Impact of Elexacaftor-Tezacaftor-Ivacaftor on Gastrointestinal Symptoms, Intestinal Ultrasound, and Pancreatic Stiffness in Cystic Fibrosis.

The Use of Intestinal Ultrasound in Ulcerative Colitis—More Than a Mucosal Disease?

Background In paediatric Inflammatory Bowel Disease (IBD) selecting the right treatment in the early stages of disease is key to prevent disease progression and to prevent unnecessary exposure to ineffective treatment. Intestinal ultrasound (IUS) is increasingly used to monitor disease activity in response to therapy. However, little is known about the early transmural changes during anti-tumour necrosis factor (anti-TNF) therapy in paediatric IBD. The aim of this study is to assess the early changes in IUS parameters and to evaluate the very early predictive value of IUS for therapy response in paediatric IBD treated with anti-TNF-α therapy. Methods In this pilot study children (aged 3-18 years) starting with anti-TNF therapy (infliximab or adalimumab) were enrolled prospectively if ultrasound at baseline showed bowel wall thickness (BWT) ≥ 2,5mm. IUS was performed at baseline and the most affected bowel segment was identified. Subsequently IUS was repeated in this segment at week 2 and week 13. Response to therapy was determined at week 13. Response and remission was defined as follows. - Therapy response: a ≥50% decrease in faecal calprotectin (FCP) in combination with a decrease in PUCAI (≥20 points or normalisation) /PCDAI (≥12.5 points or normalisation), or normalisation of FCP (<250mg/kg)) - IUS response: decrease in BWT by 25% OR decrease in BWT by >2.0 mm of the most severely affected segment compared to baseline - IUS remission/Transmural healing: BWT<2.0 mm and no Doppler signal(Limberg score) and no mesenteric fat proliferation Results Eleven IBD patients (aged 7 to 12 years; 64% female) were enrolled. IUS response was observed in 5/11 patients at week 2 (decrease in BWT -25% in all). Doppler signal decreased in 3/11(one point in Limberg score in all). After 13 weeks 4/11 patients showed therapy response and 3/11 showed IUS remission. Conclusion Transmural changes were detected by IUS as early as 2 weeks after initiating anti-TNF therapy. This pilot study observed mainly reactivity in BWT, in contrast with previous studies that initially noted changes in Doppler signal. IUS has the potential to predict therapy response at an early stage. A larger sample size is needed to accurately assess its predictive value at week 2 for treatment response.

BACKGROUND In patients with Crohn’s disease (CD), following an ileocolic resection (ICR), colonoscopy is the gold standard for the detection of endoscopic recurrence (ER). Colonoscopy, however, is invasive and not easily accepted by patients for repeated monitoring. In contrast, transabdominal intestinal ultrasound (IUS) is non-irradiating, non-invasive, and easy to repeat. The goal of this study was to assess the accuracy of IUS for ER in CD. METHODS This was a cross-sectional study of CD patients who underwent point-of-care IUS during a postoperative follow-up clinic visit within 30 days of a planned colonoscopy. Parameters on IUS included bowel wall thickness (BWT), bowel wall hyperemia (BWH), layer stratification, inflammatory fat, lymphadenopathy, and complications. C-reactive protein (CRP), fecal calprotectin (FC), endoscopic healing index (EHI) and Harvey Bradshaw Index (HBI) were also measured. ER was defined as a Rutgeerts Score (RS) ≥ i2. Primary outcome was the association between IUS parameters and ER. Secondary outcomes were the association of IUS parameters with other markers of disease activity. Univariable analysis – Fisher’s exact, Wilcoxon Rank Sum and Spearman correlation coefficient tested associations with ER. Area under the receiver operator curve (ROC) was used to determine optimal cut-off values for BWT to accurately identify ER. RESULTS Eighteen CD patients (9 female; 29 [19-40] years old), underwent IUS examination 45 [29-99] months post-ICR. All patients underwent endoscopy within 30 days of IUS examination, four (22%) for the first time post-ICR. Seven (39%) patients were on ustekinumab, four (22%) on adalimumab, two (11%) on infliximab, one (6%) on vedolizumab, and four (22%) on no therapy. ER was found in eight (44%) patients. BWT and BWH in the neo-terminal ileum and BWH at the ileocolic anastomosis were the only IUS parameters associated with ER (Table 1). BWT was 4.0 [3.2-4.8] mm in patients with ER vs. 2.0 [1.5-2.6] mm without (p=0.04). Neo-terminal ileum BWH was abnormal in six (75%) patients with ER vs. 0% without (p=0.007). BWT of 3.2 mm was the optimal cut point for predicting ER with an: AUROC of 0.82, positive predictive value of 100%, negative predictive value of 97.3%, sensitivity of 75%, and specificity of 100% (Figure 1) vs. a CRP of 10.4 mg/L (AUROC = 0.54) or FC of 1146 μg/g (AUROC = 0.56). Significant correlations were observed between neo-terminal ileum BWT and RS (ρ=0.51, p=0.04) and between BWT and CRP (ρ=-0.56, p=0.023), but not BWT and FC (ρ=-0.04, p=0.91), BWT and EHI (ρ=-0.04, p=0.91), or BWT and HBI (ρ=0.09, p=0.75). CONCLUSIONS IUS is a feasible, accurate, non-invasive monitoring tool for detection of postoperative CD recurrence. Larger prospective studies are needed to determine how IUS can be integrated in the monitoring of CD patients after surgery.

Background The Inflammatory Bowel Disease (IBD) Disk represents a self-administered questionnaire that can facilitate, in real time, assessment of IBD related disability, and IBD-related daily life burden. Surrogate markers of IBD activity tend to associate with increased disability. Intestinal ultrasound (IUS) is a non-invasive tool that can objectively and accurately define disease activity and complications in IBD patients. We investigated the correlation between IBD-Disk and IUS in IBD patients. Methods We performed a cross-sectional study that included formally diagnosed IBD patients who underwent IUS and subsequently completed the IBD-Disk questionnaire. Active disease on IUS was defined as bowel wall thickness (BWT) >3 mm at the most affected bowel segment. The overall IBD-Disk score was calculated as the sum of its 10 components, ranging from 0 to 100 (best score: 0, worst score: 100). We explored the correlation between IBD-Disk and its components with IUS. We additionally investigated the correlation of IBD-related daily life burden with IUS. (IBD-Disk total score > 40: high IBD related daily life burden vs IBD-Disk total score ≤ 40: low IBD related daily life burden). Results We included 49 patients (table 1), who underwent IUS for disease monitoring (59.2%) and symptoms suggestive of disease flare (40.8%). Median IBD-Disk total score in our cohort was 48 (IQR 18-58). Median IBD-Disk total score was 52 (IQR 47.3-61.5) in IUS active vs 16 (IQR 5-25) in IUS inactive patients (p<0.001). The area under the ROC curve of IBD-Disk total score in predicting IUS activity was 0.88 (95% C.I: 0.77-0.99, p<0.001, Figure 1). IBD-Disk score >31 predicted disease activity in IUS with 90.6% sensitivity and 88.2% specificity. We observed a moderate correlation between IBD-Disk score and BWT (ρ=0.61, p<0.001) as well as between IBD-Disk score and C-reactive protein (ρ=0.66, p<0.001). Among the components of the IBD-Disk, 8/10 manifested a moderate correlation with BWT (table 2). IBD-Disk score > 40 was found in 27/32 (84.4%) of IUS active and 2/17 (11.8%) of IUS inactive patients, while IBD-Disk score ≤ 40 was found in 5/32 (15.6%) of IUS active and 15/17 (88.2%) of IUS inactive patients respectively (p<0.001). Median BWT was 1.95 mm (IQR 1.53-4.40) in patients with IBD-Disk score ≤ 40 and 5.9 mm (IQR 4.8-6.8) in patients with IBD-Disk score > 40 (p<0.001). Conclusion IBD-Disk displayed a significant correlation with IUS evidence of disease activity in IBD patients. Active disease in IUS was significantly correlated with a high IBD-related daily life burden as expressed by IBD-Disk total score > 40. IBD-Disk could be used in clinical practice to evaluate disease activity and severity in IBD patients.

Background A less invasive examination that can estimate endoscopic remission is needed. Intestinal ultrasound (IUS) is a promising option. The bowel wall thickness (BWT) is a widely-accepted objective parameter in IUS to assess colonic inflammation, but BWT is influenced by intestinal peristalsis and the volume of luminal content. A feasible, objective index that is not affected by these factors could improve the diagnostic potential of IUS. The submucosa, which is observed as the third layer of the intestinal wall on IUS, becomes swollen and standing out in the active UC. Given BWT and submucosa thickness (SMT) can be influenced by the peristalsis and luminal content simultaneously, we hypothesized that the ratio of SMT to BWT can be an index for submucosal swelling regardless of those factors and this index can be a new parameter to estimate endoscopic remission. Methods Inclusion criteria were (1) both IUS and endoscopy (sigmoidoscopy or colonoscopy) for UC were performed in Kyorin University Hospital between April 2019 and December 2020 and (2) time-interval between IUS and endoscopy was within 2 weeks. BWT and SMT were measured based on IUS images for ascending (A/C), transverse (T/C), descending (D/C), and sigmoid colon (S/C), respectively. We defined the submucosa index (SMI) as a percentage of SMT to BWT (Figure 1). When SMT was too thin to be measured, we scored 0 for SMI. The loss of stratification (LOS) was defined as the condition where the submucosa cannot be identified even with BWT > 3 mm (Figure 2). The parts with LOS were considered as inflamed mucosa. Mayo endoscopic subscore (MES) was scored for each part of the colon based on the endoscopic images. MES of 0/1 was defined as the endoscopic remission. Informed consent was obtained in the opt-out method. This study was approved by the Institutional Review Board of Kyorin University School of Medicine (IRB No. 1668). Results In total 68 parts of the colon (A/C: 11, T/C: 12, D/C: 14, and S/C: 31) were analyzed. With ROC analysis with the Youden index, the cutoff value of BWT for endoscopic remission was 3.7 mm (AUC: 0.84). Among the parts without LOS, the cutoff value of SMI for endoscopic remission was 47.9 (AUC: 0.75). The positive predictive value for endoscopic remission of the diagnostic criteria (1) BWT ≤ 3.7 mm, (2) BWT ≤ 3.7 mm and no LOS, (3) SMI ≤ 48 (no LOS), and (4) BWT ≤ 3.7 mm, SMI ≤ 48 (no LOS) was 83.3%, 88.2%, 60.7%, and 93.3%, respectively. The negative predictive value was 88.0%, 88.2%, 90.0%, and 86.8%, respectively. Conclusion Given the feasibility and objectiveness of assessing bowel wall structure, our findings provide “proof of concept” that SMI can be an additional sonographic parameter for endoscopic remission.

Dornase alfa and hypertonic saline are mucoactive therapies that can improve respiratory symptoms in people with cystic fibrosis (CF). A recent randomized control trial showed that participants with well-preserved pulmonary function taking elexacaftor + tezacaftor + ivacaftor (ETI) who discontinued dornase alfa or hypertonic saline for 6 weeks had no clinically meaningful decline in lung function. This may prompt discussions with care providers regarding ongoing use of these medications. To compare the costs of outpatient medications between people taking ETI who continued or discontinued (1) dornase alfa or (2) hypertonic saline from 2 clinical trials and project cost differences in the US CF population if these 2 medications were used only intermittently for symptom relief instead of chronically. The SIMPLIFY study was 2 parallel multicenter trials that randomized participants 1:1 to either continue or discontinue therapy. To estimate costs, we used data from the Merative MarketScan Databases to identify people with CF from 2020 to 2021. Our primary outcomes were differences in costs of outpatient prescription drugs among those who continued vs discontinued dornase alfa and, separately, hypertonic saline. We obtained adjusted differences in median costs. To estimate the annual cost savings if the population of people with CF taking ETI used these medications only intermittently, we multiplied the proportion of people in MarketScan with CF diagnoses who were taking each of these medications by the median cost savings per year and subtracted the cost of "rescue" use. A total of 392 participants from the dornase alfa trial and 273 from the hypertonic saline trial were included in analyses. The adjusted difference in median medication costs was not significant for the hypertonic saline trial, but we observed a significantly decreased 6-week cost of medications in the dornase alfa trial (adjusted median difference in costs between discontinue and continue of $5,860 (95% CI = $4,870-$6,850); P < 0.0001). We estimated that two-thirds of people with CF use ETI and dornase alfa in the United States; if they discontinued dornase alfa except for intermittent use, the resulting annual savings would be $1.21 billion. Although the costs of dornase alfa and hypertonic saline are smaller compared with ETI, reduction in use would lead to substantial prescription drug cost savings and reduce the treatment burden. However, individual benefits of these therapies should be considered, and decisions regarding changes in therapy remain an important discussion between people with CF and their providers. Study registration number: NCT04378153.

Background Inflammatory bowel disease (IBD) is a chronic, immune-mediated disease leading to progressive bowel damage. Objective monitoring is essential to improve outcomes. Intestinal ultrasound (IUS) is an accurate, repeatable modality preferred by patients. The aim of this study was to evaluate changes in medical therapy and further tests requested, when IUS is used routinely to follow patients in an expert centre. Methods This is a single centre, prospective observational cohort study. All recruited provided informed consent with ethics approval through the University of Calgary. Patients over the age of 18 years were recruited via convenience sampling from October 1, 2020 to September 31, 2022. Patients were part of a registry where clinic-based IUS is standard of care. Patient demographics, medical treatment changes and further investigations were recorded. IUS were performed by an IBD gastroenterologist trained in advanced IUS. Patients were classified as symptomatic (Harvey Bradshaw Index [HBI] ≥5) or asymptomatic (HBI&amp;lt;5). IUS were categorised as inactive if the bowel wall thickness (BWT) was &amp;lt;3mm without colour Doppler and inflammatory mesenteric fat) or active (BWT ≥3mm, colour Doppler ≥2 and presence of inflammatory fat). Data were reviewed regarding management: medication changes were defined as dose change, addition of corticosteroids or other medication and medication change. Referral for surgical opinion was recorded. Further outcomes included faecal calprotectin, stool for infection, blood tests, endoscopy, imaging or hospital admission. Results 138 episodes of care were logged including 103(74%) with Crohn’s disease, 16(12%) with ulcerative colitis, 2(1.4%) with IBD-unclassified, 13(9.4%) without IBD investigated for symptoms and 4(2.9%) not recorded. Figure 1 shows symptomatic and active episodes compared to asymptomatic and inactive. IUS were performed: for flare symptoms in 22(16%); for monitoring in 107(78%); or to investigate symptoms in 9(6.5%). IBD medication was escalated in 22(52%) patients with active IUS disease plus symptoms and in 9(39%) asymptomatic patients with active IUS. Medication escalation was performed in 4(16%) symptomatic patients with inactive IUS and 2(4.2%) asymptomatic patients with inactive IUS based on low drug level or adverse events. One patient had medication reduced in frequency due to the IUS findings(Table 1). No hospital admissions occurred following IUS. Conclusion Active IUS triggered treatment modification in almost 40% of patients, regardless of symptoms. Future studies will assess benefits of timely treatment changes for long term outcome. IUS supports a clinician at the bedside to make timely clinical decisions that may avoid invasive testing and decrease resource limited endoscopy.

Background In patients with Crohn’s disease (CD), following an ileocolic resection (ICR), colonoscopy is the gold standard for the detection of endoscopic recurrence (ER). Colonoscopy, however, is invasive and not easily accepted by patients, particularly for repeated monitoring. In contrast, intestinal ultrasound (IUS) has the advantage of being non-irradiating, non-invasive, well-tolerated, and easy to repeat. The goal of this study was to assess the accuracy of IUS for ER in CD. Methods This was a cross-sectional study of CD patients who underwent IUS during a postoperative clinic visit within 30 days of a planned colonoscopy. Parameters on IUS included bowel wall thickness (BWT), bowel wall hyperemia (BWH; modified Limberg score 0-III), layer stratification, inflammatory fat, and complications. C-reactive protein (CRP), fecal calprotectin (FC), endoscopic healing index (EHI; Prometheus Labs, CA) and Harvey Bradshaw Index (HBI) were also measured. ER was defined as a Rutgeerts Score (RS) &amp;gt; i2. Primary outcome was the association between IUS parameters and ER. Secondary outcomes were the association of IUS parameters with other markers of disease activity. Results Eighteen CD patients (9 female; 29 [19–40] years old), underwent IUS examination 45 [29–99] months post-ICR during a routine clinic visit. Seven (39%) patients were on ustekinumab, four (22%) on adalimumab, two (11%) on infliximab, one (6%) on vedolizumab, and four (22%) on no therapy. ER was found in eight (44%) patients. BWT and BWH in the neo-terminal ileum and BWH at the ileocolic anastomosis were the only IUS parameters associated with ER (Table 1). Neo-terminal ileum BWT was 4.0 [3.2–4.8] mm in patients with ER compared to 2.0 [1.5–2.6] mm without (p=0.04). Neo-terminal ileum BWH was abnormal in six (75%) patients with ER compared to 0% without (p=0.007). BWT of 3.2 mm was the optimal cut point for predicting ER with an: AUROC of 0.82, positive predictive value of 100%, negative predictive value of 97.3%, sensitivity of 75%, and specificity of 100% (Figure 1) vs. a CRP of 10.4 mg/L (AUROC = 0.54) or FC of 1146 µg/g (AUROC = 0.56). Significant correlations were observed between neo-terminal ileum BWT and RS (ρ=0.51, p=0.04) and between BWT and CRP (ρ=-0.56, p=0.023). No correlation was observed between BWT and FC (ρ=-0.04, p=0.91), BWT and EHI (ρ=-0.04, p=0.91), or BWT and HBI (ρ=0.09, p=0.75). Conclusion IUS is a feasible, accurate, non-invasive monitoring tool for detection of postoperative CD recurrence. Larger prospective studies are needed to determine how IUS can be integrated in the monitoring of CD patients after surgery.

Background In pediatric patients with Inflammatory bowel disease (IBD), delay in diagnosis can lead to progression of disease and bowel damage. In North America, the current methods to visually assess disease activity are limited to ileocolonoscopies and MR enterography. Point-of-care intestinal ultrasound (IUS) is a non-invasive, cost-efficient tool for assessing intestinal inflammation. We aim to evaluate the correlation between IUS and endoscopic disease activity in children suspected to have IBD. Methods In this cross-sectional study, we recruited consecutive patients newly diagnosed with IBD, presenting to the IBD outpatient clinic, or hospitalized in our pediatric center between August 2020 and February 2021. In addition to ileocolonoscopy, they underwent IUS performed by one gastroenterologist who was blinded to ileocolonoscopy results at the time of performing IUS. Bowel wall thickness (BWT) was measured systematically across different bowel segments (terminal ileum, ascending, transverse, descending, sigmoid colon, and rectum) and recorded twice in longitudinal view and twice in axial view. An average segmental BWT of more than 3 mm was considered inflamed. The inflammation seen on endoscopy was graded using segmental scores of the SES-CD for patients with Crohn’s disease (CD) and the UCEIS for patients with ulcerative colitis (UC). Segments were classified as healed, mild, moderate, or severe disease activity. The association between the BWT and disease severity on endoscopy was assessed using the Kruskal-Wallis test. Numerical correlation between BWT and continuous values of the endoscopic scores was performed using Kendall’s Tau-b. Results Fifteen patients completed both IUS and ileocolonoscopy. A total of 74 bowel segments were assessed. There were 7 girls, median age of 15 years (IQR 12.5–15.5 years). 8 patients were diagnosed with CD, 5 with UC, and 2 had a normal endoscopy. Median PCDAI was 32.5 (IQR 30.0–40.0), and median PUCAI was 70 (IQR 70–75). The Kruskal-Wallis test showed that BWT was significantly associated with disease severity as measured by the SES-CD (chi-square = 14.3, p &amp;lt;0.001, df = 2) for patients with CD, and that the BWT was also significantly associated with disease severity as measured by the UCEIS (chi-squared=12.0, p&amp;lt;0.001, df=3). The numerical correlation between BWT and SES-CD for all segments was 0.43 (p&amp;lt;0.001, 95%CI 0.3–0.58), while the correlation with the UCEIS was 0.52 (p&amp;lt;0.001, 95%CI 0.4–0.66). Conclusion In pediatric patients with IBD, we found that endoscopic disease severity correlates with the degree of BWT seen on IUS. These findings support the use of IUS as an evaluation tool of disease activity in North American pediatric clinical practice.

Background Pain is a debilitating symptom in many patients with Crohn’s disease (CD) both in flare and in remission [1]. However, pain is insufficiently understood and therefore often underrepresented in disease management [2]. Thus, it is of paramount importance to raise awareness for this common but insufficiently managed IBD symptom. With this analysis, we aimed to investigate (1) the prevalence of abdominal pain (AP) and (2) the correlation of AP with further parameters including inflammatory activity assessed by intestinal ultrasound (IUS), lab parameters and patient-well-being in CD patients of the TRUST study cohort. Methods We evaluated the prevalence of pain in 230 of 234 CD patients of the prospective, non-interventional, multi-centre TRUST study. At baseline, all patients were in clinical flare (Harvey-Bradshaw index (HBI) of≥7) and received treatment intensification. IUS parameters such as bowel wall thickness (BWT) and clinical data were assessed at baseline and after 3, 6, and 12 months. AP was analysed using the HBI subscore 2. To investigate the connection between AP and inflammation, AP was correlated with BWT and C-reactive protein (CRP). Results Based on the TRUST study, we found that 95.2% of patients in clinical flare experienced AP. AP was significantly reduced within 12 weeks after treatment intensification (p &amp;lt; 0.001) but 30% (n=69) to 48.3% (n=111) of patients still experienced AP at the subsequent visits (p(T1-T2) = 0.668; p(T2-T3) = 1.000) (figure 1). Of note, 35.6%-42.5% of patients with clinical response had a lasting pain experience (figure 2). AP positively correlated with poor well-being which is in line with previously published results [3]. We found a weak positive correlation between AP and inflammatory activity, represented by BWT (not shown), and between AP and CRP (table 1). Figure 1: Percentage of patients with mild, moderate or severe abdominal pain during the study. *Friedman test with post-hoc Wilcoxon tests. Figure 2: Percentage of patients with abdominal pain and clinical response (reduction of total HBI≥3 points) at the indicated visit Table 1: Spearmann rank correlations for abdominal pain vs. poor general well-being (as measured by the HBI subscore 1) and vs. CRP at baseline Conclusion Our results clearly demonstrate that more than 1/3 of CD patients suffers from AP despite treatment intensification and clinical improvement. We found a weak correlation between AP and markers of inflammatory activity suggesting the existence of a subgroup of patients with persistent pain experience even with IBD treatment. Our data emphasize the importance of adjuvant pain management in IBD. References

Background Patient-reported Outcomes (PRO) are gaining increasing acceptance as new tools to evaluate clinical activity, especially in the context of clinical trials and evaluation of drug efficacy. However, data to support the relevance of these endpoints and their correlation to objective markers of inflammation is still lacking.1 Recently published data demonstrated the feasibility of intestinal ultrasound (IUS) as a routine monitoring technique in clinical practice for Crohn’s disease (CD) and ulcerative colitis (UC) patients.2 Thus, the importance and significance of IUS, as a patient-centric and non-invasive technique has emerged over the last years and will become more relevant in the future.With this sub-analysis of the TRUST&amp;UC study, we aimed to investigate the correlation between improvement in ultrasound parameters and PRO-2 in UC patients. Methods TRUST&amp;UC is a prospective, observational study including 244 patients with an increased bowel wall thickness (BWT) at baseline and active UC (SCCAI ≥ 5). These patients were analysed for the Simple Clinical Colitis Activity Index (SCCAI) subscores stool frequency, urgency and rectal bleeding. These parameters were documented for up to 4 visits (baseline, an optional visit at week 2, week 6 and week 12). Pathological stool frequency was defined as a stool frequency of ≥1 point (≥ 4 stools/day) and pathological rectal bleeding was defined as ≥1 point (traces of blood in stool); the combination of both subscores was defined as PRO-2. Results We found a positive moderate correlation between BWT and the investigated SCCAI-subscores (rectal bleeding and BWT at W12 r = 0.417; stool frequency and BWT at W12, r = 0.483; PRO-2 and BWT at W12, r = 0.518) and even W6, which is in accordance with previously reported correlations of various PROs and endoscopy in UC-patients.3 We demonstrate that patients with normalisation of BWT (sigmoid colon &amp;lt; 4.0 mm) had a significantly higher chance of a non-pathological PRO-2 (pathological PRO-2 yes/no: 4.25 mm and 3.20 mm for week 6 (p &amp;lt; 0.001) and 4.45 mm and 3.00 mm (p &amp;lt; 0.001) for week 12). Conclusion With this sub-analysis of the TRUST&amp;UC study we demonstrated that bowel wall thickness, assessed by intestinal ultrasound, had a moderate correlation with normalisation of patient-reported outcomes as early as week 6 and 12. Furthermore, patients with non-pathological PRO-2 had significantly decreased bowel wall thickness. This again supports the value of intestinal ultrasound in routine medical practice. References

Background To assess disease activity in ulcerative colitis (UC) intestinal ultrasound (IUS) highly correlates with endoscopic outcomes. However, data on treatment response evaluated with IUS is limited. In this study we aim to evaluate bowel wall thickness (BWT) at follow-up to determine treatment effectiveness in moderate-severe UC patients treated with tofacitinib according to central read endoscopy and histology. Methods Patients with moderate-severe UC (endoscopic Mayo score (EMS)≥2) starting tofacitinib 10 mg bid were included. Disease activity was evaluated by recorded IUS cine-loops and video-taped endoscopies with biopsies from the sigmoid (SC) and descending colon (DC) at baseline and at 8 weeks. BWT and EMS were assessed per segment (SC and DC). Histology was scored for the SC with the Robarts Histology Index (RHI). BWT, EMS and RHI were centrally read and for IUS there was a second reader. Endoscopic remission (ERem) was defined as EMS=0, endoscopic improvement (EI) as EMS≤1 and endoscopic response (ERes) as a decrease of EMS≥1. For statistical analysis a Wilcoxon signed-rank and Spearman’s test were used. Area under the ROC was used to determine optimal cut-off values. Inter-observer agreement was analyzed by intra-class correlation coefficient (ICC). Results 29 patients were included and started tofacitinib. 10% reached complete ERem after 8 weeks, respectively. Per-segment analysis for EMS showed 22% and 53% reaching ER and 40% and 60% having EI in the SC and DC, respectively. BWT in SC and DC correlated highly with the EMS (rho=0.68, rho=0.75, both p&amp;lt;0.0001) and moderately with RHI (rho=0.49, p=0.002). Patients with EMS≥2 after 8 weeks had an increased BWT (SC: 4.32 ± 1.57 mm, DC: 4.38 ± 1.58 mm) when compared to ERem (SC: 2.10 ± 0.67 mm, DC: mean: 2.00 ± 1.18 mm, both p&amp;lt;0.0001) and EI (SC: 2.29 ± 0.76 mm, DC: 2.56 ± 1.38 mm, both p&amp;lt;0.0001) in the similar segment (Figure 1 and 2). BWT decreased after 8 weeks when there was ERes (SC: mean: -2.59 ± 1.44 mm, DC: -1.82 ± 1.01 mm, both p=0.007) and did not when there was no ERes (Figure 3). BWT cut-off values for ERem are reported in Figure 4. Furthermore, agreement for BWT in the SC and DC was excellent (ICC: 0.92 and ICC: 0.89), respectively. Conclusion BWT reduction showed early endoscopic remission, improvement and response after 8 weeks of tofacitinib treatment and correlated with histology in this central read cohort. Furthermore, accurate and reliable cut-off values for BWT in SC and DC were found for endoscopic remission and improvement. Therefore, IUS should be incorporated in the standard follow-up and close monitoring of UC patients.

Background Several intestinal ultrasound (IUS) scores have been proposed to assess disease activity in ulcerative colitis (UC) combining different intestinal ultrasound parameters. However, it is not known if these scores are superior to solely measuring bowel wall thickness (BWT), the IUS parameter most strongly correlated with disease activity and showing a near perfect inter-rater agreement. This study aimed to compare the performance of BWT and 2 validated IUS scores, Milan US criteria (MUC), and the IUS-UC index in identifying active endoscopic disease. Methods Consecutive UC patients (Age ≥ 18 y) scheduled for colonoscopy or sigmoidoscopy in a single center underwent IUS within 3 weeks of the procedure, with disease activity graded using the Mayo endoscopic subscore (MES). IUS parameters assessed included BWT, color doppler signal (CDS), haustral pattern (HP), wall layer stratification (WLS), and fat wrapping. Correlations between MES and all IUS parameters, IUS-UC index, and MUC were assessed using Spearman’s rank correlation coefficient. The area under the receiver-operating characteristic (ROC) curves for detecting endoscopic activity (MES ≥ 1) for BWT, IUS-UC index, and MUC were compared. Results A total of 57 UC patients (undergoing 60 examinations) were enrolled (median age 34.8 years, 34.3% male). Twenty-five percent of patients were in clinical remission, defined by simple clinical colitis activity index SCCAI &amp;lt; 3. In comparison, 16.3% of patients had endoscopic remission (MES 0), and 33.3% had MES ≤1. The median interval between IUS and colonoscopy was 5 days. The median (IQR) BWT was 1.4mm (1.3-1.7) for MES 0, 2.1mm (1.7-2.7) for MES 1, 3.5mm (2.8-4.3) for MES 2, and 4.4mm for MES 3 (3.9-5.4). BWT, abnormal HP, CDS, IUS-UC index, and MUC showed strong correlation with endoscopic activity. The Pearson correlation coefficients were 0.834, 0.820, 0.757, 0.876, and 0.882, respectively, with all p values &amp;lt;.001. Fat wrapping showed moderate correlation (r = 0.666, p&amp;lt;.001), while loss of WLS showed a weak correlation (r = 0.391, p&amp;lt;.001). There was no significant statistical difference in the area under the receiver-operating characteristic curve for BWT, IUS-UC index, and MUC in differentiating endoscopic remission from endoscopic activity (MES≥1) (figure 1). The optimal cutoff values are presented in Table 1. Conclusion IUS-index and MUC are both sensitive and specific in detecting even mild endoscopic activity, however they didn’t show superiority over using BWT as a single parameter. Our study suggests that BWT alone is as effective as more complex IUS scores in detecting active endoscopic disease in UC. BWT may be used as a practical primary IUS parameter for the routine assessment of UC activity.

ObjectiveThis study aimed to summarize the intestinal ultrasound (IUS) and computed tomography enterography (CTE) features of cryptogenic multifocal ulcerous stenosing enteritis (CMUSE) and compare the performance of IUS and CTE in the evaluation of CMUSE in a single tertiary center.MethodsClinically or pathologically confirmed CMUSE patients between December 2009 and April 2023 were recruited. Imaging features of CMUSE patients who underwent both IUS and CTE were summarized retrospectively.ResultsTwenty-nine patients were included. All patients were found to have ileum involvement, with the majority (96.6%, 28/29) showing superficial ulcers and stenosis at endoscopy. Nineteen patients who underwent both IUS and CTE during the same period were identified for image review. Intestinal lesions were present in 19 patients (100%) both on IUS and CTE. IUS features of CMUSE included minimal to moderate thickened small bowel wall with over half of the patients presenting with hypoechogenicity and vague stratification, over one-third of patients exhibiting proximal bowel dilation and increased bowel wall vascularity in most patients; on CTE, it presented as slight to moderate thickened bowel wall with mural enhancement, multiple short circumferential strictures and mild proximal bowel dilation in most patients. There was no statistically significant difference between IUS and CTE in detecting lesions (19/19 vs. 19/19), bowel wall thickening, bowel strictures (p = 0.727), and bowel wall vascularity (p = 0.375).ConclusionIUS features of CMUSE were comparable with CTE in detecting lesions, bowel wall thickening, strictures and bowel wall vascularity, suggesting that IUS could serve as a radiation-free imaging modality for the diagnosis and surveillance of CMUSE.Critical relevance statementThis pathology is relevant for gastroenterologists, radiologists, and the medical community, as well as for patients with small bowel disorders. Intestinal ultrasound could be of value and serve as a radiation-free imaging modality in assessing cryptogenic multifocal ulcerous stenosing enteritis (CMUSE).Key PointsMore data are needed to characterize the intestinal ultrasound (IUS) findings of cryptogenic multifocal ulcerating stenosing enteritis (CMUSE).IUS features of CMUSE manifested as thickened bowel wall, with more than half of the patients presenting with hypoechogenicity with vague stratification.Computed tomography enterography (CTE) features of CMUSE included bowel wall thickening with mural enhancement, multiple short circumferential strictures, and mild small intestine dilation.IUS and CTE were comparable in detecting lesions, bowel wall thickening, bowel strictures, and bowel wall vascularity.Graphical

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