Do interventions for mood improve inflammatory biomarkers in inflammatory bowel disease?: a systematic review and meta-analysis.

BACKGROUND: Psychoneuroimmunological mechanisms and the gut-brain axis appear relevant to disease activity and progression in Inflammatory Bowel Disease (IBD). A recent review showed no effect of psychological therapies on self-reported disease activity in IBD. This meta-analysis aims to establish whether interventions targeting mood outcomes (e.g., depression, anxiety and stress) impact inflammation levels in IBD and possible moderators of these effects. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. We searched five electronic databases and included randomised controlled trials where interventions targeted mood and assessed inflammatory outcomes pre- and post-intervention in adults with IBD. Independent reviewers screened studies, extracted data, and assessed methodological quality. Data were pooled to estimate standardised mean differences (SMDs) with 95% Confidence Intervals (CIs). A random-effects robust variance estimation accounted for studies measuring multiple biomarkers. Intervention type, mood as a primary or secondary outcome, effect on mood outcomes and IBD subtype were investigated as treatment effect moderators. Where there were sufficient biomarkers, individual meta-analyses were run (Pre-registration PROSPERO: CRD42023389401). FINDINGS: 28 RCTs involving 1789 participants met inclusion criteria. Interventions demonstrated small, statistically significant effects on biomarkers (-0.35, 95% CI: -0.48, -0.22, p < 0.001) and medium effects on mood outcomes (-0.50, 95% CI: -0.73, -0.27, p < 0.001), without evidence of substantive heterogeneity or publication bias. Individual analyses showed small effects for improved faecal calprotectin (-0.19, 95% CI: -0.34, -0.03, p = 0.018) and C-Reactive Protein (-0.29, 95% CI: -0.47, -0.10, p = 0.002). Effect sizes were larger for psychological therapy interventions (compared with exercise or antidepressants) and when there was an effect (SMD ≥0.2) on mood. INTERPRETATION: Treatments which address mood outcomes have beneficial effects on generic inflammation as well as disease-specific biomarkers (faecal calprotectin and C-Reactive Protein). Psychological interventions and interventions with larger treatment effects on mood accentuated the effect on biomarkers. More research is required to understand the biological or behavioural mechanisms underlying this effect. FUNDING: The Medical Research Council and the National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre.

Dysbiosis and Associated Stool Features Improve Prediction of Response to Biological Therapy in Inflammatory Bowel Disease.

BACKGROUND & AIMS: Dysbiosis of the gut microbiota is considered a key contributor to inflammatory bowel disease (IBD) etiology. Here, we investigated potential associations between microbiota composition and the outcomes to biological therapies. METHODS: The study prospectively recruited 296 patients with active IBD (203 with Crohn's disease, 93 with ulcerative colitis) initiating biological therapy. Quantitative microbiome profiles of pretreatment and posttreatment fecal samples were obtained combining flow cytometry with 16S amplicon sequencing. Therapeutic response was assessed by endoscopy, patient-reported outcomes, and changes in fecal calprotectin. The effect of therapy on microbiome variation was evaluated using constrained ordination methods. Prediction of therapy outcome was performed using logistic regression with 5-fold cross-validation. RESULTS: At baseline, 65.9% of patients carried the dysbiotic Bacteroides2 (Bact2) enterotype, with a significantly higher prevalence among patients with ileal involvement (76.8%). Microbiome variation was associated with the choice of biological therapy rather than with therapeutic outcome. Only anti-tumor necrosis factor-α treatment resulted in a microbiome shift away from Bact2, concomitant with an increase in microbial load and butyrogen abundances and a decrease in potentially opportunistic Veillonella. Remission rates for patients hosting Bact2 at baseline were significantly higher with anti-tumor necrosis factor-α than with vedolizumab (65.1% vs 35.2%). A prediction model, based on anthropometrics and clinical data, stool features (microbial load, moisture, and calprotectin), and Bact2 detection predicted treatment outcome with 73.9% accuracy for specific biological therapies. CONCLUSION: Fecal characterization based on microbial load, moisture content, calprotectin concentration, and enterotyping may aid in the therapeutic choice of biological therapy in IBD.

Enhancing surgical precision: unveiling the impact of preoperative colonoscopy in anal fistula patients.

BACKGROUND: Anal fistula is a common benign anorectal disease that often requires surgical intervention for effective treatment. In recent years, preoperative colonoscopy as a diagnostic tool in patients with anal fistula has garnered increasing attention due to its potential clinical application value. By investigating underlying inflammatory bowel disease (IBD), polyps, and other abnormalities, preoperative colonoscopy can offer insights to refine surgical strategies and improve patient outcomes. METHODS: This retrospective study focused on 1796 patients with various benign anorectal diseases who underwent preoperative intestinal endoscopy and met surgical criteria within the preceding three years at the First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine. Among these patients, 949 diagnosed with anal fistula comprised group A, while 847 patients without anal fistula were assigned to group B for comparison. The investigation encompassed an analysis of general patient information, endoscopic findings, polyp histopathology, distribution of bowel inflammation sites, and results of inflammatory bowel disease assessments between the two patient cohorts. A subgroup analysis was also conducted on 2275 anal fistula patients with no surgical contraindications. This subgroup was categorized into Group A (949 patients who underwent preoperative intestinal endoscopy) and Group C (1326 patients who did not undergo preoperative colonoscopy). The study compared the rates of detecting endoscopic lesions and IBD-related findings between the two subgroups. RESULTS: The study initially confirmed the comparability of general patient information between groups A and B. Notably, the abnormal detection rate in group A was significantly higher than in group B (P < 0.01). In terms of endoscopic findings, the anal fistula group (group A) exhibited higher rates of detecting bowel inflammation, inflammatory bowel disease, and polyps compared to the non-anal fistula group (group B) (P < 0.05). The distribution of inflammation locations indicated higher detection rates in the terminal ileum, ileocecal region, and ascending colon for group A compared to group B (P < 0.05). Although the incidence of IBD in group A was higher than in group B, this difference did not reach statistical significance (P > 0.05). Subsequently, the analysis of the subgroup (groups A and C) revealed a significant disparity in intestinal endoscopic detection rates (P < 0.01) and statistically significant differences in detecting IBD (P < 0.05) and Crohn's disease (P < 0.05) between the two anal fistula subgroups. CONCLUSIONS: The findings of this study underscore the substantial clinical value of preoperative colonoscopy in the comprehensive evaluation of patients with anal fistula. Preoperative colonoscopy aids in ruling out localized perianal lesions caused by underlying inflammatory bowel disease, thereby mitigating the likelihood of missed diagnoses and enhancing treatment outcomes. This research highlights the importance of incorporating preoperative colonoscopy as a valuable diagnostic tool in managing anal fistula patients.

Prognostic modelling in IBD.

In the ideal world prognostication or predicting disease course in any chronic condition would allow the clinician to anticipate disease behaviour, providing crucial information for the patient and data regarding best use of resources. Prognostication also allows an understanding of likely response to treatment and the risk of adverse effects of a treatment leading to withdrawal in any individual patient. Therefore, the ability to predict outcomes from the onset of disease is the key step to developing precision personalised medicine, which is the design of medical care to optimise efficiency or therapeutic benefit based on careful profiling of patients. An important corollary is to prevent unnecessary healthcare costs. This paper outlines currently available predictors of disease outcome in IBD and looks to the future which will involve the use of artificial intelligence to interrogate big data derived from various important 'omes' to tease out a more holistic approach to IBD.

The IBD-FITT study - moderate-intensity exercise for patients with inflammatory bowel disease with moderate disease activity: an open-label randomized controlled trial.

BACKGROUND: Inflammatory bowel disease (IBD), Crohn's disease, and ulcerative colitis are chronic autoimmune lifelong diseases with fluctuating activity over time. The treatment includes medical therapy and surgery, however, there is no definite cure. Therefore, the quest for new and supplementary treatment options is imperative to improve patients' general health and quality of life. Physical activity and exercise have been suggested to be elements in both the prevention and supplementary treatment of IBD; however, this is based on limited underpowered trials. Thus, the role of exercise as a treatment option still has to be settled. We aim to investigate the effect of a 12-week exercise intervention in adult patients with moderately active IBD on three categories of outcomes (1) disease-specific health-related quality of life (IBDQ); (2) general health status of the patients, i.e., waist circumference, disease activity by clinical scorings systems (Harvey Bradshaw Index, Simple Clinical Colitis Activity Index), blood pressure, blood lipids, and non-disease specific quality of life (EQ5D) scores; and (3) explorative outcomes on biomarkers (C-reactive protein and fecal calprotectin) plus different biomarkers of immunology (cytokine panel). METHODS: We will apply a superiority design in this open-label randomized clinical trial including 150 patients equally allocated to intervention and usual care. The intervention will be based on a 12-week aerobic exercise program and will include two supervised exercise sessions of 60 min per week, combined with one weekly home training session. We have defined a moderate exercise level as 60-80% of patients' maximum heart rate. The patients in the intervention group will also be offered an online video lesson of 15-25 min on lifestyle guidance, and the same online video lesson will be offered in the comparator group. Questionnaires on quality of life will be forwarded electronically both at inclusion and at the end of the study, and the patients will have blood samples, and fecal samples for calprotectin at baseline, weeks 4 and 8, as well as after 12 weeks (study end). DISCUSSION: This will be a clinical trial investigating the effect of exercise on patients with Crohn's disease and ulcerative colitis. This trial will add to the evidence on the possible effect of exercise and might clarify whether exercise can benefit as a supplementary treatment addendum. Thus, the trial may provide a new patient-active disease management approach. TRIAL REGISTRATION: ClinicalTrials.gov NCT04816812. Date of first registration: March 23, 2021.

Randomized controlled trial of hydrolyzed fish diets in dogs with chronic enteropathy.

BACKGROUND: The role of diet in the pathogenesis and treatment of chronic enteropathies (CE) in dogs is unresolved. OBJECTIVES: To compare the ability of diets composed of hydrolyzed fish, rice starch, and fish oil without (HF) or with prebiotics, turmeric, and high cobalamin (HF+) against a limited ingredient diet containing mixed nonhydrolyzed antigens and oils (control) to resolve clinical signs and maintain serum cobalamin and folate concentrations in dogs with nonprotein losing CE (non-PLE). To determine the ability of hydrolyzed fish diets to support recovery and remission in dogs with PLE. ANIMALS: Thirty-one client-owned dogs with CE: 23 non-PLE, 8 PLE. METHODS: Randomized, blinded, controlled trial. Diets were fed for 2 weeks; responders continued for 12 weeks. Nonresponders were crossed over to another diet for 12 weeks. Response was determined by standardized clinical evaluation with long-term follow-up at 26 weeks. Concurrent medications were allowed in PLE. RESULTS: Nineteen of 23 (83%; 95% confidence interval [CI], 60%-94%) non-PLE CE responded clinically to their initial diet, with no difference between diets (P > .05). Four nonresponders responded to another diet, with sustained remission of 18/18 (100%; 95%CI, 78%-100%) at 26 weeks. Serum cobalamin concentration was increased (P < .05) and maintained by diet. Serum folate concentration decreased posttreatment (P < .05) but was restored by dietary supplementation. Hydrolyzed fish diets supported weight gain, serum albumin concentration, and recovery (P < .05) in dogs with PLE. CONCLUSIONS AND CLINICAL IMPORTANCE: Changing diet, independent of antigen restriction or supplemental ingredients, induced long-term remission in dogs with non-PLE CE. Serum cobalamin and folate concentrations were maintained by diet. Hydrolyzed fish diets supported clinical recovery and remission in PLE.

Development and implementation of a laboratory monitoring dashboard to reduce treatment gaps in inflammatory bowel disease.

PURPOSE: Patients receiving biologic therapy for inflammatory bowel disease (IBD) require routine laboratory monitoring to ensure the safety and efficacy of therapy. The purpose of this quality improvement project was to evaluate the implementation of a dashboard to prevent treatment gaps by prospectively identifying patients with IBD and outdated laboratory results receiving biologics. METHODS: We performed a pre/post analysis of dashboard implementation to assess the number of patients with overdue laboratory work resulting in treatment gaps. The dashboard combined data from the electronic health record (EHR) and pharmacy claims database to identify patients on a biologic with laboratory tests (white blood cell count, liver transaminases, C-reactive protein, and erythrocyte sedimentation rate) completed 5 or more months ago and/or a tuberculosis screen completed 11 or more months ago. After implementation, specialty pharmacists reviewed the dashboard and communicated via EHR if a new prescription and laboratory tests were needed. Messages were sent 4 weeks in advance of the next refill-eligible date. Mixed methods were used for analysis of qualitative data, including surveys, and quantitative data, assessing treatment gap length. RESULTS: A total of 40 patients who had outdated laboratory values and required a new prescription (15 before dashboard implementation and 25 after implementation) were included in the analysis. The frequency of a treatment gap decreased from 80% (n = 12) in the preimplementation phase to 32% (n = 8) in the postimplementation phase. The median gap length was shorter after dashboard implementation, decreasing from 21 days (range, 3-97 days) to 11 days (range, 2-23 days). CONCLUSION: Utilization of a quality measures dashboard decreased treatment gaps in patients with IBD receiving biologic therapy. Integrated specialty pharmacists are uniquely positioned to monitor adherence to laboratory monitoring parameters for patients on biologics.

Could Mucosal TNF Transcript as a Biomarker Candidate Help Optimize Anti-TNF Biological Therapy in Patients With Ulcerative Colitis?

Anti-tumor necrosis factor (TNF) biological therapy has generally been accepted as a standard therapeutic option in inflammatory bowel disease (IBD) patient who are refractory to steroids or immunomodulators. However, the primary and secondary nonresponse rates to anti-TNF bioagents in patients with IBD are high. To improve the response rate, anti-TNF bioagents must be offered to the appropriate IBD patients, and the withdrawal of anti-TNF bioagents needs to be done at the right time. In this context, reliable and reproducible biomarkers can provide important supportive information for clinicians to make correct decisions based on the patient's individual situation. In this review, we summarized the current understanding of using mucosal TNF transcript (TNF) to improve the precision of anti-TNF biological therapy strategies in patients with ulcerative colitis (UC). Analysis of published literature showed that mucosal TNF could affect the precision of the early identification of candidates who will benefit from anti-TNF therapy prior to treatment, the assessment of response and mucosal healing, and the prediction of discontinuation of anti-TNF biological therapy and relapse after drug withdrawal. Challenges and limitations of using mucosal TNF as a biomarker in applying individualized anti-TNF biological therapy in patients with UC still remain and need to be further investigated.

Endoscopic Disease Activity and Biologic Therapy Are Independent Predictors of Suboptimal Bowel Preparation in Patients with Inflammatory Bowel Disease Undergoing Colonoscopy.

BACKGROUND AND AIMS: Optimal bowel preparation (BP) is critical for endoscopic assessment of inflammation and dysplasia in patients with inflammatory bowel disease (IBD). Comorbidities and patient-related factors have been associated with suboptimal BP (SOBP) in the general population. We sought to identify disease-specific characteristics that may impact the quality of BP in patients with IBD. METHODS: We conducted a retrospective analysis of adult IBD patients who underwent outpatient colonoscopies between January 2014 and September 2020 at a large academic medical center. Quality of BP was documented using the Boston Bowel Preparation Scale (BBPS) or the Aronchick scale and dichotomized into "suboptimal" (BBPS 0-5 or Aronchick "fair," "poor," unsatisfactory") and "optimal" (BBPS 6-9 or Aronchick "excellent," "good"). IBD-specific and other factors associated with SOBP were evaluated using logistic regression analyses. RESULTS: Among a total of 395 IBD patients [54% males, mean age 40 years, 63% with Crohn's disease (CD), 35% with ulcerative colitis (UC)], 24.8% had SOBP. On multivariable analysis, moderate-to-severe endoscopic disease vs mild or inactive disease was associated with a higher odds of SOBP [adjusted OR 2.7(95% CI 1.52-4.94)], whereas baseline biologic use was associated with a lower odds of SOBP [aOR 0.24(0.09-0.65)] among the overall IBD cohort. Additionally, age > 65 years [aOR 2.99(1.19-7.54)] and single-dose vs split-dose BP [aOR 2.37(1.43-3.95)] were predictors of SOBP. In the subgroup analysis by IBD type, moderate-to-severe endoscopic disease predicted SOBP among both CD and UC cohorts. CONCLUSION: Endoscopic disease activity was predictive of SOBP, and biologic therapy was protective against SOBP among IBD patients.

The impact of symptom severity on the humanistic and economic burden of inflammatory bowel disease: a real-world data linkage study.

OBJECTIVE: Few studies have examined the association between inflammatory bowel disease (IBD) severity, and humanistic, and economic burden. We addressed this gap using a unique real-world data source that links self-reported patient data from the US National Health and Wellness Survey (NHWS) to claims data. METHODS: This cross-sectional study linked the 2015-2018 US NHWS data with medical, and pharmacy claims. Patients (≥18 years) who self-reported a physician diagnosis of IBD (ulcerative colitis [UC], or Crohn's disease [CD]) in the NHWS, and had a medical or pharmacy claim indicating a possible diagnosis of IBD were included. Disease symptom severity was defined by a weighted symptom score and main outcomes include health-related quality of life (HRQoL), work productivity (WPAI), healthcare resource use (HRU), and associated costs. RESULTS: Overall, 687 patients with IBD were included, of which 347 were identified with UC and 340 with CD. Validation analysis showed that 94.7% of UC and 88.7% of patients with CD who self-reported diagnosis of CD or UC in NHWS had evidence of diagnosis and/or treatment patterns in claims. Patients with both UC and CD with moderate or severe symptoms had significantly lower HRQoL, increased work productivity loss, greater HRU, and associated costs compared with patients with mild symptoms. CONCLUSIONS: Patients with moderate/severe UC or CD experience substantial humanistic, and economic burden compared with patients with mild UC or CD. These factors should be considered within treatment goals for patients in order to provide holistic care beyond the treatment of objective markers or disease severity and symptoms alone.

De-escalation of biological therapy in inflammatory bowel disease patients following prior dose escalation.

BACKGROUND: Limited data are available on biological therapy de-escalation after prior escalation in inflammatory bowel disease (IBD) patients. This study aimed to assess the frequency and success rate of de-escalation of biological therapy in IBD patients after prior dose escalation and to evaluate which measures are used to guide de-escalation. METHODS: This multicentre retrospective cohort study enrolled IBD patients treated with infliximab (IFX), adalimumab (ADA) or vedolizumab (VEDO) in whom therapy was de-escalated after prior biological escalation. De-escalations were considered pharmacokinetic-driven if based on clinical symptoms combined with therapeutic or supratherapeutic trough levels, and disease activity-driven if based on faecal calprotectin less than or equal to 200 µg/g or resolution of perianal fistula drainage or closure or endoscopic remission. Successful de-escalation was defined as remaining on the same or lower biological dose for greater than or equal to 6 months after de-escalation without the need for corticosteroids. RESULTS: In total, 206 IFX users, 85 ADA users and 55 VEDO users underwent therapy escalation. Of these patients, 34 (17%) on IFX, 18 (21%) on ADA and 8 (15%) on VEDO underwent therapy de-escalation. De-escalation was successful in 88% of IFX patients, 89% of ADA and 100% of VEDO. The probability of remaining on the de-escalated regimen or further de-escalation after 1 year was 85% for IFX, 62% for ADA and 100% for VEDO. Disease activity-driven de-escalations were more often successful (97%) than pharmacokinetic- and no marker-driven de-escalations (76%); P = 0.017. CONCLUSION: De-escalation after biological dose escalation was successful in the majority of carefully selected IBD patients. Objective assessment of remission increased the likelihood of successful de-escalation.

Diagnosis and Management of Oral Extraintestinal Manifestations of Pediatric Inflammatory Bowel Disease.

ABSTRACT: Inflammatory bowel diseases (IBD) represent a group of chronic inflammatory disorders of the gastrointestinal tract that lead to impaired quality of life and substantial health care costs. Up to 50% of pediatric IBD cases present with manifestations in the oral cavity. These may develop in nearly every oral tissue, including the soft tissues, tongue, lips, teeth, and lymph nodes. The goal of this review is to offer a systematic approach to diagnose and manage commonly encountered oral manifestations of pediatric IBD. This knowledge is critical for enhancing the comprehensive care and quality of life of children with these debilitating diseases.

Exploring Popular Social Media Networks for Patients With Inflammatory Bowel Diseases: Insights for Better Care.

GOAL: The aim was to assess topics of interest and concerns among patients with inflammatory bowel diseases (IBD) who are active online. BACKGROUND: Social media (SM) networks are a major communication tool for patients with IBD and health care professionals. PATIENTS AND METHODS: We performed an anonymized investigation of SM networks for IBD patients; I-a thematic analysis of patients' posts, II-an online survey advertised through Facebook and other popular SM networks throughout November 2019. RESULTS: Analyzing 2133 posts (2014 to 2019) revealed 18 topics of interest. The online survey was completed by 534 respondents [63%-Crohn's disease, 56%-female, median age-38 years (interquartile range: 28.7 to 51.0)]. Most respondents (70%) were followed in referral centers, and 45% were receiving biological therapy. Respondents reported high satisfaction with IBD care and health care provider professionalism. The top 5 topics of interest were diet, lifestyle, complementary and alternative medicine, diagnostic test interpretation, and specialist referrals and reviews. Cluster analysis demonstrated that gender, income, and education level were associated with specific interest and concerns. CONCLUSION: Patients' activity on SM is independent of their satisfaction with formal IBD care and rather reflects an ongoing need for information and support. These needs may be addressed both in clinical settings and through online tools.

A systematic monitoring approach to biologic therapies in inflammatory bowel disease: patients' and physicians' preferences and adherence.

OBJECTIVES: Treatment of patients with inflammatory bowel disease (IBD) should aim at achieving mucosal healing. However, monitoring schedules to support this goal remain undefined. We aimed to identify patients' and physicians' preferences regarding monitoring strategy and investigated the feasibility of such a strategy. METHODS: Elements considered relevant for monitoring were identified in questionnaire surveys among 1) patients with IBD receiving biologic agents (n = 172) and 2) their physicians (n = 87). Adherence to a monitoring strategy incorporating these elements was investigated in a retrospective cohort of patients with IBD treated with biologic agents (n = 139). RESULTS: Patients considered blood and stool samples, endoscopies, and magnetic resonance imaging (MRI) to be relevant aspects of monitoring their disease. However, patients also considered stool samples and endoscopies unpleasant. Physicians considered blood samples (99%), medical consultations (99%), fecal calprotectin (85%), endoscopy (78%), and MRI (71%) to be important aspects of IBD monitoring but considered endoscopies and MRI relevant only at clinical signs of relapse. A review of the clinical use of monitoring strategies including the elements identified above revealed high adherence for blood samples and disease activity indices (92%), but low adherence for fecal calprotectin (38%), therapeutic drug monitoring (38%), and endoscopies (32%). CONCLUSION: Important tools for evaluating mucosal healing (e.g., endoscopy) were rated highly unpleasant by patients, and physicians found endoscopies/MRI relevant only in case of relapse. These findings were reflected by low rates of adherence to use of these monitoring tools. In defining monitoring schedules to help achieve treatment goals, these important barriers must be addressed.

The effect of photobiomodulation therapy on the management of chronic idiopathic large-bowel diarrhea in dogs.

To evaluate photobiomodulation therapy's effectiveness (PBMT) in managing chronic idiopathic large-bowel diarrhea. Thirty dogs were selected and divided into a control (CG) and treatment group (TG). CG received psyllium husk at the dose of 4 tablespoons/day for 30 days. TG received PBMT with a Class IV therapeutic laser, divided into three sessions on week 1, two sessions on week 2, and one session on week 3. A daily log of fecal characteristics was maintained, and on days 0, 8, 15, and 30, a canine inflammatory bowel disease index (CIBDAI) and body condition scores (BCS) were obtained. Results were compared using a Mann-Whitney test. Multiple regression was run to predict CIBDAI, Bristol stool scores, and diarrhea from different parameters. The Kaplan-Meier test was used to compare the occurrence rate of ≥ 1 day of diarrhea and ≥ 2 days of diarrhea by 30 days. Cox regression analysis to investigate interest covariates influences the same outcome. A p < 0.05 was set. The sample included 15 Belgian Malinois Shepherd Dogs, 10 German Shepherd Dogs, and 5 Dutch Shepherd Dog, with a mean age of 3.6 ± 2.3 years and a bodyweight of 24.6 ± 8.0 kg. TG showed an improvement in all scores and clinical signs, increased body weight, and BCS. An increased time of appearance of a second episode of diarrhea was observed in both groups. Activity level contributed to the prediction of defecation frequency and CIBDAI. PBMT significantly improved clinical signs and frequency of diarrhea episodes compared to psyllium husk.

Small intestinal sampling capsule for inflammatory bowel disease type detection and management.

Although serum and fecal biomarkers (e.g., lactoferrin, and calprotectin) have been used in management and distinction between inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), none are proven to be a differential diagnostic tool between Crohn's disease (CD) and ulcerative colitis (UC). The main challenge with laboratory-based biomarkers in the stool test is the inability to indicate the location of the disease/inflammation in the gastrointestinal (GI) tract due to the homogenous nature of the collected fecal sample. For the first time, we have designed and developed a battery-free smart capsule that will allow targeted sampling of inflammatory biomarkers inside the gut lumen of the small intestine. The capsule is designed to provide a simple and non-invasive complementary tool to fecal biomarker analysis to differentiate the type of IBD by pinpointing the site of inflammatory biomarkers secretion (e.g., small or large bowel) throughout the GI tract. The capsule takes advantage of the rapid change from an acidic environment in the stomach to higher pH levels in the small intestine to dissolve a pH-sensitive polymeric coating as a means to activate the sampling process of the capsule within the small intestine. A swelling polyacrylamide hydrogel is placed inside the capsule as a milieu to collect the sampled GI fluid while also providing the required mechanical actuation to close the capsule once the sampling is completed. The hydrogel component along with the collected GI fluid can be easily obtained from the capsule through the screw-cap design for further extraction and analysis. As a proof of concept, the capsule's performance in sampling and extraction of bovine serum albumin (BSA) and calprotectin - a key biomarker of inflammation - was assessed within the physiologically relevant ranges. The ratio of extracted biomarkers relative to that in the initial sampling environment remained constant (∼3%) and independent of the sampling matrix in both in vitro and ex vivo studies. It is believed that the demonstrated technology will provide immediate impact in more effective IBD type differential diagnostic and treatment strategies by providing a non-invasive assessment of inflammation biomarkers profile throughout the digestive tract.

Improving prediction of disease outcome for inflammatory bowel disease: progress through systems medicine.

Introduction: Inflammatory bowel diseases (IBDs) are lifelong conditions causing relapsing inflammation of the intestine. In the absence of a cure, clinical management of IBDs is extremely challenging since they present with a wide range of phenotypes and disease behaviors. Hence, there is an urgent need for markers that could guide physicians in making the right choice of the rapidly growing treatment options toward a personalized care that could improve the overall outcome.Areas covered: In this review, the authors summarize existing biomarkers in IBD, discuss the challenges with the development of prognostic biomarkers and propose alternative options such as focusing on the prediction of the response to individual treatments, i.e. predictive biomarkers. The problems related to developing disease prognostic and predictive biomarkers in the field of IBDs are discussed including the difficulties in dealing with phenotypic heterogeneity particularly when performing studies in a real-life setting. The authors reviewed literature from PubMed.Expert opinion: Systems biology provides potential solutions to this problem by offering an unbiased, holistic approach to adjusting for variation in larger datasets thereby increasing the chances of identifying true associations between molecular profiles and clinical phenotypes.

Approach to the Management of Recently Diagnosed Inflammatory Bowel Disease Patients: A User's Guide for Adult and Pediatric Gastroenterologists.

Inflammatory bowel diseases (IBDs), including Crohn's disease and ulcerative colitis, are chronic, progressive, immune-mediated diseases of adults and children that have no cure. IBD can cause significant morbidity and lead to complications such as strictures, fistulas, infections, and cancer. In children, IBD can also result in growth impairment and pubertal delays. IBD is highly heterogenous, with severity ranging from mild to severe and symptoms ranging from mild to debilitating. Delay in IBD diagnosis, especially in Crohn's disease, is common and associated with adverse outcomes. Early diagnosis and prompt institution of treatment are the cornerstones for improving outcomes and maximizing health. Early diagnosis requires a low threshold of suspicion and red flags to guide early specialist referral at the primary provider level. Although the armamentarium of IBD medications is growing, many patients will not respond to treatment, and the selection of first-line therapy is critical. Risk stratification of disease severity, based on clinical, demographic, and serologic markers, can help guide selection of first-line therapy. Clinical decision support tools, genomics, and other biomarkers of response to therapy and risk of adverse events are the future of personalized medicine. After starting appropriate therapy, it is important to confirm remission using objective end points (treat to target) with continued control of inflammation with adjustment of therapy using surrogate biomarkers (tight control). Lastly, IBD therapy extends far beyond medications, and other aspects of the overall health and wellbeing of the patient are critical. These include preventive health, nutrition, and psychobehavioral support addressing patients' concerns around complementary therapy and medication adherence, prevention of disability, and ensuring open communication.