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Podocyte injury leading to albuminuria is a characteristic feature of diabetic nephropathy (DN). Hyperglycemia and advanced glycation end products (AGEs) are major determinants of DN. However, the underlying mechanisms of podocyte injury remain poorly understood. The cytosolic protein TNFAIP2/M-Sec is required for tunneling nanotubes (TNTs) formation, which are membrane channels that transiently connect cells, allowing organelle transfer. Podocytes express TNFAIP2 and form TNTs, but the potential relevance of the TNFAIP2-TNT system in DN is unknown. We studied TNFAIP2 expression in both human and experimental DN and the renal effect of tnfaip2 deletion in streptozotocin-induced DN. Moreover, we explored the role of the TNFAIP2-TNT system in podocytes exposed to diabetes-related insults. TNFAIP2 was overexpressed by podocytes in both human and experimental DN and exposre of podocytes to high glucose and AGEs induced the TNFAIP2-TNT system. In diabetic mice, tnfaip2 deletion exacerbated albuminuria, renal function loss, podocyte injury, and mesangial expansion. Moreover, blockade of the autophagic flux due to lysosomal dysfunction was observed in diabetes-injured podocytes both in vitro and in vivo and exacerbated by tnfaip2 deletion. TNTs allowed autophagosome and lysosome exchange between podocytes, thereby ameliorating AGE-induced lysosomal dysfunction and apoptosis. This protective effect was abolished by tnfaip2 deletion, TNT inhibition, and donor cell lysosome damage. By contrast, Tnfaip2 overexpression enhanced TNT-mediated transfer and prevented AGE-induced autophagy and lysosome dysfunction and apoptosis. In conclusion, TNFAIP2 plays an important protective role in podocytes in the context of DN by allowing TNT-mediated autophagosome and lysosome exchange and may represent a novel druggable target. Abbreviations: AGEs: advanced glycation end products; AKT1: AKT serine/threonine kinase 1; AO: acridine orange; ALs: autolysosomes; APs: autophagosomes; BM: bone marrow; BSA: bovine serum albumin; CTSD: cathepsin D; DIC: differential interference contrast; DN: diabetic nephropathy; FSGS: focal segmental glomerulosclerosis; HG: high glucose; KO: knockout; LAMP1: lysosomal-associated membrane protein 1; LMP: lysosomal membrane permeabilization; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; PI3K: phosphoinositide 3-kinase; STZ: streptozotocin; TNF: tumor necrosis factor; TNFAIP2: tumor necrosis factor, alpha-induced protein 2; TNTs: tunneling nanotubes; WT: wild type.

Background Inflammatory Bowel Disease (IBD) and endometriosis are chronic inflammatory diseases occurring in young women, sharing some clinical manifestations. We aimed to investigate, in a multidisciplinary approach, symptoms, type and site of pelvic endometriosis in IBD patients versus non-IBD Controls with endometriosis. Methods In a prospective nested, case-control study, all female premenopausal IBD patients showing symptoms compatible with endometriosis were enrolled. Patients were referred to dedicated gynecologists for assessing pelvic endometriosis by transvaginal sonography (TVS). Each IBD patient with endometriosis (Cases) was retrospectively matched for age (±5 years) and body mass index (±1) with 4 patients with endometriosis at TVS, but no-IBD (Controls). Data were expressed as median [range], the Mann-Whitney or Student-t and χ2 tests were used for comparisons. Results Endometriosis was diagnosed in 25 (71%) out of 35 IBD patients with compatible symptoms including 12 (52.6%) Crohn’s Disease and 13 (47.4%) Ulcerative Colitis patients. Dyspareunia and dyschezia were significantly more frequent in Cases vs Controls (25 [73.7%] vs 26 [45.6%]; p=0.03). At TVS, deep infiltrating endometriosis (DIE) and posterior adenomyosis were significantly more frequent in Cases vs Controls (25 [100%] vs 80 [80%]; p=0.03 and (19 [76%] vs 48 [48%]; p=0.02). Conclusion Endometriosis was detected in two/thirds of IBD patients with compatible symptoms. The frequency of DIE and posterior adenomyosis was higher in IBD than in Controls. A diagnosis of endometriosis, often mimicking IBD activity, should be considered in subgroups of female patients with IBD.

Background Intestinal ultrasonography (IUS) is a non-invasive, easily accessible and low-cost procedure to visualize the colon and determine disease activity, extent and treatment response in IBD. Our aim was to investigate whether ultrasonographic parameters predict short-term clinical remission in ulcerative colitis (UC). Methods Consecutive patients (pts) with moderate-to-severe UC (total Mayo score>6) starting biological therapies or small molecules were included. Patients were evaluated at baseline by clinical, biochemical, endoscopic (endoscopic Mayo score), and IUS assessments. IUS, doppler and elastographic parameters assessed at baseline before starting therapy were: bowel wall thickening (BWT), echopattern, blood flow (adapted Limberg’ score), Milan Ultrasound criteria (MUC) and shear wave elastography values. The most affected colonic segment was used for all imaging assessments. Clinical remission at 3 months was defined as partial Mayo Score=0-1. Predictive factors of clinical remission at 3 months were analyzed by logistic regression. ROC curve analysis was used to identify the best cut-off of BWT in predicting clinical remission. Results Thirty-one UC pts were enrolled (12 males [39%]; median age: 45 years, range 18-72; median disease duration: 108 months, range 3-312). Sixteen per cent of pts had left colitis and 84% had extensive UC according to the Montreal criteria. Forty-eight per cent of pts were treated with Anti-TNFs, 39% with vedolizumab, 10% with ustekinumab and 3% with tofacitinib. At baseline, 84% of patients had moderate disease and 16% severe disease according to the total Mayo score. A lower total Mayo score and partial mayo score at baseline were predictive of clinical remission at 3 months after starting biological therapy or small molecules than endoscopic Mayo score (OR 0.58, 95% CI 0.33-0.99, p=0.03; OR 0.55, 95% CI 0.29-0.99, p=0.037; OR 0.57, 95% CI 0.16-1.93, p=0.36, respectively; Figure 1, panels A-C). A lower BWT, Limberg’ score and MUC at baseline were predictive of clinical remission at 3 months (OR 0.19, 95% CI 0.05-0.72, p=0.0023; OR 0.22, 95% CI 0.06-0.77, p=0.004; OR 0.48, 95% CI 0.21-0.83, p=0.001, respectively; Figure 1, panels D-F). The most accurate cut-off value of BWT for predicting clinical remission was Conclusion IUS easily predicts early clinical remission in patients with moderate-to-severe UC after therapy.

Background Data on the outcomes of surgery due to IBD in pregnant patients is scarce, and primarily dates back more than 3 decades ago. Primary aim: to evaluate the evolution of pregnancies and offspring after surgery due to IBD. Secondary aims: to describe the indications for surgery, the surgical techniques used, and the frequency of caesarean section concomitant to surgery for IBD Methods SCAR is a retrospective, multicenter study approved by ECCO COllaborative Network For Exceptionally Rare Case Reports (CONFER). Patients operated on due to IBD during pregnancy after 1998 (first biologic agent approved) were included. Data on patients’ demographics, IBD characteristics, medical treatments, IBD activity, pregnancy outcomes, surgery, delivery, foetal and maternal outcomes, were recorded Results 44 IBD patients were included (figure 1), all singleton pregnancies. Seven patients (16%) were diagnosed with IBD during pregnancy, 75% had Crohn’s disease (51% fistulizing behavior), and 23% had ulcerative colitis. 34% had previously undergone surgery due to IBD. Several complementary examinations were performed during pregnancy without complications (figure 2) Patients were being administered the following medications: corticosteroids (61%), biologicals (57%), thiopurines (23%) with 20% being on biologics and thiopurines. 93% of surgeries were performed in University hospitals, (2nd Trimester: 55%; 3rd trimester: 27%) with 77% of them being urgent surgeries (figure 3) One patient had hemoperitoneum during surgery, and 27% had postsurgical complications. No woman died. 62.5% of deliveries were induced (figure 4), 70% of them by C-section, with 51% of mothers having a prolonged hospitalization. There were 40 newborns alive and 4 miscarriages/stillbirths (1 in the 1st, 2 in the 2nd, and 1 in the 3rd trimester): 2 occurred during surgery and 2 occurred 2 weeks after surgery. 14% of the surgeries during the 2nd trimester and 64% of those in the 3rd trimester ended up with a simultaneous C-section or delivery. Of the 40 newborns alive, there were 9 healthy (24%), 61% premature, and 47% with low birth weight. A total of 42% of newborns needed hospitalization (25% in the intensive care unit, mainly due to respiratory distress) Conclusion The need for surgery for IBD during pregnancy remains an extremely serious situation. Maternal and foetal mortality are lower than previously described, most likely due to better supporting care. However, even in the current years, 30% of the mothers and 80% of newborns have complications, and 25% of the offspring need admission to the intensive care unit. Therefore, surgical management should be performed by a multidisciplinary team, involving gastroenterologists, colorectal surgeons, obstetricians and neonatal specialists.

In a prospective study, SARS-CoV-2 IgG seroprevalence was assessed during the second pandemic wave (W2) in a cohort of Inflammatory Bowel Disease (IBD) patients using biologics. The secondary aim was to compare, in the same cohort, the frequency of seropositivity and of COVID-19 during the second vs. the first (W1) wave.From November 2020 to March 2021, SARS-CoV-2 IgG seropositivity and the prevalence of COVID-19 were assessed in a cohort of IBD patients using biologics already studied at W1.age ≥ 18 years; diagnosis of IBD; follow-up; written consent.SARS-CoV-2 vaccination. Risk factors for infection, compatible symptoms, history of infection or COVID-19, nasopharyngeal swab test were recorded. Data were expressed as median [range]. The χ2 test, Student's t-test, logistic regression analysis was used.IBD cohort at W1 and W2 included 85 patients: 45 CD (52.9%), 40 UC (47.1%). When comparing the same 85 patients at W2 vs. W1, a higher SARS-CoV-2 seroprevalence at W2 was at the limit of the statistical significance (9.4% vs. 2.3%; p=0.05). The prevalence of COVID-19 at W2 vs. W1 was 3.5% (3/85) vs. 0% (0/85) (p=0.08). Contacts with COVID-19 patients and symptoms compatible with COVID-19 were more frequent at W2 vs. W1 (18.8 % vs. 0%; p=0.0001; 34.1% vs. 15.3%; p=0.004). At W2, history of contacts and new onset diarrhea were more frequent in seropositive patients [4/8 (50%) vs. 12/77 (15.6%); p=0.01 and 4/8 (50%) vs. 2/77 (2.6%); p=0.0001]. At W2, the risk factors for seropositivity included cough, fever, new onset diarrhea, rhinitis, arthromyalgia, dysgeusia/anosmia at univariate (p0.05), but not at multivariate analysis. History of contacts was the only risk factor for seropositivity at univariate (p=0.03), but not at multivariate analysis (p=0.1).During W2, characterized by a high viral spread, IBD and biologics appeared not to increase the prevalence of SARS-CoV-2 infection or COVID-19 disease. New onset diarrhea mimicking IBD relapse may be observed in patients with SARS-CoV-2 infection.

Background Colorectal cancer (CRC) risk is increased in patients (pts) with long-standing colitis related to Inflammatory Bowel Disease (IBD). A higher frequency mucinous and signet-ring colonic adenocarcinoma has been suggested in IBD, but data regarding risk factors for these aggressive CRC are currently lacking. Primary aim was to assess the frequency of mucinous and signet-ring adenocarcinoma in IBD pts with CRC. Secondary aim was to assess risk factors for these histotypes of CRC. Methods From January 2002 to July 2022, all IBD pts with concomitant CRC were retrospectively enrolled. Inclusion criteria: 1) age ≥18; 2) well-defined diagnosis of IBD and CRC; 3) available histological and surgical report. Exclusion criteria: Missing data. Characteristics of IBD were reported according to standard criteria. Data were expressed as median [range]. Student-t Test and χ2 test were used for comparisons. Univariate logistic regression model was applied for assessing risk factors for mucinous and signet-ring adenocarcinoma (OR [95%CI]). Results The study population included 40 IBD pts with concomitant CRC: 24 (60%) with Ulcerative Colitis (UC) and 16 (40%) with Crohn’s Disease (CD). CRC included standard adenocarcinoma in 23 (57.5%) and mucinous or signet-ring in 17 (42.5%) pts. CD was more frequently stricturing in pts with standard adenocarcinoma (7 [77.8%] vs 1 [14.4%], p=0.04). CRC most frequently involved the rectum in pts with mucinous or signet-ring adenocarcinoma vs standard adenocarcinoma (4 [17.4%] vs 8 [47.1%]; p=0.04). Other IBD characteristics did not differ between standard and mucinous or signet-ring adenocarcinoma, including: age at CRC diagnosis (61 [30-80] vs 53 [29.80]; p=0.61), gender (F): 8 [34.8%] vs 5 [29.4%]; p=0.98), IBD duration at CRC diagnosis (14 [1-45] vs 17 [1-36]; p=0.74), smoking status (p=0.78), IBD type (UC: 14 [60.9%] vs 9 [56.3%]; p=0.84), UC extent and CD localization, frequency of perianal disease (p=0.37), thiopurine (p=0.55) or biologic (p=0.55) use. The proportion of pts surgically treated for CRC (20 [86.9%] vs 17 [100%], p=0.34) and the frequency of CRC-related death (3 [13.1%] vs 5 [29.4%]; p=0.37) were also comparable between groups. At diagnosis, CRC stage was comparable between pts with standard vs mucinous or signet-ring adenocarcinoma (stage I: 6 [26.1%] vs 1 [5.9%]; p=0.21; II: 9 [39.1%] vs 4 [23.5%]; p=0.48; III: 5 [21.7%] vs 7 [41.2%]; p=0.34); IV: 3 [13.1%] vs 2 [11.8%]; p=0.71). At univariate analysis, no specific risk factors for mucinous and signet-ring colonic adenocarcinoma were detected. Conclusion In the tested cohort of IBD patients with CRC, mucinous and signet-ring adenocarcinomas were observed in almost half of cases, although no specific risk factors were identified.

Background The use of ustekinumab (UST) and vedolizumab (VDZ) as second line therapy in Crohn’s disease (CD) patients failing tumour necrosis factor alpha inhibitors is still debated. The aim of the study was to compare in a large multicentre observational retrospective cohort, the effectiveness of UST and VDZ as second line therapy as assessed by clinical and objective outcomes including endoscopy and gastro intestinal (GI)-imaging. Methods Clinical response, remission and steroid-free remission at week 26 and 52 were evaluated in a retrospective cohort of CD patients previously experienced TNF-alpha inhibitors (primary or secondary failure, and intolerant). Objective response and remission were evaluated by one or more techniques including ileocolonoscopy, magnetic resonance (MR)/computer tomography (CT) enteroclysis and small bowel ultrasound (US) performed within 3 months before the beginning of the treatment and after one year of therapy. Inverse propensity of treatment weighting (IPTW) and propensity score matching (PMS) methods were used for statistical analysis. Results 470 CD patients (239 UST and 231 VDZ) were included in the study. At week 26 clinical response, clinical remission and steroid free remission were similar between the two groups (Figure 1) At week 52, clinical remission and steroid-free remission rates were significantly higher in VDZ-treated patients (clinical remission: UST 42.5% vs VDZ 55.5%, p=0.01; steroid-free clinical remission UST 40.6% vs VDZ 51.1%, p=0.038; Figure 1). 302 patients (135 UST and 167 VDZ) had objective evaluation of disease activity at baseline and week 52. At week 52 objective response and remission rates were similar between the groups. (Figure 2). Clinical response at week 26 predicted steroid-free remission at week 52 in both UST- and VDZ-treated patients. Safety profiles were similar between the two groups. Conclusion One-year treatment with VDZ was associated with higher rate of clinical remission as compared to UST, but no difference was observed between the two groups when objective outcomes were investigated

BackgroundMicronutrients play immunomodulatory roles through interactions with innate and adaptive immunity influencing the pro/anti-inflammatory balance. Serum levels depend on multiple factors such as gender, nutrition, and gut microbiome. Micronutrient deficiencies (MNDs) are associated with a pro-inflammatory status and co-morbidities in patients with chronic inflammatory diseases. No studies focused on potential interplay between MNDs and disease phenotype in Enteropathic Spondyloarthritis (ESpA) in which the combination of SpA with inflammatory bowel diseases (IBD) might dramatically affect micronutrients status.ObjectivesWe analysed the occurrence of anemia (Hb ≤12 g/dl) and deficiencies of ferritin (Fe, ≤15 ng/dL), vitamin D [25(OH)D, ≤20 ng/ml], vitamin B12 (VB12, ≤200 pg/ml), and folic acid (FA, ≤ 4ng/mL) in ESpA patients. The interplay of MNDs with gender, metabolic parameters, HLA-B27 susceptibility, type of SpA and IBD, disease activity, and treatments was also explored.MethodsSelection criteria of this cross-sectional descriptive study consisted of having a diagnosis of ESpA, regardless of its type, in an age of ESpA onset ≥18 and ≤80 years, among patients who were admitted to a combined Gastro-Intestinal and RHEumatologic “GI–Rhe” clinic (Tor Vergata University Hospital, Rome, Italy). Exclusion criteria were represented by active IBD, pregnancy or lactation, kidney and/or liver failure, alcohol abuse, neoplasia, ongoing supplementations. SpA disease activity was assessed by ASDAS-CRP and functional status by HAQ-S. All the enrolled patients underwent blood chemistry analysis to determine parameters including CRP, uric acid (SUA), Fe, 25(OH)D, VB12, FA, and HLA-B27 typing.ResultsWe included 164 patients comprising 109 females and 55 age-matched males. A diagnosis of Crohn’s Disease (CD) occurred in 70% of patients while Ulcerative Colitis (UC) represented a third of the cohort. Peripheral (per) and axial (ax) SpA were equally distributed (50%vs50%). Patients with ax-SpA displayed a greater prevalence of CD than UC (p=0.02) while UC was prevalent in per-SpA (p=0.02). B27+ was revealed in 19% of our cohort: B27+ patients had a higher prevalence of ax-SpA (p=0.016) and a more severe disease activity (p=0.02) than B27-. Moreover, B27 positivity and uveitis were prevalent in ax-SpA compared to per-SpA (p=0.009 and p=0.01, respectively). According to univariate analysis, males showed higher SUA (P=0.004) and BMI (p=0.03) than females. Conversely, females showed a higher prevalence of anemia than males (p=0.002). A third of ESpA cohort showed FA (31.6%) and 25(OH)D (27.8%) deficiency while VB12 defect was less frequent (18.2%) and was registered almost entirely in B27- ESpA (p=0.02). CD-ESpA showed a lower mean VB12 (p=0.04) and a higher prevalence of ocular/skin co-morbidities (p=0.02) and ax-SpA (p=0.04) than UC-ESpA. Accordingly, CD-ESpA were on bDMARDs more than UC-ESpA (p=0.04).ConclusionOur findings document that FA and 25(OH)D deficiencies represent the main MNDs among ESpA patients while VB12 seems to be deficient mostly in patients with CD and almost exclusively in B27- patients. Otherwise, B27+ in ESpA results to be associated mainly with disease phenotype and treatments. In ESpA, the gender of patients appears to impact principally on dysmetabolism highlighting the role for nutritional interventions particularly in males. The interplay of MNDs with B27 and dysmetabolism in ESpA deserves further investigations also taking into account CD/UC localization and behavior.References[1]Park YE, et al. Incidence and risk factors of micronutrient deficiency in patients with IBD and intestinal Behçet’s disease: folate, vitamin B12, 25-OH-vitamin D, and ferritin. BMC Gastroenterol. 2021;21(1):32.doi: 10.1186/s12876-021-01609-8.[2]Conigliaro P, et al. Impact of a multidisciplinary approach in enteropathic spondyloarthritis patients. Autoimmun Rev. 2016;15(2):184-90.doi: 10.1016/j.autrev.2015.11.002.Disclosure of InterestsNone declared

Treatments used in Inflammatory Bowel Disease (IBD) have been associated with enhanced risk of viral infections and viral reactivation, however, it remains unclear whether IBD patients have increased risk of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. The aim of the study was to examine the prevalence of SARS-CoV-2 IgG positivity in IBD patients followed at our referral center. The role of treatments for IBD and risk factors for infection were also evaluated.In a prospective study, all IBD patients followed at our referral centre between May 27th and July 21st, 2020 and fulfilling the inclusion criteria were tested for SARS-CoV-2 IgG. Specific IgG antibodies were evaluated by a commercial ELISA kit and SARS-CoV-2 nasopharyngeal swab was performed in seropositive patients.Two-hundred and eighteen patients, 128 Crohn's disease (CD) and 90 Ulcerative colitis (UC) [age 44, (19-77) years; ongoing biologics in 115 (52.7%)] were enrolled. No patient had major SARS-CoV-2-related symptoms. SARS-CoV-2 IgG were detected in 3 out of 218 (1.37%) patients with IBD (2 CD and 1 UC), all on biologics (2.6%). In all of the 3 seropositive patients, the nasopharyngeal swab was negative. There was no relationship between SARS-CoV-2 seroprevalence and the demographic/clinical characteristics of IBD patients. In contrast, history of recent travel was more frequent in the SARS-CoV-2 seropositive patients (2/3; 66.6%) than in SARS-CoV-2 seronegative patients [7/215 (3.25%); p0.0001].The prevalence of SARS-CoV-2 IgG seropositivity in IBD patients appears to be comparable to the non-IBD population and not influenced by ongoing treatments. Risk factors for infection common to the general non-IBD population should be considered when managing patients with IBD.

Crohn's Disease (CD) has been associated with non-Hodgkin lymphoma. Follicular Lymphoma (FL) limited to the liver is extremely rare, accounting for 1% to 4.4% of all Primary Hepatic Lymphoma (PHL).In 2018, an 85-years old male patient with post-operative recurrence of ileal CD referred rare episodes of fever and mild diffuse abdominal pain. Since cholecystectomy in 2001, clinical history was characterized by recurrent episodes of cholangitis and common bile duct stones. In 2018, ultrasonography and MRI showed a solid focal hepatic lesion (FHL)(4.5 cm x 2.5 cm) in the IV hepatic segment. The radiographic aspect of the lesion was unusual. Initially, focal nodular hyperplasia was suspected. Clinical history of cholangitis and radiological findings subsequently suggested a diagnosis of Hepatic Abscess (HA). A progressive enlargement of the FHL (7.3 cm x 5.8 cm) despite antibiotic treatments, led to perform a liver biopsy. Histological and immunophenotypical analysis of the FHL (7.5 cm x 5.4 cm) enabled a final diagnosis of FL. The "in situ" hybridization for Epstein-Barr virus (EBER) was negative. No additional lesions related to FL were initially detected, thus suggesting a very rare case of PHL in an old patient with CD never treated with thiopurines.This case report highlights the need to consider a rare diagnosis of FL of the liver in patients showing a challenging focal hepatic lesion of unknown origin.

Background Ustekinumab (UST) is increasingly used in Italy for the treatment of refractory Crohn’s disease (CD), however very few data concerning real-life experience has been reported. Therefore, the aim of this study was to assess the long-term effectiveness of UST in refractory CD patients treated in a large Italian cohort. Methods A retrospective study was conducted in 5 Italian tertiary centers. All adult CD patients who started UST because of anti-tumor necrosis factor (TNF) failure were included. The co-primary outcomes were steroid-free clinical remission (defined as Harvey Bradshaw Index, HBI ≤4) at weeks 26 and 52. Secondary outcomes were changes in HBI score, changes in C-reactive protein (CRP) values, normalization of CRP (≤0.5 mg/dl) at weeks 8, 26, and 52, and adverse events. Categorical variables were expressed as frequency and percentage. Unpaired t-test was used to compare variables. A p-value Results Between Nov 2018 and Feb 2020,140 patients (51.4% male; median age 45.0 years, IQR 36.3-54.0; median disease duration 16.0 years, IQR 8.0-22.0) were included. The majority of patients had ileocolonic disease (L1, 38.6%; L2, 11.4%; L3, 50.0%) and an inflammatory phenotype (B1, 50.7%; B2, 31.0%; B3, 18.3%). All patients had previously been exposed to at least one anti-TNF agent, 27.1% to 2 anti-TNF agents, and 20.0% to vedolizumab . At inclusion 15.7% of patients received corticosteroids and 8.6% immunomodulators. All patients received an intravenous dose of 6 mg/kg, followed by subcutaneous administration of 90 mg every 8 (90%) or 12 weeks (10%) according to clinical judgment. The proportion of patients achieving steroid-free clinical remission was 61.0% and 64.2% at weeks 26 and 52 respectively. A significant decrease in the mean HBI was reported from baseline to week 8 (6.8 ± 3.6 vs 4.5 ± 3.1; p Conclusion To our knowledge this is one of the largest Italian cohort followed up to 1 year, and the results confirm that UST is an effective and safe treatment in refractory CD patients.

Background The role of histological activity in clinical management of ulcerative colitis (UC) is under investigation. Primary aim was, in a prospective study, to assess the role of histological activity as predictor of clinical relapse in a cohort of UC patients (patients) undergoing colonoscopy and followed-up for 1 year. Secondary aim was to assess the correlation between clinical, endoscopic and histological activity scores. Methods From February 2016 to February 2017 consecutive UC patients with clinical indication for colonoscopy were enrolled and clinically followed-up for 1 year. Inclusion criteria: (1) UC diagnosis; (2) Age > 18, ≤ 80 years; (3) regular follow-up; (4) indication for colonoscopy. During colonoscopy ≥2 biopsies was taken from ≥1 macroscopically involved and, possibly, from ≥1 uninvolved area. The day of colonoscopy clinical activity was assessed by the Mayo partial score, endoscopic activity by the Mayo endoscopic score, histological activity by the Geboes Simplified Score (GSS). Scores blindly assessed by three investigators. Statistical analysis: data expressed as mean [range], Spearman’s correlation coefficients, Cox hazards regression model used for univariate and multivariate analyses to identify predictors of clinical relapse at 1 year (HR[95% CI]). Results UC cohort included 77 UC patients. Characteristics of these 77 UC patients: 43 (55.8%) males, age 51 [24–80]; UC duration 14.7 [1–48] years. UC extent included n (%): 33 (42.8%) pancolitis, 24 (31.2%) left-sided, 20 (26%) proctitis. The day of colonoscopy, UC was clinically active in 15 (19.4%), inactive in 62 (80.6%) patients. Endoscopic activity was observed in 39 (50.6%) patients, histological activity (GSS≥ 3.1) in 37(48%) patients. Moderate correlations were observed between clinical and endoscopic scores (r = 0.439;p < 0.0001) clinical and histological scores (r = 0.32;p = 0.0045), endoscopic and histological scores (r = 0.653;p < 0.0001). During the clinical follow-up at 1 year, UC clinical relapse occurred in 24 (31%) patients, while 53 (69%) patients maintained clinical remission. At baseline colonoscopy, 11/24 (46%) UC patients were clinically active, 15/24 (63%) showed endoscopic activity and 16/24 (67%) patients histological activity. Univariate analysis identified clinical activity (HR 4.82 [2.15–10.82]; p < 0.001) and histological activity (HR 2.599 [1.11–6.08]; p < 0.027) as significant predictive factors for clinical relapse at 1 year. Multivariate model confirmed histological activity as predictive marker of clinical relapse (HR 2.44 [1.04–5.75]; p < 0.041). Conclusion Histological activity provided independent information for clinical relapse in a cohort of UC patients prospectively followed up for 1 year. Histological activity had a significant correlation with the endoscopic and clinical activity scores.