Search

Macrophages play an important role in the pathogenesis of celiac disease (CD) because they are involved in both inflammatory reaction and antigen presentation. We analyzed the expression of CD-associated HLA-DQ2.5 risk alleles on macrophages isolated by two cohorts of adult patients, from the U.S. and Italy, at different stages of disease and with different genotypes. After isolating and differentiating macrophages from PBMC, we assessed the HLA genotype and quantified the HLA-DQ2.5 mRNAs by qPCR, before and after gliadin stimulation. The results confirmed the differences in expression between DQA1*05:01 and DQB1*02:01 predisposing alleles and the non-CD associated alleles, as previously shown on other types of APCs. The gliadin challenge confirmed the differentiation of macrophages toward a proinflammatory phenotype, but above all, it triggered an increase of DQA1*05:01 mRNA, as well as a decrease of the DQB1*02:01 transcript. Furthermore, we observed a decrease in the DRB1 genes expression and a downregulation of the CIITA transactivator. In conclusion, our findings provide new evidences on the non-coordinated regulation of celiac disease DQ2.5 risk genes and support the hypothesis that gliadin could interfere in the three-dimensional arrangement of chromatin at the HLA locus.

In the absence of a codified refugee rights framework in Jordan and Lebanon, legal actors must be creative in the development of strategies and approaches to ensure the protection of refugee rights in practice.

Background Diagnosis of Crohn’s disease (CD) requires ileo-colonoscopy (IC) and cross-sectional evaluation. Recently, “echoscopy” has been used effectively in several settings, although data about its use for CD diagnosis are still limited. Our aim was to evaluate the diagnostic accuracy of handheld bowel sonography (HHBS) in comparison with magnetic resonance enterography (MRE) for CD diagnosis. Methods From September 2019 to June 2021, we prospectively recruited consecutive subjects attending our third level IBD Unit for suspected CD. Patients underwent IC, HHBS, and MRE in random order with operators blinded about the result of the other procedures. Bivariate correlation between MRE and HHBS was calculated by Spearman coefficient (r). To test the consistency between MRE and HHBS for CD location and complications, the Cohen’s k measure was applied. Results Crohn’s disease diagnosis was made in 48 out of 85 subjects (56%). Sensitivity, specificity, positive predictive values, and negative predictive values for CD diagnosis were 87.50%, 91.89%, 93.33%, and 85% for HHBS; and 91.67%, 94.59%, 95.65%, and 89.74% for MRE, without significant differences in terms of diagnostic accuracy (89.41% for HHBS vs 92.94% for MRE, P = NS). Magnetic resonance enterography was superior to HHBS in defining CD extension (r = 0.67; P < .01) with a better diagnostic performance than HHBS for detecting location (k = 0.81; P < .01), strictures (k = 0.75; P < .01), abscesses (k = 0.68; P < .01), and fistulas (k = 0.65; P < .01). Conclusion Handheld bowel sonography and MRE are 2 accurate and noninvasive procedures for diagnosis of CD, although MRE is more sensitive in defining extension, location, and complications. Handheld bowel sonography could be used as effective ambulatory (or out-of-office) screening tool for identifying patients to refer for MRE examination due to high probability of CD diagnosis.

(1) Background: Sarcopenia has a high incidence in Crohn’s disease (CD) with considerable heterogeneity among ethnicities and variable impact on clinical outcomes. Aim: to assess the impact of sarcopenia on clinical outcomes in a cohort of Caucasian patients with active CD undergoing CT-enterography (CTE) for clinical assessment. We further investigated the prevalence of sarcopenia and its predictors. (2) Methods: Caucasian CD patients with moderate–severe clinical activity, who underwent CTE in an emergency setting, were retrospectively recruited. The skeletal muscle index (SMI) at the third lumbar vertebra was used to detect sarcopenia in the early stages. Clinical malnutrition was defined according to global clinical nutrition criteria. Clinical outcomes included the rate of surgery and infections within one year. (3) Results: A total of 63 CD patients (34 M; aged 44 ± 17 years) were recruited, and 48 patients (68.3%) were sarcopenic. Malnutrition occurred in 28 patients (44.4%) with a significant correlation between body mass index (BMI) and sarcopenia (r = 0.5, p < 0.001). The overall rate of surgery was 33%, without a significant difference between sarcopenic and non-sarcopenic (p = 0.41). The rate of infection in patients with sarcopenia was significantly higher than in non-sarcopenic (42%vs15%, p = 0.03). BMI (OR 0.73,95%, CI 0.57–0.93) and extraintestinal manifestations (EIM) (OR 19.2 95%, CI 1.05–349.1) were predictive of sarcopenia (p < 0.05). (4) Conclusions: Sarcopenia was associated with an increased rate of infections, and it was observed in 68.3% of the Caucasian cohort with active CD.

Background Assessment of mucosal healing is important for the management of patients with inflammatory bowel disease (IBD), but endoscopy can miss microscopic disease areas that may relapse. Histological assessment is informative, but no single scoring system is widely adopted. We previously proposed an eight-item histological scheme for the easy, fast reporting of disease activity in the intestine. The aim of the present study was to evaluate the performance of our Simplified Histologic Mucosal Healing Scheme (SHMHS). Methods Between April and May 2021 pathologists and gastroenterologists in Italy were invited to contribute to this multicenter study by providing data on single endoscopic–histological examinations for their IBD patients undergoing treatment. Disease activity was expressed using SHMHS (maximum score, 8) and either Simple Endoscopic Score for Crohn’s Disease (categorized into grades 0–3) or Mayo Endoscopic Subscore (range 0–3). Results Thirty hospitals provided data on 597 patients (291 Crohn’s disease; 306 ulcerative colitis). The mean SHMHS score was 2.96 (SD = 2.42) and 66.8% of cases had active disease (score ≥ 2). The mean endoscopic score was 1.23 (SD = 1.05), with 67.8% having active disease (score ≥ 1). Histologic and endoscopic scores correlated (Spearman’s ρ = 0.76), and scores for individual SHMHS items associated directly with endoscopic scores (chi-square p Conclusions SHMHS captures the main histological features of IBD. Routine adoption may simplify pathologist workload while ensuring accurate reporting for clinical decision making.

The management of moderate to severe ulcerative colitis has undergone significant changes over the past 15 years due to the regulatory approval of several new drugs. In particular, following the approval of the first biological, i.e. infliximab, a number of further biological drugs, such as adalimumab, golimumab, vedolizumab and ustekinumab, and small molecules, such as tofacitinib, have been approved, thus enriching the therapeutic armamentarium for ulcerative colitis. Choice of therapy must take into consideration not only the need to induce and maintain disease remission according to the patient's profile, but also age, co-morbidities, and prior treatments. To guide these decisions, the Italian Group for the Study of Inflammatory Bowel Disease has developed clinical guidelines that supersede its earlier document from 2011. These new guidelines were developed following the GRADE methodology for rating the quality of the evidence and for determining the strength of the recommendations. This article presents the methodology and results, in the form of 20 statements with commentary on the use of the five biologics and tofacitinib for managing the intestinal manifestations of active ulcerative colitis and for maintaining remission. A separate technical review reports the analyses of the evidence upon which the present recommendations are based.

Purpose: Over 50% of patients suffering from Crohn's disease (CD) require surgery in their lifetime. Predictors/risk factors of post-operative morbidity and mortality in CD are poorly investigated. We aimed to assess the risk factors of post-operative morbidity/mortality in CD. Methods: We performed a retrospective cohort study in which all CD patients operated and followed up at our tertiary Inflammatory Bowel Disease Centre from 2014 to 2019 were enrolled. For each patient, we evaluated patient-dependent, disease-dependent and surgery-dependent variables. All patients underwent small bowel and/or colic resections. Results: Of the 165 operated patients, forty-two (25.5%) developed post-operative complications (major complication rate = 9.8%) including wound infection (12.1%), respiratory complications (4.8%), prolonged ileum (4.2%), anastomotic leak (3.6%), urinary infections (3%), abdominal abscess (2.4%), anastomotic bleeding (3.6%), abdominal bleeding (1.2%) and obstruction (0.6%). Two subjects (1.2%) required re-operation within 30 days, and one died. A surgery duration

Intussusception is a common condition of bowel obstruction in pediatric patients. However, 5% of all cases occur in adults, mostly aged over fifty, with no difference based on sex, representing about 1% of all causes of bowel obstruction. Compared to pediatric population, it is triggered by a pathologic lead point in about 85% of cases, represented in 60% of cases by malignant and benign neoplasms. Among these neoplasms, an inflammatory fibroid polyp (IFP), a benign neoplastic submucosal lesion also known as Vanek's tumor, is considered a very uncommon cause of adult intussusception. Clinical presentation could differ by location and size of tumor, and may include abdominal pain, nausea, vomiting, diarrhea or constipation, bleeding, weight loss, palpable abdominal mass, bowel obstruction, and gastrointestinal bleeding. Considering its common and non-specific symptoms, radiologic imaging plays a key role in the diagnosis of an IFP, especially computed tomography (CT) scan, which represents the most sensitive modality to confirm intussusception. However, bowel sonography (BS) has become an accurate procedure in various pathological intestinal diseases, also including intussusception. In this paper, we report a rare case of ileo-ileal intussusception secondary to Vanek's tumor diagnosed by BS.

Objectives Anti-TNFα agents have been a staple of Crohn's disease treatment for 20 years, but they have weaknesses. New treatments have more recently become available. The aim of this paper is to examine the Crohn's disease patient population for whom anti-TNF treatments are not preferred and where new mechanisms of action should be considered. Methods A representative sample of 100 Italian physicians with documented expertise with biological treatment of moderate-to-severe Crohn's disease were interviewed. A literature review on Crohn's disease treatment was also conducted to identify patient populations for whom anti-TNFs are unsuitable. Results On the basis of the interviewed physicians, about 9% of moderate-to-severe Crohn's disease patients were noneligible to anti-TNFα due to contraindication or possible risk of intolerance, while 11% had discontinued anti-TNFα treatment due to complications or intolerance/hypersensitivity. Patients with severe heart disease and at high risk of infections were more frequently considered unsuitable. The proportion of patients considered unsuitable among elderly patients and in those with recurrent infections, cancer, and other comorbidities ranged between 40 and 60%. Conclusions We provided additional quantitative and qualitative information to help identify patients who are less suitable to anti-TNF agents, who could benefit from newer biologic agents with different mechanisms of action.

Sclerosing mesenteritis (SM) is an idiopathic disorder affecting mesentery, characterized by fat necrosis, chronic inflammation and fibrosis. The clinical presentation varies from asymptomatic cases to acute abdomen. The diagnosis is suggested by imaging but can be definitely established only by biopsies. In this paper, we discuss ultrasonography-based management of SM.

Background Transmural remission in Crohn’s disease (CD) has been associated with improved long-term clinical outcomes including reduced hospitalization, surgery, escalation of treatment, and a decrease in clinical relapse over endoscopic remission alone. Albeit transmural remission rate (TRR) in CD patients treated with anti-TNF drugs in first line has been well explored, data on TRR using vedolizumab (VDZ) or ustekinumab (UST) as second-line therapy for CD are still scarce. The aim of this study was to evaluate the TRR in CD patients in maintenance treatment, comparing adalimumab (ADA) in first line with VDZ/UST in second line. Methods From 2018 to 2021 we performed a real world observational longitudinal study evaluating the TRR in all consecutive CD patients in a 2-years maintenance treatment with ADA in first line compared with those treated by VDZ or UST in second line. HBI, fecal calprotectin (FC), SES-CD, and bowel wall thickness (BWT) at ultrasound were analyzed in all patients at the baseline (T0) and after 2 years of maintenance treatment (T1). Clinical remission was defined when HBI was Results One hundred and forty-one CD patients (78 ADA, 31 VDZ, 32 UST) were included in the study. At T1, transmural remission rate was recorded in 39.7% of CD patients treated in first line with ADA, and in 22.5% and 18.7% for VDZ and UST, respectively, in second line (ADA vs VDZ/UST: p Conclusion Our findings showed that in CD patients in maintenance treatment with biologics, ADA in first line showed a higher TRR compared with VDZ/UST in second line. Moreover, VDZ and UST showed similar TRR and other outcomes when used in second line.

Background Partial enteral nutrition (PEN) is a consolidated treatment in children with active Crohn’s disease (CD). However, the benefit of PEN is not well-established for adults with CD. Based on the assumption that diet could aid in treating active disease, we aimed to assess the effectiveness of PEN in combination with biological therapy on transmural response/remission and selected clinical outcomes in adults with CD who lost response to biologics Methods We performed a single-centre retrospective observational study by including patients who received PEN due to loss of response to biologics. The primary endpoint was the rate of transmural response/remission at 6 months. We defined transmural remission as a bowel wall thickness ≤3 mm, while transmural response as a decrease in BWT≥25%. Secondary endpoints included clinical remission, defined as Harvey Bradshaw Index Results A total of 42 patients,25 males (59,5%) with mean age of 36,1 ±15,6 yo and a mean duration of disease of 138,0 ±113,1 months were enrolled [Table 1]. Overall, 14 patients completed PEN at 8 weeks, with a rate of adherence of 33,3%. Whilst 16(38.1%) patients stopped the treatment for intolerance and maintained only biological therapy and 12(28.6%) underwent surgery before 6 months follow-up.At 6 months, patients treated with PEN in combination with biologic had a transmural response of 64,9% compared to 25% treated only with biologics (p=0.03). In both groups, no patients achieved transmural remission. Nevertheless, clinical remission was obtained in 9 (64,3%) patients treated with PEN + biologic compared to 4 (25%) with biologic (p=0.03). Overall,3 patients (18.7%) underwent surgery, all of them were intolerant to PEN. Patients who interrupted PEN and maintained biologics had a higher rate 56,2% of dose escalation/interval and 68,7% changed therapy at six months compared to 7,1% and 14,2% respectively treated with PEN+biologic (p Conclusion For patients who lost response to biological therapy, the combination with PEN was associated with transmural response and clinical remission. Multiple failures to biologics were associated with adherence to PEN. Hence, the use of PEN dietary should be considered in difficult-to-treat patients

Background A considerable amount of evidence supports the immunomodulatory role of the appendix in the development and course of Ulcerative Colitis. Indeed, the appendix could act as either a reservoir for commensal bacteria or as the "priming site” for the cytokine production and the immunological cascade triggering inflammation in the colon. Therefore a potential role of the appendix in etiopathogenesis, treatment, prophylaxis and in the colectomy rate in UC has been hypothesized. Given the lack of randomized data on the topic, the ADVANCED-UC trial aims to assess to role of appendectomy in inducing remission in refractory left sided Ulcerative Colitis. Methods Consecutive patients with left-sided UC refractory to conventional treatment and candidate to biologics will be randomized in the standard group (anti-TNF alpha) or in the intervention group (laparoscopic appendectomy). Primary endpoints: Steroid Free Clinical Remission, Endoscopic remission and Assessment of Quality of Life at 3 and 12 months. Secondary endpoints: Clinical Response, Failure Rate, Complication rate and Histological Remission at 3 and 12 months; Colectomy rate at 12, 24 and 60 months. To obtain a significance level of 5% and a test power of 90%, it is required a sample size of 148 patients (74 patients per group), assuming a 25% success rate in the control group and a 50% success rate in the experimental group. The study has been already approved by our local IRB (num. 340/21) and has been granted with the Spring Award from the Surgical Research Network by the Crohn’s and Colitis Foundation (CCF). We plan to start the enrollment in 2023 and we are currently recruiting potential participating centers, to run a multicenter, randomized controlled trial Results The findings of this study could support a change of treatment paradigm for patients refractory to conventional therapy: indeed, while an appendectomy can protect UC patients from the future use of expensive or potentially dangerous drugs, or even major surgery, the initial additional costs and potential side effects of appendectomy will be offset by substantial health gains and reduced costs later in time. On the other hand, patients undergoing appendectomy which do not experience disease remission and are forced to start biologics will be followed up for the evaluation of the colectomy rate to evaluate the possible synergic effect of appendectomy and biologics in reducing the need for total colectomy in the long term. Conclusion The aim of this study is to define the role and effects of laparoscopic appendectomy as a therapeutic option in patients with UC refractory to conventional therapy who are candidates, in the first instance, for biologic anti-TNF-a therapy.

Background The orally administered small molecule drug pan-Jak inhibitor tofacitinib (TFB) appears to be effective in the treatment of ulcerative colitis (UC), however, available real world studies are limited by the cohort size. In addition, TFB may also be efficacious in patients with acute severe colitis (ASUC) as a rescue therapy. We aimed to conduct an international cohort study, to investigate the efficacy and safety of TFB in patients with moderate to severe colitis and ASUC. Methods This was a retrospective, international multi-centre, cohort study including 23 tertiary referral centres. UC patients with at least 6 weeks of TFB treatment were included. Physicians categorized the indication as rescue therapy (RT) and chronic activity (CA). Baseline demographic and clinical data, clinical/endoscopic activity indexes, laboratory parameters (including CRP, faecal calprotectin, liver enzymes, lipids, iron homeostasis), adverse events, and hospitalization/colectomy rates were collected at w0, w2-6, w8-14, w22-30 and w48-56 intervals. Steroid-free remission, colectomy rates, primary non-response (PNR) and loss-of response (LOR) rates, and safety was studied. Results A total of 391 UC patients (mean age: 39.2±14.1 years, male/female ratio 208/183; mean follow-up period 33.7±18.1 weeks) were included. 107 patients (27.4%) received TFB as a rescue therapy. Most of the patients received it as a third line treatment (37.4%). Steroid-free remission (SFR) rates were 21.3% (RT: 25.0%, CA: 22.3%) at w14, and 40.1% (RT: 32.5%, CA: 42.2%) at w52. In total, baseline pMayo (OR: 0.856; p=0.007) was negatively associated with w12 SFR, while line of treatment (OR: 0.749; p=0.047) and age (OR: 1.022; p=0.038) influenced the w52 SFR in the CA group. The w12 colectomy rate was 5.1%, and no difference was observed between groups (RT: 8.5%; CA: 3.8%), however, w52 colectomy rate was higher in the RT group (19.2% compared to 5.9%; p Conclusion TFB is effective in both moderate to severe UC, and in patients with ASUC as a rescue therapy. TFB treatment resulted in high rates of SFR and mucosal healing in short- and long term even after anti-TNF and vedolizumab failure. Higher baseline disease activity and number of previous biological therapies negatively influenced efficacy. Serious adverse events were rare.

Background Intestinal ultrasound (IUS) is an effective and easy-to-use tool in monitoring Crohn’s disease (CD) lesions during different biological therapies. Aim of our study was to evaluate whether lesion improvement during biological therapy could predict transmural healing. Methods We performed a prospective study enrolling CD patients (pts) with indication to biological therapies. IUS and doppler US parameters at baseline, at 3 and 12 months were: bowel wall thickening (BWT), lesion length, echopattern, complications, blood flow according to Limberg’ score. Transmural healing (TH) was defined as normalization of all parameters; IUS responders were defined as pts with improvement of BWT associated with decreased lesion length, Limberg’ score improvement, and no worsening of the other parameters. Delta (Δ) signified the difference between IUS parameters at baseline and at 3 months. Changes in parameters and in Δ values at baseline and after 3 months were analyzed using Mann Whitney test; the area under (a ROC) curve was calculated. Differences between combination of parameters were tested by Chi-square test. Results One hundred and fifteen CD pts were enrolled (63.5% males; median age 37 years; median disease duration 96 months). Forty-nine per cent of pts had L1, 9% had L2, 42% had L3 according to the Montreal criteria. TH rate at 12 months was 20% and IUS responder rate was 43%. At baseline, no statistical differences in terms of BWT were observed between pts achieving TH vs no TH. Similarly, no differences were observed in pts defined as IUS responders vs non responders. Patients achieving TH at 12 months had a higher ΔBWT than patient without TH (p=0.0004). On ROC curve, ΔBWT improvement of 1.25 mm showed sensitivity and specificity of 73% and 61%, respectively, in predicting pts who achieved TH. Similarly, IUS responder group at 12 months had a higher ΔBWT than patients IUS non-responder group (p Conclusion An early ΔBWT, and a combination of a ΔBWT and Limberg’ score improvement showed high diagnostic accuracy in predicting pts who achieved TH and IUS responder at 12 months. This information may help clinical decision making in terms of prompt optimization or switching/swapping therapies in CD.

Background Ulcerative colitis (UC) diagnosis and monitoring still require ileo-colonoscopy (IC) as the reference standard. Bowel sonography (BS) has recently emerged as a non-invasive assessment tool, and Milan Ultrasound Criteria (MUC) score has been validated to estimate and predict UC disease activity. Recently, hand-held BS (HHBS) has been used effectively in several clinical settings (e.g. cardiology, orthopedy, gynaecology), while data about its use in UC are still limited. We aimed to evaluate the diagnostic accuracy of HHBS compared to conventional bowel sonography (BS) in predicting UC extension and activity compared to endoscopy. Methods From November 2021 to September 2022, we prospectively enrolled consecutive UC patients afferent to our third-level IBD Unit for IC evaluation. Patients underwent IC, HHBS, and BS, and the operators were blinded by the other procedure results. Endoscopy was considered the reference standard for UC extension. Cohen’s k test was applied after MUC dichotomization to test the concordance between BS-MUC and HHBS-MUC following Allocca et al. (MUC >6.2: yes/no). Results At the end of the study, 86 patients with UC were examined. No significant difference was recorded between BS and HHBS in terms of UC at the per-segment extension (p: N.S.) (table 1), and both procedures were comparable regarding colonic wall thickness (CWT) and colonic wall pattern (CWP) assessment (figure 1 and 2). Regarding the prediction of endoscopic activity, BS and HHBS displayed excellent agreement when applying the MUC score system (k = 0.86, p Conclusion Hand-held bowel sonography and BS are comparable in defining UC extension and MUC evaluation in the UC setting. HHBS could be reliable for detecting disease activity and estimating its extension, providing close monitoring of the treat-to-target paradigm. It also represents a non-invasive, easily practicable investigation during a physical examination, allowing immediate medical decisions with significant time and cost advantages.

Aluminum is an element found in nature and in cosmetic products. It can interfere with the metabolism of other cations, thus inducing gastrointestinal disorder. In cosmetics, aluminum is used in antiperspirants, lipsticks, and toothpastes. The aim of this work is to investigate aluminum bioavailability after accidental oral ingestion derived from the use of a toothpaste containing a greater amount of aluminum hydroxide than advised by the Scientific Committee on Consumer Safety (SCCS). To simulate in vitro toothpaste accidental ingestion, the INFOGEST model was employed, and the amount of aluminum was measured through the ICP-AES analysis. Tissue barrier integrity was analyzed by measuring transepithelial electric resistance, and the tissue architecture was checked through light microscopy. The margin of safety was also calculated. Overall, our results indicate that the acute exposure to aluminum accidentally ingested from toothpastes is safe for the final user, even in amounts higher than SCCS indications.

DNA barcoding is a versatile approach that has revolutionized taxonomy and other akin topics in biology and ecology, due to its simplicity and relatively costless procedures. The method consists in the production of one or a few amplicons from informative genetic regions via Sanger sequencing. These markers are selected because they tend to evolve at a similar pace as speciation, allowing to discriminate organismal species. The applicability of this technique is here portrayed for the taxonomical identification of marine sponges (phylum: Porifera) as an exemplification.

In the present study, we were interested to investigate how autistic traits (including systemizing and empathy) and academic degree influence individuals’ visuospatial abilities. To this end, 352 university students completed the Autism Spectrum Quotient (AQ), the Empathy Quotient, the Systemizing Quotient (SQ) and visuospatial tests measuring figure disembedding and mental rotation of two-dimensional figures. Engineering-design students (architecture and engineering) were the most accurate in disembedding and mentally rotating figures, followed by students of physical sciences (computer science, chemistry, physics, etc.) and fact-based humanities (languages, classics, law); biological (psychology and neuroscience, etc.) and systems-based social scientists (economics and commerce) were the least accurate. Engineering-design students also showed higher SQ scores with respect to the other four academic degree subjects, with students of biological sciences showing lower SQ scores. Importantly, results from a path analysis revealed that SQ (but not AQ) exerted an indirect effect on figure disembedding and mental rotations through the influence of the academic degree. Thus, the present findings reveal shadydifferences in systemizing degree and visuospatial performance withinsystemizing-based degree subjects.Implications for education are discussed.