Oral Budesonide and low serum albumin levels at surgery are associated with a higher risk of postoperative intra-abdominal septic complications after primary ileocaecal resection for Crohn's disease: A retrospective analysis of 853 consecutive patients.

BACKGROUND AND AIMS: The terminal ileum is the most frequent site of Crohn's Disease (CD) that necessitates surgery. Of the postoperative complications (POCs) associated with ileocaecal resection for CD, intra-abdominal septic complications (IASCs) include anastomotic leak, abscesses, and entero-cutaneous fistula. We aimed to identify predictors of IASCs and severe POCs (Clavien-Dindo ≥3) after primary ileocaecal resection for CD. METHODS: This is a retrospective single-centre cohort study including all consecutive primary ileocaecal resection for CD in a tertiary IBD centre between 2004 and 2021. RESULTS: A total of 853 patients underwent primary ileocaecal resection for CD. 307 (36.6 %) patients were receiving antibiotics, 253 (29.8 %), systemic steroids, and 178 (21.0 %) oral budesonide at surgery. At 90 days, 260 (30.8 %) patients developed POCs, 62 (7.3 %) severe POCs, and 56 (6.6 %) IASCs. At multivariate analysis, severe POCs were associated with lower preoperative albumin levels (OR1.58, 95 %CI 1.02-2.50, p = 0.040) and a history of cardiovascular diseases (OR2.36, 95 %CI 1.08-7.84, p = 0.030). IASCs were associated with lower preoperative albumin levels (OR1.81, 95 %CI 1.15-2.94, p = 0.011) and oral budesonide (OR2.07, 95 %CI 1.12-3.83, p = 0.021) with a dose-dependent effect. CONCLUSIONS: The independent association, dose-dependent effect, and biological plausibility of budesonide and IASCs suggest a robust causal effect. Oral budesonide should be carefully assessed before primary ileocaecal resection for CD.

The effect of anti-TNF drugs on the intestinal microbiota in patients with spondyloarthritis, rheumatoid arthritis, and inflammatory bowel diseases.

Spondyloarthritis (SpA), rheumatoid arthritis (RA), and inflammatory bowel diseases (IBD) are chronic inflammatory autoimmune diseases that are associated with alterations in the composition of the intestinal microbiota (i.e., dysbiosis). For SpA and RA, a gut-joint-enthesis axis is hypothesized and recent data suggests that dysbiosis may contribute directly to initiating and perpetuating joint and spine inflammation. Biologic drugs targeting tumor necrosis factor (TNF) are effective in treating these diseases and have been shown to partially restore the disrupted microbiome. Hence, drugs that affect both the intestinal and joint components of these diseases, such as anti-TNF drugs, may act on the intestinal microbiome. However, despite the remarkable efficacy of anti-TNF-α treatments, non-responders are frequent, and predictors of patient outcomes have not been identified. In this narrative review, we summarize recent research on the downstream effects of anti-TNF drugs on the intestinal microbiota in SpA, RA, and IBD. We also discuss whether these changes could have a role as predictive biomarkers of anti-TNF response.

Poor prognostic factors of pharmacokinetic origin predict outcomes in inflammatory bowel disease patients treated with anti-tumor necrosis factor-α.

Introduction: We evaluated baseline Clearance of anti-tumor necrosis factors and human leukocyte antigen variant (HLA DQA1*05) in combination as poor prognostic factors (PPF) of pharmacokinetic (PK) origin impacting immune response (formation of antidrug antibodies) and disease control of inflammatory bowel disease (IBD) patients treated with infliximab or adalimumab. Methods: Baseline Clearance was estimated in IBD patients before starting treatment using weight and serum albumin concentrations. HLA DQA1*05 carrier status (rs2097432 A/G or G/G variant) was measured using real time polymerase chain reaction. The outcomes consisted of immune response, clinical and biochemical remission (C-reactive protein<3 mg/L in the absence of symptoms), and endoscopic remission (SES-CD<3). Statistical analysis consisted of logistic regression and nonlinear mixed effect models. Results and discussion: In 415 patients enrolled from 4 different cohorts (median age 27 [IQR: 15-43] years, 46% females), Clearance>0.326 L/day and HLA DQA1*05 carrier status were 2-fold more likely to have antidrug antibodies (OR=2.3, 95%CI: 1.7-3.4; p<0.001, and OR=1.9, 95%CI: 1.4-2.8; p<0.001, respectively). Overall, each incremental PPF of PK origin resulted in a 2-fold (OR=2.16, 95%CI: 1.7-2.7; p<0.11) [corrected] higher likelihood of antidrug antibody formation. The presence of both PPF of PK origin resulted in higher rates of antidrug antibodies (p<0.01) and lower clinical and biochemical remission (p<0.01). Each incremental increase in PPF of PK origin associated with lower likelihood of endoscopic remission (OR=0.4, 95%CI: 0.2-0.7; p<0.001). Prior biologic experience heightened the negative impact of PPF of PK origin on clinical and biochemical remission (p<0.01). Implementation of proactive therapeutic drug monitoring reduced it, particularly during maintenance and in the presence of higher drug concentrations (p<0.001). We conclude that PPF of PK origin, including both higher Clearance and carriage of HLA DQA1*05, impact outcomes in patients with IBD.

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.

Signatures of disease outcome severity in the intestinal fungal and bacterial microbiome of COVID-19 patients.

Background: COVID-19, whose causative pathogen is the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), was declared a pandemic in March 2020. The gastrointestinal tract is one of the targets of this virus, and mounting evidence suggests that gastrointestinal symptoms may contribute to disease severity. The gut-lung axis is involved in the immune response to SARS-CoV-2; therefore, we investigated whether COVID-19 patients' bacterial and fungal gut microbiome composition was linked to disease clinical outcome. Methods: In May 2020, we collected stool samples and patient records from 24 hospitalized patients with laboratory-confirmed SARS-CoV-2 infection. Fungal and bacterial gut microbiome was characterized by amplicon sequencing on the MiSeq, Illumina's integrated next generation sequencing instrument. A cohort of 201 age- and sex-matched healthy volunteers from the project PRJNA661289 was used as a control group for the bacterial gut microbiota analysis. Results: We observed that female COVID-19 patients had a lower gut bacterial microbiota richness than male patients, which was consistent with a different latency in hospital admittance time between the two groups. Both sexes in the COVID-19 patient study group displayed multiple positive associations with opportunistic bacterial pathogens such as Enterococcus, Streptococcus, and Actinomyces. Of note, the Candida genus dominated the gut mycobiota of COVID-19 patients, and adult patients showed a higher intestinal fungal diversity than elderly patients. We found that Saccharomycetales unassigned fungal genera were positively associated with bacterial short-chain fatty acid (SCFA) producers and negatively associated with the proinflammatory genus Bilophila in COVID-19 patients, and we observed that none of the patients who harbored it were admitted to the high-intensity unit. Conclusions: COVID-19 was associated with opportunistic bacterial pathogens, and Candida was the dominant fungal taxon in the intestine. Together, we found an association between commensal SCFA-producers and a fungal genus that was present in the intestines of patients who did not experience the most severe outcome of the disease. We believe that this taxon could have played a role in the disease outcome, and that further studies should be conducted to understand the role of fungi in gastrointestinal and health protection.

Corrigendum: Poor prognostic factors of pharmacokinetic origin predict outcomes in inflammatory bowel disease patients treated with anti-tumor necrosis factor-α.

[This corrects the article DOI: 10.3389/fimmu.2024.1342477.].

The contribution of ultrasound in the diagnostic pathway of a symptomatic hepatocellular adenoma arising from ectopic liver.

Ectopic liver (EL) is a rare congenital anomaly characterized by the presence of a mass composed of hepatic tissue localized in a different anatomical location with no connection to the native liver. Usually an incidental finding, EL can rarely cause symptoms such as abdominal pain due to torsion, intraperitoneal bleeding, compression, obstruction, or neoplastic transformation, both benign and malignant. EL is often suspected after instrumental investigations such as ultrasound, CT and MRI, however a definitive diagnosis is necessarily bioptic. Here we report a case of a 22-year-old Italian female patient with acute abdominal pain, who underwent abdominal ultrasound, CEUS with Sonovue®, CT scan and ultrasound-guided biopsy which raised the suspicion of hepatocellular adenoma (H-HCA). After a laparoscopic excision of the lesion a diagnosis of H-HCA was formulated.

Nutritional Biomarkers for the Prediction of Response to Anti-TNF-α Therapy in Crohn's Disease: New Tools for New Approaches.

Crohn's disease (CD) is a chronic disorder of the digestive tract characterized by an uncontrolled immune-mediated inflammatory response in genetically predisposed individuals exposed to environmental risk factors. Although diet has been identified as one of the major environmental risk factors, the role of nutrients in the clinical management of CD patients has not yet been fully investigated. In this prospective observational study, fifty-four patients diagnosed with active Crohn's disease and undergoing anti-TNF-α biological therapy were enrolled and subjected to nutrient intake analysis through a daily food diary. Their nutrient intake and blood values were analyzed before and after 6 months of biological therapy. After 6 months of anti-TNF-α, four patients dropped out of the study, leaving 29 patients in clinical remission and 21 still with active disease that remained the same. The aim of this study was to identify nutrients whose intake or blood values may be associated with patients' responses to biological therapy. In the diet, patients remaining with active CD showed very similar nutrient dietary intake compared to patients achieving remission except for a trend for lower starting zinc intake, below the reference value. In the blood, instead, patients who did not respond to biological therapy showed significantly lower plasma values of iron and taurine before starting biological anti-TNF-α treatment.

Adalimumab Clearance, Rather Than Trough Level, May Have Greatest Relevance to Crohn's Disease Therapeutic Outcomes Assessed Clinically and Endoscopically.

OBJECTIVE: We postulated that adalimumab [ADA] drug clearance [CL] may be a more critical determinant of therapeutic outcome than ADA concentration. This was tested in Crohn's disease [CD] patients undergoing ADA maintenance treatment. METHODS: CD patients from four cohorts received ADA induction and started maintenance therapy. Therapeutic outcomes consisted of endoscopic remission [ER], sustained C-reactive protein [CRP] based clinical remission [defined as CRP levels below 3 mg/L in the absence of symptoms], and faecal calprotectin [FC] level below 100 µg/g. Serum albumin, ADA concentration, and anti-drug antibody status were determined using immunochemistry and homogeneous mobility shift assay, respectively. CL was determined using a nonlinear mixed effect model with Bayesian priors. Statistical analysis consisted of Mann-Whitney test and logistic regression with calculation of odds ratio. Repeated event analysis was conducted using a nonlinear mixed effect model. RESULTS: In 237 enrolled patients [median age 40 years, 45% females], median CL was lower in patients achieving ER as compared with those with persistent active endoscopic disease [median 0.247 L/day vs 0.326 L/day, respectively] [p <0.01]. There was no significant difference in ADA concentration between patients in endoscopic remission compared with those with recurrence [median 9.3 µg/mL vs 11.7 µg/mL, respectively]. Sustained CRP-based clinical remission and FC levels below 100 µg/g were generally associated with lower CL and higher ADA concentration. Repeated event analysis confirmed those findings with better performances of CL than concentration in associating with ER and other outcomes. CONCLUSION: Lower ADA clearance is associated with an improved clinical outcome for patients with Crohn's disease and may be a superior pharmacokinetic measure than concentration.

Timing of proper introduction, optimization and maintenance of anti-TNF therapy in IBD: Results from a Delphi consensus.

BACKGROUND: Crohn's disease and ulcerative colitis are inflammatory bowel diseases (IBDs) with a rapidly growing worldwide incidence. The last decades presented rapid progress in pharmacological treatment leading in many cases to clinical and endoscopic remission, including biological treatment with anti-TNF agents. AIM: The exact timing of introduction, optimization and maintenance of anti-TNF therapy in IBDs is not thoroughly covered in current guidelines. METHODS: We used the Delphi panel methodology to gather the IBD experts' views and achieve consensus for clinical recommendations on introducing and maintaining anti-TNF therapy for patients with IBDs. RESULTS: Twelve recommendations achieved a high level of consensus in two assessment rounds by 52 (1st round) and 47 (2nd round) IBD experts. CONCLUSION: In many clinical situations, the early use of anti-TNF therapy is recommended. Nowadays, the cost-efficacy profile of anti-TNF biosimilars makes them the first-line drug in a substantial proportion of patients, thus providing the opportunity to increase access to biological therapy.

Systematic review with meta-analysis: Diagnostic performance of faecal calprotectin in distinguishing inflammatory bowel disease from irritable bowel syndrome in adults.

BACKGROUND: Symptoms of inflammatory bowel disease (IBD) often overlap with those of irritable bowel syndrome (IBS). AIM: To evaluate the diagnostic performance of faecal calprotectin in distinguishing patients with IBD from those with IBS METHODS: We searched MEDLINE, Embase, Scopus, and Cochrane Library databases up to 1 January 2023. Studies were included if they assessed the diagnostic performance of faecal calprotectin in distinguishing IBD from IBS (defined according to the Rome criteria) using colonoscopy with histology or radiology as reference standard in adults. We calculated summary sensitivity and specificity and their 95% confidence intervals (CI) using a random-effect bivariate model. The risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies II. RESULTS: We included 17 studies with a total of 1956 patients. The summary sensitivity was 85.8% (95% CI: 78.3-91), and the specificity was 91.7% (95% CI: 84.5-95.7). At a prevalence of IBD of 1%, the negative predictive value was 99.8%, while the positive predictive value was only 9%. Subgroup analyses showed a higher sensitivity in Western than in Eastern countries (88% vs 73%) and at a cut-off of ≤50 µg/g than at >50 µg/g (87% vs. 79%), with similar estimates of specificity. All studies were at "high" or "unclear" risk of bias. CONCLUSIONS: Faecal calprotectin is a reliable test in distinguishing patients with IBD from those with IBS. Faecal calprotectin seems to have a better sensitivity in Western countries and at a cut-off of ≤50 µg/g.

The Bidirectional Link between Nutritional Factors and Inflammatory Bowel Diseases: Dietary Deficits, Habits, and Recommended Interventions-A Narrative Review.

Inflammatory bowel diseases comprise Crohn's disease and ulcerative colitis, two chronic inflammatory disorders of the digestive tract that develop in adolescence and early adulthood and show a rising pattern in industrialized societies, as well as in developing countries, being strongly influenced by environmental pressures such as nutrition, pollution and lifestyle behaviors. Here, we provide a narrative review of the bidirectional link between nutritional factors and IBD, of dietary deficits observed in IBD patients due to both the disease itself and dietary habits, and of the suggested nutritional interventions. Research of the literature was conducted. Clinical and basic research studies consistently demonstrate that diet could alter the risk of developing IBD in predisposed individuals. On the other hand, dietary interventions represent a valid tool in support of conventional therapies to control IBD symptoms, rebalance states of malnutrition, promote/maintain clinical remission and improve patients' quality of life. Although there are no official dietary guidelines for patients with IBD, they should receive nutritional advice and undergo oral, enteral, or parenteral nutritional supplementation if needed. However, the dietary management of malnutrition in IBD patients is complex; future clinical studies are required to standardize its management.

Vedolizumab for the Treatment of Chronic Pouchitis.

BACKGROUND: Approximately half the patients with ulcerative colitis who undergo restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) will subsequently have pouchitis, and among those patients, one fifth will have chronic pouchitis. METHODS: We conducted a phase 4, double-blind, randomized trial to evaluate vedolizumab in adult patients in whom chronic pouchitis had developed after undergoing IPAA for ulcerative colitis. Patients were assigned (in a 1:1 ratio) to receive vedolizumab intravenously at a dose of 300 mg or placebo on day 1 and at weeks 2, 6, 14, 22, and 30. All the patients received concomitant ciprofloxacin from weeks 1 to 4. The primary end point was modified Pouchitis Disease Activity Index (mPDAI)-defined remission (an mPDAI score of ≤4 and a reduction from baseline of ≥2 points in the mPDAI total score; scores range from 0 to 12, with higher scores indicating more severe pouchitis) at week 14. The mPDAI is based on clinical symptoms and endoscopic findings. Other efficacy end points included mPDAI-defined remission at week 34, mPDAI-defined response (a reduction from baseline of ≥2 points in the mPDAI score) at weeks 14 and 34, and PDAI-defined remission (a PDAI score of ≤6 and a reduction from baseline of ≥3 points; scores range from 0 to 18, with higher scores indicating more severe pouchitis) at weeks 14 and 34. The PDAI is based on clinical symptoms, endoscopic findings, and histologic findings. RESULTS: Among the 102 patients who underwent randomization, the incidence of mPDAI-defined remission at week 14 was 31% (16 of 51 patients) with vedolizumab and 10% (5 of 51 patients) with placebo (difference, 21 percentage points; 95% confidence interval [CI], 5 to 38; P = 0.01). Differences in favor of vedolizumab over placebo were also seen with respect to mPDAI-defined remission at week 34 (difference, 17 percentage points; 95% CI, 0 to 35), mPDAI-defined response at week 14 (difference, 30 percentage points; 95% CI, 8 to 48) and at week 34 (difference, 22 percentage points; 95% CI, 2 to 40), and PDAI-defined remission at week 14 (difference, 25 percentage points; 95% CI, 8 to 41) and at week 34 (difference, 19 percentage points; 95% CI, 2 to 37). Serious adverse events occurred in 3 of 51 patients (6%) in the vedolizumab group and in 4 of 51 patients (8%) in the placebo group. CONCLUSIONS: Treatment with vedolizumab was more effective than placebo in inducing remission in patients who had chronic pouchitis after undergoing IPAA for ulcerative colitis. (Funded by Takeda; EARNEST ClinicalTrials.gov number, NCT02790138; EudraCT number, 2015-003472-78.).

Differential Brain Structural and Functional Patterns in Crohn's Disease Patients are Associated with Different Disease Stages.

BACKGROUND: Crohn's disease (CD) is an inflammatory, chronic disorder that alternates between a quiescent phase and inflammatory flare-ups. Research has begun to elucidate the impact of CD in modulating brain structure and function. The previous neuroimaging studies mainly involved CD patients in remission (CD-R); therefore, little is known about how inflammation influences brain-related features in different stages of the disease. We carried out a magnetic resonance imaging (MRI) study to explore whether the different levels of disease activity may differentially affect brain structure and function. METHODS: Fourteen CD-R patients, 19 patients with mild to moderate inflammatory activity (CD-A), and 18 healthy controls (HCs) underwent an MRI scan including structural and functional sequences. RESULTS: Between-group comparisons showed morphological and functional brain differences distinctively associated with the stage of disease activity. The CD-A patients had reduced gray matter within the posterior cingulate cortex (PCC) relative to CD-R patients. Analysis on resting fMRI data showed the following patterns: (1) increased connectivity within the left fronto-parietal network (in the superior parietal lobe) in CD-R patients relative to CD-A patients; (2) decreased connectivity in the motor network (in parietal and motor areas) in the CD-A group relative to the HC group; (3) reduced connectivity in the motor network and (4) in the language network (in parietal areas and in the PCC) in CD-R patients relative to HC. CONCLUSIONS: The present findings represent a further step towards understanding brain morphological and functional changes in the active vs remission stages of CD patients.

We found morphological and functional brain changes associated with different stages of disease activity in Crohn's disease. These findings may represent the neural correlates of fatigue, irritable bowel syndrome­like symptoms, and cognitive-emotional impairments; these could be useful for evaluating disease progression.

Percutaneous Drainage vs. Surgery as Definitive Treatment for Anastomotic Leak after Intestinal Resection in Patients with Crohn's Disease.

BACKGROUND: Anastomotic leak (AL) remains one of the most relevant complications after intestinal resection for Crohn's disease (CD). While surgery has always been considered the standard treatment for perianastomotic collection, percutaneous drainage (PD) has been proposed as a potential alternative. METHODS: Retrospective study in consecutive patients treated with either PD or surgery for AL after intestinal resection for CD between 2004 and 2022. AL was defined as a perianastomotic fluid collection confirmed by radiological findings. Patients with generalized peritonitis or clinical instability were excluded. PRIMARY AIM: To compare the success rate of PD vs. surgery. Secondary aims: To compare the outcomes at 90 days after the procedures; to identify the variables associated with the indication for PD. RESULTS: A total of 47 patients were included, of which 25 (53%) underwent PD and 22 (47%) surgery. The success rate was 84% in the PD and 95% in the surgery group (p = 0.20). There were no significant differences between the PD and surgery group in postoperative medical and surgical complications, discharge, readmission or reoperation rates at 90 days. PD was more likely to be performed in patients with later diagnosis of AL (OR 1.25, 95% CI 1.03-1.53, p = 0.027), undergoing ileo-colic anastomosis alone (OR 3.72, 95% CI 2.29-12.45, p = 0.034) and treated after 2016 (OR 6.36, 95% CI 1.04-39.03, p = 0.046). CONCLUSION: The present study suggests that PD is a safe and effective procedure to treat anastomotic leak and perianastomotic collection in CD patients. PD should be indicated in all eligible patients as an effective alternative to surgery.

Dietary Habits and Nutrient Deficiencies in a Cohort of European Crohn's Disease Adult Patients.

Wrong dietary habits, such as the Western-style diet, are considered important risk factors for the development of Inflammatory Bowel Diseases (IBDs). Nevertheless, the role of dietary patterns in the clinical management of IBD patients has not been fully investigated yet. Fifty-four patients diagnosed with active Crohn's disease (CD) were enrolled and subjected to nutritional intake analysis through a weekly food diary. Nutritional patterns were analyzed, and nutrient intake was compared with those of 30 healthy subjects (HS). Blood levels of cholesterol, folic acid, minerals (K, Mg, Fe) and amino acids, were measured in CD patients to assess the presence of nutritional deficiencies. CD patients, with respect to HS, consumed significantly lower amounts of fiber, vitamins (A, E, C, B6, folic acid) and ß-carotene. Their calcium, potassium, phosphorus, iron, magnesium, copper and iodine intake were also found to be significantly lower. In blood, CD patients had significantly lower concentrations of total cholesterol, potassium, iron, and amino acids. Active CD patient diet was significantly different from those of HS and may contribute to the establishment of nutritional deficiencies. Intestinal malabsorption was evidenced in these patients. Correction of the diet with specific nutritional plans is a necessary therapeutic step for these patients. ClinicalTrials.gov: NCT02580864.

Effectiveness of swapping to ustekinumab after vedolizumab failure in patients with multi-refractory Crohn's disease.

BACKGROUND: Ustekinumab (UST) and vedolizumab (VDZ) are biologic therapies for moderate-to-severe Crohn's disease (CD) in patients who failed or had contraindication to anti-TNF treatment. AIMS: To evaluate ustekinumab efficacy as third-line treatment after swapping from VDZ for failure. METHODS: We conducted a monocentric, retrospective, observational study where CD patients were followed for 12 months from the beginning of UST therapy. We assessed clinical activity (HBI) and laboratory markers (CRP) at the initiation of UST therapy (T0) and after 2(T2), 6(T6) and 12(T12) months. Endoscopic activity was recorded at T0 and T12. We registered data regarding their clinical history and previous biologic treatments. Steroid-free clinical remission was defined as HBI ≤ 4 without need for steroids. Clinical response was defined as HBI reduction of at least three points or the suspension of steroids. RESULTS: 27 CD patients treated with UST after VDZ failure had a minimum follow up of 12 months and were included. All patients had previously been treated with anti-TNF agents. After 12 months, steroid-free clinical remission was evident in 15 (55.5%) patients, 5 (18.5%) had clinical response, while 7 (26%) had suspended for failure or persisted on treatment after optimization. CONCLUSIONS: Ustekinumab should be considered as third-line biologic treatment in multi-refractory CD patients.

Prevalence, Pathogenesis and Management of Anemia in Inflammatory Bowel Disease: An IG-IBD Multicenter, Prospective, and Observational Study.

BACKGROUND: Anemia is a common extraintestinal manifestation of inflammatory bowel disease (IBD), with a 6% to 74% prevalence and a negative impact on patient survival and quality of life, although the prevalence is apparently declining due to improved disease treatment. We aimed to investigate the prevalence, pathogenesis, and clinical correlates of anemia in Italian patients with IBD. METHODS: A multicenter, prospective, observational study, involving 28 Italian gastroenterology centers, was conducted to investigate the epidemiology and consequences of IBD-associated anemia. Clinical and laboratory data of anemic patients were obtained at study enrolment. RESULTS: Anemia was diagnosed in 737 of 5416 adult IBD outpatients (prevalence 13.6%); females were more commonly affected than males (odds ratio, 1.5; 95% confidence interval [CI], 1.2-1.7) and had more severe anemia. In the majority of cases, anemia was due to iron deficiency (62.5% of cases; 95% CI, 58.3%-66.6%), either isolated or in association with inflammation and/or vitamin deficiencies; anemia of inflammation accounted for only 8.3% of cases. More severe anemia was associated with increasing fatigue and worse quality of life. Only 68.9% of anemic patients with iron deficiency (95% CI, 63.4%-73.8%) and 34.6% of those with vitamin deficiencies (95% CI, 26.2%-44.2%) were properly treated with supplementation therapy. CONCLUSIONS: In Italy, the prevalence of IBD-associated anemia is lower than previously reported. Anemia of IBD is most commonly due to iron deficiency and contributes to fatigue and poor quality of life, but remains untreated in a large proportion of patients with iron and/or vitamin deficiencies. This study is registered at clinicaltrials.gov as NCT02872376.

The prevalence of inflammatory bowel disease­associated anemia is 13.6%. The prevalence is higher among females younger than 50. Anemia is usually due to iron deficiency and adversely affects fatigue and quality of life. Many patients with iron or vitamin deficiency (31% and 65%, respectively) remain untreated.

Capsule endoscopy in Crohn's disease surveillance: A monocentric, retrospective analysis in Italy.

Background: Crohn's disease (CD) is a potentially debilitating condition that burdens Italian healthcare substantially. The symptomatic management relies on prompt therapy adjustment to reduce flares and follow-up diagnostic inputs to maximise remission. Capsule endoscopy (CE) has introduced advantages in CD diagnostics, allowing the direct inspection of the entire gastrointestinal mucosa. The diagnostic procedure is comparable in effort to standard ileocolonoscopy (IC) but requires no anaesthesia. Whether CE follow-up improves clinical outcomes remains to be defined. Objectives: To provide a preliminary evaluation of CE in terms of clinical outcomes with respect to the standard of care ileocolonoscopy/MRE in Italy. Methods: This retrospective analysis utilises anonymised, monocentric data from the S. Orsola-Malpighi Hospital IBD database in Bologna, Italy, collected between 1999 and 2019. Out of 421 adult patient records, 100 were included in the analysis (50 per arm, matched per demographic and clinical characteristics). The CE represented the intervention arm, whereas ileocolonoscopy/magnetic resonance enterography was the standard of care. The use of biologics, symptomatology course, and surgery were the outcomes. Results: The two techniques performed similarly overall. In general, no significant difference emerged in the use of biologics. The use of biologics appears reduced in the CE group, only in L4 patients after the first follow-up year. Similarly, surgery was seemingly less frequent among L4 patients in the CE group. No difference was found between groups in flare occurrence and duration. CE patients might have experienced longer and earlier first remissions, but no long-term difference persisted. Conclusions: The CE group showed an apparent reduction in biologics and surgery, limiting to L4 diagnoses. More extensive, prospective, multicentre, randomised studies must corroborate these preliminary findings.