Stefano Fusco

Background/Objectives: Accurate risk stratification of intraductal papillary mucinous neoplasms (IPMNs) remains clinically challenging. This study evaluates a structured imaging-based scoring approach for IPMN risk stratification, referred to as the Tübingen Dignity Score (TDS), and compares its diagnostic performance with established methods. Methods: In this retrospective study, imaging findings from patients with suspected IPMN were analyzed using MRI, CT, and ultrasound. The TDS was applied as an imaging-based scoring system. Diagnostic performance was assessed in a histopathological subset and compared with MRI-based assessment and Fukuoka criteria. Results: MRI showed high sensitivity (94.4%) but limited specificity (57.1%). Fukuoka criteria showed high sensitivity (100%) and high specificity (91.3%) in this cohort, although with a lower positive predictive value. In contrast, the TDS showed high specificity (100%) and positive predictive value, but lower sensitivity (40%), reflecting a different diagnostic profile. These findings indicate a trade-off between sensitivity and specificity across the evaluated approaches. However, the limited number of malignant cases limits the robustness and generalizability of these estimates. Conclusions: The TDS may serve as a complementary, imaging-based tool within a multimodal diagnostic framework for IPMN. Its potential value lies in supporting clinical decision-making in selected cases, particularly where established criteria yield inconclusive results. Given the limited sample size, retrospective single-center design, and exploratory nature of this study, external prospective multicenter validation is required before routine clinical application can be recommended.

Background: Crohn’s disease-associated intestinal strictures represent a major source of morbidity and frequently require endoscopic or surgical intervention. However, patients with stricturing Crohn’s disease demonstrate substantial clinical heterogeneity regarding disease localization, penetrating complications, systemic manifestations, metabolic alterations, and treatment exposure. This study aimed to explore phenotypic heterogeneity within patients with Crohn’s disease-associated intestinal strictures. Methods: In this retrospective exploratory cohort study, 96 patients with Crohn’s disease-associated intestinal strictures treated at a tertiary referral center between 2014 and 2024 were included. Clinical, structural, metabolic, and treatment-related variables were analyzed. Univariate analyses were performed using chi-square, Fisher’s exact test, Student’s t-test, or Mann–Whitney U test as appropriate. Exploratory multivariable logistic regression models were constructed to explore relationships between different clinical phenotypes and disease-related characteristics, including extraintestinal manifestations (EIMs), smoking status, penetrating disease manifestations, hepatic steatosis, stenosis localization, and abscess formation. Given the limited sample size and event numbers in several subgroup analyses, all multivariable analyses were considered exploratory and hypothesis-generating. Results: The cohort demonstrated a heterogeneous clinical presentation with a high prevalence of perianal disease, penetrating complications, prior intestinal surgery, and biologic therapy exposure. Female sex (OR 4.63, p = 0.044), autoimmune disease (OR 23.5, p = 0.049), rectal stenosis (inverse association; OR 0.08, p = 0.041), and exposure to multiple biologic therapies (OR 20.11, p = 0.036) remained associated with EIMs after multivariable adjustment. Smoking status was associated with anastomotic stenosis (OR 3.16, p = 0.023) and inversely associated with female sex (OR 0.35, p = 0.036). Phenotype-oriented analyses further suggested clustering of penetrating disease manifestations, including associations between intestinal fistulas, perianal fistulas, and abscess formation. Hepatic steatosis demonstrated exploratory associations with intestinal fistulas, intestinal resection, and appendectomy. Several analyses demonstrated wide confidence intervals and should therefore be interpreted cautiously. Conclusions: This exploratory retrospective cohort study highlights the substantial clinical heterogeneity observed among patients with Crohn’s disease-associated intestinal strictures. Different structural, systemic, penetrating, behavioral, and metabolic disease manifestations may indicate potentially overlapping phenotypic patterns within stricturing Crohn’s disease. Given the retrospective design, limited sample size, and exploratory statistical approach, these findings should be interpreted cautiously and require validation in larger prospective studies.

Esophagitis is a frequent, but at the molecular level poorly characterized condition with diverse underlying etiologies and treatments. Correct diagnosis can be challenging due to partially overlapping histological features. By proteomic profiling of routine diagnostic FFPE biopsy specimens (n = 55) representing controls, Reflux- (GERD), Eosinophilic-(EoE), Crohn’s-(CD), Herpes simplex (HSV) and Candida (CA)-esophagitis by LC-MS/MS (DIA), we identified distinct signatures and functional networks (e.g. mitochondrial translation (EoE), immunoproteasome, complement and coagulations system (CD), ribosomal biogenesis (GERD)), and pathogen-specific proteins for HSV and CA. Moreover, combining these signatures with histological parameters in a machine learning model achieved high diagnostic accuracy (100% training set, 93.8% test set), and supported diagnostic decisions in borderline/challenging cases. Applied to a young patient representing a use case, the external GERD diagnosis could be revised to CD and ICAM1 was identified as highly abundant therapeutic target. This resulted in CyclosporinA as a personalized treatment recommendation by the local multidisciplinary molecular inflammation board. Our integrated AI-assisted morphoproteomic approach allows deeper insights in disease-specific molecular alterations and represents a promising tool in esophagitis-related precision medicine.

Transglutaminase 2 (TG2) plays a pivotal role in the pathogenesis of celiac disease (CeD) by deamidating dietary gluten peptides, which facilitates antigenic presentation and a strong anti-gluten T cell response. Here, we elucidate the molecular mechanisms underlying the efficacy of the TG2 inhibitor ZED1227 by performing transcriptional analysis of duodenal biopsies from individuals with CeD on a long-term gluten-free diet before and after a 6-week gluten challenge combined with 100 mg per day ZED1227 or placebo. At the transcriptome level, orally administered ZED1227 effectively prevented gluten-induced intestinal damage and inflammation, providing molecular-level evidence that TG2 inhibition is an effective strategy for treating CeD. ZED1227 treatment preserved transcriptome signatures associated with mucosal morphology, inflammation, cell differentiation and nutrient absorption to the level of the gluten-free diet group. Nearly half of the gluten-induced gene expression changes in CeD were associated with the epithelial interferon-γ response. Moreover, data suggest that deamidated gluten-induced adaptive immunity is a sufficient step to set the stage for CeD pathogenesis. Our results, with the limited sample size, also suggest that individuals with CeD might benefit from an HLA-DQ2/HLA-DQ8 stratification based on gene doses to maximally eliminate the interferon-γ-induced mucosal damage triggered by gluten.

Background: Adult patients suffering from Crohn’s disease (CD) are often dissatisfied with the information they receive from their physicians about nutrition and its impact on CD inflammation activity. Only a few publications are available about patients’ internet research on nutrition in CD. The study aim is to elucidate the internet information sources of adult CD patients regarding nutritional advice via a questionnaire. Methods: A questionnaire with 28 (general and specific) questions for outpatients at our tertiary center with CD was created and used for an analysis of their information sources about nutrition in CD. Four CD and/or nutritional medicine experts examined the 21 most relevant websites referring to nutritional advice for CD patients. Results: One hundred and fifty CD patients reported their Internet research behavior for nutritional advice and their dietary habits. Many CD patients prefer to consult the Internet instead of asking their general practitioner (GP) for nutritional recommendations. Most of the websites providing nutritional advice for CD patients are of very poor quality and cannot be recommended. We found significant correlations between (a) nutritional habits of CD patients, (b) their information sources and several demographic or CD-related factors. There is a lack of websites which provide high-quality, good nutritional advice to CD patients. Conclusions: The majority of the examined websites did not provide sufficient information according to the CD guidelines and nutritional medicine guidelines. A higher quality level of website content (e.g., on social media or on university/center websites) provided by experienced physicians is required to secure trustworthy and reliable nutritional information in CD.

Background: SARS-CoV-2 infection and associated COVID-19 disease can lead to critical illness with a risk of developing a multiple organ failure. Subsequently, this may lead to various pathological sequelae, such as secondary sclerosing cholangitis after surviving COVID-19 (SSC-COVID). Objective: The aim is to retrospectively analyze a cohort of hospitalized patients with first-wave (February 2020–June 2020) SARS-CoV-2 infection and persisting unclear cholangiopathy to determine the incidence of SSC-COVID and its risk factors. Results: A total of 249 patients were hospitalized at the university hospital in Tübingen, Germany, with SARS-CoV-2 infection during the first wave of the pandemic. Of these, 35.3% (88/249) required intensive care treatment; 16.5% (41/249) of them died due to the complications of COVID-19; 30.8% (64/208) of surviving patients could be followed up und were retrospectively analyzed at our center. The incidence of confirmed SSC-COVID was 7.8% (5/64). All SSC-COVID patients had an ICU stay >20 days, for invasive ventilation, positioning treatment, vasopressor treatment, but possible risk factors for SSC were not significant due to the small number of patients. Conclusions: SSC-COVID is an emerging disease in post-COVID patients with a high incidence in our single-center cohort. SSC-COVID should be considered as a differential diagnosis, if unclear cholangiopathy or cholestasis persists after SARS-CoV-2 infection.

Background and aims: Postpolypectomy syndrome (PPS) is a relevant adverse event that can appear after polypectomy. Several publications mention postpolypectomy syndrome using different criteria to define it. The aim of this study is to detect potential risk factors and predictors for developing PPS and to define the main criteria of PPS. Methods: In this retrospective monocentric study, 475 out of 966 patients who underwent colonoscopy with polypectomy from October 2015 to June 2020 were included. The main criterion of PPS is defined as the development of postinterventional abdominal pain lasting more than six hours. Results: A total of 9.7% of the patients developed PPS, which was defined as local abdominal pain around the polypectomy area after six hours. A total of 8.6% of the study population had abdominal pain within six hours postintervention. A total of 3.7% had an isolated triad of fever, leukocytosis, and increased CRP in the absence of abdominal pain. Increased CRP combined with an elevated temperature over 37.5 °C seems to be a positive predictor for developing PPS. Four independent risk factors could be detected: serrated polyp morphology, polypoid configurated adenomas, polyp localization in the cecum, and the absence of intraepithelial neoplasia. Conclusions: Four independent risk factors for developing PPS were detected. The combination of increased CRP levels with elevated temperature seems to be a predictor for this pathology. As expected, the increasing use of cold snare polypectomies will reduce the incidence of this syndrome. Key summary: Our monocentric study on 966 patients detected four independent risk factors for developing PPS: pedunculated polyp, resected polyps in the cecum, absence of IEN, and serrated polyp morphology. The combination of increased CRP levels with elevated temperature seems to be a predictor for this pathology.

Background: The acute and chronic pancreatitis (CP) can lead to severe complications like walled-off necrosis, large symptomatic pseudocyst or multiorgan failure. The treatment of these complications is multivariate and can differ from conservative, symptomatic treatment or minimal-invasive, endoscopic transgastral stenting to transgastral necrosectomy. Objectives: This study aims to analyse the clinical course for patients that develop local complications of severe pancreatitis. Design: This is a retrospective observational single-centre study on 46 patients with severe pancreatitis. Methods: In this retrospective single-centre study, 46 out of 474 inpatients from January 2014 to December 2020, who were treated because of an acute or CP, developed acute pancreatitis complications and could be included. We analysed and compared the clinical course of different treatments (lumen apposing metal stents, transgastral double pigtail stent, endoscopic retrograde cholangiopancreatography, operation, conservative treatment) and different complications (walled-off necrosis (WON), pancreatic pseudocyst (PPC)). Results: Forty-six patients developed an acute complication due to severe pancreatitis. Twenty-seven patients developed a WON, while 19 patients suffered from PPC. 48% of the whole cohort had an alcoholic aetiology of pancreatitis. 78% were treated with antibiotics, 48% suffered from infected pancreatitis and 22% needed intensive care treatment. WON patients more often had a longer hospitalization of more than 21 days. PPC patients were correlated with an alcoholic aetiology, whereas WON patients were inversely correlated with an alcoholic aetiology. Increased lactate dehydrogenase, lipase, and C-reactive protein levels as well as leucocyte count could be associated with a higher probability to exhibit a WON instead of another local complication. The mortality rate was low with 7% in our study. Conclusion: WON and PPC differ in certain patients and laboratory characteristics such as aetiology, elevated laboratory values, antibiotic treatment or the duration of hospitalization. Invasive treatment is not required in all severe pancreatitis cases.

Background: Endoscopic retrograde cholangiopancreaticography (ERCP) is the standard endoscopic procedure for the diagnosis and treatment of diseases of the pancreas and bile ducts. Cholangioscopy provides direct visualization of the bile ducts. It offers the possibility of more detailed diagnostic and therapeutic indications. Today, cholangioscopy is often performed as a single-operator (SOC) procedure. Objectives: We were interested in the clinical efficacy of our SOC procedure in comparison with published studies, and performed this retrospective data analysis of all our consecutive patients from 2016 to 2022 to analyze the feasibility, safety, and efficacy of SOC. Design and Methods: A retrospective single-center analysis of patients undergoing SOC at a tertiary center from 2016 to 2022 ( N = 196) was performed. Demographic data, indication for SOC, exam-specific data, efficacy, and complications were included. Sensitivity and specificity for diagnosing indeterminate biliary strictures were calculated. Results: The most common indications for SOC were indeterminate biliary strictures ( n = 117; 60%), treatment of biliary stones ( n = 45; 23%), and other indications ( n = 34; 17%), for example, foreign body removal or intraoperative SOC. In 97% of the SOC ( n = 191), the procedure was technically successful. The diagnostic or therapeutic goal was achieved in 91% of SOC ( n = 173). In the subgroup where the SOC result was confirmed by subsequent surgery ( n = 93), sensitivity was 86%, specificity 99%, and SOC treatment of stones was successful in 89%. Complications occurred in (20%; n = 37). The majority of these patients ( n = 18; 10%) had minor bleeding requiring no intervention. Conclusion: SOC is an effective and safe procedure that should be the standard of care when primary diagnostic and/or therapeutic ERCP has failed. The sensitivity and specificity for determining the dignity of biliary strictures and the efficacy for the treatment of difficult-to-treat stones are reproducibly very high.