Effect of Tofacitinib on One-Year Colectomy Risk in Anti-TNF Refractory Ulcerative Colitis: A Prospective Multicenter Italian Study.

BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor recently approved to induce and maintain remission in ulcerative colitis (UC). AIMS: Considering the number of anti-TNF non-responders, this study aims to assess the effectiveness and safety of tofacitinib in a cohort of multi-failure patients with moderate-to-severe UC at 52 weeks. METHODS: From January 2021 to March 2023, we performed a prospective multicenter study observing adult patients with moderate-to-severe UC starting tofacitinib after an anti-TNF failure for a 52-week-long period. Effectiveness and safety were assessed in terms of colectomy rate, clinical remission and response, endoscopic remission, steroid-free clinical remission, and rate of adverse events. RESULTS: We included 58 patients with UC with an age of 42 ± 14.4 years, 59% males, 96.6% left-sided or pancolitis, who were failure to a single (65.5%) or more than one anti-TNF (34.5%). Only 6 (10.3%) patients underwent colectomy. Colectomy was clinically associated with the necessity and the number of extra cycles of tofacitinib 10 mg bid at W8 (p = 0.023) and W24 (p = 0.004), and with a higher partial Mayo score at W8 (p = 0.025). At W52, clinical remission, clinical response, and steroid-free clinical remission were 53.4%, 43.1%, and 48.3%, respectively. Of 22 performed colonoscopies at W52, 11 (50%) showed endoscopic remission. Adverse events occurred in 14 (24.1%) patients, but only 2 (3.4%) led to tofacitinib discontinuation. CONCLUSIONS: In a real-life setting of patients with anti-TNF refractory UC, tofacitinib has proved to be effective in preventing colectomy and inducing clinical and endoscopic remission at 52 weeks with a good safety profile.

Gastrointestinal bleeding in patients with hereditary hemorrhagic telangiectasia: Long-term results of endoscopic treatment.

Background and study aims This longitudinal prospective study evaluated the long-term outcome of endoscopic treatment of gastrointestinal bleeding in hereditary hemorrhagic telangiectases (HHT), its safety and outcome predictors. Patients and methods Consecutive patients with HHT and either anemia disproportionate to epistaxis or overt gastrointestinal bleeding received endoscopic treatment of gastrointestinal telangiectases with argon plasma coagulation (APC). Hemoglobin levels and transfusion requirements were evaluated before and after treatment. Treatment effectiveness was classified as: 1) complete: hemoglobin level during the follow-up ≥9 g/dL; 2) complete with recurrence: hemoglobin ≥9 g/dL for at least 12 months with subsequent drop to <9 g/dL; or 3) absent: no improvement of hemoglobin level. Adverse events (AEs) were classified as mild, moderate, severe or fatal. Correlations were searched between treatment outcome and demographic/genetic characteristics, number, size and site of telangiectases, and hepatic arterio-venous malformations grade. Results Forty-seven patients with HHT were enrolled. At median follow-up of 134 months (range 20-243 months), 41 of 47 patients showed treatment response (complete or with recurrence) after one (14/47) or more (27/47) endoscopic treatments. Median hemoglobin levels were 7.0 g/dL and 11.9 g/dL at baseline and at the end of follow-up, respectively. Transfusion requirement decreased from 22.8 to 7.3 red cell unit/year. A higher baseline number of telangiectases was associated with a lower chance of response ( P =0.008). Only one severe AE (0.4%, jejunal perforation) was recorded. Conclusions Endoscopic treatment of gastrointestinal teleangiectases for gastrointestinal bleeding in patients with HHT is effective in the long term and safe.

Impact of improved upper endoscopy quality on detection of gastric precancerous lesions.

OBJECTIVE: Intestinal metaplasia (IM) is the point of no return in gastric carcinogenesis, and patients with extensive (antrum plus corpus) IM are at high risk of developing gastric cancer. We evaluated the impact of improved gastroscopy quality on the detection of gastric IM in an Italian area at high risk for gastric cancer. METHODS: Data of consecutive patients with gastric biopsies according to the updated Sydney System observed in 2013, 2016 and 2019 resulting in IM diagnosis were retrieved. In the first period, endoscopy was performed with standard white light instruments. In the second period, preendoscopic gastric preparation was administered, and the examinations lasting at least 7 min with standard endoscopes were performed. In the third period, the latter procedure was followed, with virtual chromoendoscopy equipped instruments. The prevalence of IM in any gastric site and that of extensive IM were compared among the three periods. RESULTS: Data of 3485 patients were available. The detection of IM in at least one gastric site increased from 29.9 to 33.6% and 34.5% (95% CI, 32.1-36.8) in the first, second and third period, respectively. The difference was statistically significant between the first and last (P = 0.02; OR, 1.24; 95% CI, 1.04-1.48) period. When considering extensive IM, the detection increased from 4.28 to 6.1% and 5.44%, although the difference failed to reach statistical significance (P = 0.076). CONCLUSION: Our data showed that implementation of a quality protocol increased the probability to detect IM in the stomach, allowing us to select patients deserving stricter follow-up.

Efficacy of a computer-aided detection system in a fecal immunochemical test-based organized colorectal cancer screening program: a randomized controlled trial (AIFIT study).

BACKGROUND: Computer-aided detection (CADe) increases adenoma detection in primary screening colonoscopy. The potential benefit of CADe in a fecal immunochemical test (FIT)-based colorectal cancer (CRC) screening program is unknown. This study assessed whether use of CADe increases the adenoma detection rate (ADR) in a FIT-based CRC screening program. METHODS: In a multicenter, randomized trial, FIT-positive individuals aged 50-74 years undergoing colonoscopy, were randomized (1:1) to receive high definition white-light (HDWL) colonoscopy, with or without a real-time deep-learning CADe by endoscopists with baseline ADR > 25 %. The primary outcome was ADR. Secondary outcomes were mean number of adenomas per colonoscopy (APC) and advanced adenoma detection rate (advanced-ADR). Subgroup analysis according to baseline endoscopists' ADR (≤ 40 %, 41 %-45 %, ≥ 46 %) was also performed. RESULTS: 800 individuals (median age 61.0 years [interquartile range 55-67]; 409 men) were included: 405 underwent CADe-assisted colonoscopy and 395 underwent HDWL colonoscopy alone. ADR and APC were significantly higher in the CADe group than in the HDWL arm: ADR 53.6 % (95 %CI 48.6 %-58.5 %) vs. 45.3 % (95 %CI 40.3 %-50.45 %; RR 1.18; 95 %CI 1.03-1.36); APC 1.13 (SD 1.54) vs. 0.90 (SD 1.32; P  = 0.03). No significant difference in advanced-ADR was found (18.5 % [95 %CI 14.8 %-22.6 %] vs. 15.9 % [95 %CI 12.5 %-19.9 %], respectively). An increase in ADR was observed in all endoscopist groups regardless of baseline ADR. CONCLUSIONS: Incorporating CADe significantly increased ADR and APC in the framework of a FIT-based CRC screening program. The impact of CADe appeared to be consistent regardless of endoscopist baseline ADR.

Diagnostic yield of small bowel capsule endoscopy in obscure gastrointestinal bleeding: a real-world prospective study.

Small bowel capsule endoscopy (SBCE) visualizes the small bowel (SB) mucosa. Gastrointestinal (GI) bleeding from SB accounts for the majority of SBCE indications. We aimed to assess, in a "real-world" prospective study, the diagnostic yield of SBCE in a cohort of consecutive patients with obscure gastrointestinal bleeding (OGIB). Secondary end point was to assess the frequency of adverse events and the role of SBCE in determining the diagnostic work-up and clinical outcome. From 2016 to 2018, all patients referred for SBCE examination were enrolled. Indication for SBCE was re-assessed by 2 dedicated gastroenterologists. Inclusion criteria: (1) age ≥ 18 and ≤ 85 years; (2) diagnosis of OGIB; 3) non-diagnostic standard bidirectional endoscopy; (4) informed consent. Exclusion criteria: (1) deglutition impairment; (2) SBCE contraindications; (3) pregnancy. The cohort included 50 patients [males 18 (36%), age 68 (27-83)]. SBCE indication: patients with ongoing overt OGIB (Group A) (n = 11; 22%), previous overt OGIB (Group B) (n = 14; 28%), occult bleeding (with Iron Deficiency Anaemia) (Group C) (n = 25; 50%). SBCE detected clinically relevant lesions in 46 (92%) cases. Clinically relevant lesions were more frequent in Group C (24/25; 96%), followed by Group A (10/11; 91%) and Group B (12/14; 85.5%). After SBCE, treatment was medical (60%); endoscopic (14%), surgical (36%) or conservative (18%). Clinical follow-up showed complete resolution in 63.2%, partial/absent resolution in 18.4% of cases. In a prospective study, the high diagnostic yield of SBCE supports its role as first-line investigation in patients with OGIB. However, this achievement requires an accurate and timely assessment by dedicated gastroenterologists.

Premedication with simethicone and N-acetylcysteine for improving mucosal visibility during upper gastrointestinal endoscopy in a Western population.

Background and study aim Pre-endoscopic use of a preparation with tensioactive and mucolytic agents improved gastric mucosa visualization in Eastern studies. Data on Western population are scanty. Patients and methods This prospective, endoscopist-blinded, randomized study enrolled patients who underwent esophagogastroduodenoscopy in a single center. Before endoscopy patients, were randomized to receive or not receive an oral preparation with simethicone and N-acetylcysteine in water. A pretested score (Crema Stomach Cleaning Score [CSCS]) for gastric mucosa cleaning evaluation was used. In detail, the stomach was divided into the antrum, body, and fundus and a score of 1 to 3 was assigned to each part (the higher the score, the better the preparation), and a total value ≤ 5 was considered as insufficient. Time between endoscope insertion and clean achievement (mouth to clean time) or the end of examination (mouth to mouth time) was recorded. Results A total of 197 patients were enrolled. The mean overall CSCS value and mucosal cleaning in all parts was better in treated patients than in controls. Prevalence total score ≤ 5 was significantly lower in patients treated before endoscopy. Need for water flush occurred less frequently in treated patients ( P  < 0.0001). The mouth to clean time was lower in the treated than in the control group (2.3 ±â€Š1.6 vs 3.8 ±â€Š1.6 min; P  < 0.001), whereas no significant difference in mouth to mouth time emerged. Conclusions Data from this study show that premedication with simethicone and N-acetylcysteine results in significantly better endoscopic visualization of gastric mucosa, and the proposed CSCS could be useful for standardizing this evaluation.

Risk of COVID 19 in patients with inflammatory bowel diseases compared to a control population.

BACKGROUND: It is unclear whether patients with inflammatory bowel disease (IBD) are at increased risk of COVID-19. OBJECTIVES: This observational study compared the prevalence of COVID-19 symptoms, diagnosis and hospitalization in IBD patients with a control population with non-inflammatory bowel disorders. METHODS: This multicentre study, included 2733 outpatients (1397 IBD patients and 1336 controls), from eight major gastrointestinal centres in Lombardy, Italy. Patients were invited to complete a web-based questionnaire regarding demographic, historical and clinical features over the previous 6 weeks. The prevalence of COVID-19 symptoms, diagnosis and hospitalization for COVID-19 was assessed. RESULTS: 1810 patients (64%) responded to the questionnaire (941 IBD patients and 869 controls). IBD patients were significantly younger and of male sex than controls. NSAID use and smoking were more frequent in controls. IBD patients were more likely treated with vitamin-D and vaccinated for influenza. Highly probable COVID-19 on the basis of symptoms and signs was less frequent in the IBD group (3.8% vs 6.3%; OR:0.45, 95%CI:0.28-0.75). IBD patients had a lower rate of nasopharyngeal swab-PCR confirmed diagnosis (0.2% vs 1.2%; OR:0.14, 95%CI:0.03-0.67). There was no difference in hospitalization between the groups (0.1% vs 0.6%; OR:0.14, 95%CI:0.02-1.17). CONCLUSION: IBD patients do not have an increased risk of COVID-19 specific symptoms or more severe disease compared with a control group of gastroenterology patients.

Finger clubbing in inflammatory bowel disease: association with upper small bowel lesions and need of surgery in Crohn's disease.

OBJECTIVE: Finger clubbing has been associated with inflammatory bowel disease (IBD). AIMS: In a prospective single-center study, we aimed to assess the frequency of finger clubbing in a cohort of IBD patients. Whether finger clubbing is associated with clinical characteristics of IBD was also investigated. METHODS: IBD patients with a detailed clinical history were enrolled. Finger clubbing was assessed by visual inspection. Data were expressed as median (range), chi-square, t-test. Multivariate logistic regression analysis was used to assess risk factors for finger clubbing, when considering demographic and clinical characteristics, smoking habits and chronic pulmonary diseases (CPD). RESULTS: Finger clubbing was searched in 470 IBD patients: 267 Crohn's disease and 203 ulcerative colitis. Finger clubbing was more frequent in Crohn's disease than in ulcerative colitis: 45/267 (16.8%) vs. 15/203 (7.3%) [odds ratio (OR), 2.54 (1.37-4.70); P = 0.003]. Crohn's disease involved the ileum (59.9%), colon (4.5%), ileum-colon (25.8%) and upper gastrointestinal (GI) (9.8%). Ulcerative colitis extent included proctitis (E1) (13.4%), left-sided (E2) (43.3%) and pancolitis (E3) (43.3%). Upper GI lesions, but not other Crohn's disease localizations, were more frequent in patients with finger clubbing [9/45 (20%) vs. 17/222 (7.7%); P = 0.032]. Crohn's disease-related surgery was more frequent in patients with finger clubbing [36/45 (80%) vs. 107/222 (48.1%); P < 0.001]. In Crohn's disease, the only risk factors for finger clubbing were upper GI lesions and Crohn's disease-related surgery [OR, 2.58 (1.03-6.46), P = 0.04; OR, 4.07 (1.86-8.91), P = 0.006]. Ulcerative colitis extent was not associated with finger clubbing [E1: OR, 0.27 (0.02-3.44), P = 0.33; E2: OR, 0.93 (0.24-3.60), P = 0.92; E3:OR, 0.64 (0.22-1.86), P = 0.59]. In ulcerative colitis, but not in Crohn's disease, finger clubbing was more frequent in smokers [13/15 (86.6%) vs. 99/188 (52.6%); P = 0.01] and in patients with CPD [5/15 (33.3%) vs. 16/188 (8.5%); P = 0.002]. Smoking and CPD were the only risk factors for finger clubbing in ulcerative colitis [OR, 7.18 (1.44-35.78), P = 0.01; OR, 10.93 (2.51-47.45), P = 0.001]. CONCLUSION: In the tested IBD population, finger clubbing was more frequent in Crohn's disease than in ulcerative colitis. In Crohn's disease, upper GI lesions and history of Crohn's disease-related surgery were risk factors for finger clubbing, suggesting the possible role of finger clubbing as a subclinical marker of Crohn's disease severity.

Inflammatory bowel disease versus Chlamydia trachomatis infection: a case report and revision of the literature.

Infectious proctitis may mimic inflammatory bowel disease, particularly when limited to the rectum. The present case report includes findings from a 50-year-old man, soldier, referring to our Inflammatory Bowel Disease Unit with a diagnosis of rectal Crohn's disease, refractory to conventional treatments. Mild anemia, hypergammaglobulinemia and HIV-antibodies seronegativity were detected. Entero-MRI and stool examinations were negative. Ileocolonoscopy detected few rectal ulcers with irregular edges. Endosonography showed marked thickening of the rectal wall and enlarged perirectal lymphnodes. Nodal and rectal fine needle aspirate did not show atypia (PAN CK-). Rectal biopsies showed flogistic granular tissue (PAN CK-): Warthin-Starry stain was negative. Previous Treponema pallidum infection was detected. Clinical history revealed habits at risk for sexually transmitted infection. Rectal swabs for RT-PCR for Chlamydia trachomatis, Neisseria gonorrhoeae, and Herpes Simplex Virus 1-2 lead to a diagnosis of lymphogranuloma venereum. Doxycycline 100 mg and Azitromicyn 500 mg t.i.d. were given for 21 days, followed by negativity for RT-PCR for Chlamydia trachomatis at rectal swabs. Complete disappearance of symptoms and mucosal healing occurred. Due to the increased frequency of infectious diseases, sexually transmitted infection (including lymphogranuloma venereum) should be considered as possible differential diagnosis when assessing patients with inflammatory bowel disease limited to the rectum.

Use of synthetic and biological DMARDs in patients with enteropathic spondyloarthritis: a combined gastro-rheumatological approach.

OBJECTIVES: The aim of this 2-year prospective study was to assess the diagnostic and therapeutic effect of a combined gastro-rheumatological approach in enteropathic spondyloarthritis (eSpA) patients. METHODS: Inflammatory bowel disease (IBD) patients with joint pain were referred by IBD-dedicated gastroenterologists to a dedicated rheumatologist. At baseline and at 3, 6, 12, 24 months, the following parameters were recorded: clinical and biochemical variables, SpA and IBD activity scores, treatment (conventional synthetic; csDMARDs, biologics; bDMARDs). Associations between treatment and patient characteristics were evaluated by logistic regression (AOR [95% CI]). RESULTS: Overall, 229 IBD patients were referred to rheumatologists. eSpA was diagnosed in 147 (64.2%) patients: 96 (65.3%) showing peripheral and 51 (34.7%) axial involvement. IBD included Crohn's disease (CD) in 141 (61.6%) and ulcerative colitis (UC) in 88 (38.4%). bDMARD treatment increased over the follow-up (baseline-24 months: 32.7-60%; AOR 3.45 [1.93-6.2], p<0.001). bDMARD use was less frequent in elderly patients (AOR 0.73 [0.56-0.96], p=0.023), in UC (AOR 0.43 [0.2-0.94], p=0.034) and in patients with peripheral involvement (AOR 0.53 [0.3-1.04], p=0.067). csDMARD use was increased in patients with peripheral involvement (AOR 4.65 [2.09-10.33], p<0.001) and in UC (AOR 2.30 [1.13-4.67], p=0.021). CRP, ESR, ASDAS-ESR levels and BASFI significantly decreased over the follow-up, whereas the pMayo score, BASDAI and HAQ-S were unchanged. CONCLUSIONS: In this prospective study in eSpA patients, a multidisciplinary approach was shown to optimise the therapeutic management and outcome (e.g. disease activity scores). bDMARD use paralleled an improvement in disease activity scores and confirmed a good safety profile.

Impact of endoscopic ultrasound-guided fine-needle aspiration and multidisciplinary approach in the management of abdominal or mediastinal mass.

BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a useful tool for the diagnosis of suspected abdominal or mediastinal neoplastic lesions. AIM: To evaluate the impact of EUS-FNA and multidisciplinary approach on the diagnostic work-up and therapeutic management of patients with abdominal or mediastinal neoplastic lesions. PATIENTS AND METHODS: One hundred and twenty patients (69 men, median age 65 years) with a suspected abdominal or mediastinal neoplastic mass at computed tomography or MRI underwent EUS-FNA. All EUS-FNA findings and clinical data were evaluated by a multidisciplinary team (oncologists, surgeons, and gastroenterologists). EUS-FNA findings were compared with the final diagnosis made by histological evaluation of the surgical specimen or clinical outcome at follow-up. RESULTS: A correct diagnosis was obtained by EUS-FNA in 96/120 patients (80%), indicating benignancy of the lesion in 21 (18%) cases and confirming malignancy in 75 (62%). On the basis of EUS-FNA findings, chemotherapy was tailored in 57/75 (76%) patients with malignancy whereas the surgical strategy was changed in 21/120 (18%) of patients. Overall, the diagnostic accuracy of EUS-FNA was 85%. A multidisciplinary team approach enabled a correct diagnosis in patients in whom EUS-FNA was nondiagnostic and to identify five cases with false-negative EUS-FNA findings. CONCLUSION: EUS-FNA has a relevant impact on the management of suspected abdominal or mediastinal neoplastic lesions. A multidisciplinary team approach enables to overcome the EUS-FNA methodological limitations. The combination of EUS-FNA and multidisciplinary team approach could help to diagnose and tailor therapeutic options in such patients.

Appropriate nutrient supplementation in celiac disease.

Reduced levels of iron, folate, vitamin B12, vitamin D, zinc, and magnesium are common in untreated celiac disease (CD) patients probably due to loss of brush border proteins and enzymes needed for the absorption of these nutrients. In the majority of patients, removal of gluten from the diet leads to histological recovery and normalization of iron, vitamin, and mineral levels. Iron deficiency anemia is the most common extra-intestinal sign of CD and usually resolves with adherence to a gluten-free diet. However, deficiencies of both folate and vitamin B12 may persist in some patients on a gluten-free diet, thus requiring vitamin supplementation to improve subjective health status. Similarly, exclusion of gluten from the diet does not always normalize bone mineral density; in these cases, supplementation of vitamin D and calcium is recommended. Resolution of mucosal inflammation may not be sufficient to abrogate magnesium deficiency. Since gluten-free cereal products have a lower magnesium content as compared with gluten-containing counterparts, a magnesium-enriched diet should be encouraged in CD patients. In this article we discuss the frequency and clinical relevance of nutrient deficiency in CD and whether and when nutrient supplementation is needed.