The Epidemiology and Clinical Management of Short Bowel Syndrome and Chronic Intestinal Failure in Crohn's Disease in Italy: An IG-IBD Survey.

BACKGROUND/OBJECTIVES: Limited data exist on the epidemiology and clinical management of short bowel syndrome (SBS) and chronic intestinal failure (CIF) in Crohn's disease (CD). This study aimed to evaluate these aspects in Italy. METHODS: Members of the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD) were invited to complete a cross-sectional web survey. A subgroup analysis examined the influence of different clinical settings on SBS and CIF management in CD. RESULTS: A total of 47/128 (36.7%) IG-IBD centers participated. Among them, 31.9% were teduglutide (TED) prescribers, and 48.9% were academic centers. The median estimated prevalence of CIF among small bowel CD patients was 1%, and it was significantly higher in academic centers (2.0% [IQR 1-5%] vs. 0.13% [IQR 0-1%], p = 0.02). Seventy-eight percent of centers managed fewer than 10 SBS and CD patients. Routine small bowel measurement and nutritional assessment were performed in only 15% and 42.6% of centers, respectively. TED was prescribed by 12 centers to 35 patients, with a treatment success rate exceeding 50% in 81.8% of centers. CONCLUSIONS: The estimated prevalence of CIF in CD patients with small bowel involvement in Italy is 1%. The diagnosis and management practices for SBS and CIF are suboptimal, and TED use is limited.

Computer aided villi morphometric quantification in video-capsule enteroscopy: A newly developed software to quantify small bowel atrophy.

BACKGROUND AND AIMS: Small bowel capsule endoscopy (SBCE) has an established role in patients with non-responsive celiac disease (CeD). A non-invasive method to quantify small bowel atrophy is still lacking. METHODS: We analysed SBCE frames from CeD patients from 2018 to 2020. Histology was the reference standard, with atrophy defined as Marsh-Oberhuber score ≥ 3a. Three regions of interest (ROI) were blindly selected from each frame by an expert gastroenterologist and analysed using a National Institute of Health J image-processing software into a numerical scale. A 3D surface plot macro identified intestinal villi density through isolines plots. RESULTS: We acquired 306 ROIs from 57 frames with macroscopic atrophy and 45 with normal mucosa. Frames were classified as atrophic (n = 63) or non-atrophic (n = 39) per Marsh-Oberhuber classification. Median density score significantly differed between atrophic and non-atrophic frames (p < 0.001). The morphometric analysis showed a sensitivity of 77 % and a specificity of 79 % in discriminating between atrophic or non-atrophic mucosa with a 14.10 cut-off (Youden Index) and an overall AUC of 0.805 (CI 95 % 0.712-0.897). CONCLUSIONS: Our newly developed SBCE software can effectively quantify villous atrophy. Further studies are needed to validate its applicability in an external cohort.

Distribution of esophageal inflammation in patients with eosinophilic esophagitis and its impact on diagnosis and outcome.

BACKGROUND: This study aimed to assess the distribution of esophageal inflammation in patients with eosinophilic esophagitis (EoE) and its impact on diagnosis and outcome. AIMS AND METHODS: Data from consecutive adult EoE patients who were followed-up at four Italian referral centers from October 2022 to October 2023 were retrospectively collected. RESULTS: One hundred forty-nine patients were included. Proximal EoE was observed in 8.1 % of patients; distal EoE in 27.5 %; and diffuse EoE in 64.4 %. Allergic rhinitis was more prevalent in distal and diffuse than proximal EoE (72.5 % vs. 61.5 % vs 33.3 %; P = 0.049). The prevalence of asthma, atopic dermatitis, oral allergy syndrome, and gastroesophageal reflux disease was not significantly different among the three EoE extent groups. Endoscopic inflammatory features at diagnosis were more prevalent in proximal EoE (91.7 % vs. 53.8 % distal [P = 0.01] vs. 66 % diffuse[P = 0.05]). No significant differences in fibrotic features and esophageal stenoses were observed. The clinical and histological remission rates after first-line therapy were comparable in all groups. CONCLUSION: Esophageal inflammation in EoE more frequently involves the entire esophagus, followed by isolated distal and proximal involvement. No clear correlation was observed between the histological extent of EoE at diagnosis and comorbidities or treatment response.

Porphyromonas gingivalis fuels colorectal cancer through CHI3L1-mediated iNKT cell-driven immune evasion.

The interaction between the gut microbiota and invariant Natural Killer T (iNKT) cells plays a pivotal role in colorectal cancer (CRC). The pathobiont Fusobacterium nucleatum influences the anti-tumor functions of CRC-infiltrating iNKT cells. However, the impact of other bacteria associated with CRC, like Porphyromonas gingivalis, on their activation status remains unexplored. In this study, we demonstrate that mucosa-associated P. gingivalis induces a protumour phenotype in iNKT cells, subsequently influencing the composition of mononuclear-phagocyte cells within the tumor microenvironment. Mechanistically, in vivo and in vitro experiments showed that P. gingivalis reduces the cytotoxic functions of iNKT cells, hampering the iNKT cell lytic machinery through increased expression of chitinase 3-like-1 protein (CHI3L1). Neutralization of CHI3L1 effectively restores iNKT cell cytotoxic functions suggesting a therapeutic potential to reactivate iNKT cell-mediated antitumour immunity. In conclusion, our data demonstrate how P. gingivalis accelerates CRC progression by inducing the upregulation of CHI3L1 in iNKT cells, thus impairing their cytotoxic functions and promoting host tumor immune evasion.

Occurrence and characteristics of endoscopic gastric polyps in patients with autoimmune gastritis (AGAPE study): A multicentric cross-sectional study.

BACKGROUND: Autoimmune gastritis (AIG) leads to increased gastrin (G) levels due to hypo-achlorhydria, providing proliferative stimuli on the gastric mucosa. AIMS: To evaluate the incidence and characteristics of gastric polyps in AIG patients across six tertiary centers in Italy. METHODS: A multicentric, cross-sectional study enrolled patients with AIG diagnosed from January 2000 to June 2023, who underwent at least one endoscopy. Data on demographics, clinical history, biochemical profiles, and endoscopic and histopathological findings were systematically collected. RESULTS: Among 612 AIG patients followed for a median of 4 years, 222 (36.3 %) developed at least one gastric polyp. Of these, 214 were non-endocrine lesions detected in 162 patients, including 151 inflammatory (70.5 %), 29 adenomatous (13.6 %), 18 fundic gland polyps (8.4 %), 13 adenocarcinomas (6.1 %), and one MALT lymphoma. Additionally, 108 patients had gastric neuroendocrine neoplasms (gNENs), with 48 also having non-endocrine polyps. Older age and higher gastrin and chromogranin A levels were associated with polyp occurrence. No differences in OLGA/OLGIM stages or Helicobacter pylori status were noted among patients with and without lesions. CONCLUSION: This large multicentric study underscores the substantial occurrence of gastric polyps in AIG patients, including notable rates of gNENs and adenocarcinomas, emphasizing the importance of proactive endoscopic surveillance and histopathological examination for effective management.

Incomplete small bowel capsule endoscopy: Risk factors and cost-effectiveness of real-time viewing.

Background and study aims International guidelines recommend real-time viewing (RTV) in capsule endoscopy for gastric emptying monitoring, yet it is often overlooked in clinical practice. We aimed to assess risk factors for incomplete small bowel capsule endoscopy (SBCE) and evaluate the clinical relevance and cost-effectiveness of RTV implementation. Methods We included consecutive SBCEs from 2013 to 2020. RTV was not applied per local protocol. We used multivariate logistic regression to identify risk factors for incomplete SBCE, including prolonged gastric transit time (GTT) and prolonged small bowel transit time (SBTT). Results Analyzing 858 SBCEs, we observed a completion rate of 94.6%. Prolonged GTT and SBTT were present in 4.9% and 18.2% of complete SBCEs, and in 13% ( P =0.03) and 10.8% ( P =0.24) of incomplete SBCEs, respectively. Only 0.7% (6 of 858) had incomplete SBCE with prolonged GTT. In both univariate and multivariate analysis, a modifiable (prolonged GTT odds ratio [OR] 2.9; 95% confidence interval [CI] 1.1-7.5) and two unmodifiable risk factors (inpatient status OR 2.3; 95% CI 1.1-4.5) and history of incomplete SBCE (OR 4.2; 95% CI 1.3-13.7) were independently linked to higher incomplete SBCE rates. The pretest completion probability was 90.5% and 95.8% in patients with and without unmodifiable risk factors, respectively ( P <0.01). The direct cost of systematic RTV adoption and prokinetics administration would be €5059, aiming to identify and treat each case of prolonged GTT associated with incomplete SBCE. Conclusions Modern devices make incomplete SBCE rare, usually not tied to prolonged GTT. In a low-incidence scenario, widespread RTV use brings high costs and uncertain effectiveness.

Distinguishing Features of Autoimmune Gastritis Depending on Previous Helicobacter pylori Infection or Positivity to Anti-Parietal Cell Antibodies: Results From the Autoimmune gastRitis Italian netwOrk Study grOup (ARIOSO).

INTRODUCTION: To describe the clinical features and the risk of developing gastric tumors in patients with autoimmune gastritis (AIG). METHODS: This was a retrospective, longitudinal, multicenter study conducted at 8 Italian tertiary referral centers. We retrieved clinical data from all histologically proven patients with AIG. Differences between Helicobacter pylori -exposed vs H. pylori -naive and anti-parietal cell antibody (PCA)-positive vs PCA-negative patients were investigated. The rate of gastric adenocarcinoma and type 1 gastric neuroendocrine neoplasm (gNEN) was assessed. A multivariable model for factors associated with gNEN was fitted. RESULTS: A total of 1,598 patients with AIG (median age 58 years, interquartile range 46-68; F:M ratio 2.7:1) were included. H. pylori -naive patients were more likely to have a first-degree family history of AIG (14.7% vs 8.9%; P = 0.012), type 1 diabetes mellitus (4.9% vs 2.3%; P = 0.025), and pernicious anemia (30.9% vs 21.1%; P = 0.003). PCA-positive patients had significantly more associated autoimmune diseases (59.0% vs 42.9%; P < 0.001) and were more likely to have been diagnosed by a case-finding strategy (15.3% vs 2.6%; P < 0.001). Overall, 15 cases (0.9%) of gastric adenocarcinoma and 153 cases (9.6%) of gNEN occurred, with a global rate of 0.12 (95% confidence interval [CI] 0.07-0.20) and 1.22 (95% CI 1.03-1.42) per 100 person/year, respectively. Having a vitamin B12/iron deficiency manifestation at AIG diagnosis was associated with a 16.44 (95% CI 9.94-27.20 P < 0.001) hazard ratio of gNEN. DISCUSSION: The "pure" AIG pattern has typical features of an autoimmune disease and seems to be unrelated to H. pylori . In a tertiary referral setting, the risk of developing overt gastric adenocarcinoma is low, while patients with vitamin B12 deficiency complications at onset may benefit from a more intense endoscopic follow-up for early gNEN detection.

Pan-enteric Capsule Endoscopy to Characterize Crohn's Disease Phenotypes and Predict Clinical Outcomes in Children and Adults: The Bomiro Study.

BACKGROUND: Pan-enteric capsule endoscopy (PCE) provides useful information for the management of Crohn's disease (CD), especially in children. No study has evaluated the ability of PCE to characterize CD phenotypes and outcomes in children and adults. METHODS: In a prospective multicenter observational study, we recruited patients with CD >6 years from 4 centers in Italy. Patients underwent clinical, biomarker assessment and PCE. Lesions were graded using the PCE system. For each segment, the most common lesion (MCL), the most severe lesion (MSL), and the extent of involvement were defined. Disease severity, extent, and clinical outcomes were compared between children and adults. A logistic regression analysis was used to identify predictive factors for negative outcomes in both age groups. RESULTS: One hundred ninety-four consecutive patients (adults/children: 144/50) were evaluated for a total of 249 procedures. Children were more likely to have extensive disease, particularly in the colon. Higher MCL scores were independently associated with treatment escalation (odds ratio [OR], 4.09; 95% CI, 1.80-9.25; P = .001), while >30% disease extent was more indicative of clinical and endoscopic relapse (OR, 2.98; 1.26-7.08; P = .013). Disease extent was the only factor associated with endoscopic recurrence in children (OR, 4.50; 95% CI, 1.47-13.77; P = .008), while severe lesions in adults provided a better predictor of treatment escalation (OR, 4.31; 95% CI, 1.52-12.1; P = .006). Postexamination, PCE contributed to a change of therapy in 196/249 (79%) of the procedures. CONCLUSIONS: PCE allowed the characterization of CD phenotypes in children and adults by assessing disease severity and extent, which are of different importance in predicting clinical outcomes in these age groups.

The study introduces the pan-enteric capsule (PCE) as an efficient tool for assessing Crohn's disease in pediatric and adult patients, providing valuable insights into disease extent and severity, influencing treatment decisions, and improving patient care.

Follow-up evaluation and management of anemia in inflammatory bowel disease: A study by the Italian Group for Inflammatory Bowel Diseases (IG-IBD).

BACKGROUND: The RIDART I study found a 13.6% prevalence of anemia in Italian patients with inflammatory bowel disease (IBD); most cases were due to iron-deficiency anemia (IDA). AIMS: To evaluate changes in hemoglobin concentration during a 24-week follow-up of anemic patients with IBD. METHODS: Follow-up laboratory and clinical data were obtained from RIDART I study patients with anemia. Factors affecting hemoglobin concentration, the impact of anemia on fatigue and quality of life (QoL), and its relationship with treatment, disease activity and disease complications were investigated. RESULTS: Hemoglobin was 108 g/L at baseline, increased to 121 g/L at follow-up week 12 (p < 0.001) and then stabilized until week 24, but most patients remained anemic, with IDA, throughout the study. Hemoglobin improvement was greater in patients receiving either oral or parenteral iron supplementation. Following hemoglobin normalization, anemia relapse rate during follow-up was 30%. Oral iron did not cause disease reactivation. Lower follow-up hemoglobin was associated with a higher probability of having active disease, clinical complications, increased fatigue and reduced QoL. CONCLUSIONS: In anemic patients with IBD, anemia represents a long-lasting problem, in most cases persisting for up to 24 weeks, with high relapse rate and a negative impact on fatigue and QoL.

The carbon cost of inappropriate endoscopy.

BACKGROUND AND AIMS: Digestive endoscopy is a resource-intensive activity with a conspicuous carbon footprint and an estimated rate of inappropriateness. However, the carbon costs of inappropriate endoscopic procedures still remain obscure. Here we evaluated the environmental impact of inappropriate endoscopic examinations. METHODS: We calculated the carbon cost of a standard endoscopic procedure (EGD and colonoscopy [CLS]), taking into account the items (eg, disposable materials, personal protective equipment) and energy required for the endoscopy procedure itself and the cleaning process. The rates of inappropriateness and the mortality cost of carbon (MCC) of endoscopic examinations in different scenarios were calculated. RESULTS: EGD and CLS presented a carbon cost of 5.43 kg and 6.71 kg of CO2, respectively. Different scenarios were evaluated, according to the number of endoscopic procedures performed in Italy per 1000 inhabitants and the reported data on their inappropriateness. The carbon cost of inappropriate EGD and CLS in Italy was 4133 CO2 metric tons per year (MCC, .93), ranging from 3527 to 4749, and equivalent to 1,760,446 L of gasoline consumed. Applying the same data to the European population, the estimated carbon footprint of inappropriate digestive endoscopy in Europe was 30,804 metric tons. CONCLUSIONS: The environmental impact of inappropriate endoscopic procedures in Europe is remarkable. These results highlight the need to adopt novel strategies aimed at reducing both the carbon footprint of digestive endoscopy and the rate of inappropriate procedures.

Treatment options for gastrointestinal bleeding blue rubber bleb nevus syndrome: Systematic review.

OBJECTIVES: Blue rubber bleb nevus syndrome (BRBNS) is a rare challenging cause of gastrointestinal bleeding. We performed a systematic review of case reports and case series on BRBNS to gather information on the treatment options currently available. METHODS: All studies reporting a case of BRBNS in humans were evaluated. Papers were ruled out if CARE criteria and explanations on patient's selection, ascertainment, causality, and reporting were not respected or identified. PROSPERO 2021 CRD 42021286982. RESULTS: Blue rubber bleb nevus syndrome was treated in 106 cases from 76 reports. 57.5% of the population was under 18 years old, and up to 50% of the cases reported a previous treatment. Clinical success was achieved in 98 patients (92.4%). Three main types of interventions were identified: systemic drug therapy, endoscopy, and surgery. After BRBNS recurrence or previous therapy failure, systemic drug therapy emerged as a preferred second-line treatment over endoscopy (P = 0.01), but with a higher rate of reported adverse events when compared with surgery and endoscopy (P < 0.001). Endoscopic treatment was associated with a higher number of required sessions to achieve complete eradication when compared with surgery (P < 0.001). No differences between the three main areas were found in the overall follow-up time (P = 0.19) or in the recurrence rate (P = 0.45). CONCLUSION: Endoscopy, surgery, and systemic drug therapy are feasible treatment options for BRBNS. Systemic drug therapy was the favorite second-line treatment after endoscopic failure or recurrence of BRBNS, but adverse events were more frequently reported.

Superior predictive value of transmural over endoscopic severity for colectomy risk in ulcerative colitis: a multicentre prospective cohort study.

BACKGROUND AND AIMS: Endoscopic activity is associated with an increased risk of surgery in patients with ulcerative colitis [UC]. Transmural activity, as defined by Milan Ultrasound Criteria [MUC] > 6.2, reliably detects endoscopic activity in patients with UC. The present study aimed to assess in UC patients whether transmural severity is a better predictor of colectomy as compared to endoscopy. METHODS: Consecutive adult UC patients were recruited in two IBD Referral Centres and underwent colonoscopy and intestinal ultrasound in a blinded fashion. The need for colectomy was assessed at follow-up. Univariable and multivariable logistic and Cox regression analyses were performed. Receiver operating characteristic [ROC] analysis was used to compare MUC baseline values and Mayo Endoscopic Scores [MES] in predicting colectomy risk. RESULTS: Overall, 141 patients were enrolled, and 13 underwent colectomy in the follow-up period. Both MES (hazard ratio [HR]: 3.15, 95% confidence interval [CI]: 1.18-8.37, p = 0.02) and MUC [HR: 1.48, 95% CI: 1.19-1.76, p < 0.001] were associated with colectomy risk, but only MUC was independently associated with this event on multivariable analysis [HR: 1.46, 95% CI: 1.06-2.02, p = 0.02]. MUC was the only independent variable associated with colectomy risk in patients with clinically active disease (odds ratio [OR]: 1.53 [1.03-2.27], p = 0.03). MUC demonstrated higher accuracy than MES (area under ROC curve [AUROC] 0.83, 95% CI: 0.75-0.92 vs 0.71, 95% CI: 0.62-0.80) and better performance for predicting colectomy [p = 0.02]. The optimal MUC score cut-off value for predicting colectomy, as assessed by the Youden index, was 7.7. CONCLUSIONS: A superior predictive value was found for transmural vs endoscopic severity for colectomy risk in UC patients.

Reproducibility and accuracy of a pocket-size ultrasound device in assessing liver steatosis.

BACKGROUND: This diagnostic prospective study compared the feasibility and diagnostic accuracy of Pocket-size Ultrasound Devices (PUDs) against standard ultrasound (US) in detecting liver steatosis using the controlled attenuation parameter (CAP) and liver biopsy as reference standards. MATERIALS AND METHODS: Consecutive patients with chronic liver diseases were assessed for the presence of steatosis using PUD and US. A CAP cut-off value >275 dB/m was applied to establish ≥S1. A 26-patient subgroup underwent liver biopsy. PUD reproducibility was evaluated using Cohen's k statistic. Diagnostic accuracy of PUD and US was given as Sensibility (Sn), Specificity (Sp), Positive and Negative Predictive Values (PPV, NPV), positive and negative Likelihood Ratio (LR+, LR-). RESULTS: 81 consecutive patients (69% males) with multiple etiologies were enroled. PUD inter-observer agreement was good (k 0.77, 95%CI 0.62-0.93). PUD and US identified ≥S1 according to CAP values respectively with Sn 0.87, Sp 0.61, PPV 0.49, NPV 0.91, LR+ 2.04, LR- 0.07, AUROC 0.74 and Sn 0.96, Sp 0.54, PPV 0.47, NPV 0.97, LR+ 2.10, LR- 0.07, AUROC 0.75. CONCLUSIONS: PUD shows good reproducibility and diagnostic accuracy in ruling liver steatosis out, representing a useful point-of-care tool to avail of hepatologists interested in excluding NAFLD, but with basic US skills.

Attitudes towards Vaccinations in a National Italian Cohort of Patients with Inflammatory Bowel Disease.

BACKGROUND: The vaccination status of patients with inflammatory bowel disease (IBD) should be investigated before starting any treatment, and patients should eventually be vaccinated against vaccine-preventable diseases (VPDs). Patients with IBD may have suboptimal vaccination rates. The aim of this study was to evaluate the vaccination coverage, attitude towards vaccinations, and determinants among an Italian cohort of patients with IBD. METHODS: AMICI, the Italian IBD patients' association, sent an anonymous web-based questionnaire in February 2021. Previous vaccination status and patients' attitudes towards vaccinations were recorded. We examined the factors influencing their attitudes using crude and adjusted odds ratios (adjORs) with 95% confidence intervals (CIs). RESULTS: Among the 4039 patients invited, 1252 patients (including 729 women, median age 47.7 [37-58]) completed the questionnaire, with a response rate of 25.3%. Respondents declared being vaccinated against tetanus (74.1%), flu (67.7%; last season), MMR (43.3%), HBV (37.1%), pneumococcus (29.1%), meningitis (20%), HAV (16%), VZV (15.3%), and HPV (7.6%). Complete vaccination history was not remembered by 20.7% of the patients. One thousand one hundred and twelve (88.8%) expressed a positive attitude towards vaccination, 91 (7.3%) were indifferent, and 49 (3.9%) reported being opposed to vaccinations. The belief of a possible return of VPDs with a decline in vaccination coverage rates was the factor most strongly related to a positive attitude towards vaccinations (adjOR 5.67, 95% CI 3.45-9.30, p-value < 0.001). CONCLUSIONS: A low vaccination rate against some VPDs was found among a national cohort of patients with IBD, despite a generally positive attitude towards vaccinations.

Prevalence of Disease-Related Malnutrition and Micronutrients Deficit in Patients with Inflammatory Bowel Disease: A Multicentric Cross-Sectional Study by the GSMII (Inflammatory Bowel Disease Study Group).

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) patients might experience disease-related malnutrition (DRM), but prevalence and risk factors are not well defined. The primary aim of the study was to define the prevalence of DRM and micronutrient deficiency in IBD patients; the secondary aim was to assess variables related to DRM. MATERIALS AND METHODS: A multicenter, cross-sectional study was performed including consecutive adult IBD patients during a period of 2 weeks. Nutritional status was assessed with the body mass index (BMI) and the Malnutrition Universal Screening Tool. DRM was defined according to European Society for Clinical Nutrition and Metabolism guidelines. RESULTS: Among the 295 enrolled patients, the prevalence of DRM was 23%, with no statistical difference between Crohn's disease and ulcerative colitis. Compared with well-nourished patients, patients with DRM showed higher rate of hospitalization in the previous month, were more often receiving systemic steroids, and had lower hemoglobin, albumin, and prealbumin levels and higher median C-reactive protein levels. At univariate logistic regression, current hospitalization, hospitalization in the previous month, low serum albumin, low BMI, high C-reactive protein, high Crohn's Disease Activity Index, and female sex were variables related to DRM. At the multivariate logistic regression, low BMI, current hospitalization and hospitalization in the previous month were significantly associated with DRM. In 23% of IBD patients, a deficiency of at least 1 micronutrient was observed, with no difference between ulcerative colitis and Crohn's disease. CONCLUSIONS: DRM and microelements malnutrition are frequent conditions in the IBD population. DRM seems to be associated with disease activity and hospitalization.