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Objective: The role of nurses has great educational-scientific potential in COVID-19 vaccination. The aim of this work is to clarify whether the educational role of IBD nurses in vaccination is perceived by IBD patients., Materials and Methods: A cross-sectional study was carried out, through a questionnaire, to evaluate how many IBD patients received health education about vaccinations from the dedicated nurses (IBD nurses)., Results: There were four hundred questionnaires, 310 patients (77.5%) answered all questions. The nurse does not appear to help educate patients on influenza vaccination (66.1%) or pneumococcal vaccination (81.6%). Disclosed patients have many doubts about the new COVID-19 vaccination (74.4%) and many seek information (74.8%) and think that the nurse can provide the necessary information (70%)., Conclusions: IBD nurses do not seem very active in the vaccination education role, and they do not meet patients' expectations, which are conversely very high.

Objective: The management of Inflammatory Bowel Disease (IBD) has changed significantly in recent years, mainly due to the introduction of biologic medications, however, other factors may also have a role. The aim of this study was to evaluate the evolution of IBD admissions, including trends, modality of admission and rates of surgical intervention, in a tertiary care center., Patients and Methods: Hospitalization of patients with a diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) were identified between 2000 and 2013, using ICD-9-CM codes for IBD, from our hospital database. The following parameters were evaluated for each admission: type of admission (ordinary vs. day care service), mode of admission (elective vs. emergency care, for ordinary admissions only), admission code, surgical procedures and complication rates. Comparison between pre- and post-biologic therapy introduction years was also performed., Results: Between 2000 and 2013 a total of 8834 IBD-related admissions were recorded. Hospitalizations increased linearly reaching a peak in 2006, with a downward trend in the following years. The downward trend was especially marked for patients younger than 40 years. No significant differences in hospitalization trends between CD and UC were recorded. Disease flare represented the cause of hospitalization in approximately 50% of cases. Overall, 10.8% of patients underwent surgery with no difference between the two conditions. Complications occurred in 28.7% of admissions., Conclusions: Hospitalizations for IBD patients have decreased in recent years, especially in younger patients. However, a significant proportion of patients are still admitted to complete diagnostic workup, indicating the need to better implement outpatient services. A clear reduction in surgery occurrence over time could not be observed in our study.

Objective: Few models of transition have been proposed for inflammatory bowel disease (IBD). The aim of the present study is to evaluate the feasibility of a transition model and the predictive factors for success/failure., Patients and Methods: Patients with low activity or remission IBD were enrolled. Proposed model: three meetings every four-six weeks: the first one in the pediatric center (Bambino Gesù Children's Hospital); the second one, in the adult center (Foundation Polyclinic University A. Gemelli), with pediatric gastroenterologists; the last one, in the adult center, with adult gastroenterologists only. Questionnaires included anxiety and depression clinical scale, self-efficacy, quality of life, visual-analogic scale (VAS). Transition was considered successful if the three steps were completed., Results: Twenty patients were enrolled (range 18-25 years; M/F: 12/8; Ulcerative Colitis/Crohn's Disease 10/10); eight accepted the transition program, four delayed the process and eight refused. Patients who completed transition generated higher scores on the resilience scale, better scores on well-being perception, and had lower anxiety scores. Patients who failed transition were mostly women. The perceived utility of the transition program was scored 7.3 on a VAS scale., Conclusions: The proposed transition program seems to be feasible. Psychological scores may help in selecting patients and predicting outcomes.

Objective: The vaginal microbiome is a dynamic environment, depending on the results of a complex interplay between microbiota and the host. In physiological conditions, Lactobacillus species are the most represented, regulating glycogen metabolism in order to maintain normal pH. Vaginal flora has been divided into five subtypes. Pattern recognition receptors are present on both squamous epithelial cells lining the vagina and columnar cells lining the upper female genital tract. They respond directly to bacterial product expressed by vaginal microbiome. The vagina contains different immune related cells and receptors which can recognize and react with the microbial environment. Altered microbiota and altered interplay between microbiota and immune system underlie several gynecologic diseases., Materials and Methods: In this review, literature data related to vaginal microbiota, vaginal inflammation, immune system and menopause, preterm labor and miscarriage, were summarized. Relevant publications were retrieved from: PubMed, Medline, Scopus and Web of Science., Results: The vaginal microbiome and the relationship with immune system has been analyzed in different gynecologic conditions. Menopause is associated to estrogen loss which causes vaginal atrophy, reduced abundance of Lactobacilli and increased amount of other bacterial species. Estrogens influence vaginal immunity through known and unknown mechanisms. In bacterial vaginosis (BV), due to many bacterial species, there has been found an inhibition of the chemotaxis and cytokine secretion. A decreased concentration of Lactobacilli seems to be playing a role in preterm labor as well as the increased levels of pro-inflammatory cytokines. Finally, the disequilibrium in the Th1/Th2 immune adaptive response, with a shift from Th2 to Th1, appears to be playing a role in miscarriage., Conclusions: The interplay between microbiota and the host closely involves the immune system. In particular, the vaginal microbiota is classically characterized by Lactobacilli even if vaginal microbiome of asymptomatic woman of reproductive age includes multiple aerobic and facultative or obligate anaerobic species. The role of microbiota and immune system in determining gynecological and obstetric events has been studied throughout recent years reaching new advancements. Therefore, additional studies are needed to better comprehend the complexity of the issue.

Objective: Therapeutic strategies for Inflammatory Bowel Diseases (IBD: Crohn's disease and Ulcerative Colitis) have improved but the risk for HPV infection in patients under immunomodulatory/biologic treatment is unclear. Objective of the study is to identify the attitude of patients and caregivers to cervical screening. To determine the prevalence of HPV and cervical lesions in IBD patients receiving immunomodulatory/biological treatment., Patients and Methods: IBD patients treated with immunomodulators were enrolled from November 2016 to September 2017, thanks to a multidisciplinary cooperation. A survey was administered to enrolled patients as well as to a selected network of IBD expert physicians. Patients who consented underwent gynecological examination, smear, HPV DNA test, colposcopy, vaginal and cervical microbiological swabs., Results: 294 patients from AMICI Onlus Association, 119 patients from the hospital clinic, 30 doctors from national IBD centers participated to the survey. 19 patients from the IBD clinic underwent cervical screening. More than 90% of doctors consider their patients at risk of cervical cancer. A low prevalence of high-risk genotypes and related HPV lesions and an increased prevalence of bacterial vaginosis emerged in the studied population., Conclusions: Biological drugs could lead to a positive immunomodulation towards HPV infection. In IBD patients an alteration of the vaginal and intestinal microbiota seems to be coexisting.

Objective: Gut microbiota has a key role in host metabolic regulation and immune response, and its dysbiosis represents one of the main causes of gastrointestinal diseases. In this scenario, Akkermansia muciniphila is a crucial player in keeping the integrity of the gastrointestinal tract., Materials and Methods: This review focuses on the correlation between gut microbiota and intestinal homeostasis, primarily exploring A. muciniphila and its involvement in the development of metabolic disorders and gastrointestinal diseases., Results: Akkermansia muciniphila belongs to the Verrucomicrobia phylum, and it colonizes the mucus layer in the gastrointestinal tract, representing 1 to 4% of the fecal microbiota. It stimulates mucosal microbial networks, and it improves intestinal barrier function, providing crucial host immunological responses. Several studies have demonstrated the possible involvement of A. muciniphila in the development of intestinal and metabolic disorders. Indeed, adipose and glucose metabolisms are influenced by A. muciniphila, and its levels inversely correlate to inflammatory conditions, such as inflammatory bowel disease, obesity, and diabetes. Conversely, its therapeutic administration decreases their development., Conclusions: A. muciniphila exerts a key role in the maintenance of intestinal health and in host metabolic modulation. Future studies could open new horizons towards its potential therapeutic applications in gastrointestinal and extra-intestinal diseases.

Intestinal permeability is the property that allows solute and fluid exchange between intestinal lumen and intestinal mucosa. Many factors could have major impact on its regulation, including gut microbiota, mucus layer, epithelial cell integrity, epithelial junction, immune responses, intestinal vasculature, and intestinal motility. Any change among these factors could have an impact on intestinal homeostasis and gut permeability. Healthy condition is associated to normal intestinal permeability whereas several intestinal and extra intestinal disease, like inflammatory bowel disease, irritable bowel syndrome, non-alcoholic fatty liver disease among others, are associated to increased intestinal permeability. This review aims to synthesize determinants on intestinal permeability and to report methodologies useful to the measurement of intestinal permeability in clinical practice as well as in research settings.

Objective: the role of microbes and chronic inflammation in the pathogenesis of Alzheimer' disease (AD) has been postulated by many authors. On the other hand, several studies have reported the main role of H. pylori infection and/or GUT microbiota alteration in promoting chronic inflammation, thus possibly influencing both occurrence and evolution of AD. In this article, we analyze the most important and recent studies performed on this field both on humans and animals and provide possible pathogenic explanations., Results: all main and most recent animal, human, epidemiological and in-silico studies, showed a role of H. pylori and/or dysbiosis in AD, mostly through the promotion of systemic chronic inflammation and/or by triggering molecular mimicry mechanisms. In particular, H. pylori infection seems to be related to a poorer cognitive performance., Conclusions: Indeed, bacteria have been shown to affect neurodegeneration by promoting inflammation, inducing molecular mimicry mechanisms and accumulation of Aβ into the brain. These findings open the way for H. pylori eradicating trials and/or GUT microbiota remodulating strategies. Therefore, further studies are now needed in order to test whether antibiotics, pre and/or probiotics may exert a beneficial effect in the prevention of AD.

Objective: Even if pancreatic pathologies, residual fibrosis, residual amount of parenchyma, and anastomotic patency are recognized as main causes of exocrine and glycemic impairment after pancreaticoduodenectomy (PD), few data are reported concerning the role of the different pancreatic remnant treatment techniques. The objective of the study is to assess and compare exocrine functionality, glycemic pattern, nutritional status, and quality of life (QoL) after PD between pancreaticojejunostomy (PJ) and pancreatic duct occlusion (PDO), both in an objective and a subjective manner., Patients and Methods: Thirty-two patients (16 PJ and 16 PDO) were evaluated after a mean follow-up of 21 months after surgery. Exocrine insufficiency was objectively evaluated through the 13C-labelled mixed triglyceride breath test. Fasting glucose, fasting insulin, HbA1c and HOMA-IR values were used to assess glucose metabolism. For these two outcomes, anamnestic data were also collected. QoL was assessed with GIQLI, SF-36, EORTC-QLQ-C30, and EORTC-PAN-26 questionnaires., Results: The 13C-labelled mixed triglyceride breath test detected a lipid digestive insufficiency in 56% of patients after PJ and 100% after PDO respectively (p = 0.007). However, no difference was observed between the two groups regarding postoperative necessity of substitutive pancreatic enzymes. Nutritional status, fasting plasma glucose, fasting insulin, HbA1c levels, HOMA-IR values and postoperative necessity of insulin or oral antidiabetic agents were comparable between the two groups. QoL measurements showed similar results. However, in the subdomains analysis, better outcomes were reported regarding digestive symptoms and physical functioning for PJ and PDO respectively., Conclusions: Even if an objective exocrine major impairment was evidenced after PDO, this result did not impact the need for a higher rate of postoperative substitutive enzymes. In terms of glycemic pattern, nutritional status, and QoL, the two techniques turn out to be comparable.

Objective: Primary small intestinal neoplasms are uncommon tumors that are often small and difficult to identify. The aim of this paper is to describe CT technique and features in detecting and characterizing the tumors of the small bowel., Materials and Methods: This paper focuses on radiological characteristics of benign and malignant primary neoplasms of the small bowel at CT, with special reference to multidetector-CT techniques, type and modality of administration of contrast agents (by oral route or CT-enterography and by nasojejunal tube or CT-enteroclysis). This paper will also provide pictures and description of CT findings of benign and malignant primary neoplasms using examples of CT-enterography and CT-enteroclysis., Results: Among CT modalities, CT-enterography has the advantage of defining the real extension of wall lesions, possible transmural extension, the degree of mesenteric involvement and remote metastasis. Other useful modalities for the diagnosis of such lesions like capsule endoscopy and enteroscopy, provide important information but limited to mucosal changes with lower accuracy on extension and bowel wall involvement or submucosal lesions., Conclusions: Multidetector-CT, performed after distension of the small bowel with oral contrast material and intravenous injection of iodinated contrast material, is a useful method for the diagnosis and staging of small bowel neoplasms.

Gut microbiota is characterized by an inter-individual variability due to genetic and environmental factors. Among the environmental ones, dietary habits play a key role in the modulation of gut microbiota composition. There are main differences between the intestinal microbiota of subjects fed with prevalent Western diet and that of subjects with a diet rich in fibers. Specific changes in the composition of gut microbiota have been demonstrated among subjects according to a different dietary intake. A particular diet may promote the growth of specific bacterial strains, driving hosts to a consequent alteration of fermentative metabolism, with a direct effect on intestinal pH, which can be responsible for the development of a pathogenic flora. Moreover, a high-fat diet can promote the development of a pro-inflammatory gut microbiota, with a consequent increase of intestinal permeability and, consequently, of circulating levels of lipopolysaccharides. In this review, we discuss the direct role of the diet in the composition of gut microbiota and about the possible clinical consequences.

Objective: Helicobater (H.) pylori eradication rates with standard first-line triple therapy have declined to unacceptable levels. To date, amoxicillin-resistant H. pylori strains have rarely been detected. Whether increasing the dosage of amoxicillin in a standard 7 days eradicating regimen may enhance its efficacy is not known. The aim of this paper is to compare the efficacy of a 7 days high-dose amoxicillin based first-line regimen with sequential therapy., Patients and Methods: We have retrospectively analyzed data from 300 sex and age matched patients, who underwent 3 different therapeutic schemes: (1) standard LCA, lansoprazole 30 mg bid, clarithromycin 500 mg bid and amoxicillin 1000 mg bid for 7 days; (2) high dose LCA (HD-LCA), lansoprazole 30 mg bid, clarithromycin 500 mg bid and amoxicillin 1000 mg tid for 7 days; (3) sequential LACT, lansoprazole 30 mg bid plus amoxicillin 1000 mg bid for 5 days, followed by lansoprazole 30 mg bid, clarithromycin 500 mg bid and tinidazole 500 mg bid for 5 days. Eradication was confirmed by 13C-urea breath test. Compliance and occurrence of adverse effects were also assessed., Results: Eradication rates were: 55% for LCA, 75% for HD-LCA and 73% for LACT. Eradication rates were higher in HD-LCA group compared to LCA (p<0.01), while no significant differences were observed in HD-LCA group compared to LACT (p=ns). Compliance and occurrence of adverse effects were similar among groups., Conclusions: High-dose amoxicillin based eradicating treatment is superior to standard triple therapy and equivalent to sequential therapy; compared to the latter, the shorter duration may represent an advantage.

Objective: Gut barrier is a functional unit organized as a multi-layer system and its multiple functions are crucial for maintaining gut homeostasis. Numerous scientific evidences showed a significant association between gut barrier leaking and gastro-intestinal/extra-intestinal diseases., Materials and Methods: In this review we focus on the relationship between gut barrier leaking and human health. At the same time we speculate on the possible new role of gut barrier protectors in enhancing and restoring gut barrier physiology with the final goal of promoting gut health., Results: The alteration of the equilibrium in gut barrier leads to the passage of the luminal contents to the underlying tissues and thus into the bloodstream, resulting in the activation of the immune response and in the induction of gut inflammation. This permeability alteration is the basis for the pathogenesis of many diseases, including infectious enterocolitis, inflammatory bowel diseases, irritable bowel syndrome, small intestinal bacterial overgrowth, celiac disease, hepatic fibrosis, food intolerances and also atopic manifestations. Many drugs or compounds used in the treatment of gastrointestinal disease are able to alter the permeability of the intestinal barrier. Recent data highlighted and introduced the possibility of using gelatin tannate, a mucosal barrier protector, for an innovative approach in the management of intestinal diseases, allowing an original therapeutic orientation with the aim of enhancing mucus barrier activity and restoring gut barrier., Conclusions: These results suggest how the mucus layer recovering, beside the gut microbiota modulation, exerted by gut barrier protectors could be a useful weapon to re-establish the physiological intestinal homeostasis after an acute and chronic injury.

Acute diarrhea is a very common symptom, which may recognize different causes and is basically the expression of an altered homeostasis of the bowel, which overcame current classifications. When approaching patients with acute diarrhea, we should firstly check body temperature and vital parameters and secondly provide a general medical examination mainly focused on the abdomen, in order to exclude surgical causes of diarrhea, such as acute appendicitis, diverticulitis, intestinal occlusion and others. Another important aspect is the assessment of the level of hydration in order to provide the right amount of fluids. There is no current indication for the administration of loperamide in infectious diarrhea, but there is a strong rationale for new class of drugs, which may be defined as "mucous regenerators", such as gelatin tannate. Further studies are needed on this matter in order to test the effect of gelatin tannate in adult patients with acute diarrhea.

Several non invasive tests are available to assess pancreatic function, but no one is routinely used in clinical practice to diagnose chronic pancreatitis, due to their poor sensitivity in diagnosing mild pancreatic insufficiency. (13)C breath tests share the same limits of the other non invasive functional tests, but the mixed triglyceride breath test seems to be useful in finding the correct dosage of enzyme substitutive therapy to prevent malnutrition in patients with known pancreatic insufficiency.

Digestion is a complex process regulated by several factors. Among these, one of the most important is the time of gastric emptying. A delayed gastric emptying time can be caused by several factors and can generate considerable discomfort in humans. It ranges from mild to real debilitating disorders. Until now, different tests are suggested to study the gastric emptying time. The present review presents the mayor cause and the main symptoms linked to delayed gastric emptying and will focus on the (13)C-octanoid acid breath test, as a good candidate for studying solid gastric emptying time.

The high demand of Breath Tests (BT) in many gastroenterological conditions in time of limited resources for health care systems, generates increased interest in cost analysis from the point of view of the delivery of services to better understand how use the money to generate value. This study aims to measure the cost of C13 Urea and other most utilized breath tests in order to describe key aspects of costs and reimbursements looking at the economic sustainability for the hospital. A hospital based cost-analysis of the main breath tests commonly delivery in an ambulatory setting is performed. Mean salary for professional nurses and gastroenterologists, drugs/preparation used and disposable materials, purchase and depreciation of the instrument and the testing time was used to estimate the cost, while reimbursements are based on the 2013 Italian National Health System ambulatory pricelist. Variables that could influence the model are considered in the sensitivity analyses. The mean cost for C13--Urea, Lactulose and Lactose BT are, respectively, Euros 30,59; 45,20 and 30,29. National reimbursement often doesn't cover the cost of the analysis, especially considering the scenario with lower number of exam. On the contrary, in high performance scenario all the reimbursement could cover the cost, except for the C13 Urea BT that is high influenced by the drugs cost. However, consideration about the difference between Italian Regional Health System ambulatory pricelist are done. Our analysis shows that while national reimbursement rates cover the costs of H2 breath testing, they do not cover sufficiently C13 BT, particularly urea breath test. The real economic strength of these non invasive tests should be considered in the overall organization of inpatient and outpatient clinic, accounting for complete diagnostic pathway for each gastrointestinal disease.

Intestinal gases are the expression of metabolic activity of gut microbiota in the gut, particularly carbohydrates in the case of H2, CH4. Alterations in composition of gases and air handling, directly or upon challenge with food are relevant for GI and extra-GI diseases. Assessing gas composition in breath can be a very useful tool for clinic, but technical issues are crucial (breath sampling, storing and analyzing). Aim of the present review is to summarize the understanding of the importance of intestinal gases in gastro-intestinal physiology and patho-physiology. Practical considerations on how to collect samples and instruments available for the clinic have also been provided.

Breath tests are non-invasive, non-radioactive, safe, simple and effective tests able to determine significant metabolic alterations due to specific diseases or lack of specific enzymes. Carbon isotope (13)C, the stable-non radioactive isotope of carbon, is the most used substrate in breath testing, in which (13)C/(12)C ratio is measured and expressed as a delta value, a differences between readings and a fixed standard. (13)C/(12)C ratio is measured with isotope ratio mass spectrometry or non-dispersive isotope-selective infrared spectrometer and generally there is a good agreement between these techniques in the isotope ratio estimation. (13)C/(12)C ratio can be expressed as static measurement (like delta over baseline in urea breath test) or as dynamic measurement as percent dose recovery, but more dosages are necessary. (13)C Breath-tests are involved in many fields of interest within gastroenterology, such as detection of Helicobacter pylori infection, study of gastric emptying, assessment of liver and exocrine pancreatic functions, determination of oro-caecal transit time, evaluation of absorption and to a lesser extend detection of bacterial overgrowth. The use of every single test in a clinical setting is vary depending on accuracy and substrate costs. This review is meant to present (13)C the meaning of (13)C/(12)C ratio and static and dynamic measure and, finally, the instruments dedicated to its use in gastroenterology. A brief presentation of (13)C breath tests in gastroenterology is also provided.

Breath tests (BT) represent a valid and non-invasive diagnostic tool in many gastroenterological disorders. Their wide diffusion is due to the low cost, simplicity and reproducibility and their common indications include diagnosis of carbohydrate malabsorption, Helicobacter pylori infection, small bowel bacterial overgrowth, gastric emptying time and orocaecal transit time. The review deals with key points on methodology, which would influence the correct interpretation of the test and on a correct report. While a clear guideline is available for lactose and glucose breath tests, no gold standard is available for Sorbitol, Fructose or other H2 BTs. Orocaecal transit time (OCTT) defined as time between assumption of 10 g lactulose and a peak > 10 ppm over the baseline value, is a well-defined breath test. The possible value of lactulose as a diagnostic test for the diagnosis of small bowel bacterial overgrowth is still under debate. Among (13)C breath test, the best and well characterized is represented by the urea breath test. Well-defined protocols are available also for other (13)C tests, although a reimbursement for these tests is still not available. Critical points in breath testing include the patient preparation for test, type of substrate utilized, reading machines, time between when the test is performed and when the test is processed. Another crucial point involves clinical conclusions coming from each test. For example, even if lactulose could be utilized for diagnosing small bowel bacterial overgrowth, this indication should be only secondary to orocaecal transit time, and added into notes, as clinical guidelines are still uncertain.

Objective: Aim of this review is to summarize the studies carried out, with particular interest in those who dealt with otilonium bromide in treatment of IBS. Irritable bowel syndrome (IBS)., Discussion: IBS is a frequent gastrointestinal disease, characterized by a combination of several symptoms including abdominal pain or discomfort, flatulence and problems related to bowel habits (constipation and/or diarrhea). It affects about 15% of the western population, with a negative impact on the quality of life and also on health care costs. Face to such important complexity and negative impact, therapeutic options are still very limited and most of the pharmacological compounds mostly validated for short term use, are only partially controlling symptoms. Among those, anti-spasmodics are commonly used in clinical settings. Despite a discrete literature in support of these drugs, systematic collections of clinical evidence to support the use of anti-spasmodics and in particular the use of otilonium bromide in course of IBS are scarce., Results and Conclusion: Otilonium bromide is a systemically poorly absorbed antispasmodic, which has shown clear efficacy compared to placebo, in controlling symptoms related to IBS. Otilonium bromide was effective also in comparison to other drugs, such as pinaverium bromide and mebeverine, with a favorable tolerability profile. Further studies are necessary to better define duration of treatment and maximum therapeutic dose.

Background: Gastrointestinal motility disorders are often present in diabetic patients (pts). Such motility dysfunctions have been attributed to autonomic neuropathy. Impaired intestinal motility is often associated with small-bowel bacterial overgrowth (SIBO) but only few studies evaluated the relationship between autonomic neuropathy and SIBO in diabetic pts., Aim: To compare the prevalence of SIBO between type 1 diabetic (T1D) pts with and without autonomic neuropathy., Patients and Methods: 25 pts (13 males, 12 females; mean age 44.2+/-7) affected by type 1 diabetes with normal cardiovascular autonomic test (group A) and 25 type 1 diabetic pts with abnormal cardiovascular autonomic test (group B) were submitted to hydrogen lactulose breath test., Results: 2 out of 25 (8%) showed SIBO among group A, while 11 out of 25 (44%) showed SIBO among group B (p<0.01). Interestingly, among group B, the daily insulin requirements was significantly higher in SIBO-positive pts compared to SIBO-negative: 0.66+/-0.3 vs. 0.59+/-0.1 UI/kg (p<0.05)., Conclusions: Pts with autonomic neuropathy have a significantly higher prevalence of SIBO, that is also associated with a higher daily insulin requirements.

In the last decade, biologic agents, in particular infliximab and adalimum-ab, have deeply changed the therapeutic armamentarium of inflammatory bowel disease (IBD). However, these drugs have a number of contraindications and side-effects that physicians should know so to avoid and eventually manage them. Another important issue is the early introduction of immunomodulators and biologics in the therapeutic algorithm of IBD, the so called "top-down" approach compared to the traditional "step-up" approach. In this review, the indications to the use of anti-TNF-alpha molecules in IBD are briefly reported and the potential benefits and disadvantages of a more aggressive approach are discussed.

Crohn's disease (CD) and ulcerative colitis (UC) are the two major forms of inflammatory bowel disease (IBD). Although their etiology is still unknown, the pathogenic mechanisms underlying intestinal inflammation have made impressive progress in our understanding. In particular, the abnormalities underlying IBD pathogenesis are not restricted to those mediated by classical immune cells such as T and B lymphocytes, macrophages and dendritic cells, but also nonimmune cells. Interestingly, endothelium has become one of the major areas of investigation in gut inflammation.

Besides their classical haemostatic task, platelets are now recognized as novel cells deeply involved in inflammation. Compelling evidence support their role as active player in mucosal tissue injury that occurs in Crohn's disease and ulcerative colitis. In both forms of inflammatory bowel disease platelets contribute to microvascular endothelial activation and recruitment of inflammatory cells, thus fostering and amplifying mucosal inflammation.

Intercellular adhesion molecule (ICAM)-1 is a single-chain cell surface glycoprotein that plays an important role in the recruitment of leukocytes at sites of inflammation and is up-regulated in intestinal mucosa of inflammatory bowel disease (IBD). ICAM-1 gene lies on chromosome 19p13, implicated in determining susceptibility to IBD. The human ICAM-1 gene contains two polymorphic sites in codon 241 (G241R) and 469 (K469E) which have been implicated in the susceptibility to a range of degenerative and inflammatory diseases. Recently, several reports have shown discordant data regarding the association of these polymorphisms with IBD. In particular, we found an association of IBD with the E/E genotype while allele E469 was associated with a subgroup of patients with more extensive location of Crohn's disease and penetrating behaviour. However, other studies reached different conclusions. A possible explanation for the discrepancy of results is probably the influence of the different geographic distribution of the genetic mutations.