Impact of Kono-S anastomosis on quality of life after ileocolic resection in Crohn's disease: an analysis from the SuPREMe-CD trial.

AIM: Crohn's disease has debilitating effects on patients' quality of life. Currently, there are limited data on the effect of anastomotic configuration on health-related quality of life after ileocaecal resection for Crohn's disease. This study aimed to assess the impact of Kono-S anastomosis on quality of life after ileocolic resection, compared to the conventional side-to-side anastomosis. METHOD: Patients with primary or recurrent Crohn's disease participating in the ongoing SuPREMe-CD trial were interviewed about quality of life using the Inflammatory Bowel Disease Questionnaire (IBDQ). The primary endpoint was disease-specific quality of life, assessed with IBDQ. Secondary outcomes were quality of life related to bowel symptoms, systemic symptoms, social function and emotional function. RESULTS: Of the 94 patients included, 51 (54%) received the conventional side-to-side anastomosis and 43 (46%) the Kono-S anastomosis. Demographics were comparable between the two groups. The IBDQ was assessed at a mean follow-up of 54.0 ± 18.7 months from surgical intervention. The mean total IBDQ score was 155.1 ± 28.07 in the conventional group and 163.8 ± 25.23 in the Kono-S group (P = 0.11). When considering bowel symptoms and social function, mean scores were 50.7 and 23.5 in the conventional group, and 56.3 and 26.5 in the Kono-S group (P = 0.002 and P = 0.02, respectively). Kono-S anastomosis was independently associated with improved quality of life regarding bowel symptoms (P = 0.006) and social function (P = 0.03) after correcting for other confounding factors on linear regression analysis. CONCLUSION: Compared to conventional side-to-side anastomosis, patients with Kono-S anastomosis presented significantly better bowel symptoms and social function scores at 54 months after surgery.

Ultrasonography Tight Control and Monitoring in Crohn's Disease During Different Biological Therapies: A Multicenter Study.

BACKGROUND & AIMS: Bowel ultrasonography (BUS) is a noninvasive tool for evaluating bowel activity in Crohn's disease (CD) patients. Aim of our multicenter study was to assess whether BUS helps to monitor intestinal activity improvement/resolution following different biological therapies. METHODS: Adult CD patients were prospectively enrolled at 16 sites in Italy. Changes in BUS parameters [i.e. bowel wall thickening (BWT), lesion length, echo pattern, blood flow changes and transmural healing (TH: normalization of all BUS parameters)] were analyzed at baseline and after 3, 6 and 12 months of different biological therapies. RESULTS: One hundred eighty-eight out of 201 CD patients were enrolled and analyzed (116 males [62%]; median age 36 years). Fifty-five percent of patients were treated with adalimumab, 16% with infliximab, 13% with vedolizumab and 16% with ustekinumab. TH rates at 12 months were 27.5% with an NNT of 3.6. TH at 12 months after adalimumab was 26.8%, 37% after infliximab, 27.2% after vedolizumab and 20% after ustekinumab. Mean BWT improvement from baseline was statistically significant at 3 and 12 months (P < .0001). Median Harvey-Bradshaw index, C-reactive protein and fecal calprotectin decreased after 12 months from baseline (P < .0001). Logistic regression analysis showed colonic lesion was associated with a higher risk of TH at 3 months and a greater BWT at baseline was associated with a lower risk of TH at 3 months [P = .03 (OR 0.70, 95% CI 0.50-0.97)] and 12 months [P = .01 (OR 0.58, 95% CI 0.38-0.89)]. At 3 months therapy optimization during the study was the only independent factor associated with a higher risk of no ultrasonographic response [P = .02 (OR 3.34, 95% CI 1.18-9.47)] and at 12 months disease duration [P = .02 (OR 3.03, 95% CI 1.15-7.94)]. CONCLUSIONS: Data indicate that BUS is useful to monitor biologics-induced bowel activity improvement/resolution in CD.

Metabolic-associated fatty liver disease (MAFLD) in coeliac disease.

BACKGROUND AND AIMS: Coeliac disease (CD) is considered a high-risk condition for developing non-alcoholic fatty liver disease (NAFLD) and other related metabolic disorders, particularly after commencing gluten-free diet (GFD). Recently, a new concept of metabolic-associated fatty liver disease (MAFLD) has been proposed to overcome the limitations of NAFLD definition. This study aimed at exploring the prevalence of NAFLD and MAFLD in CD patients at the time of CD diagnosis and after 2 years of GFD. Furthermore, we evaluated the role of PNPLA3 rs738409 in the development of NAFLD and MAFLD in the same population. METHODS: We retrospectively enrolled all newly diagnosed CD patients who underwent clinical, laboratory and ultrasonography investigations both at diagnosis and after 2 years of follow-up. Moreover, a PNPLA3 rs738409 genotyping assay was performed. RESULTS: Of 221 newly diagnosed CD patients, 65 (29.4%) presented NAFLD at CD diagnosis, while 32 (14.5%) met the criteria for MAFLD (k = 0.57). There were no significant differences between NAFLD and MAFLD, except for the higher rate of insulin resistance (IR) of MAFLD patients (75% vs 33.8%, P < .001). At 2 years of follow-up, 46.6% of patients developed NAFLD while 32.6% had MAFLD (k = 0.71). MAFLD subjects had higher transaminases (P = .03), LDL-cholesterol (P = .04), BMI and waist circumference and higher IR than NAFLD patients. MAFLD patients showed higher non-invasive liver fibrosis scores than NAFLD subjects (APRI = 1.43 ± 0.56 vs 0.91 ± 0.62, P < .001; NFS=-1.72 ± 1.31 vs -2.18 ± 1.41, P = .03; FIB-4 = 1.27 ± 0.77 vs 1.04 ± 0.74, P = .04). About PNPLA3 polymorphisms, at 2 years follow-up, NAFLD subjects presented a higher rate of heterozygosis (40.8%) and homozygosis (18.4%) polymorphisms than non-NAFLD (26.3% and 7.6%, respectively, P = .03 and 0.02), while no correlation between PNPLA3 polymorphisms and MAFLD was seen. CONCLUSIONS: The new MAFLD definition better reflects the metabolic alterations following GFD in CD population. This new classification could be able to identify patients at higher risk of worse metabolic outcome, who need a close multidisciplinary approach for their multisystemic disease.

Treatment-based risk stratification of infections in inflammatory bowel disease: A comparison between anti-tumor necrosis factor-α and nonbiological exposure in real-world setting.

BACKGROUND AND AIM: Infective issues about anti-tumor necrosis factor (TNF)-α agents in inflammatory bowel disease (IBD) remain controversial, especially when compared with nonbiological treatments. This study aimed to evaluate the incidence and prevalence of several infections in anti-TNF-α-exposed patients compared with nonbiological treatments. METHODS: All naïve IBD subjects treated with anti-TNF-α and matched nonbiologic-exposed patients were included. RESULTS: Among 3453 patients in the database, 288 anti-TNF-α-exposed subjects and 288 nonbiologic-exposed IBD controls met inclusion criteria. Fifty-eight infections (20.1%) occurred during anti-TNF-α treatment versus 23 (8%) in the matched group (odds ratio [OR] 2.9, P < 0.001) (incidence 5.72 vs 0.96/100 patient-years, incidence ratio [IR] 6, P < 0.001). IR was higher for anti-TNF-α versus mesalamine/sulfasalazine (IR 40.8, P < 0.001), similar to azathioprine/6-mercaptopurine/methotrexate (IR 0.78, P = 0.32) and lower than corticosteroids (IR 0.05, P < 0.001). The incidence rate of serious infections was 1.3 in the anti-TNF-α-exposed versus 0.38/100 patient-years in nonexposed subjects (IR 3.44, P = 0.002), without significant difference between anti-TNF-α and azathioprine/6-mercaptopurine/methotrexate (1.3 vs 3.03/100 patient-years, IR 0.43, P = 0.1). Predictors of infections in anti-TNF-α-exposed patients were concomitant use of systemic steroids (OR 1.9, P = 0.02) or azathioprine (OR 2.6, P = 0.01) and a body mass index < 18.5 at time of infection (OR 2.2, P = 0.01). CONCLUSIONS: The risk of developing infections during anti-TNF-α therapy remains high, although not dissimilar to that found for other immunosuppressants, while concomitant immunosuppression and malnutrition appear the most important causes of infection.

Surgical Prevention of Anastomotic Recurrence by Excluding Mesentery in Crohn's Disease: The SuPREMe-CD Study - A Randomized Clinical Trial.

OBJECTIVE: This trial aimed to provide randomized controlled data comparing Kono-S anastomosis and stapled ileocolic side-to-side anastomosis. BACKGROUND: Recently, a new antimesenteric, functional, end-to-end, hand-sewn ileocolic anastomosis (Kono-S) has shown a significant reduction in endoscopic recurrence score and surgical recurrence rate in Crohn disease (CD). METHODS: Randomized controlled trial (RCT) at a tertiary referral institution. Primary endpoint: endoscopic recurrence (ER) (Rutgeerts score ≥i2) after 6 months. Secondary endpoints: clinical recurrence (CR) after 12 and 24 months, ER after 18 months, and surgical recurrence (SR) after 24 months. RESULTS: In all, 79 ileocolic CD patients were randomized in Kono group (36) and Conventional group (43). After 6 months, 22.2% in the Kono group and 62.8% in the Conventional group presented an ER [P < 0.001, odds ratio (OR) 5.91]. A severe postoperative ER (Rutgeerts score ≥i3) was found in 13.8% of Kono versus 34.8% of Conventional group patients (P = 0.03, OR 3.32). CR rate was 8% in the Kono group versus 18% in the Conventional group after 12 months (P = 0.2), and 18% versus 30.2% after 24 months (P = 0.04, OR 3.47). SR rate after 24 months was 0% in the Kono group versus 4.6% in the Conventional group (P = 0.3). Patients with Kono-S anastomosis presented a longer time until CR than patients with side-to-side anastomosis (hazard ratio 0.36, P = 0.037). On binary logistic regression analysis, the Kono-S anastomosis was the only variable significantly associated with a reduced risk of ER (OR 0.19, P < 0.001). There were no differences in postoperative outcomes. CONCLUSIONS: This is the first RCT comparing Kono-S anastomosis and standard anastomosis in CD. The results demonstrate a significant reduction in postoperative endoscopic and clinical recurrence rate for patients who underwent Kono-S anastomosis, and no safety issues.ClinicalTrials.gov ID NCT02631967.

Real-Life Effectiveness and Safety of Golimumab and Its Predictors of Response in Patients with Ulcerative Colitis.

BACKGROUND: Golimumab is a new anti-TNF-alpha monoclonal antibody for patients with ulcerative colitis. AIMS: To assess the short- and long-term effectiveness and safety of golimumab in daily clinical practice and to identify predictors of response. METHODS: Consecutive patients treated with golimumab in 22 Italian centers were enrolled. Clinical, laboratory, and endoscopic data were prospectively collected before and during treatment. A subgroup of patients completed a questionnaire to assess personal satisfaction with a golimumab autoinjector system. RESULTS: A total of 196 patients were included. After 3 months, 130 patients were responders (66.3%) and showed significant reductions in mean partial, total, and endoscopic Mayo scores and in mean ESR, C-reactive protein, and fecal calprotectin levels (p < 0.001). Multivariate analysis revealed that a higher total Mayo score (p < 0.001, OR 1.5, 95% CI 1.2-1.8) and naïve status to anti-TNF-alpha (p = 0.015, OR 3.0, 95% CI 1.2-7.5) were predictive of a favorable response. Seventy-seven (39.3%) of the 130 responders maintained a response at month 12 of therapy. There were 17 adverse events, 28 patients needed hospitalization, and 15 patients underwent surgery. Self-administration of the drug was appreciated by most patients. CONCLUSIONS: The efficacy and safety of golimumab in daily clinical practice were confirmed for the short- and long-term treatment of patients with active ulcerative colitis. Patients naïve to the anti-TNF-alpha monoclonal antibody and those with a higher total Mayo score were more likely to respond to golimumab.

The role of TMPRSS6 and HFE variants in iron deficiency anemia in celiac disease.

We investigated the role of HFE C282Y, H63D, and TMPRSS6 A736V variants in the pathogenesis of iron deficiency anemia (IDA) in celiac disease (CD) patients, at diagnosis and after 1 year of gluten-free diet (GFD). Demographic and clinical features were prospectively recorded for all CD patients between 2013 and 2017. C282Y, H63D, and A736V variants were evaluated for CD patients and controls. Finally, 505 consecutive CD patients and 539 age-matched control subjects were enrolled. At diagnosis, 229 CD subjects had IDA (45.3%), with a subgroup of anemic patients (45.4%) presented persistent IDA at follow-up. C282Y allele frequency was significantly increased in CD compared with controls (1.1% vs 0.2%, P = .001), whereas H63D and A736V allele frequencies were similar among patients and controls (P = .92 and .84, respectively). At diagnosis, C282Y variant in anemic CD patients was significantly increased compared to nonanemic group (2% and 0.5%, P = .04). At follow-up, A736V was significantly increased in IDA persistent than in IDA not persistent (57.7% vs 35.2%, P < .0001). CD patients with H63D mutation showed higher Hb, MCV, serum iron, and ferritin levels than subjects without HFE mutations. Decreased hepcidin values were observed in anemic compared to nonanemic subjects at follow-up (1.22 ± 1.14 vs 2.08 ± 2.15, P < .001). This study suggests a protective role of HFE in IDA CD patients and confirms the role of TMPRSS6 in predicting oral iron response modulating hepcidin action on iron absorption. Iron supplementation therapeutic management in CD could depend on TMPRSS6 genotype that could predict persistent IDA despite iron supplementation and GFD.

Diagnostic Accuracy of 3-Dimensional Endoanal Ultrasound in Identifying Perianal Crohn's Fistulas.

BACKGROUND: Perianal fistulizing Crohn's disease is a challenging clinical situation that requires proper management. Some features seen on the endoanal ultrasound can be helpful in discriminating between cryptoglandular and Crohn's disease fistulas. OBJECTIVE: The aim of this study was to define the diagnostic accuracy of 3-dimensional endoanal ultrasound in differentiating between Crohn's disease and cryptogenic fistulas. DESIGN: This was a prospective observational study. SETTINGS: The study was conducted in the colorectal unit of an IBD referral center. PATIENTS: Consecutive patients referred for suspected perianal sepsis from September 2015 to December 2016 were included. INTERVENTIONS: Three-dimensional endoanal ultrasonography was the studied intervention. MAIN OUTCOMES MEASURES: Sensitivity, specificity, and positive and negative likelihood ratios of 4 ultrasonographic features (Crohn's ultrasound fistula sign, the presence of a double track, debris or an abscess within the fistula track, and the maximum width of the track) in discriminating between cryptoglandular and Crohn's disease fistulas were calculated. The interobserver agreement for each feature was quantified. RESULTS: In this study, 158 patients, of whom 33 had a diagnosis of Crohn's disease, were included. The interobserver agreement was good for all of the ultrasonographic features. All of these features were more frequent in cases of Crohn's disease fistulas (p = 0.0001). The maximum width of the fistula track was highly accurate for discriminating between cryptogenic and Crohn's disease fistulas (area under the receiver operating characteristic curve = 0.922). The simultaneous presence of 2 features was suggestive of Crohn's disease fistula. In particular, the presence of a track width >4 mm in conjunction with either a double track or the Crohn's ultrasound fistula sign showed very high specificity (1.00). Conversely, a fistula track width ≤3 mm had high sensitivity (0.97). LIMITATIONS: Patients included in the cryptogenic group might be diagnosed as having Crohn's disease at follow-up. CONCLUSIONS: The combination of specific endoanal ultrasonographic features allows for highly accurate discrimination between Crohn's disease and cryptogenic fistulas. See Video Abstract at http://links.lww.com/DCR/A619.

Beyond Irritable Bowel Syndrome: The Efficacy of the Low Fodmap Diet for Improving Symptoms in Inflammatory Bowel Diseases and Celiac Disease.

BACKGROUND AND AIM: To evaluate the usefulness of a low FODMAP (Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols) diet on patients with irritable bowel syndrome (IBS), non-active inflammatory bowel diseases (IBD), and celiac disease (CD) on a gluten-free diet (GFD). METHODS: Dietetic interventional prospective study. IBS, IBD, and CD subjects were evaluated to check if they fulfilled the Rome III criteria. Each subject was educated to follow a low FODMAP diet after being evaluated by filling out questionnaires that assessed the quality of life (QoL) and symptoms experienced (IBS-SSS and SF-36), and was reevaluated after 1 and 3 months. RESULTS: One hundred twenty-seven subjects were enrolled: 56 with IBS, 30 with IBD, and 41 with CD. IBS-SSS showed that abdominal symptoms improved after 1 and 3 months of diet in all subjects, with significant difference among the 3 groups at T0 (average scores IBS: 293 ± 137, IBD: 206 ± 86, CD: 222 ± 65, p < 0.001), but no difference at T3 (IBS: 88 ± 54, IBD: 73 ± 45, CD: 77 ± 49, p = ns). By analyzing the SF-36 questionnaire, we did not observe any difference between the 3 groups, in terms of response to diet (p = ns), we observed a clinical improvement from T0 to T3 for most of the questionnaire's domains. CONCLUSIONS: A low FODMAP diet could be a valid option to counter -abdominal symptoms in patients with IBS, non-active IBD, or CD on a GFD, and thus, improve their QoL and social -relations.

FRAX Score Can Be Used to Avoid Superfluous DXA Scans in Detecting Osteoporosis in Celiac Disease: Accuracy of the FRAX Score in Celiac Patients.

The Fracture Risk Assessment (FRAX) tool has been developed to estimate patients' 10-yr probability of fracture, thus establishing which patients should undergo dual-energy X-ray Absorptiometry (DXA) scan. This study aimed to evaluate if the FRAX tool can replace or optimize the use of DXA scan in celiac disease (CD). We prospectively enrolled all CD patients aged over 40 yr diagnosed at our third-level unit. At time of CD diagnosis, all patients underwent FRAX score calculation for risk of major osteoporotic and hip fractures and DXA scan (used as gold standard) to assess the accuracy of the FRAX score. The FRAX score calculation was based on the following 10 variables: age (>40 yr), sex (M/F), body mass index, history of previous fracture (yes/no), parent fractured hip (yes/no), current smoking (yes/no), use of steroids (yes/no), rheumatoid arthritis (yes/no), secondary osteoporosis (yes/no), and alcohol ≥3 units/d (yes/no). DXA assessment was performed within 1 week from FRAX calculation. The FRAX score was dichotomized as normal or pathologic in accordance with the National Osteoporosis Guideline Group. A total of 160 CD patients were enrolled (M/F = 20/140; mean age 48.7 yr). A pathologic FRAX score was evident in 14 out of 160 patients (8.7%), whereas osteoporosis based on DXA scan was found in 10 patients (6%) (κ = 0.6); 3 patients with osteoporosis (1.9%) showed a 10-yr risk of major fracture >10% according to the National Osteoporosis Guideline Group criteria. With regard to diagnostic accuracy, the FRAX score showed sensitivity of 0%, specificity of 91%, positive predictive value of 0%, and negative predictive value of 94%. The prevalence of osteoporosis in adult CD appears to be quite low and only a small proportion of patients would require a DXA investigation. The FRAX score could be an effective tool to avoid useless DXA scans in CD patients in view of its high negative predictive value.

Coeliac disease in the elderly in a tertiary centre.

INTRODUCTION AND AIMS: Coeliac disease (CD) was believed to be a childhood disease while it can affect any age. AIM: to evaluate the prevalence of CD in elderly population, recording the main clinical features of this group respect to young patients. METHODS: We retrospectively analysed the prevalence of CD in an elderly population from 1970 to 2015. We divided patients into three age-groups (group A: 18-34 years; group B: 35-64 years; group C: ≥65 years) and compared them regarding baseline anthropometric and serological variables, clinical features at diagnosis, diagnostic mode, associated autoimmune diseases, and CD-related neoplastic complications. RESULTS: We made 2812 CD diagnoses in adults: 2.5% of them were ≥65 years at diagnosis. When comparing the three groups, we found no differences in sex, haemoglobin, serum iron, albumin, and anti-tissue transglutaminase (anti-tTG) (p = NS) while as expected, we found higher values of cholesterol, glycaemia, and triglycerides in older patients (p < 0.0001). Elderly had a higher risk of being diagnosed with malabsorption symptoms compared to younger patients (OR 2.20, 95%CI 1.3-3.74). No difference in the risk of autoimmune CD-related diseases was seen among groups. Furthermore, we observed 16 neoplastic complications, 13 of them happened in the patients diagnosed with CD aged 35-64 years. The number of CD diagnoses increased over time, particularly in elderly. CONCLUSION: CD diagnosis in elderly population is quite uncommon although not rare. Elderly CD patients have a higher risk of being diagnosed with malabsorption symptoms than younger patients but without increased risk of autoimmune and neoplastic complications.

Predictive value of "Marsh 1" type histology in subjects with suspected cealic disease.

INTRODUCTION: The diagnosis of celiac disease (CD) is based on histology in combination with anti-tissue transglutaminase (a-tTG) and anti-endomysial antibodies (EMAs). The increase of intraepithelial lymphocytes defines the Marsh 1 histology that appears not to be specific for CD. AIM: To explore the positive predictive value (PPV) and clinical relevance of Marsh 1 histology in suspected CD. METHODS: We carried out an observational prospective study including all consecutive subjects with a Marsh 1 histology. All patients were tested for a-tTG and EMAs. Diagnosis of potential CD was defined in the presence of Marsh 1 with positive a-tTG and EMAs. Patients were investigated for symptoms, CD familial aggregation, other diseases, and current medication. RESULTS: Sixty-three patients with Marsh 1 were included. Diagnosis of potential CD was made in 23 subjects (36%), so that Marsh 1 histology showed a PPV of 36%. With regard to familial aggregation, patients with potential CD showed a higher frequency of familiarity for CD (60.8% vs. 15.0%; p < 0.01). No significant difference was detected between CD and non-CD in terms of intestinal and extra-intestinal symptoms. We also documented the presence of conditions other than CD in the remaining population: 7 patients (17.5%) with immuno-mediated diseases while 5 patients (12.5%) showed Helicobacter pylori (HP) infection. About medication, 3 patients (7.5%) were on non-steroidal anti-inflammatory drugs, while another 4 (10%) patients were being treated with other drugs. CONCLUSION: The Marsh 1 type histology is not specific for CD and it can also be associated with immuno-mediated disorders, HP infection, and drugs.

Changes upon the gluten-free diet of HLA-DQ2 and TRAFD1 gene expression in peripheral blood of celiac disease patients.

Background: Celiac disease (CD) is a chronic immuno-mediated enteropathy caused by dietary gluten in genetically susceptible individuals carrying HLA (Human Leukocytes Antigen) genes that encode for DQ2.5 and DQ8 molecules. TRAFD1 (TRAF-type zinc finger domain 1) is a gene recently found associated with CD and defined as a master regulator of IFNγ signalling and of MHC class I antigen processing/presentation. There is no specific drug therapy and the only effective treatment is the gluten-free diet (GFD). The great majority of celiac patients when compliant with GFD have a complete remission of symptoms and recovery of gut mucosa architecture and function. Until now, very few studies have investigated molecular differences occurring in CD patients upon the GFD therapy. Methods: We looked at the expression of both HLA DQ2.5 and TRAFD1 risk genes in adult patients with acute CD at the time of and in treated patients on GFD. Specifically, we measured by qPCR the HLA-DQ2.5 and TRAFD1 mRNAs on peripheral blood mononuclear cells (PBMC) from the two groups of patients. Results: When we compared the HLA-DQ mRNA expression, we didn't find significant variation between the two groups of patients, thus indicating that GFD patients have the same capability to present gliadin antigens to cognate T cells as patients with active disease. Conversely, TRAFD1 was more expressed in PBMC from treated CD subjects. Notably, TRAFD1 transcripts significantly increased in the patients analyzed longitudinally during the GFD, indicating a role in the downregulation of gluten-induced inflammatory pathways. Conclusion: Our study demonstrated that HLA-DQ2.5 and TRAFD1 molecules are two important mediators of anti-gluten immune response and inflammatory process.

Effectiveness of Partial Enteral Nutrition as Add-On to Biologics in Patients With Refractory and Difficult-to-Treat Crohn's Disease: A Pilot Study.

Background: Partial enteral nutrition (PEN) is a well-established treatment for children with Crohn's disease (CD). However, its efficacy in adults with CD remains uncertain. We aimed to assess the effectiveness of PEN as an add-on to escalated biological therapy in adults with CD who have lost response to biologics. Methods: We conducted a retrospective observational study including patients who had lost response to biologics and received PEN in combination with escalated treatment, compared to those treated only with escalated therapy. The primary endpoint was steroid-free clinical remission (CR) at 24 weeks. Secondary endpoints included transmural healing (TH) and response (TR) rates along with selected clinical outcomes. Results: Forty-two patients were screened; 12 (28.6%) were excluded for complicated disease and 30 (71.4%) were included in the final analysis. Fourteen (46.7%) patients completed PEN treatment at 8 weeks, while 16 patients (53.3%) discontinued treatment due to intolerance and continued with escalation of biologic (BT group). At 24 weeks, 9 patients (64.3%) in the PEN group achieved CR, compared to 4 patients (25%) in the BT group (P = .03). The TR rate was 64.9% in the PEN group and 25% in the BT group (P = .03). Patients receiving PEN exhibited an increase in albumin levels compared to those in the BT group (Δ = 0.5; P = .02). A higher rate of therapy changes (68.7%) was observed in the BT group compared to 14.2% in the PEN group (P = .004). Prior failure to 2 lines of biological therapy was associated with adherence to PEN (OR = 1.583; CI = 1.06-2.36; P = .01). Conclusions: In patients who had lost response to biologics, PEN in combination with escalated biologics was associated with CR and TR and improved nutritional status. Hence, the addition of PEN should be considered for patients with difficult-to-treat CD.

The impact of inflammatory bowel diseases on patients' quality of life and work functionality: an observational study.

BACKGROUND: To assess the employment status, quality of life and work functionality in patients affected by Inflammatory Bowel Diseases (IBD). METHODS: Patients (n. 216) were enrolled between June 2020- October 2021. Personal, clinical and occupational features were investigated. The Short Inflammatory Bowel Disease Questionnaire and the Work Productivity and Activity Impairment questionnaire were administered. RESULTS: Among the enrolled patients, 114 (53%) were employed. Mean absenteeism and presenteeism percentages of 10% and 37% were determined, with 44% and 39% of daily and work activity impairment, respectively. A poor Health-Related Quality of Life (HRQoL) was retrieved (47 ± 12). Extra-intestinal manifestations, disease activity and HRQoL resulted associated with occupational outcomes. CONCLUSIONS: IBD can impact patients' work functionality. The association between clinical, psychological and occupational issues suggest the relevance for a multidisciplinary management of the disease.

"The crackers challenge": A reassuring low-dose gluten challenge in adults on gluten-free diet without proper diagnosis of coeliac disease.

BACKGROUND: Gluten-free diet (GFD) is the one therapy in coeliac disease (CeD). Unfortunately, some patients adopt GFD before the diagnostic work-up. The guidelines suggest a 14-day gluten intake > 3 gr to get CeD diagnosis, although many subjects refuse this approach. Other evidence showed that the intake of 50 mg/day of gluten for 3 months could be useful for CeD diagnosis. AIMS: We performed a dietary study, administering a low dose of gluten in form of "crackers" (about 60-120 mg of gluten/day) for 3 months, to get a final diagnosis of CeD in subjects already on GFD. METHODS: We enrolled adult patients with a suspicion of CeD on self-prescribed GFD. All subjects performed the crackers challenge for 3 months. At the end, all patients were analysed for CeD serology and if positive underwent endoscopy/histology. Also, we recorded the grade of satisfaction for the gluten challenge and the onset of adverse events. RESULTS: We enrolled 120 patients. All patients concluded the challenge without relevant adverse events. Serological positivity was detected in 54 patients (45%). Histology showed atrophy in 87% and Marsh 1-2 grade in 13% of patients. Ninety-nine patients (83%) were satisfied by this challenge. CONCLUSIONS: The "crackers challenge" is a useful and safe diagnostic approach in people on self-administered GFD.

Segmental colitis associated with diverticulosis (SCAD) in a colorectal cancer screening population: Prevalence, endoscopic features and oncological outcomes.

BACKGROUND: Segmental colitis associated with diverticulosis (SCAD) is characterized by a chronic inflammatory response involving the inter-diverticular colonic mucosa, sparing the rectum and the right colon. AIMS: to assess the prevalence of SCAD in a CRC screening program and to evaluate the differences in terms of oncological outcomes between SCAD and diverticulosis. METHODS: retrospective analysis from a prospectively-maintained database including all subjects undergoing first screening colonoscopy. RESULTS: 1518 patients were included (51.8 % male, mean age 63.48 ± 6.39). Adenomas were detected in 638 patients (ADR 42 %), CRC was diagnosed in 5.7 %. Diverticulosis was described in 37.5 %, while SCAD in 4.5 %. Among them, 69.6 % presented crescentic-fold disease, 20.3 % mild-to-moderate UC-like pattern, 8.7 % CD-like pattern and 1.4 % severe UC-like pattern. When SCAD was compared to uncomplicated/asymptomatic diverticulosis (501 patients), we found no differences in terms of gender (p = 0.46) or age (p = 0.47). Interestingly, the use of anticoagulant/antiplatelet (p = 0.79), anti-hypertensive (p = 0.89) or anti-hyperglycaemic drugs (p = 0.52) had no effect on SCAD onset as compared to diverticulosis. SCAD patients had significant lower rate of adenomas (ADR 31.9% vs 47.3 %, p = 0.018, OR 0.52, 95 %CI 0.31-0.89), and lower-but not significant-rate of CRC (1.4% vs 6.2 %, p = 0.14, OR 0.22, 95 %CI 0.02-1.66). CONCLUSIONS: SCAD can be diagnosed in about 5 % of population undergoing screening colonoscopy and in 12 % of those with diverticulosis. SCAD seems to be associated with a reduced rate of adenomas or CRC as compared with diverticulosis.