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Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAM, Background: There has been resurgence in the use of bismuth quadruple therapy (proton pump inhibitor, bismuth, tetracycline and metronidazole) for treating Helicobacter pylori infection thanks to a three-in-one single-capsule formulation. Objective: To evaluate the effectiveness and safety of the single-capsule bismuth quadruple therapy. Methods: Data were collected in a multicentre, prospective registry of the clinical practice of gastroenterologists on the management of H. pylori infection, where patients were registered at the Asociación Española de Gastroenterologia REDCap database on an electronic case report form until January 2020. Effectiveness by modified intention-to-treat and per-protocol as well as multivariable analysis were performed. Independent factors evaluated were: age, gender, indication, compliance, proton pump inhibitor dose and treatment line. Results: Finally, 2100 patients were prescribed single-capsule bismuth quadruple therapy following the technical sheet (i.e., three capsules every 6 h for 10 days). The majority of these patients were naive (64%), with an average age of 50 years, 64% women and 16% with peptic ulcer. An overall modified intention-to-treat effectiveness of 92% was achieved. Eradication was over 90% in first-line treatment (95% modified intention-to-treat, n = 1166), and this was maintained as a rescue therapy, both in second (89% modified intention-to-treat, n = 375) and subsequent lines of therapy (third to sixth line: 92% modified intention-to-treat, n = 236). Compliance was the factor most closely associated with treatment effectiveness. Adverse events were generally mild to moderate, and 3% of patients reported a severe adverse event, leading to discontinuation of treatment in 1.7% of cases. Conclusions: Single-capsule bismuth quadruple therapy achieved H. pylori eradication in approximately 90% of patients in real-world clinical practice, both as a first-line and rescue treatment, with good compliance and a favourable safety profile, The author(s) would like to thank the Spanish Association of Gastroenterology (AEG) for providing the electronic case report form service free of charge. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This project was promoted and funded by the European Helicobacterand Microbiota Study Group, and received support from the Spanish Association of Gastroenterology (AEG) and the Centro de Investigación Biomedica en Red de Enfermedades Hepaticas y Digestivas

Regulatory T cells (Tregs) are important for the induction and maintenance of peripheral tolerance therefore, they are key in preventing excessive immune responses and autoimmunity. In the last decades, several reports have been focussed on understanding the biology of Tregs and their mechanisms of action. Preclinical studies have demonstrated the ability of Tregs to delay/prevent graft rejection and to control autoimmune responses following adoptive transfer in vivo. Due to these promising results, Tregs have been extensively studied as a potential new tool for the prevention of graft rejection and/or the treatment of autoimmune diseases. Currently, solid organ transplantation remains the treatment of choice for end-stage organ failure. However, chronic rejection and the ensuing side effects of immunosuppressants represent the main limiting factors for organ acceptance and patient survival. Autoimmune disorders are chronic diseases caused by the breakdown of tolerance against self-antigens. This is triggered either by a numerical or functional Treg defect, or by the resistance of effector T cells to suppression. In this scenario, patients receiving high doses of immunosuppressant are left susceptible to life-threatening opportunistic infections and have increased risk of malignancies. In the last 10 years, a few phase I clinical trials aiming to investigate safety and feasibility of Treg-based therapy have been completed and published, whilst an increasing numbers of trials are still ongoing. The first results showed safety and feasibility of Treg therapy and phase II clinical trials are already enrolling. In this review, we describe our understanding of Tregs focussing primarily on their ontogenesis, mechanisms of action and methods used in the clinic for isolation and expansion. Furthermore, we will describe the ongoing studies and the results from the first clinical trials with Tregs in the setting of solid organ transplantation and autoimmune disorders. Finally, we will discuss strategies to further improve the success of Treg therapy.

Introduction: Gastric cancer is the second leading cause of cancer all over the world. Unfortunately, several gastric cancers are diagnosed in an advanced stage and chemotherapy and/or target therapies remain the only options to treat patients. Areas covered: Herein we evaluate the new molecular proposal of gastric cancer classification, offering the possibility to recognize different pathogenetic mechanisms and molecular biomarkers potentially useful for target therapies. Expert commentary: The possibility of introducing new specific tests for identification of molecular biomarkers critical for targeted therapies response represents the new frontier in the selection of gastric cancer patients to improve their survival. Besides HER2, already used in clinical settings as a target biomarker for biological therapy in gastric cancer patients with tissue cancer cells overexpressing HER2, other promising target biomarkers which are deregulated in gastric cancer, such as MET and FGFR, could be identified in tissue and then used for therapeutic purposes. In addition immunotherapy represents the most promising possibility of advanced gastric cancer treatment. In particular, as in other solid tumors, PD-1/PDL1 pathway has emerged in several clinical trials as an interesting therapeutic target.

Splenectomy is a time-honoured well established approach for patients with steroid-resistant immune thrombocytopenia (ITP). However, due to the more recent availability of therapeutic options alternative to splenectomy, such as rituximab and agonists of the thrombopoietin-receptor, the choice of second-line therapy is challenging. Platelet kinetics has been widely used to predict response to splenectomy. We describe the outcome of 70 chronic ITP patients who performed a platelet kinetic study after failure of front-line corticosteroids and subsequently underwent open splenectomy. After a median follow-up from surgery of 20 years, 62 (88.5%) patients responded to splenectomy and 9 patients (13%) relapsed. Achieving a complete response (CR) significantly predicted a higher probability long-term stable response. The pattern of platelet sequestration was predominantly splenic in 52 patients (74%), predominantly hepatic in 12 patients (17%), and diffuse in 6 (9%). Patients with nonsplenic (diffuse and hepatic) sequestration showed significantly lower overall responses compared to patients with splenic captation (P = 0.002). A nonsplenic sequestration significantly correlated with lower CR rate and, among CR patients, predicted an increased risk of relapse. Also, the probability of stable responses in nonsplenic uptake patients was substantially lower than in patients with splenic uptake (85% vs. 50%, P = 0.0083). Platelet life span and platelet turnover did not correlate with response and relapse rate. Overall, splenic sequestration was able to predict not only a better quality, but also a higher durability of the responses. However, it should be enphasized that the response rate and duration of response even in patients with nonsplenic uptake were similar or even superior to those reported in patients treated with rituximab as first option. © 2014 Wiley Periodicals, Inc.

Prevalence of gastroduodenal lesions is changing in the last decades. Prevalence of Helicobacter pylori infection, non-steroidal anti-inflammatory drugs (NSAIDs), and proton pump inhibitor (PPI) therapy may be involved in such a phenomenon. We assessed gastroduodenal lesions prevalence in a nationwide study.Consecutive patients who underwent upper endoscopy for the first time in 24 Italian centres between January 2012 and 31 March 2012 were enrolled. Prevalence of gastric ulcer (GU), duodenal ulcer (DU), gastric erosions (GE), duodenal erosions (DE), gastric polyp (GP), Barrett's oesophagus (BE), and neoplasia was assessed.Overall, 1054 (M/F: 388/666; Mean age: 57.5 ± 5 years) patients were enrolled. H. pylori infection was detected in 356 (33.9%) patients, 358 (34%) were taking NSAIDs, and 532 (50.5%) PPIs. PPI therapy was associated with a significantly lower H. pylori detection rate (27.8% vs 39.8%; OR: 0.6, 95% CI 0.45-0.77; P0.001). GU, DU, GE, DE, GP and BE were detected in 17 (1.6%), 13 (1.2%), 150 (14.2%), 50 (4.7%), 51 (4.8%) and 17 (1.6%), respectively. Moreover, 3 (0.3%) distal gastric cancers were observed. H. pylori infection remained the most prevalent factor for all gastroduodenal lesions, but gastric polyp. One third of patients with GU and GE were taking only NSAIDs therapy.The prevalence of peptic ulcer was very low (3%), with a similar rate between DU and GU. As many as half patients were on ongoing PPI therapy. Such a therapy could affect both the detection rate of H. pylori infection and the real prevalence of gastroduodenal lesions.

Background: Ulcerative colitis may impair anorectal function, causing disabling symp-toms such as incontinence and/or increase in the stool frequency, urgency and tenesmus. Data on anorectal function in these patients evaluated by conventional anorectal manometry are conflicting. Objectives: The aim of this prospective study was to assess by means of high resolution anorectal manometry the anorectal function in patients with mild-to-moderate ulcerative colitis at presentation and after remission. Anorectal function of ulcerative colitis patients was compared to that observed in healthy volunteers. Methods: 20 patients with mild to moderate left-sided ulcerative colitis or proctitis and 20 healthy volunteers were prospectively enrolled. All ulcerative colitis patients underwent high resolution ano-rectal manometry before treatment and after clinical remission. Results: Ulcerative colitis patients showed similar values for anal sphincter function as healthy vol-unteers, whereas rectal threshold volume for the first sensation, desire to defecate, urgency to defecate and maximum discomfort were significantly lower than in healthy volunteers (p Conclusions: Ulcerative colitis patients show altered rectal function, with increased rectal sensitivity and lower compliance, compared to controls. This altered function is restored after successful treat-ment of the underlying inflammatory process. Finally high resolution anorectal manometry provides useful information on anorectal functionality and, in our opinion, should be preferred over conven-tional manometry.

Regenerative medicine aims to replace damaged tissues by stimulating endogenous tissue repair or by transplanting autologous or allogeneic cells. Due to their capacity to produce unlimited numbers of cells of a given cell type, pluripotent stem cells, whether of embryonic origin or induced via the reprogramming of somatic cells, are of considerable therapeutic interest in the regenerative medicine field. However, regardless of the cell type, host immune responses present a barrier to success. The aim of this study was to investigate in vitro the immunological properties of human pluripotent stem cell (PSC)-derived hepatocyte-like cells (HLCs). These cells expressed MHC class I molecules while they lacked MHC class II and co-stimulatory molecules, such as CD80 and CD86. Following stimulation with IFN-γ, HLCs upregulated CD40, PD-L1 and MHC class I molecules. When co-cultured with allogeneic T cells, HLCs did not induce T cell proliferation; furthermore, when T cells were stimulated via αCD3/CD28 beads, HLCs inhibited their proliferation via IDO1 and tryptophan deprivation. These results demonstrate that PSC-derived HLCs possess immunoregulatory functions, at least in vitro.

Background: Patients affected by gastrointestinal disorders often experience sexual dysfunction (SD). This creates stress and anxiety which impact on patients’ and/or their partners’ quality of life. A multidisciplinary approach to SD is often advisable in these patients. This survey assessed if gastroenterologists routinely discuss SD with their patients and the barriers toward discussing SD in clinical practice. Methods: A 29-item questionnaire was sent to members of the Italian Society of Gastroenterology and Digestive Endoscopy (SIGE). A descriptive analysis of responses was performed. Results: Out of 714 eligible gastroenterologists, 426 (59.7%), responded.The majority (>70%) never/infrequently investigated SD with their patients and, similarly, most patients never discussed SD during the visit. The most reported reasons were lack of knowledge (58%), time (44%), and embarrassment (30%). However, more than 70% of respondents indicated that all specialists should be able to manage sexual problems, and more than 80% declared that it would be useful for gastroenterologists to attend courses dedicated to the problem of SD. Conclusion: Despite the high prevalence of SD, counselling was not routinely performed in gastroenterological care. Lack of education/knowledge appeared as the most important factor. Most of responders felt that attending a course on SD might increase the awareness of SD.

Objectives Patients with inflammatory bowel disease were excluded from trials that led to the approval of anti-COVID-19 vaccines and are worthy of real-life studies providing information on the safety of these vaccines in this clinical setting. Methods A prospective observational study was performed to estimate BNT162b2 mRNA COVID-19 Vaccine local and systemic adverse events (AEs) incidence related to administration in patients with inflammatory bowel disease through a questionnaire administered at the first, second, and third doses. Disease activity by Mayo Partial Score and Harvey-Bradshaw Index was also evaluated. Results Eighty patients with a median age of 47.5 years were initially enrolled. The local AEs rate was 26.25%, 58.75%, and 28.37% at the first, second, and third doses of the vaccine, respectively. In contrast, the systemic AEs rate was 52.2%, 48.75%, and 43.24%. Clinic-demographic predictor variables for AEs were not identified. Vaccination did not affect disease activity and no statistically significant difference in disease activity index scores was observed between the three doses. No serious adverse events were observed. Conclusion This vaccine was safe in a population of patients with inflammatory bowel disease and, therefore, could be safely administered in this clinical setting.

Gut microbiota is involved in immune modulation and immune checkpoint inhibitors (ICIs) efficacy. Single-arm phase II CAVE-mCRC and CAVE-LUNG clinical trials investigated cetuximab + avelumab combination in RAS wild-type (WT) metastatic colorectal cancer (mCRC) and chemo-refractory nonsmall cell lung cancer (NSCLC) patients, respectively. A comprehensive gut microbiota genetic analysis was done in basal fecal samples of 14 patients from CAVE-mCRC trial with circulating tumor DNA (ctDNA) RAS/BRAF WT and microsatellite stable (MSS) disease. Results were validated in a cohort of 10 patients from CAVE-Lung trial. 16S rRNA sequencing revealed 23 027 bacteria species in basal fecal samples of 14 patients from CAVE-mCRC trial. In five long-term responding patients (progression-free survival [PFS], 9-24 months) significant increases in two butyrate-producing bacteria, Agathobacter M104/1 (P=.018) and Blautia SR1/5 (P=.023) were found compared to nine patients with shorter PFS (2-6months). A significantly better PFS was also observed according to the presence or absence of these species in basal fecal samples. For Agathobacter M104/1, median PFS (mPFS) was 13.5months (95% confidence interval [CI], 6.5-20.5months) vs 4.6months (95% CI, 1.8-7.4months); P=.006. For Blautia SR1/5, mPFS was 5.9months (95% CI, 2.2-9.7months) vs 3.6months (95% CI, 3.3-4.0months); P=.021. Similarly, in CAVE-Lung validation cohort, Agathobacter M104/1 and Blautia SR1/5 expression were associated with PFS according to their presence or absence in basal fecal samples. Agathobacter and Blautia species could be potential biomarkers of outcome in mCRC, and NSCLC patients treated with cetuximab + avelumab. These findings deserve further investigation.

Background: During the COVID-19 pandemic in Italy, decisions were taken to adopt re-strictive legislative measures, such as the first half of the 2020 lockdown. In those months, patients with inflammatory bowel disease experienced social isolation and reduced access to health care. Objective: We aimed to evaluate, in this condition, the presence of remission subgroups that were most impacted by the lockdown. Methods: During the first Italian lockdown, we recruited patients with remission of inflammatory bowel disease by administering an online questionnaire including patient demographics, the Beck Anxiety Questionnaire Inventory, the Beck Depression Inventory questionnaire, and the Pittsburg Sleep Quality Index, all validated standardized questionnaires for anxiety symptom levels, depres-sion, and sleep quality. Results: Our results showed how female patients (p Conclusion: Among patients with remission of inflammatory bowel disease, female patients, pa-tients with Crohn’s disease, and people aged between 50 and 70 years should be considered for screening for anxiety and depression disorders and an assessment of sleep quality.

Funder: Wellcome Trust, The central goal of regenerative medicine is to replace damaged or diseased tissue with cells that integrate and function optimally. The capacity of pluripotent stem cells to produce unlimited numbers of differentiated cells is of considerable therapeutic interest, with several clinical trials underway. However, the host immune response represents an important barrier to clinical translation. Here we describe the role of the host innate and adaptive immune responses as triggers of allogeneic graft rejection. We discuss how the immune response is determined by the cellular therapy. Additionally, we describe the range of available in vitro and in vivo experimental approaches to examine the immunogenicity of cellular therapies, and finally we review potential strategies to ameliorate immune rejection. In conclusion, we advocate establishment of platforms that bring together the multidisciplinary expertise and infrastructure necessary to comprehensively investigate the immunogenicity of cellular therapies to ensure their clinical safety and efficacy.

Inflammatory bowel diseases (IBD) are chronic multifactorial diseases characterized by partially unclear pathogenic mechanisms including changes in intestinal microbiota. Despite the microbiota, alteration is well established in IBD patients, as reported by 16RNA sequencing analysis, an important goal is to define if it is just a consequence of the disease progression or a trigger factor of the disease itself. To date, gut microbiota composition and gut microbiota-related metabolites seem to affect the host healthy state both by modulating metabolic pathways or acting on the expression of different genes through epigenetic effects. Because of this, it has been suggested that intestinal microbiota might represent a promising therapeutic target for IBD patients. : The aim of this review is to summarize both the most recent acquisitions in the field of gut microbiota and its involvement in intestinal inflammation together with the available strategies for the modulation of microbiota, such as prebiotics and/or probiotics administration or fecal microbiota transplantation.

Background The gut-brain axis plays a potential role in numerous physiological and pathological conditions. Several substances link stomach with central nervous system. In particular, hypothalamo-pituitary-adrenocortical axis, thyrotropin-releasing factor-containing nerve fibers and capsaicin-sensitive nerves are principal mediators of the harmful and protective central nervous system-mediated effects on gastric mucosa. Also, existing evidence indicates that nitric oxide, prostaglandins and calcitonin gene-related peptide play a role as final effectors of gastric protection. Methods We undertook a structured search of bibliographic databases for peer-reviewed research literature with the aim of focusing on the role of gut-brain axis in gastric damage and protection. In particular, we examined manuscripts dealing with the role of steroids, thyrotropin-releasing hormone, prostaglandins, melatonin, hydrogen sulfide and peptides influencing food intake (i.e. leptin, cholecystokinin, peptide YY, central glucagon–like peptide-1, and ghrelin). Also, the role of GABAergic and glutamatergic pathways in gastric mucosal protection have been examined. Results We found and reviewed 61 peer-reviewed papers dealing with the major aspects related to the role of gut brain axis in gastric mucosal damage and protection. Conclusions A dense neuronal network links stomach with central nervous system and a number of neurotransmitters and peptides functionally and anatomically related to central nervous system play a major role in contributing to gastric mucosal integrity. Exploiting the mechanisms underlying the connection between brain and gut may lead to a better understanding of the pathophysiology of gastric mucosal injury and to an improvement in the prevention and, eventually, management of gastric damage.

Background: Clinical trials have shown a good efficacy of the “three-in-one” formulation of bismuth quadruple therapy (BQT) for Helicobacter (H.) pylori eradication. We aimed to assess the efficacy and safety of the three-in-one BQT in clinical practice, and investigate the effect of probiotic supplementation, in Italy. Materials and Methods: A retrospective database, multicentre observational study was conducted in seven Italian Hospitals. Consecutive H. pylori-positive patients who received the three-in-one BQT for 10days were included in the analysis. H. pylori eradication was assessed by histology,13C-urea breath test, or stool antigen test. Compliance and adverse events were evaluated by interview. Results: A total of 376 patients were included in the intention-to-treat (ITT) and 352 in the per protocol (PP) analyses. One hundred and ninety-three subjects received probiotics supplementation. Overall, eradication rates were 90.2% (95% Confidence Interval (CI):86.7-93.0) in ITT and 94.6% (95% CI: 91.7-96.7) in PP analyses. The compliance was good (≥90% of treatment taken) in 94.9% of patients. The proportion of patients with a good compliance was not different with and without probiotics supplementation (94.8% vs 95.1%). Eradication rates were equally high for first-line (91.4%), second-line (87.5%), and third-line treatments (91.7%) in the ITT analysis (P=.48). Adverse events were reported by 32.4% of patients, but only 6.1% of patients discontinued treatment. Conclusions: The three-in-one BQT is highly effective and well tolerated for H. pylori eradication in daily clinical practice. Probiotics supplementation fails to improve compliance.

The wound healing and the barrier restoration of the gastrointestinal (GI) mucosa must be continuously ensured to allow homeostasis of the gastrointestinal tract and of all the surrounding tissues. Several lines of the evidence report a key role of innate immunity, and in particular of Pattern Recognition Receptors (PRRs), in controlling the homeostasis of GI tract by sensing commensal and pathogen bacteria, activating the immune response and regulating epithelial repair, thus guaranteeing the morphological and functional recovery of the injured tissue. We will discuss the role of a particular class of PRRs - the Formyl Peptide Receptors - in the homeostasis of GI mucosa. We here report the results of studies that strongly suggest the possibility that the activation of FPRs is crucial in the maintenance of homeostasis of the GI tract and provide indications of the potential clinical relevance of new treatment regimens involving FPR modulation for several GI disorders.

Titanium dioxide (TiO2) is enclosed in many consumer products including pharmaceuticals, cosmetics, and foods. TiO2 (E171) is daily ingested as mixed nano- and submicron-sized particles since it is approved as a white colorant in Europe in a wide variety of food products, Noteworthy, the relevant risk assessment has never been satisfactorily concluded and growing alarms for human hazards deriving from TiO2 exposure are incrementally reported. The objective of the present study was to establish conceivable mechanisms by which nano-sized TiO2 particles affect physiological function of the intestinal epithelium layer. The well-established Caco-2 cell line differentiated for 21 days on permeable supports was used as a predictive model of the human intestinal mucosa to identify the biological response triggered by TiO2 particles. Exposure to 42 μg/mL TiO2 nanoparticles disrupted the tight junctions-permeability barrier with a prompt effect detectable after 4 h incubation time and wide effects on barrier integrity at 24 h. Transport and ultrastructural localization of TiO2 nanoparticles were determined by ICP-OES, TEM and ESI/EELS analysis, respectively. Nano-sized particles were efficiently internalized and preferentially entrapped by Caco-2 monolayers. Storage of TiO2 nanoparticles inside the cells affected enterocytes viability and triggered the production of pro-inflammatory cytokines, including TNF-α and IL-8. Taken together these data indicate that nano-sized TiO2 particles exert detrimental effects on the intestinal epithelium layer.

Inflammation may play a role in cancer. However, the contribution of cytokine-mediated crosstalk between normal hemopoietic stem/progenitor cells (HSPCs) and their (inflammatory) microenvironment is largely elusive. Here we compared survival, phenotype, and function of neonatal (umbilical cord blood (CB)) and adult (normal G-CSF-mobilized peripheral blood (mPB)) CD34+cells afterin vitroexposure to combined crucial inflammatory factors such as interleukin- (IL-) 1β, IL-6, tumor necrosis factor- (TNF-)α, or tissue inhibitor of metalloproteinases-1 (TIMP-1). To mimic bone marrow (BM) niche, coculture experiments with normal BM stromal cells (BMSCs) were also performed. We found that combined inflammatory cytokines increased only thein vitrosurvival of CB-derived CD34+cells by reducing apoptosis. Conversely, selected combinations of inflammatory cytokines (IL-1β + TNF-α, IL-6 + TNF-α, and IL-1β + TNF-α + TIMP-1) mainly enhanced thein vitroCXCR4-driven migration of mPB-derived CD34+cells. TNF-α, alone or in combination, upregulated CD44 and CD13 expression in both sources. Finally, BMSCs alone increased survival/migration of CB- and mPB-derived CD34+cells at the same extent of the combined inflammatory cytokines; importantly, their copresence did not show additive/synergistic effect. Taken together, these data indicate that combined proinflammatory stimuli promote distinctin vitrofunctional activation of neonatal or adult normal HSPCs.

Background Quality of bowel cleansing in hospitalized patients undergoing colonoscopy is often unsatisfactory. No study has investigated the inpatient or outpatient setting as cause of inadequate cleansing. Aims To assess degree of bowel cleansing in inpatients and outpatients and to identify possible predictors of poor bowel preparation in the two populations. Methods Prospective multicentre study on consecutive colonoscopies in 25 regional endoscopy units. Univariate and multivariate analysis with odds ratio estimation were performed. Results Data from 3276 colonoscopies were analyzed (2178 outpatients, 1098 inpatients). Incomplete colonoscopy due to inadequate cleansing was recorded in 369 patients (11.2%). There was no significant difference in bowel cleansing rates between in- and outpatients in both colonic segments. In the overall population, independent predictors of inadequate cleansing both at the level of right and left colon were: male gender (odds ratio, 1.20 [1.02–1.43] and 1.27 [1.05–1.53]), diabetes mellitus (odds ratio, 2.35 [1.68–3.29] and 2.12 [1.47–3.05]), chronic constipation (odds ratio, 1.60 [1.30–1.97] and 1.55 [1.23–1.94]), incomplete purge intake (odds ratio, 2.36 [1.90–2.94] and 2.11 [1.68–2.65]) and a runway time >12 h (odds ratio, 3.36 [2.40–4.72] and 2.53 [1.74–3.67]). Conclusions We found no difference in the rate of inadequate bowel preparation between hospitalized patients and outpatients.

Background: Mesalazine 1 g suppository/die is used for mild to moderately active ulcerative proctitis (UP). Whether addiction of Multi Matrix System (MMX) mesalazine increases the remission rate of UP and prevents proximal extension of disease is unknown. Methods: This is a retrospective study on 116 outpatients with UP who had been treated with one of the following regimens: (1) MMX mesalazine 1.2 g/die plus mesalazine suppositories for 8 ± 2 weeks and, subsequently, MMX mesalazine 1.2 g/die plus rectal mesalazine 1 g every other day for at least 6 months; (2) mesalazine 1 g suppositories/die alone for 8 ± 2 weeks and, subsequently, rectal mesalazine 1 g every other day for 6 more months. Patients were evaluated clinically at 2 months (±2 weeks) and endoscopically at 6 months (±2 weeks). For categorical variables, Pearson chi-square test was used. Results: A total of 46 of 55 patients (84%) on combined therapy and 49 of 61 patients (80%) on rectal mesalazine reached clinical remission (p > 0.05; OR 0.79, 95% CI 0.30–2.07). At 6 months follow-up, proximal extension of disease was observed in 7 of 55 (14%) patients on combined therapy and in 18 of 61 (29%) patients on rectal mesalazine alone (p < 0.05; OR 2.87, 95% CI 1.09–7.53). Conclusions: Oral MMX mesalazine plus rectal mesalazine combined treatment is associated with prevention of proximal extension of the disease compared with rectal mesalazine alone.

Irritable bowel syndrome (IBS) is characterized by visceral hypersensitivity likely related to altered processing of sensory stimuli along the brain-gut axis. Previous neuroimaging studies demonstrated structural and functional alteration of several brain areas involved in bodily representation, e.g. the insula, in patients with IBS. By means of resting-state functional magnetic resonance imaging (rs-fMRI) we searched for alteration of functional connectivity within the network involved in self-bodily consciousness. We found significant inverse correlation between hypochondriasis assessed through a clinical questionnaire and connectivity between posterior cingulate cortex and left supramarginal gyrus, extending into the adjacent superior temporal gyrus. Moreover, we observed a significant and positive correlation between a clinical questionnaire assessing interoception and connectivity between left anterior ventral insula and two clusters located in supramarginal gyrus bilaterally. Our findings highlight an “abnormal network synchrony” reflecting functional alteration, in the absence of structural and micro-structural changes, which might represent a possible therapeutic target for Irritable Bowel Syndrome.

Background: Inflammatory bowel disease (IBD) is a multi-factorial systemic disorder which involves immune, genetic and environmental factors. Stress, in its various forms, plays an important role in gastrointestinal diseases and, in particular, in IBD. Methods: Here, we focus on the environmental stressors in different aspects of IBD (pathogenesis, course and severity of disease) and, in particular, will evaluate the mechanisms by which they may influence IBD. Results: The effect of stress on IBD might be mediated by autonomic nervous system and hypothalamic pituitary adrenal axis. These nervous pathways are part of the so called “brain-gut axis” which links gastrointestinal integrity and functions to central nervous system acting through the increase of intestinal permeability, bacterial translocation and cytokines network. Conclusion: The incidence of emotional disorders is higher in Crohn’s Disease and Ulcerative Colitis compared to general population. Moreover, depression and anxiety influence the course and the severity of the underlying intestinal disease. Hence, it is important to consider appropriate psychological therapy in IBD patients.

BACKGROUND: Urotensin (U)-II receptor (UTR) has been previously reported to be over-expressed in a number of tumours. Whether UTR-related pathway plays a role in colon carcinogenesis is unknown. METHODS: We evaluated UTR protein and mRNA expression in human epithelial colon cancer cell lines and in normal colon tissue, adenomatous polyps and colon cancer. U-II protein expression was assessed in cancer cell lines. Moreover, we evaluated the effects of U-II(4-11) (an UTR agonist), antagonists and knockdown of UTR protein expression through a specific shRNA, on proliferation, invasion and motility of human colon cancer cells. RESULTS: Cancer cell lines expressed U-II protein and UTR protein and mRNA. By immunohistochemistry, UTR was expressed in 5-30% of epithelial cells in 45 normal controls, in 30-48% in 21 adenomatous polyps and in 65-90% in 48 colon adenocarcinomas. UTR mRNA expression was increased by threefold in adenomatous polyps and eightfold in colon cancer, compared with normal colon. U-II(4-11) induced a 20-40% increase in cell growth while the blockade of the receptor with specific antagonists caused growth inhibition of 20-40%. Moreover, the knock down of UTR with a shRNA or the inhibition of UTR with the antagonist urantide induced an approximately 50% inhibition of both motility and invasion. CONCLUSIONS: UTR appears to be involved in the regulation of colon cancer cell invasion and motility. These data suggest that UTR-related pathway may play a role in colon carcinogenesis and that UTR may function as a target for therapeutic intervention in colon cancer.

Aims: To compare metabolic control under lispro and recombinant regular human insulin (RHI) in people with diet-unresponsive type 2 diabetes mellitus (T2DM) and compensated non-alcoholic liver disease (CLD). Methods: 108 people with T2DM and CLD were randomly allocated to RHI or lispro according to a 12 + 12 week cross-over protocol. A 1-week continuous glucose monitoring (CGM) session was performed at the end of each treatment period followed by a standard meal test with a 12 IU lispro or RHI shot ahead. Results: CGM showed higher glycemic excursions under RHI than under lispro (p < 0.01) with lower glucose levels in the late post-absorption phase (p < 0.05) and even more during the night (p < 0.01). Post-challenge incremental areas under the curve (δAUC) were undistinguishable for insulin but lower for glucose, while insulin peaked higher and earlier and glycemic excursions were lower with lispro than with RHI (0.05 < p < 0.001). Conclusions: Lispro granted lower early postprandial glucose levels and late postprandial hypoglycemic rates and therefore might represent the treatment of choice for people with T2DM and compensated CLD. This might depend on its faster/shorter-living effects, as well as, on the lower liver glucose output expected from its earlier hepatic distribution.

In the last years, rituximab (RTX) and agonists of the thrombopoietin receptor (TPO-R) eltrombopag and romiplostim have provided new treatment options in persistent and chronic immune thrombocytopenia (ITP). Here, we analyzed the changes in therapeutic choices over time and their impact on clinical outcomes in a cohort of 557 ITP outpatients followed at the "L. and A. Seràgnoli" Institute of Hematology, Bologna, Italy, from 1980 to 2015. Overall 397 patients (71%) required front-line corticosteroids, mainly prednisone. Over the decades, splenectomy was delayed from second to third-line, but was steadily used in around 15-25% of patients refractory or relapsing after first-line treatment. Consensually, RTX and TPO-R agonists emerged as second and third-line therapy of choice, respectively. Splenectomy was associated with the best response rates and the lower incidences of relapse, while the relapse rate after RTX was comparable to that observed with corticosteroids and other immunosuppressive agents. The introduction of TPO-R agonists gave an alternative to the administration of immunosuppressive drugs and probably contributed to moderate the incidence of infectious complications that remained stable over the decades, despite an increasing use of RTX from the 2000s onwards. Overall responses were similar over time, with over 97% achieving a response in all time-periods. However, the cumulative risk of bleeding significantly decreased [14.3% (1980-89) vs. 7% (1990-99) vs. 5.6% (2000-09) vs. 0.2% (2010-15)] (P

tBackground: Anaemia (AN) is frequently associated with inflammatory bowel diseases (IBD) and cannegatively influence the quality of life of patients.Aim: To evaluate the prevalence and causes of AN in IBD.Methods: We prospectively performed a one-year multicentre observational study including all IBD casesattending six Units. We also investigated patients’ main serological parameters.Results: The study population included 965 IBD patients (582 CD; 383 UC), of whom 142 were in-patientsand 823 out-patients. AN was diagnosed in 134 out of 965 IBD patients (14%). No significant difference inAN prevalence was observed between CD and UC. The prevalence of AN was higher in the hospitalized IBD(26% in- vs. 11.7% out-patients; p < 0.01; OR 2.2) and in active disease (CD: 34% active vs. 16% inactive;p < 0.01; OR 2.1 – UC: 26% active vs. 19% inactive; p = 0.03; OR 1.3). Iron deficiency was present in 72patients (53.7%), AN of chronic diseases in 12 (8.2%), mixed type AN in 11 (8.2%), thalassemia in 9 (6.7%),and macrocytic AN in 8 (5.9%).Conclusions: In Southern Italy, AN is common in IBD and is more frequent in active disease and hospitalizedpatients. Iron deficiency still remains the major cause of AN in IBD.

In vitrodifferentiation of mesenchymal stromal cells (MSC) into osteocytes (human differentiated osteogenic cells, hDOC) before implantation has been proposed to optimize bone regeneration. However, a deep characterization of the immunological properties of DOC, including their effect on dendritic cell (DC) function, is not available. DOC can be used either as cellular suspension (detached, Det-DOC) or as adherent cells implanted on scaffolds (adherent, Adh-DOC). By mimickingin vitrothese two different routes of administration, we show that both Det-DOC and Adh-DOC can modulate DC functions. Specifically, the weak downregulation of CD80 and CD86 caused by Det-DOC on DC surface results in a weak modulation of DC functions, which indeed retain a high capacity to induce T-cell proliferation and to generate CD4+CD25+Foxp3+T cells. Moreover, Det-DOC enhance the DC capacity to differentiate CD4+CD161+CD196+Th17-cells by upregulating IL-6 secretion. Conversely, Adh-DOC strongly suppress DC functions by a profound downregulation of CD80 and CD86 on DC as well as by the inhibition of TGF-βproduction. In conclusion, we demonstrate that different types of DOC cell preparation may have a different impact on the modulation of the host immune system. This finding may have relevant implications for the design of cell-based tissue-engineering strategies.

Helicobacter pylori releases VacA both as free-soluble and as outer membrane vesicle (OMV)-associated toxin. In this study, we investigated the amount of VacA released in each of the two forms and the role of each form in VacA-induced cell vacuolation in vitro. We found that: (1) free-soluble toxin accounted for about 75% of released VacA, while the remaining 25% was OMV-associated; (2) although OMV-associated VacA caused a statistically significant vacuolation, virtually all the vacuolating activity of a H. pylori broth culture filtrate was due to free-soluble VacA. While it is widely accepted that OMVs may represent an important vehicle for delivering virulence factors to the gastric mucosa, our results suggest that OMV-associated VacA could play a pathobiological role different from that of free-soluble toxin. This conclusion fits with mounting evidence that VacA exerts a large pattern of pathobiological effects among which cell vacuolation might not be the main one.

Background: Aim was to evaluate the efficacy and tolerability of a moxifloxacin-containing second-line triple regimen in patients whose previous Helicobacter pylori eradication treatment failed. Methods: Prospective multicentre study including patients in whom a triple therapy or a non-bismuth-quadruple- therapy failed. Moxifloxacin (400 mg qd), amoxicillin (1 g bid), and esomeprazole (40 mg bid) were prescribed for 14 days. Eradication was confirmed by C-13-urea-breath-test. Compliance was determined through questioning and recovery of empty medication envelopes. Results: 250 patients were consecutively included (mean age 48 +/- 15 years, 11% with ulcer). Previous (failed) therapy included: standard triple (n = 179), sequential (n = 27), and concomitant (n = 44); 97% of patients took all medications, 4 were lost to follow-up. Intention-to-treat and per-protocol eradication rates were 82.4% (95% CI, 77-87%) and 85.7% (95% CI, 81-90%). Cure rates were similar independently of diagnosis (ulcer, 77%; dyspepsia, 82%) and previous treatment (standard triple, 83%; sequential, 89%; concomitant, 77%). At multivariate analysis, only age was associated with eradication (OR = 0.957; 95% CI, 0.933-0.981). Adverse events were reported in 25.2% of patients: diarrhoea (9.6%), abdominal pain (9.6%), and nausea (9.2%). Conclusion: 14-day moxifloxacin-containing triple therapy is an effective and safe second-line strategy in patients whose previous standard triple therapy or non-bismuth quadruple (sequential or concomitant) therapy has failed, providing a simple alternative to bismuth quadruple regimen. (C) 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Background: Occult HBV infection (OBI) is defined by the persistence of HBV in the liver without serum HBsAg and HBVDNA. It represents a life-threatening event during immunosuppressive chemotherapies. An OBI occurs in approximately 18% of HBcAb + patients. International guidelines suggest surveillance for HBV markers in immunosuppressed patients. In Non-Hodgkin Lymphoma (NHL), the prevalence of OBI reactivation remains to be established. Methods: In order to determine the prevalence of occult HBV reactivation in a large cohort of patients during chemotherapy for NHL, we analysed 498 NHL patients in a centre of Southern Italy. We evaluated HBV markers, NHL type, treatment type and occurrence of HBV reactivation. Results: Forty % of patients were treated with monoclonal antibodies and 60.3% without. Ninety-six patients were HBcAb+, HBsAg-. HBV reactivation occurred in ten subjects of this subgroup. All of them were successfully treated with Lamivudine. None of the patients experienced liver-related death. The prevalence of OBI reactivation was of 10.42% in HBcAb + HBsAb-patients. This event occurred in 50% of patients treated with mild immunosuppressive therapies. Each reactivation was treated with Lamivudine. Discussion: This report suggests that a strict surveillance is important and cost-effective in HBcAb + HBsAg- NHL patients treated with mild immunosuppressive therapies, in order to detect an occult HBV reactivation.

Ulcerative colitis may be associated with a number of skin lesions such as erythema nodosum and pyoderma gangrenosum. We here describe an unusual case of a 33-year-old-caucasian male with ulcerative colitis and skin lesions diagnosed as leukocytoclastic vasculitis. An initial treatment with oral deflazacort led to little benefit, while treatment with oral mesalazine caused remission of the skin and intestinal manifestations in 2 weeks. © 2008 Editrice Gastroenterologica Italiana S.r.l.

Mucosa-associated lymphoid tissue (MALT) lymphomas comprise a group of indolent B-cell non-Hodgkin lymphomas (NHL), which are rare in pediatric age. The clinical presentation of MALT lymphomas varies according to the location of the lymphoma. We report on a case of MALT lymphoma involving the appendix in a 6-year-old girl. A 6-year-old girl was referred to our institution in May 2005 with a diagnosis of appendicitis. The abdominal ultrasound showed slight effusion in the pelvic fossa. The patient underwent laparoscopic appendectomy using the three-trocar technique. The appendix appeared moderately hyperaemic with slight enlargement of the two-thirds of the distal portion. The postoperative course was uneventful and the girl was discharged on day 1 without any complication. The morphological and immunohistochemical examination showed typical findings of low-grade MALT lymphoma (positivity for CD20, no immunostaing for CD5 and CD10, positivity for anti-lambda light chain and low positivity for Ki-67). Further extensive examinations (abdominal MRI, gastroscopy, colonscopy and capsule endoscopy of the ileum) revealed that the lymphoma was limited to the distal two-third of the appendix (stage IA) and was not associated with any specific infection. At a recent follow-up the patients appeared to be doing well. Appendiceal MALToma is a rather uncommon pathology and, to our knowledge, there is only one report of appendiceal intussusception associated with appendiceal maltoma. According to our experience, low-grade MALToma can be managed by simple appendectomy. The histological examination should be the rule whenever an appendectomy is performed in children.

In recent years, vast progress in basic science and technology has ramatically changed scientific perspectives by opening the new orizon of translational medicine. The term “translational” refers to he bench-to-bedside paradigm and addresses the process of applyng ideas, insights and discoveries generated through basic science chemistry, biology, genetics) to improve diagnosis, prevention and reatment of human diseases [1]. The bench-to-bedside process can be divided into several steps, rom basic inquiry into pathophysiology to the identification of otentially targetable pathways, up to the development of new rugs. The final track resides in clinical testing of therapeutic agents nd evaluation of their efficacy. Traditionally, these steps are perormed by independent experts, starting from the basic scientist, hrough the chemistry expert/drug developer, ending with the clincal scientist. These professionals most of the time are physically eparated, and very often use a different terminology with diffiulties in cooperation and communication. The identification of translational approach recognizes the strong need for a close nteraction between individuals in science. Furthermore, sharing nformation among players also favours feedback from the cliniian to the basic scientist, thus making research at least a two-way rocess, from bench-to-bedside and from bedside-to-bench [2]. In the last two decades, gastroenterology has become an area f dynamic translational research, with some targets already sucessfully translated into practice and policy, and some others still rogressing into clinically effective drugs in a number of different onditions (Supplementary Figure S1). Epitome of how bidirecional translation has been fruitful in this field is the discovery of he central role of the potent pro-inflammatory cytokine tumour

Eosinophils participate in the immune response against Helicobacter pylori, but little is known about their role in the gastritis associated to the infection. We recently demonstrated that the Hp(2-20) peptide derived from H. pylori accelerates wound healing of gastric mucosa by interacting with N-formyl peptide receptors (FPRs) expressed on gastric epithelial cells. The aim of the present study was to investigate whether eosinophils play a role in the repair of gastric mucosa tissue during H. pylori infection. Immunohistochemistry and transmission electron microscopy were used to detect eosinophils in gastric mucosal biopsies. Eosinophil re-distribution occurred in the gastric mucosa of H. pylori-infected patients: their density did not change in the deep mucosal layer, whereas it increased in the superficial lamina propria just below the foveolar epithelium; eosinophils entered the epithelium itself as well as the lumen of foveolae located close to the area harboring bacteria, which in turn were also engulfed by eosinophils. The H. pylori-derived peptide Hp(2-20) stimulated eosinophil migration through the engagement of FPR2 and FPR3, and also induced production of VEGF-A and TGF-β, two key mediators of tissue remodeling. We also demonstrate that Hp(2-20) in vivo induced eosinophil infiltration in rat gastric mucosa after injury brought about by indomethacin. This study suggests that eosinophil infiltrate could modulate the capacity of gastric mucosa to maintain or recover its integrity thereby shedding light on the role of eosinophils in H. pylori infection. Copyright © by BIOLIFE, s.a.s.

Background A higher prevalence of coeliac disease has recently been reported among patients with HCV-related chronic hepatitis. Moreover, development of clinically overt coeliac disease has been described in a number of HCV-related chronic hepatitis patients during α-interferon therapy. This prospective study was designed to evaluate 1) the prevalence of coeliac disease in patients with HCV-related chronic hepatitis; 2) the prevalence of HCV infection in patients with coeliac disease; 3) whether PEG interferon-α treatment might favour the development of coeliac disease in patients with chronic hepatitis C. Materials and methods Two hundred-ten consecutive patients (M/F = 140/70, range of age 35–58 years, median age 46.5 years) with biopsy proven chronic hepatitis C underwent serological screening for antiendomysial and tissue transglutaminase IgA antibodies. One hundred ninety-four coeliac patients (M/F = 52/142, range of age 18–74 years, median age 34 years) were screened for HCV antibodies. Positivity for HCV antibodies in coeliac disease patients was confirmed by detection of serum HCV-RNA by RT-PCR. This work was carried out in accordance to ethical guidelines of Declaration of Helsinki and was approved by Institutional Ethics Committee of the Second University of Naples. All patients gave informed written consent. Results 1) none of the 210 HCV-related chronic hepatitis patients were positive for coeliac disease serologic screening; 2) prevalence of HCV infection among coeliac patients was 1.54% (3/194) which is comparable to that reported in the Southern Italy population; 3) PEG interferon-α treatment was not associated with development of coeliac disease either clinical or serological. Conclusions 1) coeliac disease is not associated with HCV infection; 2) PEG interferon-α does not trigger celiac disease.

Background & Aims Helicobacter pylori have become resistant to antimicrobial agents, reducing eradication rates. A 10-day sequential regimen that contains levofloxacin was efficient, safe, and cost saving in eradicating H pylori infection in an area with high prevalence of clarithromycin resistance. We performed a noninferiority randomized trial to determine whether a 5-day levofloxacin-containing quadruple concomitant regimen was as safe and effective as the 10-day sequential regimen in eradicating H pylori in previously untreated patients. Methods We randomly assigned patients with H pylori infection to groups that were given 5 days of concomitant therapy (esomeprazole 40 mg twice daily, amoxicillin 1 g twice daily, levofloxacin 500 mg twice daily, and tinidazole 500 mg twice daily; n=90) or 10 days of sequential therapy (esomeprazole 40 mg twice daily, amoxicillin 1g twice daily for 5 days followed by esomeprazole 40 mg twice daily, levofloxacin 500 mg twice daily, and tinidazole 500 mg twice daily for 5 more days; n=90). Antimicrobial resistance was assessed by the E-test. Efficacy, adverse events, and costs were determined. Results Intention-to-treat analysis showed similar eradication rates for concomitant (92.2%; 95% confidence interval [CI], 84.0%–95.8%) and sequential therapies (93.3%; 95% CI, 86.9%–97.3%). Per-protocol eradication results were 96.5% (95% CI, 91%–99%) for concomitant therapy and 95.5% for sequential therapy (95% CI, 89.6%–98.5%). The differences between sequential and concomitant treatments were 1.1% in the intention-to-treat study (95% CI; −7.6% to 9.8%) and −1.0% in the per-protocol analysis (95% CI; −8.0% to 5.9%). The prevalence of antimicrobial resistance and incidence of adverse events were comparable between groups. Concomitant therapy cost $9 less than sequential therapy. Conclusions Five days of levofloxacin-containing quadruple concomitant therapy is as effective and safe, and less expensive, in eradicating H pylori infection than 10 days of levofloxacin-containing sequential therapy.

Natural medicinal products have been used for millennia for the treatment of several ailments. Although many have been superseded by conventional pharmaceutical approaches, there is currently a resurgence in the interest in natural products by the general public and the use of complementary and alternative medicine is increasing rapidly in developed countries. Also, pharmaceutical industries are more and more interested in examining their potential as sources of novel medicinal compounds which may act as growth factor or show immunomodulatory or anti-microbial activity. The subgroup of natural bioactive compounds that bridge the gap between food products and drugs are termed nutraceuticals or functional foods. In contrast with most standard medicinal compounds, nutraceuticals are generally used to prevent rather than to treat disease. Many of the claims for such products are supported by very limited scientific evidence. However, there has recently been a great interest at evaluating the mechanism by which natural products exert their beneficial effects in the gastrointestinal tract. In particular, a major area of interest is for the use of biologically active chemical components of plants, i.e. phytochemicals, in a number of gastrointestinal disorders. While the major focus of phytochemical research has been on cancer prevention, several products of plant origin are being used and/or under study for a variety of other gastrointestinal problems. In this review we discuss the scientific evidence supporting the potential use of nutraceuticals as agents capable to prevent or accelerate healing of gastrointestinal mucosal damage, with a focus on polyphenol extracts obtained from apple.

Helicobacter pylori (H. pylori) has co-evolved with humans to be transmitted from person to person and to colonize the stomach persistently. A well-choreographed equilibrium between the bacterial effectors and host responses permits microbial persistence and health of the host, but confers a risk for serious diseases including gastric cancer. During its long coexistence with humans, H. pylori has developed complex strategies to limit the degree and extent of gastric mucosal damage and inflammation, as well as immune effector activity. The present editorial thus aims to introduce and comment on major advances in the rapidly developing area of H. pylori/human gastric mucosa interaction (and its pathological sequelae), which is the result of millennia of co-evolution of, and thus of reciprocal knowledge between, the pathogen and its human host.

Obesity is increasingly being recognized as a risk factor for a number of benign and malignant gastrointestinal conditions. However, literature on the underlying pathophysiological mechanisms is sparse and ambiguous. There is compelling evidence that both overnutrition and undernutrition negatively interfere with the immune system. Overnutrition has been found to increase susceptibility to the development of inflammatory diseases, autoimmune diseases and cancer. In the regulation of immune and inflammatory processes, white adipose tissue plays a critical role, not only as an energy store but also as an important endocrine organ. The obese state is characterised by a low-grade systemic inflammation, mainly as a result of increased adipocytes as well as fat resident- and recruited-macrophage activity. In the past few years, various products of adipose tissue including adipokines and cytokines have been characterised and a number of pathways linking adipose tissue metabolism with the immune system have been identified. Activation of the innate immune system plays a major role in hepatic steatosis. Non-alcoholic fatty liver disease includes a wide spectrum of diseases, from pure steatosis to non-alcoholic steatohepatitis in the absence of significant alcohol consumption. Although steatosis is considered a non-progressive disease, non-alcoholic steatohepatitis may deteriorate in advanced chronic liver diseases, cirrhosis, and hepatocellular carcinoma. An important parallel between obesity-related pathology of adipose tissue and liver pertains to the emerging role of macrophages, and growing evidence suggests that Kupffer cells critically contribute to progression of non-alcoholic fatty liver disease. Moreover, a close link between specific immune activation and atherosclerosis has been well established, suggesting that fat can directly trigger immune responses. This review discusses the role of fat as "a matter of disturbance for the immune system" with a focus on hepatic steatosis.

Background and aims Antimicrobial drug resistance is a major cause of the failure of Helicobacter pylori eradication and is largely responsible for the decline in eradication rate. Quadruple therapy has been suggested as a first-line regimen in areas with clarithromycin resistance rate >15%. This randomised trial aimed at evaluating the efficacy of a levofloxacin-containing sequential regimen in the eradication of H pylori -infected patients in a geographical area with >15% prevalence of clarithromycin resistance versus a clarithromycin-containing sequential therapy. Methods 375 patients who were infected with H pylori and naive to treatment were randomly assigned to one of the following treatments: (1) 5 days omeprazole 20 mg twice daily + amoxicillin 1 g twice daily followed by 5 days omeprazole 20 mg twice daily + clarithromycin 500 mg twice daily + tinidazole 500 mg twice daily; or (2) omeprazole 20 mg twice daily + amoxicillin 1 g twice daily followed by omeprazole 20 mg twice daily + levofloxacin 250 mg twice daily + tinidazole 500 mg twice daily; or (3) omeprazole 20 mg twice daily + amoxicillin 1 g twice daily followed by omeprazole 20 mg twice daily + levofloxacin 500 mg twice daily + tinidazole 500 mg twice daily. Antimicrobial resistance was assessed by the E-test. Efficacy, adverse events and costs were determined for each group. Results Eradication rates in the intention-to-treat analyses were 80.8% (95% CI, 72.8% to 87.3%) with clarithromycin sequential therapy, 96.0% (95% CI, 90.9% to 98.7%) with levofloxacin-250 sequential therapy, and 96.8% (95% CI, 92.0% to 99.1%) with levofloxacin-500 sequential therapy. No differences in prevalence of antimicrobial resistance or incidence of adverse events were observed between groups. Levofloxacin-250 therapy was cost-saving compared with clarithromycin sequential therapy. Conclusion In an area with >15% prevalence of clarithromycin resistant H pylori strains, a levofloxacin-containing sequential therapy is more effective, equally safe and cost-saving compared to a clarithromycin-containing sequential therapy.

BACKGROUND AND STUDY AIM: The aim of this study was to assess the prevalence of nonpolypoid lesions (NPLs) in Italy and their risk of containing neoplasia or advanced histology. PATIENTS AND METHODS: This was a multicenter cross-sectional observational study on consecutive patients undergoing total colonoscopy over a 3-month period in 80 Italian centers. RESULTS: In all, 27,400 total colonoscopies were analyzed. Cancer was diagnosed in 801 patients (2.9 %). A total of 6553 precancerous lesions were detected in 5609 patients. Of these, 4154 patients (74.1 %) had polypoid lesions and 1455 patients (25.9 %) had NPLs. Therefore, the prevalence of NPLs was 5.3 % (95 %CI 5.0 - 5.6). NPLs larger than 10 mm were detected in 254 patients (17.5 %). NPLs were more predominant in the proximal colon (OR 2.92, 95 %CI 2.56 - 3.43; P < 0.0001 vs. polypoid lesions). Neoplastic tissue was diagnosed in 79.0 % and advanced histology (high-grade intraepithelial neoplasia or more) in 20.9 % of resected lesions. The risk of advanced histology was similar for polypoid and nonpolypoid lesions when adjusted for size. Depressed lesions had the highest risk of advanced histology (OR 10.56, 95 %CI 6.02 - 18.55; P < 0.0000 vs. flat-elevated). Age was an independent predictor of both neoplasia and advanced histology ( P = 0.0001). CONCLUSIONS: NPLs are relatively common in the Italian population, with a prevalence similar to that in other Western series. NPLs are not more aggressive than polypoid lesions, except for those with depressed morphology. Georg Thieme Verlag KG Stuttgart. New York.

Helicobacter pylori-derived peptide RpL1 aa 2–20 (Hp(2–20)) in addition to its antimicrobial action exerts several immunomodulatory effects in eukaryotic cells by interacting with formyl peptide receptors (FPRs). It has recently been shown that activation of FPRs facilitates intestinal epithelial cell restitution. We investigated whether Hp(2–20) induces healing of injured gastric mucosa and assessed the mechanisms underlying any such effect. We investigated the expression of FPRs in two gastric epithelial cell lines (MKN-28 and AGS) at mRNA and protein level. To determine whether FPRs were functional we performed chemotaxis experiments and proliferation assays and studied the Hp(2–20)-activated downstream signaling pathway. The effect of Hp(2–20) on mucosal healing was evaluated in rats after indomethacin-induced injury. Here we show that: (1) FPRs were expressed in both cell lines; (2) Hp(2–20) stimulated migration and proliferation of gastric epithelial cells; (3) this effect was specifically mediated by formyl peptide receptor-like 1 (FPRL1) and FPRL2 and was associated with activation of FPR-related downstream signaling pathways; (4) Hp(2–20) up-regulated the expression and secretion of vascular endothelial growth factor; and (5) Hp(2–20) accelerated healing of rat gastric mucosa after injury brought about by indomethacin at both the macroscopic and microscopic levels. In conclusion, by interacting with FRPL1 and FPRL2, H. pylori-derived Hp(2–20) induces cell migration and proliferation, as well as the expression of vascular endothelial growth factor, thereby promoting gastric mucosal healing. This study provides further evidence of the complexity of the relationship between H. pylori and human gastric mucosa, and it suggests that a bacterial product may be used to heal gastric mucosal injury.

A 56-year-old Caucasian man was hospitalized because of diffuse skin rash and ulcer-like dyspepsia. Skin biopsy showed psoriatic-like dermatitis with perivascular infiltrate of eosinophils and lymphocytes. Laboratory data were normal.

BACKGROUND/AIMS:Prevalence of HCV infection in non-Hodgkin's lymphoma is high. The impact of antiviral therapy on the natural history of this subgroup of lymphomas after a successful chemotherapy regimen is still an argument of debate. METHODS:We retrospectively examined 343 chemotherapy-treated patients referred to our centre for five consecutive years. Clinical and histological characteristics, disease free-survival (DFS) and overall-survival (OS) were compared in HCV-positive (69/343) and HCV-negative (274/343) patients. Twenty-five HCV-positive patients received antiviral treatment following chemotherapy discontinuation. Uni- and multivariate analyses were performed. RESULTS: 20% of lymphomas were HCV-positive. Indolent histology was prevalent in the HCV-positive group (p

Objectives:Helicobacter pylori infection is a major health problem worldwide, and effective eradication of the infection is mandatory. The efficacy of recommended eradication regimens is approximately 70%. To avoid treatment failure and the consequent development of secondary resistance(s), it is important to choose the most appropriate first-line treatment regimen. This choice should also be made based on the knowledge of the antimicrobial resistance peculiar to a given geographical area. We evaluated the prevalence of antimicrobial-resistant H pylori strains isolated from naive patients and from patients with previous unsuccessful treatments.Methods:This study examined 109 H pylori-infected subjects (Group 1) who had never received an eradication treatment and 104 H pylori-infected subjects (Group 2) who had failed one or more eradication treatments. Resistance to amoxicillin (AMO), tetracycline (TET), clarithromycin (CLA), metronidazole (MET) and levofloxacin (LEV) was determined using the epsilometer test. The significance of differences was evaluated by the χ2 test.Results:The prevalence of antimicrobial resistance was 0% versus 3.1% to AMO, 0% versus 2% to TET, 27% versus 41.3% to MET (pH pylori strains resistant to multiple antimicrobials.Conclusions:This study confirms the high prevalence of H pylori strains resistant to CLA and MET, and indicates that unsuccessful treatments significantly increase resistance. Choosing eradication regimens other than standard triple therapy as a first-line therapy should be advisable in areas with high primary antimicrobial resistance prevalence.

A shift from Th1 (IFN-gamma) towards Th2 (IL-4)-type immune response was found in patients with gastric cancer and dysplasia. Recently, IL-13 has been described as a central mediator of Th2-dominant immune response in different inflammatory diseases. AIM AND METHODS: to analyse, by Enzyme-Linked-Immuno-SPOT (ELISPOT) assay and immunohistochemistry, the IL-13 production of mononuclear cells obtained from gastric biopsies of 19 H. pylori-negative subjects and 23 H. pylori-positive patients. RESULTS: By ELISPOT, we did not find any significant variation of the spot range number of IL-13, IL-4 and IFN-gamma secreting cells, irrespective of H. pylori status. After antigenic exposition, the spot range for IL-13, IL-4 and IFN-gamma significantly increased (p

The CpG island methylator phenotype is characterized by DNA hypermethylation in the promoters of tumor suppressor genes with silencing of transcription. Hypermethylation of the promoter of hMLH1 and subsequent microsatellite instability occurs in approximately 12% of sporadic colorectal cancers (CRC). Annurca apple, a variety of southern Italy, is rich in polyphenols that are associated with anticancer properties. Populations in southern Italy have lower incidences of CRC than elsewhere in the western world. We evaluated the mechanisms of putative anticancer effects of Annurca polyphenol extract (APE) in in vitro models of CRC. We extracted polyphenols from Annurca apples and treated RKO, SW48, and SW480 cells with APE and assessed the cell viability, apoptosis, and cell cycle. DNA methylation of selected tumor suppressor genes was evaluated after treatment with APE and was compared with the synthetic demethylating agent 5-aza-2'deoxycytidine (5-aza-2dC). DNA methyltransferase (DNMT)-1 and -3b levels were evaluated. Decreased cell viability and induction of apoptosis was evident after treatment. We found no significant changes in cell cycle dynamics. We observed significant increases of p53 protein expression in RKO after treatment. APE treatment strongly reduced DNA methylation in the promoters of hMLH1, p14(ARF), and p16(INK4a) with consequent restoration of normal expression. These effects were qualitatively comparable with those obtained with 5-aza-2dC. We observed a significant reduction in expression of DNMT proteins after treatment without changes in messenger RNA. In conclusion, APE have potent demethylating activity through the inhibition of DNMT proteins. The lack of toxicity in Annurca extracts makes them excellent candidates for the chemoprevention of CRC.