Abstract Background The Apulian Network for Inflammatory Bowel Disease (AN-IBD) is a prospective observational regional database recently approved by the Ethics Committee in Apulia (Italy), enrolling all IBD patients with an established diagnosis and focusing on the safety and effectiveness of all licensed therapies. We aimed to evaluate the safety profile of IBD therapies registered in patients enrolled in the participating centres and to record the occurring adverse events. Methods The AN-IBD involves 19 centres across Apulia, selected based on their capacity to prescribe advanced IBD therapies. In the six months following the ethical approval, we recorded unselected patients in the database and stratified them by disease type, age, sex and type of treatment. The occurrence of infusion reactions (local and systemic), infections, IBD-related hospitalization, need for colectomy, malignancies, thromboembolic events, and laboratory alterations were recorded. Their severity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Results A total of 420 patients were enrolled, consisting of 251 males (59,76%) and 169 females (40,24%), with a median age of 44 years. Among them, 243 (57,86%) were diagnosed with ulcerative colitis, 156 (37,14%) with Crohn’s disease and 21 (5%) with unclassified colitis. Overall, 341 patients (81,19%) were treated with advanced therapy, including biologic therapy and small molecules. A total of 33 (7,85%) adverse events were recorded comprehensively, and most of them were graded as moderate according to the CTCAE. Twenty-three patients were treated with biologic therapy (70%), seven with small molecules (21%), one with immunomodulators (3%) and two with conventional therapy (6%). The most common adverse events were infusion reactions, with fourteen cases recorded (42%), followed by eight cases of infective complications (24%), predominantly due to cytomegalovirus reactivation. Other recorded adverse events included IBD-related surgery (15%), malignancies (9%) and altered liver enzymes (9%). Conclusion These preliminary findings evaluate the real-world prevalence and nature of adverse events among the population enrolled in our newly developed multicentre regional cohort. The establishment of this new database, given the absence of a national registry, will allow for closer monitoring of IBD patients undergoing conventional and advanced therapies and will increase awareness of the safety of these treatments.

Abstract Background Upadacitinib (UPA), a selective anti-JAK1, has obtained refundability from the Italian National Health System in July 2023 for its use in patients with Ulcerative Colitis (UC) refractory to other therapies, including anti-TNF-α, anti-integrins and ustekinumab. At present, no Italian data are available yet about its effectiveness and safety in Real World. Methods A retrospective assessment of clinical and endoscopic activity was performed according to the Mayo score. The primary endpoints were to evaluate the effectiveness and safety of UPA. Results We enrolled 186 patients with a median follow-up of 24 weeks weeks (M/F 105/76, median age 41). Clinical remission was achieved in 31% (57/186) and 70% (55/78, p<0-05) patients at 8-week and 24-week follow-ups, respectively; clinical response was achieved in 103/186 (55%) and 68/78 (87%, p<0.5) patients at 8-week and 24-week follow-ups, respectively. Adverse events occurred in 5 (2.6%) patients and severe in 1 (0.5%). Conclusion Our realworld data confirm that UPA is effective and safe in UC patients. It performs remarkably better when used as the first/second line of treatment.

Abstract Background Filgotinib (FILGO), a selective anti-JAK1, has obtained refundability from the Italian National Health System in February 2023 for its use in patients with Ulcerative Colitis (UC) refractory to other therapies, including anti-TNF-α, anti-integrins and ustekinumab. At present, no Italian data are available yet about its effectiveness and safety in Real World. Methods A retrospective assessment of clinical and endoscopic activity was performed according to the Mayo score. The primary endpoints were to evaluate the effectiveness and safety of FILGO. Results We enrolled 102 patients with a median follow-up of 24 weeks (M/F 54/48, median age 47). The clinical remission and clinical response rates at 8 weeks were 12% (13/102) and 29% (30/102), respectively, and 51% (20/39, p<0.01) and 82% (32/39, p<0.01) at 24-week follow-ups, respectively. Adverse events occurred in 6 (5.8%) patients and severe in 2 (1.9%). Conclusion Our realworld data confirm that FILGO is effective and safe in UC patients. It performs remarkably better when used as the first/second line of treatment.

Abstract Background Upadacitinib is a selective Jak-1 inhibitor approved for treating Inflammatory Bowel disease (IBD). Its efficacy and safety have been assessed in pivotal trials. Few real-world experiences of Upadacitinib in IBD patients have been published so far. We aimed to investigate the effectiveness and safety of Upadacitinib in a cohort of IBD patients in clinical practice. Methods This multicenter, observational study was performed among the Apulian Network for Inflammatory Bowel Disease (AN-IBD). All consecutive patients with IBD starting Upadacitinib from its introduction were included. Results We enrolled 68 patients with Ulcerative Colitis (UC) and 9 with Crohn’s Disease (CD. The mean age of the patients was 40.2 ± 14.2 (range 19 - 74) and 45.3 ± 11.8 (range 26 - 62) for UC and CD, respectively. Regarding gender, 51 patients were male (66.2%). The mean disease duration was 11.8 ± 8.4 (range 3 - 31) for UC patients and 11.4 ± 8.6 (range 2 - 26) for CD patients. As for disease extension, patients with UC were divided into three groups: pancolitis (n=31, 45.5%), distal colitis (n=33, 48.5%), and proctitis (n=4, 6%). In CD patients, 5 had ileitis (55.6%), 2 colitis (22%), 1 ileocolitis (11.2%) and 1 jejunoileitis (11.2%). The response and remission rates after 8 weeks were 39% and 52% in UC patients. The response and remission rates after 12 weeks were 66% and 16% in CD patients. The primary non-response rate was 9.5% and 16% in UC and CD, respectively. Regarding safety, two cases of herpes reactivation were observed (1 herpes zoster in a non-vaccinated patient, and 1 herpes simplex infection, both managed with antiviral therapy). One patient experienced mild anemia, rapidly corrected after switching to 15 mg/day. One non-responder underwent an urgent colectomy. Conclusion These preliminary data confirm the efficacy of upatacitinib in inducing responses in IBD patients (both UC and CD) with a very low rate of primary failure. No new safety issues were identified.

BackgroundUstekinumab (UST) is an interleukin-12/interleukin-23 receptor antagonist recently approved for treating ulcerative colitis (UC) but with limited real-world data. Therefore, we evaluated the effectiveness and safety of UST in patients with UC in a real-world setting.Research design and methodsThis is a multicenter, retrospective, observational cohort study. The primary endpoints were the clinical remission rate (partial Mayo score, PMS, <= 1) and the safety of UST. Other endpoints were corticosteroid-free remission (CSFR) rate, clinical response rate (PMS reduction of at least 2 points), and fecal calprotectin (FC) reduction at week 24.ResultsWe included 256 consecutive patients with UC (M/F 139/117, median age 52). The clinical remission and clinical response rates at eight weeks were 18.7% (44/235) and 53.2% (125/235), respectively, and 27.6% (42/152) and 61.8% (94/152) at 24 weeks, respectively. At 24 weeks, CSFR was 20.3% (31/152), and FC significantly dropped at week 12 (p = 0.0004) and 24 (p = 0.038). At eight weeks, patients naive or with one previous biologic treatment showed higher remission (p = 0.002) and clinical response rates (p = 0.018) than patients previously treated with >= 2. Adverse events occurred in six patients (2.3%), whereas four patients (1.6%) underwent colectomy.ConclusionThis real-world study shows that UST effectively and safely treats patients with UC.

Abstract Background Current data about long-term use of vedolizumab (VDZ) in ulcerative colitis (UC) versus Crohn’s disease (CD) patients are limited. We aimed to assess whether there are differences in term of long-term efficacy and safety of VDZ in UC vs. CD patients. Methods Clinical activity was scored according to the Mayo score in UC and to the Harvey-Bradshaw Index (HBI) in CD. The primary endpoints were the achievement of clinical remission within 6 month of treatment, maintenance of clinical remission during a long follow-up, and safety. Secondary endpoints were clinical response to treatment, achievement of mucosal healing (MH), steroid discontinuation, and treatment optimization during the follow-up. Results The study group consisted of 729 patients (475 patients with UC and 254 CD patients with CD) with a median follow-up of 18 (interquartile range 6-36) months. Clinical remission at the 6th month of treatment was achieved in 488 (66.9%) patients, higher in CD patients (74.4 vs. 62.9, p<0.000) while, at the maximal follow-up, it was achieved and maintained in 81.5% of patients (UC vs. CD, p=0.667). At uni- and multivariate analysis, reaching clinical remission at the 6th month of treatment (p=0.001) and being naïve to biologics were significantly associated with longer clinical remission (p<0.0001). Long-term follow up clinical response was significantly higher in UC vs. CD (p=0.023) and surgery occurred more frequently in CD (p=0.04), while no difference were found between UC and CD about the other secondary endpoints Conclusion Overall, no significant differences were found about the long-term use of VDZ in UC vs. CD. However, we identified some parameters the can help the physician to predict the long-term efficacy of this drug.

OBJECTIVE: Ustekinumab (UST) is an anti-IL12/23 antibody for the treatment of Crohn’s Disease (CD). The aim of this study was to compare the efficacy and safety of UST in a large population-based cohort of CD patients who failed previous treatment with other biologics. PATIENTS AND METHODS: 194 CD patients (108 males and 86 females, mean age 48 years (range 38-58 years) were retrospectively reviewed. 147 patients were already treated with anti-TNFα (75.8%), and 47 (24.2%) patients were already treated with anti-TNFα and vedolizumab. Concomitant treatment with steroids was present in 177 (91.2%) patients. RESULTS: At week 12, clinical remission was achieved in 146 (75.2%) patients. After a mean follow-up of 6 months, clinical remission was maintained in 135 (69.6%) patients; at that time, mucosal healing was assessed in 62 (31.9%) patients, and it was achieved in 33 (53.2) patients. Three (1.5%) patients were submitted to surgery. Steroid-free remission was achieved in 115 (59.3%) patients. Both serum C-Reactive Protein and Fecal Calprotectin (FC) levels were significantly reduced with respect to baseline levels during follow-up. A logistic regression, UST therapy as third-line therapy (after both anti-TNFα and vedolizumab), FC >200 µg/g, and HBI ≥8 were significantly associated with lack of remission. Adverse events occurred in 5 (2.6%) patients, and four of them required suspension of treatment. CONCLUSIONS: UST seemed to be really effective and safe in CD patients unresponsive to other biologic treatments, especially when used as second-line treatment.

Background: Moderate-to-severe active ulcerative colitis (UC) may be treated with anti-TNFα. Since the Adalimumab (ADA) distribution in Italy by National Health System (April 2014), its use in UC patients follows rigid entry criteria and a standard schedule of evaluation of clinical outcomes. Aim of this study was to assess the efficacy and safety of Adalimumab in inducing remission or clinical response in outpatients UC patients treated in Italian primary Inflammatory Bowel Diseases centres. Methods: Fifty-seven consecutive UC patients with at least 12-week follow-up were enrolled. The primary endpoint was clinical remission reaching, defined as Mayo score or partial Mayo score ≤2 after 12 weeks. The secondary endpoints included: (1) clinical response to treatment, defined as partial Mayo score reduction of at least 2 points; (2) safety of the drug, defined as occurrence of adverse events during treatment. Results: Demographic characteristics of the enrolled population are reported in table 1. At 8-week follow-up, clinical response was obtained in 36/57 (63.2%) patients and clinical remission was achieved in 22/57 (38.6%) patients. At 12-week follow-up, clinical response was obtained in 35/55 (63.6%) patients and clinical remission was achieved in 21/55 (38.2%) patients. Significantly, no adverse events neither colectomy were recorded during the 12-week trial. Conclusions: Real-life effectiveness of adalimumab in inducing UC remission is promising, also in patients had already been exposed to infliximab beforehand. Larger groups of patients, with longer follow-up, are warranted to confirm such results.

Mortality associated with acute upper gastrointestinal bleeding is described high despite advances in diagnosis and therapy but, at our knowledge, study on the recent epidemiology, of acute upper gastrointestinal haemorrhage, on PPI epoch, are few Endoscopic and more recent pharmacologic treatment has recently been shown to reduce rebleeding rates and perhaps mortality. These advances in therapy are becoming more widely adopted and may influence the outcomes of patients with upper gastro intestinal bleeding (UGIB). Aim of the study was 1) verify the mortality rate of patients with UGIB in a nationwide survey, 2) evaluate the treatment role on the outcomes considered, 3) provide a predictive model of mortality taking in account also the therapeutic role. The data presented were collected over 12 months as part of a national audit of the management and outcome of acute upper gastrointestinal haemorrhage. From march 2003 to march 2004 a population based, unselected, multicentre, prospective survey, with 175 items, was conducted from 23 hospitals receiving emergency admissions in various regions equally distributed. 1175 cases of acute upper gastrointestinal haemorrhage ,in which patients aged from 10 to 99 years old, were identified. Results: the mean age was 67,03 ± 15,76 SD range 10-99, males account for 62% of the serie. Non variceal bleeding (NVB) is the main cause of bleeding in 86,8% (1020 patients). The main co-morbities was hypertension 29.3% and neoplasia was present in 7.8%; Endoscopic treatment was not done in 523 (51.3%); when employed, the more frequent was injection with adrenaline solution 319 (64.2%). After endoscopy the main used pharmacological treatment was proton pump inhibitors 76.7%, while H2 antagonists used in. 3.9% Overall mortality rate was 4,5%. Of the 175 items analyzed, 14 give independent gain in the mortality predictive model: ASA class, time to recovery, age, blood pressure, cardiac frequency, haemoglobin value, neoplasia, renal failure, cirrhosis, hematemesis, blood in gastric lumen, active bleeding, endoscopic treatment failure, and rebleeding. The area under the Roc curve give a .847 value that is one of the most relevant predictive model proposed. Conlusion mortality rate from UGIB in Italy is not so high but rise with age and comorbities. The challenge is to identify those patients who have most high risk for death so that their treatment and survelliance can be optimized. Various risk.

PURPOSE:Partially hydrolyzed guar gum (PHGG) is a water-soluble dietary fiber, possessing non-gelling properties. The objective of this clinical experience was to evaluate the progress of symptoms and the modifications in the frequency of evacuation in subjects affected by IBS and regularly taking PHGG.PATIENTS AND METHODS:The group was made up of 134 out-patients of both sexes, average age 43.12, suffering from IBS, both obese and of normal weigh, with a mean number of weekly evacuations between 2 and 35. The subjects, divided in 2 groups on the basis of Body Mass Index (BMI), were submitted for 24 weeks to a balanced, low or normal calorie diet supplemented by 5 g a day of PHGG. The following information was gathered: number of weekly evacuation, typical symptoms of IBS, cholesterol, triglycerides and glucose levels. In a few subjects (n. = 34) also the plasmatic electrolyte levels, before and during PHGG intake, were evaluated.RESULTS:Both groups showed positive results in the evacuation frequency (p < 0.01 at 12th week) and a decrease, after 3 weeks of PHGG intake, in frequency of IBS symptoms such as flatulence (-55.6%), abdominal tension (-4.7%) and abdominal spasm (-35%). On the other hand an increased number of subjects showed normal levels of cholesterol (+12.2%), lipids (+26.9%) and glucose (+16%). Concentrations of plasmatic electrolytes didn't change during PHGG intake, except for a marked increase of selenium levels, compared to pre-intake levels.CONCLUSIONS:The observations obtained from this clinical experience reassert that dietary fiber supplementation is useful in cases of altered intestinal motility. PHGG, due to its water-solubility and non-gelling properties, can be useful also in IBS.

Recently a spiral bacterium different from Helicobacter Pylori (HP) was observed in the human stomach and the name of Gastrospirillum Hominis (GH) was proposed for this organism. GH presence is reported to be not associated to HP but related to chronic active gastritis. We describe the case of a 31 year old male suffering from upper abdominal symptoms, who underwent oesophagogastroduodenoscopy, which revealed a picture of duodenal hyperemia. Gastric body showed a normal mucosa and absence of HP, while active chronic gastritis associated with HP was found in the antrum. In addition few spiral bacteria showing 4-5 spirals, larger than HP were observed within the gastric crypts and beneath the mucus layer in this site. This case represents the first report from our geographic area (Southern Italy) of the possibility of finding bacteria different from HP in the human stomach. The simultaneous HP presence does not allow us to relate the chronic active gastritis of the patient with the GH like bacteria. Our finding, however, suggests the possibility that HP and GH may be simultaneously present in the course of type B antral chronic inflammation. This association was not observed in previous investigations.