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Background Patients with Crohn's disease (CD) after Ileo-colic resection may develop an endoscopic postoperative recurrence (ePOR) that reaches approximately 70% of incidence within six months. ECCO guidelines favour a stapled side-to-side anastomosis. However, the advent of the Kono-S ileocolic anastomosis, a hand-sewn antimesenteric functional end-to-end anastomosis, seems to reduce clinical risk and ePOR. Whilst the majority of the studies have assessed the rate of ePOR individually, currently there is limited data comparing surgical techniques of the anastomosis. Hence, we aimed to assess the impact of different surgical techniques on ePOR in CD Methods We searched PubMed and Embase in October 2022 for eligible studies reporting the surgical types of anastomosis and, based on these, the rate of endoscopic recurrence at a minimum of six months. Studies were grouped by conventional anastomosis vs Kono, and comparisons were made between these groups. Pooled incidence rates of ePOR were computed using random-effect modelling. Meta-regression and subgroup analyses were performed to examine the impact of the type of anastomosis on the incidence of ePOR ≥ 6 months Results Thirteen studies, including 1816 patients who underwent ileocolic resection for CD, were included. Among these patients, 282 (15.5%) received a Kono-S anastomosis, while 1534 (84.4%) had a conventional anastomosis. ePOR at ≥≥ six months showed a pooled incidence of 31.8% (95% CI, 24.8 to 39.2), with significant heterogeneity among the studies (p Funnel plot asymmetry [Figure 2] and Egger's regression test (p=0.118) indicated the absence of a publication bias Conclusion Kono-S anastomosis was associated with a significant reduction of ePOR at ≥ six months compared to the conventional anastomosis. Our findings highlight the need to standardize and implement the use of Kono-S anastomosis, particularly for difficult-to-treat patients with high risk for a post-operative recurrence

Background Approximately 25% of patients with inflammatory bowel disease (IBD) are diagnosed before age 20, making the transition from paediatric to adult healthcare challenging due to the high burden of these diseases at a critical time, such as adolescence. We aimed to assess patients’ readiness to transition from paediatric to adult IBD services and the impact on clinical outcomes. We further investigated adherence and quality of life at 12 months post- structured transition clinic Methods An observational, prospective study was conducted in a tertiary adult and paediatric IBD centre including adolescent aged≥17yo with a confirmed diagnosis of IBD before 16yo and in clinical remission who underwent “structured transition”. We collected demographics and clinical data 12 months before and after the transition visit. At the time of recruitment patients filled out the Transition Readiness Assessment Questionnaire (TRAQ) and they were defined ready based on a mean TRAQ value ≥ 3.0. The Morisky Medication Adherence Scale (MMAS) and the Short Form Health Survey (SF36) Questionnaire were completed baseline and 12 months after transition clinic. Receiving operating characteristics (ROC) curve was used to determine cut-off values of TRAQ for predicting medication adherence.We further investigated which demographic and clinical parameters could predict medication adherence. Results We enrolled 60 patients in clinical remission based on Crohn’s Disease Activity Index (CDAI) score of 115±124 for CD and pMayo 2,85±1,3 for UC, who had transitioned throughout transition clinic to adult care and completed 12 months follow-up [Table1]. Overall 42 patients (70%) were considered ready for transition, with a mean TRAQ score=3,2±0,5. The number of outpatient visits(1,86±0,75vs2,28±1,2;p Based on ROC curve a TRAQ cut-off≥3,46 could predict medication adherence with a sensibility of 55%,specificity 86% and an AUC=0,71(0,57-0,85;p=0,008)[Fig1]. At multivariate analysis, a high mean TRAQ value was associated with medication adherence at 12 months (OR:7,042CI:1,68-29,54,p=0.008) Conclusion Patients ready for transition were more likely to have fewer outpatient visits,disease flares and hospitalizations compared to not-ready patients. The quality of life did not differ pre- and post transition and between ready and not-ready patients.TRAQ score could be a reliable tool with high specificity to predict medication adherence

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 Prevention of postoperative recurrence (POR) in Crohn’s disease (CD) after ileo-colonic (IC) resection is still a highly debated topic. Prophylactic immunosuppression after surgery is currently recommended in presence of at least one clinical risk factor (RF). Due to drug-related adverse events and the relative high cost of biologics, we aimed to determine whether prevention of POR can be postponed and guided by endoscopy in CD patients with only one RF. Methods A multicentre retrospective study was conducted in 12 IG-IBD Italian centres. CD patients with only one RF for POR, including previous intestinal resection, extensive small intestine resection (>50 cm), fistulising phenotype, history of perianal disease, or active smoking were considered. Patients who performed a colonoscopy between 6 to 12 months after curative IC resection were included. Two groups were formed based on whether immunosuppressive therapy was started immediately after surgery (prophylaxis group) or guided by endoscopy (observation group). Primary endpoints were the rates of any endoscopic recurrence (Rutgeerts ≥i2a) and severe endoscopic recurrence (i4) within 12 months after surgery. Secondary outcomes were clinical recurrence (HBI≥5) rates at 6, 12 and 24 months after surgery. Results A total of 195 patients were enrolled. Out of all, 61 (31.3%) received immunoprophylaxis at a median time of 32 days [IQR 26-55] after surgery (n=14 infliximab, n=37 adalimumab, n=7 azathioprine, n=3 ustekinumab). Baseline patient characteristics are detailed in Table 1. Particularly, risk factors for POR were homogeneously distributed between the 2 groups. Colonoscopy was performed after a median time of 8 months [IQR 6-11]. No differences between immunoprophylaxis and endoscopy-driven approach was found regarding any endoscopic recurrence (36.1% in prophylaxis group vs 45.5% in observation group, p=0.10) and severe endoscopic recurrence (9.8% in prophylaxis group vs 15.7% in observation group, p=0.15). In 32 patients with a second colonoscopy at a median time of 30.5 months [IQR 22-43.75] after surgery, any recurrence and severe recurrence rates were also similar (p=0.55 and p=0.43, respectively). Early clinical recurrence at 6 months was reported in 23.4% of patients on immunoprophylaxis vs 31.5% who were not (p=0.43). Clinical recurrence rates between prophylaxis and observation group were also similar at 12 months (17.9% vs 34.8%, respectively, p=0.09) and at 24 months (17.9% vs 24.1%, respectively, p=0.63). Conclusion In CD patients with only one RF for POR, immediate immunoprophylaxis after curative IC resection does not decrease the rate of early clinical and endoscopic recurrence. Prospective and larger studies are needed to confirm our results.

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.

Previous analyses of the GIM (Gruppo Italiano Mammella) 2 study showed that addition of fluorouracil to epirubicin, cyclophosphamide, and paclitaxel in patients with node-positive early breast cancer does not improve outcome, whereas dose-dense chemotherapy induces a significant improvement in both disease-free survival and overall survival as compared with a standard schedule. Here, we present long-term results of the study.In this 2 × 2 factorial, open-label, randomised, phase 3 trial, we enrolled patients aged 18-70 years with operable, node-positive, breast cancer with Eastern Cooperative Oncology Group performance status of 0-1 from 81 hospitals in Italy. Eligible patients were randomly allocated (1:1:1:1) to one of the four following study groups: four cycles of standard-interval intravenous EC (epirubicin 90 mg/mBetween April 24, 2003, and July 3, 2006, 2091 patients were randomly assigned to treatment: 545 to q3EC-P, 544 to q3FEC-P, 502 to q2EC-P, and 500 to q2FEC-P. 88 patients were enrolled in centres providing only standard interval schedule and were assigned only to q3FEC-P and q3EC-P; thus, 2091 patients were included in the intention-to-treat analysis for the comparison of EC-P (1047 patients) versus FEC-P (1044 patients) and 2003 patients were included in the intention-to-treat analysis for the comparison of dose-dense (1002 patients) versus standard interval analysis (1001 patients). After a median follow-up of 15·1 years (IQR 8·4-16·3), median disease-free survival was not significantly different between FEC-P and EC-P groups (17·09 years [95% CI 15·51-not reached] vs not reached [17·54-not reached]; unadjusted hazard ratio 1·12 [95% CI 0·98-1·29]; log-rank p=0·11). Median disease-free survival was significantly higher in the dose-dense interval group than the standard-interval group (not reached [95% CI 17·45-not reached] vs 16·52 [14·24-17·54]; 0·77 [95% CI 0·67-0·89]; p=0·0004). The most common grade 3-4 adverse events were neutropenia (200 [37%] of 536 patients in the q3EC-P group vs 257 [48%] of 533 in the q3FEC-P group vs 50 [10%] of 496 q2EC-P vs 97 [20%] of 492) and alopecia (238 [44%] vs 249 [47%] vs 228 [46%] vs 235 [48%]). During extended follow-up, no further grade 3-4 adverse events or deaths related to toxic-effects were reported. Treatment-related serious adverse events were reported in nine (2%) patients in the q3EC-P group, seven (1%) in the q3FEC-P group, nine (2%) in the q2EC-P group, and nine (2%) in the q2FEC-P group. No treatment-related deaths occurred.Updated results from the GIM2 study support that optimal adjuvant chemotherapy for patients with high-risk early breast cancer should not include fluorouracil and should use a dose-dense schedule.Bristol-Myers Squibb, Pharmacia, Dompè Biotec Italy, Italian Ministry of Health, Fondazione Italiana per la Ricerca sul Cancro, and Alliance Against Cancer.

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

Background Recently, a new antimesenteric, functional, end-to-end, hand-sewn ileocolic anastomosis (Kono-S) has shown a significant reduction in endoscopic recurrence (ER) and surgical recurrence (SR) rate in Crohn’s disease (CD). This trial aimed to provide randomized controlled data comparing Kono-S anastomosis and conventional stapled ileocolic side-to-side anastomosis. Methods Randomized controlled trial (RCT) at a tertiary referral centre. The primary endpoint is ER rate (Rutgeerts score ≥ i2) after 6 months and surgical recurrence at 60 months. Secondary endpoints are clinical recurrence (CR) rate after 24 and 36 months, and SR after 24 and 36 months. Statistics was performed by using standard analyses. Furthermore, a sample size able to consent the detection of a reduction >30% in total endoscopic recurrence (when assuming a 60% to 65% ER expected rate in the control group and a 30% in the case group) was calculated; to allow a 10% drop-out of patients, 36 patients per group were needed (72 patients in the entire population). Results A total of 119 CD patients were included in the study. In all, 51 ileocolic CD patients were randomized in the Kono group and 68 in the conventional side-to-side group. At 6 months, 17 (33.3%) patients in the Kono group and 51 (75%) patients in the conventional group presented an ER (Rutgeerts score≥i2) at colonoscopy (p At 24 months, CR rate was 19.6% in the Kono group versus 30.9% in the conventional group (p=0.2), while SR rate was 0% in the Kono group versus 4.4% (3 patients) in the standard group (p=0.2). At 36 months, CR rate was 19.6% in the Kono-s group versus 33.8% in the conventional group (p=0.1). At 36 months, no patients (0%) in the Kono group experienced SR, while 6 patients (8.8%) in the conventional group did (p=0.03). Furthermore, when considering a median follow-up of 54 (42-60) months at interim analysis of SR, the difference between the two groups was confirmed to be significant (0% vs 8.8%; p=0.02). Conclusion This is the first RCT comparing Kono-S anastomosis and conventional side-to-side anastomosis in CD. The results demonstrate a significant reduction in postoperative endoscopic and surgical recurrence rates, no safety issues, and a favourable trend for lower clinical recurrence rate in patients who underwent Kono-S anastomosis compared to the conventional side-to-side anastomosis.

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.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.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 141 min was predictive of a better post-operative outcome (sensitivity 80.9%, specificity 43.1%, PPV 32.7%, NPV 86.9%). The multivariable analysis showed stricturing/fistulizing behaviour (OR 3.7, 95% CI 1.6-6.4, p = 0.02), need for total parenteral nutrition (OR 4.1, 95% CI 2.4-9.2, p = 0.01), pre-operative bowel cleansing (OR 0.6, 95% CI 0.41-0.83, p = 0.01) and surgery duration 141 min (OR 0.2, 95% CI 0.08-0.7, p = 0.03) as the only risk factors associated with post-operative morbidities.About 25% of CD patients develop post-operative complications. Several patient-related, disease-related and surgery-related factors should be considered risk factors for post-operative morbidity. The recognition of these factors, as well as a multidisciplinary approach to the pre-operative management of CD, could reduce post-operative complications.

Crohn's disease is a chronic inflammatory bowel disease characterized by transmural inflammation and fistula formation. Perianal fistulas are a common complication of Crohn's disease and are estimated to affect up to 28% of patients in the first two decades after diagnosis, particularly those with colonic disease and rectal involvement. Complex perianal fistulas in Crohn's disease are challenging to treat, severely impair patients' quality of life and cause substantial morbidity. Allogeneic, expanded, adipose-derived stem cells (Cx601) are a promising new therapeutic approach, although their high cost is often discouraging. We aimed at assessing the safety and efficacy of this treatment in patients with complex perianal fistulas in patients with Crohn's disease. Therefore, we conducted a meta-analysis in order to evaluate this new therapeutic approach before introducing it as standard of care. We examined 8 studies published in the last 10 years, 5 of which were selected for the final analysis. The primary outcome assessed was the combined fistula remission (clinical + imaging) assessed through the clinical examination and MRI, the control being the traditional medical strategies (ie, antibiotics, immunomodulators and anti-tumour necrosis factor agents). We registered a total of 128 events (lack of remission) in the control group vs 94 in the experimental one (Confidence Interval for OR of 0,12-0,31, P < 0,001). Our “in silico” assessment is reliable, being the introduction of (Cx601) an innovative and effective treatment. Further insights will be provided by the INSPIRE registry, a multinational post-marketing study whose main objective is the evaluation of the real-world clinical effectiveness and safety of (Cx601) in patients affected by Crohn's disease with complex perianal fistulas for a duration of 36 months, to which our University “Federico II” is actively taking part. Key messages Disability reduction is an important goal in cronh therapeutic path of care. Our “in silico” assessment may support the introduction of (Cx601) an innovative and effective treatment.

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

Background Endoscopic post-operative recurrence (ePOR) is common following ileocecal resection (ICR) in patients with Crohn’s disease (CD), reaching up to, 70% at, 1-year. In clinical trials, prophylaxis with anti-TNF therapies demonstrated a decrease in ePOR to around, 20% at, 1-year. Here we aimed to compare the effectiveness of vedolizumab (VDZ) and ustekinumab (UST) to anti-TNFs for preventing ePOR after curative ICR in adults with CD in a real-world setting. Methods This was a retrospective multicenter study, assessing patients with CD >17years who underwent ICR between, 2015–2019, started prophylaxis within six months of surgery, and underwent an ileocolonoscopy ≥ four months after prophylaxis. ePOR (Rutgeerts score ≥ i2 or colonic-segmental-SES-CD≥6) was assessed at, 12, 24, 36-months periods post-surgery. Multivariate logistic regression was used to assess risk factors for ePOR, and IPTW was performed to compare the effectiveness between agents. Results Included, 297 patients [53.9% males, age-at-diagnosis, 24(19–32) years (median;IQR), age-at-ICR, 34(26–43)years (median;IQR), 18.5% current-smokers]. Of these, 17.2% had previous-ICR, 8.1% were biologic naïve, 65.7% anti-TNF experienced, and, 28.6% exposed to, 2 biologics. Overall, 224, 39 and, 34 patients received respectively anti-TNFs, VDZ or UST for prevention of POR. Patients on VDZ and UST were more likely to be biologic experienced or post previous-ICR. ePOR rates for the entire cohort, anti-TNF, VDZ and UST were:, 41.8%, 40.2%, 33%, and, 61.8% at, 12-months, 49.0%, 46.5%, 44.4%, and, 72.4% at, 24- months, and, 48.6%, 47.9%, 44.0% and, 62.5% at, 36-months, respectively. Risk factors for ePOR: past infliximab (Adj.OR =1.73 [95% CI:, 1.01–2.97], p=0.045) or adalimumab (Adj.OR = 2.32 [95% CI:, 1.35–4.01], p=0.002), and technical aspects of anastomosis. After controlling for the disparities between groups by the IPTW method risk of ePOR at, 12-months was comparable between patients on anti-TNFs vs VDZ or anti-TNFs vs UST. However, comparison between VDZ vs UST groups revealed that patients on UST were at a higher risk for ePOR at, 12-months (OR=3.75 [95% CI:, 1.33–10.6]), p=0.012. Conclusion Prevention of ePOR was successful in ~60% of patients at, 12-months period. Patients on prophylaxis VDZ or UST consisted of a distinct, more refractory group with higher rates of ePOR. Post-operative treatment with UST or VDZ resulted in a similar risk of ePOR when compared to post-operative prophylaxis with anti-TNF after controlling for disease severity.

Background Coronavirus disease 2019 (COVID-19), had two pandemic waves in 2020, respectively in April and November. In the general population, the first wave has been characterized by a higher prevalence in Northern Italy and a higher mortality rate compared to the second one. The aim of this study was to compare the characteristics of IBD patients and negative outcomes of COVID-19 (pneumonia, hospitalization, ventilatory support, death) between the two pandemic waves in Italy. Methods Prospective observational cohort study. Patients with diagnosis of IBD and confirmed SARS-CoV-2 infection were enrolled. Differences between first and second wave were tested for significance using the Student’s t test and Fisher’s test, as appropriate. A two-tailed p value Results We enrolled 937 IBD patients from 47 participating IBD centres across Italy (219 in the first wave, 718 in the second wave). There were no significant differences between the first and the second wave in terms of age (46.3 ± 16.0 vs. 44.1 ± 15.5 years, p=0.06) and gender (female 45.7% vs. 48.2%, p= 0.54). In the first wave, a lower percentage of patients was affected by Crohn’s disease (CD): 92 (42.0%) vs. 399 (55.6%) (p Conclusion IBD patients had higher number of COVID-19 negative outcomes in the first wave than in second wave. In the first wave, a significantly higher percentage of patients were from Northern Italy, but no significant differences in negative outcomes were observed in comparison with those from Central- Southern Italy. Overall, findings in IBD population are coherent with those observed in the general population.

Different types of vasculitis can occur in patients with inflammatory bowel disease [IBD], but large vessels vasculitis seems to be the most prevalent. Indeed, the presence of both Crohn's disease [CD] and Takayasu's arteritis [TAK] has previously been reported, with higher prevalence in young women between the second and the third decade of life. This article aims to provide clinicians with an accurate picture of the most common clinical features and current treatment strategy for patients with both CD and TAK.We described the coexistence of CD and TAK in three young women and also performed an extensive literature review about the association of these two immune-related disorders. Research on PubMed server was performed typing the terms "Takayasu's arteritis and inflammatory bowel disease", "Takayasu's arteritis and Crohn's disease", and "Takayasu's arteritis and Ulcerative colitis".Although the association of CD with TAK is uncommon, due to the severity of both diseases, concomitance in the same patient may significantly complicate the diagnostic and therapeutic work-up. In addition, since TAK can compromise intestinal vasculature, it may possibly exacerbate the clinical course of patients with IBD. All patients we reported underwent surgery due to IBD complications and two of them started biological therapy with different outcomes.Early detention of these conditions has a great importance for both gastroenterologists and immunologists, for ensuring a tailored multidisciplinary management, possibly in order to identify a common therapy for these two immune-related disorders.

Background While mucosal (MH) and transmural healing (TH) predict relevant clinical outcomes in Crohn’s disease (CD), little is known about the real significance and clinical impact of deep remission (DR). The aim of this study was to better explore the concept of DR, towards a direct correlation between MH, TH and biomarkers. Methods A real-world observational longitudinal study was performed to evaluate the rate of clinical remission (CR), MH and TH, and the fecal calprotectin (FC)/C-reactive protein (CRP) levels in all consecutive patients with CD undergoing maintenance treatment with biologics. A ROC curve was constructed to define the best FC and CRP cut-offs associated with MH and TH. Finally, CD patients achieving CR, MH and TH, in association with the target FC and CRP values, were considered in DR. Results Among, 118 CD patients, CR, MH and TH were achieved in, 74 (62.7%), 52 (44.1%) and, 38 patients (32.2%), respectively. After, 2 years, the mean FC levels decreased from, 494 ±, 515.4 μg/gr to, 260 ±, 354.9 μg/gr (p Conclusion A FC cut-off of, 94 μg/gr and a normal CRP could be included in the definition of DR in association with CR, MH and TH. Thus, DR can be achieved in approximately, 30% of CD patients during maintenance treatment with biologics.

Background Idiopathic Thrombocytopenic Purpura (ITP) is an acquired haematological disorder with an incidence of 1 to 6 per 100.000, with reported comorbidity in patients with Inflammatory Bowel Disease (IBD). The current study aimed to evaluate the clinical presentation and outcome of ITP in IBD patients. Methods This multicenter retrospective case series was performed as part of the ECCO Collaborative Network of Exceptionally Rare case reports (CONFER) project. Cases of patients with ITP and IBD were collected by participating investigators. Clinical data were recorded in a standardised collection form. Results This report includes 20 patients with concurrent ITP and IBD: 15 were males, median age was 34 [Interquartile range (IQR) 25–56]. 12 subjects had a diagnosis of ulcerative colitis and 8 of Crohn’s disease. The diagnosis of IBD preceded the ITP diagnosis in 17 patients (median time between diagnosis was 7 years [IQR 1–14 years]). Among those, 10 patients were in IBD clinical remission at ITP diagnosis. Nine were treated with mesalamine, one with thiopurine, 4 with tumor necrosis factor-alpha (TNF) blockers, and 3 with no treatment. The mean platelet count at the presentation of ITP was 41.7±38.6 ×109/L. 6 patients had rectal bleeding, 8 had purpura, 6 had mucosal petechia, 2 had epistaxis, and 6 patients were asymptomatic. Regarding ITP treatment, 11 were treated with corticosteroids, 1 with Anti-RhD immunoglobulin, 7 with intravenous immunoglobulins (IVIG), 2 with rituximab and 2 patients eventually required splenectomy. All patients whose first presentation of ITP was rectal bleeding were treated medically with successful control of the ITP and IBD, None of them required splenectomy. 3 patients required colectomy with long-term follow-up, indicated by the IBD and not due to massive bleeding as a complication of ITP. With long-term follow-up, all patients had thrombocytes count above 50 ×109/L, and 18 were in IBD clinical remission. Conclusion Most ITP cases in this case series occurred after the IBD diagnosis and responded well to regular ITP treatment. The course of the ITP in the IBD patients follows a regular course, including response to medical therapy and low rates of splenectomy.

RATIONALE The study of surfactant organization in vacuum allows surfactant–surfactant interaction to be unveiled in the absence of surrounding solvent molecules. Knowledge on their chemical-physical properties may also lead to the definition of more efficient gas-phase carriers, air-cleaning agents and nanoreactors. In addition, the presence of lanthanide-group ions adds unique photochemical properties to surfactants. METHODS The structural features, stability and fragmentation patterns of charged aggregates formed by lanthanide-functionalized surfactants, ytterbium and erbium bis(2-ethylhexyl)sulfosuccinate ((AOT)3Yb and (AOT)3Er), have been investigated by electrospray ionization mass spectrometry (ESI-MS), tandem mass spectrometry (ESI-MS/MS) and energy-resolved mass spectrometry (ER-MS). RESULTS The experimental data indicate that the self-assembling of (AOT)3Yb and (AOT)3Er in the gas phase leads to the formation of a wide range of singly charged aggregates differing in their aggregation number, relative abundance and stability. In addition to specific effects on aggregate organization due to the presence of lanthanide ions, ER-MS experiments show rearrangements and in-cage reactions activated by collision, eventually including alkyl chain intra-cluster migration. CONCLUSIONS Analysis of the experimental findings suggests that the observed chemical transformations occur within an organized supramolecular assembly rather than in a random association of components. The fragmentation pathways leading to the neutral loss of a fragment of nominal mass 534 Da, assigned as C28H54O7S, from some positively charged aggregates has been rationalized. Copyright © 2014 John Wiley & Sons, Ltd.

We report on the direct assessment of the degree of substitution (DS) of carboxymethyl cellulose (CMC) by High Resolution Magic Angle Spinning (HR-MAS)