Meta-analysis: Intestinal ultrasound to evaluate colonic contents and constipation.

BACKGROUND: Constipation can be diagnosed clinically using the Rome criteria. Ultrasound (US), which lacks the radiation exposure of conventional X-ray, holds promise as a non-invasive tool to evaluate colonic contents and constipation. AIM: To examine the role of US in the assessment of constipation. METHODS: We performed a systematic search of Embase (OVID, 1984), Medline (Ovid, 1946), Cochrane Central, ClinicalTrials.gov and Australia New Zealand Clinical Trials Registry from database inception to 26 January 2024 according to PRISMA guidelines and prospectively registered with PROSPERO. All studies using US to assess constipation or colonic contents in either adults or children were included. Rectal diameter measurements were pooled in meta-analysis. Risk of bias was assessed using the Newcastle Ottawa Scales and Joanna Briggs Institute checklists. RESULTS: Of 12,232 studies screened, 51 articles (6084 patients; 3422 children) describing US to assess symptoms in patients with constipation were included. Most studies used Rome criteria to diagnose constipation. Rectal diameter was associated with clinical constipation in 29 paediatric studies (3331 patients). Meta-analysis showed the mean rectal diameter of constipated patients was significantly higher than controls (mean difference 12 mm, 95% confidence intervals (CI): 6.48, 17.93, p < 0.0001, n = 16 studies). Other features of constipation on US included posterior acoustic shadowing and echogenicity of luminal contents. CONCLUSION: US is an appealing imaging modality to assess luminal contents and constipation. Further well-designed studies are required to validate US metrics that accurately identify constipation.

Latent profiles of fatigue in inflammatory bowel disease.

INTRODUCTION: Fatigue is prevalent in people with inflammatory bowel disease (IBD) and has been associated with IBD activity, sleep quality, depression, and anxiety. This study aimed to identify fatigue profiles or clusters through latent profile analysis. METHODS: An online questionnaire was administered through three tertiary IBD centres, social media and through Crohn's Colitis Australia. Fatigue was assessed via the Functional assessment of chronic illness measurement system fatigue subscale (FACIT-F), a validated assessment of fatigue and its severity. Validated measures of anxiety, depression, IBD activity and sleep quality were also included. Latent profile analysis was performed including fatigue, sleep quality, active IBD, and depression and anxiety. The relationships between profiles and IBD and demographic data were investigated. RESULTS: In a cohort of 535 respondents, 77% were female, the median age was 41 years (range 32-52 years), and the majority had Crohn's disease (62%). Severe fatigue was seen in 62%. Latent profile analysis identified four distinct profiles differing by fatigue score - low fatigue, at-risk profile, active IBD, and a poor mental health profile. Female gender, obesity and opioid usage were associated with higher risk of being in the active IBD and poor mental health profile. Age over 40 was associated with lower risk of being in the poor mental health profile. CONCLUSION: Latent profile analysis identifies four classes of fatigue in an IBD cohort with associations with specific risk factors for fatigue along with specific IBD and demographic attributes. This has implications for the classification of fatigue in IBD and treatment algorithms.

Habitual dietary fibre and prebiotic intake is inadequate in patients with inflammatory bowel disease: findings from a multicentre cross-sectional study.

BACKGROUND: Recommendations for dietary fibre intake in patients with inflammatory bowel disease are highly variable. Despite the potential benefits of prebiotic fibres on the gut microbiome, many patients with inflammatory bowel disease follow a low fibre diet. The present study comprehensively evaluated intakes of total and prebiotic fibres in patients with inflammatory bowel disease, aiming to determine the adequacy of fibre intake and factors that may influence intake. METHODS: Outpatients with a formal diagnosis of inflammatory bowel disease were recruited to this multicentre cross-sectional study. Habitual dietary fibre intake including prebiotic fibre types was measured using a validated comprehensive nutrition assessment questionnaire. Adequacy of total fibre intake was compared with Australian Nutrient Reference Values. Multiple linear regressions were performed to determine factors influencing fibre intake. RESULTS: Of 92 participants, 52% had Crohn's disease, 51% were male and the mean age was 40 years. Overall, only 38% of the cohort consumed adequate total fibre (median 24 g day-1 , interquartile range 18.5-32.9 g day-1 ). Adequate fibre consumption was significantly less common in males than females (21.3% versus 55.6%, P = 0.002). Resistant starch intake (median 2.9 g day-1 , interquartile range 2.1-4.8 g day-1 ) was significantly less than the proposed recommendations (20 g day-1 ). Disease-related factors such as phenotype and disease activity were not found to influence fibre intake. CONCLUSIONS: Patients with inflammatory bowel disease habitually consume inadequate fibre, particularly prebiotic fibre resistant starch. The potential deleterious effects of low prebiotic intake on the gut microbiome and disease-related outcomes in inflammatory bowel disease are unknown and warrant further research.

Adjunctive fecal microbiota transplantation in supportive oncology: Emerging indications and considerations in immunocompromised patients.

FMT has gained enormous momentum in the treatment of acute inflammatory and infectious diseases. Despite an encouraging safety profile, FMT has been met with caution in the oncological setting due to perceived infectious risks in immunocompromised patients. Theoretical risks aside, the application of FMT in oncology may stand to benefit patients, via modulation of treatment efficacy and the mitigation of treatment complications. Here, we summarize most recent safety data of FMT in immunocompromised cohorts, including people with cancer, highlighting that FMT may actually provide protection against bacterial translocation via introduction of a diverse microbiome and restoration of epithelial defenses. We also discuss the emerging translational applications of FMT within supportive oncology, including the prevention and treatment of graft vs. host disease and sepsis, treatment of immunotherapy-induced colitis and restoration of the gut microbiome in survivors of childhood cancer.

NOX1 loss-of-function genetic variants in patients with inflammatory bowel disease.

Genetic defects that affect intestinal epithelial barrier function can present with very early-onset inflammatory bowel disease (VEOIBD). Using whole-genome sequencing, a novel hemizygous defect in NOX1 encoding NAPDH oxidase 1 was identified in a patient with ulcerative colitis-like VEOIBD. Exome screening of 1,878 pediatric patients identified further seven male inflammatory bowel disease (IBD) patients with rare NOX1 mutations. Loss-of-function was validated in p.N122H and p.T497A, and to a lesser degree in p.Y470H, p.R287Q, p.I67M, p.Q293R as well as the previously described p.P330S, and the common NOX1 SNP p.D360N (rs34688635) variant. The missense mutation p.N122H abrogated reactive oxygen species (ROS) production in cell lines, ex vivo colonic explants, and patient-derived colonic organoid cultures. Within colonic crypts, NOX1 constitutively generates a high level of ROS in the crypt lumen. Analysis of 9,513 controls and 11,140 IBD patients of non-Jewish European ancestry did not reveal an association between p.D360N and IBD. Our data suggest that loss-of-function variants in NOX1 do not cause a Mendelian disorder of high penetrance but are a context-specific modifier. Our results implicate that variants in NOX1 change brush border ROS within colonic crypts at the interface between the epithelium and luminal microbes.

Systematic review with meta-analysis: faecal microbiota transplantation for the induction of remission for active ulcerative colitis.

BACKGROUND: Faecal microbiota transplantation (FMT) is emerging as a novel therapy for ulcerative colitis (UC). Interpretation of efficacy of FMT for UC is complicated by differences among studies in blinding, FMT administration procedures, intensity of therapy and donor stool processing methods. AIM: To determine whether FMT is effective and safe for the induction of remission in active UC. METHODS: Medline (Ovid), Embase and the Cochrane Library were searched from inception through February 2017. Original studies reporting remission rates following FMT for active UC were included. All study designs were included in the systematic review and a meta-analysis performed including only randomised controlled trials (RCTs). RESULTS: There were 14 cohort studies and four RCTs that used markedly different protocols. In the meta-analysis of RCTs, clinical remission was achieved in 39 of 140 (28%) patients in the donor FMT groups compared with 13 of 137 (9%) patients in the placebo groups; odds ratio 3.67 (95% CI: 1.82-7.39, P<.01). Clinical response was achieved in 69 of 140 (49%) donor FMT patients compared to 38 of 137 (28%) placebo patients; odds ratio 2.48 (95% CI: 1.18-5.21, P=.02). In cohort studies, 39 of 168 (24%; 95% CI: 11%-40%) achieved clinical remission. CONCLUSIONS: Despite variation in processes, FMT appears to be effective for induction of remission in UC, with no major short-term safety signals. Further studies are needed to better define dose frequency and preparation methods, and to explore its feasibility, efficacy and safety as a maintenance agent.

Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE): Determining Therapeutic Goals for Treat-to-Target.

OBJECTIVES: The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) program was initiated by the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD). It examined potential treatment targets for inflammatory bowel disease (IBD) to be used for a "treat-to-target" clinical management strategy using an evidence-based expert consensus process. METHODS: A Steering Committee of 28 IBD specialists developed recommendations based on a systematic literature review and expert opinion. Consensus was gained if ≥75% of participants scored the recommendation as 7-10 on a 10-point rating scale (where 10=agree completely). RESULTS: The group agreed upon 12 recommendations for ulcerative colitis (UC) and Crohn's disease (CD). The agreed target for UC was clinical/patient-reported outcome (PRO) remission (defined as resolution of rectal bleeding and diarrhea/altered bowel habit) and endoscopic remission (defined as a Mayo endoscopic subscore of 0-1). Histological remission was considered as an adjunctive goal. Clinical/PRO remission was also agreed upon as a target for CD and defined as resolution of abdominal pain and diarrhea/altered bowel habit; and endoscopic remission, defined as resolution of ulceration at ileocolonoscopy, or resolution of findings of inflammation on cross-sectional imaging in patients who cannot be adequately assessed with ileocolonoscopy. Biomarker remission (normal C-reactive protein (CRP) and calprotectin) was considered as an adjunctive target. CONCLUSIONS: Evidence- and consensus-based recommendations for selecting the goals for treat-to-target strategies in patients with IBD are made available. Prospective studies are needed to determine how these targets will change disease course and patients' quality of life.

Low muscle mass and sarcopenia: common and predictive of osteopenia in inflammatory bowel disease.

BACKGROUND: Body composition is poorly studied in inflammatory bowel disease (IBD). Sarcopenia describes a loss of muscle mass and strength. AIM: To assess the prevalence of low lean mass (LM), sarcopenia and associated morbidity in an adult IBD cohort. METHODS: Cross-sectional data were gathered on pre-menopausal 18- to 50-year-old patients with IBD. Whole-body dual-energy X-ray absorptiometry, anthropometric assessment and grip strength were performed. Low LM was defined as ≥1 s.d. below the population mean for appendicular skeletal muscle index [ASMI (kg)/height (m)²], and sarcopenia as both ASMI and grip strength ≥1 s.d. below population mean. Multivariate regression analyses were performed. RESULTS: Of 137 participants (median age 31 years, BMI 24.8 kg/m(2) ), 56% were male and 69% had Crohn's disease (CD). Low LM and sarcopenia were observed in 21% and 12% of patients, respectively, and osteopenia/osteoporosis in 38% of patients (mean lumbar spine t-score -0.3 ± s.d. 1.1). Grip strength predicted low LM and sarcopenia better than did body mass index (BMI) (OR 4.8 vs. OR 0.7 for low-LM, P < 0.05 both). Normal BMI was falsely reassuring in 72% and 76% of patients with low ASMI and sarcopenia, respectively. Low LM and sarcopenia (OR = 3.6, P = 0.03; OR = 6.3, P = 0.02; respectively), but not BMI nor fat mass, predicted osteopenia/osteoporosis. CONCLUSIONS: Low lean mass and sarcopenia are common in patients with IBD, and important to recognise as they predict osteopenia/osteoporosis. Grip strength testing should be incorporated into routine clinical practice to detect low lean mass deficits, which may go unrecognised using BMI alone.

Introducing vedolizumab to clinical practice: who, when, and how?

Vedolizumab (VDZ), a humanized monoclonal antibody that selectively targets α4ß7 integrin, is approved for use in inflammatory bowel disease (IBD). Here we review the evidence for the safety and efficacy of VDZ in IBD, in order to identify patients likely to benefit from therapy and to integrate VDZ into clinical practice. A bibliographic search was performed of the online databases MEDLINE, EMBASE, PubMed, and the Cochrane Library, using the key words 'inflammatory bowel diseases' OR 'ulcerative colitis' OR 'Crohn's disease' AND 'vedolizumab' OR 'MLN0002' OR 'integrin alpha4beta7' OR 'anti-integrin'. Eight-nine articles were returned using the primary search. Eight randomized controlled trials, one Cochrane review, and two network meta-analyses were identified. VDZ is well tolerated with a low rate of adverse events (similar to placebo), and is associated with minimal systemic immunosuppression. VDZ is effective for induction and maintenance of remission in outpatients with moderate to severe ulcerative colitis (UC) or Crohn's disease (CD) who have failed conventional and anti-tumor necrosis factor (anti-TNF) therapy. VDZ is also a first-line alternative to anti-TNF therapy in UC. The efficacy of VDZ is best assessed at, or beyond, 10 weeks of therapy. The safety, tolerability, and efficacy profile of VDZ place it as a new therapy in IBD, though further trials directly comparing VDZ with other biological agents as well as pragmatic studies to evaluate cost-effectiveness are necessary.

Systematic review: histological remission in inflammatory bowel disease. Is 'complete' remission the new treatment paradigm? An IOIBD initiative.

BACKGROUND AND AIMS: Advances in the medical management of inflammatory bowel disease (IBD) have altered treatment targets. Endoscopic mucosal healing is associated with better outcomes in IBD, though less is known about the significance of achieving histological remission. Our aim was to perform a systematic review to investigate whether histological or 'complete' remission constitutes a further therapeutic target in IBD. METHODS: A bibliographic search was performed on the 1st of October 2013 and subsequently on the 1st of March 2014 of online databases (OVID SP MEDLINE, OVID EMBASE, National Pubmed Central Medline, Cochrane Library, ISI, conference abstracts), using MeSH terms and key words: ("inflammatory bowel diseases" OR "crohn disease" OR "ulcerative colitis" OR "colitis") AND ("mucosal healing" OR "histological healing" OR "pathological healing" OR "histological scoring" OR "pathological scoring"). RESULTS: The search returned 2951 articles. 120 articles were cited in the final analysis. There is no validated definition of histological remission in IBD. There are 22 different histological scoring systems for IBD, none of which are fully validated. Microscopic inflammation persists in 16-100% of cases of endoscopically quiescent disease. There is evidence that histological remission may predict risk of complications in ulcerative colitis beyond endoscopic mucosal healing, though data are scarce in Crohn's disease. CONCLUSIONS: Histological remission in IBD represents a target distinct from endoscopic mucosal healing, not yet routinely sought in clinical trials or practice. There remains a need for a standardized and validated histological scoring system and to confirm the prognostic value of histological remission as a treatment target in IBD.