• biologic therapy
• biomarkers
• inflammatory bowel disease
• patient stratification
• personalized medicine
• precision medicine

• crohn’s disease
• differential diagnostic models
• metalloproteinases
• microarray
• robust rank aggregation
• ulcerative colitis

• Crohn disease
• inflammatory bowel disease
• recent advance
• therapeutics
• ulcerative colitis

• Jilin Scientific and Technological Development Program
• National Natural Science Foundation of China
• Jilin University

• Crohn's disease
• biological medicines
• endoscopy
• thiopurines

• Biologics
• Immunomodulators
• Inflammatory bowel disease
• Steroid

• Adalimumab
• Crohn’s disease
• Infliximab
• Tofacitinib
• Ulcerative colitis
• Ustekinumab
• Vedolizumab

• Colitis, Ulcerative/diagnosis
• Colitis, Ulcerative/epidemiology
• Colitis, Ulcerative/therapy
• Consensus
• Crohn Disease
• Humans
• Inflammatory Bowel Diseases/diagnosis
• Inflammatory Bowel Diseases/epidemiology
• Inflammatory Bowel Diseases/therapy
• United Arab Emirates/epidemiology

The landscape of pediatric inflammatory bowel disease is rapidly evolving. The therapeutic advances seen in the adult arena are rapidly being adopted by pediatric gastroenterologists and evaluated in both controlled trials and real-world experience. Though anti-tumor necrosis factor agents have been the primary therapy over the last decade, recently there has been an expansion of therapeutic targets and alternative mechanism of action drugs with a focus on individualized and personalized therapy. By reviewing epidemiology, pathophysiology, and goals of treatment, we hope to frame the discussion of current and novel therapeutics for the pediatric gastroenterologist. As scientific discovery continues to push the envelope in defining our understanding of pediatric inflammatory bowel disease, the current era of therapeutics gives us hope that a cure may be realized soon.

• Child
• Humans
• Inflammatory Bowel Diseases
• Tumor Necrosis Factor-alpha

Cronkhite-Canada syndrome is a rare disease of unknown etiology and the optimal treatment for this syndrome is unknown.

We present the case of a man who at the age of 66.0 years was diagnosed with Cronkhite-Canada syndrome (CCS). In addition to watery diarrhea, alopecia, and a complete loss of toenails and fingernails, the patient had been suffering from dysgeusia and rapid weight loss of more than 10.0 kg within a few months. The patient had recently incurred a distal radius fracture. During the initial endoscopy an extensive polyposis of the stomach and jejunum was found. The diagnosis of CCS was made and after initiation of a steroid therapy his diarrhea improved immediately. A discontinuation of the steroid therapy was not possible and mesalazine (1000 mg t.i.d.) was added to prednisolone (10.0 mg/d). This therapy led to a remission within 6.0 months with weight gain and normalization of serum albumin levels. The prednisolone dose was reduced to 7.5 mg/d. During the following year, the steroids could be further reduced and nails had regrown again. Within three years, all polyps had disappeared and the steroid therapy was finished while the dosage of mesalazine was reduced in a stepwise fashion. Four years later, the mesalazine was stopped and more than 14.0 years after the initial diagnosis the patient is still in complete remission without any treatment.

The optimal treatment for CCS is unknown. In our case, the initial combination therapy of corticosteroids plus mesalazine followed by a mesalazine monotherapy has led to a remarkable long-lasting remission with complete resolution of all intestinal polyps.

• Alopecia
• Cronkhite-Canada syndrome
• Mesalazine
• Non-hereditary polyposis
• Onychodystrophy

• diabetes
• dietary fiber
• metabolic syndrome
• microbiota
• polysaccharide

• Animals
• Bacteria/metabolism
• Dietary Fiber/metabolism
• Digestion
• Fermentation
• Gastrointestinal Microbiome
• Humans
• Intestines/microbiology
• Polysaccharides/metabolism

Crohn’s disease (CD) is a lifelong illness with substantial morbidity, although new therapies and treatment paradigms have been developed. We provide guidance for treatment of ambulatory patients with mild to severe active luminal CD.

We performed a systematic review to identify published studies of the management of CD. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Statements were developed through an iterative online platform and then finalized and voted on by a group of specialists.

The consensus includes 41 statements focused on 6 main drug classes: antibiotics, 5-aminosalicylate, corticosteroids, immunosuppressants, biologic therapies, and other therapies. The group suggested against the use of antibiotics or 5-aminosalicylate as induction or maintenance therapies. Corticosteroid therapies (including budesonide) can be used as induction, but not maintenance therapies. Among immunosuppressants, thiopurines should not be used for induction, but can be used for maintenance therapy for selected low-risk patients. Parenteral methotrexate was proposed for induction and maintenance therapy in patients with corticosteroid-dependent CD. Biologic agents, including tumor necrosis factor antagonists, vedolizumab, and ustekinumab, were recommended for patients failed by conventional induction therapies and as maintenance therapy. The consensus group was unable to clearly define the role of concomitant immunosuppressant therapies in initiation of treatment with a biologic agent.

Optimal management of CD requires careful patient assessment, acknowledgement of patient preferences, evidence-based use of existing therapies, and thorough assessment to define treatment success.

• 5-ASA
• Guidance
• Mucosal Healing
• TNF

• Consensus
• Crohn’s disease
• Evidence
• Guidelines
• Inflammatory bowel disease
• Ulcerative colitis

• Colitis, Ulcerative/diagnosis
• Colitis, Ulcerative/epidemiology
• Colitis, Ulcerative/physiopathology
• Colitis, Ulcerative/therapy
• Consensus
• Crohn Disease/diagnosis
• Crohn Disease/epidemiology
• Crohn Disease/physiopathology
• Crohn Disease/therapy
• Early Detection of Cancer
• Humans
• Japan
• Proctocolectomy, Restorative
• Risk Factors

• Age of Onset
• Anti-Bacterial Agents/therapeutic use
• Biomarkers/blood
• Child
• Endoscopy, Gastrointestinal/methods
• Evidence-Based Medicine
• Gastrointestinal Agents/therapeutic use
• Genetic Predisposition to Disease
• Humans
• Immunosuppressive Agents/therapeutic use
• Inflammatory Bowel Diseases/diagnosis
• Inflammatory Bowel Diseases/drug therapy
• Inflammatory Bowel Diseases/physiopathology

• UL1 TR001425 NCATS NIH HHS

Crohn's disease (CD) is a chronic, progressive, and disabling inflammatory bowel disease (IBD) with an uncertain etiopathogenesis. CD can involve any site of the gastrointestinal tract from the mouth to the anus, and is associated with serious complications, such as bowel strictures, perforations, and fistula formation. The incidence and prevalence rates of CD in Korea are still lower compared with those in Western countries, but they have been rapidly increasing during the recent decades. Although there are no definitive curative modalities for CD, various medical and surgical therapies have been applied for the treatment of this disease. Concerning CD management, there have been substantial discrepancies among clinicians according to their personal experience and preference. To suggest recommendable approaches to the diverse problems of CD and to minimize the variations in treatment among physicians, guidelines for the management of CD were first published in 2012 by the IBD Study Group of the Korean Association for the Study of Intestinal Diseases. These are the revised guidelines based on updated evidence, accumulated since 2012. These guidelines were developed by using mainly adaptation methods, and encompass induction and maintenance treatment of CD, treatment based on disease location, treatment of CD complications, including stricture and fistula, surgical treatment, and prevention of postoperative recurrence. These are the second Korean guidelines for the management of CD and will be continuously revised as new evidence is collected.

• Crohn disease
• Guideline
• Management

• clinical study
• in vivo dissolution
• local gastrointestinal concentration
• mesalamine
• modified release
• pharmacokinetics

• Crohn's disease
• DAI
• Indomethacin
• Naltrexone
• Sulfasalazine

• Animals
• Crohn Disease/chemically induced
• Crohn Disease/drug therapy
• Crohn Disease/pathology
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drug Therapy, Combination
• Ileum/drug effects
• Ileum/pathology
• Indomethacin
• Intestinal Mucosa/drug effects
• Intestinal Mucosa/pathology
• Male
• Naltrexone/pharmacology
• Naltrexone/therapeutic use
• Narcotic Antagonists/pharmacology
• Narcotic Antagonists/therapeutic use
• Rats
• Sulfasalazine/pharmacology
• Sulfasalazine/therapeutic use
• Treatment Outcome

• Aminosalicylic Acids/therapeutic use
• Anti-Inflammatory Agents, Non-Steroidal/therapeutic use
• Budesonide/therapeutic use
• Crohn Disease/drug therapy
• Delayed-Action Preparations
• Gastrointestinal Agents/therapeutic use
• Humans
• Induction Chemotherapy/methods
• Mesalamine/therapeutic use
• Randomized Controlled Trials as Topic
• Sulfasalazine/therapeutic use

• Crohn
• IBD
• consensus
• definition
• diagnosis
• epidemiology
• gastroenterology
• guidelines
• incidence
• investigation

Oral mesalazine (also known as mesalamine) is a 5-aminosalicylic acid compound used in the treatment of mild to moderate ulcerative colitis, with high rates of efficacy in induction and maintenance of remission. The therapeutic effect of mesalazine occurs topically at the site of diseased colonic mucosa. A myriad of oral mesalazine preparations have been formulated with various drug delivery methods to minimize systemic absorption and maximise drug availability at the inflamed colonic epithelium. It remains unclear whether different oral mesalazine formulations are bioequivalent. This review aims to evaluate the differences between mesalazine formulations based on the currently available literature and explore factors which may influence the selection of one agent above another.

• Colitis
• Ulcerative
• Drug delivery systems
• Mesalamine
• Sulfasalazine
• Therapeutic equivalency

• Administration, Oral
• Adrenal Cortex Hormones/therapeutic use
• Anti-Inflammatory Agents/administration & dosage
• Anti-Inflammatory Agents/adverse effects
• Anti-Inflammatory Agents, Non-Steroidal/therapeutic use
• Budesonide/administration & dosage
• Budesonide/adverse effects
• Crohn Disease/drug therapy
• Humans
• Induction Chemotherapy/methods
• Mesalamine/therapeutic use
• Randomized Controlled Trials as Topic

The goals of treatment for active Crohn’s disease (CD) are to achieve clinical remission and improve quality of life. Conventional therapeutics for moderate-to-severe CD include 5-aminosalicylic acid, corticosteroids, purine analogs, azathioprine, and 6-mercaptopurine. Patients who fail to respond to conventional therapy are treated with tumor necrosis factor (TNF)-α inhibitors such as infliximab and adalimumab, but their efficacy is limited due to primary nonresponse or loss of response. It is suggested that this requires switch to another TNF-α inhibitor, a combination therapy with TNF-α blockade plus azathioprine, or granulocyte and monocyte adsorptive apheresis, and that other therapeutic options having different mechanisms of action, such as blockade of inflammatory cytokines or adhesion molecules, are needed. Natalizumab and vedolizumab are neutralizing antibodies directed against integrin α4 and α4β7, respectively. Ustekinumab is a neutralizing antibody directed against the receptors for interleukin-12 and interleukin-23. Here, we provide an overview of therapeutic treatments that are effective and currently available for CD patients, as well as some that likely will be available in the near future. We also discuss the advantages of managing patients with refractory CD using a combination of TNF-α inhibitors plus azathioprine or intensive monocyte adsorptive apheresis.

• adalimumab
• combination therapy
• complete remission
• granulocyte and monocyte adsorptive apheresis

Distinction between Crohn’s disease of the colon-rectum and ulcerative colitis or inflammatory bowel disease (IBD) type unclassified can be of pivotal importance for a tailored clinical management, as each entity often involves specific therapeutic strategies and prognosis. Nonetheless, no gold standard is available and the uncertainty of diagnosis may frequently lead to misclassification or repeated examinations. Hence, we have performed a literature search to address the problem of differential diagnosis in IBD colitis, revised current and emerging diagnostic tools and refined disease classification strategies. Nowadays, the differential diagnosis is an untangled issue, and the proper diagnosis cannot be reached in up to 10% of patients presenting with IBD colitis. This topic is receiving emerging attention, as medical therapies, surgical approaches and leading prognostic outcomes require more and more disease-specific strategies in IBD patients. The optimization of standard diagnostic approaches based on clinical features, biomarkers, radiology, endoscopy and histopathology appears to provide only marginal benefits. Conversely, emerging diagnostic techniques in the field of gastrointestinal endoscopy, molecular pathology, genetics, epigenetics, metabolomics and proteomics have already shown promising results. Novel advanced endoscopic imaging techniques and biomarkers can shed new light for the differential diagnosis of IBD, better reflecting diverse disease behaviors based on specific pathogenic pathways.

• Crohn’s disease
• Ulcerative colitis
• Inflammatory bowel disease unclassified
• Advanced endoscopic imaging
• Biomarkers
• Histopathology

• Colitis, Ulcerative/diagnosis
• Colitis, Ulcerative/therapy
• Crohn Disease/diagnosis
• Crohn Disease/therapy
• Diagnosis, Differential
• Diagnostic Techniques, Digestive System
• Humans
• Predictive Value of Tests
• Prognosis

• 5-aminosalicylic acid
• Crohn disease
• antitumor necrosis factor-alpha
• budesonide
• immunomodulators

Although the chemopreventive effect of 5-aminosalicylates on patients with ulcerative colitis has been extensively studied, the results remain controversial. This updated review included more recent studies and evaluated the effectiveness of 5-aminosalicylates use on colorectal neoplasia prevention in patients with ulcerative colitis.

Up to July 2013, we searched Medline, Embase, Web of Science, Cochrane CENTRAL, and SinoMed of China for all relevant observational studies (case-control and cohort) about the effect of 5-aminosalicylates on the risk of colorectal neoplasia among patients with ulcerative colitis. The Newcastle-Ottawa Scale was used to assess the quality of studies. Adjusted odds ratios (ORs) were extracted from each study. A random-effects model was used to generate pooled ORs and 95% confidence intervals (95%CI). Publication bias and heterogeneity were assessed.

Seventeen studies containing 1,508 cases of colorectal neoplasia and a total of 20,193 subjects published from 1994 to 2012 were analyzed. 5-aminosalicylates use was associated with a reduced risk of colorectal neoplasia in patients with ulcerative colitis (OR 0.63; 95%CI 0.48–0.84). Pooled OR of a higher average daily dose of 5-aminosalicylates (sulfasalazine ≥ 2.0 g/d, mesalamine ≥ 1.2 g/d) was 0.51 [0.35–0.75]. Pooled OR of 5-aminosalicylates use in patients with extensive ulcerative colitis was 1.00 [0.53–1.89].

Our pooled results indicated that 5-aminosalicylates use was associated with a reduced risk of colorectal neoplasia in patients with ulcerative colitis, especially in the cases with a higher average daily dose of 5-aminosalicylates use. However, the chemopreventive benefit of 5-aminosalicylates use in patients with extensive ulcerative colitis was limited.

• Colitis, Ulcerative/complications
• Colorectal Neoplasms/complications
• Colorectal Neoplasms/prevention & control
• Humans
• Mesalamine/pharmacology
• Risk

• adalimumab
• azathioprine
• certolizumab pegol
• crohn’s disease
• inflammatory bowel disease
• infliximab
• mercaptopurine
• methotrexate
• natalizumab
• ulcerative colitis

• Antibodies, Anti-Idiotypic/adverse effects
• Antibodies, Anti-Idiotypic/therapeutic use
• Azathioprine/adverse effects
• Azathioprine/therapeutic use
• Biological Products/adverse effects
• Biological Products/therapeutic use
• Humans
• Immunosuppressive Agents/adverse effects
• Immunosuppressive Agents/therapeutic use
• Inflammatory Bowel Diseases/drug therapy
• Integrins/antagonists & inhibitors
• Mercaptopurine/adverse effects
• Mercaptopurine/therapeutic use
• Methotrexate/adverse effects
• Methotrexate/therapeutic use
• Risk Assessment
• Tumor Necrosis Factor-alpha/antagonists & inhibitors
• Withholding Treatment

• R01 HS018975 AHRQ HHS
• T32 DK067872 NIDDK NIH HHS
• R01 HS-018975 AHRQ HHS
• T32 DK-067872 NIDDK NIH HHS

• Animals
• Colitis, Ulcerative/therapy
• Crohn Disease/therapy
• Humans
• Inflammatory Bowel Diseases/therapy
• Ovum/transplantation
• Randomized Controlled Trials as Topic
• Remission Induction/methods
• Therapy with Helminths/adverse effects
• Therapy with Helminths/methods
• Trichuris

• AE
• C-reactive protein
• CD
• CDAI
• CI
• CRP
• Crohn's disease
• Crohn's disease activity index
• ESR
• IBD
• Inflammatory Bowel Disease
• Maintenance Therapy
• Microbiota
• OR
• PP
• adverse event
• confidence interval
• erythrocyte sedimentation rate
• inflammatory bowel disease
• mITT
• modified intent-to-treat
• odds ratio
• per-protocol

• Crohn’s Disease
• abdominal pain
• inflammatory bowel disease (IBD)
• irritable bowel syndrome (IBS)
• narcotic bowel syndrome
• small intestinal bacterial overgrowth
• ulcerative colitis
• visceral hypersensitivity

• Crohn’s disease
• adherence
• anti-TNFα agents
• certolizumab pegol

• Crohn Disease/drug therapy
• Granulocyte-Macrophage Colony-Stimulating Factor/adverse effects
• Granulocyte-Macrophage Colony-Stimulating Factor/therapeutic use
• Humans
• Immunologic Factors/adverse effects
• Immunologic Factors/therapeutic use
• Induction Chemotherapy/methods
• Randomized Controlled Trials as Topic
• Recombinant Proteins/adverse effects
• Recombinant Proteins/therapeutic use

• Canadian Institutes of Health Research

During the last decade a large number of biological agents against tumor necrosis factor-α (TNF-α), as well as many biochemical substances and molecules specifically for the medical treatment of patients with inflammatory bowel disease (IBD), have been developed. This enormous progress was a consequence of the significant advances in biotechnology along with the increased knowledge of the underlying pathophysiological mechanisms involved in the pathogenesis of IBD. However, conventional therapies remain the cornerstone of treatment for most patients. During recent years conventional and biologic IBD therapies have been optimized. Newer mesalazine formulations with a reduced pill size and only one dose per day demonstrate similar efficacy to older formulations. New corticosteroids retain the efficacy of older corticosteroids while exhibiting a higher safety profile. The role of antibiotics and probiotics has been further clarified. Significant progress in understanding thiopurine metabolism has improved the effective dose along with adjunctive therapies. Quite a large number of substances and therapies, including biologic agents other than TNF-α inhibitors, unfractionated or low-molecular-weight heparin, omega-3 polyunsaturated fatty acids, microbes and microbial products, leukocytapheresis, and other substances under investigation, could offer important benefits to our patients. In this paper we review the established and emerging therapeutic strategies in patients with Crohn’s disease and ulcerative colitis.

• Crohn’s disease
• antibiotics
• biologic agents
• immunosuppressives
• inflammatory bowel disease
• mesalazine
• treatment
• ulcerative colitis