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The gluten-free diet (GFD) is the cornerstone treatment for coeliac disease (CD). However, a healthy GFD is more complex than the only exclusion of gluten-containing foods. Most celiac patients do not receive nutritional advice and tend to consume industrial gluten-free products (GFPs), which often lack fiber, vitamins, and other micronutrients while being rich in saturated fats and refined sugars. This review focuses on the main potential metabolic disorders and nutritional deficiencies in CD patients at diagnosis and dissects the main nutritional and metabolic issues due to a non-balanced GFD. Nutritional tips to achieve an adequate dietary approach in CD are provided. We also compared the main nutritional components of naturally gluten-free cereals (including pseudocereals) to give an exhaustive overview of the possible healthy alternatives to processed GFPs. Clinicians and dietitians should be systematically involved in the diagnosis of CD to monitor the appropriateness of GFD and the patient’s nutritional status over time.

The need to shed light on the unknown aspects of pathophysiology of common disorders, such as gastrointestinal ones, has led researchers through last decades to study and define the role of microorganisms within the human intestine and their interactions with the host. The progress of technology has permitted the overcoming of culture-based methods to study microbes and paved the way to molecular techniques, which allow the analysis of microbial genome, microbial functions, and metabolism. These progresses opened a window on the world of microbiology and permitted to deepen into the key role played by gut microbiota and dysbiosis in health status and diseases, both gastrointestinal and extraintestinal. So, scientists focused their attention in developing new strategies to restore eubiosis and to manipulate gut microbes by modifying dietary habits, administrating antibiotics, probiotics, and prebiotics and using fecal microbiota transplantation as treatment of gastrointestinal, infectious, cardiovascular, metabolic, immune-mediated, neuro-psychiatric, and oncological disorders. The next challenges will be to elaborate standard protocols with definite outcomes predictors in disease-specific settings.

BACKGROUND Professions distinguished by repeated vocal stress carry a high risk of developing gastroesophageal reflux symptoms (GERS) which may affect vocal performance. AIMS To investigate the prevalence of self-reported GERS in professional opera soloists. METHODS A validated questionnaire regarding self-reported GERS (heartburn, regurgitation, chest pain, dysphagia, hoarseness, and cough) and lifestyle habits was administered to 116 professional opera soloists (mean age 34.1 ± 7.3 years, F:M ratio 1:1.1). Age and sex-matched opera choristers and control subjects were used as control. Prevalence rate ratios (PRRs) adjusted for confounding factors were evaluated. RESULTS Among GERS, belching (33.6%), heartburn (19.8%), and dysphagia (15.5%) were the most commonly reported by soloists. In particular, a higher risk of heartburn (PRR 2.61, 95% CI 1.45-4.69) and dysphagia (PRR 2.58, 95% CI 1.31-5.10) was reported in soloists as compared to choristers. The prevalence of obesity and late dinner was higher in both choristers and soloists in comparison to the population sample (p

Faecal microbiota transplantation (FMT) is an important therapeutic option for Clostridium difficile infection. Promising findings suggest that FMT may play a role also in the management of other disorders associated with the alteration of gut microbiota. Although the health community is assessing FMT with renewed interest and patients are becoming more aware, there are technical and logistical issues in establishing such a non-standardised treatment into the clinical practice with safety and proper governance. In view of this, an evidence-based recommendation is needed to drive the practical implementation of FMT. In this European Consensus Conference, 28 experts from 10 countries collaborated, in separate working groups and through an evidence-based process, to provide statements on the following key issues: FMT indications; donor selection; preparation of faecal material; clinical management and faecal delivery and basic requirements for implementing an FMT centre. Statements developed by each working group were evaluated and voted by all members, first through an electronic Delphi process, and then in a plenary consensus conference. The recommendations were released according to best available evidence, in order to act as guidance for physicians who plan to implement FMT, aiming at supporting the broad availability of the procedure, discussing other issues relevant to FMT and promoting future clinical research in the area of gut microbiota manipulation. This consensus report strongly recommends the implementation of FMT centres for the treatment of C. difficile infection as well as traces the guidelines of technicality, regulatory, administrative and laboratory requirements.

Wheat grains have a complex structure which contains an organized distribution of nutrients. Cooking induces gluten formation. Celiac Disease and Wheat Allergy are well known wheat-related disorders, the first being a gluten-dependent autoimmune enteropathy, the latter a hypersensitivity IgE - mediated reaction. The pathogenetic mechanism of non-celiac gluten sensitivity is still under investigation. The clinical diagnosis is: the presence, in relation to the ingestion of gluten containing foods, of intestinal and extra- intestinal symptoms in patients where celiac disease and wheat allergy have already been excluded. There is ongoing evidence that non- gluten derived proteins have an important pathogenetic role in non-celiac gluten sensitivity and probably also in celiac disease: Amylase Trypsin Inhibitors-ATIs are proteins that are also present in rye and barley; they are triggers of innate immune response in non-celiac gluten sensitivity. They may also exacerbate immunomediate inflammatory bowel diseases. Gluten-free diet is the only effective therapy both in celiac disease and non-celiac gluten sensitivity. Alternative therapeutic strategies are under investigation in Celiac Disease: -exogenous enzyme gluten digestion to obtain less toxic fragments; - molecules able to be remodeling enterocyte tight junctions which become permeable in celiac disease. Researches should be devoted to creating a less toxic grain, while to date grain has been genetically modified to increase gluten content. We advise a future for researches in agronomy. A role for functional and nutraceutical foods must be investigated. Another emerging issue is due to the consciousness of wheat/gluten-microbiota-brain and mind interactions.

Stable isotope analysis in the reconstruction of human palaeodiets can yield clues to early human subsistence strategies, origins and history of farming and pastoralist societies, and intra- and intergroup social differentiation. In the last 10 years, the method has been extended to the pathological investigation. Stable isotope analysis to better understand a diet-related disease: celiac disease in ancient human bones was carried out. To do this, we analyzed the nitrogen and carbon isotopic composition of human (n = 37) and faunal (n = 8) bone remains from the archaeological site of Cosa at Ansedonia, on the Tyrrhenian coast near Orbetello (Tuscany), including the skeletal remains of a young woman (late 1st century–early 2nd century Common Era [CE]) with morphological and genetic features suggestive of celiac disease. We compared the young woman's isotopic data with those of other individuals recovered at the same site but from two later time periods (6th century CE; 11–12th century CE) and with literature data from other Italian archaeological sites dating to the same period. Her collagen δ13C and δ15N values differed from those of the samples at the same site, and from most but not all of the contemporary sites. Although the woman's diet appears distinct, chronic malnutrition resulting from severe malabsorption of essential nutrients due to celiac disease may have affected the isotopic composition of her bone collagen. Am J Phys Anthropol 154:349–356, 2014. © 2014 Wiley Periodicals, Inc.

Treatment of Helicobacter pylori infection is becoming a very relevant problem especially in industrialized Countries. Although different therapeutic regimens are currently available, treatment failure remains a growing problem in daily medical practice. Several factors could play a role in the eradication failure, but the most relevant are antibiotic resistance and patient's compliance. While Helicobacter pylori resistance to amoxicillin is rare, clarithromycin and metronidazole resistance varies significantly from close to zero up to 25%. However, metronidazole in vitro resistance exhibits a lower impact on eradication success because resistance in vitro does not reflect that in vivo. Specific guidelines have then been published, mostly based on antibiotic resistance among different geographic areas. Basically, first-line and second-line regimens have been well defined; concerning third-line treatment Maastricht III guidelines suggest to adopt a culture-based approach. Culture is, however, expensive, invasive and available only in few specialized centres. An alternative approach may be to use an empirical strategy, based on the avoidance of repeating similar eradicating schemes in the same patients during the course of different eradicating regimens. For this approach we propose the acronym DANCE (Different Antibiotic No Culture Eradicating) strategy. When correctly applied, this approach showed to reach successful eradication in up to 99.5% of Helicobacter pylori-positive patients.

Aliment Pharmacol Ther 2011; 34: 1088–1097 Summary Background Ulcerative colitis (UC) is characterised by impaired fatty-acid oxidation; l-carnitine has a key role in fatty-acid metabolism and short-chain fatty acids such as butyrate and propionate are important energy source for intestinal epithelial cells. Aim To evaluate efficacy and safety of colon-release propionyl-l-carnitine (PLC) in patients with mild-to-moderate UC receiving stable oral aminosalicylate or thiopurine therapy. Methods In a multicentre, phase II, double-blind, parallel-group trial, patients were randomised to receive PLC 1 g/day, PLC 2 g/day or placebo. Main inclusion criteria were as follows: age 18–75; disease activity index (DAI) score 3–10 inclusive, be under oral stable treatment with aminosalicylate or thiopurine. The primary endpoint was clinical/endoscopic response, defined as a decrease in DAI score ≥ 3 points or remission, defined as a DAI score ≤ 2 with no individual sub-score > 1. Results Of 121 patients who were randomised, 57 of 79 (72%) patients receiving PLC (combined 1 g and 2 g cohort) had a clinical/endoscopic response vs. 20 of 40 (50%) receiving placebo (P = 0.02). Specifically, in PLC 1 g/day group, 30 of 40 (75%) patients had clinical/endoscopic response (P = 0.02 vs. placebo) and 27 of 39 (69%) in the PLC 2 g/day group (P = 0.08 vs. placebo). Rates of remission were 22/40 (55%), 19/39 (49%), 14/40 (35%) in the PLC 1 g, PLC 2 g, and placebo groups, respectively. PLC had a similar safety profile to placebo; the most common adverse events were gastrointestinal. Conclusion Propionyl-l-carnitine 1 g/day should be investigated further as a co-treatment for mild-to-moderate ulcerative colitis (NCT-01026857).

The multiple drug intolerance syndrome is a clinical entity characterized by adverse drug reactions to at least three drugs, chemically, pharmacologically and immunogenically unrelated, manifested upon three different occasions, and with negative allergy testing. Symptoms referred by the patients are often subjective, of neurovegetative origin. The aim of the study is to characterize patients suffering from the multiple drug intolerance syndrome from a psychological point of view, and to compare them to healthy subjects. We studied 30 women suffering from the multiple drug intolerance syndrome. All subjects underwent the following psychodiagnostic tests: (1) the State Trait Anxiety Inventory-Form Y, (2) the Zung Self-rating Anxiety Scale, (3) the Zung Self-rating Depression Scale, (4) the Quality of life enjoyment and satisfaction questionnaire, (5) the Minnesota Multiphasic Inventory-2, (6) the Toronto Alexithymia Scale. The study group was compared to 30 healthy women. When compared with the control group, our patients showed: a higher anxiety, a higher grade of depression, this difference was statistically significant (p < 0.01); a high difference (p < 0.01) between the two groups as regards somatic symptoms; a higher grade of alexithymia (p < 0.01); and a worse quality of life, in all the analyzed ambits. These findings clearly demonstrate the importance of psychological symptoms in patients with the multiple drug intolerance syndrome, and show that a complex allergy and psychological work-up is mandatory in the management of these patients.

Crohn's disease and ulcerative colitis represent the two major forms of inflammatory bowel disease (IBD). Recent research points out the role of uncontrolled intestinal inflammation in the pathogenesis of IBD. Therefore, there is a growing interest in developing novel biologic therapies targeting specific molecules of the inflammatory cascade. Among them, anti-tumor necrosis factor (anti-TNF) agents (i.e. infliximab, adalimumab, certolizumab pegol) have proved to be effective, particularly for patients with refractory IBD. These biological therapies have changed, at least partially, the clinical course and medical management of IBD. However, the administration of anti-TNF drugs has also been associated with serious side-effects, which have raised concerns on the application of these drugs in clinical practice. The goal of this review is to provide an update and analyze the pros and cons of using anti-TNF therapies in the treatment of IBD.

Aliment Pharmacol Ther 2010; 32: 209–214 Summary Background Non-steroidal anti-inflammatory drugs (NSAIDs) can cause serious gastrointestinal side effects. Faecal calprotectin assay represents a simple and practical method for diagnosis of NSAID enteropathy. Intestinal micro-organisms are necessary for the development of NSAID-induced small bowel lesions and hence it has been suggested that probiotics could protect against NSAID enteropathy. Aim To evaluate the effect of a probiotic mixture in comparison with placebo on faecal calprotectin concentrations (FCCs) in healthy volunteers receiving indomethacin. Methods In a double-blind, cross-over trial, 20 healthy volunteers ingested a daily dose of probiotic mixture (VSL#3) or placebo for 21 days. From day 16 to day 19, all subjects were also administered 50 mg/day of indomethacin. FCCs were measured the day before starting probiotic/placebo ingestion (T0), and every day from day 15 to day 21. Results During dosing with probiotic, median FCCs were significantly increased only at day 17 with respect to T0 values, whereas during dosing with placebo, they were significantly increased at every day from day 17 to day 21 with respect to T0 values. Conclusions Treatment with VSL#3 before and during indomethacin therapy significantly reduces FCCs in healthy subjects with respect to placebo, suggesting that this approach could be useful in decreasing indomethacin-induced intestinal inflammation.

Aliment Pharmacol Ther 31, 375-386 Summary Background The administration of parnaparin sodium as oral colon-release tablets (CB-01-05 MMX®) has been proposed as a novel approach for the treatment of ulcerative colitis (UC). Aim To assess the efficacy and the tolerability of 8 weeks’ oral daily administration of 210 mg of parnaparin sodium compared with placebo in subjects treated with stable-doses of oral aminosalicylates. Methods This multicenter, randomized, double-blind proof of concept trial compared the efficacy of CB-01-05 MMX® 210 mg tablets to placebo in 141 subjects with mild to moderately active left-sided UC treated with stable-doses of aminosalicylates. The efficacy was assessed by clinical activity index (CAI), endoscopic index (EI) and histological score (HS). Results A total of 121 subjects (61 in test group and 60 in control group) formed the per protocol (PP) population. After 8 weeks of treatment, clinical remission was achieved in 83.6% of the CB-01-05 MMX® group, and in 63.3% in the comparator group (P = 0.011). This effect was also significantly evident in the test group at week 4 (P = 0.028). A significant difference was also detected in rectal bleeding, (disappeared respectively in 75.4% and 55.0%; P = 0.018), and in mucosal friability (recovered respectively in 80.3% and in 56.7%; P = 0.005). Conclusions CB-01-05 MMX® was safe and significantly effective in treating subjects with mild-to-moderate left-sided UC treated with stable-doses of aminosalicylates.

Celiac disease (CD) is an autoimmune gluten-dependent enteropathy characterized by atrophy of the intestinal villi that improves after a gluten-free diet. CD is often associated with extraintestinal manifestations. In the past few years, growing evidence has documented the involvement of skin diseases among the extraintestinal manifestations of CD. This association could be related to the impairment of intestinal absorption and motility, other than to immunological and hormonal changes. The aim of this review is to report all CD-associated skin manifestations described in the literature and to analyze the possible mechanisms involved in this association. The opportunity to evaluate the possible presence of CD in patients affected by skin disorders is discussed.

Abdominal angina is an underrecognized cause of postprandial abdominal pain and weight loss. Diagnosis is often delayed and requires both a careful exclusion of more common causes and a high degree of clinical suspicion, based on the patient's age, the coexistence of multiple risk factors for atherosclerosis, and the presence of vasculopathy in other districts. Appropriate investigations include duplex ultrasound, traditional angiography, magnetic resonance angiography, computed tomography angiography, and tonometry. The purpose of this review is to discuss the pathophysiology and clinical presentation of chronic mesenteric ischemia and to suggest a diagnostic flowchart for this complex condition.

Low high-density lipoprotein-cholesterol (HDL-C) concentration correlates with increased cardiovascular risk. A great prevalence of celiac disease (CD) was reported among patients with low HDL-C concentration, and gluten-free diet (GFD) treatment seems to normalize lipid profile. We evaluated blood lipids and body composition in 26 CD patients with low HDL-C level (1.0 mmol/L) at diagnosis and after GFD.A case-control study.The diagnosis was based on histologic evidence of subtotal or total duodenal villous atrophy. Patients were studied before and after GFD treatment (14.2+/-1.4 mo) with biopsy-proven return to normal of the duodenal mucosa. HDL-C was enzymatically assessed after precipitation of very low-density lipoprotein and low-density lipoprotein with heparin-magnesium. Apolipoprotein (Apo)-AI level was assessed by immunoturbidimetric assay; triglycerides by an enzymatic colorimetric method. Body composition was assessed by dual-energy x-ray absorptiometry.Body composition improved after GFD, with increasing body weight (P0.05) essentially owing to increased fat mass (FM) (P0.01), rather than fat-free mass (P=0.064). Total cholesterol and HDL-C were lower in untreated compared with treated patients (P0.001 and P0.0001). Apo-AI level increased significantly after GFD (1.20+/-0.22 vs. 1.46+/-0.17 g/L; P0.0001). Apo-AI, sex, and FM were all significant determinants of HDL-C level; a positive correlation (R=0.68; P0.0001) was found between increase in HDL-C level and in FM after GFD treatment.Restoration of lipid profile in CD patients after GFD treatment may be explained by an increase in both Apo-AI secretion by intestinal cells and body fat stores.

Background Hepatitis C virus (HCV) transmission is mainly due to parenteral exposure; however, in absence of such risk factor, there are reports of intrafamilial spread of HCV and observational studies suggest an increased risk for households of infected subjects. The aim of our study was to systematically review and meta-analyse studies about HCV prevalence among households of HCV patients in Italy. Methods PubMed and Embase were searched to identify Italian studies about HCV intrafamilial transmission. Keywords used were: ‘HCV’, ‘Hepatitis C’, ‘intrafamilial’, ‘family’ and ‘Italy’. Selected studies were reviewed to assess the quality and meta-analysed using StatsDirect software. Results 25 studies were selected. The pooled overall prevalence was 9% (95% CI 7.1% to 11.1%). The highest pooled prevalence was found among sexual partners of index cases: 14.7% (95% CI 10.7% to 19.2%) globally and 9.9% (95% CI 3.6% to 18.8%) and 17.6% (95% CI 12.1% to 24%) in northern and central-southern regions, respectively. The meta-analysis of high-quality studies yielded the lowest HCV prevalence. Conclusion To be a HCV patient household is a risk factor for HCV and counselling for these households should be provided.

Resume La maladie periodique (fievre familiale mediterraneenne) est une maladie hereditaire, a transmission autosomique recessive, faisant partie des maladies auto-inflammatoires. Elle est caracterisee par des episodes recidivants, de courte duree (en moyenne 24 a 72 heures) et de resolution spontanee, comportant de la fievre et l’inflammation d’une sereuse. La maladie periodique est la plus frequente des fievres periodiques au sein des maladies auto-inflammatoires qui constituent un groupe heterogene et recemment identifie, de maladies caracterisees par des acces febriles recidivants, sans auto-anticorps, ni lymphocytes T specifiques de l’antigene. Habituellement, les crises sont declenchees par des stimuli anodins et peuvent etre precedees d’une phase prodromique. Le gene responsable de la fievre familiale mediterraneenne, appelee MEFV, est situe sur le chromosome 16 (16p13) et code pour la proteine pyrine-marenostrine. Le mecanisme physiopathologique precis de la maladie periodique necessite d’etre encore determine. Le nouveau complexe macromoleculaire appele inflammasome, qui semble jouer un role tres important dans le controle de l’inflammation, pourrait etre implique dans la pathogenie de la maladie periodique. La complication la plus severe a long terme est l’amylose AA qui atteint surtout les reins et peut entrainer une insuffisance renale chronique. Des facteurs de risque, a la fois genetiques et non genetiques, du developpement de l’amylose secondaire ont ete identifies. Actuellement, le seul traitement efficace de la maladie periodique est la colchicine. De nouvelles molecules ont ete essayees chez des patients refractaires a la colchicine, mais des etudes supplementaires portant sur des effectifs suffisants sont necessaires avant d’aboutir a des conclusions formelles.

Retroperitoneal fibrosis (RPF) is a disease characterized by inflammatory fibrotic processes affecting the retroperitoneal structures. Familial Mediterranean Fever (FMF) is an autosomal recessive disorder, characterized by fever and attacks of sterile serositis. Colchicine is the only suitable drug for prevention of acute episodes. We describe a case of association between RPF and FMF in a 48-year-old male, in whom therapy with colchicine, besides preventing acute episodes, allowed RPF regression. To date the association between FMF and RPF and the use of colchicine therapy alone for RPF has not been described.

Autoimmune enteropathy is a rare disorder characterized by severe and protracted diarrhea, weight loss from malabsorption and immune-mediated damage to the intestinal mucosa, generally occurring in infants and young children, although some cases of adult onset have been reported in the literature. Pathogenetic mechanisms involve immunological disorders, in which the presence of antienterocyte autoantibodies, although detected since first description, seems now to be secondary. As occurs frequently in autoimmunity, subjects with autoimmune enteropathy may be affected by other autoimmune disorders, sometimes leading to particular forms, i.e. the IPEX syndrome and the APECED syndrome. The prognosis of autoimmune enteropathy patients depends on the severity of digestive symptoms (including fecal output), on the severity and extension of histological lesions along the gastrointestinal apparatus, and on the presence of extra-intestinal involvement. Management of autoimmune enteropathy patients is based on nutritional support and adequate hydration to ensure optimal growth and development, together with immunosuppressive therapy. Recently, biological agents have been introduced, with apparent beneficial effects.

— The relative distribution of T lymphocyte subsets, as defined by the monoclonal antibodies OKT, was determined by cytofluorimetric analysis in peripheral blood and in cells isolated from liver biopsies of 31 patients with chronic active hepatitis (CAH). The percentage of peripheral blood lymphocytes binding OKT8 (directed against cytotoxic/suppressor T cells) was found to be elevated in patients with HBsAg and HBeAg positive chronic active hepatitis. Patients with CAH who had seroconverted to anti-HBe, had an increased number of OKT3-positive cells in their blood, which was directed against a common T cell surface antigen, associated with a decreased number of OKT8 positive cells. Lymphocytes isolated from liver biopsies of patients with CAH presented a general increase of OKT8-positive cells associated with a decreased number of OKT4-positive (helper/inducer) T cells. It is likely that OKT8-positive cells found in liver biopsies represent cytotoxic T cells directed against either viral or liver cell determinants.

Six acute phase proteins (haptoglobin, alpha 1-acid glycoprotein, alpha 1-antitrypsin, alpha 2-macroglobulin, C reactive protein and transferrin) have been measured in the sera of chronic liver disease (CLD) patients with different aetiology (viral, autoimmune and alcoholic) and histology (steatosis, chronic persistent hepatitis, chronic active hepatitis, cirrhosis), and in patients with liver cancer. 1) The most striking changes concerned alpha 2-macroglobulin (increased) and haptoglobin (decreased) levels. 2) Transferrin was lower in alcoholic liver disease than in viral CLD, CRP was lower in autoimmune than in viral or alcoholic CLD, and alpha 1-acid glycoprotein was lower in viral and alcoholic CLD than in autoimmune CLD. Acute phase protein assay may prove useful in differential diagnosis, particularly when specific markers are not available (autoimmune, non A, non B, alcoholic liver diseases). 3) No significant differences related to aetiology (B, non A non B, D viruses) were observed in viral CLD. 4) Patients who progressed to CLD after acute viral hepatitis type B or non A non B did not show different APP levels from those who had recovered when tested 8-12 months after the acute phase. 5) The pattern of APP changes observed in primary liver cell carcinoma was different from both the cirrhotic pattern and the pattern presented by other tumours with or without liver metastasis.

PURPOSE: Hepatic hydrothorax is defined as the accumulation of pleural effusion in a cirrhotic patient in the absence of pulmonary or cardiac disease. Peritoneal fluid can pass into the pleural space through diaphragmatic fenestrations. The demonstration of such passage is important to establish the diagnosis of hepatic hydrothorax and can be achieved by intraperitoneal injection of nuclear contrast agents. Our aim was to evaluate the ability of contrast enhanced ultrasound in the detection of peritoneal-pleural communications. MATERIALS AND METHODS: Seven patients with cirrhotic ascites and pleural effusion were studied in order to make a diagnosis of hepatic hydrothorax. SonoVue was injected into the peritoneal cavity (9.8 mL), and the peritoneal and pleural cavities were monitored by ultrasound. All patients were then studied using a nuclear scan. RESULTS: Passage of SonoVue from the peritoneal to the pleural cavities was seen in 5 patients. In 2 patients, no passage of contrast agent was detectable. Nuclear scan was consistent with contrast enhanced ultrasound in all patients. CONCLUSION: This study shows that the presence of peritoneal-pleural communications can be demonstrated by real time contrast enhanced ultrasound, whose results are comparable to those of nuclear scan. Contrast enhanced ultrasound is cheaper and could theoretically be performed wherever ultrasound facilities are available.

Veno-occlusive disease (VOD) of the liver is a severe complication of high-dose chemotherapy and allogeneic or autologous stem cell transplantation with potential fatal outcome. We report a case of severe VOD in a patient with a high-grade B-cell lymphoma. Liver-venule occlusion was confirmed by liver biopsy. Supportive care, fibrinolytic treatment with recombinant tissue plasminogen activator and defibrotide maintenance therapy led to complete resolution of VOD demonstrated at liver biopsy and with a follow-up of 44 months after autologous peripheral blood stem cell transplantation. The literature on VOD has been reviewed.

Background The optimal band imaging (OBI) system is a new technology that can select better spectral images decomposed from ordinary endoscopic images. This technology, first introduced as "FUJI Intelligent Color Enhancement," enhances the contrast of the mucosal surface without the use of dyes. Objective This study aimed to evaluate the potential of OBI for predicting the duodenal villous morphologic characteristics in patients with suspected celiac disease. Design This study was designed as an open, prospective, single-center trial. Duodenoscopy was performed with a high-resolution magnification view, in association with OBI spectral processing. Duodenal villous patterns were evaluated and classified as normal, partially atrophic, or markedly atrophic. The endoscopic results were then compared with the histologic diagnosis. Setting Endoscopy unit at the A. Gemelli University Hospital of Rome, Italy. Patients Sixty-one patients undergoing upper endoscopy for clinical history of malabsorption or serologic suspicion for celiac disease were included in the study. Results From OBI sets using red, green, and blue wavelength combinations that ranged from 400 to 580 nm, the endoscopist was able to find marked villous atrophy of the duodenum in 16 subjects, partial villous atrophy in 9 subjects, and normal villi in the remaining 36 subjects. The sensitivity, specificity, and positive and negative predictive values of the OBI-based duodenoscopy were 100% accurate in the evaluation of villous patterns. Conclusions High-resolution magnification endoscopy with OBI allows clear visualization of the duodenal villous pattern. The OBI system may play a potential role in optimizing the diagnostic accuracy of endoscopy in celiac disease.

Background: Previous studies suggested an association between CagA-positive H. pylori strains and ischemic stroke. The aim of the present study was to assess the prevalence of Helicobacter pylori infection and CagA status in patients with atherosclerotic stroke in the primary care setting. Materials and methods: A total of 106 consecutive patients (age 76.6 ± 8 years; males 52%) with well-documented history of atherosclerotic stroke and 106 sex–age- (age 76.5 ± 9 years; males 52%) and social background-matched controls without relevant vascular diseases. Risk factors for ischemic stroke were recorded in all subjects. H. pylori infection was assessed by[13]C-urea breath test. A serologic assay for specific IgG against CagA was performed in infected subjects. Results: A trend toward a higher prevalence of H. pylori was observed in cases (63%) with respect to controls (54%) without reaching a statistical significance. CagA positivity was associated to a higher risk of atherosclerotic stroke (adjusted odds ratio 2.69, 95% confidence interval 1.37–5.30). Conclusions: Our findings suggest that CagA-positive strains of H. pylori are significantly associated to atherosclerotic stroke. This is not a merely confirmative study since it has been performed for the first time in the primary care setting and included only subjects with an active infection.

SUMMARY Objectives: To evaluate state and trait form of anxiety and current depression in patients affected by gastrointestinal diseases. Methods: We studied 1641 outpatients with gastrointestinal disorders, consecutively referred to our Internal Medicine outpatients from 1997 to 2005. State and trait anxiety were assessed by the State and Trait Anxiety Inventory. Current depression was assessed by the Zung self-rating depression scale. Results: Among patients, 1379 (84.1%) showed state anxiety, 1098 (67%) showed trait anxiety and 442 (27%) showed current depression. The number of gastrointestinal diseases was directly correlated to state anxiety (p < 0.001) and trait anxiety (p = 0.04). Females showed higher levels of anxiety and depression than males (p < 0.001). State anxiety was related to food allergies (p < 0.001), small intestinal bacterial overgrowth (SIBO) (p = 0.001), Hp infection (p = 0.01) and ulcerative colitis in active phase (p = 0.03). Trait anxiety was related to irritable bowel syndrome (IBS) (p < 0.001), Helicobacter pylori (Hp) infection (p = 0.001), food allergies (p = 0.001) and SIBO (p = 0.001). Current depression was related to IBS (p < 0.001) and coeliac disease (p = 0.01), SIBO (p = 0.02). A predicted probability of 0.77 ± 0.16 to have state anxiety, of 0.66 ± 0.12 to have trait anxiety and of 0.39 ± 0.14 to have depression was found in these patients. Conclusions: Most of the patients who seek medical consultation for gastrointestinal problems show an associated affective disorder. These patients should be managed by a team including gastroenterologists, psychologists and ⁄ or psychiatrists, or by a gastroenterologist having expertise in the treatment of psychological disorders. What’s known Anxiety and depression represent a common feature in patients affected by gastrointestinal diseases. These affective disorders can be present as a personality trait or in a reactive form. What’s new The study supports that the approach to patients affected by gastrointestinal diseases should be managed by a team including gastroenterologists, psychologists and ⁄ or psychiatrists, or alternatively they should be managed by gastroenterologist having expertise in the treatment of psychological disorders. 1

Even ascites appears mainly as sign of portal hypertension in patiens with liver cirrhosis, in some case depends on a different lying condition such as right congestive heart failure, peritoneal carcinomatosis or tuberculosis. In these cases, paracentesis represents the key tool for diagnosis. We report a case of cardiac ascites in a 71-years-old woman who developed in four-month an abdominal distension. Preliminary exams showed exudative ascites related to portal hypertension, a pelvic mass with caseous apparence, and inflammatory status ad an elevation of CA-125. Successive evaluation exluded peritoneal carcinomatosis or tuberculosis, underlyng a tricuspidal regurgitation. The literature on ascites has also been reviewed.

Summary Introduction: Liver fibrosis (LB) assessment plays an important role in hepatology. A common characteristic of all chronic liver diseases is the occurrence and progression of fibrosis towards cirrhosis. Besides its plain interest for prognosis purposes, determining the fibrosis reveals the natural history of the disease and the risk factors associated with its progression to guide the antifibrotic action of different treatments. Discussion: Today, in clinical practice there are three available methods for the evaluation of LB. Biopsy, which is still considered as the ‘gold standard’ method. Serological markers and their mathematical combination are suggested in the last years in alternative to LB. More recently, transient elastography (TE) was proposed. TE is a simple and noninvasive method for measuring liver stiffness. This technique is based on the progression speed of an elastic shear wave within the liver. Conclusions: Currently, there are just a few studies capable of evaluating the TE effectiveness in chronic liver diseases, mainly in patients infected with hepatitis C virus (HCV). Its application must also be studied in the monitoring of patients suffering from chronic HCV infection and subjected to a treatment that can modify their degree of liver fibrosis. The results of TE must be interpreted according to the clinical background of the specialist.

All the anomalous reactions secondary to food ingestion are defined as ‘adverse reactions to food’. In 1995 the European Academy of Allergology and Clinical Immunology suggested a classification on the basis of the responsible pathogenetic mechanism; according to this classification, non-toxic reactions can be divided into ‘food allergies’ when they recognize immunological mechanisms, and ‘food intolerances’ when there are no immunological implications. The diagnostic approach to adverse reactions to food is based on accurate clinical history and objective examination, and further execution of specific tests when allergy or intolerance is suspected. The therapy for food allergies is the elimination of the food to which hypersensibility has been found; this strategy can lead, especially in pediatric age, to tolerance. If elimination diets cannot be completely performed, or if it is not possible to identify the food to eliminate, some drugs (e.g. antihistaminics, steroids, etc.) can be administered. Specific allergen immunotherapy has been recently introduced. Fundamental is food allergy prevention, especially in high-risk subjects. The therapeutic approach to secondary food intolerances is based principally on primitive disease resolution; on the other hand, some specific treatments (e.g. β-galactosidases in lactose malabsorption) are available in case of primary intolerance.

Introduction Short-chain fatty acids affect enterocyte metabolism and differentiation. Butyric acid in particular is already used in ulcerative rectal colitis, pouchitis and antibiotic-induced diarrhoea. Aims To assess the efficacy of butyrate in the treatment of irritable bowel syndrome (IBS). Patients Fifty patients with IBS were treated using enteric-coated sodium butyrate tablets at a dosage of 1 g/day for 30 days. Methods The patients were divided into two subgroups: constipation-predominant IBS and diarrhoea-predominant IBS. The IBS variant and symptom scores of patients were recorded before and after treatment. Results Treatment with butyric acid reduced in normalisation of status in 68% and 71% of patients in the diarrhoea-predominant IBS group vs. 14% and 16% of patients in the constipation-predominant IBS group (respectively for the intent-to-treat and per-protocol analyses) (p Conclusions Oral administration of butyrate may be effective in regulating status and improving gastrointestinal symptoms in patients with the diarrhoea-predominant irritable bowel syndrome.

A 24-week, double-blind, randomized study at 13 centres compared the efficacy and safety of 20 mg famotidine nocte and 150 mg ranitidine h.s. for the prevention of duodenal ulcer recurrence. All participants had been successfully treated for an acute duodenal ulcer with 40 mg famotidine nocte. Patients were endoscoped at baseline and at 24 weeks, unless symptoms warranted earlier examination: of the 208 patients enrolled, 86 who received famotidine and 84 who received ranitidine met all protocol criteria and were considered evaluable. Intention to treat and per protocol analyses showed non-significant trends in favour of famotidine (P = 0.44 and 0.16, respectively). During the 24-week observation period, 16.3% of the famotidine group and 25% of the ranitidine group had an ulcer recurrence (95% CI of percentage difference -0.22 + 0.04). At 24 weeks, relief of day and night pain was reported by 81.2% and 91.8% of the famotidine-treated patients, respectively. The corresponding figures in the ranitidine group were 73.5% and 85.5%. No laboratory abnormalities related to the study-drugs were noted and only two drug related (possibly or probably) adverse experiences were reported, both in the famotidine group. The data from this study therefore, supports the conclusion that the efficacy of 20 mg famotidine nocte is comparable to that of ranitidine in preventing duodenal ulcer recurrence, with comparable tolerability for long-term therapy.

Background & Aims: A specific, occupation-related susceptibility of professional singers to experience gastroesophageal reflux was hypothesized. We investigated the prevalence of gastroesophageal reflux symptoms in a series of professional opera choristers in comparison with a general population sample. Methods: A total of 351 professional opera choristers from well-known choirs in different Italian regions were identified and a sample of 578 subjects residing in the same areas with a similar distribution in age and sex was selected. Reflux symptoms in the year preceding the survey together with selected individual characteristics and lifestyle habits were investigated in both study groups through a structured questionnaire. Prevalence rate ratios, adjusted for sex, age, body mass index, smoking status, alcohol consumption, and other confounding factors, were computed. Results: Opera choristers reported a statistically significant higher prevalence of heartburn, regurgitation, cough, and hoarse voice than the population sample, with adjusted prevalent rate ratios of 1.60 (95% confidence interval [CI], 1.32–1.94), 1.81 (95% CI, 1.42–2.30), 1.40 (95% CI, 1.18–1.67), and 2.45 (95% CI, 1.97–3.04), respectively. Regurgitation appeared to be associated consistently with the cumulative lifetime duration of singing activity (P = .04) and with the weekly duration of singing activity (P = .005) when different multivariate models were applied. Conclusions: Opera choristers reported a higher prevalence of reflux symptoms than the population sample. Future studies will be needed to clarify whether gastroesophageal reflux in professional opera choristers is stress-induced and therefore may be considered as a work-related disease.

ummary Background Rifaximin is a broad spectrum non-absorbable antibiotic used for treatment of small intestinal bacterial overgrowth. Doses of 1200 mg/day showed a decontamination rate of 60% with low side-effects incidence. Aims To assess efficacy, safety and tolerability of rifaximin 1600 mg with respect to 1200 mg/day for small intestinal bacterial overgrowth treatment. Methods Eighty consecutive small intestinal bacterial overgrowth patients were enrolled. Diagnosis of small intestinal bacterial overgrowth based the clinical history and positivity to H2/CH4 glucose breath test. Patients were randomized in two 7-day treatment groups: rifaximin 1600 mg (group 1); rifaximin 1200 mg (group 2). Glucose breath test was reassessed 1 month after. Compliance and side-effect incidence were also evaluated. Results One drop-out was observed in group 1 and two in group 2. Glucose breath test normalization rate was significantly higher in group 1 with respect to group 2 both in intention-to-treat (80% vs. 58%; P

OBJECTIVES The pathogenesis of inflammatory bowel disease seems to depend on the combination of genetic and environmental factors. To evaluate genetic susceptibility, one approach is to search for specific markers in apparently unaffected family members of patients. Our aim was to evaluate fecal calprotectin concentrations (FCCs) in first-degree relatives of patients with ulcerative colitis (UC). PATIENTS Fifty-five patients with UC and 167 healthy first-degree relatives were recruited; 38 of the patients' spouses were also enrolled. One hundred fifty healthy subjects participated as the control group. METHODS FCCs were determined by ELISA. FCCs were compared among the groups by Kruskal-Wallis analysis of variance (ANOVA) test followed by Mann-Whitney U test. RESULTS Significantly greater FCCs were found in first-degree relatives of patients with UC (76.0 [34.7-129.6] microg/g) as compared with controls (31.6 [17.0-45.0]) (P < 0.0001). Fecal calprotectin levels in patients with UC (256.0 [153.0-356.0] microg/g) were significantly higher as compared with first-degree relatives, spouses (43.8 [18.6-89.0] microg/g), and controls (P < 0.0001 for all comparisons). FCC of relatives was significantly higher than FCC of spouses (P = 0.01). FCC of spouses had a significantly higher FCC with respect to controls (P = 0.01). CONCLUSIONS First-degree relatives of patients with UC had greater FCC values and could have a subclinical intestinal inflammation. It needs to be clarified if this finding is the consequence of genetic predisposition, of environmental factors, or the interaction of both, and if relatives with high FCC have a greater risk of developing the disease.

Coeliac disease (CD), an autoimmune gluten-dependent enteropathy, can be associated with several extra-intestinal manifestations, including neurological disorders. At present, no data are available on the presence of hearing loss disorder in coeliac patients. The aim of the present study was to investigate the prevalence of hearing loss in coeliac patients compared with that in healthy controls.Twenty-four adult coeliac patients and 24 healthy subjects matched for gender, age, smoking and drinking habits were enrolled in the study. Among the coeliac patients, 6 were newly diagnosed and 18 patients were on a gluten-free diet for at least one year.A hearing loss was found in 10 (47.1%) coeliac patients and 2 (9.1%) healthy controls. All CD patients with hearing loss presented a sensorineural hearing loss. The prevalence of hearing loss was significantly higher in coeliac patients than in healthy controls (p = 0.01) but it was not significantly different between untreated (33.3%) and treated (44.4%) coeliac patients (p: NS).Despite the low number of subjects evaluated, the present study showed a higher prevalence of hearing loss in coeliac patients than in healthy controls, suggesting an association between CD and hearing loss. Immunological processes such as ear-specific and non-specific autoantibodies and vasculitis could be the basis of this association. Further longitudinal investigations on a larger sample size will be necessary to confirm the present data.

Sialorrhea is frequent and invalidating in patients with amyotrophic lateral sclerosis (ALS) or Parkinson's disease (PD). Botulinum toxin (BTX) emerged as an alternative to traditional treatments. We evaluated efficacy and tolerability of ultrasound-guided BTX-B injections in parotids and submandibular glands in 18 patients with ALS or PD. At 1 week, both objective (cotton rolls weight) and subjective evaluations (dedicated clinical scales) documented sialorrhea reduction (p

Objective: The quantification of basophil activation by flow cytometry is a useful tool for the assessment of immediate-type responses to food allergens and the prediction of clinical tolerance in food allergy patients. The aim of this study is to investigate how the analysis of allergen-induced CD63 up-regulation by flow cytometry can be effective in monitoring the acquisition of clinical tolerance by specific oral desensitization in food allergy. To our knowledge, this is the first study to examine this topic. Materials and methods: Three male patients affected by cow’s milk allergy underwent successful oral desensitization to cow’s milk. In order to monitor the acquired clinical tolerance that occurred after treatment, we performed laboratory tests for total and specific IgE, specific IgG4 and the Basophil Activation Test (BAT) both at baseline and at the end of the desensitization protocol. Results: Using a fluorescent enzyme immunoassay, the comparison of specific cow’s milk antibodies before and after treatment showed a decrease of specific IgE levels, without reaching normal values, and an increase of specific IgG4 levels. A complete suppression of cow’s milk proteins (a-lactoalbumin, b-lactoglobulin and casein) induced CD63 regulation was observed in all three reported cases. Conclusions: Using flow cytometry, food allergen-specific basophil responses could be monitored in order to identify an acquired tolerance induced by desensitization treatment. Although further studies are needed to develop this important new topic, it was interesting to note that the BAT seemed to be more sensitive and characterized by a close correlation with clinical tolerance.

Knowledge on the role of Helicobacter pylori (HP) infection is continually evolving, and treatment is becoming more challenging due to increasing bacterial resistance. Since the management of HP infection is changing, an update of the national Italian guidelines delivered in 2007 was needed. In the III Working Group Consensus Report 2015, a panel of 17 experts from several Italian regions reviewed current evidence on different topics relating to HP infection. Four working groups examined the following topics: (1) “open questions” on HP diagnosis and treatment (focusing on dyspepsia, gastro-oesophageal reflux disease, non-steroidal anti-inflammatory drugs or aspirin use and extra-gastric diseases); (2) non-invasive and invasive diagnostic tests; (3) treatment of HP infection; (4) role of HP in the prevention of gastric cancer. Statements and recommendations were discussed and a consensus reached in a final plenary session held in February 2015 in Bologna. Recommendations are based on the best current evidence to help physicians manage HP infection in Italy. The guidelines have been endorsed by the Italian Society of Gastroenterology and the Italian Society of Digestive Endoscopy.

Summary Recent preclinical and clinical studies have suggested that baclofen, the prototypic γ-aminobutyric acid B (GABAB) receptor agonist, is a promising pharmacological compound for use in the treatment of alcohol dependence. In particular, baclofen has been found to suppress symptoms of alcohol withdrawal syndrome with an efficacy comparable with that of the ‘gold standard’ diazepam. Moreover, baclofen has proven effective in the prevention of relapse due to its ability to reduce alcohol intake and craving in alcoholic patients. Baclofen proved to be manageable, producing no significant side effects and displaying no addictive properties. The efficacy of the drug in the management of both alcohol withdrawal syndrome and relapse prevention should entail a vastly simplified pharmacotherapy of alcohol dependence.

Probiotics are described as "friendly bacteria" that could improve the intestine defense by interacting with the resident microflora. There is a large body of evidence suggesting that consumption of functional food containing probiotics exerts positive effects on human health. Several clinical trials have highlighted the efficiency of probiotics in the prevention and treatment of different gastrointestinal disorders including the prevention of antibiotic associated diarrhea, the remission in patients with inflammatory bowel disease, beneficial effects against Helicobacter pylori infection, positive effects in patients affected by allergies and atopic diseases. The clinical benefits of probiotics use are mainly attributed to their antimicrobial substances production and their positive interactions with the enterocytes to reinforce the intestinal epithelial barrier. Moreover, there is evidence suggesting that probiotics stimulate both specific and non-specific host immune responses. Recently, have been published some experiments performed with the DNA microarray technology which provided a global gene screening of the complex bacteria-host interplay. Nevertheless, the molecular mechanisms by which probiotics enhance the intestinal host defense are still not completely elucidated. Here, we review the experiments and clinical studies to date on the complex mechanisms regulating the communication between probiotics and their hosts.

Summary Background Aminosalicylates are the mainstay of therapy to prevent relapse of quiescent ulcerative colitis. The rationale for using probiotics is based on the evidence implicating intestinal bacteria in the pathogenesis of this disorder. Aim To evaluate the efficacy of Lactobacillus GG alone or in combination with mesalazine vs. mesalazine as maintenance treatment in ulcerative colitis. Patients and methods 187 ulcerative colitis patients with quiescent disease were randomized to receive Lactobacillus GG 18 × 109 viable bacteria/day (65 patients), mesalazine 2400 mg/day (60 patients) or Lactobacillus GG + mesalazine (62 patients). Disease activity index, endoscopic and histological scores were determined at 0, 6 and 12 months and in case of relapse. The primary end point was to evaluate sustained remission. Results Overall analysis showed no difference in relapse rate at 6 (P = 0.44) and 12 months (P = 0.77) among the three treatment groups. However, the treatment with Lactobacillus GG seems to be more effective than standard treatment with mesalazine in prolonging the relapse-free time (P

In the last few years many studies have shown the potential role of different triggers in the pathogenesis of several autoimmune diseases. In particular, in Sjogren's syndrome the presence of a genetic background is considered determining, but environmental factors have recently been described as triggers or precipitators. In this report, we describe the case of a young woman affected by celiac disease in which an Ascaris lumbricoides infestation and estrogen therapy could have played a role in the development of Sjogren's syndrome.

Summary Background The ‘immersion’ technique during upper endoscopy allows the visualization of duodenal villi and the detection of total villous atrophy. Aim To evaluate the accuracy of the immersion technique in detecting total villous atrophy in suspected coeliac patients. The accuracy in diagnosing coeliac disease and the potential cost-sparing of a biopsy-avoiding approach, based on selection of individuals with coeliac disease-related antibodies and on endoscopic detection of absence of villi, were also analysed. Methods The immersion technique was performed in 79 patients with positive antibodies and in 105 controls. Duodenal villi were evaluated as present or absent. As reference, results were compared with histology. Diagnostic approaches, including endoscopy with or without biopsy, were designed to investigate patients with coeliac disease-related antibodies and total villous atrophy. A cost-minimization analysis was performed. Results All patients with positive antibodies had coeliac disease. The sensitivity, specificity, positive and negative predictive values of endoscopy to detect total villous atrophy was always 100%. The sensitivity, specificity, positive and negative predictive values of biopsy-avoiding or biopsy-including strategies in diagnosing coeliac disease when villi were absent was always 100%. The biopsy-avoiding strategy was cost-sparing. Conclusions Upper endoscopy is highly accurate in detecting total villous atrophy coeliac patients. A biopsy-avoiding approach is both accurate and cost-sparing to diagnose coeliac disease in subjects with marked duodenal villous atrophy.