Inflammatory Intestinal Diseases最新文献

Background: Fecal microbiota transplantation (FMT) is an emerging therapeutic strategy for inflammatory bowel disease (IBD). Every step of the FMT process, from donor recruitment and patient selection to pretreatment protocols, administration techniques, and post-FMT interventions, can significantly influence treatment outcomes. These components are interrelated, and even subtle differences in methodology may affect the overall efficacy of FMT for IBD. This review aimed to outline the current clinical experience and findings regarding FMT for IBD during the application process.

Summary: Donor screening has traditionally focused on safety. In recent years, although safety remains essential, increasing attention has been paid to the donor selection efficacy. Particularly, identifying patients who are most likely to benefit from FMT is crucial because timely and appropriate patient selection can prevent delays in effective treatment. Pretreatment strategies and FMT procedures remain hot topics of current research. Approaches, such as antibiotic pretreatment, may enhance microbial engraftment; however, the optimal antibiotic combination remains unclear. Bowel lavage is commonly used to reduce the microbial burden and facilitate donor microbiota colonization, whereas corticosteroid pretreatment has shown conflicting results. There are various routes of administration, and oral capsules are gaining popularity owing to their safety and patient acceptability. Stool preparation factors, including the use of single versus pooled donors, anaerobic processing, and storage form (fresh, frozen, or freeze-dried), can significantly influence microbial viability and clinical outcomes. Repeated FMTs tend to be more effective than single infusions; nonetheless, the optimal frequency remains unclear. Post-FMT interventions, such as dietary modifications and supplementation with prebiotics, such as pectin and alginic acid, are also promising strategies.

Key messages: Despite encouraging results, variations in treatment protocols, donor characteristics, and host factors continue to obscure the definitive predictors of FMT success. Further randomized controlled trials and mechanistic studies are required to standardize these procedures and optimize their long-term efficacy.

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Introduction: Up to 85% of pediatric patients affected by Crohn's disease experience growth failure. This study aims to elucidate the effects of anti-tumor necrosis factor (TNF) biologics on patient growth.

Methods: This retrospective analysis examined height, height velocity and weight in pediatric patients with Crohn's disease from the Swiss Inflammatory Bowel Disease Cohort Study between 2007 and 2020 (n = 97). Z-scores were determined according to age and gender of a healthy pediatric population. Growth of patients treated with anti-TNF biologics and immunomodulators was analyzed by linear regression over 5 years and compared within each subgroup by paired Student t tests 1 year (T1), 2 years (T2), and 5 years (T5) after treatment initiation.

Results: Mean height and weight z-scores at diagnosis were -0.3 ± 1.3 and -1.0 ± 1.6, respectively (age at diagnosis 11.1 ± 2.7 years, 52.0% male). Initial treatment was led by azathioprine (58.3%) and infliximab (19.8%). Patients treated with biologics exhibited significant height increase at T1 (p = 0.022), with an overall flat height evolution (y = 0.00x - 0.31), whereas significant weight increase was maintained at T5 (p = 0.0005, y = 0.13x - 0.50). Patients on immunomodulators showed a height increase (y = 0.15x - 0.20) and a significant weight increase at T2 (p = 0.0047, y = 0.10x - 0.41). Height velocity z-scores showed a significant increase across both genders. Factors contributing to a decreased height z-score included male sex, age 10 and below at diagnosis, a concomitant corticosteroid treatment and a top-down treatment strategy.

Conclusion: Our findings indicate that anti-TNF biologics are associated with significant short-term height and long-term weight gains in pediatric patients with Crohn's disease, similar to those observed with immunomodulators.

Introduction: Fecal calprotectin (FCP) is a key biomarker for gastrointestinal inflammation, aiding in differentiating irritable bowel syndrome from active inflammatory bowel disease (IBD). Metabolic bariatric surgeries (MBSs), such as Roux-en-Y gastric bypass or sleeve gastrectomy, alter gastrointestinal physiology, potentially affecting the applicability of standard FCP cutoff values in this population.

Methods: This retrospective study included 340 patients who underwent MBS and subsequent FCP testing between January 2000 and June 2024. Patients with preoperative IBD were excluded. The primary outcome was to identify the optimal FCP cutoff values for relevant colonoscopy findings. Secondary outcomes included median FCP levels, colonoscopy results, and subgroup analyses based on sex, surgery type, and time to gastrointestinal evaluation.

Results: The median FCP level across all patients was 51 µg/g (IQR 30-82). Among 124 patients undergoing colonoscopy, the median FCP was 61 µg/g (IQR 34-104). There was no significant difference between patients with (69.5 µg/g, n = 50) or without (59 µg/g, n = 74) relevant findings, including malignancy or IBD (p = 0.101). No significant differences in FCP levels were observed between subgroups based on cholecystectomy status, biliopancreatic limb length, types of surgery, body mass index, time to presentation since MBS, or proton pump inhibitor use. ROC analysis identified an optimal cut off of 59.5 µg/g (sensitivity: 64.6%; specificity: 63.4%; area under the curve: 0.653; Youden's index 0.280).

Conclusion: In patients following MBS, the optimal FCP cutoff value would be at 59.5 µg/g. However, given the low Youden's index and the minimal difference compared to the standard cutoff value of 50 µg/g, maintaining this standard, seems more practical in clinical settings.

Introduction: The association with Helicobacter pylori infection and inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is conflicting, with the former studies reporting a protective effect while others report increased inflammation. This study examines the effect of H. pylori infection on systemic inflammation - C-reactive protein levels - among IBD patients.

Methods: This retrospective cross-sectional study was conducted at Imam Abdulrahman Bin Faisal University Hospital, Al Khobar, Saudi Arabia, by reviewing the electronic medical records of 630 patients diagnosed with H. pylori infection, CD, or UC from January 2020 to December 2024. The levels of CRP were measured with a turbidimetric immunoassay of high sensitivity and categorized as normal or less than or equal to 1 mg/dL, moderate with a value of 1-10 mg/dL, or raised if the value is above 10 mg/dL. Kruskal-Wallis and Mann-Whitney U tests were used for statistical comparisons of CRP levels between groups.

Results: Mean CRP levels were highest in H. pylori-positive CD patients (12.69 mg/dL), UC patients (11.18 mg/dL), compared to H. pylori-negative matches (6.74 mg/dL for CD and 4.55 mg/dL for UC). The H. pylori-only group had the lowest average in CRP (2.62 mg/dL). Differences in patient categories were significant (p < 0.001); CD had 50% cases with elevated CRP, 40% for UC, and 60% for moderate elevations in H. pylori-only patients.

Conclusion: H. pylori infection is also accompanied by higher systemic inflammation in IBD, specifically in CD, characterized by high CRP.

Introduction: Both mesalazine and ozanimod are oral treatment options for patients with moderately active ulcerative colitis (UC).

Methods: Comparative analysis comparing efficacy endpoints of an 8-week non-inferiority induction study (TP0503) with 3.2 g/day mesalazine (n = 321) to the True North 10-week induction study of 1 mg/day ozanimod (n = 281). We compared the efficacy of oral mesalazine (Asacol) as monotherapy and ozanimod (Zeposia) as add-on therapy to mesalazine, without concomitant corticosteroids, following induction treatment in mesalazine-exposed but immunomodulator- and advanced therapy-naïve UC patients. Endpoints from the non-inferiority study were re-calculated using the definitions from the True North study.

Results: The two cohorts had similar age (45 ± 14 years vs. 44 ± 13.5 years) and baseline disease severity (total Mayo score; 8.5 ± 0.8 vs. 8.6 ± 1.1) for mesalazine- and ozanimod-treated patients, respectively. No differences were observed in patients achieving clinical response (reduction from baseline in the 3-component Mayo score [sum of rectal bleeding subscore/RBS, stool frequency subscore/SFS, and Mayo endoscopic score/MES) of ≥2 points and ≥35%, and a reduction from baseline in the RBS of ≥1 point or an absolute RBS ≤1} (58% vs. 58%; p = 0.917) and clinical remission (RBS = 0, SFS ≤1 [and decreases of ≥1 point from baseline SFS], and MES ≤1) (22% vs. 28%; p = 0.074) treated with mesalazine (at 8 weeks) and ozanimod (at 10 weeks), respectively. A higher percentage of patients treated with ozanimod achieved endoscopic improvement (MES ≤1 without friability) compared to mesalazine (38% vs. 29%, p = 0.018).

Conclusion: Among individuals previously exposed to mesalazine, a similar effect on clinical efficacy was observed between patients treated with mesalazine and those treated with ozanimod.

Introduction: E6011 is a newly developed humanized monoclonal antibody that binds to and neutralizes fractalkine with high specificity and affinity. In a previous phase 1, open-label study, E6011 demonstrated good tolerability and preliminary efficacy in Japanese patients with mild to moderate active Crohn's disease (CD).

Methods: In this early phase 2, double-blind, placebo-controlled study, we examined the efficacy and safety of E6011 in patients with moderate to severe active CD in a 12-week, double-blind period and the long-term efficacy and safety of E6011 in a subsequent open-label period for a maximum of 52 weeks. The primary efficacy endpoint was the percentage of patients who achieved a decrease in the CD activity index (CDAI) by ≥100 points from baseline at week 12.

Results: Of the planned 40 participants, enrollment was closed after 25 had been enrolled, primarily because of the delay in patient enrollment during the COVID-19 pandemic. A decrease in CDAI by ≥100 points was achieved in 33.3% (4/12) in the E6011 group and 23.1% (3/13) in the placebo group at week 12, resulting in a posterior difference of 9.6% (95% credible interval -23.7% to 42.7%). The probability of the difference between groups being ≥25% was 18.3%, which did not exceed the prespecified threshold of 50%. E6011 was safe and well tolerated in the 12-week, double-blind period. No new safety issues were reported in patients treated until week 40.

Conclusion: E6011 was safe and well tolerated in patients with moderate to severe active CD. Owing to the small sample size in this study, further studies are necessary to accurately evaluate its efficacy.

Background: For both men and women, family planning, including decisions regarding marriage and childbearing, is a significant life event that contributes to overall "happy life." Patients with chronic diseases such as inflammatory bowel disease face not only concerns about common pregnancy-related complications but also disease-specific challenges, including the potential effects of medications on the fetus and the risk of disease exacerbation during pregnancy. In response to these concerns, patients may occasionally make misguided decisions, such as the self-discontinuation of necessary treatment, increasing the risk of adverse health outcomes for both maternal health and fetal development.

Summary: Preconception care aims to address these concerns by providing guidance to mitigate factors that may negatively impact maternal and fetal health. This includes optimizing behavioral, personal, and environmental determinants of health. In this review article, we discuss the role of preconception care in supporting an optimized pregnancy, safe delivery, and healthy postpartum period for the patients wishing to have babies.

Key messages: Proper preconception counseling can improve the pregnancy outcomes. Healthcare professionals play a crucial role in preconception care by providing patients with accurate medical knowledge and guidance, enabling them to make informed decisions and ensuring a safe and well-prepared pregnancy and childbirth.

Introduction: It is crucial to predict the effectiveness of advanced therapies before their administration in ulcerative colitis (UC). Only a few studies have revealed predictive histological factors. Here, we sought to determine whether conventional histology of pretreatment endoscopic biopsy specimens can predict the response to integrin inhibitors.

Methods: In the present single-center retrospective study, we examined histopathological findings before initiating an integrin inhibitor. Primary response (PR) was defined as a ≥3-point decrease in the partial Mayo score at 14 weeks. Logistic regression was used to identify the factors predictive for a PR.

Results: We analyzed 21 biological and Janus kinase inhibitor-naïve patients with UC. The median baseline Mayo score was 7 (IQR, 6-8), and the C-reactive protein was 0.36 (IQR, 0.11-0.74). Histological findings included large lymphoid follicles (LF) in 61.9% (13/21), basal plasma cell infiltration in 52.4% (11/21), and eosinophilic infiltration (EO) in 42.9% (9/21). PR at 14 weeks was achieved in 57.1% (12/21). Among PR patients, LF was present in 91.7% (11/12), BP in 41.7% (5/12), and EO in 25.0% (3/12). PR was observed in 76.9% (10/13) of LF-positive patients vs. 12.5% (1/8) of LF-negative patients (p = 0.01). LF was significantly associated with the response to integrin inhibitors, whereas BP and EO were not.

Conclusion: The presence of LF in biopsy specimens predicts the response to integrin inhibitors in patients with UC. Conventional histological examinations may aid in predicting therapeutic responses to advanced therapies.