Interaction of obesity and inflammatory bowel disease

Inflammatory bowel disease(IBD) is a chronic inflammatory condition of unknown etiology that is thought to result from a combination of genetic, immunologic and environmental factors. The incidence of IBD has been increasing in recent decades, especially in developing and developed nations, and this is hypothesized to be in part related to the change in dietary and lifestyle factors associated with modernization. The prevalence of obesity has risen in parallel with the rise in IBD, suggesting a possible shared environmental link between these two conditions. Studies have shown that obesity impacts disease development and response to therapy in patients with IBD and other autoimmune conditions. The observation that adipose tissue produces pro-inflammatory adipokines provides a potential mechanism for the observed epidemiologic links between obesity and IBD, and this has developed into an active area of investigative inquiry. Additionally, emerging evidence highlights a role for the intestinal microbiota in the development of both obesity and IBD, representing another potential mechanistic connection between the two conditions. In this review we discuss the epidemiology of obesity and IBD, possible pathophysiologic links, and the clinical impact of obesity on IBD disease course and implications for management.

Glucocorticosteroid therapy in inflammatory bowel diseases: From clinical practice to molecular biology

Inflammatory bowel diseases(IBDs),such as ulcerative colitis and Crohn's disease,are chronic pathologies associated with a deregulated immune response in the intestinal mucosa,and they are triggered by environmental factors in genetically susceptible individuals.Exogenous glucocorticoids(GCs)are widely used as anti-inflammatory therapy in IBDs.In the past,patients with moderate or severe states of inflammation received GCs as a first line therapy with an important effectiveness in terms of reduction of the disease activity and the induction of remission.However,this treatment often results in detrimental side effects.This downside drove the development of second generation GCs and more precise(non-systemic)drugdelivery methods.Recent clinical trials show that most of these new treatments have similar effectiveness to first generation GCs with fewer adverse effects.The remaining challenge in successful treatment of IBDs concerns the refractoriness and dependency that some patients encounter during GCs treatment.A deeper understanding of the molecular mechanisms underlying GC response is key to personalizing drug choice for IBDs patients to optimize their response to treatment.In this review,we examine the clinical characteristics of treatment with GCs,followed by an in depth analysis of the proposed molecular mechanisms involved in its resistance and dependence associated with IBDs.This thorough analysis of current clinical and biomedical literature may help guide physicians in determining a course of treatment for IBDs patients and identifies important areas needing further study.

Inflammatory bowel disease: A descriptive study of 716 local Chilean patients

AIM: To demographically and clinically characterize inflammatory bowel disease (IBD) from the local registry and update data previously published by our group.METHODS: A descriptive study of a cohort based on a registry of patients aged 15 years or older who were diagnosed with IBD and attended the IBD program at Clínica Las Condes in Santiago, Chile. The registry was created in April 2012 and includes patients registered up to October 2015. The information was anonymously downloaded in a monthly report, and the information on patients with more than one visit was updated. The registry includes demographic, clinical and disease characteristics, including the Montreal Classification, medical treatment, surgeries and hospitalizations for crisis. Data regarding infection with Clostridium difficile (C. difficile) were incorporated in the registry in 2014. Data for patients who received consultations as second opinions and continued treatment at this institution were also analyzed.RESULTS: The study included 716 patients with IBD: 508 patients (71%) were diagnosed with ulcerative colitis (UC), 196 patients (27%) were diagnosed with Crohn’s disease (CD) and 12 patients (2%) were diagnosed with unclassifiable IBD. The UC/CD ratio was 2.6/1. The median age was 36 years (range 16-88), and 58% of the patients were female, with a median age at diagnosis of 29 years (range 5-76). In the past 15 years, a sustained increase in the number of patients diagnosed with IBD was observed, where 87% of the patients were diagnosed between the years 2001 and 2015. In the cohort examined in the present study, extensive colitis (50%) and colonic involvement (44%) predominated in the patients with UC and CD, respectively. In CD patients, non-stricturing/non-penetrating behavior was more frequent (80%), and perianal disease was observed in 28% of the patients. There were significant differences in treatment between UC and CD, with a higher use of corticosteroids, and immunosuppressive and biological therapies was observed in the patients with CD (P < 0.05 and P < 0.01). Significant surgical differences were also observed: 5% of the UC patients underwent surgery, whereas 38% of the CD patients required at least one surgery (P < 0.01). The patients with CD were hospitalized more often during their disease course than the patients with UC (55% and 35% of the patients, respectively; P < 0.01). C. difficile infection was acquired by 5% of the patients in each group at some point during the disease course. Nearly half of the patients consulted at the institution for a second opinion, and 32% of these individuals continued treatment at the institution.CONCLUSION: IBD has continued to increase in the study cohort, slowly approaching the level reported in developed countries.

Evolving role of endoscopy in inflammatory bowel disease:Going beyond diagnosis

Inflammatory bowel disease,encompassing Crohn’s disease(CD)and ulcerative colitis,are chronic immune-mediated inflammatory bowel diseases(IBD)that primarily affect the gastrointestinal tract with periods of activity and remission.Large body of evidence exist to strengthen the prognostic role of endoscopic evaluation for both disease activity and severity and it remains the gold standard for the assessment of mucosal healing.Mucosal healing has been associated with improved clinical outcomes with prolonged remission,decreased hospitalization,IBD-related surgeries and colorectal cancer risk.Therefore,endoscopic objectives in IBD have been incorporated as part of standard care.With the known increased risk of colorectal cancer in IBD,although prevention strategies continue to develop,regular surveillance for early detection of neoplasia continue to be paramount in IBD patients’care.It is thanks to evolving technology and visualization techniques that surveillance strategies are continuously advancing.Therapeutic endoscopic options in IBD have also been expanding,from surgery sparing therapies such as balloon dilation of fibrostenotic strictures in CD to endoscopic mucosal resection of neoplastic lesions.In this review article,we discuss the current evidence on the use of endoscopy as part of standard of care of IBD,its role in surveillance of neoplasia,and the role of interventional endoscopic therapies.

Hepatobiliar manifestations in inflammatory bowel disease: A practical approach

Inflammatory bowel diseases(IBD)are associated with various hepatobiliary disorders.They can occur at any moment in the course of the disease or associated with the treatment.The prevalence of liver dysfunction can reach up to 50%in different studies.Nonalcoholic fatty liver disease is considered the most common hepatobiliary complication in IBD,while primary sclerosing cholangitis is the most specific.Management of hepatic manifestations in IBD involves a multidisciplinary approach that includes a high index of suspicion and joint management with hepatologists.The medical confrontation with abnormal liver tests must include an exhaustive study to determine if these patterns can be related to IBD,associated diseases or to the therapies used.

Endoscopic colorectal cancer surveillance in inflammatory bowel disease: Considerations that we must not forget

Inflammatory bowel disease(IBD),encompassing Crohn's disease and ulcerative colitis,is a chronic immune-mediated inflammatory disease that primarily affects the gastrointestinal tract and is characterized by periods of activity and remission.The inflammatory activity of the disease involving the colon and rectum increases the risk of colorectal cancer(CRC)over the years.Although prevention strategies are evolving,regular surveillance for early detection of neoplasia as a secondary prevention strategy is paramount in the care of IBD patients.In this review article,we discuss the current evidence of the risks of developing CRC and evaluate the best available strategies for screening and surveillance,as well as future opportunities for cancer prevention.

Role of capsule endoscopy in inflammatory bowel disease:Anything new?

Capsule endoscopy(CE)is a recently developed diagnostic method for diseases of the small bowel that is non-invasive,safe,and highly tolerable.Its role in patients with inflammatory bowel disease has been widely validated in suspected and established Crohn’s disease(CD)due to its ability to assess superficial lesions not detected by cross-sectional imaging and proximal lesions of the small bowel not evaluable by ileocolonoscopy.Because CE is a highly sensitive but less specific technique,differential diagnoses that can simulate CD must be considered,and its interpretation should be supported by other clinical and laboratory indicators.The use of validated scoring systems to characterize and estimate lesion severity(Lewis score,Capsule Endoscopy Crohn’s Disease Activity Index),as well as the standardization of the language used to define the lesions(Delphi Consensus),have reduced the interobserver variability in CE reading observed in clinical practice,allowing for the optimization of diagnoses and clinical management strategies.The appearance of the panenteric CE,the incorporation of artificial intelligence,magnetically-guided capsules,and tissue biopsies are elements that contribute to CE being a promising,unique diagnostic tool in digestive tract diseases.

Are we ready to use new endoscopic scores for ulcerative colitis?

For ulcerative colitis(UC),the variability in inflammatory activity along the colon poses a challenge in management.The focus on achieving endoscopic healing in UC is evident,where the UC Endoscopic Index of Severity and Mayo Endoscopic Subscore are commonly used for evaluation.However,these indices primarily consider the most severely affected region.Liu et al recent study validates the Toronto Inflammatory Bowel Disease Global Endoscopic Reporting(TIGER)score offering a comprehensive assessment of inflammatory activity across diverse segments of the colon and rectum and a reliable index correlating strongly with UC Endoscopic Index of Severity and moderately with Mayo Endoscopic Subscore(MES).Despite recommendation,certain aspects warrant further invest-igation.Fecal calprotectin,an intermediate target,correlates with TIGER and should be explored.Determining TIGER scores defining endoscopic remission and response,evaluating agreement with histological activity,and assessing inter-endoscopist agreement for TIGER require scrutiny.Exploring the correlation between TIGER and intestinal ultrasound,akin to MES,adds value.

Heart failure as an adverse effect of infliximab for Crohn's disease: A case report and review of the literature

BACKGROUND Anti-tumor necrosis factor agents were the first biologic therapy approved for the management of Crohn's disease(CD).Heart failure(HF)is a rare but potential adverse effect of these medications.The objective of this report is to describe a patient with CD who developed HF after the use of infliximab.CASE SUMMARY A 50-year-old woman with a history of hypertension and diabetes presented with abdominal pain,diarrhea,and weight loss.Colonoscopy and enterotomography showed ulcerations,areas of stenosis and dilation in the terminal ileum,and thickening of the intestinal wall.The patient underwent ileocolectomy and the surgical specimen confirmed the diagnosis of stenosing CD.The patient started infliximab and azathioprine treatment to prevent post-surgical recurrence.At 6 mo after initiating infliximab therapy,the patient complained of dyspnea,orthopnea,and paroxysmal nocturnal dyspnea that gradually worsened.Echocardiography revealed biventricular dysfunction,moderate cardiac insufficiency,an ejection fraction of 36%,and moderate pericardial effusion,consistent with HF.The cardiac disease was considered an infliximab adverse effect and the drug was discontinued.The patient received treatment with diuretics for HF and showed improvement of symptoms and cardiac function.Currently,the patient is using anti-interleukin for CD and is asymptomatic.CONCLUSION This reported case supports the need to investigate risk factors for HF in inflammatory bowel disease patients and to consider the risk-benefit of introducing infliximab therapy in such patients presenting with HF risk factors.

Treatment of acute severe ulcerative colitis using accelerated infliximab regimen based on infliximab trough level:A case report

BACKGROUND Acute severe ulcerative colitis (ASUC) is a complication of ulcerative colitisassociated with high levels of circulating tumor necrosis factor alpha, due to theintense inflammation and faster stool clearance of anti-tumor necrosis factordrugs. Dose-intensified infliximab treatment can be beneficial and is associatedwith lower rates of colectomy. The aim of the study was to present a case of apatient with ASUC and megacolon, treated with hydrocortisone and acceleratedscheme of infliximab that was monitored by drug trough level.CASE SUMMARYA 22-year-old female patient diagnosed with ulcerative colitis, presented withdiarrhea, rectal bleeding, abdominal pain, vomiting, and distended abdomen.During investigation, a positive toxin for Clostridium difficile and colonic dilatationof 7 cm consistent with megacolon were observed. She was treated with oralvancomycin for pseudomembranous colitis and intravenous hydrocortisone forsevere colitis, which led to the resolution of megacolon. Due to the persistentsevere colitis symptoms, infliximab 5 mg/kg was prescribed, monitored by drugtrough level (8.8 μg/mL) and fecal calprotectin of 921 μg/g (< 30 μg/g). Based onthe low infliximab trough level after one week from the first infliximab dose, thepatient received a second infusion at week 1, consistent with the acceleratedregimen (infusions at weeks 0, 1, 2 and 6). We achieved a positive clinical andendoscopic response after 6 mo of therapy, without the need for a colectomy.CONCLUSIONInfliximab accelerated infusions can be beneficial in ASUC unresponsive to thetreatment with intravenous corticosteroids. Longitudinal studies are necessary todefine the best therapeutic drug monitoring and treatment regimen for thesepatients.