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Crohn Disease: HELP
Articles from Oregon
Based on 34 articles published since 2009

These are the 34 published articles about Crohn Disease that originated from Oregon during 2009-2019.
+ Citations + Abstracts
Pages: 1 · 2
1 Review Depression and anxiety in patients with Inflammatory Bowel Disease: A systematic review. 2016

Neuendorf, Rachel / Harding, Aubrey / Stello, Noelle / Hanes, Douglas / Wahbeh, Helané. ·Helfgott Research Institute, National College of Natural Medicine, Portland, OR, USA. Electronic address: Neuendorf@gmail.com. · Helfgott Research Institute, National College of Natural Medicine, Portland, OR, USA. · Helfgott Research Institute, National College of Natural Medicine, Portland, OR, USA; Department of Neurology, Oregon Health and Science University, Portland, OR, USA. ·J Psychosom Res · Pubmed #27411754.

ABSTRACT: OBJECTIVE: An increasing number of studies have been conducted to look at anxiety and depression in IBD; however, there is no clear consensus on the prevalence of anxiety and depression in this population. The objective of this systematic review was to compile the existing data on the prevalence of all mood and anxiety disorders in Inflammatory Bowel Disease patients. METHODS: A series of comprehensive literature searches of Medline, Cochrane Library, PsycINFO, CINAHL, Embase, AMED, and ProQuest Dissertations were performed through March 2014. Inclusion criteria included peer-reviewed, published scientific articles that reported a measurement of mood or anxiety among IBD patients. Only studies with adults (≥18years old) and with more than 10 patients were included. Methodological quality was assessed for all included studies. RESULTS: 171 articles were identified with a total of 158,371 participants. Pooled prevalence estimate for anxiety disorders was 20.5% [4.9%, 36.5%] and 35.1% [30.5, 39.7%] for symptoms of anxiety. IBD patients in active disease had higher prevalence of anxiety of 75.6% [65.5%, 85.7%] compared to disease remission. Pooled prevalence of depression disorders was 15.2% [9.9%, 20.5%] and was 21.6% [18.7%, 24.3%] for symptoms of depression. The prevalence of depressive symptoms was higher in Crohn's disease (25.3% [20.7%, 30.0%]) compared to UC, and higher with active disease (40.7% [31.1%, 50.3%]) compared to IBD patients in remission. CONCLUSION: Results from this systematic review indicate that patients with IBD have about a 20% prevalence rate of anxiety and a 15% prevalence rate of depression.

2 Review Family history of inflammatory bowel disease among patients with ulcerative colitis: a systematic review and meta-analysis. 2014

Childers, Ryan E / Eluri, Swathi / Vazquez, Christine / Weise, Rayna Matsuno / Bayless, Theodore M / Hutfless, Susan. ·Division of Gastroenterology, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA. Electronic address: childerr@ohsu.edu. · Department of Medicine, Johns Hopkins University, 601 North Caroline Street, Baltimore, MD 21287, USA. · Division of Gastroenterology & Hepatology, Department of Medicine, Johns Hopkins University, 600N Wolfe St, Baltimore, MD 21287, USA. · Bloomberg School of Public Health, Johns Hopkins University, USA. ·J Crohns Colitis · Pubmed #24974207.

ABSTRACT: BACKGROUND AND AIMS: Despite numerous shared susceptibility loci between Crohn's disease and ulcerative colitis, the prevalence of family history among ulcerative colitis patients is not well-established and considered to be less prevalent. A systemic review and meta-analysis were conducted to estimate the prevalence of family history of inflammatory bowel disease in ulcerative colitis patients, and its effect on disease outcomes. METHODS: PubMED was searched to identify studies reporting the prevalence of family history of inflammatory bowel disease among ulcerative colitis patients. Definitions of family history, study type, and subtypes of family history prevalence were abstracted, as were disease outcomes including age at ulcerative colitis diagnosis, disease location, surgery and extraintestinal manifestations. Pooled prevalence estimates were calculated using random effects models. RESULTS: Seventy-one studies (86,824 patients) were included. The prevalence of a family history of inflammatory bowel disease in ulcerative colitis patients was 12% (95% confidence interval [CI] 11 to 13%; range 0-39%). Family history of ulcerative colitis (9%; 22 studies) was more prevalent than Crohn's disease (2%; 18 studies). Patients younger than 18years of age at time of diagnosis had a greater family history of inflammatory bowel disease (prevalence 15%, 95% CI: 11-20%; 13 studies). There were no differences in disease location, need for surgery, or extraintestinal manifestations among those with a family history, although very few studies reported on these outcomes. CONCLUSIONS: Overall, 12% of ulcerative colitis patients have a family history of inflammatory bowel disease, and were more likely to have a family history of ulcerative colitis than Crohn's disease. Pediatric-onset ulcerative colitis patients were more likely to have a family history of inflammatory bowel disease.

3 Review Surgical management of Crohn's disease. 2013

Lu, Kim C / Hunt, Steven R. ·Division of Gastrointestinal and General Surgery, Department of Surgery, Oregon Health & Science University, Portland, OR 97239, USA. luk@ohsu.edu ·Surg Clin North Am · Pubmed #23177070.

ABSTRACT: Although medical management can control symptoms in a recurring incurable disease, such as Crohn's disease, surgical management is reserved for disease complications or those problems refractory to medical management. In this article, we cover general principles for the surgical management of Crohn's disease, ranging from skin tags, abscesses, fistulae, and stenoses to small bowel and extraintestinal disease.

4 Review Small-bowel endoscopy. 2012

Eisen, G M. ·The Oregon Clinic, Division of Gastroenterology, Oregon Health and Science University, Portland, Oregon 97210, USA. ·Gastrointest Endosc · Pubmed #22898411.

ABSTRACT: -- No abstract --

5 Clinical Trial Effect of secukinumab on clinical and radiographic outcomes in ankylosing spondylitis: 2-year results from the randomised phase III MEASURE 1 study. 2017

Braun, Jürgen / Baraliakos, Xenofon / Deodhar, Atul / Baeten, Dominique / Sieper, Joachim / Emery, Paul / Readie, Aimee / Martin, Ruvie / Mpofu, Shephard / Richards, Hanno B / Anonymous4140890. ·Department of Rheumatology, Rheumazentrum Ruhrgebiet, Ruhr-University Bochum, Herne, Germany. · Division of Arthritis/Rheumatic Diseases (OPO9), Oregon Health & Science University, Portland, Oregon, USA. · Department of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands. · Charité University Medicine Berlin, Berlin, Germany. · Leeds Musculoskeletal Biomedical Research Unit/Institute Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK. · Department of Immunology and Dermatology, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA. · Department of Immunology and Dermatology, Novartis Pharma AG, Basel, Switzerland. ·Ann Rheum Dis · Pubmed #27965257.

ABSTRACT: OBJECTIVE: To evaluate the effect of secukinumab, an interleukin-17A inhibitor, on clinical signs and symptoms and radiographic changes through 2 years in patients with ankylosing spondylitis (AS). METHODS: In the phase III MEASURE 1 study, patients were randomised to receive intravenous secukinumab 10 mg/kg (at baseline, week 2 and week 4) followed by subcutaneous secukinumab 150 mg (intravenous 150 mg; n=125) or 75 mg (intravenous 75 mg; n=124) every four weeks, or matched placebo (n=122). Placebo-treated patients were re-randomised to subcutaneous secukinumab 150 or 75 mg from week 16. Clinical efficacy assessments included Assessment of SpondyloArthritis international Society 20 (ASAS20) response rates through week 104. Radiographic changes at week 104 were assessed using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). RESULTS: 97 (77.6%) and 103 (83.1%) patients in the intravenous 150 mg and intravenous 75 mg groups, respectively, completed week 104. In the full analysis set (intent-to-treat), ASAS20 response rates at week 104 were 73.7% and 68.0% in the intravenous 150 mg and intravenous 75 mg groups, respectively. Among patients with evaluable X-rays who were originally randomised to secukinumab (n=168), mean change in mSASSS from baseline to week 104 was 0.30±2.53. Serious adverse events were reported in 12.2% and 13.4% of patients in the 150 mg and 75 mg groups, respectively. CONCLUSIONS: Secukinumab improved AS signs and symptoms through 2 years of therapy, with no unexpected safety findings. Data from this study suggest a low mean progression of spinal radiographic changes, which will need to be confirmed in longer-term controlled studies. TRIAL REGISTRATION NUMBER: NCT01358175.

6 Clinical Trial Secukinumab, an Interleukin-17A Inhibitor, in Ankylosing Spondylitis. 2015

Baeten, Dominique / Sieper, Joachim / Braun, Jürgen / Baraliakos, Xenofon / Dougados, Maxime / Emery, Paul / Deodhar, Atul / Porter, Brian / Martin, Ruvie / Andersson, Mats / Mpofu, Shephard / Richards, Hanno B / Anonymous270853 / Anonymous280853. ·From the Academic Medical Center, University of Amsterdam, Amsterdam (D.B.) · Charité University Medicine Berlin, Berlin (J.S.), and Rheumazentrum Ruhrgebiet, Herne (J.B., X.B.) - both in Germany · Paris Descartes University and Department of Rheumatology, Hôpital Cochin, Paris (M.D.) · Leeds Musculoskeletal Biomedical Research Unit, Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, United Kingdom (P.E.) · Oregon Health and Science University, Portland (A.D.) · Novartis Pharmaceuticals, East Hanover, NJ (B.P., R.M.) · and Novartis Pharma, Basel, Switzerland (M.A., S.M., H.B.R.). ·N Engl J Med · Pubmed #26699169.

ABSTRACT: BACKGROUND: Secukinumab is an anti-interleukin-17A monoclonal antibody that has been shown to control the symptoms of ankylosing spondylitis in a phase 2 trial. We conducted two phase 3 trials of secukinumab in patients with active ankylosing spondylitis. METHODS: In two double-blind trials, we randomly assigned patients to receive secukinumab or placebo. In MEASURE 1, a total of 371 patients received intravenous secukinumab (10 mg per kilogram of body weight) or matched placebo at weeks 0, 2, and 4, followed by subcutaneous secukinumab (150 mg or 75 mg) or matched placebo every 4 weeks starting at week 8. In MEASURE 2, a total of 219 patients received subcutaneous secukinumab (150 mg or 75 mg) or matched placebo at baseline; at weeks 1, 2, and 3; and every 4 weeks starting at week 4. At week 16, patients in the placebo group were randomly reassigned to subcutaneous secukinumab at a dose of 150 mg or 75 mg. The primary end point was the proportion of patients with at least 20% improvement in Assessment of Spondyloarthritis International Society (ASAS20) response criteria at week 16. RESULTS: In MEASURE 1, the ASAS20 response rates at week 16 were 61%, 60%, and 29% for subcutaneous secukinumab at doses of 150 mg and 75 mg and for placebo, respectively (P<0.001 for both comparisons with placebo); in MEASURE 2, the rates were 61%, 41%, and 28% for subcutaneous secukinumab at doses of 150 mg and 75 mg and for placebo, respectively (P<0.001 for the 150-mg dose and P=0.10 for the 75-mg dose). The significant improvements were sustained through 52 weeks. Infections, including candidiasis, were more common with secukinumab than with placebo during the placebo-controlled period of MEASURE 1. During the entire treatment period, pooled exposure-adjusted incidence rates of grade 3 or 4 neutropenia, candida infections, and Crohn's disease were 0.7, 0.9, and 0.7 cases per 100 patient-years, respectively, in secukinumab-treated patients. CONCLUSIONS: Secukinumab at a subcutaneous dose of 150 mg, with either subcutaneous or intravenous loading, provided significant reductions in the signs and symptoms of ankylosing spondylitis at week 16. Secukinumab at a subcutaneous dose of 75 mg resulted in significant improvement only with a higher intravenous loading dose. (Funded by Novartis Pharma; ClinicalTrials.gov numbers, NCT01358175 and NCT01649375.).

7 Article Metastatic vulvovaginal Crohn disease in the setting of well-controlled intestinal disease. 2018

Woody, Meghan M / Holliday, Alex C / Gavino, Alde Carlo P / McReynolds, Abby / Soldano, Anthony C. ·Department of Dermatology, Oregon Health and Sciences University, Portland, USA. · Virginia Tech Carilion School of Medicine, Roanoke, USA. · Tru-Skin Dermatology, Cedar Park, Texas, USA. · Dell Medical School, University of Texas Southwestern, Austin, USA. ·Cutis · Pubmed #30235375.

ABSTRACT: The cutaneous manifestations of Crohn disease (CD) are varied and include pyoderma gangrenosum, erythema nodosum, and metastatic CD (MCD). The latter is defined as the occurrence of granulomatous lesions at a skin site distant from the gastrointestinal tract. Metastatic CD involving the vulva and perineum is rare and thus often is difficult to diagnose. It may precede, coincide with, or develop after the initial diagnosis of intestinal disease. A variety of clinical presentations have been described, including widespread nonspecific pain and swelling, erythematous papules and plaques, and nonhealing ulcers. The diagnosis often is delayed because of a low index of suspicion brought about by the rarity of the disease and its diverse and confusing manifestations. A skin biopsy usually confirms the diagnosis by revealing noncaseating granulomas in the dermis. Multiple oral and parenteral therapies are available, with surgical intervention reserved for resistant cases. We present a case of vulvovaginal MCD in the setting of well-controlled intestinal disease.

8 Article Diagnosis and management of peristomal pyoderma gangrenosum: A systematic review. 2018

Afifi, Ladan / Sanchez, Isabelle M / Wallace, Matthew M / Braswell, Sara F / Ortega-Loayza, Alex G / Shinkai, Kanade. ·Department of Dermatology, University of California, San Francisco, San Francisco, California. · Department of Dermatology, Virginia Commonwealth University, Richmond, Virginia. · Department of Dermatology, Oregon Health and Science University, Portland, Oregon. · Department of Dermatology, University of California, San Francisco, San Francisco, California. Electronic address: kanade.shinkai@ucsf.edu. ·J Am Acad Dermatol · Pubmed #29288099.

ABSTRACT: BACKGROUND: Peristomal pyoderma gangrenosum (PPG) is an uncommon subtype of pyoderma gangrenosum. PPG is a challenging condition to diagnose and treat; no evidence-based guidelines exist. OBJECTIVE: We sought to identify important clinical features of PPG and effective treatments available for its management. METHODS: A systematic literature review of PPG was performed using PubMed, Medline, and Embase databases. RESULTS: We describe 335 patients with PPG from 79 studies. Clinical features include a painful, rapidly progressing ulcer with undermined, violaceous borders with a history of ostomy leakage and local skin irritation or trauma. Systemic steroids are first-line therapy; infliximab and adalimumab provide concomitant control of active inflammatory bowel disease. Combination local and systemic therapy was commonly used. Wound dressings, vehicle selection, and appropriate ostomy devices to minimize leakage, irritation, and pressure-induced ischemia can improve healing. Distinct from classic ulcerative pyoderma gangrenosum, surgical approaches, such as stoma closure and resection of active inflammatory bowel disease, have an effective role in PPG management. LIMITATIONS: PPG is a rare disease lacking randomized trials or diagnostic guidelines. Treatment duration and follow-up time among studies are variable. CONCLUSIONS: Key clinical characteristics of PPG are highlighted. Several treatments, including a more prominent role for surgical intervention, may be effective for PPG treatment.

9 Article Utility of Fecal Calprotectin in Evaluation of Chronic Gastrointestinal Symptoms in Primary Care. 2018

Ramraj, Ramya / Garcia, Amy / Mosen, David / Waiwaiole, Lisa / Smith, Ning. ·1 Kaiser Permanente Northwest, Portland, OR, USA. · 2 Oregon Health & Science University, Portland, OR, USA. · 3 Kaiser Permanente Center for Health Research, Portland, OR, USA. ·Clin Pediatr (Phila) · Pubmed #29192504.

ABSTRACT: Fecal calprotectin (FC) is a marker of intestinal inflammation. Data are limited on utility of routine FC testing in pediatric primary care. Participants 0 to 18 years old who had an FC test in the years 2010-2014 were retrospectively identified. Those with less than a year of follow-up or a prior diagnosis of inflammatory bowel disease (IBD) were excluded. In all, 84% (689/822) had normal FC; no participant with normal FC was diagnosed with IBD in the subsequent 12 months. Also, 16% (133/822) had elevated FC, and 31% of those (42/133) were diagnosed with IBD. FC values for IBD and non-IBD groups were 1084 µg/g (interquartile range [IQR] = 514.4-2000) and 27.05 µg/g (IQR = 15.6-62.6; P < .001), respectively. Abdominal pain was the primary indication. In this cohort, sensitivity of FC for IBD is 100%, and specificity is 88%. The FC test can be an excellent tool in the primary care setting to exclude IBD and avoid unnecessary referrals and colonoscopies.

10 Article Similar birth-cohort patterns in Crohn's disease and multiple sclerosis. 2018

Sonnenberg, Amnon / Ajdacic-Gross, Vladeta. ·Division of Gastroenterology and Hepatology, Oregon Health & Science University, Portland, OR, USA. · Swiss Multiple Sclerosis Registry (SMSR), Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland. ·Mult Scler · Pubmed #28155575.

ABSTRACT: BACKGROUND: The etiology of Crohn's disease and multiple sclerosis is unknown. Genetic susceptibility and environmental factors are believed to play a role in both diseases. OBJECTIVES: To compare the long-term time trends of the two diseases and thus gain insight about their etiology. METHODS: We analyzed mortality data of Crohn's disease and multiple sclerosis from Canada, England, Italy, the Netherlands, Switzerland, and the United States during the past 60 years. Age-period-cohort (APC) analyses based on logit models served to disentangle the separate influences of age, period, and cohort effects on the overall time trends. RESULTS: The long-term time trends of Crohn's disease and multiple sclerosis have been shaped by strikingly similar birth-cohort patterns. In both diseases alike, mortality increased in all generations born prior to 1910. It peaked among generations born between 1910 and 1930 and then declined in all subsequent generations. Similar birth-cohort patterns of Crohn's disease and multiple sclerosis were found in each country analyzed separately. CONCLUSION: The birth-cohort patterns indicate that the development of Crohn's disease and multiple sclerosis is influenced by exposure to environmental risk factors during an early period of life. These environmental risk factors may be similar or even identical in Crohn's disease and multiple sclerosis.

11 Article Molecular probing of TNF: From identification of therapeutic target to guidance of therapy in inflammatory diseases. 2018

Chu, Cong-Qiu. ·Division of Arthritis and Rheumatic Diseases, Oregon Health & Science University and VA Portland Health Care System, Portland, OR 97239, United States. Electronic address: chuc@ohsu.edu. ·Cytokine · Pubmed #27633266.

ABSTRACT: Therapy by blocking tumor necrosis factor (TNF) activity is highly efficacious and profoundly changed the paradigm of several inflammatory diseases. However, a significant proportion of patients with inflammatory diseases do not respond to TNF inhibitors (TNFi). Prediction of therapeutic response is required for TNFi therapy. Isotope labeled anti-TNF antibodies or TNF receptor have been investigated to localize TNF production at inflammatory tissue in animal models and in patients with inflammatory diseases. The in vivo detection of TNF has been associated with treatment response. Recently, fluorophore labeled anti-TNF antibody in combination with confocal laser endomicroscopy in patients with Crohn's disease yielded more accurate and quantitative in vivo detection of TNF in the diseased mucosa. More importantly, this method demonstrated high therapeutic predication value. Fluorophore labeled TNF binding aptamers in combination with modern imaging technology offers additional tools for in vivo TNF probing.

12 Article American Gastroenterological Association Institute Technical Review on the Management of Crohn's Disease After Surgical Resection. 2017

Regueiro, Miguel / Velayos, Fernando / Greer, Julia B / Bougatsos, Christina / Chou, Roger / Sultan, Shahnaz / Singh, Siddharth. ·Inflammatory Bowel Disease Center and Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. · Division of Gastroenterology, University of California San Francisco, San Francisco, California. · Pacific Northwest Evidence-based Practice Center, Oregon Health & Science University, Portland, Oregon. · Department of Medicine, University of Minnesota and VA Health Care System, Minneapolis, Minnesota. · Divisions of Gastroenterology and Biomedical Informatics, Department of Medicine, University of California, San Diego, La Jolla, California. ·Gastroenterology · Pubmed #27840073.

ABSTRACT: -- No abstract --

13 Article Prognosis of small bowel adenocarcinoma in Crohn's disease compares favourably with de novo small bowel adenocarcinoma. 2017

Wieghard, N / Mongoue-Tchokote, S / Young, J I / Sheppard, B C / Tsikitis, V L. ·Department of Surgery, Oregon Health and Science University, Portland, Oregon, USA. · Knight Cancer Institute, Oregon Health and Science University - Biostatistics Shared Resource, Portland, Oregon, USA. ·Colorectal Dis · Pubmed #27659145.

ABSTRACT: AIM: Limited data exist on Crohn's disease (CD)-associated small bowel adenocarcinoma (SBA). A large-scale retrospective cohort study was conducted comparing the clinical features and outcome of CD-associated SBA and de novo SBA. METHOD: Data for patients with small bowel adenocarcinoma were gathered from the 1992-2010 United States Surveillance, Epidemiology and End Results cancer registry-Medicare linked database. We identified 2123 patients, of whom 179 had CD-associated and 1944 de novo SBA. The main outcome measures were overall survival (OS) and cancer-specific survival (CSS). RESULTS: CD-associated SBA was most commonly located in the ileum (62% vs 31%, P < 0.0001). CD patients were diagnosed at an earlier stage (I/II), compared with de novo SBA (55% vs 32%, P < 0.0001), and were more likely to undergo surgery (81% vs 72%, P = 0.0016). Chemotherapy use was similar (25% vs 21%, P = 0.1886). Patients with CD-associated SBA had better 5-year OS (43% vs 34%, P = 0.0121) but a similar CSS (65% vs 64%, P = 0.77). There was no difference in the OS between the cohorts when stratified by stage. On multivariate analysis, CD was not significantly related to OS [hazard ratio (HR) 0.97, 95% CI: 0.79-1.20, P = 0.7889]. Surgery and the extent of lymphadenectomy improved OS for all SBA patients (HR 0.73, 95% CI: 0.60-0.88, P = 0.001), whereas chemotherapy did not (HR 1.13, 95% CI: 0.99-1.28, P = 0.0665). CONCLUSION: Patients with CD-associated SBA present at an earlier stage than patients with de novo SBA, they receive more surgery but similar rates of chemotherapy, and have similar OS and CSS. The presence of CD does not worsen survival after treatment of SBA.

14 Article Retrospective Binary-Trait Association Test Elucidates Genetic Architecture of Crohn Disease. 2016

Jiang, Duo / Zhong, Sheng / McPeek, Mary Sara. ·Department of Statistics, Oregon State University, Corvallis, OR 97331, USA. · Department of Statistics, University of Chicago, Chicago, IL 60637, USA. · Department of Statistics, University of Chicago, Chicago, IL 60637, USA; Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA. Electronic address: mcpeek@uchicago.edu. ·Am J Hum Genet · Pubmed #26833331.

ABSTRACT: In genetic association testing, failure to properly control for population structure can lead to severely inflated type 1 error and power loss. Meanwhile, adjustment for relevant covariates is often desirable and sometimes necessary to protect against spurious association and to improve power. Many recent methods to account for population structure and covariates are based on linear mixed models (LMMs), which are primarily designed for quantitative traits. For binary traits, however, LMM is a misspecified model and can lead to deteriorated performance. We propose CARAT, a binary-trait association testing approach based on a mixed-effects quasi-likelihood framework, which exploits the dichotomous nature of the trait and achieves computational efficiency through estimating equations. We show in simulation studies that CARAT consistently outperforms existing methods and maintains high power in a wide range of population structure settings and trait models. Furthermore, CARAT is based on a retrospective approach, which is robust to misspecification of the phenotype model. We apply our approach to a genome-wide analysis of Crohn disease, in which we replicate association with 17 previously identified regions. Moreover, our analysis on 5p13.1, an extensively reported region of association, shows evidence for the presence of multiple independent association signals in the region. This example shows how CARAT can leverage known disease risk factors to shed light on the genetic architecture of complex traits.

15 Article Automated and Accurate Estimation of Gene Family Abundance from Shotgun Metagenomes. 2015

Nayfach, Stephen / Bradley, Patrick H / Wyman, Stacia K / Laurent, Timothy J / Williams, Alex / Eisen, Jonathan A / Pollard, Katherine S / Sharpton, Thomas J. ·Gladstone Institute of Cardiovascular Disease, San Francisco, California, United States of America. · Department of Evolution and Ecology, Department of Medical Microbiology and Immunology, UC Davis Genome Center, University of California, Davis, Davis, California, United States of America. · Department of Epidemiology and Biostatistics and Institute for Human Genetics, University of California, San Francisco, San Francisco, California, United States of America. · Department of Microbiology, Department of Statistics, Oregon State University, Corvallis, Oregon, United States of America. ·PLoS Comput Biol · Pubmed #26565399.

ABSTRACT: Shotgun metagenomic DNA sequencing is a widely applicable tool for characterizing the functions that are encoded by microbial communities. Several bioinformatic tools can be used to functionally annotate metagenomes, allowing researchers to draw inferences about the functional potential of the community and to identify putative functional biomarkers. However, little is known about how decisions made during annotation affect the reliability of the results. Here, we use statistical simulations to rigorously assess how to optimize annotation accuracy and speed, given parameters of the input data like read length and library size. We identify best practices in metagenome annotation and use them to guide the development of the Shotgun Metagenome Annotation Pipeline (ShotMAP). ShotMAP is an analytically flexible, end-to-end annotation pipeline that can be implemented either on a local computer or a cloud compute cluster. We use ShotMAP to assess how different annotation databases impact the interpretation of how marine metagenome and metatranscriptome functional capacity changes across seasons. We also apply ShotMAP to data obtained from a clinical microbiome investigation of inflammatory bowel disease. This analysis finds that gut microbiota collected from Crohn's disease patients are functionally distinct from gut microbiota collected from either ulcerative colitis patients or healthy controls, with differential abundance of metabolic pathways related to host-microbiome interactions that may serve as putative biomarkers of disease.

16 Article Trends in the Surgical Management of Crohn's Disease. 2015

Geltzeiler, Cristina B / Hart, Kyle D / Lu, Kim C / Deveney, Karen E / Herzig, Daniel O / Tsikitis, Vassiliki L. ·Department of Surgery, Division of Colorectal Surgery, Oregon Health & Science University, 3181 S.W. Sam Jackson Park Rd., Mail Code L223A, 97239, Portland, OR, USA. · Department of Surgery, Division of Colorectal Surgery, Oregon Health & Science University, 3181 S.W. Sam Jackson Park Rd., Mail Code L223A, 97239, Portland, OR, USA. tsikitis@ohsu.edu. ·J Gastrointest Surg · Pubmed #26286366.

ABSTRACT: INTRODUCTION: Although medical management of Crohn's disease has changed in recent years, it is unclear whether surgical management has altered. We examined rate changes of surgical interventions, stoma constructions, and subset of ileostomy and colostomy constructions. MATERIALS AND METHODS: We reviewed the Nationwide Inpatient Sample database from 1988 to 2011. We examined the number of Crohn's-related operations and stoma constructions, including ileostomies and colostomies; a multivariable logistic regression model was developed. RESULTS: A total of 355,239 Crohn's-related operations were analyzed. Operations increased from 13,955 in 1988 to 17,577 in 2011, p < 0.001. Stoma construction increased from 2493 to 4283, p < 0.001. The subset of ileostomies increased from 1201 to 3169, p < 0.001 while colostomies decreased from 1351 to 1201, p = 0.05. Operation percentages resulting in stoma construction increased from 18 to 24 %, p < 0.001. Weight loss (OR 2.25, 95 % CI 1.88, 2.69) and presence of perianal fistulizing disease (OR 2.91, 95 % CI 2.31, 3.67) were most predictive for requiring stoma construction. CONCLUSIONS: Crohn's-related surgical interventions and stoma constructions have increased. The largest predictors for stoma construction are weight loss and perianal fistulizing disease. As a result, nutrition should be optimized and the early involvement of a multidisciplinary team should be considered.

17 Article Prevalence of Antibodies Against JC Virus in Patients With Refractory Crohn's Disease and Effects of Natalizumab Therapy. 2015

Bellaguarda, Emanuelle / Keyashian, Kian / Pekow, Joel / Rubin, David T / Cohen, Russell D / Sakuraba, Atsushi. ·Inflammatory Bowel Disease Center, The University of Chicago Medicine, Chicago, Illinois. · Division of Gastroenterology and Hepatology, Department of Medicine, Oregon Health and Science University, Portland, Oregon. · Inflammatory Bowel Disease Center, The University of Chicago Medicine, Chicago, Illinois. Electronic address: asakurab@medicine.bsd.uchicago.edu. ·Clin Gastroenterol Hepatol · Pubmed #26001336.

ABSTRACT: BACKGROUND & AIMS: Natalizumab, a humanized antibody against the α4 integrin subunit, effectively induces and maintains remission in patients with Crohn's disease (CD) refractory to conventional treatments. Progressive multifocal leukoencephalopathy is a rare but fatal brain infection caused by John Cunningham (JC) virus and has been associated with natalizumab use. We assessed the prevalence of and risk factors for antibodies to JC virus in serum of patients with refractory CD who were candidates for, or already were receiving, natalizumab. We also assessed the effects of natalizumab treatment of these patients. METHODS: In a retrospective study, we analyzed clinical charts from 191 patients with CD (74 males; mean age, 38.7 y; mean duration of disease, 14.9 y) tested for serum JC virus antibody from December 2012 through May 2014 at 2 medical centers in the United States. We calculated JC virus antibody prevalence and compared the characteristics of patients who tested negative vs those who tested positive, to identify risk factors. We also assessed the rate of subsequent natalizumab use, surgery, and seroconversion during natalizumab therapy. RESULTS: A total of 129 of the patients (67.5%) tested positive for serum JC virus antibody. Multivariate analysis showed that past use of thiopurine was a risk factor for testing positive for JC virus antibody (odds ratio, 7.8; 95% confidence interval, 2.0-30.4; P = .003). Twenty-two of the patients who tested negative for JC virus antibody (35.5%) and 16 of the 129 patients who tested positive (12.4%) had been treated with natalizumab. Cox regression analysis determined that natalizumab use was the only factor associated with avoiding subsequent surgery (hazard ratio, 0.23; 95% confidence interval, 0.06-0.98). Seroconversion (from testing negative to positive for JC virus antibody) occurred in 1 of the 22 patients (4.5%) who initially tested negative during natalizumab therapy. CONCLUSIONS: The prevalence of CD patients exposed to JC virus is comparable with that of the general population. In this retrospective study, prior thiopurine use was associated with an increased risk for testing positive for JC virus antibody. Natalizumab use reduced the risk of subsequent surgery.

18 Article Low Prevalence of Colon Polyps in Chronic Inflammatory Conditions of the Colon. 2015

Sonnenberg, Amnon / Genta, Robert M. ·1] Miraca Life Sciences, Irving, Texas, USA [2] Oregon Health & Science University, Portland, Oregon, USA. · 1] Miraca Life Sciences, Irving, Texas, USA [2] University of Texas Southwestern Medical Center; Dallas, Texas, USA. ·Am J Gastroenterol · Pubmed #25916222.

ABSTRACT: OBJECTIVES: Previous studies have reported a low prevalence of colon polyps in patients with microscopic colitis. The aim of the study was to test whether such inverse associations applied to other inflammatory diseases of the colon. METHODS: In a case-control study among 130,204 patients undergoing colonoscopy for the work-up of diarrhea, we compared the prevalence of colon polyps in a case population of patients with inflammatory bowel disease (IBD), microscopic colitis, histologic signs of active colitis, diverticulitis, or ischemic colitis, and in a control population with normal colon mucosa. Case and control subjects were compared using odds ratios and their 95% confidence intervals adjusted for age and sex. RESULTS: In 11,176 patients with microscopic colitis, the prevalence of hyperplastic polyps, serrated adenomas, and tubular adenomas were all reduced: odds ratios=0.46 (95% confidence intervals=0.43-0.49), 0.24 (0.19-0.30), and 0.35 (0.33-0.38), respectively. In 4,435 patients with IBD, the corresponding values were: 0.18 (0.15-0.21), 0.24 (0.16-0.35), and 0.18 (0.15-0.21), respectively. In 6,501 patients with histologically active colitis, the corresponding values were: 0.58 (0.53-0.63), 0.57 (0.46-0.70), and 0.63 (0.58-0.68), respectively. No such consistent reduction in polyp prevalence was found in patients with diverticulitis or ischemic colitis. CONCLUSIONS: Chronic inflammatory conditions of the colon are associated with a decreased prevalence of colon polyps.

19 Article Strictureplasty for Treatment of Crohn's Disease: an ACS-NSQIP Database Analysis. 2015

Geltzeiler, Cristina B / Young, J Isaac / Diggs, Brian S / Keyashian, Kian / Deveney, Karen / Lu, Kim C / Tsikitis, V Liana / Herzig, Daniel O. ·Department of Surgery, Oregon Health and Science University, 3181 S.W. Sam Jackson Park Rd., Mail Code L223A, Portland, OR, 97239, USA, budde@ohsu.edu. ·J Gastrointest Surg · Pubmed #25617078.

ABSTRACT: INTRODUCTION: Strictureplasty is an alternative to resection for treatment of Crohn's disease (CD) strictures. It preserves bowel length, and specialized centers report favorable outcomes. Strictureplasty rates, however, are thought to be low, and it was recently removed from required cases for colon and rectal surgery residents. We examined operative characteristics, and trends in its use using a large national database. MATERIALS AND METHODS: We examined the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database from 2005 to 2012, identifying patients with CD who underwent strictureplasty. We identified patient characteristics, outcome variables, and trends in utilization of strictureplasty. RESULTS: A total of 9172 patients underwent surgery for CD. Two hundred fifty-six (2.8 %) underwent strictureplasty. Median preoperative albumin was 3.6. Preoperative steroid use and weight loss rates were 39 and 8 %. Rates of wound infection and organ space infection were 11 and 4 %. Rate of reoperation was 6 %. Outcomes did not change significantly over time (all p = NS). The proportion of CD operations that included a strictureplasty decreased from 5.1 to 1.7 % (OR 0.902 with each additional year, 95 % CI (0.852, 0.960), p < 0.001). CONCLUSION: Strictureplasty as treatment for CD is decreasing in the ACS-NSQIP database. Infectious complications and reoperation rates following strictureplasty are low and have not changed over time.

20 Article Significance of the epithelioid granuloma in biopsies of Crohn's colitis. 2014

Turner, Kevin / Genta, Robert M / Lujan, Giovanni / Robiou, Cristian / Sonnenberg, Amnon. ·*Miraca Life Sciences Research Institute, Irving, Texas; and †Department of Medicine, Oregon Health & Sciences University, Portland, Oregon. ·Inflamm Bowel Dis · Pubmed #25208107.

ABSTRACT: BACKGROUND: The relevance of granulomas in biopsy specimens from patients with Crohn's disease is largely unknown. Most previous studies have been performed on small samples and have produced conflicting results. This study was designed to compare the demographic, clinical, and histopathologic characteristics of a large cohort of documented patients with Crohn's disease with and without epithelioid granulomas. METHODS: Data of all patients with Crohn's disease were extracted from a computerized database of 1.3 million subjects who underwent colonoscopy and had their biopsy specimens diagnosed by a single group of gastrointestinal pathologists. The influence of age, gender, patient symptoms, and histopathologic finding on the presence of granuloma was analyzed. RESULTS: There were 10,456 patients with Crohn's disease: 952 (9%) patients harbored granulomas (cases) and 9504 (91%) patients (controls) had none. Cases were significantly younger than controls: 42.4 ± 17.9 versus 48.0 ± 16.4 years (P < 0.0001). Cases presented with more symptoms than controls (odds ratio, 95% confidence interval): diarrhea (2.29, 2.28-2.31), anemia (2.06, 2.02-2.10), vomiting (2.13, 2.07-2.19), abdominal pain (1.75, 1.72-1.78), hematochezia (1.97, 1.94-2.00), and weight loss (3.94, 3.93-3.94). In a multivariate logistic regression analysis, younger age, presence of chronic active colitis, and symptoms of weight loss remained independent statistically significant predictors for the presence of granulomas. CONCLUSIONS: In colonic biopsies from patients with Crohn's disease, granulomas constitute a rare finding. Presence of granulomas is associated with younger patient age, more severe histopathologic expression of the underlying disease, and more clinical symptoms.

21 Article Ubiquitous occurrence of birth-cohort patterns in inflammatory bowel disease. 2014

Sonnenberg, Amnon. ·Portland VA Medical Center and the Oregon Health and Science University, Portland, Oregon, USA. ·Eur J Gastroenterol Hepatol · Pubmed #24987824.

ABSTRACT: BACKGROUND AND AIMS: The aim of the present study was to demonstrate the ubiquitous occurrence of the birth-cohort phenomenon of inflammatory bowel disease among US whites and nonwhites, as well as males and females. METHODS: Mortality from Crohn's disease and ulcerative colitis in the USA between 1950 and 2010 were analyzed to discern underlying birth-cohort patterns affecting both their time trends. Age-standardized cohort mortality ratio was used as a summary statistic to represent the overall mortality associated with consecutive birth-cohorts. RESULTS: The cohort-age contours of Crohn's disease aligned to form one hyperbola with an initial rise between 1865 and 1935 and a subsequent decline. This pattern was confirmed by the time trends of the corresponding standardized cohort mortality ratio values. In ulcerative colitis, the individual cohort-age contours also aligned into one hyperbola that appeared shifted towards earlier generations by about 30 years when compared with Crohn's disease. Similar trends were observed in men and women or whites and nonwhites analyzed separately. CONCLUSION: The birth-cohort patterns indicate that exposure to two separate risk factors must have occurred in both diseases during an early period of life. In the USA, these exposures have changed over historical times similarly in both sexes and different ethnic groups.

22 Article Birth-cohort patterns in Crohn's disease and ulcerative colitis. 2014

Sonnenberg, Amnon. ·Division of Gastroenterology, Portland VA Medical Center, Oregon Health & Science University, Portland, Oregon, USA. ·Eur J Gastroenterol Hepatol · Pubmed #24216571.

ABSTRACT: AIM: To test the long-term time trends of mortality from inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), for the presence of birth-cohort phenomena. METHODS: We analyzed mortality data from the national statistical offices of Canada, England and Wales, Italy, the Netherlands, Switzerland, and the USA for the past 60-80 years. Age-specific rates of death were plotted against the period of death, as period-age contours, and against the period of birth, as cohort-age contours. RESULTS: In all six countries alike, the general time trends of IBD have been shaped by an underlying birth-cohort pattern. This pattern was also observed in the data of CD and UC analyzed separately. UC mortality increased in all generations born during the 19th century. It peaked among generations born shortly before the turn of the century and then decreased in all subsequent generations born throughout the 20th century. Compared with UC, the birth-cohort pattern of CD was delayed by 30-50 years. CONCLUSION: In addition to one risk factor responsible for the general occurrence of IBD and possibly UC alone, there exists at least one additional risk factor responsible for CD. Exposure to both separate risk factors must occur during early life.

23 Article Geographic distributions of microscopic colitis and inflammatory bowel disease in the United States. 2012

Sonnenberg, Amnon / Genta, Robert M. ·Portland VA Medical Center, Portland, Oregon 97239, USA. sonnenbe@ohsu.edu ·Inflamm Bowel Dis · Pubmed #22374913.

ABSTRACT: BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are characterized by similar geographic distributions. We used a large database of pathology reports to analyze the geographic distribution of microscopic colitis (MC) and compare it with those of UC and CD. METHODS: A population of 671,176 individual patients with colonic biopsies was studied stratified by gender and state of residence. The occurrence of each diagnosis MC, UC, or CD, was expressed as proportional rate per 1000 colonoscopies with biopsies from each individual state. RESULTS: UC and CD tended to be common in states in the Northeast or North Central regions of the U.S. and relatively rare among several southern states. MC appeared to follow a somewhat inverse pattern, as it was most common among some states from the Southwest (Colorado, New Mexico, Arizona, Nevada) and other states of southern latitude, such as Florida, Georgia, California, but relatively uncommon among states in the Northeast. The geographic distributions of UC and CD were significantly correlated with each other (R = 0.60 and P = 0.0004). No significant correlation was observed between MC and UC or CD. CONCLUSIONS: The differences in epidemiologic behavior point at a dissimilar set of risk factors that shape the occurrence of MC as opposed to UC or CD.

24 Article Occupational mortality associated with inflammatory bowel disease in the United States 1984-1998. 2012

Sonnenberg, Amnon / Walker, James T. ·Department of Veterans Affairs Medical Center, Portland, Oregon, USA. sonnenbe@ohsu.edu ·Inflamm Bowel Dis · Pubmed #21710539.

ABSTRACT: BACKGROUND: The occurrence of Crohn's disease (CD) and ulcerative colitis (UC) is shaped by environmental influences. Many such environmental risk factors vary potentially with occupational exposure. We used a large national database to study the occupational variation of mortality associated with CD and UC. METHODS: The National Occupational Mortality Surveillance database contains data from the death certificate linked with information about the occupation and industry of each deceased individual. Deaths were grouped by gender, ethnicity, disease type, occupation, and industry. Mortality by occupation and industry were expressed as age-adjusted proportional mortality ratio. RESULTS: A total of 3110 inflammatory bowel disease (IBD) patients were included in the present analysis. IBD mortality was low among blue collar workers and high among white collar workers. It was low among farming occupations, manufacturing occupations, and manual laborers. It was high among secretaries, professionals, sales workers, homemakers, managerial occupations, and teachers. There was a strong correlation between the occupational distribution of CD and UC that applied to men and women alike. The overall distribution among different industries corroborated the patterns observed with respect to the occupational distribution. CONCLUSIONS: The correlations between the occupational distribution of CD and UC support the contention that environmental influences shape the occurrence of both diseases. Such influence must vary by occupation and, to a lesser extent, also by industry. It must be similar for both types of IBD.

25 Article Assessment and management of low bone density in inflammatory bowel disease and performance of professional society guidelines. 2011

Etzel, Jason P / Larson, Meaghan F / Anawalt, Bradley D / Collins, Judith / Dominitz, Jason A. ·Division of Gastroenterology, Department of Medicine, Oregon Health and Science University, Portland, Oregon, USA. ·Inflamm Bowel Dis · Pubmed #21910174.

ABSTRACT: BACKGROUND: Inflammatory bowel disease (IBD) patients have increased prevalence of osteoporosis, leading to guideline recommendations for bone mineral density (BMD) testing. The study aim was to identify predictors of BMD testing and treatment and assess guideline effectiveness to identify IBD patients with osteoporosis. METHODS: Records of all IBD patients at seven medical facilities were reviewed for clinical data and BMD testing from January 1996 through October 2006. RESULTS: A total of 2035 patients had 317 bone density tests performed. Osteopenia was found in 48% of patients, osteoporosis in 26%. Among patients meeting guideline criteria for BMD testing and ≥1 year of follow-up, 23.3% underwent testing. The strongest predictors of testing were menopause (adjusted hazard ratio [AHR] 3.02) and receiving care at a tertiary center (AHR 2.56). Testing rates were low in patients with age ≥60 years, ulcerative colitis, and a history of inpatient IBD treatment. Osteoporotic patients received calcium/vitamin D and bisphosphonates in 59% and 75% of cases, respectively. Osteoporotic males had a 37% rate of hypogonadism. Guideline criteria do not distinguish patients with osteoporosis. The criteria had a sensitivity, specificity, positive predictive value, and negative predictive value of 84%, 23%, 27%, and 81% for osteoporosis in the tested population, respectively. CONCLUSIONS: Osteoporosis is highly prevalent in the IBD population, but BMD testing and osteoporosis treatments are underutilized. Male hypogonadism is common in osteoporotic IBD patients. Guidelines do not identify IBD patients with osteoporosis.