Bowel wall thickness measured by intestinal ultrasound as a marker of endoscopic disease activity in patients with Crohn's disease.

Background Transabdominal bowel ultrasound (TABUS) is an ideal tool to assess the bowel wall thickness (BWT) of children with Crohn’s disease (CD) due to its minimal invasiveness. Recently the Simple Ultrasound Activity Score for CD (SUS-CD) was developed and validated in adults using the Simple Endoscopic Score for CD (SES-CD). Our aim was to determine how the SUS-CD performed in children at diagnosis in comparison to endoscopy. Methods Pediatric patients (0–18 years old) with suspected inflammatory bowel disease (IBD) were prospectively enrolled through the Edmonton Pediatric IBD Clinic in Alberta, Canada. Patients underwent a baseline TABUS to visualize the intestine (excluding rectum, which is difficult to see with TABUS), blood work and endoscopy. The weighted pediatric CD activity index (wPCDAI) assessed disease activity, and SES-CD assessed endoscopic disease. Modified SUS-CD (excluding rectal sub score) was calculated using BWT scores (0=<3mm, 1=3–4.9mm, 2=5–7.9mm, 3=>8mm) and colour doppler scores (0=no or 1 vessel, 1=2–5 vessels, 2=>5 vessels per cm2) for each segment (terminal ileum, right colon, transverse colon, left colon) and compared to SES-CD. Modified SUS-CD was correlated to wPCDAI score, C-reactive protein (CRP) and fecal calprotectin (FCP). Using SPSS, anova and Chi square were used to assess for an association between TABUS parameters and wPCDAI. Spearman’s rank (rho) and Pearson’s correlation (r) were used to assess for a correlation between modified SUS-CD with SES-CD, wPCDAI, CRP and FCP. Results 40 patients recruited, 35 had CD (mean age 12.6(2.85)) and 5 were normal and scanned for suspected IBD (mean age 12.2(3.75)). Median wPCDAI and SES-CD scores for CD patients were 61(IQR 35.6–77.5) and 15(IQR 7.5–21) respectively. Fat proliferation was associated with severe CD based on wPCDAI (p<0.05). The modified SUS-CD score correlated well with the modified SES-CD score (rho=0.79,r=0.76,p<0.001,R2 linear=0.465). When the BWT threshold was lowered by 0.5mm for each BWT category, correlation improved (rho=0.80,r=0.82,p<0.001,R2 Linear=0.541). Using a similar lower threshold for BWT, a receiver operating characteristic curve analysis revealed an area under the curve of 0.87 and 0.90 for detecting mild endoscopic activity and moderate endoscopic activity, respectively. There was a significant correlation between SUS-CD and wPCDAI score (r=0.56,p<0.01), CRP (r=0.55,p<0.01) and FCP (r=0.56,p<0.01). Conclusion Fat proliferation was associated with more severe CD. The modified SUS-CD correlated well with modified SES-CD score, wPCDAI, CRP and FCP. Correlation improved when BWT threshold in each category was dropped by 0.5mm. These data support the use of TABUS as an effective adjunct to the assessment of pediatric CD.

High rates of screen failure for the minimum Simple Endoscopic Score for Crohn's Disease (SES-CD) plague Crohn's disease (CD) clinical trials. We aimed to determine the accuracy of segmental intestinal ultrasound (IUS) parameters and scores to detect segmental SES-CD activity. A single-center, blinded, cross-sectional cohort study of children and young adult patients with CD undergoing IUS and ileocolonoscopy, comparing segmental IUS bowel wall thickness (BWT), hyperemia (modified Limberg score [MLS]), and scores to detect segmental SES-CD activity: (i) SES-CD ≤2, (ii) SES-CD ≥6, and (iii) SES-CD ≥4 in the terminal ileum (TI) only. Primary outcome was accuracy of BWT, MLS, and IUS scores to detect SES-CD ≤2 and SES-CD ≥6. Secondary outcomes were accuracy of TI BWT, MLS, and IUS scores to detect SES-CD ≥4 and correlation with the SES-CD. Eighty-two patients (median [interquartile range] age 16.5 [12.9-20.0] years) underwent IUS and ileocolonoscopy of 323 bowel segments. Segmental BWT ≤3.1 mm had a similar high accuracy to detect SES-CD ≤2 as IUS scores (area under the receiver operating curve [AUROC] 0.833 [95% confidence interval 0.76-0.91], 94% sensitivity, and 73% specificity). Segmental BWT ≥3.6 mm and ≥4.3 mm had similar high accuracy to detect SES-CD ≥6 (AUROC 0.950 [95% confidence interval 0.92-0.98], 89% sensitivity, 93% specificity) in the colon and an SES-CD ≥4 in the TI (AUROC 0.874 [0.79-0.96], 80% sensitivity, and 91% specificity) as IUS scores. Segmental IUS scores strongly correlated with the SES-CD. Segmental IUS BWT is highly accurate to detect moderate-to-severe endoscopic inflammation. IUS may be the ideal prescreening tool to reduce unnecessary trial screen failures.

Background Crohn’s disease (CD) and ulcerative colitis (UC) are characterized by intestinal inflammation and increased extracellular matrix (ECM) remodeling, which are key pathophysiological mechanisms in patients with IBD and highly related to mucosal damage. Alterations in intestinal ECM turnover as well as macrophage and neutrophil activity may be reflected by secreted products that are released into the systemic circulation. In this study, we aimed to investigate associations between serum biomarkers of neutrophil activity (serum calprotectin) and collagen degradation (mucosal damage), and disease activity in patients with IBD. Methods Serological biomarkers of collagen formation (PRO-C3, PRO-C4, PRO-C6), matrix metalloproteinase (MMP)-mediated collagen degradation (C1M, C3M, C4M, C4G, C6Ma3) and intestinal inflammation (VICM [macrophage activity], human neutrophil elastase-derived fragment of calprotectin (CPa9-HNE [serum calprotectin, neutrophil activity]) were measured using Protein FingerPrint assay (PFA) technology in 100 patients with IBD (CD: n=44; UC: n=56). Biochemical disease activity was assessed using C-reactive protein (CRP) levels and available faecal calprotectin (FCal) levels. Endoscopic disease activity was determined using the Simple Endoscopic Score for CD (SES-CD) and Mayo endoscopic subscore for UC. Results C1M strongly associated with elevated CRP levels (defined as >5mg/L, P<0.001) in patients with IBD and significantly associated with faecal calprotectin levels in patients with UC (Spearman’s ρ=0.75, P<0.001). In patients with CD, C1M reasonably discriminated between patients with mild and moderate-to-severe endoscopic disease activity (AUC=0.73, P=0.01), whereas this discrimination was more subtle in patients with UC (AUC=0.68, P=0.08). CPa9-HNE levels were significantly increased in patients with elevated CRP levels (P=0.002 for both CD and UC) and associated best with faecal calprotectin levels in patients with CD compared with UC (CD: ρ=0.43, P=0.06; UC: ρ=0.20, P=0.45). Finally, CPa9-HNE levels were able to discriminate between mild and moderate-to-severe endoscopic disease activity in patients with CD (AUC=0.75, P<0.01). Conclusion C1M and CPa9-HNE levels associate with biochemical (CRP, FCal) and endoscopic disease activity in patients IBD, where C1M demonstrated higher accuracy in UC and CPa9-HNE appeared to be more useful in CD in this cohort. Therefore, C1M and CPa9-HNE could serve as surrogate biomarkers for the assessment of disease activity in patients with UC and CD, respectively. Our results should be validated in additional prospective, larger patient cohorts to corroborate these findings.

Inflammatory Bowel Disease Clinical

Background Mucosal healing is the ultimate treatment goal in inflammatory bowel disease (IBD). Endoscopic examination is the gold standard to determine disease activity in IBD, as routine activity measures, such as C-reactive protein (CRP), faecal calprotectin and clinical disease indices are inconsistent in representing luminal disease activity. Therefore, there is a great need for non-invasive biomarkers to assess mucosal inflammation. The aim of this study was to build an accurate prediction model of endoscopic disease activity in patients with quiescent and active IBD, based on a combination of serum inflammatory biomarkers. Methods Serum concentrations of 10 inflammatory biomarkers were analysed in 118 IBD patients (64 Crohn’s disease (CD), 54 ulcerative colitis (UC)) prior to biological treatment and 20 healthy controls. In 71 IBD patients, endoscopic disease activity was assessed by the Simple Endoscopic Score for CD (SES-CD) and Mayo endoscopic subscore for UC. Nonparametric ROC estimation with bootstrap inference was used to establish the best combination of inflammatory biomarkers predicting endoscopic disease activity. Results Six (6) inflammatory biomarkers (serum amyloid A (SAA), Eotaxin-1, IL-6, IL-8, IL-17A and TNF-α) all individually showed better prediction of IBD disease activity compared with routine measures (CRP, faecal calprotectin and HBI/SCCAI scores). The best combination of predictive inflammatory biomarkers consisted of serum SAA, IL-6, IL-8 and Eotaxin-1, showing an optimism-adjusted area under the ROC curve of 0.84 (95% CI: 0.73–0.94, P < 0.0001), which predicted significantly better (P = 0.002) than serum CRP levels with an AuROC of 0.57 (95% CI: 0.43–0.72, P = 0.32). The resulting combined calculated probability had a maximum sensitivity of 90.7% and specificity of 68.4% in correctly classifying IBD patients into the low and high endoscopic disease activity category (Youden’s J statistic = 0.58). Conclusions The combination of SAA, IL-6, IL-8 and Eotaxin-1 is superior over routine measures in predicting endoscopic disease activity in IBD. Serum inflammatory biomarkers are valuable tools for monitoring intestinal inflammation and guiding therapeutic decisions.

Background Redox imbalance and systemic oxidative stress are implicated in the pathophysiology of inflammatory bowel disease (IBD). Oxidative stress previously demonstrated strong associations with endoscopic disease activity in IBD1,2. In this study, we aimed to prospectively evaluate a panel of redox proteins, including circulating total free thiols (FTs), low-molecular-weight thiols including cysteine, glutathione (GSH), and homocysteine, ischemia-modified albumin (IMA), and thioredoxin-1, as biomarkers for endoscopic disease activity in patients with IBD. Methods Patients with IBD (n = 111) undergoing surveillance endoscopy were prospectively enrolled. Blood samples were collected at endoscopy along with clinical and biochemical disease activity assessments. Endoscopic disease activity was graded using the Mayo endoscopic subscore for patients with ulcerative colitis (UC) or the Simple Endoscopic Score for Crohn’s disease (SES-CD) for patients with Crohn’s disease (CD). Serum and plasma biomarkers (FTs, GSH, IMA, homocysteine, cysteine, thioredoxin-1) were measured by ELISA. Multivariable logistic regression analysis was used to investigate associations with disease activity, while adjusting for relevant confounders including sex, age and systemic steroid usage. Results Among all biomarkers, only serum GSH remained significantly associated with active endoscopic disease in multivariable analysis (adjusted odds ratio (OR) per doubling: 4.19, p = 0.04) (Fig. 1A). This was most evident in CD (p = 0.05), but not significant in UC (p = 0.10). IMA only showed a univariable association (p &amp;lt; 0.05) (Fig. 1B). ROC analysis identified GSH as the most accurate oxidative stress marker in distinguishing quiescent from active endoscopic disease (AUC=0.71 in CD; 0.65 in UC) (Fig. 1C). All these biomarkers were individually outperformed by fecal calprotectin (AUC=0.77). However, combining calprotectin with these oxidative stress markers substantially improved discriminative capacity (AUC=0.95) (Fig. 1D). Conclusion Serum GSH may serve as a systemic biomarker of endoscopic disease activity in IBD, particularly in patients with CD. While less accurate than fecal calprotectin alone, systemic oxidative stress markers strongly enhance its diagnostic performance, suggesting complementary value for disease monitoring.

Objective: To explore the clinical value of fecal calprotectin (FC) for evaluating disease activity in patients with Crohn’s disease (CD) and its relationship with disease location.Methods: Patients with CD were enrolled retrospectively, and clinical data, including FC levels, were collected. Clinical activity was assessed using the Crohn’s disease activity index (CDAI). Endoscopic activity was assessed using a simple endoscopic score for Crohn’s disease (SES-CD). The partial SES-CD (pSES-CD) was scored for the size of ulcers in each segment as defined by the SES-CD and was calculated as the sum of segmental ulcer scores.Results: This study included 273 CD patients. The FC level was significantly positively correlated with the CDAI and SES-CD, with correlation coefficients of 0.666 and 0.674, respectively. The median FC levels in patients with clinical remission and mildly active and moderately–severely active disease were 41.01, 164.20, and 444.45 μg/g. These values were 26.94, 66.77, and 327.22 μg/g during endoscopic remission and mildly and moderately–severely active stages, respectively. Compared with c-reactive protein (CRP), the erythrocyte sedimentation rate (ESR), and other biomarker parameters, FC was better at predicting disease activity for CD patients. For an FC <74.52 μg/g, the area under the curve (AUC) for predicting clinical remission was 0.86, with a sensitivity of 89.47% and a specificity of 71.70%. Moreover, endoscopic remission was predicted with a sensitivity of 68.02% and a specificity of 85.53%. The AUC was 0.83, and the cutoff value was 80.84 μg/g. In patients with ileal and (ileo) colonic CD, FC was significantly correlated with the CDAI, SES-CD, and pSES-CD. The correlation coefficients were 0.711 (CDAI), 0.473 (SES-CD), and 0.369 (pSES-CD) in patients with ileal CD and 0.687, 0.745, and 0.714 in patients with (ileo) colonic CD, respectively. For patients in remission, those in the active stage, and those with large or very large ulcers, differences in FC levels were not significant between patients with ileal and (ileo) colonic CD.Conclusion: FC is a reliable predictor of disease activity in patients with CD, including those with ileal CD. FC is thus recommended for the routine follow-up of patients with CD.

Leucine-rich alpha-2 glycoprotein (LRG) is a novel serum biomarker for inflammation in inflammatory bowel disease (IBD). This prospective study aimed to compare the value of LRG with C-reactive protein (CRP) and fecal calprotectin for evaluating clinical and endoscopic disease activity in patients with IBD. At entry, clinical and endoscopic disease activity was assessed in 267 patients with IBD (ulcerative colitis [UC] 203; Crohn's disease [CD] 64), and the levels of LRG, CRP and fecal calprotectin were measured. The accuracy of the biomarkers for the detection of clinical and endoscopic disease activity was determined by the area under the receiver operating characteristic curve. Leucine-rich alpha-2 glycoprotein showed a significant relationship with the clinical and endoscopic severity in both UC and CD (both diseases, P < .0001). In the clinical assessment of UC, the accuracy of LRG was significantly higher than that of CRP (0.73 vs 0.63; P < .001). In the endoscopic assessment of UC, the accuracy of LRG was significantly higher than that of CRP (P = .01), but it was significantly lower than that of fecal calprotectin (P = .009; LRG, 0.80; CRP, 0.72; fecal calprotectin, 0.91). In the clinical and endoscopic assessment of CD, the accuracy was not significantly different between the biomarkers (clinical activity: LRG, 0.71; CRP, 0.64; fecal calprotectin, 0.66; in endoscopic activity: LRG, 0.79; CRP, 0.78; fecal calprotectin, 0.81). Leucine-rich alpha-2 glycoprotein is a reliable serum biomarker for the assessment of clinical and endoscopic disease activity in patients with IBD. It can be an alternative to CRP for the assessment of UC.

Crohn's disease (CD) is a chronic inflammatory bowel disease characterized by relapsing and remitting inflammation of the gastrointestinal tract. Reliable and non-invasive methods to assess disease activity are crucial for guiding treatment and improving patient outcomes. This study investigates how intestinal ultrasound (IUS) parameters and fecal calprotectin (FC) levels correlate with endoscopic severity scores in Crohn's disease (CD). AIM ANDOBJECTIVE: To assess the effectiveness of IUS as a complementary tool to conventional methods in predicting disease severity in CD by correlating IUS parameters, specifically bowel wall thickness (BWT) and color Doppler flow (CDF), with FC levels and Simple Endoscopic Score for Crohn's Disease (SES-CD). A cross-sectional observational study was conducted on 45 patients with confirmed CD at the Department of Gastroenterology. Clinical data, FC levels, SES-CD scores, and IUS measurements were collected and analyzed. The correlation between BWT, FC, and SES-CD scores was assessed using Pearson correlation, and the sensitivity and specificity of combined IUS and FC parameters were calculated. The study found significant correlations between higher CDF scores and increased FC levels in the ileum (P = 0.002) and ascending colon (P < 0.001). BWT showed a significant positive correlation with SES-CD in the descending colon (r = 0.440, P = 0.003) and rectosigmoid (r = 0.366, P = 0.014). The combination of BWT > 3mm and FC > 250µg/g demonstrated high sensitivity and specificity, particularly in the ileum (sensitivity 88.6%, specificity 78.9%) and descending colon (sensitivity 80.9%, specificity 87.7%). Combining IUS parameters, particularly BWT and CDF, with FC levels provides a robust method for predicting disease severity in CD. This approach can enhance disease monitoring, reduce reliance on invasive procedures, and improve patient management in clinical practice.

Background:Crohn’s disease (CD) is a chronic inflammatory bowel disease. Monitoring the disease activity and providing appropriate treatment are essential for improving long-term prognosis. Endoscopy remains the gold standard for assessing disease activity; however, it is invasive and costly. Recently, we identified gelsolin as a promising serum biomarker for endoscopic disease activity in ulcerative colitis.Objective:To investigate serum gelsolin levels as a potential biomarker for mucosal activity in the small bowel and colon of patients with CD. Furthermore, we aimed to compare the performance of gelsolin with that of C-reactive protein (CRP) in detecting mucosal activity.Design:A retrospective observational study at a single tertiary care center.Methods:Serum gelsolin and CRP were measured in 82 patients with CD and 16 healthy controls. Endoscopic disease activity was assessed using the Applied Simple Endoscopic Score for CD (aSES-CD). We conducted receiver operating characteristic curves and correlation analyses. In addition, subgroup analyses were performed to evaluate differences in the biomarker performance between ileal and ileocolonic types of CD.Results:Serum gelsolin levels were significantly lower in patients with CD than in healthy controls (p < 0.001). Gelsolin levels were negatively correlated with aSES-CD, particularly in patients with the ileocolonic-type CD, and showed a stronger correlation with endoscopic activity than CRP. The area under the curve for gelsolin was 0.8377, with a cutoff of 13 µg/mL, yielding 75% and 83% sensitivity and specificity, respectively.Conclusion:Serum gelsolin is a prospective noninvasive biomarker that outperforms CRP in detecting endoscopic disease activity in patients with ileocolonic-type CD.

Intestinal ultrasound (IUS) is a noninvasive tool to assess bowel inflammation. There is a paucity of data on its accuracy in pediatric patients. The aim of this study is to evaluate the diagnostic performance of bowel wall thickness (BWT) measured using IUS compared with endoscopic disease activity in children suspected of having inflammatory bowel disease (IBD). We conducted a single-center cross-sectional pilot study of pediatric patients suspected to have previously undiagnosed IBD. Endoscopic inflammation was graded using segmental scores of the Simple Endoscopic Score for Crohn's Disease (SES-CD) and the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and classified as having healthy, mild, or moderate/severe disease activity. Association between BWT and endoscopic severity was assessed using the Kruskal-Wallis test. The diagnostic performance of BWT to detect active disease at endoscopy was evaluated using the area under the receiver operating characteristic curve; sensitivity and specificity were calculated. In all, 174 bowel segments in 33 children were assessed by IUS and ileocolonoscopy. An elevated median BWT was associated with increased bowel segment disease severity, classified by the SES-CD (P < .001) and the UCEIS (P < .01). Using a cutoff value of 1.9 mm, we found that the BWT had an area under the receiver operating characteristic curve of 0.743 (95% CI, 0.67-0.82), a sensitivity of 64% (95% CI, 53%-73%), and a specificity of 76% (95% CI, 65%-85%) to detect inflamed bowel. Increasing BWT is associated with increasing endoscopic activity in pediatric IBD. Our study suggests that the optimal BWT cutoff value for detecting active disease may be less than that seen in adults. Additional pediatric studies are needed.

Fecal biomarkers have emerged as an important tool for assessing and monitoring disease activity in patients with inflammatory bowel diseases (IBDs). We performed a prospective head-to-head comparison of the diagnostic accuracy of both fecal calprotectin (fCal) and neopterin (fNeo), and serum C-reactive protein in predicting endoscopic disease severity in patients with IBD. A total of 133 consecutive patients with IBD (78 Crohn's disease [CD] and 55 ulcerative colitis [UC]) undergoing a colonoscopy provided fecal samples for the measurement of fCal and fNeo concentrations and a blood sample for the serum C-reactive protein measurement. Endoscopic disease activities were scored independently according to the Simple Endoscopic Score for CD in patients with CD and to the Rachmilewitz Index in patients with UC. The respective performances of the fecal markers with respect to endoscopic disease severity were assessed by computing correlations, sensitivities, specificities, and overall accuracies at adjusted cutoffs and also test operating characteristics. The fCal and fNeo concentrations differed significantly in clinically and endoscopically active IBD when compared with those in patients with inactive disease. Both fCal and fNeo concentrations correlated closer with endoscopic scores in UC (r = 0.75 and r = 0.72, respectively; P < 0.0001 for both) than in CD (r = 0.53 and r = 0.47, respectively; P < 0.0001 for both). Using cutoffs of 250 μg/g for fCal and 200 pmol/g for fNeo, both fecal markers had similar overall accuracies to predict endoscopic activity in patients with CD (74%) and also a higher and similar accuracies (88% and 90%, respectively) in patients with UC, whereas accuracies of C-reactive protein were slightly lower in patients with CD and UC. The fNeo is a novel reliable surrogate biomarker with the potential to identify patients with IBD with active mucosal lesions and represents an alternative marker as accurate as fCal to predict and monitor the severity of mucosal damages in patients with IBD.

Background Pediatric patients with newly diagnosed Crohn’s disease (CD) often undergo magnetic resonance enterography (MRE) to assess bowel not accessible by endoscopy and to evaluate for CD complications. In contrast to intestinal ultrasound (IUS), MRE access is quite limited, expensive, and not feasible for young patients. Little is known about how MRE and IUS compare, with a recent systematic review reporting inconclusive results when comparing diagnostic accuracy in pediatric CD. This study therefore aimed to compare MRE and IUS at diagnosis of pediatric CD. Methods Pediatric patients (≤18 years old) seen for suspected CD were prospectively consecutively enrolled (2019-2022) and underwent endoscopy (Simple Endoscopic Score for Crohn Disease (SES-CD)), MRE, IUS (performed by IUS trained pediatric gastroenterologists), calprotectin, blood work and assessment (weighted Pediatric Crohn Disease Activity Index (wPCDAI)). A blinded pediatric radiologist read all MREs. An interim analysis was done after 21 patients before the final analysis. Statistical analyses included descriptive statistics and Pearson chi-square. Results 58 patients (n=38, 66% male) were included; median age 13 years (IQR 10-15, range 6-17). Disease activity at diagnosis was moderate: median SES-CD 14 (IQR 10-21), wPCDAI 48 (IQR 34-59), calprotectin 1455ug/g (IQR 840-2454), C-reactive protein 47mg/L (IQR 27-72), and erythrocyte sedimentation rate 33mm/hr (IQR 18-46). Jejunum and proximal ileum involvement had high levels of agreement between MRE and IUS for non-inflamed bowel, but less agreement for inflammation (Figure 1). There was higher agreement for inflamed distal ileum compared to proximal ileum or jejunum (Figure 1). MRE and IUS performed similarly in identifying endoscopically inflamed bowel, with the highest accuracy for the terminal ileum (TI) (Figure 2). Both were more accurate for moderate/severe (segment SES-CD≥7) vs. mild/moderate/severe disease (segment SES-CD≥3) (Figure 2). For patients with endoscopic TI strictures (n=8/58, 14%), this was seen on MRE (n=8/8, 100%) more often than IUS (n=5/8, 63%). Those without endoscopic TI strictures were still reported on MRE (n=15/50, 30%), more than IUS (n=2/50, 4%). There were no significant differences in MRE vs. IUS bowel wall thickness measurements in all segments of the small and large bowel (p&amp;gt;0.05). Conclusion IUS and MRE performed similarly in distal small bowel and colonic CD assessment in both the identification and measurement of inflamed bowel. More proximal small bowel disease may be over reported by MRE or under reported by IUS. MRE also over reported TI stricturing disease. Both may miss mild CD. For initial and longitudinal pediatric CD assessment, repeating IUS rather than MRE is a viable option.

Objective: By investigating the correlation between quantitative parameters of contrast enhanced ultrasound (CEUS) and commonly used activity assessment indicators of Crohn's disease (CD), and comparing the predictive power of laboratory inflammatory indicators with CEUS on Crohn's disease (CD), the significance of CEUS was evaluated. Methods: A case-control study. From October 2019 to December 2021, the clinical data of 67 patients with CD who were diagnosed by endoscopy and underwent contrast-enhanced ultrasonography were retrospectively analyzed in the First Affiliated Hospital with Nanjing Medical University, and their routine ultrasound and CEUS parameters, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fecal calprotectin (FC), Crohn's disease activity index (CDAI) and simplified endoscopic score for Crohn's disease (SES-CD) were collected. Using SES-CD as the standard, the patients were divided into a remission group and an active group, and the correlation of laboratory inflammatory indexes and contrast-enhanced ultrasound parameters with CDAI and SES-CD were evaluated. Besides, the ROC curve was used to analyze the predictive efficacy of each index on CD endoscopic activity. Results: A total of 67 patients were included in this study. According to the SES-CD score, there were 17 patients in the remission group and 50 patients in the active group. Except for the coefficient of the enhancement wash in slope and time to peak (TTP), the peak intensity (PI), area under the angiography curve, and laboratory inflammatory indexes were significantly different between the two groups (P<0.05), which also showed a moderate positive correlation with CDAI and SES-CD (P<0.05). ROC analysis showed that among the non-invasive indicators, PI and area under the angiography curve had the highest AUCs for predicting CD endoscopic activity, which were 0.912 and 0.891, respectively; with SES-CD taking >3 as the cut-off value, the corresponding sensitivities were 78.0% and 72.0%, with specificities of 100.0% and 94.1%, respectively. Conclusion: CEUS can objectively and repeatedly evaluate the disease activity of CD patients, and has great clinical application value, which can be used as a reliable imaging method for diagnosis and follow-up of patients with Crohn's disease.

Background The endoscopic healing index (EHI) is a novel multi-protein serum biomarker test developed and validated to assess endoscopic disease activity in patients with Crohn’s disease (CD). Evidence for the use of EHI to guide decision-making during infliximab (IFX) treatment remains scarce. Therefore, we aimed to characterise the relationships between IFX dose, serum IFX concentrations, EHI, and endoscopic remission (ER). Methods Data were obtained from 118 biologic naïve adult patients with CD enrolled in the phase 4 TAILORIX trial (EudraCT 2011 003038 14). All patients had confirmed active CD at baseline based on clinical, biological, and endoscopic criteria. IFX and EHI (scores ranging from 0–100) were measured using a homogenous mobility shift assay (HMSA) and immunoassay, respectively (Prometheus Laboratories). First, the previously published population pharmacokinetic (popPK) model of the TAILORIX study population was revisited to describe the HMSA data. The effect of EHI, faecal calprotectin (FC), C-reactive protein (CRP), and serum albumin (ALB) on IFX clearance was evaluated. Next, a minimal continuous-time Markov model was developed to describe the time course of EHI within patients. EHI was considered as a three-stage ordinal variable (scores 0–19, 20–49, and 50–100) with the lowest score stage (0–19) indicative of ER. The course-modifying effect of IFX on EHI was assessed. Finally, a generalised linear model was used to describe the relationship between EHI and the probability of attaining ER (Simple Endoscopic Score for CD [SES-CD] ≤2). The predictive ability of EHI for ER was compared with that of FC, CRP, ALB, and IFX using a receiver operating characteristic (ROC) curve analysis. Results The revisited two-compartment popPK model described the IFX data with adequate descriptive and predictive accuracies. EHI, FC, CRP, and ALB at week (w)0 were not found to explain interpatient variability in IFX clearance. In contrast, higher IFX at w14 was associated with a higher probability of achieving EHI &amp;lt;20 at w14 (Figure 1). The probability of attaining EHI &amp;lt;20 at w14 was predicted to increase more than four-fold when IFX at w14 was targeted at 10 mg/L instead of 5 mg/L (Table 1). EHI and FC equally well predicted the probability of attaining ER at the same time point (Figure 2, Table 2). Conclusion EHI, FC, ALB, and CRP at w0 should not be considered for a priori IFX dose optimisation. Nevertheless, a posteriori IFX dose optimisation (based on IFX concentrations measurements) towards a predefined IFX concentration at w14 may lead to lower post-induction EHI scores and thus improved ER rates. An IFX target of 10 mg/L at w14 is associated with four-fold higher normalisation of EHI as compared to the commonly used target of 5 mg/L.