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Item does not contain fulltext BACKGROUND: Etrolizumab is a gut-targeted anti-β7 integrin monoclonal antibody. In a previous phase 2 induction study, etrolizumab significantly improved clinical remission versus placebo in patients with moderately to severely active ulcerative colitis. We aimed to compare the safety and efficacy of etrolizumab with infliximab in patients with moderately to severely active ulcerative colitis. METHODS: We conducted a randomised, double-blind, double-dummy, parallel-group, phase 3 study (GARDENIA) across 114 treatment centres worldwide. We included adults (age 18-80 years) with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6-12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) who were naive to tumour necrosis factor inhibitors. Patients were required to have had an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. Participants were randomly assigned (1:1) to receive subcutaneous etrolizumab 105 mg once every 4 weeks or intravenous infliximab 5 mg/kg at 0, 2, and 6 weeks and every 8 weeks thereafter for 52 weeks. Randomisation was stratified by baseline concomitant treatment with corticosteroids, concomitant treatment with immunosuppressants, and baseline disease activity. All participants and study site personnel were masked to treatment assignment. The primary endpoint was the proportion of patients who had both clinical response at week 10 (MCS ≥3-point decrease and ≥30% reduction from baseline, plus ≥1-point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) and clinical remission at week 54 (MCS ≤2, with individual subscores ≤1); efficacy was analysed using a modified intention-to-treat population (all randomised patients who received at least one dose of study drug). GARDENIA was designed to show superiority of etrolizumab over infliximab for the primary endpoint. This trial is registered with ClinicalTrials.gov, NCT02136069, and is now closed to recruitment. FINDINGS: Between Dec 24, 2014, and June 23, 2020, 730 patients were screened for eligibility and 397 were enrolled and randomly assigned to etrolizumab (n=199) or infliximab (n=198). 95 (48%) patients in the etrolizumab group and 103 (52%) in the infliximab group completed the study through week 54. At week 54, 37 (18·6%) of 199 patients in the etrolizumab group and 39 (19·7%) of 198 in the infliximab group met the primary endpoint (adjusted treatment difference -0·9% [95% CI -8·7 to 6·8]; p=0·81). The number of patients reporting one or more adverse events was similar between treatment groups (154 [77%] of 199 in the etrolizumab group and 151 [76%] of 198 in the infliximab group); the most common adverse event in both groups was ulcerative colitis (55 [28%] patients in the etrolizumab group and 43 [22%] in the infliximab group). More patients in the etrolizumab group reported serious adverse events (including serious infections) than did those in the infliximab group (32 [16%] vs 20 [10%]); the most common serious adverse event was ulcerative colitis (12 [6%] and 11 [6%]). There was one death during follow-up, in the infliximab group due to a pulmonary embolism, which was not considered to be related to study treatment. INTERPRETATION: To our knowledge, this trial is the first phase 3 maintenance study in moderately to severely active ulcerative colitis to use infliximab as an active comparator. Although the study did not show statistical superiority for the primary endpoint, etrolizumab performed similarly to infliximab from a clinical viewpoint. FUNDING: F Hoffmann-La Roche.

Fecal calprotectin has been widely studied in inflammatory bowel disease (IBD) under clinical and therapeutic settings. It showed a good correlation with clinical, endoscopic, and histologic findings. For these reasons, fecal calprotectin is currently one of the most useful tools in IBD care, both in diagnosis and in clinical management. The development of biologic drugs allowed a deeper control of disease, which sometimes reaches histological healing; this is associated with a reduced risk of relapses and complications. The management of IBD treatment is currently carried out with a treat-to-target approach, and mucosal healing is considered at present to be the optimal therapeutic target, but the future is going through histologic remission. Fecal calprotectin is probably the best marker of mucosal healing, but it is correlated also with histologic remission: moreover, it has been recently studied as a possible therapeutic target in the CALM study. We carried out a comprehensive literature review in order to evaluate the role of fecal calprotectin at present and in the future in the management of IBD therapies.

Gastroesophageal reflux disease (GERD) is one of the most frequent gastrointestinal disorders. Proton pump inhibitors (PPIs) are effective in healing lesions and improving symptoms in most cases, although up to 40% of GERD patients do not respond adequately to PPI therapy. Refractory GERD (rGERD) is one of the most challenging problems, given its impact on the quality of life and consumption of health care resources. The definition of rGERD is a controversial topic as it has not been unequivocally established. Indeed, some patients unresponsive to PPIs who experience symptoms potentially related to GERD may not have GERD; in this case the definition could be replaced with “reflux-like PPI-refractory symptoms.” Patients with persistent reflux-like symptoms should undergo a diagnostic workup aimed at finding objective evidence of GERD through endoscopic and pH-impedance investigations. The management strategies regarding rGERD, apart from a careful check of patient's compliance with PPIs, a possible change in the timing of their administration and the choice of a PPI with a different metabolic pathway, include other pharmacologic treatments. These include histamine-2 receptor antagonists (H2RAs), alginates, antacids and mucosal protective agents, potassium competitive acid blockers (PCABs), prokinetics, gamma aminobutyric acid-B (GABA-B) receptor agonists and metabotropic glutamate receptor-5 (mGluR5) antagonists, and pain modulators. If there is no benefit from medical therapy, but there is objective evidence of GERD, invasive antireflux options should be evaluated after having carefully explained the risks and benefits to the patient. The most widely performed invasive antireflux option remains laparoscopic antireflux surgery (LARS), even if other, less invasive, interventions have been suggested in the last few decades, including endoscopic transoral incisionless fundoplication (TIF), magnetic sphincter augmentation (LINX) or radiofrequency therapy (Stretta). Due to the different mechanisms underlying rGERD, the most effective strategy can vary, and it should be tailored to each patient. The aim of this paper is to review the different management options available to successfully deal with rGERD.

Chronic constipation (CC) is one of the most common gastroenterological diagnoses in clinical practice. Treatment includes several steps, depending on the severity of symptoms. Lifestyle modifications and increased intake of fiber and water are suggested by most health professionals. Unfortunately, the recommendations in this regard are the most varied, often conflicting with each other and not always based on solid scientific arguments. This paper aims to clarify this topic by providing practical indications for the management of these patients in every day clinical practice. The literature available on this topic is scarce, and dietary studies have important methodological biases. However, fiber, mainly by binding water and acting as bulking agents and/or as prebiotics for the intestinal microbiota, and mineral water, especially if rich in magnesium and/or bicarbonate, are useful tools. An adequate, well-designed diet should be a cornerstone of any effective treatment for chronic constipation. High-quality studies on larger samples are mandatory to give scientific validity to the role of the food in CC therapy and to enable professionals to choose the best approach for their patients, combining nutritional and pharmacological agents.

Several interventional procedures are available to treat moderate-to-critical acute pancreatitis (AP) in its late phase. The ongoing debate on these options, together with the scarcity of reported quality of life (QoL) information in the Literature, prompted us to conduct a review of our experience.All the patients treated at our referral Center for moderate-to-critical AP according to Determinant-Based Classification (DBC) were retrospectively reviewed. Patients treated conservatively or operated within 4 weeks were excluded. The included patients were managed following a "tailored" interventional-surgical approach, which did not exclude the possibility to skip one or more steps of the classic "step-up" approach, based on the patient's clinical course, and divided into four groups, according to the first procedure performed: percutaneous drainage (PD), endoscopic approach (END), internal derivation (INT), and necrosectomy (NE). In-hospital and mid-term follow-up variables were analyzed.The study sample consisted in 47 patients: 11 patients were treated by PD, 11 by END, 13 by INT, and 12 by NE. A significant distribution of the DBC severity (p = 0.029) was registered among the four groups. Moreover, the NE group had statistically significant reduced SF-36 scores in the domain of social functioning at 3 months (p = 0.011), at 1 year (p = 0.002), and at 2 years (p = 0.001); role limitations due to physical health at 6 months (p = 0.027); and role limitations due to emotional problems at 1 year (p = 0.020).In the "late phase" of moderate to critical AP requiring an invasive management, PD, END, INT, and NE are all effective options, depending on patents' status and necrosis location. A "tailored" interventional-surgical management could be pursued, but up-front more invasive approaches are at higher risk of worse QoL.The manuscript was registered at clinicaltrials.gov in 04/2021 and identified with NCT04870268.

Background: Guidelines on Irritable Bowel Syndrome (IBS) are usually developed by specialists, with a possible translational gap in primary care. Aims: To evaluate the knowledge of IBS of Italian General Practitioners (GPs) and the difference compared to doctors in Training for General Practice (ITGPs). Methods: A questionnaire was completed by 170 GPs and 64 ITGPs. Results: The Rome Criteria and Bristol Scale are more familiar to ITGPs than GPs. The most frequently used diagnostic symptoms are abdominal pain, bowel movement frequency and bloating. GPs and ITGPs think that bloating and abdominal discomfort should be introduced into the definition of IBS. Intestinal motility disorders and psychological factors are considered to be the most probable cause of IBS. GPs report more frequently than ITGPs that the patient's request and difficulties in managing the disorder are reasons for a gastroenterological referral. Conclusions: There is still a gap between the indications provided by the experts and clinical practice, and this seems greater on the part of GPs than ITGPs. Abdominal pain and bowel frequency changes are considered the main symptoms for diagnosing IBS, but most GPs and ITGPs would like to include bloating among the diagnostic criteria. It would be highly desirable to develop commonly shared guidelines between gastroenterologists and GPs.

Objective Occupational stress represents a significant precipitating factor in different diseases but its role in Irritable Bowel Syndrome (IBS) needs to be clarified. The present cross-sectional study aimed at investigating the prevalence of IBS diagnosis in a sample of health workers and exploring the potential relationships between IBS, work-related stress levels and work ability. Methods 653 health workers undergoing periodical occupational health surveillance at the Occupational and Preventive Medicine Unit of a major University Hospital in central Italy, were consecutively recruited and screened for IBS diagnosis, according to ROMA IV criteria. The rating scales IBS Severity Scoring System (IBS-SSS), Demand–Control–Support Questionnaire (DCSQ) and Work Ability Index (WAI) were used to assess respectively IBS severity, occupational stress and work ability levels. Results IBS prevalence in the sample was 16.8%. Participants suffering from IBS were characterized by a higher prevalence of psychiatric diagnosis and sleep disturbances, higher levels of job strain and isostrain as well as by lower levels of work ability compared to non affected subjects. Moreover, the severity of IBS correlated positively with occupational stress and both were negatively associated with work ability. Conclusions The present results suggest the need for preventive, organizational and management strategies at workplace aimed at protecting the health and well-being but also productivity of the worker with IBS.

Background: Ulcerative colitis (UC) is a chronic relapsing disease, which needs a continue monitoring, especially during biological therapies. An increasing number of patients is treated with anti-Tumor Necrosis factor (TNF) drugs, and current research is focalized to identify biomarkers able to monitor the disease and to predict therapeutic outcome.Methods: We enrolled consecutive UC patients treated with anti-TNF, naïve to biologic drugs. Therapeutic outcome was evaluated after 54 weeks of treatment in terms of clinical remission (Partial Mayo Score -PMS- Results: Out of 44 UC patients enrolled, 22 achieved clinical remission and mucosal healing after 54 weeks. At baseline, when Protein A was used as coating, UC patients non-responders showed a reduced reactivity to Jacalin (JAC) in comparison with NHS (p = 0.04). After one year of treatment, a decrease in JAC binding was seen only in responders, in comparison with baseline (p = 0.04). When JAC binding was tested selecting IgG by means of Fab anti-IgG Fab, UC patients displayed an increased reactivity after anti-TNF therapy (p < 0,0001 vs controls). At baseline, PMS inversely correlates with JAC binding when Fab anti-IgG Fab was used in solid phase (r2 = 0,2211; p = 0,0033). Patients with higher PMS at baseline (PMS ≥5) presented lower binding capacity for JAC in comparison with NHS and with lower PMS patients (p = 0,0135 and p = 0,0089, respectively).Conclusion: Ig glycosylation was correlated with clinical and endoscopic activity in patients with UC. JAC protein A-selected Ig showed a possible role in predicting therapeutic effectiveness. If these data would be confirmed, Ig glycosylation could be used as biomarker in UC.

Aims This is a prospective observational web-based survey aimed to assess the impact of SARS-CoV-2 pandemic onGastroenterology Units in Italy. Methods All members of the Italian Society of Gastroenterology (SIGE) were invited to answer a 39-point multiple-choiceweb-based survey between March 30 thand April 7 th2020. Results Data of 121 hospitals from all 20 Italian regions were analyzed. Overall, 10.7 % of Gastroenterology divisions havebeen converted to COVID Units. Outpatients consultations, endoscopic and ultrasound procedures were limited to urgenciesand oncology indications in 85.1 %, 96.2 % and 72.2 % of Units, respectively, and 46.7 % of Units suspended the screeningfor colorectal cancer.In order to guarantee the ordinary follow-up of outpatients, 83/121 (68.6 %) divisions activated aremote consultancy service (63.9 % by phone, 31.3 % by email, 4.8 % by video). Overall, 112/121 (92.6 %) GI Units issued and followed a specific protocol for the management of patients with suspectedor confirmed SARS-CoV-2 infection. The 72.2 % of the staff received proper training for the use of personal protective equipment, although 45.5 % did not havesufficient devices for an adequate replacement. With regard to PPE availability, N95/FFP2-3 masks were available in 91/121 (75.2 %), surgical masks in 115/121 (95.0 %),gloves in 117/121 (96.7 %), disposable gown in 100/121 (82.6 %), hairnet in 104/121 (85.9 %), goggles in 78/121 (64.5 %)and boots in 57/121 (47.1 %) of divisions. Finally, in 41/121 GI divisions (33.9 %) there was at least one healthcare professional who got infected, in a total of 132subjects, of which 121/132 from divisions not-converted to COVID Units and 75/132 from high-prevalence areas. Conclusions Substantial changes of practice and reduction of procedures have been recorded in the entire country duringthe first wave of the pandemic. The long-term impact of such modifications is difficult to estimate but potentially very riskyfor many digestive diseases.

Eosinophilic esophagitis is a chronic disease whose incidence and prevalence are increasing, based on a genetic-driven interaction between environment and immune system. Several gene loci involved in the development of the disease have been identified. A two-step mechanism has been hypothesized: a thymic stromal lymphopoietin-induced allergic sensitization followed by upregulation of CAPN14-related esophageal-specific pathways. Environment seems to have a larger effect than genetic variants. Factors that could play a role are allergens, drugs, colonizing bacteria and possibly Helicobacter Pylori infection. Acting on these modifiable risk factors may be a tool to prevent the disease. EoE is characterized by a typical eosinophilic infiltrate limited to the esophageal epithelium, supported by a Th2-mediated immune response, found in other atopic conditions. The key of the pathogenesis is the disfunction of the epithelial barrier which allow the interaction between allergens and inflammatory cells. Eosinophilic-predominant inflammation leads to the typical wall remodeling, histologically characterized by epithelial and smooth muscle hyperplasia, lamina propria fibrosis and neo-angiogenesis. These alterations find their clinical expression in the pattern of symptoms: dysphagia, food impaction, chest pain, heartburn.

In the absence of secondary causes, eosinophilic esophagitis (EoE) is a chronic, local, progressive, T-helper type 2 immune-mediated disorder characterized by symptoms of esophageal dysfunction and eosinophil-predominant inflammation. In the last 20 years, the incidence and prevalence of EoE have risen sharply, and the chances of encountering affected patients in clinics and endoscopy rooms have increased. Nevertheless, it is estimated that the mean diagnostic delay of EoE is 4–6 years in both children and adults. Unfortunately, the longer the disease stays unrecognized, the likelier it is for the patient to have persistent or increased esophageal eosinophilic inflammation, to complain of non-resolving symptoms, and to develop fibrotic complications. Early detection depends on the recognition of initial clinical manifestations that vary from childhood to adulthood and even among patients of the same age. The disease phenotype also influences therapeutic approaches that include drugs, dietary interventions, and esophageal dilation. We have herein reviewed epidemiologic, clinical, endoscopic, and histologic features and therapeutic options of EoE focusing on differences and similarities between children and adults that may certainly serve in daily clinical practice.

Artificial intelligence (AI) has enormous potential to support clinical routine workflows and therefore is gaining increasing popularity among medical professionals. In the field of gastroenterology, investigations on AI and computer-aided diagnosis (CAD) systems have mainly focused on the lower gastrointestinal (GI) tract. However, numerous CAD tools have been tested also in upper GI disorders showing encouraging results. The main application of AI in the upper GI tract is endoscopy; however, the need to analyze increasing loads of numerical and categorical data in short times has pushed researchers to investigate applications of AI systems in other upper GI settings, including gastroesophageal reflux disease, eosinophilic esophagitis, and motility disorders. AI and CAD systems will be increasingly incorporated into daily clinical practice in the coming years, thus at least basic notions will be soon required among physicians. For noninsiders, the working principles and potential of AI may be as fascinating as obscure. Accordingly, we reviewed systematic reviews, meta-analyses, randomized controlled trials, and original research articles regarding the performance of AI in the diagnosis of both malignant and benign esophageal and gastric diseases, also discussing essential characteristics of AI.

Eosinophilic esophagitis (EoE) is a unique form of non-immunoglobulin E-mediated food allergy, restricted to the esophagus, characterized by esophageal eosinophil-predominant inflammation and dysfunction. The diagnosis requires an esophago-gastroduodenoscopy with esophageal biopsies demonstrating active eosinophilic inflammation with 15 or more eosinophils/high-power field, following the exclusion of alternative causes of eosinophilia. Food allergens trigger the disease, withdairy/milk, wheat/gluten, egg, soy/legumes, and seafood the most common. Therapeutic strategies comprise dietary restrictions, proton pump inhibitors, topical corticosteroids, biologic agents, and esophageal dilation when strictures are present. However, avoidance of trigger foods remains the only option targeting the cause, and not the effect, of the disease. Because EoE relapses when treatment is withdrawn, dietary therapy offers a long-term, drug-free alternative to patients who wish to remain off drugs and still be in remission. There are currently multiple dietary management strategies to choose from, each having its specific efficacy, advantages, and disadvantages that both clinicians and patients should acknowledge. In addition, dietary regimens should be tailored around each individual patient to increase the chance of tolerability and long-term adherence. In general, liquid elemental diets devoid of antigens and elimination diets restricting causative foods are valuable options. Designing diets on the basis of food allergy skin tests results is not reliable and should be avoided. This review summarizes the most recent knowledge regarding the clinical use of dietary measures in EoE. We discussed endpoints, rationale, advantages and disadvantages, and tailoring of diets, as well as currently available dietary regimens for EoE.

BACKGROUND Therapeutic drug monitoring is a useful clinical decision aid in managing patients with inflammatory bowel disease treated with anti-tumor necrosis factor (anti-TNF). Various techniques are available to evaluate drug trough levels, and among these a point-of-care (POC) method has been proposed to overcome the limitations inherent to other methodologies. In this study we aimed to evaluate the capability of POC to discriminate between relapse and remission disease phases, and to assess the concordance of the POC and homogeneous mobility shift assay (HMSA) results. METHODS Drug trough level of 46 Crohn's disease patients treated with either adalimumab or infliximab were evaluated with both a POC technique and an HMSA at various time points (week-16 and -48) during anti-TNF treatment. RESULTS Median adalimumab trough level of patients in remission were significantly higher as compared to relapsing patients using both HMSA (week 16, P = 0.0001; week48, P = 0.001) and POC (week 16, P = 0.0003; week 48, P = 0.0012), and similar results were observed with infliximab trough level at week 16 (HMSA, P = 0.019; POC, P = 0.0072). Overall, we observed a good correlation between the techniques for both infliximab (r = 0.76; P

Anemia is a frequent complication of ulcerative colitis, and is frequently caused by iron deficiency. Oral iron supplementation displays high rates of gastrointestinal adverse effects. However, the formulation of sucrosomial iron (SI) has shown higher tolerability. We performed a prospective study to compare the effectiveness and tolerability of oral SI and intravenous ferric carboxy-maltose (FCM) in patients with ulcerative colitis in remission and mild-to-moderate anemia. Patients were randomized 1:1 to receive 60 mg/day for 8 weeks and then 30 mg/day for 4 weeks of oral SI or intravenous 1000 mg of FCM at baseline. Hemoglobin and serum levels of iron and ferritin were assessed after 4, 8, and 12 weeks from baseline. Hemoglobin and serum iron increased in both groups after 4 weeks of therapy, and remained stable during follow up, without significant treatment or treatment-by-time interactions (p = 0.25 and p = 0.46 for hemoglobin, respectively, p = 0.25 and p = 0.26 for iron, respectively). Serum ferritin did not increase over time during SI supplementation, while it increased in patients treated with FCM (treatment effect, p = 0.0004, treatment-by-time interaction effect, p = 0.0002). Overall, this study showed that SI and FCM displayed similar effectiveness and tolerability for treatment of mild-to-moderate anemia in patients with ulcerative colitis under remission.

Irritable Bowel Syndrome (IBS) is a very common functional gastrointestinal disease. Its pathogenesis is multifactorial and not yet clearly defined, and hence, its therapy mainly relies on symptomatic treatments. Changes in lifestyle and dietary behavior are usually the first step, but unfortunately, there is little high-quality scientific evidence regarding a dietary approach. This is due to the difficulty in setting up randomized double-blind controlled trials which objectively evaluate efficacy without the risk of a placebo effect. However, a Low Fermentable Oligo-, Di- and Mono-saccharides And Polyols (FODMAP) Diet (LFD) and Gluten Free Diet (GFD) are among the most frequently suggested diets. This paper aims to evaluate their possible role in IBS management. A GFD is less restrictive and easier to implement in everyday life and can be suggested for patients who clearly recognize gluten as a trigger of their symptoms. An LFD, being more restrictive and less easy to learn and to follow, needs the close supervision of a skilled nutritionist and should be reserved for patients who recognize that the trigger of their symptoms is not, or not only, gluten. Even if the evidence is of very low-quality for both diets, the LFD is the most effective among the dietary interventions suggested for treating IBS, and it is included in the most updated guidelines.

A low-FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) diet (LFD) is a possible therapy for irritable bowel syndrome (IBS). This study investigates the short- and long-term efficacy and nutritional adequacy of an LFD and the patients&rsquo, long-term acceptability. Patients&rsquo, adherence and ability to perceive the &ldquo, trigger&rdquo, foods were also evaluated. Seventy-three IBS patients were given an LFD (T0) and after 2 months (T1), 68 started the reintroduction phase. At the end of this period (T2), 59 were advised to go on an Adapted Low-FODMAP Diet (AdLFD) and 41 were evaluated again after a 6&ndash, 24 month follow-up (T3). At each time, questionnaires and Biolectrical Impedance Vector Analysis (BIVA) were performed. The LFD was effective in controlling digestive symptoms both in the short- and long-term, and in improving quality of life, anxiety and depression, even if some problems regarding acceptability were reported and adherence decreased in the long term. The LFD improved the food-related quality of life without affecting nutritional adequacy. When data collected at T0 were compared with those collected at T2, the perception of trigger foods was quite different. Even if some problems of acceptability and adherence are reported, an LFD is nutritionally adequate and effective in improving IBS symptoms also in the long term.

INTRODUCTION: Biological therapies are widely used for the treatment of ulcerative colitis. However, only a low proportion of patients achieve clinical remission and even less mucosal healing. There is currently scarce knowledge about the early markers of therapeutic response, with particular regard to mucosal healing. The aim of this prospective study was to evaluate the role of fecal calprotectin (FC) as early predictor of mucosal healing. METHODS: A prospective observational study was conducted on patients with ulcerative colitis, who started biological therapy with infliximab, adalimumab, golimumab, or vedolizumab at our center. All patients underwent colonoscopy, performed by 2 blinded operators, at baseline and week 54 or in case of therapy discontinuation because of loss of response. FC was assessed at baseline and week 8 and evaluated as putative predictor of mucosal healing at week 54. RESULTS: We enrolled 109 patients, and 97 were included in the analysis. Twenty-six patients (27%) experienced loss of response. Over 71 patients (73%) with clinical response at week 54, clinical remission was obtained in 60 patients (61.9%) and mucosal healing in 45 patients (46.4%). After 8 weeks of treatment, FC predicted mucosal healing at week 54 (P < 0.0001). Sensitivity, specificity, positive predictive value, and negative predictive value were estimated to be 75%, 88.9%, 86.6%, and 75.5%, respectively, based on a cutoff of 157.5 mg/kg. DISCUSSION: The present study suggests that FC assessment after 8 weeks of treatment with all the biological drugs could represent a promising early marker of response to therapy in terms of mucosal healing.

Crohn's disease (CD) is an inflammatory bowel disease of unknown etiology. However, increasing evidence suggests Mycobacterium avium subspecies paratuberculosis (MAP) as a putative causative agent: 1) MAP is the etiological agent of Johne's disease, a granulomatous enteritis affecting ruminants, which shares clinical and pathological features with CD; 2) MAP has been detected in tissues and blood samples from CD patients; 3) case reports have documented a favorable therapeutic response to anti-MAP antibiotics. Area covered: This review provides an appraisal of current information on MAP characteristics, diagnostic methodologies and emerging drug treatments. The authors focus on RHB-104, a novel oral formulation containing a fixed-dose combination of clarithromycin, clofazimine and rifabutin, endowed with synergistic inhibitory activity on MAP strains isolated from CD patients. Expert opinion: Based on encouraging in vitro data, RHB-104 has entered recently the clinical phase of its development, and is being investigated in a randomized, placebo-controlled phase III trial aimed at evaluating its efficacy and safety in CD. Provided that the overall clinical development will support the suitability of RHB-104 for inducing disease remission in CD patients with documented MAP infection, this novel antibiotic combination will likely take a relevant position in the therapeutic armamentarium for CD management.

Background Pathogenesis of acute diverticulitis and diverticular bleeding remains poorly defined, and few data compare directly risk factors for these complications. Aims to assess differences in clinical features, lifestyles factors and concurrent drug use in patients with acute diverticulitis and those with diverticular bleeding. Methods Data were obtained from the REMAD Registry, an ongoing 5-year prospective, observational, multicenter, cohort study conducted on 1,217 patients. Patient- and clinical- related factors were compared among patients with uncomplicated diverticular disease, patients with previous acute diverticulitis, and patients with previous diverticular bleeding. Results Age was significantly lower (OR 0.48, 95% CI: 0.34–0.67) and family history of diverticular disease was significantly higher (OR 1.60, 95% CI: 1.11–2.31) in patients with previous diverticulitis than in patients with uncomplicated diverticular disease, respectively. Chronic obstructive pulmonary disease was significantly higher in patients with previous diverticular bleeding as compared with both uncomplicated diverticular disease (OR 8.37, 95% CI: 2.60–27.0) and diverticulitis (OR 4.23, 95% CI: 1.11–16.1). Conclusion This ancillary study from a nationwide Registry showed that some distinctive features identify patients with acute diverticulitis and diverticular bleeding. These information might improve the assessment of risk factors for diverticular complications.

Irritable bowel syndrome (IBS), a common functional gastrointestinal disorder, is classified according to bowel habits as IBS with constipation (IBS-C), with diarrhea (IBS-D), with alternating constipation and diarrhea (IBS-M), and unsubtyped (IBS-U). The mechanisms leading to the different IBS forms are mostly unknown. This study aims to evaluate whether specific fecal bacterial taxa and/or short-chain fatty acids (SCFAs) can be used to distinguish IBS subtypes and are relevant for explaining the clinical differences between IBS subcategories. We characterized five fecal samples collected at 4-weeks intervals from 40 IBS patients by 16S rRNA gene profiling and SCFA quantification. Finally, we investigated the potential correlations in IBS subtypes between the fecal microbial signatures and host physiological and clinical parameters. We found significant differences in the distribution of Clostridiales OTUs among IBS subtypes and reduced levels of SCFAs in IBS-C compared to IBS-U and IBS-D patients. Correlation analyses showed that the diverse representation of Clostridiales OTUs between IBS subtypes was associated with altered levels of SCFAs; furthermore, the same OTUs and SCFAs were associated with the fecal cytokine levels and stool consistency. Our results suggest that intestinal Clostridiales and SCFAs might serve as potential mechanistic biomarkers of IBS subtypes and represent therapeutic targets.

Background Gastroesophageal reflux disease (GERD) is one of the most common gastrointestinal disorders worldwide, with relevant impact on the quality of life and health care costs.The aim of our study is to assess the prevalence of GERD based on self-reported symptoms among university students in central Italy. The secondary aim is to evaluate lifestyle correlates, particularly eating habits, in GERD students using automatically recorded transactions through cashiers at university canteen. Methods A web-survey was created and launched through an app, ad-hoc developed for an interactive exchange of information with students, including anthropometric data and lifestyle habits. Moreover, the web-survey allowed users a self-diagnosis of GERD through a simple questionnaire. As regard eating habits, detailed collection of meals consumed, including number and type of dishes, were automatically recorded through cashiers at the university canteen equipped with an automatic registration system. Results We collected 3012 questionnaires. A total of 792 students (26.2% of the respondents) reported typical GERD symptoms occurring at least weekly. Female sex was more prevalent than male sex. In the set of students with GERD, the percentage of smokers was higher, and our results showed that when BMI tends to higher values the percentage of students with GERD tends to increase. When evaluating correlates with diet, we found, among all users, a lower frequency of legumes choice in GERD students and, among frequent users, a lower frequency of choice of pasta and rice in GERD students. Discussion The results of our study are in line with the values reported in the literature. Nowadays, GERD is a common problem in our communities, and can potentially lead to serious medical complications; the economic burden involved in the diagnostic and therapeutic management of the disease has a relevant impact on healthcare costs. Conclusions To our knowledge, this is the first study evaluating the prevalence of typical GERD–related symptoms in a young population of University students in Italy. Considering the young age of enrolled subjects, our prevalence rate, relatively high compared to the usual estimates, could represent a further negative factor for the future economic sustainability of the healthcare system. Electronic supplementary material The online version of this article (10.1186/s12876-018-0832-9) contains supplementary material, which is available to authorized users.

Recent introduction of direct antiviral agents (DAAs) has completely changed the scenario regarding hepatitis C virus (HCV) treatment. Certain countries' economic health programs prioritize DAAs according to specific clinical features of HCV-infected patients. The aim of this study was to define epidemiological, demographic and clinical characteristics of HCV-infected patients in the Tuscany region of central Italy.We enrolled HCV patients with chronic viral hepatitis who were referred to the outpatient services of 16 hospitals in Tuscany from 1 January 2015 to 31 December 2015. Case report forms contained patient information including main demographic data, blood chemistry data, viral hepatitis markers, instrumental evaluations (liver biopsy or transient elastometry, liver ultrasound), eligibility for DAAs, and liver transplantation or therapy already in progress.Of all patients considered, 2919 HCV patients were enrolled (mean age: 57.44 ± 15.15; 54% males, 46% females). All routes of transmission were well represented (intravenous drug use in 20.7%; nosocomial/dental care in 20.6%; and coagulation factors/blood transfusions in 13.3%). Diabetes was the highest represented comorbidity (20.8%), followed by metabolic syndrome (15.5%) and ischemic heart disease (6.2%). The most prevalent HCV genotypes were 1b (47.4%) and 2 (16.5%). In the whole cohort of patients, 32.8% were cirrhotic (40 patients were listed for liver transplantation). Signs of portal hypertension were present mostly in the group older than 45 years (92.3%). Extrahepatic HCV-related diseases were present in 13.3% of cases (cryoglobulinemic syndrome in 58.3% and B-cell non-Hodgkin's lymphoma in 10.5%).Our study provides evidence of a high prevalence of epidemiological changes in HCV infection with a major prevalence of advanced liver disease, such as portal hypertension, in this elderly cohort of patients.

Background Ulcerative colitis (UC) is a chronic relapsing disease, which needs a continue monitoring, especially during biological therapies. An increasing number of patients is treated with anti-Tumor Necrosis factor (TNF) drugs, and current research is focalized to identify biomarkers able to monitor the disease and to predict therapeutic outcome. Methods We enrolled consecutive UC patients treated with anti-TNF, naïve to biologic drugs. Therapeutic outcome was evaluated after 54 weeks of treatment in terms of clinical remission (Partial Mayo Score -PMS- Results Out of 44 UC patients enrolled, 22 achieved clinical remission and mucosal healing after 54 weeks. At baseline, when Protein A was used as coating, UC patients non-responders showed a reduced reactivity to Jacalin (JAC) in comparison with NHS (p=0,04). After one year of treatment, a decrease in JAC binding was seen only in responders, in comparison with baseline (p=0,04). When JAC binding was tested selecting IgG by means of Fab anti-IgG Fab, UC patients displayed an increased reactivity after anti-TNF therapy (p Conclusion Ig glycosylation was correlated with clinical and endoscopic activity in patients with UC. JAC protein A-selected Ig showed a possible role in predicting therapeutic effectiveness. If these data would be confirmed, Ig glycosylation could be used as biomarker in UC.

OBJECTIVES: Role of reflux and mechanisms of response to proton pump inhibitor (PPI) therapy in eosinophilic esophagitis (EoE) have not yet been fully elucidated. Comprehensive assessment by impedance-pH monitoring could clarify these issues. METHODS: Prospective multicenter study comparing EoE patients with healthy controls and gastroesophageal reflux disease cases. Patients with EoE were evaluated off- and on PPI; responsiveness was assessed by histology. Impedance-pH appraisal included chemical clearance, assessed with the postreflux swallow-induced peristaltic wave (PSPW) index, and mucosal integrity measured with mean nocturnal baseline impedance (MNBI). RESULTS: Sixty consecutive patients with EoE were compared with 60 age- and sex-matched healthy controls and 60 subjects with gastroesophageal reflux disease. The number of total refluxes was higher, while the PSPW index was lower in patients with EoE than in healthy controls. Off PPI, a lower MNBI gradient between the mid and distal esophagus distinguished 20 patients with PPI-refractory EoE from 40 patients with PPI-responsive EoE and was a predictor of PPI failure. On PPI, a lower PSPW index was the sole reflux parameter distinguishing PPI-refractory from PPI-responsive EoE; all reflux parameters improved in PPI-responsive patients, whereas the PSPW index was not modified in PPI-refractory cases and was independently associated with PPI-responsiveness. MNBI in the distal and mid esophagus improved much more in PPI-responsive than in PPI-refractory EoE. DISCUSSION: Reflux plays a role in the pathogenesis of EoE, more relevant in PPI-responsive cases. Low impedance gradient between the mid and distal esophagus may be useful to predict PPI refractoriness. PPIs mainly act by improving chemical clearance, i.e., by an antireflux action supporting long-term prescription in PPI-responsive EoE.

To investigate the possible relationship between the use of Angiotensin II Receptor Blockers (ARBs) or Angiotensin-Converting-Enzyme Inhibitors (ACE-i) and unspecified intestinal malabsorption (IM) within the Italian and German real-life context.a retrospective cohort of patients with a new unspecified IM diagnosis during the period 1 January 2010-31 December 2013 was extracted from Italian IMS Health Longitudinal Patient Database and German IMS Disease Analyzer. Only patients with at least one prescription of ARB or ACE-i medication during the 6 months preceding the IM diagnosis were included and then followed up for 12 months to assess treatment exposure.After stratification by year and molecule, the proportion of patients experiencing an unspecified IM diagnosis on total patients receiving ARBs or ACE-i ranged from 0% to 0.14%, showing no relevant differences between molecules and no time trends.this study indicates that ACE-i or ARBs were rarely associated to an unspecified IM diagnosis. No relevant difference between each specific ACE-i and ARB was highlighted.

Proton pump inhibitors (PPIs) display a number of limitations and unmet clinical needs that have prompted the development of novel drugs to improve the outcomes of acid-related diseases, including the eradication of H. pylori. In this context, a new synthesized potassium-competitive acid blocker (P-CAB), vonoprazan, showed higher suppression of gastric acid secretion. Areas covered: This review discusses the current knowledge regarding the efficacy of vonoprazan in the treatment of acid-related diseases, with a particular focus on its use in Helicobacter pylori eradication. Expert opinion: Vonoprazan showed some advantages over PPIs in terms of the pharmacokinetic and pharmacodynamic profile: fast onset of action without requiring acid activation and specific administration timing, more potent and prolonged inhibition of acid secretion, including a better nighttime acid control, and a less antisecretory variability. Recent evidence suggests that vonoprazan can be preferred to PPIs as maintenance therapy for reflux esophagitis and eradication of Helicobacter pylori owing to its stronger antisecretory effect. Moreover, vonoprazan displays favorable safety and tolerability profiles, even though long-term studies on the effects of vonoprazan are required.

Background Anti-tumor necrosis factor drugs (anti-TNFs) are widely used for the treatment of ulcerative colitis (UC). However, many patients experience loss of response during the first year of therapy. An early predictor of clinical remission and mucosal healing is needed. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are markers of subclinical inflammation poorly evaluated in UC patients treated with anti-TNFs. The aim of this multicenter study was to evaluate whether NLR and PLR could be used as prognostic markers of anti-TNF treatment response. Methods Patients with UC who started anti-TNF treatment in monotherapy were evaluated. Patients with concomitant corticosteroid treatment ≥20 mg were excluded. We calculated NLR, PLR, and fecal calprotectin before treatment and after induction. The values of NLR and PLR were correlated with clinical remission and mucosal healing at the end of follow-up (54 weeks) using the Mann-Whitney U test and then multivariate analysis was conducted. Results Eighty-eight patients were included. Patients who reached mucosal healing after 54 weeks of therapy displayed lower levels of both baseline NLR and PLR (P = 0.0001 and P = 0.04, respectively); similar results were obtained at week 8 (P = 0.0001 and P = 0.001, respectively). Patients who presented with active ulcers at baseline endoscopic evaluation had higher baseline NLR and PLR values compared with those without detected ulcers (P = 0.002 and P = 0.0007, respectively). Conclusions BothNLR and PLR showed a promising role as early predictors of therapeutic response to anti-TNF therapy in UC patients. If confirmed in larger studies, classification and regression trees proposed in this article could be useful to guide clinical decisions regarding anti-TNF treatment.

Background In Italy, the spread of the COVID-19 pandemic has stressed the entire healthcare system and required a huge re-organization of many Divisions, including those of Gastroenterology. Aims to assess the impact of COVID-19 pandemic on Gastroenterology Divisions across Italy. Methods All members of the Italian Society of Gastroenterology (SIGE) were invited to answer a web-based survey. Results Data of 121 hospitals from all 20 Italian regions were analyzed. Overall, 10.7% Gastroenterology Divisions have been converted to Covid Units. Outpatients consultations, endoscopic and ultrasound procedures were limited to urgencies and oncology indications in 85.1%, 96.2% and 72.2% of Units, respectively, and 46.7% of them suspended the screening for colorectal cancer. Moreover, 72.2% of the staff received a training for use of personal protective equipment, although 45.5% did not have sufficient devices for adequate replacement. Overall, 132 healthcare workers in 41 Gastroenterology Divisions were found to be infected. Conclusion This is the first study to evaluate, at a country level, the impact of COVID-19 outbreak on Gastroenterology Divisions. Substantial changes of practice and reduction of procedures have been recorded in the entire country. The long-term impact of such modifications is difficult to estimate but potentially very risky for many digestive diseases.

Background: Mean nocturnal baseline impedance (MNBI) and postreflux swallow-induced peristaltic wave (PSPW) index are novel impedance-based markers of reflux, but the effect of bile reflux on these metrics is unknown. The aim of this study was to evaluate bile reflux, MNBI, and PSPW index in patients with endoscopy-negative GERD partially responsive to PPI therapy. Methods: All patients underwent off-PPI endoscopy, esophageal manometry, multichannel intraluminal impedance pH (MII-pH), and bile reflux monitoring. Abnormal esophageal acid exposure time (AET) was required for inclusion. Symptom intensity (using 10-cm visual analog scales), and conventional and novel MII-pH metrics were compared between patients with and without abnormal bile reflux. Key Results: We evaluated 42 NERD patients (29 males, mean age: 53.4±13.years), mean AET 6.1±2%, of which 21 had abnormal bile reflux (Group A, 10.2±4.9%), and 21 had normal bile reflux (Group B, 0.4±0.1%, P&nbsp

Aims Vedolizumab (VDZ) prevents migration of activated leucocytes into inflamed mucosa. This study aimed to assess the patterns of serum cytokines in ulcerative colitis (UC) patients at baseline and during VDZ treatment, and to investigate their association with mucosal healing and clinical remission. Methods We enrolled consecutive UC patients eligible for treatment with VDZ. A panel of serum cytokines were measured by fluorescence assay at weeks 0, 6 and 22. Colonoscopy was performed at baseline and week 54, to evaluate mucosal healing. The time trends of serum cytokines were analysed by log-linear mixed effect models, and their prognostic accuracy was evaluated by logistic regression. Results Out of 27 patients included in the analysis, at week 54 mucosal healing was achieved in 12 (44%) and clinical remission in 17 (63%). Mucosal healing was associated with higher interleukin (IL)-8 values at baseline and with significant decrease in IL-6 and IL-8 levels over the first 6 weeks. A significant reduction of IL-6 and IL-8 levels over the first 6 weeks of treatment was associated also with clinical remission. Logistic models including, among the predictors, IL-6 and IL-8 at baseline and their changes over the first 6 weeks of treatment had 83% sensitivity and 87% specificity to predict mucosal healing, and 82% sensitivity and 90% specificity to predict clinical remission. Conclusion In UC patients, the serum patterns of IL-6 and IL-8 at baseline and over the first 6 weeks of treatment with VDZ could be useful to predict therapeutic outcome.

Currently, the manometric study represents the gold standard for the evaluation of gastrointestinal motility allowing to evaluate the propagation of peristalsis or the presence of relaxation of the sphincter apparatus by recording the pressure variations offered by the closure of the intestinal lumen against a catheter, as a function of time. Over the years, manometric systems have evolved from simple balloons to perfused and solid-state catheters, and, at the same time, display and analysis methods have evolved from strip chart recorders to computerized systems. In particular, the most recent and significant improvement of these systems began in the 1990s with the advent of high-resolution manometry, whose catheters are provided with more numerous and closely spaced pressure sensors. With these modifications, much more information can be acquired, as data are not lost in the gaps that are typically present in a conventional catheter. Moreover, this novel technology provides color-countered topographic plots based on amplitude, space, and time, depicting a continuum of dynamic pressure changes along lengths and time, thus allowing a better understanding of the normal and abnormal motor function, and therefore a more accurate diagnosis of gastrointestinal motor disorders. Besides, data are presented in a simplified and visually attractive manner, in contrast to the use of linear plots of amplitude signals alone in conventional manometry. However, there are still limits of the method and further studies are needed in order to rigorously evaluate the incremental clinical utility of high-resolution manometry compared to non-high resolution manometry.

Food is often considered to be a precipitating factor of irritable bowel syndrome (IBS) symptoms. In recent years, there has been a growing interest in FODMAPs (Fermentable Oligo-, Di-, Mono-saccharides, And Polyols), which can be found in many common foods. A low FODMAP diet (LFD) is increasingly suggested for IBS treatment. However, long-term, large, randomized controlled studies are still lacking, and certainties and doubts regarding LFDs have grown, often in a disorderly and confused manner. Some potential LFD limitations and concerns have been raised, including nutritional adequacy, cost, and difficulty in teaching the diet and maintaining it. Most of these limitations can be solved with the involvement of a skilled nutritionist, who can clearly explain the different phases of the LFD and ensure nutritional adequacy and compliance. Further studies should focus on new methods of teaching and learning the LFD and on predictors of response. Moreover, particular interest should be focused on the possible use of LFD in gastrointestinal diseases other than functional disorders and, possibly, also in non-gastrointestinal diseases. The aim of the present review was to clarify the effective and appropriate indications and limitations of an LFD and to discuss its possible future uses.

The gluten-free diet (GFD) has gained increasing popularity in recent years, supported by marketing campaigns, media messages and social networks. Nevertheless, real knowledge of gluten and GF-related implications for health is still poor among the general population. The GFD has also been suggested for non-celiac gluten/wheat sensitivity (NCG/WS), a clinical entity characterized by intestinal and extraintestinal symptoms induced by gluten ingestion in the absence of celiac disease (CD) or wheat allergy (WA). NCG/WS should be regarded as an “umbrella term” including a variety of different conditions where gluten is likely not the only factor responsible for triggering symptoms. Other compounds aside from gluten may be involved in the pathogenesis of NCG/WS. These include fructans, which are part of fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs), amylase trypsin inhibitors (ATIs), wheat germ agglutinin (WGA) and glyphosate. The GFD might be an appropriate dietary approach for patients with self-reported gluten/wheat-dependent symptoms. A low-FODMAP diet (LFD) should be the first dietary option for patients referring symptoms more related to FODMAPs than gluten/wheat and the second-line treatment for those with self-reported gluten/wheat-related symptoms not responding to the GFD. A personalized approach, regular follow-up and the help of a skilled dietician are mandatory.

Simple Summary Esophageal cancer (EC) has a poor prognosis when the diagnosis is delayed, but curative treatment is possible if the diagnosis is timely. The disease subtly progresses before symptoms prompt patients to seek medical attention. Effective pre-symptomatic screening strategies may improve the outcome of the disease. Recent evidence provided insights into early diagnosis of EC via blood tests, advanced endoscopic imaging, and artificial intelligence. Accordingly, we reviewed available strategies to diagnose early EC. Abstract Esophageal cancer (EC) is the seventh most common cancer and the sixth cause of cancer death worldwide. Histologically, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) account for up to 90% and 20% of all ECs, respectively. Clinical symptoms such as dysphagia, odynophagia, and bolus impaction occur late in the natural history of the disease, and the diagnosis is often delayed. The prognosis of ESCC and EAC is poor in advanced stages, being survival rates less than 20% at five years. However, when the diagnosis is achieved early, curative treatment is possible, and survival exceeds 80%. For these reasons, mass screening strategies for EC are highly desirable, and several options are currently under investigation. Blood biomarkers offer an inexpensive, non-invasive screening strategy for cancers, and novel technologies have allowed the identification of candidate markers for EC. The esophagus is easily accessible via endoscopy, and endoscopic imaging represents the gold standard for cancer surveillance. However, lesion recognition during endoscopic procedures is hampered by interobserver variability. To fill this gap, artificial intelligence (AI) has recently been explored and provided encouraging results. In this review, we provide a summary of currently available options to achieve early diagnosis of EC, focusing on blood biomarkers, advanced endoscopy, and AI.