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Background: High-Flow through Nasal Cannula (HFNC) is a system delivering heated humidified air-oxygen mixture at a flow up to 60 L/min. Despite increasing evidence in hypoxemic acute respiratory failure, a few is currently known in chronic obstructive pulmonary disease (COPD) patients., Objective: To describe the rationale and physiologic advantages of HFNC in COPD patients, and to systematically review the literature on the use of HFNC in stable and exacerbated COPD patients, separately., Methods: A search strategy was launched on MEDLINE. Two authors separately screened all potential references. All (randomized, non-randomized and quasi-randomized) trials dealing with the use of HFNC in both stable and exacerbated COPD patients in MEDLINE have been included in the review., Results: Twenty-six studies have been included. HFNC: 1) provides heated and humidified airoxygen admixture; 2) washes out the anatomical dead space of the upper airway; 3) generates a small positive end-expiratory pressure; 4) guarantees a more stable inspired oxygen fraction, as compared to conventional oxygen therapy (COT); and 5) is more comfortable as compared to both COT and non-invasive ventilation (NIV). In stable COPD patients, HFNC improves gas exchange, the quality of life and dyspnea with a reduced cost of muscle energy expenditure, compared to COT. In exacerbated COPD patients, HFNC may be an alternative to NIV (in case of intolerance) and to COT at extubation or NIV withdrawal., Conclusion: Though evidence of superiority still lacks and further studies are necessary, HFNC might play a role in the treatment of both stable and exacerbated COPD patients., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Coeliac disease (CD) and gluten-related disorders represent an important cornerstone of the daily practice of gastroenterologists, endoscopists and dedicated histopathologists. Despite the knowledge of clinical, serological and histological typical lesions, there are some conditions to consider for differential diagnosis. From the first description of histology of CD, several studies were conducted to define similar findings suggestive for microscopic enteritis. Considering the establishment of early precursor lesions, the imbalance of gut microbiota is another point still requiring a detailed definition. This review assesses the importance of a right overview in case of suspected gluten-related disorders and the several conditions mimicking a similar histology., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: Noninvasive ventilation (NIV) may facilitate withdrawal of invasive mechanical ventilation (i-MV) and shorten intensive care unit (ICU) length of stay (LOS) in hypercapnic patients, while data are lacking on hypoxemic patients. We aim to determine whether NIV after early extubation reduces the duration of i-MV and ICU LOS in patients recovering from hypoxemic acute respiratory failure., Methods: Highly selected non-hypercapnic hypoxemic patients were randomly assigned to receive NIV after early or standard extubation. Co-primary end points were duration of i-MV and ICU LOS. Secondary end points were treatment failure, severe events (hemorrhagic, septic, cardiac, renal or neurologic episodes, pneumothorax or pulmonary embolism), ventilator-associated pneumonia (VAP) or tracheobronchitis (VAT), tracheotomy, percent of patients receiving sedation after study enrollment, hospital LOS, and ICU and hospital mortality., Results: We enrolled 130 consecutive patients, 65 treatments and 65 controls. Duration of i-MV was shorter in the treatment group than for controls [4.0 (3.0-7.0) vs. 5.5 (4.0-9.0) days, respectively, p = 0.004], while ICU LOS was not significantly different [8.0 (6.0-12.0) vs. 9.0 (6.5-12.5) days, respectively (p = 0.259)]. Incidence of VAT or VAP (9% vs. 25%, p = 0.019), rate of patients requiring infusion of sedatives after enrollment (57% vs. 85%, p = 0.001), and hospital LOS, 20 (13-32) vs. 27(18-39) days (p = 0.043) were all significantly reduced in the treatment group compared with controls. There were no significant differences in ICU and hospital mortality or in the number of treatment failures, severe events, and tracheostomies., Conclusions: In highly selected hypoxemic patients, early extubation followed by immediate NIV application reduced the days spent on invasive ventilation without affecting ICU LOS.

Background and Objectives: Transthoracic echocardiography may potentially be useful to obtain a prompt, accurate and non-invasive estimation of cardiac output. We evaluated whether non-cardiologist intensivists may obtain accurate and reproducible cardiac output determination in hemodynamically unstable mechanically ventilated patients., Methods: We studied 25 hemodynamically unstable mechanically ventilated intensive care unit patients with a pulmonary artery catheter in place. Cardiac output was calculated using the pulsed Doppler transthoracic echocardiography technique applied to the left ventricular outflow tract in apical 5 chamber view by two intensive care unit physicians who had received a basic Transthoracic Echocardiography training plus a specific training focused on Doppler, left ventricular outflow tract and velocity-time integral determination., Results: Cardiac output assessment by transthoracic echocardiography was feasible in 20 out of 25 enrolled patients (80%) and showed an excellent inter-operator reproducibility (Pearson correlation test r=0.987; Cohen's K=0.840). Overall, the mean bias was 0.03L.min -1 , with limits of agreement -0.52 and +0.57L.min -1 . The concordance correlation coefficient (ρ c ) was 0.986 (95% IC 0.966-0.995) and 0.995 (95% IC 0.986-0.998) for physician 1 and 2, respectively. The value of accuracy (C b ) of CO TTE measurement was 0.999 for both observers. The value of precision (ρ) of CO TTE measurement was 0.986 and 0.995 for observer 1 and 2, respectively., Conclusions: A specific training focused on Doppler and VTI determination added to the standard basic transthoracic echocardiography training allowed non-cardiologist intensive care unit physicians to achieve a quick, reproducible and accurate snapshot cardiac output assessment in the majority of mechanically ventilated intensive care unit patients., (Copyright © 2018 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.)

Background: Protocols for treating recurrent Clostridium difficile infection (rCDI) through faecal microbiota transplantation (FMT) are still not standardised. Our aim was to evaluate the efficacy of different FMT protocols for rCDI according to routes, number of infusions and infused material., Methods: MEDLINE, Embase, SCOPUS, Web of Science and the Cochrane Library were searched through 31 May 2017. Studies offering multiple infusions if a single infusion failed to cure rCDI were included. Data were combined through a random effects meta-analysis., Results: Fifteen studies (1150 subjects) were analysed. Multiple infusions increased efficacy rates overall (76% versus 93%) and in each route of delivery (duodenal delivery: 73% with single infusion versus 81% with multiple infusions; capsule: 80% versus 92%; colonoscopy: 78% versus 98% and enema: 56% versus 92%). Duodenal delivery and colonoscopy were associated, respectively, with lower efficacy rates ( p  = 0.039) and higher efficacy rates ( p  = 0.006) overall. Faecal amount ≤ 50 g ( p  = 0.006) and enema ( p  = 0.019) were associated with lower efficacy rates after a single infusion. The use of fresh or frozen faeces did not influence outcomes., Conclusions: Routes, number of infusions and faecal dosage may influence efficacy rates of FMT for rCDI. These findings could help to optimise FMT protocols in clinical practice.

Helicobacter pylori is one of the most common gastrointestinal infection affecting humans worldwide. Hp colonizes the stomach with preferential trophism for the antrum. Hp infection is associated with the development of a chronic gastritis and subsequently with several gastric diseases such as peptic disease, gastric carcinoma and MALT lymphoma. Moreover, Helicobacter pylori infection has also been reported in literature to be associated with many other extra-gastric conditions including sideropenic anemia, thrombocytopenia, neurological, liver and cardiovascular diseases. For some conditions the association is supported by solid literature data and also by the identification of the possible physiopathogenetic mechanism involved. In other cases, the link is only reported by association studies often with conflicting results. In this context, diabetes mellitus, cardiovascular disorders and liver steatosis have all been reported to be associated with Helicobacter pylori infection. Interestingly, these conditions share many characteristics and they often overlap as they represent the expression of the so called metabolic syndrome. Aim of the review was to summarize the available data regarding the association between Helicobacter Pylori infection and diabetes mellitus, cardiovascular disorders and liver steatosis.

Acute diarrhea is a burdensome disease with potentially harmful consequences, especially in childhood. Despite its large use in clinical practice, the efficacy of the probiotic Bacillus clausii in treating acute childhood diarrhea remains unclear. Our objective was to systematically review the efficacy of Bacillus clausii in the treatment of acute childhood diarrhea. The following electronic databases were systematically searched up to October 2017: MEDLINE (via PubMed/OVID), EMBASE (via OVID), Cochrane Central Database of Controlled Trials (via CENTRAL), Google Scholar, and ClinicalTrials.gov. Only randomized controlled trials were included. The overall effect for the meta-analysis was derived by using a random effects model. Six randomized controlled trials (1298 patients) met the eligibility criteria. Data arising from pooled analysis showed that Bacillus clausii significantly reduced the duration of diarrhea (mean difference = -9.12 h; 95% confidence interval [CI]: -16.49 to -1.75, p = 0.015), and the duration of hospitalization (mean difference = -0.85 days; 95% CI: -1.56 to -0.15, p = 0.017), compared with control. There was a trend of decreasing stool frequency after Bacillus clausii administration compared with the control group (mean difference = -0.19 diarrheal motions; 95% CI: -0.43 to -0.06, p = 0.14). Bacillus clausii may represent an effective therapeutic option in acute childhood diarrhea, with a good safety profile.

Background: Faecal microbiota transplantation (FMT) is a highly effective treatment against recurrent Clostridium difficile infection. Far less evidence exists on the efficacy of FMT in treating severe Clostridium difficile infection refractory to antibiotics., Aim: To compare the efficacy of two FMT-based protocols associated with vancomycin in curing subjects with severe Clostridium difficile infection refractory to antibiotics., Methods: Subjects with severe Clostridium difficile infection refractory to antibiotics were randomly assigned to one of the two following treatment arms: (1) FMT-S, including a single faecal infusion via colonoscopy followed by a 14-day vancomycin course, (2) FMT-M, including multiple faecal infusions plus a 14-day vancomycin course. In the FMT-M group, all subjects received at least two infusions, while those with pseudomembranous colitis underwent further infusions until the disappearance of pseudomembranes. The primary outcome was the cure of refractory severe Clostridium difficile infection., Results: Fifty six subjects, 28 in each treatment arm, were enrolled. Twenty one patients in the FMT-S group and 28 patients in the FMT-M group were cured (75% vs 100%, respectively, both in per protocol and intention-to-treat analyses; P = 0.01). No serious adverse events associated with any of the two treatment protocols were observed., Conclusions: A pseudomembrane-driven FMT protocol consisting of multiple faecal infusions and concomitant vancomycin was significantly more effective than a single faecal transplant followed by vancomycin in curing severe Clostridium difficile infection refractory to antibiotics. Clinical-Trials.gov registration number: NCT03427229., (© 2018 John Wiley & Sons Ltd.)

Competing Interests: The authors declare no conflict of interest.

Background: Clostridium difficile infection (CDI) is characterized by a relevant intestinal neutrophil infiltrate. So far, role of fecal calprotectin in CDI, has been investigated only in few studies, mainly focused on diagnosis of the disease., Aim: By a longitudinal design, we assess fecal calprotectin concentrations (FCCs) in subjects with CDI, evaluating the correlation between fecal marker and response to therapy., Methods: Clinical (diarrhea scoring) and laboratory (FCCs and leucocytes count) evaluation was performed in 56 subjects with CDI at time of diagnosis (T 0 ) and after a week from starting of therapy (T 1 ). Clinical response to therapy at T 1 was related with both T 0 and T 1 FCC values. FCCs were also related to all-cause 30-day mortality, recurrence and death, both of them within 90 days., Results: FCCs at T 1 were significantly increased in subjects with persistence of diarrhea in respect to the other ones (285.5 ± 270 µg/g vs 150.7 ± 147 µg/g, respectively; p < .05). Patients who did not respond to therapy showed higher, but not significative, FCCs at T 0 than patients who responded. No correlation was found among FCCs, both at T 0 and T 1 , and the other outcomes., Conclusions: Longitudinal evaluation of FCCs in patients with CDI could support physicians in clinical management of disease, for example in term of duration (10 vs 14 days) or type (first vs second line therapy). Further and larger studies could confirm the eventual role of this marker in prognostic algorithms, mainly in prediction of recurrence.

Fecal microbiota transplantation (FMT) is the transplantation of microbial gut contents from a healthy individual into the gastrointestinal tract of a person with a disease, with a view to increasing the recipient's gut microbial diversity and bacterial richness and restoring microbial homeostasis. FMT has been proven to be a safe and effective treatment for Clostridium difficile infection (CDI) and it is now a recommended treatment for recurrent or refractory infection. FMT is not currently recommended for use outside of CDI due to concerns regarding outcome and safety; however, several case series and randomized controlled trials have described its use in a research environment for a few gastrointestinal conditions related to intestinal dysbiosis including ulcerative colitis (UC), Crohn's disease (CD) and irritable bowel syndrome (IBS). The most successful reports of the clinical efficacy of FMT in gastrointestinal conditions outside of CDI have been in treating UC. We summarize the current literature regarding the use of FMT in UC, including methodology, clinical efficacy and safety concerns, and identify pitfalls and areas for future development. We also describe the available evidence to date on the use of FMT in CD, IBS and other conditions related to intestinal dysbiosi., (Copyright 2018 Clarivate Analytics.)

The prevalence of nonalcoholic fatty liver disease and the consequent burden of metabolic syndrome have increased in recent years. Although the pathogenesis of nonalcoholic fatty liver disease is not completely understood, it is thought to be the hepatic manifestation of the dysregulation of insulin-dependent pathways leading to insulin resistance and adipose tissue accumulation in the liver. Recently, the gut-liver axis has been proposed as a key player in the pathogenesis of NAFLD, as the passage of bacteria-derived products into the portal circulation could lead to a trigger of innate immunity, which in turn leads to liver inflammation. Additionally, higher prevalence of intestinal dysbiosis, larger production of endogenous ethanol, and higher prevalence of increased intestinal permeability and bacterial translocation were found in patients with liver injury. In this review, we describe the role of intestinal dysbiosis in the activation of the inflammatory cascade in NAFLD.

Few data exist on differences in gut microbiota composition among principal gastrointestinal (GI) diseases. We evaluated the differences in gut microbiota composition among uncomplicated diverticular disease (DD), irritable bowel syndrome (IBS) and inflammatory bowel diseases (IBD) patients. DD, IBS, and IBD patients along with healthy controls (CT) were enrolled in our Italian GI outpatient clinic. Stool samples were collected. Microbiota composition was evaluated through a metagenomic gene-targeted approach. GI pathology represented a continuous spectrum of diseases where IBD displayed one extreme, while CT displayed the other. Among Phyla, Biplot PC2/PC3 and dendogram plot showed major differences in samples from IBS and IBD. DD resembled species CT composition, but not for Bacteroides fragilis. In IBS, Dialister spp. and then Faecalibacterium prausnitzii were the most representative species. Ulcerative colitis showed a reduced concentration of Clostridium difficile and an increase of Bacteroides fragilis. In Crohn's disease, Parabacteroides distasonis was the most represented, while Faecalibacterium prausnitzii and Bacteroides fragilis were significantly reduced. Each disorder has its definite overall microbial signature, which produces a clear differentiation from the others. On the other hand, shared alterations constitute the "core dysbiosis" of GI diseases. The assessment of these microbial markers represents a parameter that may complete the diagnostic assessment., (© 2017 S. Karger AG, Basel.)

Aim: To evaluate if a single and/or combined (clinical, endoscopic and radiological) assessment could predict clinical outcomes in Crohn's disease (CD)., Methods: We prospectively evaluated 57 CD cases who underwent both a colonoscopy and a CT-enterography (CTE). Harvey-Bradshaw Index (HBi), SES-CD (and/or Rutgeerts score) and the radiological disease activity were defined to stratify patients according to clinical, endoscopic and radiological disease activity respectively. Hospitalizations, surgery, therapeutic changes and deaths were evaluated up to 36 months (time 1) for 53 patients., Results: CTE and endoscopy agreed in stratifying disease activity in 47% of cases (k = -0.05; p = 0.694), CTE and HBi in 35% (k = 0.09; p = 0.08), endoscopy and HBi in 39% (k = 0.13; p = 0.03). Taken together, CTE, endoscopy and HBi agreed only in 18% of cases (k = 0.01; p = 0.41). Among the 11 cases with mucosal healing, only 3 (27%) showed transmural healing. Patients with endoscopic activity needed significantly more changes of therapy compared to patients with endoscopic remission (p = 0.02). Patients with higher transmural or clinical activity at baseline required significantly more hospitalizations (p < 0.01). Hospitalization rate decreases with an increase in the number of parameters indicating remissions at baseline (p = 0.04)., Conclusions: Clinical, endoscopic and radiological assessments offer complementary information and could predict different mid-term outcomes in CD., (© 2018 S. Karger AG, Basel.)

Clostridium difficile infection (CDI) is one of the most common healthcare-associated infections in the world and is a leading cause of morbidity and mortality in hospitalized patients.Although several antibiotics effectively treat CDI, some individuals do not respond to these drugs and may be cured by transplanting stool from healthy donors. This procedure, termed Faecal Microbiota Transplantation (FMT), has demonstrated remarkable efficacy as a treatment for recurrent CDI.FMT has also been investigated in other diseases and disorders where perturbations to the gut microbiota have been theorized to play a causative role in pathogenesis and severity, such as inflammatory bowel disease (IBD). Although FMT is currently not recommended to cure IBD patients in clinical practice, several studies have recently been carried out with promising results. The aim of future research is therefore to standardize protocols and develop FMT as a therapeutic option for these patients.This review summarizes data on the use of FMT as a treatment for CDI and IBD, with special attention given to studies conducted in European countries.

The wide assemblage of microorganisms inhabiting our gastrointestinal tract is an attractive field for overwhelming contemporary research in several aspects of the human health. Most recent molecular techniques, as the use of rRNAs or whole genome sequencing, definitely overcame traditional culture techniques in giving outline of the intestinal bacterial richness. Moreover, the crosstalk between host and intestinal microbes is considered a cornerstone affecting the host's metabolism, immunity, autoimmunity and autoinflammation and elaborate networks linked to several organs. The aim of this review is to summarize the broad spectrum of available pieces of information in this setting and to assess the current knowledge of the intestinal microbiota anatomy and physiology, in the perspective of future therapies modulating the gut microbial balance.

Gut microbiota is known to play a main role in regulating both health and disease in humans. Strategies for the therapeutic modulation of gut microbiota are therefore expected to give a relevant contribution in the management of disorders associated with its impairment. Among these options, one of the most renowned is fecal microbiota transplantation (FMT). A growing body of evidence showed clearly that FMT is an effective treatment against recurrent Clostridium difficile infection. Moreover, it was shown to be a promising therapy for the management of several noncommunicable disorders, including inflammatory bowel diseases and metabolic disorders. Standardization of procedural protocols for different disorders will surely increase the therapeutic power of FMT. The aim of this narrative review was to make an overview of methodology, indications, and future perspectives of FMT for the management of disorders associated with gut microbiota impairment.

Introduction: Colorectal cancer (CRC) is the third most common cancer in males and second in females, and the fourth most common cause of cancer death worldwide. Currently, about 60-70% of diagnosed cases in symptomatic patients are detected at an advanced stage of disease. Earlier stage detection through the use of screening strategies would allow for better outcomes in terms of reducing the disease burden. Areas covered: The aim of this paper is to review the current published evidence from literature which assesses the performance and effectiveness of different screening tests for the early detection of CRC. Expert commentary: Adequate screening strategies can reduce CRC incidence and mortality. In the last few decades, several tests have been proposed for CRC screening. To date, there is still insufficient evidence to identify which approach is definitively superior, and no screening strategy for CRC can therefore be defined as universally ideal. The best strategy would be the one that can be economically viable and to which the patient can adhere best to over time. The latest guidelines suggest colonoscopy every 10 years or annual fecal immuno-chemical test (FIT) for people with normal risk, while for individuals with high risk or hereditary syndromes specific recommendations are provided.

Background: During a fluid challenge, the changes in cardiac performance and peripheral circulatory tone are closely related to the position of the ventricle on the Frank-Starling curve. Some patients have a good haemodynamic response to a fluid challenge, others hardly any response. The early haemodynamic effects of a fluid challenge could predict the final response before the entire fluid volume has been administered., Objective: To assess whether a multivariate logistic regression model, including pulse pressure variation (PPV), cardiac cycle efficiency (CCE), arterial elastance and the difference between the dicrotic pressure and both systolic and mean arterial pressure (SAP - Pdic and MAP - Pdic) can predict cardiac responsiveness early during a fluid challenge in comparison with the standard procedure described elsewhere., Design: Observational study., Setting: Elective surgical patients undergoing laparotomy, enrolled in two Italian University Hospitals., Patients: Fifty adult surgical patients, ventilated with a lung protective strategy, were enrolled and data from 46 were analysed., Interventions: A fluid challenge consisting of 500 ml of crystalloid infused over 10 min., Main Outcome Measures and Analysis: The changes in CCE, arterial elastance, SAP - Pdic and MAP - Pdic were compared using analysis of variance. A multivariate logistic regression analysis utilising baseline values and the first minute measuring a variation statistically significant for the considered variables., Results: At baseline, PPV correctly identified 70% of patients (89% of non-responders; 42% of responders). The model, including baseline PPV, ΔCCE and ΔSAP - Pdic, correctly identified the efficiency of fluid challenge in 87% of patients (84.2% of responders; 92.5 of non-responders) after 5 min from fluid challenge infusion., Conclusion: In this pilot study conducted in a population of surgical patients mechanically ventilated with a VT less than 8 ml kg, a dynamic model of fluid challenge assessment, including PPV, ΔCCE and ΔSAP - Pdic, enhances the prediction of fluid challenge response after 5 min of a 10-min administration., Trial Registration: ACTRN12616001479493.

Introduction: Infliximab is an effective treatment for inflammatory bowel disease (IBD). Studies differ regarding the influence of body mass index (BMI) on the response to infliximab, with the majority of studies indicating that increased BMI may be associated with a poorer response to Infliximab. However, the pharmacokinetic mechanisms causing this have not yet been reported., Aims: Examine the correlation between BMI/immunosuppressant use with clinical response, trough and post-infusion levels of infliximab, tumour necrosis factor-α(TNF-α) and anti-drug antibodies(ATI), and determine if these factors can predict future response., Methods: We collected serum from 24 patients receiving Infliximab before and 30 minutes following infusion. Clinical parameters were collected retrospectively and prospectively. ELISA measurements of infliximab, TNF-α and ATI were performed., Results: We confirmed that patients with higher infliximab trough levels have a better response rate and that patients with an elevated BMI display a higher rate of loss of response (20%). Patients with a higher BMI had elevated post-infusion levels of infliximab. Additionally, the ratio of IFX/TNF-α trough levels correlated with clinical response to the following infusion., Conclusion: This study confirms that an elevated BMI is associated with a poorer response to infliximab. For the first time, we describe that a higher BMI correlates with higher post-infusion levels, however this does not correlate with a higher rate of response to the drug, suggesting that circulating drug levels do not correlate with tissue levels. Furthermore, in our small cohort of patients, we identified a possible predictive marker of future response to treatment which may be used to guide dose escalation and predict non-response to infliximab.

We assessed the effects of varying doses of remifentanil on respiratory drive and timing in patients receiving Pressure Support Ventilation (PSV) and Neurally Adjusted Ventilatory Assist (NAVA). Four incrementing remifentanil doses were randomly administered to thirteen intubated patients (0.03, 0.05, 0.08, and 0.1μg·Kg -1 ·min - 1) during both PSV and NAVA. We measured the patient's (Ti/Ttot neu ) and ventilator (Ti/Ttot mec ) duty cycle, the Electrical Activity of the Diaphragm (EAdi), the inspiratory (Delay trinsp ) and expiratory (Delay trexp ) trigger delays and the Asynchrony Index (AI). Increasing doses of remifentanil did not modify EAdi, regardless the ventilatory mode. In comparison to baseline, remifentanil infusion >0.05μg/Kg -1 /min -1 produced a significant reduction of Ti/Ttot neu and Ti/Ttot mec, by prolonging the expiratory time. Delay trinsp and Delay trexp were significantly shorter in NAVA, respect to PSV. AI was not influenced by the different doses of remifentanil, but it was significantly lower during NAVA, compared to PSV. In conclusion remifentanil did not affect the respiratory drive, but only respiratory timing, without differences between modes., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Noninvasive ventilation (NIV) is generally delivered using pneumatically-triggered and cycled-off pressure support (PS P ) through a mask. Neurally adjusted ventilatory assist (NAVA) is the only ventilatory mode that uses a non-pneumatic signal, i.e., diaphragm electrical activity (EAdi), to trigger and drive ventilator assistance. A specific setting to generate neurally controlled pressure support (PS N ) was recently proposed for delivering NIV by helmet. We compared PS N with PS P and NAVA during NIV using a facial mask, with respect to patient comfort, gas exchange, and patient-ventilator interaction and synchrony., Methods: Three 30-minute trials of NIV were randomly delivered to 14 patients immediately after extubation to prevent post-extubation respiratory failure: (1) PS P , with an inspiratory support ≥8 cmH 2 O; (2) NAVA, adjusting the NAVA level to achieve a comparable peak EAdi (EAdi peak ) as during PS P ; and (3) PS N , setting the NAVA level at 15 cmH 2 O/μV with an upper airway pressure (Paw) limit to obtain the same overall Paw applied during PS P . We assessed patient comfort, peak inspiratory flow (PIF), time to reach PIF (PIF time ), EAdi peak , arterial blood gases, pressure-time product of the first 300 ms (PTP 300-index ) and 500 ms (PTP 500-index ) after initiation of patient effort, inspiratory trigger delay (Delay TR-insp ), and rate of asynchrony, determined as asynchrony index (AI%). The categorical variables were compared using the McNemar test, and continuous variables by the Friedman test followed by the Wilcoxon test with Bonferroni correction for multiple comparisons (p < 0.017)., Results: PS N significantly improved patient comfort, compared to both PS P (p = 0.001) and NAVA (p = 0.002), without differences between the two latter (p = 0.08). PIF (p = 0.109), EAdi peak (p = 0.931) and gas exchange were similar between modes. Compared to PS P and NAVA, PS N reduced PIF time (p < 0.001), and increased PTP 300-index (p = 0.004) and PTP 500-index (p = 0.001). NAVA and PS N significantly reduced Delay TR-insp , as opposed to PS P (p < 0.001). During both NAVA and PS N , AI% was <10% in all patients, while AI% was ≥10% in 7 patients (50%) with PS P (p = 0.023 compared with both NAVA and PS N )., Conclusions: Compared to both PS P and NAVA, PS N improved comfort and patient-ventilator interaction during NIV by facial mask. PS N also improved synchrony, as opposed to PS P only., Trial Registration: ClinicalTrials.gov, NCT03041402 . Registered (retrospectively) on 2 February 2017.

Functional bowel disorders (FBD), mainly irritable bowel syndrome (IBS) and functional constipation (FC, also called chronic idiopathic constipation), are very common worldwide. Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, although less common, has a strong impact on patients' quality of life, as well as being highly expensive for our healthcare. A definite cure for those disorders is still yet to come. Over the years, several therapeutic approaches complementary or alternative to traditional pharmacological treatments, including probiotics, prebiotics, synbiotics, fibre and herbal medicinal products, have been investigated for the management of both groups of diseases. However, most available studies are biased by several drawbacks, including small samples and poor methodological quality. Probiotics, in particular Saccharomyces boulardii and Lactobacilli (among which Lactobacillus rhamnosus), synbiotics, psyllium, and some herbal medicinal products, primarily peppermint oil, seem to be effective in ameliorating IBS symptoms. Synbiotics and fibre seem to be beneficial in FC patients. The probiotic combination VSL#3 may be effective in inducing remission in patients with mild-to-moderate ulcerative colitis, in whom Escherichia coli Nissle 1917 seems to be as effective as mesalamine in maintaining remission. No definite conclusions can be drawn as to the efficacy of fibre and herbal medicinal products in IBD patients due to the low number of studies and the lack of randomized controlled trials that replicate the results obtained in the individual studies conducted so far. Thus, further, well-designed studies are needed to address the real role of these therapeutic options in the management of both FBD and IBD., Linked Articles: This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc., (© 2016 The British Pharmacological Society.)

Objectives: Faecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection (CDI). Although a single faecal infusion is usually sufficient to eradicate CDI, a considerable number of patients need multiple infusions to be cured. The aim of this study was to identify predictors of failure after single faecal infusion in patients with recurrent CDI., Methods: We included patients with recurrent CDI prospectively treated with FMT by colonoscopy. By means of univariate and multivariate analysis, variables including female gender, age, number of CDI recurrences, severity of CDI, hospitalization, inadequate bowel preparation, unrelated donor, and use of frozen faeces, were assessed to predict failure after single faecal infusion., Results: Sixty-four patients (39 women; mean age 74 years) were included. Of them, 44 (69%) were cured by a single faecal infusion, whereas 20 (31%) needed repeat infusions. Overall, FMT cured 62 of 64 (97%) patients. In the subgroup of patients with severe CDI, only eight of 26 (30%) were cured with a single infusion. At multivariate analysis, severe CDI (OR 24.66; 95% CI 4.44-242.08; p 0.001) and inadequate bowel preparation (OR 11.53; 95% CI 1.71-115.51; p 0.019) were found to be independent predictors of failure after single faecal infusion., Conclusions: Severe CDI and inadequate bowel preparation appear to be independent predictors of failure after single faecal infusion in patients treated with FMT by colonoscopy for recurrent CDI. Our results may help to optimize protocols and outcomes of FMT in patients with recurrent CDI., (Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

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., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Malnutrition is a major complication of inflammatory bowel disease (IBD). This mini review is focusing on main determinants of malnutrition in IBD, the most important components of malnutrition, including lean mass loss and sarcopenia, as an emerging problem. Each one of these components needs to be well considered in a correct nutritional evaluation of an IBD patient in order to build a correct multidisciplinary approach. The review is then focusing on possible instrumental and clinical armamentarium for the nutritional evaluation., Competing Interests: The authors declare that they have no competing interests.

Background: Compared to pneumatically controlled pressure support (PSP), neurally adjusted ventilatory assist (NAVA) was proved to improve patient-ventilator interactions, while not affecting comfort, diaphragm electrical activity (EAdi), and arterial blood gases (ABGs). This study compares neurally controlled pressure support (PSN) with PSP and NAVA, delivered through two different helmets, in hypoxemic patients receiving noninvasive ventilation for prevention of extubation failure., Methods: Fifteen patients underwent three (PSP, NAVA, and PSN) 30-min trials in random order with both helmets. Positive end-expiratory pressure was always set at 10 cm H2O. In PSP, the inspiratory support was set at 10 cm H2O above positive end-expiratory pressure. NAVA was adjusted to match peak EAdi (EAdipeak) during PSP. In PSN, the NAVA level was set at maximum matching the pressure delivered during PSP by limiting the upper pressure. The authors assessed patient comfort, EAdipeak, rates of pressurization (i.e., airway pressure-time product [PTP] of the first 300 and 500 ms after the initiation of patient effort, indexed to the ideal pressure-time products), and measured ABGs., Results: PSN significantly increased comfort to (median [25 to 75% interquartile range]) 8 [7 to 8] and 9 [8 to 9] with standard and new helmets, respectively, as opposed to both PSP (5 [5 to 6] and 7 [6 to 7]) and NAVA (6 [5 to 7] and 7 [6 to 8]; P < 0.01 for all comparisons). Regardless of the interface, PSN also decreased EAdipeak (P < 0.01), while increasing PTP of the first 300 ms from the onset of patient effort, indexed to the ideal PTP (P < 0.01) and PTP of the first 500 ms from the onset of patient effort, indexed to the ideal PTP (P < 0.001). ABGs were not different among trials., Conclusions: When delivering noninvasive ventilation by helmet, compared to PSP and NAVA, PSN improves comfort and patient-ventilator interactions, while not ABGs. (Anesthesiology 2016; 125:1181-9).

Aim: To explore the influence of Infliximab (IFX) on cancer progression in a murine model of colonic cancer associated to chronic colitis., Methods: AOM/DSS model was induced in C57BL/6 mice. Mice were injected with IFX (5 mg/kg) during each DSS cycle while control mice received saline. Body weight, occult blood test and stool consistency were measured to calculate the disease activity index (DAI). Mice were sacrificed at week 10 and colons were analyzed macroscopically and microscopically for number of cancers and degree of inflammation. MTT assay was performed on CT26 to evaluate the potential IFX role on metabolic activity and proliferation. Cells were incubated with TNF-α or IFX or TNF-α plus IFX, and cell vitality was evaluated after 6, 24 and 48 h. The same setting was used after pre-incubation with TNF-α for 24 h., Results: IFX significantly reduced DAI and body weight loss in mice compared with controls, preserving also colon length at sacrifice. Histological score was also reduced in treated mice. At macroscopic analysis, IFX treated mice showed a lower number of tumor lesions compared to controls. This was confirmed at microscopic analysis, although differences were not statistically significant. In vitro , IFX treated CT26 maintained similar proliferation ability at MTT test, both when exposed to IFX alone and when associated to TNF-α., Conclusion: IFX did not increase colonic cancer risk in AOM-DSS model of cancer on chronic colitis nor influence directly the proliferation of murine colon cancer epithelial cells., Competing Interests: Conflict-of-interest statement: To the best of our knowledge, no conflict of interest exists.

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

Besides being part of anti-Helicobacter pylori treatment regimens, proton pump inhibitors (PPIs) are increasingly being used to treat dyspepsia. However, little is known about the effects of PPIs on the human gastric microbiota, especially those related to H. pylori infection. The goal of this study was to characterize the stomach microbial communities in patients with dyspepsia and to investigate their relationships with PPI use and H. pylori status. Using 16S rRNA gene pyrosequencing, we analyzed the mucosa-associated microbial populations of 24 patients, of whom 12 were treated with the PPI omeprazole and 9 (5 treated and 4 untreated) were positive for H. pylori infection. The Proteobacteria, Firmicutes, Bacteroidetes, Fusobacteria, and Actinobacteria phyla accounted for 98% of all of the sequences, with Helicobacter, Streptococcus, and Prevotella ranking among the 10 most abundant genera. H. pylori infection or PPI treatment did not significantly influence gastric microbial species composition in dyspeptic patients. Principal-coordinate analysis of weighted UniFrac distances in these communities revealed clear but significant separation according to H. pylori status only. However, in PPI-treated patients, Firmicutes, particularly Streptococcaceae, were significantly increased in relative abundance compared to those in untreated patients. Consistently, Streptococcus was also found to significantly increase in relation to PPI treatment, and this increase seemed to occur independently of H. pylori infection. Our results suggest that Streptococcus may be a key indicator of PPI-induced gastric microbial composition changes in dyspeptic patients. Whether the gastric microbiota alteration contributes to dyspepsia needs further investigation., Importance: Although PPIs have become a popular treatment choice, a growing number of dyspeptic patients may be treated unnecessarily. We found that patients treated with omeprazole showed gastric microbial communities that were different from those of untreated patients. These differences regarded the abundances of specific taxa. By understanding the relationships between PPIs and members of the gastric microbiota, it will be possible to envisage new strategies for better managing patients with dyspepsia., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Diverticulosis of the colon is a common condition in western countries. Acute diverticulitis may occur in 10% to 25% of the patients, sometimes associated with the presence of complications such as abscess, fistula, and perforation. Early diagnosis and accurate assessment of acute diverticulitis are necessary to start an efficacious treatment promptly, either conservatively or by surgery. The clinical picture may mimic other abdominal conditions; therefore, imaging techniques such as ultrasound or computed tomography are usually recommended, although they are expensive, examiner dependent, and potentially harmful. Recently, there has been increasing interest about the role of biological markers in diverticular disease as noninvasive, reliable, and inexpensive tools, conceivably able to support physicians in the diagnosis, the assessment of activity, and the monitoring of acute diverticulitis. By a MEDLINE search, most of the relevant data derived from C-reactive protein showed that it strongly supported the diagnosis of acute diverticulitis at values of >50 mg/L. It also represents a stronger marker compared with other serum biomarkers, able to correlate with the histologic severity in acute diverticulitis, the risk of perforation, and the response to therapy. Regarding fecal biomarkers, an interesting role has been reported for fecal calprotectin. It significantly correlates with inflammatory infiltrate. More relevantly, it correlates with the response to therapy and may predict the recurrence of colonic diverticulitis, as it is reliable in detecting subclinical intestinal inflammation, as reported already for inflammatory bowel disease. These represent encouraging results, but need to be confirmed in further larger studies.

Background: A careful endoscopic surveillance of Barrett's oesophagus is warranted to prevent esophageal cancer., Aim: To identify the preferred location of non-circumferential Barrett's oesophagus and associated dysplasia within the esophageal circumference., Methods: We retrospectively reviewed a prospectively maintained database of patients with non-circumferential lesions. The location of metaplastic lesions and dysplastic lesions within the esophageal circumference was identified as on a clock face, and their distribution in the 4 quadrants was compared., Results: Of overall 443 patients with Barrett's oesophagus, 192 (43%) were eligible for our study. Multiple lesions were diagnosed in 110 (57%) of them, for a total amount of 352 metaplastic areas. Barrett's oesophagus lesions were located significantly more in the posterior wall of the oesophagus (38.4%), rather than in the right wall (28.8%), the anterior wall (22.6%), or the left wall (10.2%) (P<0.0001). Among all metaplastic lesions, 28 were associated with dysplasia (7.9%), and one with adenocarcinoma (0.3%). Dysplastic lesions were significantly more common in the posterior wall (39.3%) than, respectively, in the anterior wall (35.8%), the right wall (21.4%) or the left wall (3.5%) (P=0.03)., Conclusion: Our results show that the posterior wall of the oesophagus is the preferential location of both Barrett's oesophagus and associated dysplasia., (Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: The objective of this study was to assess the relationship between insulin resistance and apoptotic endothelial-derived microparticles (EMPs) in patients with chronic heart failure (CHF)., Methods: The study involved 300 CHF patients (186 males) aged 48-62 years with angiographically proven coronary artery disease and/or previously defined myocardial infarction. Insulin resistance was assessed by the homeostasis model assessment for insulin resistance (HOMA-IR). EMPs phenotype was determined by flow cytofluorometry., Results: Depending on HOMA-IR cut-off point (over and <2.77 mmol/L×μU/mL) all patients were divided into two cohorts with (n=171) or without (n=129) IR, respectively. Circulating EMPs were higher in CHF patients with IR than in patients without IR. Interestingly, EMPs were directly related to NYHA functional class of CHF, HOMA-IR, NT-pro-BNP, hs-CRP and BMI. There was a significant association between the level of EMPs and HbA1c, gender (r=0.318, p<0.001 for male), age and smoking. On univariate and multivariate regression analysis we found that the NYHA class of CHF,NT-pro-BNP, hs-CRP, and left ventricular ejection fraction (LVEF) appeared to be independent predictors of increased circulatory apoptotic EMPs. The addition of HOMA-IR to the standard model (NYHA class CHF) improved the relative IDI by 19.9% for increased EMPs. For category-free NRI, 10% of events and 24% of non-events were correctly reclassified by the addition of HOMA-IR to the standard model for increased circulating EMPs., Conclusions: IR may be a contributing factor increasing circulating levels of apoptotic EMPs in non-diabetic CHF patients.

Gut virome has been shown to yield some beneficial effects on humans, being deeply involved in physiology, inflammation, immunity, and disease. Together with transkingdom interactions, it can interplay with genetic variation in the host to establish specific phenotypes. These interactions can lead to phenotypes not observed with either the virus or the host variation alone. Unfavorable alteration of gut virome composition has been implicated in chronic, and perhaps also systemic, immune disorders, such as in the pathogenesis of inflammatory bowel disease. This review focuses on what is currently known regarding the role of commensal gut virome in chronic gut inflammation, and speculate on the important translational implications in regard to gut virome modulation in inflammatory bowel disease with the end goal of promoting gut health.

Introduction: Irritable bowel syndrome is a functional gastrointestinal disorder with a multifactorial etiology. Alterations of intestinal motility and immunity, gut-brain interactions, as well as gut microbiota dysbiosis contribute to the development of irritable bowel syndrome. Therefore, gut microbiota modulation by non-absorbable antibiotics is a therapeutic option in patients with IBS., Areas Covered: Published articles including patients with irritable bowel syndrome reporting data about rifaximin activity and safety have been searched throughout the literature and selected., Expert Opinion: The optimal antibiotic molecule should be local-acting, long-acting and safe-acting. Rifaximin is a non-absorbable antibiotic with additional anti-inflammatory and gut microbiota-modulating activity. It is effective in inducing symptoms relief in patients with IBS, even after repeated treatment courses. Rifaximin-related side effects in patients with IBS are reported to be mild and infrequent; microbial resistance is rare and transient, due to the high local concentration of the drug and to the absence of horizontal transmission. Clostridium difficile infection is not usual in patients receiving rifaximin in absence of predisposing conditions such as hospitalization and immunosuppression, which are uncommon in patients affected by irritable bowel syndrome. Nevertheless rifaximin is an antibiotic active against Clostridium difficile infection. Rifaximin has limited metabolic interactions and is not expected to interfere with drug metabolism in patients with normal hepatic function. These properties make rifaximin a safe antibiotic for gut microbiota modulation in patients with IBS.

Ulcerative colitis (UC) is a chronic inflammatory disease, whose etiology is still unclear. Its pathogenesis involves an interaction between genetic factors, immune response and the "forgotten organ", Gut Microbiota. Several studies have been conducted to assess the role of antibiotics and probiotics as additional or alternative therapies for Ulcerative Colitis. Escherichia coli Nissle (EcN) is a nonpathogenic Gram-negative strain isolated in 1917 by Alfred Nissle and it is the active component of microbial drug Mutaflor(®) (Ardeypharm GmbH, Herdecke, Germany and EcN, Cadigroup, In Italy) used in many gastrointestinal disorder including diarrhea, uncomplicated diverticular disease and UC. It is the only probiotic recommended in ECCO guidelines as effective alternative to mesalazine in maintenance of remission in UC patients. In this review we propose an update on the role of EcN 1917 in maintenance of remission in UC patients, including data about efficacy and safety. Further studies may be helpful for this subject to further the full use of potential of EcN.

Background: EndoFaster is novel device able to perform real-time ammonium measurement in gastric juice allowing H. pylori diagnosis during endoscopy. This large study aimed to validate the accuracy of EndoFaster for real-time H. pylori detection., Methods: Consecutive patients who underwent upper endoscopy in two centres were prospectively enrolled. During endoscopy, 4 ml of gastric juice were aspirated to perform automatic analysis by EndoFaster within 90 seconds, and H. pylori was considered present (>62 ppm/ml) or absent (≤62 ppm/ml). Accuracy was measured by using histology as gold standard, and (13)C-urea breath test (UBT) in discordant cases. Accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) were calculated., Results: Overall, 189 patients were enrolled, but in seven (3.4%) the aspirated gastric juice amount was insufficient to perform the test. The accuracy, sensitivity, specificity, PPV, and NPV were 87.4%, 90.3%, 85.5%, 80.2%, 93.1%, respectively, and 92.6%, 97.1%, 89.7%, 85.9%, 98.0%, respectively, when H. pylori status was reclassified according to the UBT result in discordant cases., Conclusions: This study found a high accuracy/feasibility of EndoFaster for real-time H. pylori diagnosis. Use of EndoFaster may allow selecting those patients in whom routine gastric biopsies could be avoided.

Background: Infliximab is effective in inflammatory bowel disease through several mechanisms, possibly acting at the mucosal level., Aim: To assess the role of infliximab on intestinal mucosa and whether it contributes to mucosal healing., Methods: Human colonic mucosal biopsies were incubated with or without infliximab. Cultured biopsies were evaluated for histological staining, CD68, CD3, E-cadherin and phospho-extracellular signal-regulated kinases (ERK) expression, and apoptosis. A scratch assay and MTT assay were performed with Caco2 cells in the presence of infliximab and/or tumour necrosis factor (TNF)-α or treated with supernatants obtained from human peripheral blood mononuclear cells or human intestinal fibroblasts treated with TNF-α and infliximab alone or in association., Results: Infliximab-treated biopsies displayed a better histological appearance, reduced inflammation with an increase of E-cadherin, phospho-ERK and apoptosis. Supernatants showed lower TNF-α, IL-17, IL-6 and IL-8 concentration, with an increase in fibroblast-growth-factor. Motility at scratch assay and proliferation at MTT assay of Caco2 cells displayed differential modulation by TNF-α and infliximab, directly or through supernatants of human intestinal fibroblasts and human peripheral blood mononuclear cells exposed to them., Conclusion: Infliximab contributes to the mucosal healing process by acting directly at an intestinal mucosal level; infliximab indirectly affects epithelial cell migration and proliferation by acting on both fibroblasts and leukocytes., (Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Inflammatory bowel disease (IBD) is the results of a chronic inflammatory process deriving from disequilibrium between self-microbiota composition and immune response., Methods: New evidence, coming from Clostridium difficile infection, clearly showed that active and powerful modulation of microbiota composition by fecal microbiota composition (FMT) is safe, easy to perform, and efficacious, opening new frontiers in gastrointestinal and extra-intestinal diseases. FMT has been proposed also for IBD as well as other non-gastrointestinal conditions related to intestinal microbiota dysfunctions, with good preliminary data., Results: In this setting, ulcerative colitis (UC) represents one of the most robust potential indications for FMT after C difficile colitis., Conclusions: In the present review, we focus on FMT and its application on ulcerative colitis, clarifying mechanisms of actions and efficacy data, trough completion of a meta-analysis on available randomized, controlled trial data in UC. Because microbiota is so crucially involved in this topic, a short review of microbial alterations in UC will also be performed., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The worldwide prevalence of obesity more than doubled between 1980 and 2014. The obesity pandemic is tightly linked to an increase in energy availability, sedentariness and greater control of ambient temperature that have paralleled the socioeconomic development of the past decades. The most frequent cause which leads to the obesity development is a dysbalance between energy intake and energy expenditure. The gut microbiota as an environmental factor which influence whole-body metabolism by affecting energy balance but also inflammation and gut barrier function, integrate peripheral and central food intake regulatory signals and thereby increase body weight. Probiotics have physiologic functions that contribute to the health of gut microbiota, can affect food intake and appetite, body weight and composition and metabolic functions through gastrointestinal pathways and modulation of the gut bacterial community.

Objectives: Interest of patients and physicians in celiac disease is growing worldwide, but without a corresponding increase in the awareness of the disease. Many patients are diagnosed as celiacs even without completing the whole diagnostic process, with consequent risk of misdiagnosis and delay in the evaluation of other diseases. The objective of this study was to assess the rates of prior celiac disease misdiagnosis among patients referred to a tertiary care center., Methods: From June 2013 to December 2014, we prospectively recruited patients referred for the first time to our Celiac Disease Center. Patients with a previous diagnosis of celiac disease underwent a diagnostic revaluation by second reading of duodenal tissue slides, dosage of specific antibodies, and/or duodenal biopsy sampling; HLA status was investigated in pertinent cases., Results: A total of 198 subjects were recruited. Of these, 91 "naïve" patients (46%) started the diagnostic screening for celiac disease; 58 of them (64-29% of the whole sample) were diagnosed as celiacs. The remaining 107 patients (54%) came with a previous diagnosis of celiac disease: of these, 52 (49-26% of the whole sample) presented with confirmed diagnosis of celiac disease, whereas 55 (51-28% of the whole sample) underwent diagnostic revaluation. After the reassessment, diagnosis was rejected in 43 cases (78-22% of the whole sample) and confirmed in the remaining 12 (22-6% of the whole sample). Overall, diagnosis was confirmed in only 64 of the 107 subjects with a previous diagnosis (60-32% of the whole sample). Diagnosis of celiac disease was more frequently confirmed in "naïve" patients compared those with a questionable previous diagnosis (64% vs. 22%; P<0.0001)., Conclusions: A considerable number of patients referred to a tertiary care center are inaccurately diagnosed with celiac disease. Although we cannot exclude that uncertain diagnosis was a reason for the referral, we suggest greater adherence to guidelines to minimize the burden of celiac disease misdiagnosis.