Background Inflammatory bowel disease (IBD), including Crohn\'s disease (CD) and ulcerative colitis (UC), presents significant challenges, particularly in pediatric patients. Vitamin D deficiency has been associated with IBD, but its role in disease activity and remission remains unclear. This study investigates the relationship between serum vitamin D levels and IBD markers, including Pediatric Crohn\'s Disease Activity Index (PCDAI), Pediatric Ulcerative Colitis Activity Index (PUCAI), fecal calprotectin levels, and endoscopy findings. It also explores racial and ethnic disparities in these relationships. Methodology A retrospective study was conducted involving 51 pediatric patients with IBD from the Nemours Children\'s Health EMR system. Inclusion criteria required documented serum vitamin D levels at diagnosis and post-treatment, and at least one post-treatment assessment of PUCAI/PCDAI, calprotectin, or endoscopy. The study employed Spearman and Pearson correlation tests to analyze the associations between vitamin D levels and IBD markers. Ethnicity and race were analyzed using t-tests and chi-square tests. Results No statistically significant correlations were found between changes in serum vitamin D levels and IBD markers (endoscopy results, calprotectin levels, PUCAI/PCDAI scores) for both UC and CD. Analysis of racial and ethnic disparities revealed that Hispanic patients had significantly higher post-treatment calprotectin levels compared to non-Hispanics, although other markers showed no significant differences. Vitamin D levels did not significantly differ between racial or ethnic groups. Conclusions This study found no significant correlation between serum vitamin D levels and IBD activity markers in pediatric patients. Despite initial hypotheses, vitamin D levels do not appear to be useful in assessing IBD remission or disease state. Racial and ethnic disparities in IBD severity were observed, but further research with larger sample sizes and more consistent data collection is needed to draw more definitive conclusions.

BACKGROUND: Complicated perianal disease (cPD) may be the sole presentation of Crohn\'s disease (CD). The role of small-bowel capsule endoscopy (SBCE) in the diagnostic algorithm of cPD is unclear. We aimed to evaluate the role of SBCE as a diagnostic tool, in patients with cPD, after a negative standard workup for CD.
METHODS: A multicenter, retrospective, cross-sectional study, in patients with cPD, and negative standard workup for CD (ileocolonoscopy and cross-sectional imaging), who underwent SBCE for suspected CD. Demographics, biomarkers, and the Lewis Score (LS) were recorded and analyzed. An LS ≥ 135 was considered a positive SBCE for diagnosing CD.
RESULTS: Ninety-one patients were included: 65 (71.4%) males; median age: 37 (29-51) years; cPD duration: 25.1 (12.5-66.1) months. Positive SBCE: 24/91 (26.4%) patients. Fecal calprotectin (FC) positively correlated with LS (r = 0.81; p < 0.001). FC levels of 100 µg/g and 50 µg/g had a sensitivity of only 40% and 55% to rule out small-bowel CD, with a negative predictive value (NPV) of only 76% and 80%, respectively.
CONCLUSIONS: SBCE contributed to CD diagnosis in a quarter of patients with cPD after a negative standard workup. FC levels correlated with the degree of inflammation defined by the LS. However, the NPV of FC was low, suggesting that SBCE should be considered for patients with cPD even after a negative standard workup.

UNASSIGNED: Small bowel capsule endoscopy (SBCE) is an essential tool for evaluation of small bowel (SB) Crohn disease (CD). Fecal calprotectin (FC) represents an important biomarker of intestinal inflammation, widely used in ulcerative colitis and CD. Our aim was to evaluate the role of FC for diagnosing inflammatory activity in patients with isolated SB CD and how it correlates with SBCE findings.
UNASSIGNED: This is a retrospective study conducted in a tertiary inflammatory bowel disease referral center that included patients with SB CD who underwent SBCE between January 2017 and February 2023. FC value was obtained from the closest stool examination to SBCE.
UNASSIGNED: One hundred ninety-six patients were included: 123 were women (63%) with a mean age of 44.2 years. In the SBCE, 127 (65%) patients had a Lewis Score ≥135 and, among the 94 patients with FC >200 μg/g, 23 had LS <135, 36 had LS between 135 and 790, and 35 had LS ≥790. FC levels were predictive of endoscopic lesions in SBCE, with significant correlation between FC level and total LS (Pearson correlation coefficient 0.43, P<.001). The sensitivity and specificity were calculated for each cut-off value being respectively 78% and 45% for FC = 100 μg/g, 69% and 59% for FC = 150 μg/g and 67% and 67% for FC = 200 μg/g.
UNASSIGNED: FC showed moderate correlation with endoscopic findings in SBCE in SB CD. It is, therefore, a reasonable marker for predicting significant inflammatory lesions in SBCE; however, none of the cut-off had a high sensitivity or specificity.

UNASSIGNED: Fecal calprotectin (FC) is a noninvasive biomarker used in inflammatory bowel disease (IBD) management and risk stratification of nonspecific gastrointestinal symptoms. Leukocyte esterase is an inexpensive and widely available point-of-care inflammatory marker present on urinalysis test strips. We aim to assess the diagnostic accuracy of fecal leukocyte esterase (FLE) relative to FC and endoscopy and demonstrate its use as an alternative biomarker for IBD.
UNASSIGNED: In this prospective cohort study, 70 patients who had FC ordered as part of standard clinical care also received FLE testing. FLE levels were compared with various FC cutoff values and endoscopy and pathology findings as the gold standard.
UNASSIGNED: As the FC cutoff increased from 50 to 500 μg/g, FLE sensitivity increased from 67% to 95% while the specificity decreased from 86% to 76%. The area under the receiver operating characteristic (AUROC) curve increased from 0.79 to 0.90. An FLE of ≥1+ had the best test characteristics. Among patients who underwent endoscopic evaluation, FLE demonstrated an identical sensitivity (75%) and specificity (86%) to FC in predicting endoscopic inflammation. AUROC was 0.80 for FLE and 0.85 for FC with an optimal cutoff of ≥2+ and 301 μg/g, respectively. When used to distinguish between patients with active IBD and no/inactive IBD, FLE had a sensitivity of 84% and specificity of 90%, comparable with the 84% and 83%, respectively, of FC. AUROC was 0.88 for FLE and 0.91 for FC with an optimal cutoff of ≥2+ and 145 μg/g, respectively.
UNASSIGNED: FLE demonstrates adequate correlation and comparable accuracy with FC in predicting endoscopic inflammation and distinguishing between patients with active vs inactive IBD.

UNASSIGNED: Patients with diverticular disease (DD) frequently have abnormal bowel movements. However, it is unknown whether the entity of these alterations is associated with the severity of DD. We aimed to assess bowel habits and their relationship with the severity of DD according to Diverticular Inflammation and Complication Assessment (DICA) classification, Combined Overview on Diverticular Assessment (CODA) score, and fecal calprotectin (FC).
UNASSIGNED: An international, multicenter, prospective cohort study was conducted in 43 centers. A 10-point visual analog scale (VAS) was used to assess the severity of constipation and diarrhea. The association of constipation and diarrhea with DICA classification, CODA score, and basal FC was tested using non-parametric tests. Survival methods for censored observations were applied to test the association of constipation and diarrhea with the incidence of acute diverticulitis over a 3-year follow-up.
UNASSIGNED: Of 871 patients with DD were included in the study. Of these, 208 (23.9%) and 199 (22.9%) reported a VAS score for constipation and diarrhea at least 3 at baseline, respectively. Higher constipation and diarrhea scores were associated with increasing DICA classification, CODA score and basal FC (P< 0.001). Constipation and diarrhea scores were independently associated with an increased hazard of developing acute diverticulitis (hazard ratio [HR]constipation = 1.15 per 1-VAS point increase, 95% confidence interval [CI], 1.04-1.27; P=0.004; and HRdiarrhea =1.14; 95% CI, 1.03-1.26; P=0.014, respectively).
UNASSIGNED: In newly diagnosed patients with DD, higher endoscopic and combined scores of DD severity were associated with higher scores of constipation and diarrhea at baseline. Both constipation and diarrhea were independent prognostic factors of acute diverticulitis.

OBJECTIVE: Fecal calprotectin (FC) is known to be a sensitive biomarker of colonic inflammation but to a lesser degree of small bowel (SB) inflammation. Moreover, data on FC\'s diagnostic levels in different SB segments are scarce. We aimed to examine FC\'s diagnostic levels along the SB-axis in CD.
METHODS: This was a post-hoc aggregated analysis of five prospective studies of adult CD patients, who underwent FC testing and SB video capsule endoscopy (VCE). Lewis score (LS) inflammation in different SB segments was tested for correlation with FC level after exclusion of colonic disease. The diagnostic levels of FC for SB inflammatory topographical-gradient were assessed using a receiver operating characteristic.
RESULTS: 214 patients were included (age:30 [24-43] year-old, males-57%). For a similar SB inflammatory-activity (LS≥135), FC levels incrementally increased from proximal to distal SB segments (63 [30-121] versus 190 [78-549], p=0.005) and from distal SB segment to the colon (190 [78-549] versus 542 [185-1000], p=0.010). The best FC cutoffs to identify isolated mild proximal/distal SB-inflammation (LS≥135) were 77μgg and 123μgg, respectively. A cutoff of 234μgg was best to detect more significant proximal inflammation (LS≥350) when only mild distal SB-inflammation was present. In sensitivity analyses, this proximal-to-distal FC gradient was maintained when LS≥350 and LS≥790 were used as the inflammatory reference-values. Unlike FC, the magnitude of CRP elevation was unrelated to the topography of inflammation along the SB-axis.
CONCLUSIONS: FC may serve as a topographical biomarker of CD-activity, with its sensitivity to identify mucosal inflammation increases from proximal to distal SB segments.

Inflammatory bowel diseases (IBD) remain challenging in terms of understanding their causes and in terms of diagnosing, treating, and monitoring patients. Modern diagnosis combines biomarkers, imaging, and endoscopic methods. Common biomarkers like CRP and fecal calprotectin, while invaluable tools, have limitations and are not entirely specific to IBD. The limitations of existing markers and the invasiveness of endoscopic procedures highlight the need to discover and implement new markers. With an ideal biomarker, we could predict the risk of disease development, as well as the possibility of response to a particular therapy, which would be significant in elucidating the pathogenesis of the disease. Recent research in the fields of machine learning, proteomics, epigenetics, and gut microbiota provides further insight into the pathogenesis of the disease and is also revealing new biomarkers. New markers, such as BAFF, PGE-MUM, oncostatin M, microRNA panels, αvβ6 antibody, and S100A12 from stool, are increasingly being identified, with αvβ6 antibody and oncostatin M being potentially close to being presented into clinical practice. However, the specificity of certain markers still remains problematic. Furthermore, the use of expensive and less accessible technology for detecting new markers, such as microRNAs, represents a limitation for widespread use in clinical practice. Nevertheless, the need for non-invasive, comprehensive markers is becoming increasingly important regarding the complexity of treatment and overall management of IBD.

BACKGROUND: Microbial imbalance is thought to play a role in the pathogenesis of Diverticular Disease (DD).
OBJECTIVE: We aimed to assess the efficacy of a symbiotic mixture (Prolactis GG Plus®) in the treatment of moderate to severe DD, scored according to the Diverticular Inflammation and Complication Assessment (DICA) classification.
METHODS: A retrospective study was conducted enrolling the following patients: at the first diagnosis of DD; in whom DD was diagnosed with colonoscopy and scored according to DICA classification; treated with Prolactis GG Plus® two times/daily for 2 consecutive months; in whom the severity of the abdominal pain was scored with a 10-points visual-analogue scale (VAS) at baseline and the end of follow-up; in whom fecal calprotectin (FC) was assessed at baseline and the end of follow-up as μg/g.
RESULTS: Twenty-four patients were identified (10 males, 14 females; 16 as DICA 2, and 8 as DICA 3). Prolactis GG Plus® decreased the severity of abdominal pain both in DICA 2 (p =0.02) and DICA 3 patients (p =0.01), while FC decreased significantly in DICA 2 (p <0.02) but not in DICA 3 (p =0.123) patients. Acute diverticulitis occurred during the follow-up in two DICA 3 patients but none DICA 2 patients. Add-on therapy was required by eight DICA 2 (50%) and six DICA 3 patients (75%).
CONCLUSIONS: In newly diagnosed patients with DD, the symbiotic mixture Prolactis GG Plus® can be a potential treatment for moderate (DICA 2) DD as a single treatment.

OBJECTIVE: Close monitoring of disease activity in IBD patients is essential to avoid long term complications. Although endoscopic assessment is the ideal monitoring tool, the usage of noninvasive biomarkers is more practical and patient friendly. We aimed to study the performance of Interleukin-6(IL-6) and Serum Amyloid A(SAA) as serum biomarkers in assessment of the disease activity of IBD patients in correlation to C-reactive protein (CRP), Fecal Calprotectin (FC) and endoscopic indices.
METHODS: 83 IBD (26 CD and 57 UC) patients on stable treatment regimen were recruited. Serum markers included CRP, CBC, IL-6, SAA were analyzed, together with FC. These markers were compared with the endoscopic and clinical disease parameters. Harvey-Bradshaw Index (HBI) and the Simple Clinical Colitis Activity Index (SCCAI) were used to assess clinical activity in CD and UC patients, respectively. Endoscopic activity was recorded using the Simple Endoscopic Score (SES) for Crohn\'s disease or the Mayo Endoscopic Score (MES) for ulcerative colitis.
RESULTS: In prediction of disease activity, IL-6, SAA and CRP demonstrated good area under receiver operating characteristics (AUC) (>0.7), with FC being the best (0.94) for endoscopically active disease (P < 0.01). Combining FC and IL-6 or SAA improved its discriminative accuracy with an AUC (∼0.96).
CONCLUSIONS: FC most accurately predicts endoscopic disease activity in IBD patients, in comparison to other studied serological biomarkers. The serum IL-6 and SAA are potential predictors of endoscopic disease activity, and they might be valuable for assessment of disease activity. Finally, a composite score of FC and SAA or IL-6 can increased its diagnostic accuracy.

BACKGROUND: While fecal calprotectin (Fcal) is now recommended, the positioning of intestinal ultrasonography (IUS) is still unknown to monitor patients with CD.
OBJECTIVE: To assess the agreement between IUS performed by a novice sonographer and Fcal to detect active CD and to compare these two monitoring tools to determine the need for therapeutic escalation.
METHODS: In this cross-sectional prospective study, we consecutively included CD patients ≥ 18 years-old with concomitant IUS and Fcal testing within 7 days. IUS was performed by a novice sonographer. The endpoints were the agreement between IUS and Fcal (> 150 µg/g) to detect active CD and the need for therapeutic escalation.
RESULTS: Among 66 patients undergoing IUS, 56 patients had also Fcal testing. The agreement between IUS and Fcal to detect an active CD was 80.4% (κ-coefficient = 0.536 ± 0.127). Fcal, IUS or both had respectively the following positive (76.9%[54.0-99.8], 70.0%[49.9-90.1], and 81.8%[59.0-100.0]) and negative (81.4%[69.8-93.0], 88.9%[78.6-99.2], and 80.0%[68.3-91.7]) predictive values to detect active CD requiring therapeutic escalation. Using a 10 points-acceptability numerical scale, IUS presented with a better acceptability than Fcal (9.5 ± 1.2 vs 8.0 ± 2.3, p < 0.0001). Contrary to the agreement with Fcal and the performances of IUS to identify the need for therapeutic escalation, the duration of IUS procedure decreased over time (correlation coefficient = - 0.54, p = 0.001) and plateaued between 15 and 20 min-long from the 24th procedure.
CONCLUSIONS: IUS and fecal calprotectin do not give the same information and could be complementary to monitor patients with CD.