Ioannis E. Koutroubakis

Background and Objectives: Ozanimod is approved for the treatment of ulcerative colitis (UC). The aim of the present study was to evaluate the clinical, biochemical, and endoscopic outcomes. Materials and Methods: This was a retrospective, multicenter, cohort study. Clinical, biochemical, endoscopic, and safety data were collected from medical records. Τhe primary outcome was clinical response at week 12. Secondary outcomes included clinical remission, endoscopic improvement and remission, biochemical outcomes, treatment persistence, and safety. Clinical outcomes were assessed at weeks 12 and 48, while treatment persistence was evaluated over the complete 48-week follow-up period, using Kaplan–Meier analysis. Clinical response was defined as a ≥30% reduction in partial Mayo score and remission as a partial Mayo score < 3, with no individual sub-score > 1 and a rectal bleeding sub-score of 0. Clinical response and remission were primarily assessed using an observed-case approach, with an additional sensitivity analysis classifying discontinuations due to lack of efficacy as treatment failures. Results: A total of 79 patients were included (62.0% male; median age 44 years, IQR 31–56). Prior biologic exposure was recorded in 29.1%, and 64.6% were previously exposed to oral corticosteroids. Among patients with available clinical assessment at week 12 (n = 62), clinical response and clinical remission were achieved in 77.4% and 71.0%, respectively. Among patients with available data at week 12 (n = 32), endoscopic improvement was observed in 65.6%, while endoscopic remission was achieved in 15.6%. At week 48, among 26 evaluable patients, clinical response and remission rates were 96.2% and 84.6%, respectively; when discontinuations due to lack of efficacy were considered treatment failures, the corresponding rates were 52.1% and 45.8%. Treatment persistence did not differ significantly according to overall prior biologic exposure, whereas previous vedolizumab exposure was associated with lower treatment persistence over the week 48 follow-up (log-rank p = 0.037). In multivariable Cox regression, previous vedolizumab exposure remained associated with an increased hazard of treatment discontinuation (adjusted HR 3.07, 95% CI 1.23–7.67; p = 0.016). Adverse events were reported in 13.9% of patients. Conclusions: Ozanimod demonstrated good efficacy and a favorable safety profile in patients with moderate UC.

Background and Aims: Pancreatic hyperenzymemia in inflammatory bowel disease (IBD) is an under-recognized and challenging condition, as elevated pancreatic enzymes may arise from heterogeneous mechanisms and do not necessarily reflect true pancreatic disorder. This multicenter study aimed to characterize the clinical spectrum, diagnostic work-up, and outcomes of hyperenzymemia in IBD. Methods: This retrospective multicenter study was conducted within the PANDORA network, including 34 international IBD centers. For the present analysis, only centers providing patient-level data on pancreatic hyperenzymemia were considered. Collected variables included demographic, clinical, biochemical, imaging, and therapeutic data. Cases were categorized into three predefined phenotypes: chronic asymptomatic pancreatic hyperenzymemia (CAPH), reclassified acute pancreatitis not meeting Atlanta criteria (recAP), and autoimmune pancreatitis (AIP). Results: A total of 148 IBD patients with elevated pancreatic enzymes were included (CAPH 54.7%, RecAP 35.1%, AIP 10.1%). Ulcerative colitis (UC) accounted for 56.8% of cases and Crohn’s disease (CD) for 43.2%. Overall, 73.6% of patients were asymptomatic at the time of enzyme elevation. Marked hyperenzymemia (≥3× ULN) occurred in 22.3% of patients and was more frequent in RecAP than in CAPH or AIP (50.0%, 6.2%, and 13.3%, respectively). IBD was clinically active in 48.6% of patients, with higher rates in CD. Notably, the clinical meaning of hyperenzymemia differed across IBD phenotypes: in CD it was more often associated with active inflammation, whereas in UC it more frequently prompted advanced imaging and led to the identification of AIP. Imaging strategies differed significantly across phenotypes, and drug withdrawal was common in CAPH and RecAP but unnecessary in AIP. Only two rechallenges confirmed a drug-related mechanism. Conclusions: Pancreatic hyperenzymemia in IBD encompasses a spectrum of conditions with different implications. A phenotype-oriented diagnostic approach is essential to avoid misclassification and unnecessary treatment changes.

Background/Objectives: Ustekinumab has been approved for the treatment of moderate to severe ulcerative colitis. Real-world data regarding its efficacy and the discovery of predictive factors of response need to be studied further. We aimed to evaluate the efficacy and identify predictors of response to induction treatment with ustekinumab in patients with ulcerative colitis. Methods: This is a multicenter, prospective cohort study. Clinical response (CR) at week 16 was the primary endpoint, and steroid-free clinical remission (SFCRem) and endoscopic response were the secondary endpoints. Baseline histology, mucosal gene expression, and pharmacokinetics were studied for their effect on response to treatment. Results: We included 123 patients (mean age = 50.3 years). CR was recorded in 70.8% (75/106), SFCRem in 48% (59/123), endoscopic improvement in 71.4% (40/56), and mucosal healing in 28.6% (16/56). Higher PRO-stool frequency (OR = 0.49, p = 0.027), concomitant use of 5-ASA (OR = 3.69, p = 0.021), platelet number of ≥284 × 10⁹/L (OR = 6.52, p = 0.001) at baseline, and a drop in the total count of platelets by 10⁸/L (OR = 1.23, p = 0.022) at week 8 were independently associated with CR. Elevated trough levels of ustekinumab at week 16 were associated with a higher probability of endoscopic improvement (median difference = 3784 ng/mL, p = 0.013), with an optimal cut-off value of 3500 ng/mL (AUC = 0.82, 95% CI: 0.66–0.96). Increased mucosal mRNA expression for IL-23 (p = 0.007) and IL-23R (p = 0.031) at baseline was associated with increased probability of CR. Higher continuous Geboes scores at baseline were associated with a lower probability of CR (OR = 0.80, p = 0.045), with an optimal cut-off value of 14 (AUC = 0.75, 95% CI: 0.57–0.93). Conclusions: Clinical, laboratory, and molecular markers may identify patients with ulcerative colitis who are more likely to respond to ustekinumab.

Background and aims: An increased risk of acute pancreatitis (AP) has been reported in patients with inflammatory bowel disease (IBD), but data on its prevalence, etiology, and outcomes are limited. Materials and Methods: A two-step retrospective analysis spanning 10 years (2011–2020) was conducted across 34 European centers. The first step surveyed the prevalence of AP in patients with IBD, while the second gathered data on disease characteristics, etiology, and outcomes. Results: The survey found an expected AP prevalence of 1.13% (780/68,989), though only 0.58% (n = 398) met the inclusion criteria. The mean age was 33.6 ± 14.3; 52% were female, and 56.5% had Crohn’s disease (CD). AP was clinically mild in most cases (86.9%). Among 347 patients with available imaging, no alterations were observed in 81 (23.3%), whereas edematous AP was observed in 218 (62.8%). Drugs (mainly azathioprine) were the leading cause (55.3%), followed by biliary (14.8%) and autoimmune (7.8%) causes. In 13.5% of patients, AP was considered idiopathic. During a median follow-up of 67 months [IQR 34–96] from the index episode, recurrence was observed in 13% of patients, and 1.5% developed chronic pancreatitis. CD patients exhibited distinct risk profiles, including ileal involvement and smoking, whereas ulcerative colitis (UC) patients showed more frequent autoimmune and idiopathic etiologies. Conclusions: The PANDORA study established a 0.58% prevalence of AP in IBD patients, which was lower than expected. AP is usually mild both clinically and radiologically. An ileal location in CD and extensive colitis in UC are usually reported, and azathioprine seems to be the most common cause of AP in this setting, especially a few weeks after its introduction.

Background Ulcerative colitis (UC) increases the risk for venous thromboembolism. Tissue factor (TF) initiates the extrinsic coagulation pathway (ECP). Aims To investigate the correlation of UC severity with latent ECP activation and TF expression in primary colonic stromal cells (PCSC). Methods In plasma of 38 UC patients (31 males, disease duration 151 ± 25 months) and 28 healthy controls, exosomes and microparticles (EM) were counted. Moreover, TF protein concentration, activities of EM-bound TF (EM-TFa) and coagulation factor VII (FVIIa) were assessed. In PCSC in culture, TF mRNA (F3) from 12 patients with active UC and 7 controls was evaluated. Results UC patients had 4– and 3.7– times more exosomes and microparticles, respectively, than controls. TF protein in UC was correlated with several disease severity indices, such as partial Mayo score (pMs; r 0.443), albumin (− 0.362), ESR (0.353), PLT (0.575), and endoscopic Ms (eMs 0.468). EM-TFa was also significantly higher in UC and was correlated to SIBDQ (− 0.64), albumin (− 0.624), disease extent and eMs (0.422). Refractory-to-treatment patients had significantly higher TF protein, EM-TFa and FVIIa. Even within responders, the need for steroids or biologics correlated with a 2.2–times higher EM-TFa. PCSC from active UC maintained higher F3 than controls, which was correlated to pMs (0.56), albumin (− 0.543) and eMs. Treatment with cytokines further upregulated F3. P for all comparisons was < 0.05. Conclusion Low-grade activation of the ECP associates with clinical, endoscopic UC activity and response to treatment. TF in PCSC mirrors its systemic activity and points to them as a source. Graphical Abstract

Background: This real-world analysis evaluated iron therapy supplementation in inflammatory bowel disease patients with iron-deficiency anemia, considering disease progression and healthcare resource consumption. Methods: A retrospective observational study was conducted using administrative databases of a pool of Italian healthcare entities, covering about 9.3 million beneficiaries. Between January 2010 and September 2017, adult patients were enrolled in the presence of either hospitalization or active exemption code for ulcerative colitis/Crohn’s disease, or one vedolizumab prescription. Iron-deficiency anemia was identified by at least one prescription for iron and/or hospitalization for iron-deficiency anemia and/or blood transfusion (proxy of diagnosis). Patients were divided in untreated and iron-treated during 12-month follow-up and analyzed before and after propensity score matching. Disease progression, was evaluated through inflammatory bowel disease-related hospitalizations and surgeries, and healthcare resource utilization was assessed. Results: Overall, 1753 patients were included, 1077 (61.4%) treated with iron therapy and 676 (38.6%) untreated. After propensity score matching, 655 patients were included in each group. In unbalanced cohorts, disease progression was significantly reduced in patients receiving iron therapy compared to the untreated (11.0% vs. 15.7%, P < 0.01), and this trend was maintained also after applying propensity score matching. The overall mean cost/patient was significantly lower in iron-treated than untreated (4643€ vs. 6391€, P < 0.01). Conclusion: The findings of this real-world analysis suggest that iron therapy was associated with significant benefits in inflammatory bowel disease patients with iron-deficiency anemia, in terms of both disease progression and healthcare resource utilization.

Background Obesity and liver cirrhosis represent significant health challenges, often leading to various complications. Aims This prospective study aimed to investigate the impact of a four-year bariatric intervention, focusing on adherence to the Mediterranean Diet, on anthropometric, hematologic, and biochemical parameters in obese patients with compensated liver cirrhosis. Additionally, the study evaluated the concurrent contribution of weight loss to these health indicators. Methods The study involved 62 patients with compensated liver cirrhosis (mean age 65.87 ± 6 years) and 44 healthy controls (mean age 59.11 ± 8 years), all with a BMI > 30 kg/m². Both groups underwent a weight loss intervention based on the Mediterranean diet, with a four-year follow-up. Anthropometric, biochemical and hematologic parameters were evaluated at several time points during the study and their statistical significance was assessed. Results Anthropometric parameters, including weight, BMI, waist and hip circumference, percentage of fat mass, and handgrip strength, exhibited significant improvements (p < 0.05), particularly within the first year of the intervention. Liver function tests and lipid profiles of the patients also showed significant enhancements (p < 0.05). Hematological and biochemical indices, such as hematocrit and ferritin, experienced discreet improvements in the patient cohort (p < 0.05). Conclusions This study highlights the potential of a structured bariatric intervention rooted in the Mediterranean diet to positively influence the health of obese patients with compensated liver cirrhosis. The observed improvements in anthropometric, biochemical, and hematologic parameters, particularly within the first year of the intervention, suggest the importance of dietary modifications in managing the health of this patient population.

Anemia is a prominent global health issue with a wide variety of causes and can be associated with decreased quality of life, increased hospitalization, and higher mortality, especially in older individuals. Therefore, studies further shedding light on the causes and the risk factors of this condition should be performed. The aim of the present study was to examine the causes of anemia in hospitalized patients in a tertiary hospital in Greece and identify risk factors related to higher mortality. In total, 846 adult patients with a diagnosis of anemia were admitted during the study period. The median age was 81 years, and 44.8% were male. The majority of patients had microcytic anemia, with the median mean corpuscular volume (MCV) being 76.3 fL and the median hemoglobin being 7.1 g/dL. Antiplatelets were used by 28.6% of patients, while 28.4% were using anticoagulants at the time of diagnosis. At least one unit of packed red blood cells (PRBCs) was transfused in 84.6% of patients, and a median of two PRBCs was used per patient. A gastroscopy was performed in 55%, and a colonoscopy was performed in 39.8% of patients in the present cohort. Anemia was considered to be multifactorial in almost half the cases, while the most commonly identified cause was iron deficiency anemia, more commonly with positive endoscopic findings. Mortality was relatively low, at 4.1%. Multivariate logistic regression analysis identified higher B12 levels and longer duration of hospital stay to be independently positively associated with mortality.

Background: The Inflammatory Bowel Disease-Disk (IBD-Disk) is a physician-administered tool that evaluates the functional status of patients with Inflammatory Bowel Disease (IBD). The aim of our study was to validate the content of the IBD-Disk in a Greek cohort of IBD patients. Methods: Two questionnaires [the IBD Disk and the IBD-Disability Index (IBD-DI)] were translated into Greek and administered to IBD patients at baseline visit, after 4 weeks and 6 months. Validation of the IBD Disk included measuring of concurrent validity, reproducibility, and internal consistency. Results: A total of 300 patients were included at baseline and 269 at follow-up. There was a good correlation between the total scores of the IBD-Disk and IBD-DI at baseline (Pearson correlation 0.87, p < 0.001). Reproducibility of the total IBD-Disk score was very good [intra-class correlation coefficient (ICC), 95% confidence interval (CI) 0.89 (0.86–0.91)]. Cronbach’s coefficient alpha for all items achieved 0.90 (95%CI 0.88–0.92), demonstrating a very good homogeneity of the IBD-Disk items. Female gender and extraintestinal manifestations were significantly associated with a higher IBD-Disk total score. Conclusions: The Greek version of the IBD-Disk proved to be a reliable and valid tool in detecting and assessing IBD-related disability in a Greek cohort of IBD patients.