BACKGROUND Moderate sedation can significantly increase the acceptance of preventive colonoscopy, with different sedation regimens being used. AIM To compare sedation with low-dose midazolam in combination with propofol combination therapy (PCT) with sedation with propofol monotherapy (PMT) during preventive colonoscopy. METHODS Retrospective analysis of a total of 120 patients who were sedated with either PCT or PMT. The propofol dose administered, complications such as hypotension or hypoxia, examination time and time to discharge were evaluated. In addition, the costs of the respective sedations were calculated. RESULTS The propofol dose administered was significantly higher in the PMT group than in the PCT group (217 mg vs 65 mg, P < 0.01), the examination time was significantly shorter in the PMT group (18.6 minutes vs 21.4 minutes, P = 0.02) and the time to discharge was significantly shorter in the PCT group (49.4 minutes vs 57.7 minutes, P = 0.04). No patient experienced a sedation-related complication requiring treatment. The costs of sedation in the PCT group were significantly lower than those in the PMT group. CONCLUSION Sedation with midazolam in combination with propofol is as safe for performing outpatient preventive colonoscopy as monotherapy with propofol. Combination therapy may potentially reduce costs.

Mesalazine is the first-line treatment for mild-to-moderate ulcerative colitis (UC) of any extent, as recommended by all major international and national guidelines. Approximately 85% of UC cases are classified as mild-to-moderate, making mesalazine a cornerstone therapy for the majority of patients. It rapidly induces clinical response and clinical remission, sustains steroid-free clinical, endoscopic, and histologic remission over the long term, and has a safety profile comparable to placebo. This paper reviews the recommendations for mesalazine use in the German UC guideline and provides practical advice (including do's and don'ts) for their implementation in daily clinical practice. Examples include explaining the expected timeline and nature of the clinical response to mesalazine treatment; outlining the practical implications of the dose-dependency of the drug's therapeutic effect; and emphasizing the importance of rectal mesalazine as the first-line treatment for proctitis. Additionally, we conducted a systematic literature search to evaluate whether mesalazine should be continued after escalation to biologics or small molecules. While no clear evidence of short-term clinical benefit was found, there was also no evidence of harm. In light of the potential long-term chemoprotective effect of mesalazine, continuation may be considered on a case-by-case basis. Lastly, we provide an overview of the various mesalazine formulations available in Germany, detailing how they are not interchangeable due to differences in drug-release profiles, excipients, and dosing strengths. Understanding these differences may help clinicians personalize treatment, improving adherence and clinical outcomes.

Pyoderma gangrenosum (PG) is a rare but challenging extraintestinal manifestation (EIM) of inflammatory bowel disease (IBD), affecting 6–48% of IBD patients. This retrospective study analyzes affected patients and evaluates therapeutic strategies for both IBD remission and PG resolution. A multicenter retrospective analysis was conducted on patients with IBD and PG in 8 tertiary centers in Germany and Austria. Demographic data, prior therapies, surgeries, treatment of PG were collected, and treatment responses assessed. The cohort included 50 patients (median age: 43 years; 68% female). Crohn’s disease (CD) was present in 58%, ulcerative colitis (UC) in 42%. Fifty percent of patients had prior surgery, 68% having an intestinal stoma. 48% were experienced to biologic therapy, predominantly anti-TNF therapy (83%). PG mainly affected the lower extremities (52%) and peristomal areas (24%). Systemic steroids were used in 52% of patients and led to PG resolution in only 12%. Anti-TNF therapy was the main approach, used in 68% of patients, with resolution achieved in 80%. Calcineurin inhibitors were given to 26% of patients and induced resolution in 38%. Three of six non-responders were successfully switched to infliximab. Overall PG resolution was achieved in 80%, correlating with IBD remission in 78%. The median time to PG resolution was five months. Anti-TNF therapy was an effective treatment for PG in IBD patients, even in those with prior non-response to calcineurin inhibitors. Systemic steroids showed low response rates. PG healing mostly aligned with IBD remission, underlining the need for tailored long-term therapy.

Pyoderma gangrenosum (PG) is a rare but challenging extraintestinal manifestation (EIM) of inflammatory bowel diseases (IBD), affecting 6%–48% of IBD patients. This retrospective study analyzed affected patients and evaluated therapeutic strategies for both IBD remission and PG resolution. A multicenter retrospective analysis was conducted on patients with IBD and PG in eight tertiary IBD centers. Demographic data, prior therapies, surgeries, and treatment of PG were collected retrospectively, and treatment responses were assessed. The cohort included 50 patients (median age: 43 years; 68% female). Crohn’s disease was present in 58% and ulcerative colitis in 42%. Fifty percent of patients had prior surgery, 68% had an intestinal stoma in their medical history. 48% were experienced with biologic therapy, predominantly anti-tumor necrosis factor (TNF) therapy (83%). PG mainly affected the lower extremities (52%) and peristomal areas (24%). Systemic steroids were used in 52% (26/50) and led to PG resolution in only 11.5% (3/26). Anti-TNF therapy was the main approach, used in 68% (34/50) of patients, with resolution achieved in 80% (27/34). Calcineurin inhibitors were given to 26% (13/50) of patients and induced resolution in 38% (5/13). Three of six non-responders were successfully switched to infliximab. Overall, PG resolution was achieved in 80% (40/50), correlating with IBD remission in 78% (31/40) of these patients. The median time to PG resolution was 4 months. Anti-TNF therapy was an effective treatment for PG in IBD patients, even in those with prior nonresponse to calcineurin inhibitors. Systemic steroids showed low response rates. PG healing mostly aligned with IBD remission, underlining the need for tailored long-term therapy.

Colectomy is the surgical treatment of choice in patients with severe or complicated ulcerative colitis. Post-colectomy enteritis (PCE) is a rare condition that can develop after proctocolectomy and has been described only in a few individual cases so far. We report the case of a 46-year-old patient with severe and treatment-refractory ulcerative colitis who underwent colectomy. A few days after surgery, the patient presented with acute anemia and hematemesis. Esophagogastroduodenoscopy showed massive inflammation of the duodenum and jejunum. The life-threateningly ill patient was admitted to the intensive-care unit and treated for severe PCE with ciclosporin and corticosteroids. PCE is a distinct inflammation of the small intestine shortly after colectomy. The patient recovered fully and was discharged after prolonged recovery and long-term intensive care therapy.

BACKGROUND:Real-world evidence studies of ustekinumab (UST) in ulcerative colitis (UC) are needed because randomized controlled trials do not represent unselected patient populations in everyday clinical practice. Patients with UC were recruited when starting biologic therapy for the first time or switching to a new biologic therapy. This study assessed the effectiveness of maintenance therapy with UST in comparison to anti-TNF or vedolizumab (VDZ) at 12 months. METHODS:Between 2020 and 2022, 507 UC patients starting biologic therapy for the first time or switching to a new biologic therapy were enrolled at 34 inflammatory bowel disease (IBD)-specialized centers in Germany. After excluding patients receiving other biologics or small molecules, as well as those with stomas or missing outcomes, the final sample consisted of 476 patients. The outcomes were clinical response, clinical remission (CR), and steroid-free remission. Propensity score (PS) adjustment with inverse probability of treatment weighting was used to reduce the effect of confounding due to physician selection of therapy. RESULTS:A total of 476 patients with UC were included in the analysis (UST: 147, anti-TNF: 168, VDZ: 161). Treatment persistence over 12 months differed significantly (P < .001) between UST (93.9%), VDZ (87.0%), and anti-TNF (75.0%). The PS-weighted effectiveness of UST in the mITT analysis at month 12 was not significantly different from anti-TNF or VDZ (CR: UST 26.9%, anti-TNF 34.7%, VDZ 40.9%; P = .063). CONCLUSIONS:In the prospective RUN-UC study with PS-weighted groups, UST showed higher treatment persistence but no significant difference in maintenance effectiveness compared to anti-TNF or VDZ in UC.

Abstract Background Observational real-world evidence (RWE) studies on the effectiveness of ustekinumab (UST) in ulcerative colitis (UC) are needed in addition to RCTs, which may not represent everyday clinical practice. For this reason, the prospective, controlled, propensity score (PS)-adjusted RUN-UC study was conducted on UC patients starting a new biologic therapy with a follow-up period of up to 3 years. The aim of the present analysis was to evaluate the effectiveness of 2-year maintenance therapy with UST vs. anti-TNF or vedolizumab (VDZ). Methods Between 2020-2022, 507 UC patients starting a new therapy with UST or other biologics were enrolled in 34 IBD-experienced centres in Germany. After the exclusion of patients with a stoma, small molecules and missing outcomes, the final sample consisted of 483 patients. Clinical remission (CR) (pMayo ≤ 1 plus a bleeding subscore=0) and steroid-free remission (CR and no systemic use of steroids or oral budesonide) were considered as outcomes. PS adjustment with inverse probability of treatment weighting (IPTW) was implemented to reduce confounders' effect. Results A total of 483 UC-patients [153 UST (bio-naïve: 13), 165 anti-TNF (ADA: 30.3%, IFX: 61.8%, GOL: 7.9%) (bio-naïve: 114) and 165 VDZ (bio-naïve: 106)] were included in the analysis. The PS-adjustment reduced systemic differences in the baseline parameters (UST/anti-TNF/VDZ: 43.1/46.1/50.9% males, 23.5/24.2/20.6% EIMs), in particular, the "bio-experienced" characteristic was also equalised, between the groups. Treatment persistence over 24 months showed differences between UST (68.6%), VDZ (73.3%) and anti-TNF (58.8%) (p=0.012), but this was only statistically significant for VDZ vs anti-TNF (p=0.005) but not for UST vs VDZ (p> 0.05) and UST vs anti-TNF (p>0.05) (Figure 1). The PS-weighted 24-month effectiveness (n=367) of UST (mITT analysis) in terms of clinical remission and steroid-free remission (Table 1) differed between the following groups (CR: UST 33.3%, anti-TNF 30.2%, VDZ 48.0%) compared to VDZ (p=0.031), but not compared to anti-TNF (UST vs anti-TNF p>0.05 and anti-TNF vs VDZ p=0.005). A sub-analysis evaluating steroid-free remission in bio-experienced patients after one prior anti-TNF treatment showed no statistical difference. was (UST 41.5%, anti-TNF 20.0% and VDZ 43.8%; p=0.130). Conclusion In this prospective RUN-UC study with PS-weighted groups, UST, anti-TNF and VDZ showed a more variable 24-month effectiveness, favouring VDZ over UST and anti-TNF. However, in a subgroup of bio-experienced patients with only one anti-TNF before baseline, steroid-free remission was numerically but not statistically higher with UST and VDZ than with anti-TNF.

Objective:Despite high stand-alone performance, studies demonstrate that artificial intelligence (AI)-supported endoscopic diagnostics often fall short in clinical applications due to human-AI interaction factors. This video-based trial on Barrett's esophagus aimed to investigate how examiner behavior, their levels of confidence, and system usability influence the diagnostic outcomes of AI-assisted endoscopy. Methods:The present analysis employed data from a multicenter randomized controlled tandem video trial involving 22 endoscopists with varying degrees of expertise. Participants were tasked with evaluating a set of 96 endoscopic videos of Barrett's esophagus in two distinct rounds, with and without AI assistance. Diagnostic confidence levels were recorded, and decision changes were categorized according to the AI prediction. Additional surveys assessed user experience and system usability ratings. Results:AI assistance significantly increased examiner confidence levels (p < 0.001) and accuracy. Withdrawing AI assistance decreased confidence (p < 0.001), but not accuracy. Experts consistently reported higher confidence than non-experts (p < 0.001), regardless of performance. Despite improved confidence, correct AI guidance was disregarded in 16% of all cases, and 9% of initially correct diagnoses were changed to incorrect ones. Overreliance on AI, algorithm aversion, and uncertainty in AI predictions were identified as key factors influencing outcomes. The System Usability Scale questionnaire scores indicated good to excellent usability, with non-experts scoring 73.5 and experts 85.6. Conclusions:Our findings highlight the pivotal function of examiner behavior in AI-assisted endoscopy. To fully realize the benefits of AI, implementing explainable AI, improving user interfaces, and providing targeted training are essential. Addressing these factors could enhance diagnostic accuracy and confidence in clinical practice.

Background/Objectives: Patients with inflammatory bowel disease (IBD) are at an increased risk of various cancers; such as colorectal cancer; skin cancer; bile duct cancer; or lymphoma; with IBD itself not being the sole cause. Inappropriate or ineffective IBD therapy with a continuous inflammatory burden within the gut leads to an increased risk of malignancy. Our study aimed to investigate the risk of malignancy in our patient cohort; focusing on concomitant therapy; disease duration; and inflammatory burden. Methods: A total of 333 consecutive adult patients with IBD (Crohn’s disease; ulcerative colitis; and IBD unclassified) were included in this study. Data from patients were collected retrospectively using patient charts. The patients were treated in the gastroenterological outpatient clinic of the University Hospital of Augsburg; Germany; between 1 January 2014 and 31 December 2018. Results: The study group included 333 patients; 32 (9.61%) of whom suffered from malignancy (any form). Men (n = 21; 65.62%) tended to develop malignancy more often than women (n = 11; 34.38%, p = 0.051). It was also observed that the probability of developing cancer was 2.40 times higher in male patients than in female patients in our cohort. However, this trend was non-significant (HR = 2.412; p = 0.075). Furthermore; the probability of developing cancer increased with the increasing age at the time of the first diagnosis of IBD (HR = 1.088; p < 0.025). A total of 20 patients (6.00%) received their cancer diagnosis after being diagnosed with IBD. The majority of those patients had skin (n = 6; 30.00%) or colon cancer (n = 5; 25.00%). Other diseases such as CML; NHL; HL; HCC; liver sarcoma; prostate cancer; breast cancer; seminoma; thyroid cancer (a second cancer in one of the patients); or CUP syndrome/lung cancer were diagnosed in single patients. Patients with IBD and colon cancer (n = 5; 25.00%) shared some of the known risk factors for tumour development; such as a long-lasting IBD (n = 5; 100.00%), diagnosis at a young age (under 30; n = 3; 60.00%), and the coexistence of PSC (n = 1; 20.00%). The cancer prevalence rate was relatively low in our cohort despite the use of diverse biologics and immunosuppressive drugs. Faecal calprotectin was confirmed as a relevant tool for inflammation monitoring in this cohort. Conclusions: In our study cohort; we could show a low prevalence rate of malignancy in IBD. There were more malignancies in men and in patients who were diagnosed with IBD at later ages. It can be observed that the prevalence rate of cancer was relatively low despite the use of diverse biologics and immunosuppressive drugs; which is the major conclusion of this study. Additionally; the known correlation between elevated levels of faecal calprotectin and gut inflammation was confirmed through our statistical analysis. The use of calprotectin as a non-invasive screening tool for gut inflammation is advised.

Abstract Background JAK inhibitors (JAKi) can induce and maintain remission in inflammatory bowel disease (IBD). Around 5% of IBD patients develop primary sclerosing cholangitis (PSC). Given the potential involvement of JAK/STAT signaling in PSC pathogenesis, JAKi may have a role in modulating IBD-related PSC. We aim to explore the course of PSC in IBD-PSC patients on JAKi for IBD. Methods Following a call-for-cases via ECCO CONFER (Round 10), we retrospectively collected baseline and outcome data for both PSC and IBD, before and after JAKi treatment, including laboratory tests, imaging and endoscopic findings, histopathology and adverse effects. The data were analyzed both descriptively and comparatively. A p-value of less than 0.05 was considered statistically significant. Results We collected data from 58 patients (53 ulcerative colitis), with a median of disease duration of 5.5 (IQR 2-9) years (Table 1). The median age at PSC diagnosis was 26 (18.25-40.5) years. Each patient had been treated with a median of 2.5 different types of drugs before starting JAKi; 57% received tofacitinib, 26% upadacitinib, 17% filgotinib. At the time of data analysis, the median time of JAKi exposure was 32 (15.75-69) weeks and we will refer to that median time of exposure when analysing each data related to JAKi exposure. At baseline, alkaline phosphatase (ALP) was elevated in 71% of patients (median, 292 U/L, 185-471). After JAKi exposure, ALP dropped to a median of 203.5 U/L (138.7-394.5), p=0.0004. Among this specific group, 30% of subjects reached normal ALP values. Gamma-glutamyl transferase (GGT) was elevated in 80% of patients (350 U/L, 164-552) and dropped to a median value of 127 U/L (95-270), p=0.0055; 13% of this specific group reached normal values of GGT after JAKi exposure. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were high in 58% and 50% of patients, respectively; following JAKi exposure, the median value of both went down significantly. After a median time of 32 weeks of JAKi treatment, 39,6% of patients had to change therapy: 23% due to primary non-response, 62% due to lack of response, 15% underwent colectomy. Patients who had to change therapy were divided into: switch group, treated with additional 40 (36-46) weeks with a different JAKi; swap group, swapped to biologic for additional 27 (24-40) weeks. Better control of liver biomarkers was observed in the switch group (Figure 1). Conclusion Treatment with JAKi can positively impact liver inflammation in terms of cholestasis and cytolysis indexes in patients with PSC and concomitant IBD. References Schregel I, Ramos GP, Ioannou S, Culver E, Färkkilä M, Schramm C; International PSC Study Group. Evaluation of Tofacitinib in Primary Sclerosing Cholangitis and Associated Colitis: A Multicenter, Retrospective Study. Clin Gastroenterol Hepatol. 2023;21(13):3448-3450.e3. doi: 10.1016/j.cgh.2023.01.014. Khrom M, Long M, Dube S, Robbins L, Botwin GJ, Yang S, Mengesha E, Li D, Naito T, Bonthala NN, Ha C, Melmed G, Rabizadeh S, Syal G, Vasiliauskas E, Ziring D, Brant SR, Cho J, Duerr RH, Rioux J, Schumm P, Silverberg M, Ananthakrishnan AN, Faubion WA, Jabri B, Lira SA, Newberry RD, Sandler RS, Xavier RJ, Kugathasan S, Hercules D, Targan SR, RB Sartor, Haritunians T, McGovern DPB. Comprehensive association analyses of Extraintestinal Manifestations in Inflammatory Bowel Disease. Gastroenterology. 2024;167(2):315-332. doi: 10.1053/j.gastro.2024.02.026. Dold L, Kalthoff S, Frank L, Zhou T, Esser P, Lutz P, Strassburg CP, Spengler U, Langhans B. STAT Activation in Regulatory CD4 (+) T Cells of Patients with Primary Sclerosis Cholangitis. Immune Inflamm Dis. 2024;12(4):e1248. doi: 10.1002/iid3.1248.

Crohn's disease is a chronic inflammatory bowel disease (IBD) that can manifest throughout the entire gastrointestinal tract from mouth to anus. It is characterized by so-called "skip lesions", which are affected sections of the intestine interspersed with healthy sections. In recent years, there have been significant progress and an expansion of medical treatment options for Crohn's disease with the approval of many new substances. Treatment goals have also become more ambitious, going beyond clinical symptom control to mucosal healing and, according to the STRIDE II criteria, to transmural healing in Crohn's disease in the future. If these goals are achieved, patients with Crohn's disease have a good chance of remaining in long-term remission and can expect fewer complications such as disease progression, hospitalization, anemia, fistulas, strictures, or surgeries. Despite having access to a variety of different substance classes in the treatment of Crohn's disease, in everyday practice we can see that these medications are not effective for some patients in the long-term. There is a so-called "therapeutic ceiling" in IBD, meaning that only about 40-50% of those affected are successfully managed long-term with one substance. Therefore, new medical treatment options for Crohn's disease always represent an opportunity to treat patients even better.

Introduction: We aim to investigate the contribution of interstitial lung disease (ILD) to mortality in patients with inflammatory bowel disease (IBD). Methods: We performed a comprehensive retrospective, population-based epidemiological study across the United States from 2001 to 2020, using the Wide-ranging Online Data for Epidemiologic Research database. Mortality data were classified according to the International Classification of Diseases, Tenth Revision, with the codes J84 for ILD, K50 for Crohn’s disease, and K51 for ulcerative colitis. To discern patterns, age-adjusted mortality rates (AMR) were computed, stratified by sex, geographic census region, and racial/ethnic demographics. Results: From 2001 to 2020, there were 57,967 reported deaths among patients with IBD with an AMR per million significantly rising from 10.989 in 2001–2005 to 11.443 in 2016–2020 (P < 0.0001). ILD was a contributor to death in 1.19% (692/57,967) of these cases, with AMR rising from 0.092 to 0.143 per million (P = 0.010). The percentage of ILD-related deaths in the IBD population increased from 1.02% to 1.30% over 2 decades. ILD was a more common cause of death in patients with Crohn’s disease than with ulcerative colitis (54.6% vs 45.4%), with a significant increase for both conditions from 2001 to 2020 (P < 0.05). An upward trend in ILD-related mortality was observed in both sexes (P < 0.05) and within the White population (P = 0.010).

Introduction: Patients with inflammatory bowel disease (IBD) receiving immunosuppressive therapy might have an increased risk of developing a severe course of SARS-CoV-2 infection. The aim of this study was to investigate the development of antibodies in immunosuppressed patients with IBD compared to a healthy control group and to determine the effect of immunomodulators on the level of anti-SARS-CoV-2 IgG antibody levels before and after a third vaccination against SARS-CoV-2. Methods: This is a single-center study with a retrospective observational design. Seventy-one IBD patients matched by propensity score to 71 healthy employees (control group) were included. Blood was taken from both groups at predetermined times before and after the third booster vaccination. Results: All patients with IBD (n = 71, 100%) received immunomodulatory therapy. The mean antibody level before the third vaccination was 1,352.88 U/mL (SD = 1,011.489) in the IBD group and was not lower compared to the control group (p = 0.088). Gender, age, and disease duration had no significant impact on the development of antibody levels. Patients with TNF-alpha blockers had significantly lower antibody titers (p = 0.011) compared to the control group. Patients with integrin inhibitor therapy had significantly higher antibody titers (p = 0.003) than the controls. After the third vaccination, an increase in antibody titers was recorded in all patients in the IBD group. Conclusion: We recorded an antibody titer in all patients with IBD that was not significantly lower compared to healthy controls despite immunomodulatory therapy. The booster vaccination led to an increase in antibody levels in all patients with IBD.