We assessed whether baseline endoscopic and clinical scores of diverticular disease (DD) may predict the severity of acute diverticulitis (AD), hospital admission and length of hospital stay (HS). We conducted a 3-year, multicentre, prospective cohort study involving 2215 patients. DD was scored according to the Diverticular Inflammation and Complication Assessment (DICA) classification and the Combined Overview on Diverticular Assessment (CODA) score. Higher baseline DICA and CODA scores were associated with increased risk of complicated AD [relative risk ratio (RRR) = 5.57; 95

Mechanisms underlying symptomatic uncomplicated diverticular disease (SUDD) remain unclear. Here, we explored alterations in the gut microbiota associated with SUDD. Patients visiting outpatient clinics for refractory abdominal pain at five Japanese centers between February 2021 and May 2022 were prospectively enrolled. Patients diagnosed with SUDD (n = 29) and those with diverticulosis but not meeting the SUDD criteria (non-SUDD; n = 35) were included. Asymptomatic individuals served as healthy controls (HC; n = 68). Fecal samples were analyzed using 16 S rRNA gene sequencing. α-diversity indices were significantly lower in the SUDD and non-SUDD groups than in the HC group. β-diversity also differed significantly among groups. The abundance of the Ruminococcus gnavus group was higher in the SUDD group than in the non-SUDD and HC groups, whereas that of Coprococcus was lower. Butyrate-producing bacteria were less abundant in the SUDD group. Prediction-based (PICRUSt2) metagenomic analysis suggested upregulation of pathways, such as exopolysaccharide biosynthesis and cell cycle, in the SUDD group. Patients with SUDD exhibited dysbiosis, which may contribute to pathogenesis via impaired epithelial homeostasis, such as decreased mucosal butyrate concentration. The findings of this exploratory, observational study represent associations that require confirmation via direct functional and metabolomic measurements.

INTRODUCTION:Colonic diverticulosis is the most common structural abnormality of the colon in developed countries, with an increasing global prevalence. Approximately 20-25% of affected individuals develop symptoms, collectively referred to as diverticular disease. Given its wide clinical spectrum, evolving pathophysiological insights and growing disease burden, updated guidance is essential. METHODS:This International Consensus, developed by 32 experts from 14 countries through a structured Delphi process based on the PICO framework and GRADE methodology, provides evidence-based recommendations across five domains: epidemiology and pathogenesis; clinical features; diagnosis; medical therapy; and surgical management. RESULTS:Key statements define diverticulosis as the presence of diverticula without symptoms and diverticular disease as diverticula associated with symptoms or complications. High dietary fibre intake is protective whereas smoking, obesity and the use of non-steroidal anti-inflammatory drugs, corticosteroids, opioids or immunotherapy increase risk. Imaging is essential in suspected acute diverticulitis: ultrasound may be appropriate in experienced hands, while CT remains preferred for complicated cases. Diverticulosis itself requires no treatment. In symptomatic uncomplicated diverticular disease, dietary fibre, selected probiotics, mesalazine and rifaximin may help relieve symptoms. Routine antibiotic use is not recommended for acute uncomplicated diverticulitis, and elective surgery should be individualised, prioritising quality of life considerations over episode count. CONCLUSIONS:These Consensus statements aim to standardise and optimise the diagnosis, management and prevention of diverticular disease across diverse healthcare systems, while highlighting research priorities such as microbiome characterisation, genetic risk profiling and long-term outcomes of selective antimicrobial and surgical strategies.

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.

Background and AimSymptomatic uncomplicated diverticular disease (SUDD) causes persistent pain and impairs patient quality of life; however, its pathogenesis remains unknown. This study investigated the relationship between SUDD and the inflammatory effects of intestinal bile acids (BAs).MethodsFive institutional cohorts with 361 total patients who received outpatient treatment for abdominal symptoms (from 2020 to 2022) were included in this prospective cohort study. All patients underwent colonoscopy. SUDD was defined as the presence of recurrent abdominal symptoms—pain in the lower quadrant lasting >24 h—in patients with diverticulosis at the site of pain. Patients with diverticula were classified into SUDD and non-SUDD groups. The healthy control (HC) group comprised people with no history of medications and no evidence of colonic diverticula. Liquid chromatography-mass spectrometry determined the concentration of fecal BAs. Fecal calprotectin and blood endotoxin activity assay (EAA) levels were measured.ResultsTotal fecal BA concentrations did not differ between HC and non-SUDD patients; however, BA levels were significantly higher in patients with SUDD. Fecal calprotectin and blood EAA levels were significantly higher in the SUDD and non-SUDD groups than in the HC group, and in the SUDD group than in the non-SUDD group. Total BA was mildly positively correlated with fecal calprotectin and blood EAA.ConclusionFecal BA concentrations were significantly increased in patients with SUDD compared with patients without SUDD or healthy subjects, suggesting that fecal BAs might be involved in the pathogenesis of SUDD and that controlling fecal BA levels may be therapeutic for SUDD.

OBJECTIVE:The onset of acute diverticulitis (AD) is a significant concern, yet the optimal preventive strategy is unclear. METHODS:This multicentre, prospective cohort study included 1945 patients with newly diagnosed colonic diverticula and scored according to Diverticular Inflammation and Complication Assessment (DICA) classification. At baseline, patients were assigned to one of five treatment strategies: no treatment, a high-fibre diet, mesalamine, rifaximin, or a combination of mesalamine and rifaximin. The primary outcome was the development of AD within 3 years. Energy balancing weighting and multivariable weighted Cox regression were used to estimate the causal treatment effects from nonrandomised data. RESULTS:During the follow-up period, 140 cases of AD were reported. The crude 3-year risk was: 3.3% (no treatment), 5.9% (high-fibre diet), 9.5% (mesalamine), 11.8% (rifaximin), and 17.1% (mesalamine plus rifaximin). Mesalamine was associated with a lower hazard risk of AD compared to rifaximin [hazard ratio (HR) = 0.42; 95% confidence interval (CI): 0.19-0.94] and combination therapy (HR = 0.37; 95% CI: 0.15-0.88). Rifaximin was associated with a higher hazard risk compared to no treatment. Mesalamine was most beneficial for patients classified as DICA 2, with a 77% (HR = 0.23; 95% CI: 0.08-0.62) and 84% (HR = 0.16; 95% CI: 0.05-0.53) lower hazard of AD compared to rifaximin and combination therapy, respectively. CONCLUSION:Mesalamine may be a better alternative in patients classified as DICA 2; however, its benefit over no treatment remains uncertain.

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.

INTRODUCTION:Diverticulitis is the most common complication related to the diverticulosis of the colon. Since there are some concerns about the management of complicated diverticulitis, the aim of this review was to analyze current medical and surgical approaches to complicated diverticulitis and evolving advances in its management. AREA COVERED:An analysis of the current PubMed literature about the medical and surgical management of complicated diverticulitis was performed. EXPERT OPINION:Attentive evaluation of the characteristics of complicated diverticulitis may make the difference when approaching its management: detection of large abscesses, or perforation with significant free air in the abdomen remain typical predictors of failed medical management, therefore often requiring surgery. However, recent data support the medical approach as first choice in managing small abscesses or small perforation with small bubble of free air in the abdomen. Further studies have to point out better the evolution of the medical approach also in patients with complicated diverticulitis.

BACKGROUND AND AIMS:Chronic atrophic gastritis (CAG) is a known precancerous condition that can lead to the development of gastric cancer (GC). Low serum pepsinogen (PG) I levels have been proposed as a non-invasive marker for chronic atrophic gastritis of the stomach body, but the adequate upper cut-off for diagnosis remains controversial, as values ranging from 30 to 50 mcg/L are currently considered as a "grey zone". We aimed to identify patients with chronic atrophic gastritis (CAG) of the stomach body amongst subjects with PG-I levels ranging between 30 and 50 mcg/L by means of a proton pump inhibitor (PPI) challenge. METHODS:We selected 102 patients with baseline PG-I <60 mcg/L in whom upper gastrointestinal endoscopy with protocol biopsies staged according to OLGA system had been performed. Subsequently, all patients underwent a PPI challenge (consisting of PG-I testing after taking Esomeprazole 40 mg daily for 1 week). This population was divided into 5 groups according to PG-I levels: group A (PG-I< 30 mcg/L); group B (PG-I: 31-35 mcg/L); group C (PG-I: 36-40 mcg/L); group D (PG-I: 41-50 mcg/L); group E (PG-I: 51-60 mcg/L). By using the ROC curve, a cut-off of 30% increase from baseline PG-I was chosen. RESULTS:A statistically significant relationship between PG-I levels and OLGA staging was found, being 100% in the group of PG-I < 30mcg/L. Based on the value of the cut-off of 30% (calculated by ROC curve) corresponding to the delta increase between PG-I baseline value and after a one-week full dose of PPI, the positive predictive value was 95%, the negative predictive value 86%, the sensitivity 83% and the specificity 96%. CONCLUSIONS:The use of the PPI challenge allows to identify subjects with CAG showing pepsinogen I values ranging between 30 and 50 mcg/L.

Introduction:Diverticular disease (DD) of the colon has a number of phenotypes, including asymptomatic diverticulosis and complicated diverticulitis with bowel perforation or bleeding. The factor that affects the phenotype of this condition and leads to a wide range of clinical presentations is unknown. The formation of fistulas associated with diverticulitis has long been recognized, and they are treated according to ad hoc indications. We hypothesized that the formation of fistulas in diverticular disease exhibits such a wide range of variable anatomic features that it may be considered a distinct form of the condition, fistulating diverticulitis (FD). Methods:We conducted a narrative review based on 50 years of publications covering a wide range of diverticulitis-associated fistulas, both common and uncommon. Results:While there is abundant literature on common fistulas, such as colovesical and colovaginal fistulas, little is known about rarer fistulas, such as coloenteric fistulas, colocutaneous fistulas, and genitourinary tract fistulas. The majority of these fistulas are treated surgically, which is in contrast to the trend toward conservative management that is predominant in acute or chronic diverticulitis. Discussion:Epidemiological and histological evidence support the hypothesis that FD may be a feature of chronic DD that requires individual management. Histopathology shows similarities with Crohn's disease. It remains unknown which underlying immune or genetic factors may be affecting the clinical presentation of these patients, leading to fistulation. We contend that there is adequate published evidence to characterize a distinct phenotype of FD that can involve the entire GI tract and other organs. Surgical guidelines may need to be modified to treat this small but important group, which predominantly requires surgical treatment.

Introduction Colonic diverticulosis is the most common structural abnormality of the colon in developed countries, with an increasing global prevalence. Approximately 20-25% of affected individuals develop symptoms, collectively referred to as diverticular disease. Given its wide clinical spectrum, evolving pathophysiological insights and growing disease burden, updated guidance is essential. Methods This International Consensus, developed by 32 experts from 14 countries through a structured Delphi process based on the PICO framework and GRADE methodology, provides evidence-based recommendations across five domains: epidemiology and pathogenesis; clinical features; diagnosis; medical therapy; and surgical management. Results Key statements define diverticulosis as the presence of diverticula without symptoms and diverticular disease as diverticula associated with symptoms or complications. High dietary fibre intake is protective whereas smoking, obesity and the use of non-steroidal anti-inflammatory drugs, corticosteroids, opioids or immunotherapy increase risk. Imaging is essential in suspected acute diverticulitis: ultrasound may be appropriate in experienced hands, while CT remains preferred for complicated cases. Diverticulosis itself requires no treatment. In symptomatic uncomplicated diverticular disease, dietary fibre, selected probiotics, mesalazine and rifaximin may help relieve symptoms. Routine antibiotic use is not recommended for acute uncomplicated diverticulitis, and elective surgery should be individualised, prioritising quality of life considerations over episode count. Conclusions These Consensus statements aim to standardise and optimise the diagnosis, management and prevention of diverticular disease across diverse healthcare systems, while highlighting research priorities such as microbiome characterisation, genetic risk profiling and long-term outcomes of selective antimicrobial and surgical strategies.

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.

Abstract Background Risankizumab has been recently approved for the treatment of moderate-to-severe Crohn's disease (CD). It is a humanized IgG1 monoclonal antibody that binds to the p19 subunit of IL-23, selectively inhibiting IL-23. Due to the limited available real-world data on its effectiveness, this study aims to assess the short-term effectiveness and safety of risankizumab induction in a large, real-life Italian cohort of CD patients. Methods From September 2023, following AIFA reimbursement, until now, all consecutive CD patients treated with risankizumab in 14 Italian centers were retrospectively enrolled. Only patients who completed the induction phase of risankizumab, with at least a 12-weeks follow-up were included in the final analysis. Clinical characteristics, disease activity scores, steroid usage, and adverse effects were collected. The primary endpoint was steroid-free clinical remission (SFCR) (Harvey Bradshaw Index [HBI] <5) at 12 weeks. Secondary endpoints included clinical response (≥3 point decrease in HBI and/or HBI <5), biochemical remission (CRP≤ 5 mg/L), remission of extra-intestinal manifestations (EIMs), occurrence of disease complications, and adverse events. Results To date, 147 patients have been enrolled, with 67 completing the 12-week follow-up. Of these, 34 (50.7%) patients had received ≥3 biologics, and 38 (56.7%) had previous intestinal resections. Fifty-four patients underwent colonoscopy within the last 6 months before starting risankizumab, exhibiting a mean SES-CD of 10.9±6.0 and a mean Rutgeerts score of 3.1±1.4. The rates of SFCR and clinical response at week 12 were 58.2% (39/67) and 76.1% (51/67) respectively, while 53.7% (22/41) and 65.9% (27/41) in ustekinumab exposed patients. Fecal calprotectin levels decreased from 963.6±1346.0 to 311.8±403.0 at week 12. Thirty-eight patients (56.7%) achieved normal CRP levels at week 12. Clinical remission of rheumatological and dermatological EIMs was observed at week 12 in 16.7% (3/18) and 75.0% (6/8) of patients, respectively. Two patients developed disease complications, including one case of worsening of the disease and one of new fistula development. This latter patient discontinued treatment before week 12. Additionally, two patients (3.0%) experienced minor adverse events after risankizumab administration. No patients underwent surgery during the 12-weeks follow-up. Conclusion In a large cohort of refractory CD patients with multiple prior drug failures, including frequent failures with ustekinumab, nearly 60% achieved SFCR following risankizumab induction. Risankizumab demonstrated good effectiveness in managing dermatological EIMs, but less effectiveness in rheumatological EIMs. The safety profile of risankizumab was consistent with existing literature.

Abstract Background Inflammatory bowel diseases (IBDs), Crohn's disease (CD) and ulcerative colitis (UC), are chronic and immune-mediated diseases with a relapsing-remitting trend. The overall incidence of these diseases is increasing. However, it is estimated that more than one third of patients experienced symptoms for more than one year before diagnosis. Delay in IBD diagnosis has several clinical, therapeutic and economic implications. Early diagnosis and proper treatment are the cornerstones for improving the standard of care for these patients. This study aims to evaluate the diagnostic delay (DD) in patients with IBD and to analyze the clinical burden of the delay in IBD diagnosis in patients treated with biological drugs. Methods An observational and retrospective study was performed in IBD patients, regularly followed in four IBD Units. Data regarding delay in IBD diagnosis were assessed through a questionnaire evaluating the disease course. Moreover, data about biologics dispensation were obtained from the medical records in the period 2020-2022 Results 344 IBD patients were enrolled (UC 228, CD 116, M 198, F 146). Median age at diagnosis was 42 years (IQR 9-82); Median DD was 12 months (IQR: 6-24). No significant difference was found in median DD between UC [12 months (IQR: 4.5-12.0)] and CD patients [12 months (IQR: 12-48)]. However, the proportion of patients with a DD >24 months was significantly (p=0.007) higher in CD (41/110 = 37,3%) than in UC patients (20/220=9%). After a median disease duration of 10 years (IQR: 4-17), overall, 164 patients (49.7%) were exposed to one biologic agent, 105 patients (31.8%) were exposed to two biologic agents, 61 (18.5%) to three or more biologic agents. 18,5% of patients (61/330) underwent surgery. The statistical analysis showed that DD >24 months was not statistically significant associated with history of ≥ 2 biological drugs (p=0.51). Conversely, there was association with surgical treatment (p=0.004). Conclusion The diagnostic delay in IBD represents a challenge with clinical and, therapeutic impact. It’s crucial to cooperate with general practitioner and gastroenterologists not dedicated to IBD in order to reduce the diagnostic delay and guarantee an effective, appropriate and early treatment that will improve the patients’ quality of life and meanwhile reduce the health care system costs.

Diverticular disease (DD) is widespread worldwide. The role of gut microbiota (GM) in DD is not entirely understood. Here we discuss the significance of the current knowledge on GM in the different stages of DD and how crucial these acquisitions are for designing diagnostic and therapeutic trials in this field.