for monitoring disease activity and predicting clinical course in inflammatory bowel disease (IBD) as they originate from the inflamed tissue. Here the authors report an aptamer-based proteomic screen, and discover several stool proteins that predict remission at four weeks.
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- 2021
15. ID: 3526084 INTERNATIONAL CONSENSUS ON PEDIATRIC ENDOSCOPY REPORTING ELEMENTS: A REPORT FROM THE PEDIATRIC ENDOSCOPY QUALITY IMPROVEMENT NETWORK (PENQUIN)
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Elizabeth C. Utterson, Priya Narula, David R. Mack, Veronik Connan, Iva Hojsak, Jorge Amil, Anthony R. Otley, Salvatore Oliva, Matthew R Riley, Kevan Jacobson, Robert E. Kramer, Douglas S. Fishman, Ian H. Leibowitz, Marta Tavares, Raoul I. Furlano, Graham McCreath, Peter M. Gillett, Quin Liu, Mike Thomson, Diana G. Lerner, Catharine M. Walsh, Jenifer R. Lightdale, Herbert Brill, Matjaz Homan, Hien Q. Huynh, Petar Mamula, Joel R. Rosh, Lusine Ambartsumyan, Patrick Bontems, and Nicholas M. Croft
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medicine.medical_specialty ,Pediatric endoscopy ,Quality management ,business.industry ,Pédiatrie ,Gastroenterology ,Medicine ,Gastro-entérologie ,Radiology, Nuclear Medicine and imaging ,Medical physics ,business - Abstract
info:eu-repo/semantics/published
- Published
- 2021
16. Ustekinumab in Paediatric Patients with Moderately to Severely Active Crohn's Disease: Pharmacokinetics, Safety, and Efficacy Results from UniStar, a Phase 1 Study
- Author
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Stanley A. Cohen, Dan Turner, Anne M. Griffiths, Omoniyi J. Adedokun, Douglas A Jacobstein, Christopher D. O'Brien, Jeffrey S. Hyams, Lakshmi Padgett, Joel R. Rosh, and Natalie A. Terry
- Subjects
Male ,Crohn’s disease ,medicine.medical_specialty ,paediatric ,Adolescent ,Injections, Subcutaneous ,Population ,Gastroenterology ,Pediatrics ,ustekinumab ,Eccojc/1160 ,Eccojc/1040 ,Pharmacokinetics ,Crohn Disease ,Double-Blind Method ,Interquartile range ,Internal medicine ,Ustekinumab ,medicine ,Humans ,Adverse effect ,education ,Child ,AcademicSubjects/MED00260 ,Crohn's disease ,education.field_of_study ,Maintenance dose ,business.industry ,Antibodies, Monoclonal ,General Medicine ,Original Articles ,medicine.disease ,Treatment Outcome ,Tolerability ,Administration, Intravenous ,Female ,Patient Safety ,business ,medicine.drug - Abstract
Background and Aims The objective was to evaluate the pharmacokinetics, safety/tolerability, and efficacy of ustekinumab in children with moderately to severely active Crohn’s disease. Methods In this Phase 1, multicentre, 16-week, double-blind, induction dose-ranging study [NCT02968108], patients aged 2- Results A total of 44 patients were randomised and treated with ustekinumab [n = 23 lower dose; n = 21 higher dose]; median [interquartile range] age was 13.0 [12–16] years. Pharmacokinetics were similar to those in adults with Crohn’s disease. However, serum ustekinumab concentrations were lower among those with body weight Conclusions The pharmacokinetics/safety profiles were generally consistent with those observed in adults with Crohn’s disease. These results suggest a different dosing regimen may be required for patients
- Published
- 2021
17. The Current Role of Methotrexate in Patients With Inflammatory Bowel Disease
- Author
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Joel R, Rosh
- Subjects
Column - Published
- 2021
18. Stratification of Risk of Progression to Colectomy in Ulcerative Colitis using Measured and Predicted Gene Expression
- Author
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Suresh Venkateswaran, Melvin B. Heyman, Neal S. LeLeiko, Judy H. Cho, Robert N. Baldassano, T Walters, Ashish S. Patel, Brendan M. Boyle, Andrew Kasarskis, Ling-Shiang Chuang, Emebet Mengesha, Greg Gibson, Talin Haritunians, Nai Yun Hsu, Joshua D. Noe, Cary G. Sauer, David R. Mack, Yael Haberman, Jarod Prince, Susan S. Baker, Marian Pfefferkorn, Sini Nagpal, Mayte Suárez-Fariñas, Subra Kugathasan, Lee A. Denson, Anne M. Griffiths, James Markowitz, Bruce J. Aronow, Dalia Arafat, Sonia Davis Thomas, Rebekah Karns, Joel R. Rosh, Nathan Gotman, Angela Mo, Sapana Shah, Paul A. Rufo, Mamta Giri, Kyle Gettler, Dermot P.B. McGovern, Jeffrey S. Hyams, and Carmen Argmann
- Subjects
Oncology ,medicine.medical_specialty ,Framingham Risk Score ,business.industry ,medicine.medical_treatment ,Genome-wide association study ,Disease ,medicine.disease ,Ulcerative colitis ,Clinical trial ,Gene expression profiling ,Internal medicine ,medicine ,business ,Colectomy ,Genetic association - Abstract
SUMMARYAn important goal of clinical genomics is to be able to estimate the risk of adverse disease outcomes. Between 5% and 10% of ulcerative colitis (UC) patients require colectomy within five years of diagnosis, but polygenic risk scores (PRS) utilizing findings from GWAS are unable to provide meaningful prediction of this adverse status. By contrast, in Crohn’s disease, gene expression profiling of GWAS-significant genes does provide some stratification of risk of progression to complicated disease in the form of a Transcriptional Risk Score (TRS). Here we demonstrate that both measured (TRS) and polygenic predicted gene expression (PPTRS) identify UC patients at 5-fold elevated risk of colectomy with data from the PROTECT clinical trial and UK Biobank population cohort studies, independently replicated in an NIDDK-IBDGC dataset. Prediction of gene expression from relatively small transcriptome datasets can thus be used in conjunction with transcriptome-wide association studies to stratify risk of disease complications.
- Published
- 2021
19. Procedural Volume and Colectomy Complications
- Author
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Joel R. Rosh and Neal S. LeLeiko
- Subjects
medicine.medical_specialty ,Hospitals, Low-Volume ,Hepatology ,business.industry ,medicine.medical_treatment ,Gastroenterology ,Surgery ,Humans ,Medicine ,Colitis, Ulcerative ,Child ,business ,Colectomy ,Volume (compression) - Published
- 2019
20. Characterization of Stool Virome in Children Newly Diagnosed With Moderate to Severe Ulcerative Colitis
- Author
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Susan S. Baker, David R. Mack, Lee A. Denson, Alexandra Oleynik, Brendan M. Boyle, Sapana Shah, Cary G. Sauer, James Markowitz, Robert N. Baldassano, Xiaoyu Che, Anne M. Griffiths, Rafal Tokarz, Joel R. Rosh, W. Ian Lipkin, Bohyun Lee, Subra Kugathasan, T Walters, Neal S. Leleiko, Stephen Sameroff, Teresa Tagliafierro, and Jeffrey S. Hyams
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Adolescent ,Original Basic Science Articles ,Severity of Illness Index ,Gastroenterology ,Virus ,Feces ,03 medical and health sciences ,0302 clinical medicine ,children ,Gyrovirus ,Internal medicine ,Severity of illness ,Prevalence ,Humans ,Immunology and Allergy ,Medicine ,Human virome ,Child ,Irritable bowel syndrome ,ulcerative colitis ,virome ,biology ,business.industry ,High-Throughput Nucleotide Sequencing ,Prognosis ,biology.organism_classification ,medicine.disease ,Ulcerative colitis ,United States ,3. Good health ,030104 developmental biology ,Virus Diseases ,Case-Control Studies ,Child, Preschool ,DNA, Viral ,Viruses ,Cohort ,Colitis, Ulcerative ,Female ,030211 gastroenterology & hepatology ,business ,Follow-Up Studies - Abstract
Background Viral infections have been suggested as possible triggers for the onset of ulcerative colitis (UC). Methods We employed VirCapSeq-Vert, a high-throughput sequencing virus capture platform, to examine the stool virome of children with newly diagnosed moderate to severe UC. We surveyed fecal samples collected at presentation, after symptom remission, and from a control group diagnosed with irritable bowel syndrome. Results Seventy subjects with UC (mean age 13 years, 45 had moderate symptoms, 25 had severe, 69 of 70 had a Mayo endoscopy subscore 2/3) were studied. We detected a wide range of animal viruses that were taxonomically classified into 12 viral families. A virus was present in 50% of fecal samples collected at presentation, 41% of samples collected after remission, and 40% of samples in our control group. The most frequently identified viruses were diet-based gyroviruses. The UC cohort had a significantly higher prevalence of anelloviruses compared with the control cohort. However, we did not identify a single virus that can be implicated in the onset of UC and did not find an association between UC disease severity and viral presence. Conclusion Presence of virus in stool was not associated with the onset of pediatric UC., We used VirCapSeq-VERT, a high-throughput sequencing virus capture platform, to examine the stool virome of children with newly diagnosed moderate to severe ulcerative colitis. We did not identify a link between a viral infection and the onset of ulcerative colitis.
- Published
- 2019
21. Serum Protein Biomarkers of Fibrosis Aid in Risk Stratification of Future Stricturing Complications in Pediatric Crohn's Disease
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David M. Lubman, Ryan W. Stidham, Anne M. Griffiths, Lee A. Denson, Joel R. Rosh, Joshua D. Noe, Jeffrey S. Hyams, Ajay S. Gulati, Shervin Rabizadeh, Wallace Crandall, Marla Dubinsky, Jing Wu, Robert N. Baldassano, Subra Kugathasan, and Peter D.R. Higgins
- Subjects
Male ,Proteomics ,medicine.medical_specialty ,Proteomics methods ,Pediatric Crohn's disease ,Serum protein ,Constriction, Pathologic ,Disease ,Risk Assessment ,Article ,03 medical and health sciences ,0302 clinical medicine ,Crohn Disease ,Fibrosis ,Internal medicine ,medicine ,Humans ,Child ,Inflammation ,Extracellular Matrix Proteins ,Hepatology ,business.industry ,Disease progression ,Gastroenterology ,medicine.disease ,Intestines ,Multicenter study ,030220 oncology & carcinogenesis ,Risk stratification ,Disease Progression ,Female ,030211 gastroenterology & hepatology ,business ,Biomarkers - Abstract
Avoiding fibrostenotic complications is of paramount concern in the management of Crohn's disease (CD). We sought to investigate the association of candidate biomarkers of fibrosis collected at diagnosis with the future development of fibrostenotic CD.Using the Risk Stratification and Identification of Immunogenetic and Microbial Markers of Rapid Disease Progression in Children with Crohn's Disease cohort, a multicenter prospective observational pediatric inception cohort, subjects with an inflammatory phenotype (B1) at diagnosis who later converted to a stricturing phenotype (B2) within 3 years were compared with those who remained B1. Serum collected at diagnosis underwent both parallel reaction monitoring-targeted proteomic analysis and conventional enzyme-linked immunosorbent assay for 10 candidate biomarkers of intestinal fibrosis. Cox proportional hazard regression was used for multivariable analysis of time-dependent outcomes.In 116 subjects 58 subjects with verified B1 phenotype at diagnosis who later converted to B2 disease were compared with 58 subjects who remained B1 over 3 years of follow-up. Extracellular matrix protein 1 (ECM1) levels in the upper quartile (hazard ratio [HR] 3.43, 95% confidence limit [CL] 1.33, 8.42) were associated with future fibrostenotic disease. ASCA IgA (HR 4.99, 95% CL 1.50, 16.68) and CBir levels (HR 5.19, 95% CL 1.83, 14.74) were also associated with future intestinal fibrostenosis, although ECM1 continued to demonstrate independent association with conversion to B2 even with adjustment for serologies in multivariable analysis (HR 5.33, 95% CL 1.29, 22.13).ECM1 and other biomarkers of fibrosis may aid in determining the risk of uncomplicated inflammatory disease converting to B2 stricturing phenotypes in children with CD. Prospective validation studies to verify test performance and optimize clinical utilization are needed before clinical implementation.
- Published
- 2019
22. 983: OUTCOME OF INDUCTION THERAPY WITH VEDOLIZUMAB IN CHILDREN: RESULTS FROM THE PROSPECTIVE, MULTICENTER, VEDOKIDS STUDY
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Zivia Shavit-Brunschwig, Ronen E. Stein, Marina Aloi, Oren Ledder, Gili Focht, Darja Urlep, Jeffrey S. Hyams, Efrat Broide, Batia Weiss, Jeremiah Levine, Dror Shouval, Manar Matar, Amit Assa, Joel R. Rosh, Séamus Hussey, James Markowitz, Anat Yerushalmy-Feler, Erasmo Miele, Ron Shaoul, Richard K. Russell, and Dan Turner
- Subjects
Hepatology ,Gastroenterology - Published
- 2022
23. The Effect of Early-Life Environmental Exposures on Disease Phenotype and Clinical Course of Crohn's Disease in Children
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Marla Dubinsky, Melvin B. Heyman, Ashwin N. Ananthakrishnan, Scott B. Snapper, Anne M. Griffiths, Joel R. Rosh, James Markowitz, Livia Lindoso, Thomas D. Walters, Michael C. Stephens, Susan S. Baker, David R. Mack, Jeffrey S. Hyams, Dedrick E. Moulton, Ajay S. Gulati, Marian D. Pfefferkorn, Kajari Mondal, Maria Oliva-Hemker, Stephen L. Guthery, Suresh Venkateswaran, Anthony R. Otley, Cortney R. Ballengee, David J. Keljo, Jonathan Evans, Robert N. Baldassano, Ashish S. Patel, Lee A. Denson, Hari K. Somineni, Subra Kugathasan, Barbara S. Kirschner, Shervin Rabizadeh, Wallace Crandall, Joshua D. Noe, David Ziring, Stanley N. Cohen, Richard Kellermayer, and Neal S. LeLeiko
- Subjects
Male ,0301 basic medicine ,Time Factors ,Adolescent ,Colon ,Constriction, Pathologic ,Disease ,Severity of Illness Index ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,Crohn Disease ,Pregnancy ,Risk Factors ,Severity of illness ,medicine ,Humans ,Longitudinal Studies ,Prospective Studies ,Microbiome ,Child ,Immunologic Tolerance ,Crohn's disease ,Hepatology ,business.industry ,Smoking ,Infant, Newborn ,Gastroenterology ,Environmental Exposure ,medicine.disease ,Phenotype ,Hospitalization ,Breast Feeding ,030104 developmental biology ,Prenatal Exposure Delayed Effects ,North America ,Immunology ,Disease Progression ,Female ,Tobacco Smoke Pollution ,030211 gastroenterology & hepatology ,business ,Follow-Up Studies - Abstract
Environmental factors play an important role in the pathogenesis of Crohn's Disease (CD). In particular, by virtue of the instability of the microbiome and development of immunologic tolerance, early life factors may exert the strongest influence on disease risk and phenotype.We used data from 1119 CD subjects recruited from RISK inception cohort to examine the impact of early life environment on disease progression. Our primary exposures of interest were breastfeeding in infancy and exposure to maternal, active, or passive smoke. Our primary outcomes were development of complicated (stricturing or penetrating) disease, and need for CD-related hospitalization, and surgery. Multivariable logistic regression models were used to define independent associations, adjusting for relevant covariates.Our study cohort included 1119 patients with CD among whom 15% had stricturing (B2) or penetrating disease (B3) by 3 years. 331 patients (35%) and 95 patients (10.6%) required CD-related hospitalizations and surgery respectively. 74.5% were breastfed in infancy and 31% were exposed to smoking among whom 7% were exposed to maternal smoke. On multivariable analysis, a history of breastfeeding was inversely associated with complicated (B2/B3 disease) 0.65, CI 95% 0.44-96; P = 0.03) in pediatric CD. Maternal smoking during pregnancy was associated with increased risk of hospitalization during the 3-year follow-up period (OR 1.75, CI 95% 1.05-2.89; P = 0.03).Early life environmental factors influence the eventual phenotypes and disease course in CD.
- Published
- 2018
24. Diagnosis and classification of ileal pouch disorders: consensus guidelines from the International Ileal Pouch Consortium
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Jason Schairer, Sandra El-Hachem, Samir A. Shah, Ellen Scherl, Raymond K. Cross, Mark S. Silverberg, Sunanda V. Kane, Akira Sugita, Stuart Bentley-Hibbert, Joseph A Picoraro, Dino Tarabar, Rocio Sedano, Gursimran Kochhar, David A. Schwartz, Darrell S. Pardi, Bincy Abraham, Maia Kayal, Shannon Chang, André D'Hoore, Udayakumar Navaneethan, Bo Shen, Revital Kariv, Jonathan Segal, Francis A Farraye, Jessica Philpott, David T. Rubin, Ravi P. Kiran, Xiuli Liu, Paulo Gustavo Kotze, Severine Vermeire, James McCormick, Philip Fleshner, Charles N. Bernstein, Joel R. Rosh, Priya Sehgal, William J. Sandborn, and David H. Bruining
- Subjects
Male ,medicine.medical_specialty ,Consensus ,medicine.medical_treatment ,Colonic Pouches ,Anastomotic Leak ,Guidelines as Topic ,Disease ,Anastomosis ,Pouchitis ,Familial adenomatous polyposis ,Quality of life ,Medicine ,Humans ,Colectomy ,Hepatology ,business.industry ,Proctocolectomy ,Proctocolectomy, Restorative ,Gastroenterology ,Middle Aged ,medicine.disease ,Ulcerative colitis ,Surgery ,Adenomatous Polyposis Coli ,Disease Progression ,Quality of Life ,Colitis, Ulcerative ,Female ,Pouch ,business - Abstract
Restorative proctocolectomy with ileal pouch-anal anastomosis is an option for most patients with ulcerative colitis or familial adenomatous polyposis who require colectomy. Although the construction of an ileal pouch substantially improves patients' health-related quality of life, the surgery is, directly or indirectly, associated with various structural, inflammatory, and functional adverse sequelae. Furthermore, the surgical procedure does not completely abolish the risk for neoplasia. Patients with ileal pouches often present with extraintestinal, systemic inflammatory conditions. The International Ileal Pouch Consortium was established to create this consensus document on the diagnosis and classification of ileal pouch disorders using available evidence and the panellists' expertise. In a given individual, the condition of the pouch can change over time. Therefore, close monitoring of the activity and progression of the disease is essential to make accurate modifications in the diagnosis and classification in a timely manner.
- Published
- 2021
25. Pediatric Endoscopy Quality Improvement Network (PEnQuIN) quality standards and indicators for pediatric endoscopists and endoscopists in training: a joint NASPGHAN/ESPGHAN guideline
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David R. Mack, Robert E. Kramer, Hien Q. Huynh, Raoul I. Furlano, Ian H. Leibowitz, Priya Narula, Marta Tavares, Anthony R. Otley, Quin Y. Liu, Veronik Connan, Salvatore Oliva, Peter M. Gillett, Iva Hojsak, Patrick Bontems, Lusine Ambartsumyan, Douglas S. Fishman, Graham McCreath, Catharine M. Walsh, Jenifer R. Lightdale, Elizabeth C. Utterson, Petar Mamula, Kevan Jacobson, Diana G. Lerner, Matthew R Riley, Herbert Brill, Joel R. Rosh, Matjaž Homan, Jorge Amil-Dias, Mike Thomson, and Nicholas M. Croft
- Subjects
medicine.medical_specialty ,Quality management ,medicine.medical_treatment ,media_common.quotation_subject ,MEDLINE ,Delphi method ,Endoscopy, Gastrointestinal ,children ,Ileum ,pediatric endoscopy ,Humans ,Medicine ,Intubation ,Medical physics ,Quality (business) ,Child ,Grading (education) ,Cecum ,Pediatric gastroenterology ,media_common ,training ,business.industry ,Gastroenterology ,Colonoscopy ,Guideline ,Quality Improvement ,Pediatrics, Perinatology and Child Health ,business ,clinical competence/standards ,endoscopy ,gastrointestinal/∗standards ,key performance indicators ,pediatric gastroenterology/∗standards ,performance measures - Abstract
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.
- Published
- 2021
26. Contributors
- Author
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H. Hesham A-Kader, Sophia Abdulhai, Kareem Abu-Elmagd, Maisam Abu-El-Haija, Douglas G. Adler, Lindsey Albenberg, Estella M. Alonso, Ruchi Amin, Orhan Atay, Renata Auricchio, Robert D. Baker, Susan S. Baker, Katherine Baldwin, Jessica Barry, Todd H. Baron, Bradley Barth, Dorsey M. Bass, Lee M. Bass, Jaime Belkind-Gerson, Marc A. Benninga, Natalie Bhesania, Andrea Bischoff, Samuel Bitton, Samra S. Blanchard, Athos Bousvaros, Brendan Boyle, Jennifer Brewer, Jefferson N. Brownell, Steven W. Bruch, Brendan T. Campbell, Jacob Campbell, Michael Gerard Caty, Carolina S. Cerezo, Ryaz Chagpar, Beth Chatfield, Rebecca N. Cherry, Gail Cohen, Mitchell B. Cohen, Arnold G. Coran, Guilherme Costa, Gail A.M. Cresci, Eileen Crowley, Michael Cruise, Steven J. Czinn, Zev Davidovics, Luis De La Torre, Anthony L. DeRoss, David Devadason, Rajitha Devadoss Venkatesh, Carlo Di Lorenzo, Jennifer L. Dotson, Tracy R. Ediger, Bijan Eghtesad, John F. Eisses, Mounif El Yousif, Karan McBride Emerick, Steven H. Erdman, Rima Fawaz, Ariel E. Feldstein, Melissa Fernandes, Laura S. Finn, Kristin Nicole Fiorino, Douglas S. Fishman, Joel A. Friedlander, Masato Fujiki, John Fung, Ivan Fuss, David Galloway, Donald E. George, Fayez K. Ghishan, Raffaelle Girlanda, Donna Gitt, Deborah A. Goldman, Sue Goodine, Glenn R. Gourley, Nicole Green, Gabrielle Grisotti, Sandeep K. Gupta, Nedim Hadzic, Sanjiv Harpavat, Koji Hashimoto, Maheen Hassan, James E. Heubi, Sohail Z. Husain, Séamus Hussey, Jeffrey S. Hyams, Warren Hyer, Paul E. Hyman, Sabine Iben, Veronica E. Issac, Maureen M. Jonas, Marsha Kay, Mohit Kehar, Deidre Kelly, Karlo Kovacic, Shaun Michael Kunisaki, Jacob A. Kurowski, Jacob C. Langer, Frances C. Lee, Rose Lee, Neal S. LeLeiko, Chris A. Liacouras, Henry Lin, Quin Y. Liu, Kathleen M. Loomes, Peter L. Lu, Sarah Shrager Lusman, Cara Mack, Anshu Maheshwari, Petar Mamula, Michael A. Manfredi, James F. Markowitz, Jonathan E. Markowitz, Maria R. Mascarenhas, Ryann Mayer, Patrick McKiernan, Adam G. Mezoff, Ethan A. Mezoff, Giorgina Mieli-Vergani, Franziska Mohr, Jasmeet Mokha, Hayat Mousa, Lindsay Moye, Simon Murch, Karen F. Murray, Robert Naples, Jaimie D. Nathan, Vicky Lee Ng, Vi Nguyen, Samuel Nurko, Jodie Oauhed, Tina Ogholikhan, Keith T. Oldham, Mohammed Osman, Nadia Ovchinsky, Jennifer Panganiban, Alberto Pena, Robert E. Petras, Marian D. Pfefferkorn, David Piccoli, Travis Piester, Beth Pinkos, Thomas Plesec, Stephanie Polites, Todd Ponsky, Christine Rader, Kadakkal Radhakrishnan, Yannis Reissis, Leonel Rodriguez, Ricardo J. Rodriguez, Isabel Rojas, Ellen S. Rome, Joel R. Rosh, Rachel M. Ruiz, Benjamin Sahn, Atif Saleem, Kate A. Samela, Neha R. Santucci, Miguel Saps, Eleanor H. Sato, Thomas T. Sato, Erica C. Savage, Federico G. Seifarth, Praveen Kumar Conjeevaram Selvakumar, Jason Shapiro, Allan E. Siperstein, Joseph Skelton, Scott Snapper, Oliver S. Soldes, Manu R. Sood, Marisa Gallant Stahl, Shikha S. Sundaram, Francisco A. Sylvester, Jonathan E. Teitelbaum, Natalie A. Terry, Peter Townsend, Riccardo Troncone, Kate Vance, Yvan Vandenplas, Robert S. Venick, David S. Vitale, Jerry Vockley, Eugene Vortia, Mana H. Vriesman, Ghassan T. Wahbeh, R. Matthew Walsh, Suz Warner, Robert Wyllie, Jessica L. Yasuda, Donna Zeiter, and Hengqi (Betty) Zheng
- Published
- 2021
27. Cystic Fibrosis and Congenital Anomalies of the Exocrine Pancreas
- Author
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Sarah Shrager Lusman, Nadia Ovchinsky, and Joel R. Rosh
- Published
- 2021
28. Dual Biologic Therapy in an Adolescent With Camurati-Engelmann Disease and Crohn Disease
- Author
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Ahmad Salah Sami and Joel R. Rosh
- Published
- 2022
29. Maintenance Golimumab Treatment in Pediatric UC Patients With Moderately to Severely Active UC: PURSUIT PEDS PK Long-Term Study Results
- Author
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Joel R. Rosh, Anne M. Griffiths, Jeffrey S. Hyams, Geneviève Veereman, Melvin B. Heyman, Omoniyi J. Adedokun, Daphne Chan, Christopher D. O'Brien, Richard Strauss, Ghassan Wahbeh, Dan Turner, John P. Lynch, Lakshmi Padgett, Pediatrics, Clinical sciences, and Growth and Development
- Subjects
medicine.medical_specialty ,Tuberculosis ,clinical response ,Autoimmune Disease ,030226 pharmacology & pharmacy ,Gastroenterology ,03 medical and health sciences ,Rare Diseases ,0302 clinical medicine ,Pharmacokinetics ,Clinical Research ,Internal medicine ,Internal Medicine ,medicine ,Pediatrics, Perinatology, and Child Health ,ulcerative colitis ,Pediatric ,clinical remission ,business.industry ,Inflammatory Bowel Disease ,SERUM SICKNESS-LIKE REACTION ,Cancer ,medicine.disease ,Ulcerative colitis ,Golimumab ,Good Health and Well Being ,Long term learning ,Disease remission ,030211 gastroenterology & hepatology ,Digestive Diseases ,business ,medicine.drug - Abstract
Background Long-term safety, pharmacokinetics, and efficacy of open-label golimumab therapy in children with moderate–severe ulcerative colitis were evaluated. Methods Week-6 golimumab responders (Mayo score decrease of ≥30% and ≥3 points from baseline, rectal bleeding subscore of 0/1 or ≥1 decrease from baseline) entered the long-term extension at week 14 and received maintenance therapy (subcutaneous, q4w). Patients ≥45 kg could receive at-home treatments at week 18. Pharmacokinetic, safety, and efficacy results were summarized through week 126 (2 years). Results Among 35 enrolled children, 21 (60%) responded at week 6 and 20 entered the long-term extension (median age of 14.5 years and median weight of 46.1 kg). Eleven of 20 patients (55%) completed 2 years of treatment. No anaphylactic or serum sickness-like reactions, opportunistic infections, malignancies, tuberculosis, or deaths occurred. The safety profile of golimumab from weeks 14 through 126 and that observed through week 14 was generally consistent. Median trough golimumab concentrations in evaluable patients were consistent from weeks 14 (1.39, interquartile range 0.67–3.60) through 102 (1.18, 0.78–2.16), but higher at week 110 (4.10, 1.30–4.81). The incidence of antigolimumab antibodies increased from 10% (2/20) at week 30 to 25.0% (5/20) at week 126; 1 patient had neutralizing antibodies. At week 110, 50% (10/20) of patients were in remission (ie, Pediatric Ulcerative Colitis Activity Index Conclusions Among children with ulcerative colitis who initially responded to golimumab induction and received q4w maintenance treatment in the long-term extension, 50% showed continued clinical benefit through 2 years. No new safety signals were observed.
- Published
- 2020
30. Mucosal Inflammatory and Wound Healing Gene Programs Reveal Targets for Stricturing Behavior in Pediatric Crohn's Disease
- Author
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Susan S. Baker, David R. Mack, Phillip Minar, Ashish S. Patel, Neal S. Leleiko, Jennifer L. Dotson, Bruce J. Aronow, Suresh Venkateswaran, Samuel Tegge, Marla Dubinsky, Brianne Shuler, Scott B. Snapper, Dedrick E. Moulton, Yael Haberman, Robert Baldassano, Jeffrey S. Hyams, Ajay S. Gulati, Daniel Shapiro, David Ziring, Michael C. Stephens, Rebekah Karns, Richard Kellermayer, Ranjana Gokhale, Stanley A. Cohen, Thomas D. Walters, Sudhir Ghandikota, Maria Oliva-Hemker, Anthony R. Otley, Joshua D. Noe, Sandra C. Kim, Lee A. Denson, Tzipi Braun, Jonathan R. Dillman, Joel R. Rosh, Subra Kugathasan, Greg Gibson, Anne M. Griffiths, Melvin B. Heyman, Allison Ta, Phillip J. Dexheimer, James Markowitz, Anil G. Jegga, Stephen L. Guthery, and Steven J. Steiner
- Subjects
0301 basic medicine ,medicine.medical_specialty ,pediatric Crohn Disease ,Clinical Sciences ,small molecule ,Crohn's Disease ,Disease ,Gastroenterology ,Transcriptome ,surgery ,03 medical and health sciences ,0302 clinical medicine ,Paediatric Crohn disease ,Clinical Research ,Internal medicine ,Gene expression ,medicine ,Genetics ,Gene ,Pediatric ,Crohn's disease ,Gastroenterology & Hepatology ,business.industry ,Inflammatory Bowel Disease ,Mucous membrane ,Original Articles ,General Medicine ,Gene signature ,medicine.disease ,Gene expression profiling ,030104 developmental biology ,medicine.anatomical_structure ,030211 gastroenterology & hepatology ,ileum ,business ,Digestive Diseases ,transcriptome - Abstract
Background and Aims Ileal strictures are the major indication for resective surgery in Crohn’s disease [CD]. We aimed to define ileal gene programmes present at diagnosis and linked with future stricturing behaviour during 5-year follow-up, and to identify potential small molecules to reverse these gene signatures. Methods Antimicrobial serologies and pre-treatment ileal gene expression were assessed in a representative subset of 249 CD patients within the RISK multicentre paediatric CD inception cohort study, including 113 that are unique to this report. These data were used to define genes associated with stricturing behaviour and for model testing to predict stricturing behaviour. A bioinformatics approach to define small molecules which may reverse the stricturing gene signature was applied. Results A total of 19 of the 249 patients developed isolated B2 stricturing behaviour during follow-up, while 218 remained B1 inflammatory. Using deeper RNA sequencing than in our previous report, we have now defined an inflammatory gene signature including an oncostatin M co-expression signature, tightly associated with extra-cellular matrix [ECM] gene expression, in those who developed stricturing complications. We further computationally prioritise small molecules targeting macrophage and fibroblast activation and angiogenesis which may reverse the stricturing gene signature. A model containing ASCA and CBir1 serologies and a refined eight ECM gene set was significantly associated with stricturing development by Year 5 after diagnosis {AUC (area under the curve) (95th CI [confidence interval]) = 0.82 [0.7–0.94)}. Conclusions An ileal gene programme for macrophage and fibroblast activation is linked to stricturing complications in treatment of naïve pediatric CD, and may inform novel small molecule therapeutic approaches.
- Published
- 2020
31. Similar Long-Term Outcomes in Children Presenting With Abscess vs Phlegmon at Diagnosis of Crohn Disease
- Author
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Joel R. Rosh, Maua H. Mosha, Sarah M Rosenheck, Mary C. Kennedy, Brendan M. Boyle, Meghan Gibson, Barbara Joanna Niklinska-Schirtz, Annette Langseder, S. Kugathasan, Andrew W. Fondell, Jeffrey S. Hyams, Jason Shapiro, and Ross M Maltz
- Subjects
Pediatrics ,medicine.medical_specialty ,Crohn's disease ,business.industry ,Crohn disease ,Gastroenterology ,medicine.disease ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Phlegmon ,medicine ,Long term outcomes ,030211 gastroenterology & hepatology ,business ,Abscess - Abstract
Background Limited data are available for long-term outcomes of pediatric patients with abdominal abscess or phlegmon at diagnosis of Crohn disease. Methods We performed a retrospective chart review of such children over a recent 6-year period at 5 pediatric inflammatory bowel diseases. Results Fifty-two patients (mean age 15.9 ± 1.8 years) were reviewed. Thirty-six had an abscess and 27 (75%) required resectional therapy compared to 16 with phlegmon which 10 (63%) requiring surgery. Overall (37/52) 71% had surgery which was performed within 6 months in 32 (86%). Conclusions A similar high surgical rate exists whether pediatric patients with Crohn disease present with abscess or phlegmon.
- Published
- 2020
32. Analysis of Using the Total White Blood Cell Count to Define Severe New-onset Ulcerative Colitis in Children
- Author
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Joel R. Rosh, Susan S. Baker, Alison Marquis, David R. Mack, Anne M. Griffiths, Melvin B. Heyman, Sonia M. Thomas, Brendan M. Boyle, Ashish S. Patel, Steve Steiner, Thomas D. Walters, Joshua D. Noe, Lee A. Denson, Robert Baldassano, David Keljo, Paul A. Rufo, Neal S. LeLeiko, Subra Kugathasan, James Markowitz, Cary G. Sauer, Bradley Saul, and Jeffrey S. Hyams
- Subjects
Male ,medicine.medical_specialty ,Colonoscopy ,Disease ,macromolecular substances ,Blood Sedimentation ,Gastroenterology ,Severity of Illness Index ,Article ,03 medical and health sciences ,Leukocyte Count ,0302 clinical medicine ,030225 pediatrics ,White blood cell ,Internal medicine ,Severity of illness ,medicine ,Humans ,Colitis ,Child ,medicine.diagnostic_test ,business.industry ,medicine.disease ,Ulcerative colitis ,medicine.anatomical_structure ,Erythrocyte sedimentation rate ,Pediatrics, Perinatology and Child Health ,Cohort ,030211 gastroenterology & hepatology ,Colitis, Ulcerative ,Female ,business - Abstract
OBJECTIVES: The aim of this study was to assess common laboratory tests in identifying severe ulcerative colitis in children at diagnosis. METHODS: A cohort of 427 children 4 to 17 years of age newly diagnosed with ulcerative colitis (UC) was prospectively enrolled. Boosted classification trees were used to characterize predictive ability of disease attributes based on clinical disease severity using Pediatric Ulcerative Colitis Activity Index (PUCAI), severe (65+) versus not severe (
- Published
- 2020
33. Using IBD-REFER: A Substitute for Clinical Judgement?
- Author
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Joel R. Rosh and Jeffrey Dueker
- Subjects
medicine.medical_specialty ,business.industry ,Clinical judgement ,Gastroenterology ,Medicine ,business ,Intensive care medicine - Published
- 2020
34. Natural History of Very Early Onset Inflammatory Bowel Disease in North America: A Retrospective Cohort Study
- Author
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Ying Lu, Joel R. Rosh, Helen M. Pappa, Marisa G. Stahl, Joseph A. Galanko, Alka Goyal, Karoline Fiedler, Michael D. Kappelman, Jeffrey S. Hyams, Eileen Crowley, Michael C. Stephens, Jennifer A. Strople, Johan Van Limbergen, Melvin B Heyman, Ross M Maltz, A. Muise, Eric I Benchimol, Joshua D. Noe, Anthony L. Guerrerio, Mark Deneau, Lina Karam, Marian Pfefferkorn, Neal S. Leleiko, Raza Alkhouri, Judith R. Kelsen, Scott B. Snapper, Anne M. Griffiths, Leah Siebold, Dedrick Mouton, Keith J. Benkov, Basavaraj Kerur, Paediatric Gastroenterology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, APH - Digital Health, and APH - Health Behaviors & Chronic Diseases
- Subjects
Pancolitis ,medicine.medical_specialty ,Pediatrics ,medicine.medical_treatment ,Constriction, Pathologic ,Inflammatory bowel disease ,surgery ,Crohn Disease ,Interquartile range ,Epidemiology ,medicine ,Immunology and Allergy ,Humans ,Child ,VEOIBD ,Colectomy ,Retrospective Studies ,Crohn's disease ,business.industry ,Gastroenterology ,Retrospective cohort study ,medicine.disease ,Ulcerative colitis ,Child, Preschool ,Chronic Disease ,North America ,epidemiology ,Colitis, Ulcerative ,medicine.symptom ,Leading Off ,business - Abstract
Background The incidence of very early onset inflammatory bowel disease (VEOIBD) is increasing, yet the phenotype and natural history of VEOIBD are not well described. Methods We performed a retrospective cohort study of patients diagnosed with VEOIBD (6 years of age and younger) between 2008 and 2013 at 25 North American centers. Eligible patients at each center were randomly selected for chart review. We abstracted data at diagnosis and at 1, 3, and 5 years after diagnosis. We compared the clinical features and outcomes with VEOIBD diagnosed younger than 3 years of age with children diagnosed with VEOIBD at age 3 to 6 years. Results The study population included 269 children (105 [39%] Crohn’s disease, 106 [39%] ulcerative colitis, and 58 [22%] IBD unclassified). The median age of diagnosis was 4.2 years (interquartile range 2.9–5.2). Most (94%) Crohn’s disease patients had inflammatory disease behavior (B1). Isolated colitis (L2) was the most common disease location (70% of children diagnosed younger than 3 years vs 43% of children diagnosed 3 years and older; P = 0.10). By the end of follow-up, stricturing/penetrating occurred in 7 (6.6%) children. The risk of any bowel surgery in Crohn’s disease was 3% by 1 year, 12% by 3 years, and 15% by 5 years and did not differ by age at diagnosis. Most ulcerative colitis patients had pancolitis (57% of children diagnosed younger than 3 years vs 45% of children diagnosed 3 years and older; P = 0.18). The risk of colectomy in ulcerative colitis/IBD unclassified was 0% by 1 year, 3% by 3 years, and 14% by 5 years and did not differ by age of diagnosis. Conclusions Very early onset inflammatory bowel disease has a distinct phenotype with predominantly colonic involvement and infrequent stricturing/penetrating disease. The cumulative risk of bowel surgery in children with VEOIBD was approximately 14%–15% by 5 years. These data can be used to provide anticipatory guidance in this emerging patient population.
- Published
- 2020
35. Efficacy of Adalimumab for Treatment of Perianal Fistula in Children with Moderately to Severely Active Crohn’s Disease: Results from IMAgINE 1 and IMAgINE 2
- Author
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Anne M. Robinson, Jen Fue Maa, Frank M. Ruemmele, Joel R. Rosh, Marla Dubinsky, William A. Faubion, Jeffrey S. Hyams, Andreas Lazar, Dan Turner, Gabriela Alperovich, and Samantha Eichner
- Subjects
Male ,Pediatrics ,medicine.medical_specialty ,Adolescent ,Fistula ,Population ,Short Report ,Anti-Inflammatory Agents ,Placebo ,Severity of Illness Index ,law.invention ,Anti-TNF ,03 medical and health sciences ,0302 clinical medicine ,Crohn Disease ,Double-Blind Method ,Randomized controlled trial ,law ,Severity of illness ,Adalimumab ,fistula ,Humans ,Rectal Fistula ,Regeneration ,Medicine ,Child ,education ,Crohn's disease ,education.field_of_study ,Dose-Response Relationship, Drug ,Tumor Necrosis Factor-alpha ,business.industry ,Gastroenterology ,General Medicine ,medicine.disease ,Clinical trial ,Treatment Outcome ,030220 oncology & carcinogenesis ,Female ,030211 gastroenterology & hepatology ,Drug Monitoring ,business ,medicine.drug - Abstract
Background and Aims Adalimumab has been shown to be more effective than placebo in healing fistulae in adults with moderately to severely active Crohn’s disease. The efficacy and safety of adalimumab in healing fistulae in children/adolescents with Crohn’s disease from the 52-week IMAgINE 1 clinical trial, and its open-label extension IMAgINE 2, are reported. Methods Children/adolescents with perianal fistulae at baseline of IMAgINE 1 were assessed for fistula closure and improvement during IMAgINE 1 [Weeks 0–52] and from Week 0 of IMAgINE 2 [Week 52 of IMAgINE 1] through to Week 240 of IMAgINE 2 using non-responder imputation. Results A total of 36 children/adolescents had fistulae at baseline of IMAgINE 1 and were included in the analysis. Fistula closure and improvement were observed in 44.4% and 52.8%, respectively, at Week 12. Rates of closure and improvement were maintained throughout the analysis period to Week 292. No new safety signals were identified. Conclusions In children/adolescents with moderately to severely active, fistulizing Crohn’s disease, adalimumab induced perianal fistula closure and improvement within 12 weeks of treatment, with rates that were sustained for more than 5 years. The safety profile of adalimumab in patients with fistulae at baseline was similar to that of the overall population in IMAgINE 1/2. ClinicalTrials.gov identifiers: IMAgINE 1 (NCT00409682); IMAgINE 2 (NCT00686374).
- Published
- 2018
36. Evolution of Pediatric Inflammatory Bowel Disease Unclassified (IBD-U): Incorporated With Serological and Gene Expression Profiles
- Author
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Joel R. Rosh, Anne M. Griffiths, James Markowitz, Kajari Mondal, Suresh Venkateswaran, Madeline Bertha, Marla Dubinsky, Cary G. Sauer, Shervin Rabizadeh, Joshua D. Noe, Raguraj Chandradevan, Hari K. Somineni, Nusrat Harun, Subra Kugathasan, Scott B. Snapper, Cortney R. Ballengee, Wallace Crandall, Neal S. Leleiko, Lee A. Denson, Thomas D. Walters, Jeffrey S. Hyams, Tatyana Hofmekler, and Mi-Ok Kim
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Adolescent ,Disease ,digestive system ,Inflammatory bowel disease ,Serology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Immunology and Allergy ,Prospective Studies ,Child ,Prospective cohort study ,Irritable bowel syndrome ,business.industry ,Infant, Newborn ,Gastroenterology ,Infant ,Inflammatory Bowel Diseases ,Prognosis ,medicine.disease ,Ulcerative colitis ,digestive system diseases ,Natural history ,030104 developmental biology ,Child, Preschool ,Cohort ,Female ,030211 gastroenterology & hepatology ,Transcriptome ,business ,Biomarkers ,Immunosuppressive Agents ,Follow-Up Studies - Abstract
Background Inflammatory bowel disease (IBD) mainly consists of Crohn's disease (CD) and ulcerative colitis (UC). About 10%-15% of patients with IBD cannot be firmly diagnosed with CD or UC; hence, they are initially diagnosed as inflammatory bowel disease unclassified (IBD-U). Having a firm diagnosis is clearly preferred to guide treatment choices, and better understanding of the nature of IBD-U is required. Methods We performed an analysis of a subset of pediatric subjects from an inception IBD cohort of patients initially enrolled in a prospective multicenter study (the RISK study). Initial diagnosis and 2-year follow-up data from the subjects diagnosed with IBD-U were analyzed. An expert panel verified final diagnosis using predefined criteria as a guide. Serological and disease-relevant ileal and rectal tissue gene expression profiles were investigated. The use and the time to initiate anti-TNFα treatment was analyzed among the outcome groups. Results A total of 1411 subjects were enrolled with initial diagnosis of IBD, and among them, 136 subjects were initially diagnosed as IBD-U at enrollment. And 26% were reclassified as UC and 14% as CD within 2 years of diagnosis, while 60% remained as IBD-U. Of those who were reclassified, there was a 2:1 ratio, UC (n = 35) to CD (n = 19). The molecular and serological features of IBD-U at the end of follow-up were very similar to UC and very different from CD. There was less likelihood of receiving anti-TNFα agents if the diagnosis was IBD-U compared with CD (P < 0.0001). Conclusions In our cohort, 60% of the IBD-U subjects remained as unclassified at 2 years; of those subsequently classified, a higher percentage followed a course more similar to UC. Most of the IBD-U subjects at diagnosis had serological and molecular signatures that are very similar to UC. Although the atypical presentations made the clinician to make an interim diagnosis of IBD-U, results of the molecular and serological factors performed at the time of diagnosis suggests that they were very similar to UC. However, long-term studies are needed to better understand the natural history and molecular characterization of pediatric onset IBD-U. 10.1093/ibd/izy136_video1Video 1.Video 1. Watch now at https://academic.oup.com/ibd/article-lookup/doi/10.1093/ibd/izy136izy136.video15791389938001.
- Published
- 2018
37. IBD LIVE Case Series: Case 9: Do Race and Extraintestinal Manifestations Affect Treatment of Severe Crohn’s Colitis?
- Author
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Walter A. Koltun, David J. Keljo, Alka Goyal, Myron H. Brand, Corey A. Siegel, Miguel Regueiro, Siobhan Proksell, Joel R. Rosh, Raymond K. Cross, Brian Theisen, Samir A. Shah, Kim L. Isaacs, Hans H Herfarth, Peter L. Davis, and Julia B. Greer
- Subjects
Adult ,Male ,medicine.medical_specialty ,Crohn's colitis ,Colonoscopy ,Affect (psychology) ,Inflammatory bowel disease ,Gastroenterology ,03 medical and health sciences ,Race (biology) ,0302 clinical medicine ,Crohn Disease ,X ray computed ,Internal medicine ,Humans ,Immunology and Allergy ,Medicine ,medicine.diagnostic_test ,Tumor Necrosis Factor-alpha ,business.industry ,Crohn disease ,medicine.disease ,Black or African American ,Tomography x ray computed ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,Tomography, X-Ray Computed ,business - Published
- 2018
38. Expediting Drug Development for Pediatric Inflammatory Bowel Disease: A Discussion With Stakeholders
- Author
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Richard B. Colletti, Athos Bousvaros, Shehzad Ahmed Saeed, Andrew E. Mulberg, Eric Zuckerman, Harland S. Winter, Anne M. Robinson, Perdita Taylor-Zapata, Jeffrey S. Hyams, Joachim Musaus, Kerry Jo Lee, and Joel R. Rosh
- Subjects
medicine.medical_specialty ,Expediting ,business.industry ,Gastroenterology ,Pharmacology ,medicine.disease ,Inflammatory bowel disease ,03 medical and health sciences ,0302 clinical medicine ,Drug development ,030225 pediatrics ,Pediatrics, Perinatology and Child Health ,medicine ,030211 gastroenterology & hepatology ,Intensive care medicine ,business - Published
- 2018
39. S3341 When It Is Not Inflammatory Bowel Disease: IBD Mimics Presented at IBD Live
- Author
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Colleen R. Kelly, Joel R. Rosh, Hans H Herfarth, Andrew R. Watson, Abbas Rupawala, L. Campbell Levy, Raymond K. Cross, Badr F. Al Bawardy, Francis A. Farraye, Kofi Clarke, Tanya Bruckel, Jill Gaidos, Erin Forster, Sean Fine, Jana G. Hashash, Alka Goyal, Jeffrey Dueker, Mark Lazarev, Miguel Regueiro, Myron H. Brand, Chris Ward, John S. Hanson, Corey A. Siegel, Steven D. Wexner, Samir A. Shah, and Benjamin L. Cohen
- Subjects
medicine.medical_specialty ,Hepatology ,business.industry ,Internal medicine ,Gastroenterology ,medicine ,medicine.disease ,business ,Inflammatory bowel disease - Published
- 2021
40. Subcutaneous Golimumab in Pediatric Ulcerative Colitis
- Author
-
Geneviève Veereman, Richard Strauss, Anne M. Griffiths, Daphne Chan, Omoniyi J. Adedokun, Dan Turner, Lakshmi Padgett, Jeffrey S. Hyams, Melvin B. Heyman, Ghassan Wahbeh, Joel R. Rosh, Clinical sciences, and Growth and Development
- Subjects
Male ,medicine.medical_specialty ,Pancolitis ,Adolescent ,Injections, Subcutaneous ,Population ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Pharmacokinetics ,Refractory ,Interquartile range ,Internal medicine ,medicine ,Humans ,Immunology and Allergy ,Tissue Distribution ,Child ,education ,Adverse effect ,education.field_of_study ,business.industry ,Remission Induction ,Antibodies, Monoclonal ,Golimumab ,Clinical trial ,Treatment Outcome ,Child, Preschool ,030220 oncology & carcinogenesis ,Colitis, Ulcerative ,Female ,030211 gastroenterology & hepatology ,medicine.symptom ,business ,Follow-Up Studies ,medicine.drug - Abstract
BACKGROUND: Current treatments for pediatric ulcerative colitis (UC) are limited. We evaluated the pharmacokinetics and clinical benefits of subcutaneous golimumab, an anti-tumor necrosis factor agent, in moderately-to-severely active pediatric patients with UC refractory to conventional therapy. METHODS: We report a multicenter, open-label study of golimumab with a pharmacokinetics phase (week 0-14). Patients had moderately-to-severely active UC and were naive to anti-tumor necrosis factor treatment. At weeks 0 and 2, patients received golimumab induction dosed by weight (
- Published
- 2017
41. IBD LIVE Series—Case 8
- Author
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Joel R. Rosh, Heba Iskandar, Julia B. Greer, David J. Keljo, David G. Binion, Francis A. Farraye, Andrew Tinsley, Walter A. Koltun, Alyssa M. Krasinskas, Miguel Regueiro, Corey A. Siegel, L. Campbell Levy, Kim L. Isaacs, and Hans H Herfarth
- Subjects
Adult ,medicine.medical_specialty ,Drug Resistance ,MEDLINE ,Drug resistance ,Esophageal Diseases ,Inflammatory bowel disease ,Young Adult ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Crohn Disease ,Refractory ,Humans ,Immunology and Allergy ,Medicine ,Hidradenitis suppurativa ,Young adult ,Crohn's disease ,business.industry ,Gastroenterology ,Treatment options ,Prognosis ,medicine.disease ,Dermatology ,Hidradenitis Suppurativa ,Research Design ,Female ,030211 gastroenterology & hepatology ,business ,Immunosuppressive Agents - Published
- 2017
42. Communicating the benefits and risks of inflammatory bowel disease therapy to patients and families
- Author
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Joel R. Rosh and Joseph A. Picoraro
- Subjects
medicine.medical_specialty ,Decision Making ,MEDLINE ,Risk Assessment ,Inflammatory bowel disease ,Experiential learning ,03 medical and health sciences ,0302 clinical medicine ,Crohn Disease ,Professional-Family Relations ,Informed consent ,030225 pediatrics ,Humans ,Medicine ,Patient participation ,Child ,Intensive care medicine ,Physician-Patient Relations ,Informed Consent ,business.industry ,Communication ,Lived experience ,Patient Preference ,medicine.disease ,Combined Modality Therapy ,Harm ,Pediatrics, Perinatology and Child Health ,Colitis, Ulcerative ,030211 gastroenterology & hepatology ,Patient Participation ,business ,Risk assessment - Abstract
Purpose of review Treatment options for inflammatory bowel disease (IBD) have rapidly expanded as the treatment paradigm has shifted from controlling symptoms to reducing lifetime inflammatory burden. Families are confronted with the actual and perceived risks of this ever-expanding array of choices. We aim to review the shared decision-making process in pediatric IBD to ensure an optimal therapeutic plan for the child and their family. Recent findings Mucosal healing is a critical treatment target in pediatric IBD but it may not coincide with clinical symptoms. Evidence-based therapies carry important risks, some of which may be less severe than previously suspected, and a family's understanding of these risks plays a crucial role in how they make health decisions. To form an effective shared therapeutic plan, the physician must incorporate an understanding of the values of both the child and family along with their lived experience of illness. Summary To limit harm and promote health in pediatric IBD, the physician must communicate collaboratively with the child and their family to form mutually understood goals of care - both subjective experiential and objective biological - and appreciate actual and perceived risks of treatment options to effectively educate families and navigate toward the best treatment choices. VIDEO ABSTRACT.
- Published
- 2017
43. MACHINE LEARNING FOR CROHN’S DISEASE PHENOTYPE MODELING USING BIOPSY IMAGES
- Author
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Scott B. Snapper, Joel R. Rosh, Shervin Rabizadeh, Ashish S. Patel, Christopher A. Moskaluk, Anne M. Griffiths, Stanley N. Cohen, Erin Bonkowski, Maria Oliva-Hemker, Joshua D. Noe, Dedrick E. Moulton, Richard Kellermayer, Jeffrey S. Hyams, Barbara S. Kirschner, Susan S. Baker, David R. Mack, David Ziring, Lee A. Denson, Sandra C. Kim, Ajay S. Gulati, Lubaina Ehsan, Anthony R. Otley, Subra Kugathasan, Thomas D. Walters, Jennifer L. Dotson, Marian D. Pfefferkorn, Jason Shapiro, Robert N. Baldassano, Saurav Sengupta, Stephen L. Guthery, James Markowitz, Melvin B. Heyman, and Sana Syed
- Subjects
Crohn's disease ,Pathology ,medicine.medical_specialty ,Hepatology ,medicine.diagnostic_test ,business.industry ,Biopsy ,Gastroenterology ,Medicine ,Immunology and Allergy ,business ,medicine.disease ,Phenotype - Abstract
Background Predicting Crohn’s disease (CD) phenotype development has proven challenging due to difficulties in biopsy image interpretation of histologically similar yet biologically distinct phenotypes. At initial diagnosis, mostly CD patients are classified as B1 (inflammatory behavior), they typically either retain B1 phenotype or develop more complicated B2 (stricturing), B3 (internal penetrating), or B2/B3 phenotypes (defined by Montreal Classification). Prediction of phenotype development based on baseline biopsies can radically improve our clinical care by altering disease management. Biopsy-based image analysis via Convolutional Neural Networks (CNNs) has been successful in cancer detection, but investigation into its utility for CD phenotypes is lacking. We applied a machine learning CNN model to classify CD phenotypes and histologically normal ileal controls. Methods Baseline hematoxylin & eosin (H&E) stained ileal biopsy slides were obtained from the Cincinnati Children’s Hospital Medical Center’s RISK validation sub cohort. At University of Virginia, biopsy slides were digitized, and a ResNet101 CNN model was trained. High resolution images were patched into 1000x1000 pixels with a 50% overlap and then resized to 256x256 pixels for training (80-20 split was kept between training and testing sets to ensure same patient patches were not mixed). Gradient Weighted Activating Mappings (GradCAMs) were used to visualize the model’s decision making process. Results We initially trained the model for CD vs. controls where it achieved 97% accuracy in detecting controls. We further trained it for classifying CD phenotypes (n=16 B1, n=16 B2, n=4 B3, n=13 B2/B3; phenotype decision at 5 year). It displayed a higher accuracy in detecting B2 (85%) while there were overlaps in the detection of other phenotypes (Figure 1). For B2, Grad-CAM heatmaps highlighted central pink areas within the lamina propria as the model’s regions of interests which were present when other phenotypes were misclassified as B2 (Figure 2). Conclusions: Here we highlight the potential utility of a machine learning image analysis model for describing CD phenotypes using H&E stained biopsies. Previous studies have shown B2 to be associated with increased activation for extracellular matrix genes (connective tissue component). Our GradCAM results support this finding as the pink central areas utilized by the model for classifying B2 could be connective tissue. Further confirmation via molecular phenotyping including Sirius Red immunohistochemistry is underway. Our work supports prediction of CD phenotypes using baseline biopsies at diagnosis and has potential to influence individualized care for children with CD.
- Published
- 2021
44. 423 TARGETED ASSESSMENT OF MUCOSAL IMMUNE GENE EXPRESSION PREDICTS CLINICAL OUTCOMES IN CHILDREN WITH ULCERATIVE COLITIS
- Author
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Robert N. Baldassano, Brendan M. Boyle, Yael Haberman, Joelynn Dailey, David R. Mack, Sejal R. Fox, Thomas D. Walters, Michael J. Rosen, Anne M. Griffiths, Cary G. Sauer, James Markowitz, Sapana Shah, Ashish S. Patel, Kathryn Clarkston, Subra Kugathasan, Joel R. Rosh, Lee A. Denson, Rebekah Karns, Marian D. Pfefferkorn, Neal S. Leleiko, and Jeffrey S. Hyams
- Subjects
Hepatology ,Expression (architecture) ,business.industry ,Immunology ,Gastroenterology ,Medicine ,business ,medicine.disease ,Immune gene ,Ulcerative colitis - Published
- 2021
45. Sa469 PERFORMANCE OF THE SHORT PEDIATRIC CROHN'S DISEASE ACTIVITY INDEX (SPCDAI) AS A CLINICAL EFFECTIVENESS ENDPOINT
- Author
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Lilianne Kim, Laurie S. Conklin, Dan Turner, Richard Strauss, Stanley A. Cohen, Anne M. Griffiths, Richard B. Colletti, Joel R. Rosh, Jeffrey S. Hyams, and Michael D. Kappelman
- Subjects
medicine.medical_specialty ,Hepatology ,Pediatric Crohn's disease ,business.industry ,Clinical effectiveness ,Internal medicine ,Gastroenterology ,Medicine ,Activity index ,business - Published
- 2021
46. 180 CLINICAL CHARACTERISTICS, CLINICAL RESPONSE, AND CLINICAL REMISSION STATUS IN ADULTS TREATED WITH USTEKINUMAB IN THE PHASE 3 UNITI STUDIES AT WEEK 6 AND WEEK 44 BY AGE AT CROHN'S DISEASE ONSET
- Author
-
Sheri Volger, Jeffrey S. Hyams, Stanley A. Cohen, Anne M. Griffiths, Dan Turner, Ye Miao, Richard Strauss, and Joel R. Rosh
- Subjects
medicine.medical_specialty ,Crohn's disease ,Hepatology ,business.industry ,Internal medicine ,Ustekinumab ,Gastroenterology ,medicine ,business ,medicine.disease ,medicine.drug - Published
- 2021
47. Successful Closure of the Tip of the 'J' Fistula of the Ileal Pouch With Double Over-the-Scope Clips
- Author
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Yaniuska Lescaille, Ravi P. Kiran, Joel R. Rosh, and Bo Shen
- Subjects
medicine.medical_specialty ,Fistula ,medicine.medical_treatment ,Case Report ,Anastomosis ,Familial adenomatous polyposis ,03 medical and health sciences ,0302 clinical medicine ,stomatognathic system ,Suture (anatomy) ,medicine ,CLIPS ,Colectomy ,computer.programming_language ,business.industry ,Endoscopy ,General Medicine ,medicine.disease ,Ulcerative colitis ,Surgery ,stomatognathic diseases ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,Pouch ,business ,computer - Abstract
Ileal pouch-anal anastomosis is the surgical procedure of choice for patients who require colectomy for complicated ulcerative colitis with or without associated dysplasia and familial adenomatous polyposis. Leaks from the suture lines or anastomosis can lead to pouch failure. Treatment options have been radiographic drainage and surgical intervention. Endoscopic therapy has emerged a viable nonsurgical treatment option for some of the complications associated with J-pouch surgery. Here, we present a case of endoscopic management of a leak from the tip of the J-pouch with sequential application of 2 over-the-scope clips.
- Published
- 2021
48. Pediatric Inflammatory Bowel Disease
- Author
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Maire A. Conrad and Joel R. Rosh
- Subjects
medicine.medical_specialty ,Adolescent ,Colonoscopy ,Treatment goals ,Gastroenterology ,Inflammatory bowel disease ,Diagnosis, Differential ,03 medical and health sciences ,0302 clinical medicine ,Quality of life ,Internal medicine ,medicine ,Humans ,Immunologic Factors ,Child ,Glucocorticoids ,Gastrointestinal tract ,medicine.diagnostic_test ,Crohn disease ,Esophagogastroduodenoscopy ,business.industry ,Disease Management ,Inflammatory Bowel Diseases ,medicine.disease ,Ulcerative colitis ,digestive system diseases ,030220 oncology & carcinogenesis ,Pediatrics, Perinatology and Child Health ,030211 gastroenterology & hepatology ,business - Abstract
Inflammatory bowel disease (IBD), including Crohn disease, ulcerative colitis, and IBD-unspecified, is a chronic immune-mediated condition of the gastrointestinal tract in which the goal of treatment is to induce and maintain durable remission. In pediatrics, there is a wide spectrum of presenting symptoms, but esophagogastroduodenoscopy and colonoscopy are imperative to confirming the diagnosis. Treatment goals include achieving mucosal healing of the gastrointestinal tract, reaching growth potential, limiting medication toxicities, and optimizing quality of life for all patients.
- Published
- 2017
49. IBD LIVE Series—Case 7
- Author
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Benjamin H. Click, Hans H Herfarth, David G. Binion, Julia B. Greer, Samir A. Shah, Joel R. Rosh, Leonard Baidoo, Walter A. Koltun, Miguel Regueiro, Corey A. Siegel, Eva Szigethy, Peter L. Davis, and Douglas J. Hartman
- Subjects
Adult ,Male ,medicine.medical_specialty ,Delivery of Health Care, Integrated ,business.industry ,Mental Disorders ,Anti-Inflammatory Agents ,Gastroenterology ,MEDLINE ,Brain ,Inflammatory Bowel Diseases ,medicine.disease ,Connection (mathematics) ,Integrated care ,Gastrointestinal Tract ,03 medical and health sciences ,0302 clinical medicine ,Humans ,Immunology and Allergy ,Medicine ,030211 gastroenterology & hepatology ,business ,Intensive care medicine ,030217 neurology & neurosurgery ,Irritable bowel syndrome - Published
- 2017
50. Long-term Efficacy and Safety of Adalimumab in Pediatric Patients with Crohnʼs Disease
- Author
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Anne M. Robinson, Frank M. Ruemmele, Roopal Thakkar, Samantha Eichner, Jeffrey S. Hyams, Yao Li, Johanna C. Escher, Nattanan Reilly, Joel R. Rosh, William A. Faubion, Andreas Lazar, Marla Dubinsky, and Pediatrics
- Subjects
Male ,medicine.medical_specialty ,Time Factors ,Adolescent ,Anti-Inflammatory Agents ,Disease ,Time ,law.invention ,Growth velocity ,03 medical and health sciences ,0302 clinical medicine ,Crohn Disease ,Double-Blind Method ,Randomized controlled trial ,Adrenal Cortex Hormones ,law ,Internal medicine ,Adalimumab ,medicine ,open-label extension ,Humans ,Immunology and Allergy ,Adverse effect ,clinical remission ,Crohn's disease ,business.industry ,Gastroenterology ,anti–tumor necrosis factor ,Induction Chemotherapy ,medicine.disease ,Discontinuation ,Surgery ,Treatment Outcome ,linear growth velocity ,030220 oncology & carcinogenesis ,Female ,030211 gastroenterology & hepatology ,Original Clinical Articles ,Linear growth ,business ,medicine.drug - Abstract
Article first published online 26 January 2017. Supplemental Digital Content is Available in the Text, Background: IMAgINE 1 assessed 52-week efficacy and safety of adalimumab in children with moderate to severe Crohn's disease. Long-term efficacy and safety of adalimumab for patients who entered the IMAgINE 2 extension are reported. Methods: Patients who completed IMAgINE 1 could enroll in IMAgINE 2. Endpoints assessed from weeks 0 to 240 of IMAgINE 2 were Pediatric Crohn's Disease Activity Index remission (Pediatric Crohn's Disease Activity Index ≤ 10) and response (Pediatric Crohn's Disease Activity Index decrease ≥15 from IMAgINE 1 baseline) using observed analysis and hybrid nonresponder imputation (hNRI). For hNRI, discontinued patients were imputed as failures unless they transitioned to commercial adalimumab (with study site closure) or adult care, where last observation was carried forward. Corticosteroid-free remission in patients receiving corticosteroids at IMAgINE 1 baseline, discontinuation of immunomodulators (IMMs) in patients receiving IMMs at IMAgINE 2 baseline, and linear growth improvement were reported as observed. Adverse events were assessed for patients receiving ≥1 adalimumab dose in IMAgINE 1 and 2 through January 2015. Results: Of 100 patients enrolled in IMAgINE 2, 41% and 48% achieved remission and response (hNRI) at IMAgINE 2 week 240. Remission rates were maintained by 45% (30/67, hNRI) of patients who entered IMAgINE 2 in remission. At IMAgINE 2 week 240, 63% (12/19) of patients receiving corticosteroids at IMAgINE 1 baseline achieved corticosteroid-free remission and 30% (6/20) of patients receiving IMMs at IMAgINE 2 baseline discontinued IMMs. Adalimumab treatment led to growth velocity normalization. No new safety signals were identified. Conclusions: Efficacy and safety profiles of prolonged adalimumab treatment in children with Crohn's disease were consistent with IMAgINE 1 and adult Crohn's disease adalimumab trials.
- Published
- 2017
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