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Background: No biomarkers are currently available to predict therapeutic response to ustekinumab (UST) in Crohn's disease (CD). The aim of this prospective study was to identify 1 or more cytokines able to predict mucosal healing in patients with CD treated with UST., Methods: We prospectively enrolled consecutive CD patients treated with UST. At weeks 0 (baseline), 24, and 48, a panel of serum cytokines was measured by a fluorescence assay. At the same time points, fecal calprotectin (FC) was assessed. A colonoscopy was performed at baseline and at week 48, where therapeutic outcome was evaluated in terms of mucosal healing., Results: Out of 44 patients enrolled, 22 (50%) achieved mucosal healing at the end of follow-up. Response was associated with higher interleukin (IL)-23 levels (P < .01). Fecal calprotectin levels decreased over time in responders but did not change in nonresponders (test for the interaction between time and mucosal healing, P < .001)., Conclusions: This pilot study showed that IL-23 and FC could be reliable biomarkers in predicting therapeutic outcome to UST therapy in CD. In particular, the correlation between baseline serum levels of IL-23 and mucosal healing at 48 weeks is particularly strong, paving the way for its use to drive therapeutic decisions., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The presence of sarcopenia has been associated with the worst outcome of Crohn's disease (CD). At present, no studies have evaluated the impact of ustekinumab (UST) in terms of its effects on body composition. The aim of this prospective study was to evaluate whether UST treatment could modify the parameters of body composition as assessed by bioelectrical impedance assay (BIA) in patients with CD. We prospectively enrolled consecutive patients with CD treated with UST, evaluating the therapeutic outcome at week 48 in terms of clinical remission and mucosal healing. BIA was performed at baseline and at week 48, assessing body cellular mass, total body water, phase angle, and body mass index. Out of 44 patients enrolled, 26 (59%) were in clinical remission and 22 (50%) achieved mucosal healing at the end of follow up. No significant differences were observed at baseline in all the BIA parameters between responders and non-responders. Phase angle increased over time in responders, while this was not observed in non-responders (test for the interaction between time and outcome, p -value = 0.009 and 0.007 for clinical remission and mucosal healing, respectively). The same differential increase was observed for body cellular mass (test for the interaction between time and outcome, p -value = 0.03 and 0.05 for clinical remission and mucosal healing, respectively). Total body water and BMI increased homogenously over time regardless of the outcomes (tests for the association with time, p -values of 0.01). To conclude, responsiveness to UST therapy seems to be associated with body composition modifications in patients with CD. In particular, the increase in phase angle in responders suggests that a significant improvement of nutritional status occurred in these patients.

Background: There are few data regarding the diagnostic delay and its predisposing factors in coeliac disease (CD)., Aims: To investigate the overall, the patient-dependant, and the physician-dependant diagnostic delays in CD., Methods: CD adult patients were retrospectively enroled at 19 Italian CD outpatient clinics (2011-2021). Overall, patient-dependant, and physician-dependant diagnostic delays were assessed. Extreme diagnostic, i.e., lying above the third quartile of our population, was also analysed. Multivariable regression models for factors affecting the delay were fitted., Results: Overall, 2362 CD patients (median age at diagnosis 38 years, IQR 27-46; M:F ratio=1:3) were included. The median overall diagnostic delay was 8 months (IQR 5-14), while patient- and physician-dependant delays were 3 (IQR 2-6) and 4 (IQR 2-6) months, respectively. Previous misdiagnosis was associated with greater physician-dependant (1.076, p = 0.005) and overall (0.659, p = 0.001) diagnostic delays. Neurological symptoms (odds ratio 2.311, p = 0.005) and a previous misdiagnosis (coefficient 9.807, p = 0.000) were associated with a greater extreme physician-dependant delay. Gastrointestinal symptoms (OR 1.880, p = 0.004), neurological symptoms (OR 2.313, p = 0.042), and previous misdiagnosis (OR 4.265, p = 0.000) were associated with increased extreme overall diagnostic delay., Conclusion: We identified some factors that hamper CD diagnosis. A proper screening strategy for CD should be implemented., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2022 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Few data are currently available about SB5 in inflammatory bowel diseases (IBD). The aim of this study was to assess the effectiveness and safety of SB5 in a cohort of patients with IBD in stable remission switched from the adalimumab (ADA) originator and in a cohort of patients with IBD naïve to ADA., Methods: We prospectively enrolled patients with IBD who started ADA treatment with SB5 (naïve cohort) and those who underwent a nonmedical switch from the ADA originator to SB5 (switching cohort). Clinical remission and safety were assessed at baseline and at 3, 6, and 12 months. In addition, in a small cohort of patients who were switched, we assessed the ADA serum trough levels and antidrug antibodies at baseline, 3, and 6 months., Results: In the naïve cohort, the overall remission rate at 12 months was 60.42%, whereas in the switching cohort it was 89.02%. Fifty-three (36.3%) patients experienced an adverse event, and injection site pain was the most common; it was significantly more frequent in the switching cohort (P = 0.001). No differences were found in terms of ADA serum trough levels at baseline, 3, and 6 months after switching. No patient developed antidrug antibodies after the switch., Conclusions: We found that SB5 seemed effective and safe in IBD, both in the naïve cohort and in the switching cohort. Further studies are needed to confirm these data in terms of mucosal healing., (© 2021 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

During the coronavirus disease 2019 (COVID-19) pandemic, immunomodulatory therapies and hospital admission were suspected to increase the risk of infection. Nevertheless, patients with inflammatory bowel diseases (IBD) treated with intravenous (i.v.) biologics had to move to hospitals for drug infusion. We investigated the impact of hospitalisation in patients with IBD. We conducted a survey including consecutive IBD patients initially in clinical and biochemical remission treated with biologics at the end of the first lockdown period. Patients underwent the normally scheduled clinical visits, performed at hospital for i.v.-treated patients or at home for patients treated with s.c. drugs. We administered to all patients the Hospital Anxiety and Depression Scale (HADS) questionnaire and other 12 questions, specifically related to COVID-19 and its implications. A total of 189 IBD patients were recruited, 112 (59.3%) treated with i.v. drugs and 77 (40.7%) with s.c. ones. No relapses were recorded in either group (hospitalized vs. non-hospitalized, p = ns), as well as which, COVID-19 infections were not demonstrated in patients in contact with people with suspected symptoms or directly experiencing them. The total HADS score obtained by the sum of all items was also almost identical between groups (37.1 ± 2.8 vs. 37.2 ± 2.8; p = 0.98). In patients treated with i.v. drugs receiving a televisit ( n = 17), the rate of satisfaction with telemedicine (58.8%) was significantly lower compared with those treated with s.c. drugs (94.8%; p < 0.0005). Our results suggest that hospitalisation during the COVID-19 outbreak does not increase the risk of COVID-19 infection as well as the risk of IBD relapse; moreover, the similar levels of anxiety in both groups could confirm that there is no need to convert patients from i.v. to s.c. therapy.

A growing number of Italian families are adopting a vegan diet (VD) for their offspring from infancy for various reasons, with health benefits and ethics being the most common reasons. Barriers to effective communication with primary care pediatricians (PCPs) are perceived by many parents and, depending on the actors involved and the environment, a VD may affect social interactions in everyday life. A national cross-sectional survey was conducted between July and September 2020. Parents of children following a VD completed an online questionnaire. Data from 176 Italian parents were collected. About 72% (71.8%) of the children included in this study had been on a VD since weaning. Parents did not inform their primary care pediatricians (PCP) about the VD in 36.2% of the cases. In 70.8% of the cases, PCPs were perceived as skeptical or against a VD. About 70% (71.2%) of the parents relied on medical dietitians, and 28.2% on nutritionists/dietitians for dietary counseling. Parents administered an individual B12 supplement in 87.2% of the cases. To the best of our knowledge, this survey is the first which explores the relationship between vegan parents and their PCPs, the parental management of their children's diet and problems regarding the implementation of a VD in everyday life.

Nutrition has an important impact on inflammatory bowel diseases (IBD). In particular, several studies have addressed its role in their pathogenesis, showing how the incidence of IBD significantly increased in recent years. Meanwhile, nutrition should be considered a component of the treatment of the disease, both as a therapy itself, and especially in the perspective of correcting the various nutritional deficiencies shown by these patients. In this perspective, nutritional suggestions are very important even in the most severe forms of IBD, requiring hospitalization or surgical treatment. Although current knowledge about nutrition in IBD is increasing over time, nutritional suggestions are often underestimated by clinicians. This narrative review is an update summary of current knowledge on nutritional suggestions in IBD, in order to address the impact of nutrition on pathogenesis, micro- and macro-nutrients deficiencies (especially in the case of sarcopenia and obesity), as well as in hospitalized patients.

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

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

Background: Anti-tumor necrosis factor drugs (anti-TNFs) are widely used for the treatment of ulcerative colitis (UC). However, many patients experience loss of response during the first year of therapy. An early predictor of clinical remission and mucosal healing is needed. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are markers of subclinical inflammation poorly evaluated in UC patients treated with anti-TNFs. The aim of this multicenter study was to evaluate whether NLR and PLR could be used as prognostic markers of anti-TNF treatment response., Methods: Patients with UC who started anti-TNF treatment in monotherapy were evaluated. Patients with concomitant corticosteroid treatment ≥20 mg were excluded. We calculated NLR, PLR, and fecal calprotectin before treatment and after induction. The values of NLR and PLR were correlated with clinical remission and mucosal healing at the end of follow-up (54 weeks) using the Mann-Whitney U test and then multivariate analysis was conducted., Results: Eighty-eight patients were included. Patients who reached mucosal healing after 54 weeks of therapy displayed lower levels of both baseline NLR and PLR (P = 0.0001 and P = 0.04, respectively); similar results were obtained at week 8 (P = 0.0001 and P = 0.001, respectively). Patients who presented with active ulcers at baseline endoscopic evaluation had higher baseline NLR and PLR values compared with those without detected ulcers (P = 0.002 and P = 0.0007, respectively)., Conclusions: BothNLR and PLR showed a promising role as early predictors of therapeutic response to anti-TNF therapy in UC patients. If confirmed in larger studies, classification and regression trees proposed in this article could be useful to guide clinical decisions regarding anti-TNF treatment., (© 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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

Background: Ulcerative colitis is a chronic relapsing disease usually treated with mesalamine. The need of steroid therapy at diagnosis is generally considered as a poor prognostic factor., Aims: The aim of our study was to assess whether patients treated with corticosteroids at diagnosis have more clinical relapses, disease progression, or an increased risk of colectomy during a 5-year follow-up., Methods: We retrospectively evaluated patients who had received diagnosis of ulcerative colitis with a 5-year follow-up. Relapse was defined as a worsening of symptoms requiring an increase in medical treatment. Progression of disease was defined as a proximal extension of mucosal involvement, comparing the colonoscopy performed 5 years after diagnosis with the first one. The need of corticosteroid treatment at diagnosis was correlated to number of relapses, disease progression, and colectomy rate., Results: We included 230 patients, 116 of them (50%) treated with steroids at diagnosis. Multivariate analysis demonstrated that there is a strong correlation between corticosteroid use and number of relapses (p < 0.01), as well as with disease progression (p < 0.05). Seventeen patients (7.4%) underwent colectomy, but the correlation with steroids was not statistically significant., Conclusions: These data provide evidence that the need of corticosteroids at diagnosis is associated with a worse clinical outcome.

Aims: Vedolizumab (VDZ) prevents migration of activated leucocytes into inflamed mucosa. This study aimed to assess the patterns of serum cytokines in ulcerative colitis (UC) patients at baseline and during VDZ treatment, and to investigate their association with mucosal healing and clinical remission., Methods: We enrolled consecutive UC patients eligible for treatment with VDZ. A panel of serum cytokines were measured by fluorescence assay at weeks 0, 6 and 22. Colonoscopy was performed at baseline and week 54, to evaluate mucosal healing. The time trends of serum cytokines were analysed by log-linear mixed effect models, and their prognostic accuracy was evaluated by logistic regression., Results: Out of 27 patients included in the analysis, at week 54 mucosal healing was achieved in 12 (44%) and clinical remission in 17 (63%). Mucosal healing was associated with higher interleukin (IL)-8 values at baseline and with significant decrease in IL-6 and IL-8 levels over the first 6 weeks. A significant reduction of IL-6 and IL-8 levels over the first 6 weeks of treatment was associated also with clinical remission. Logistic models including, among the predictors, IL-6 and IL-8 at baseline and their changes over the first 6 weeks of treatment had 83% sensitivity and 87% specificity to predict mucosal healing, and 82% sensitivity and 90% specificity to predict clinical remission., Conclusion: In UC patients, the serum patterns of IL-6 and IL-8 at baseline and over the first 6 weeks of treatment with VDZ could be useful to predict therapeutic outcome., (© 2020 The British Pharmacological Society.)

Background: Oncostatin M is upregulated in Crohn's disease inflamed intestinal mucosa, and has been suggested as a promising biomarker to predict responsiveness to anti-TNF therapy in patients with inflammatory bowel diseases., Aim: To evaluate the suitability of serum oncostatin M as a predictive marker of response to infliximab in Crohn's disease., Methods: We included patients treated with infliximab monotherapy. All patients underwent colonoscopy at week 54 to evaluate mucosal healing. Serum oncostatin M and faecal calprotectin were measured at baseline and after 14 weeks of treatment. Mann-Whitney test was used to evaluate correlation of oncostatin M and faecal calprotectin at baseline and week 14 with mucosal healing at week 54. Their accuracy in predicting mucosal healing was assessed by area under the curve (AUC)., Results: In a cohort of 45 included patients, 27 displayed mucosal healing. At both baseline and week 14, oncostatin M levels were significantly lower in patients with mucosal healing than in patients not achieving this endpoint (P < 0.001). Faecal calprotectin levels at week 14 were lower also in responders than nonresponders (P < 0.001). Oncostatin M values at baseline and week 14 were significantly associated (Spearman correlation = 0.92, P < 0.001). The diagnostic accuracy of oncostatin M at baseline in predicting mucosal healing (AUC = 0.91) was greater than faecal calprotectin (AUC = 0.51, P < 0.001)., Conclusion: These results suggest that oncostatin M can predict the outcome of infliximab treatment. Compared with faecal calprotectin, the predictive capability of oncostatin M was appreciable at baseline, thus indicating oncostatin M as a promising biomarker for driving therapeutic choices in Crohn's disease., (© 2020 John Wiley & Sons Ltd.)

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

Fecal calprotectin (FC) has emerged as one of the most useful tools for clinical management of inflammatory bowel diseases (IBD). Many different methods of assessment have been developed and different cut-offs have been suggested for different clinical settings. We carried out a comprehensive literature review of the most relevant FC-related topics: the role of FC in discriminating between IBD and irritable bowel syndrome (IBS) and its use in managing IBD patients In patients with intestinal symptoms, due to the high negative predictive value a normal FC level reliably rules out active IBD. In IBD patients a correlation with both mucosal healing and histology was found, and there is increasing evidence that FC assessment can be helpful in monitoring disease activity and response to therapy as well as in predicting relapse, post-operative recurrence or pouchitis. Recently, its use in the context of a treat-to-target approach led to a better outcome than clinically-based therapy adjustment in patients with early Crohn's disease. In conclusion, FC measurement represents a cheap, safe and reliable test, easy to perform and with a good reproducibility. The main concerns are still related to the choice of the optimal cut-off, both for differentiating IBD from IBS, and for the management of IBD patients., Competing Interests: Conflict-of-interest statement: The authors have declared that no potential conflict of interest exists.

Background: The aim of this study was to determine the effects of a low fermentable oligo-, di- and monosaccharides and polyols (FODMAP) diet on the nutritional status and body composition, abdominal symptoms, quality of life, anxiety/depression and sleep quality of patients with irritable bowel syndrome (IBS)., Methods: Consecutive patients were given a low FODMAP diet for 8 weeks. At baseline and after 8 weeks, blood tests were taken to evaluate nutritional status and a bioelectrical impedance analysis was performed to assess body composition. Anthropometric data, IBS Symptom Severity Score, results of a bowel habits questionnaire, Bristol Stool Chart classification, SF36, Hamilton Depression Anxiety Scale outcome and Pittsburgh Sleep Quality Index were also recorded. During the 8-week diet period, the patients were phoned periodically by the nutritionist to verify their compliance., Results: Twenty-six IBS patients with a mean age of 46.2 ± 13.8 years were studied. After 8 weeks, there were no abnormalities in anthropometric data, bioelectrical impedance parameters and blood tests. The patients' IBS Symptom Severity Score improved (305.2 ± 84.1 vs 156.3 ± 106.4; p < 0.0001), as did bowel habits, Bristol Stool Chart classification, quality of life and HADS anxiety score, whereas sleeping quality and depression were unchanged. The degree of relief from symptoms and satisfaction with the diet was high., Conclusions: A low FODMAP diet improved IBS symptoms without effects on nutritional status and body composition.

Background: Chronic constipation is often diagnosed and treated by general practitioners (GPs). The aim of the study was to evaluate the management of constipation by a cohort of Italian GPs., Methods: Over the course of 1 month, 41 GPs recorded tests and therapies suggested to patients complaining of chronic constipation. They were classified according to the Rome III criteria as constipated irritable bowel syndrome (C-IBS), functional constipation (FC), or "self-perceived constipation" (SPC) (not consistent with the Rome criteria)., Results: The most frequently prescribed tests for the 229 patients (147 FC, 50 C-IBS, 32 SPC) were routine blood tests (59.3 %), abdominal ultrasounds (37.2 %), thyroid function (36.7 %), fecal occult blood tests (36.7 %), and tumor markers (35 %). Patient sex and age, GP age, and whether the diagnosis was new influenced the GP's request, but FC, C-IBS, or SPC status did not. Dietary suggestions (81.9 %), fiber supplements (59.7 %), reassurance (50.9 %), and laxatives (30.5 %) were the most frequently prescribed treatments. Antispasmodics were more frequently suggested for C-IBS patients; dietary suggestions, fiber, and enemas were more frequently prescribed in SPC patients. Patient and GP age and whether the diagnosis was new influenced the GP's choice of treatment., Conclusions: The Rome III criteria do not influence diagnostic strategies and only slightly influence therapeutic strategies of GPs. Other factors (age, gender, new or old diagnosis) have more influence on GPs choice of investigations and treatment.

Background and Aims: The key role of the brain-gut axis in the pathophysiology of irritable bowel syndrome (IBS) has been recognized. The aim of this study was to assess the possible association between IBS, neuroendocrine markers, and psychological features., Methods: One hundred and twenty-five consecutive IBS patients and 105 healthy subjects were enrolled. Plasma serotonin, plasma and urinary cortisol, and plasma neuropeptide Y levels were evaluated. All patients were given a questionnaire to assess IBS symptom severity. In 66 patients, a psychodiagnostic assessment was carried out., Results: A high incidence of specific psychological features, including state anxiety (69.69 %), trait anxiety (54.54 %), obsessions and compulsions (28.78 %), was observed in IBS patients. A positive correlation between neuropeptide Y and state anxiety (r = 0.287, p = 0.024) and simulation/social ingenuity (r = 0.269, p = 0.039) was found in these patients. In diarrhea-predominant IBS, plasma cortisol was linearly related to plasma serotonin (r = 0.5663, p < 0.001)., Conclusions: In IBS patients, a significant correlation was found between specific psychological features and neuroendocrine markers, especially plasma cortisol and neuropeptide Y; in diarrhea-predominant IBS, a correlation between plasma cortisol and serotonin was found, although it needs to be confirmed in more extensive cohorts.

5HTTLPR polymorphism of serotonin transporter yields short (S) and long (L) alleles. SS and LS genotypes are associated with reduced expression of serotonin transporter. This cross-sectional study investigated the association of 5HTTLPR with symptom severity of irritable bowel syndrome (IBS). Patients with IBS (Rome III) and healthy controls were included. Genomic DNA was extracted from saliva, and 5HTTLPR alleles were assessed by polymerase chain reaction. IBS symptom severity was evaluated by means of IBS-SSS questionnaire. Two hundreds and four IBS patients (159 females; mean age: 39.6±12.3 years; 106 with constipation: C-IBS; 98 with diarrhea: D-IBS) and 200 healthy controls (154 females; mean age: 40.4±15.8 years) were enrolled. The overall IBS-SSS value was higher in LS/SS than LL patients (319.0±71.5 versus 283.8±62.3; P = 0.0006). LS/SS patients had also higher values of abdominal pain (59.7±21.0 versus 51.0±18.8; P = 0.020) and bowel dissatisfaction (80.1±23.9 versus 70.5±22.8; P = 0.035). The overall IBS-SSS values in C-IBS and D-IBS patients were 317.2±68.3 and 296.1±71.4, respectively (P = 0.192), with significantly higher values for abdominal distension (65.0±24.4 versus 51.4±24.8; P = 0.0006), but not for bowel dissatisfaction (80.5±21.7 versus 72.9±25.7; P = 0.138). Frequencies of 5HTTLPR genotypes did not differ significantly when comparing IBS patients (overall or upon stratification in C-IBS and D-IBS) with healthy controls. In conclusion, the LS and SS genotypes are significantly correlated with IBS symptom severity, although their possible direct causal role remains to be proven. In addition, the present findings do not support an association of 5HTTLPR with IBS or its clinical presentation in terms of bowel habit predominance.

Aim: To investigate the prevalence of gastroesophageal reflux disease (GERD) in patients with a laryngoscopic diagnosis of laryngopharyngeal reflux (LPR)., Methods: Between May 2011 and October 2011, 41 consecutive patients with laryngopharyngeal symptoms (LPS) and laryngoscopic diagnosis of LPR were empirically treated with proton pump inhibitors (PPIs) for at least 8 wk, and the therapeutic outcome was assessed through validated questionnaires (GERD impact scale, GIS; visual analogue scale, VAS). LPR diagnosis was performed by ear, nose and throat specialists using the reflux finding score (RFS) and reflux symptom index (RSI). After a 16-d wash-out from PPIs, all patients underwent an upper endoscopy, stationary esophageal manometry, 24-h multichannel intraluminal impedance and pH (MII-pH) esophageal monitoring. A positive correlation between LPR diagnosis and GERD was supposed based on the presence of esophagitis (ERD), pathological acid exposure time (AET) in the absence of esophageal erosions (NERD), and a positive correlation between symptoms and refluxes (hypersensitive esophagus, HE)., Results: The male/female ratio was 0.52 (14/27), the mean age ± SD was 51.5 ± 12.7 years, and the mean body mass index was 25.7 ± 3.4 kg/m(2). All subjects reported one or more LPS. Twenty-five out of 41 patients also had typical GERD symptoms (heartburn and/or regurgitation). The most frequent laryngoscopic findings were posterior laryngeal hyperemia (38/41), linear indentation in the medial edge of the vocal fold (31/41), vocal fold nodules (6/41) and diffuse infraglottic oedema (25/41). The GIS analysis showed that 10/41 patients reported symptom relief with PPI therapy (P < 0.05); conversely, 23/41 did not report any clinical improvement. At the same time, the VAS analysis showed a significant reduction in typical GERD symptoms after PPI therapy (P < 0.001). A significant reduction in LPS symptoms. On the other hand, such result was not recorded for LPS. Esophagitis was detected in 2/41 patients, and ineffective esophageal motility was found in 3/41 patients. The MII-pH analysis showed an abnormal AET in 5/41 patients (2 ERD and 3 NERD); 11/41 patients had a normal AET and a positive association between symptoms and refluxes (HE), and 25/41 patients had a normal AET and a negative association between symptoms and refluxes (no GERD patients). It is noteworthy that HE patients had a positive association with typical GERD-related symptoms. Gas refluxes were found more frequently in patients with globus (29.7 ± 3.6) and hoarseness (21.5 ± 7.4) than in patients with heartburn or regurgitation (7.8 ± 6.2). Gas refluxes were positively associated with extra-esophageal symptoms (P < 0.05). Overall, no differences were found among the three groups of patients in terms of the frequency of laryngeal signs. The proximal reflux was abnormal in patients with ERD/NERD only. The differences observed by means of MII-pH analysis among the three subgroups of patients (ERD/NERD, HE, no GERD) were not demonstrated with the RSI and RFS. Moreover, only the number of gas refluxes was found to have a significant association with the RFS (P = 0.028 and P = 0.026, nominal and numerical correlation, respectively)., Conclusion: MII-pH analysis confirmed GERD diagnosis in less than 40% of patients with previous diagnosis of LPR, most likely because of the low specificity of the laryngoscopic findings.

Aim: To examine the links between quality of sleep and the severity of intestinal symptoms in irritable bowel syndrome (IBS)., Methods: One hundred and forty-two outpatients (110 female, 32 male) who met the Rome III criteria for IBS with no psychiatric comorbidity were consecutively enrolled in this study. Data on age, body mass index (BMI), and a set of life-habit variables were recorded, and IBS symptoms and sleep quality were evaluated using the questionnaires IBS Symptom Severity Score (IBS-SSS) and Pittsburgh Sleep Quality Index (PSQI). The association between severity of IBS and sleep disturbances was evaluated by comparing the global IBS-SSS and PSQI score (Pearson's correlation and Fisher's exact test) and then analyzing the individual items of the IBS-SSS and PSQI questionnaires by a unitary bowel-sleep model based on item response theory (IRT)., Results: IBS-SSS ranged from mild to severe (120-470). The global PSQI score ranged from 1 to 17 (median 5), and 60 patients were found to be poor sleepers (PSQI > 5). The correlation between the global IBS-SSS and PSQI score indicated a weak association (r = 0.2 and 95% CI: -0.03 to 0.35, P < 0.05), which becomes stronger using our unitary model. Indeed, the IBS and sleep disturbances severities, estimated as latent variables, resulted significantly high intra-subject correlation (posterior mean of r = 0.45 and 95% CI: 0.17 to 0.70, P < 0.05). Moreover, the correlations between patient features (age, sex, BMI, daily coffee and alcohol intake) and IBS and sleep disturbances were also analyzed through our unitary model. Age was a significant regressor, with patients ≤ 50 years old showing more severe bowel disturbances (posterior mean = -0.38, P < 0.05) and less severe sleep disturbances (posterior mean = 0.49, P < 0.05) than older patients. Higher daily coffee intake was correlated with a lower severity of bowel disturbances (posterior mean = -0.31, P < 0.05). Sex (female) and daily alcohol intake (modest) were correlated with less severe sleep disturbances., Conclusion: The unitary bowel-sleep model based on IRT revealed a strong positive correlation between the severity of IBS symptoms and sleep disturbances.

Background: Barrett's oesophagus is regarded as the most important risk factor for development of oesophageal adenocarcinoma. According to current guidelines, treatment should be limited to symptomatic Barrett's oesophagus., Aim: To evaluate the expression of Ki67, cyclooxygenase-2 (COX-2) and apoptosis in Barrett's oesophagus after 12 months of double-dose proton pump inhibitor therapy. The effectiveness of esomeprazole and pantoprazole was also compared., Methods: Seventy-seven nondysplastic Barrett's oesophagus patients underwent baseline upper endoscopy. Patients were then randomised into two groups: one group was allocated to receive esomeprazole 40 mg b.d. and the other group pantoprazole 40 mg b.d. for 12 months. A follow-up endoscopy was performed at the end of treatment. Sixty-five of 77 patients agreed to undergo oesophageal manometry and 24-h pH-metry. Barrett's oesophagus biopsies, obtained at baseline and after treatment, were analysed using immunohistochemistry to assess Ki67 and COX-2 expression; apoptosis was evaluated using TUNEL., Results: In the esomeprazole group, a significant decrease in Ki67 and COX-2 expression, as well as an increase in apoptosis, were observed (P < 0.05). By contrast, in the pantoprazole group Ki67, COX-2 and apoptosis did not vary significantly from baseline. By 24-h oesophageal pH-monitoring, a normal acid exposure time was recorded in patients treated with esomeprazole, while those allocated to pantoprazole displayed abnormal acid exposure (P < 0.05)., Conclusions: Treatment of Barrett's oesophagus patients with high-dose esomeprazole, but not pantoprazole, promoted a decrease in proliferative markers, concomitantly with a decrease in apoptotic cell death. Moreover, esomeprazole allowed a better oesophageal acid control than pantoprazole., (© 2011 Blackwell Publishing Ltd.)

Chronic intestinal pseudo-obstruction (CIP) is an infrequent complication of an active systemic lupus erythematosus (SLE). We illustrate a case of SLE inactive-related CIP. A 51-year old female with inactive SLE (ECLAM score 2) was hospitalized with postprandial fullness, vomiting, abdominal bloating and abdominal pain. She had had no bowel movements for five days. Plain abdominal X-ray revealed multiple fluid levels and dilated small and large bowel loops with air-fluid levels. Intestinal contrast radiology detected dilated loops. CIP was diagnosed. The patient was treated with prokinetics, octreotide, claritromycin, rifaximin, azathioprine and tegaserod without any clinical improvement. Then methylprednisolone (500 mg iv daily) was started. After the first administration, the patient showed peristaltic movements. A bowel movement was reported after the second administration. A plain abdominal X-ray revealed no air-fluid levels. Steroid therapy was slowly reduced with complete resolution of the symptoms. The patient is still in a good clinical condition. SLE-related CIP is generally reported as a complication of an active disease. In our case, CIP was the only clinical demonstration of the SLE.

Objectives: Helicobacter pylori is causally associated with gastritis and peptic ulcer diseases. Recent data (meta-analysis) have demonstrated that triple therapy with amoxicillin, clarithromycin, and a proton pump inhibitor has an eradication rate of only 74-76% and new therapeutic protocols may be necessary. The aim of this study was to examine whether adding bovine lactoferrin (bLf) and probiotics (Pbs) to the standard triple therapy for H. pylori infection could improve the eradication rate and reduce side effects., Methods: H. pylori infection was diagnosed in 206 patients: in 107 based on an upper endoscopy exam and a rapid urease test, and in 99 by means of the H. pylori stool antigen-test and the C(13) urea breath test (C(13) UBT). The patients were randomized into two groups: 101 patients (group A) underwent standard triple eradication therapy (esomeprazole, clarithromycin, amoxicillin), while 105 patients (group B) underwent a modified eradication therapy (standard triple eradication therapy plus bLf and Pb). Successful eradication therapy was defined as a negative C(13) UBT 8 wk after completion of the treatment. Results were evaluated by intention-to-treat (ITT) and per-protocol (PP) analysis. Data were evaluated and considered positive when P<0.05., Results: At the end of the study 175/206 patients showed negative C(13) UBT results. According to intention-to-treat analysis, the infection was eradicated in 73/101 patients from Group A and in 93/105 from Group B. PP analysis showed 73/96 patients from Group A and 93/101 from Group B to have been successfully treated. More patients from group A than from group B reported side effects from their treatment (P<0.05)., Conclusions: The results of our study suggest that the addition of bLf and Pbs could improve the standard eradication therapy for H. pylori infection--bLf serving to increase the eradication rate and Pbs to reduce the side effects of antibiotic therapy.

Abdominal pain and bowel habits alterations are common symptoms in the general population. The investigation to differentiate organic from functional bowel disorders represents a considerable burden both for patients and public health service. The selection of patients who should undergo endoscopic and/or radiological procedures is one of the key points of the diagnostic process, which should avoid the abuse of invasive and expensive tests as well as the underestimation of potentially harmful diseases. Over the coming years, clinicians and researchers will be challenged to develop strategies to increase the patient's compliance and to reduce the economic and social costs of the intestinal diseases.

Myotonic dystrophy (MD) is characterized by myotonic phenomena and progressive muscular weakness. Involvement of the gastrointestinal tract is frequent and may occur at any level. The clinical manifestations have previously been attributed to motility disorders caused by smooth muscle damage, but histologic evidence of alterations has been scarce and conflicting. A neural factor has also been hypothesized. In the upper digestive tract, dysphagia, heartburn, regurgitation and dyspepsia are the most common complaints, while in the lower tract, abdominal pain, bloating and changes in bowel habits are often reported. Digestive symptoms may be the first sign of dystrophic disease and may precede the musculo-skeletal features. The impairment of gastrointestinal function may be sometimes so gradual that the patients adapt to it with little awareness of symptoms. In such cases routine endoscopic and ultrasonographic evaluations are not sufficient and targeted techniques (electrogastrography, manometry, electromyography, functional ultrasonography, scintigraphy, etc.) are needed. There is a low correlation between the degree of skeletal muscle involvement and the presence and severity of gastrointestinal disturbances whereas a positive correlation with the duration of the skeletal muscle disease has been reported. The drugs recommended for treating the gastrointestinal complaints such as prokinetic, anti-dyspeptic drugs and laxatives, are mainly aimed at correcting the motility disorders. Gastrointestinal involvement in MD remains a complex and intriguing condition since many important problems are still unsolved. Further studies concentrating on genetic aspects, early diagnostic techniques and the development of new therapeutic strategies are needed to improve our management of the gastrointestinal manifestations of MD.

Background: Although general practitioners play a critical role in the management of irritable bowel syndrome because they deal with the most patients, guidelines are developed mainly by specialists., Aims: To evaluate the clinical features of irritable bowel patients and the general practitioners' approach to irritable bowel syndrome in Italy., Subjects and Methods: A questionnaire focusing on the management of this syndrome was completed by 28 general practitioners. Clinical features and diagnostic and treatment measures taken in 229 patients were analysed., Results: Only 35.7% of the general practitioners were familiar with the Rome II criteria. Changes in bowel habits and abdominal pain/discomfort were the most common symptoms. Constipation (74.2%) was more frequent as the main symptom than diarrhoea. Routine blood tests (76.4%) and abdominal ultrasound (42.2%) were requested more frequently than colonoscopy (31.1%). At least one specialist consultation was recommended in 63.3% of patients. Drugs (mainly antispasmodics) were prescribed more frequently for diarrhoea (91.4%) than for constipation (55.7%)., Conclusions: General practitioners are little acquainted with the Rome II criteria. Diagnostic tests and specialist consultations are often recommended; antispasmodics are the most frequently prescribed drug. Guidelines should be developed together by general practitioners and gastroenterologists to effectively manage patients at a lower cost.

Background and Aims: The clinical course of inflammatory bowel disease is characterised by a succession of relapses and remissions. The aim of our study was to assess whether the predictive value of faecal calprotectin-a non-invasive marker of intestinal inflammation-for clinical relapse is different in ulcerative colitis (UC) and Crohn's disease (CD)., Methods: Seventy nine consecutive patients with a diagnosis of clinically quiescent inflammatory bowel disease (38 CD and 41 UC) were followed for 12 months, undergoing regular clinical evaluations and blood tests. A single stool sample was collected at the beginning of the study from each patient and the calprotectin concentration was assessed by a commercially available enzyme linked immunoassay., Results: In CD, median calprotectin values were 220.1 mug/g (95% confidence interval (CI) 21.7-418.5) in those patients who relapsed during follow up, and 220.5 mug/g (95% CI 53-388) in non-relapsing patients (p=0.395). In UC, median calprotectin values were 220.6 mug/g (95% CI 86-355.2) and 67 microg/g (95% CI 15-119) in relapsing and non-relapsing patients, respectively (p<0.0001). The multivariate Cox (proportional hazard) regression model, after adjustment for possible confounding variables, showed a twofold and 14-fold increase in the relapse risk, respectively, in those patients with CD and UC in clinical remission who had a faecal calprotectin concentration higher than 150 microg/g., Conclusions: Faecal calprotectin proved to be an even stronger predictor of clinical relapse in UC than in CD, which makes the test a promising non-invasive tool for monitoring and optimising therapy.

Objectives: Serotonin reuptake is mediated by a transporter protein (SERT), and its dysfunctions can alter serotonergic transmission. The present study examines the binding profile of platelet SERT in healthy volunteers as well as in patients with diarrhea-predominant irritable bowel syndrome (D-IBS), both before and after treatment with the 5-HT(3) receptor antagonist alosetron., Methods: Binding of [(3)H]paroxetine to SERT was assayed in platelet membranes collected from D-IBS patients (12 women, age 21-73 yr) and healthy volunteers (12 women, age 24-68 yr). Both maximal binding capacity (B(max)) and dissociation constant (K(d)) were estimated. In D-IBS patients, binding parameters and symptom severity score were evaluated at baseline and after treatment with alosetron (1 mg b.i.d. for 8 wk)., Results: At baseline, B(max) and K(d) values of [(3)H]paroxetine binding were respectively lower and higher in D-IBS patients than in healthy volunteers (B(max): 518.7 +/- 155.9 vs 1151.9 +/- 187.4 fmol/mg, p < 0.001; K(d): 0.19 +/- 0.05 vs 0.06 +/- 0.02 nmol/L, p < 0.001). Symptom severity score in D-IBS patients (50.9 +/- 18.8) was negatively correlated with B(max) (r = -0.964; p < 0.001) but not K(d) values (r = -0.164; p = 0.609). After treatment with alosetron, symptom severity score decreased significantly (14.4 +/- 3.7; p < 0.001), whereas B(max) (522.7 +/- 39.7 fmol/mg) and K(d) values (0.17 +/- 0.07 nmol/L) did not change., Conclusions: The present results indicate that SERT expressed on platelet membranes of D-IBS patients is characterized by low density and binding affinity and suggest a possible correlation between the reduced capacity of serotonin reuptake and the severity of D-IBS symptoms.

Background/aim: Faecal calprotectin, a neutrophil granulocyte cytosol protein, is considered a promising marker of intestinal inflammation. We assessed and compared the faecal calprotectin concentration in patients with organic and functional chronic intestinal disorders., Patients and Methods: The study was carried out, using a commercially available ELISA test, measuring calprotectin in stool samples collected from 131 patients with inflammatory bowel diseases, 26 with intestinal neoplasms, 48 with irritable bowel syndrome and 34 healthy subjects., Results: Median faecal calprotectin was significantly increased in Crohn's disease (231 microg/g, 95% confidence interval (CI) 110-353 microg/g), ulcerative colitis (167 microg/g, 95% CI 59-276 microg/g), and neoplasms (105 microg/g, 95% CI 0-272 microg/g), whereas normal values were found in patients with irritable bowel syndrome (22 microg/g, 95% CI 9-35 microg/g) and in healthy subjects (11 microg/g, 95% CI 3-18 microg/g). A positive correlation was observed with clinical activity scores in Crohn's disease and ulcerative colitis. In both groups, patients with clinically active disease showed higher calprotectin levels than those observed in patients with quiescent disease (405 microg/g, 95% CI 200-610 microg/g vs. 213 microg/g, 95% CI 85-341 microg/g in CD patients, p<0.05, and 327 microg/g, 95% CI 104-550 microg/g vs. 123 microg/g, 95% CI 40-206 microg/g in UC patients, p<0.001)., Conclusions: Faecal calprotectin appears to be a promising and non-invasive biomarker of intestinal inflammation. If these findings are confirmed, it may provide a useful test for the diagnosis and follow up of inflammatory bowel diseases.

Aim: Psychological and/or psychiatric disorders (PSY) and functional gastrointestinal disorders (FGID) are often linked. Pelvic floor dyssynergia (PFD) is one of the most frequent FGID, but few studies have investigated its possible relationship with PSY. The aim of the present study was to evaluate whether an increased prevalence of PSY, and of what types, exist in patients affected with PFD., Methods: Thirty-four female patients PFD and 34 age- and gender-matched control subjects were evaluated. The prevalence rates of axis I psychiatric disorders (DSM IV) and of pathological temperaments (Schneider-Akiskal criteria) were determined., Results: PSY were detected in 29 patients (85.3%) and in 11 controls (32.3%), (p=0.000). A family load was present in 7 patients (20.6%) and in 2 controls (5.9%), (NS). Sixteen patients (47.0%) and no control subjects were diagnosed as having axis I psychiatric disorders (p=0.000); anxiety disorders were the most frequently represented condition. A pathological temperament was found in 28 patients (82.3%) (primarily the phobic-anxious temperament) and in 11 control subjects (32.3%),(p=0.000)., Conclusions: This study shows that there is a higher prevalence of PSY in PFD patients than in controls in particular, anxiety disorders and the phobic-anxious temperament. We would recommend that a psychiatric evaluation be carried out in patients with PFD, especially before starting rehabilitation therapy for obstructed defecation, as the presence of psychiatric disorders could alter the course and decrease the efficacy of such a rehabilitation program.

Background: Helicobacter pylori has attracted increasing attention among gastroenterologists because of its pathogenic potential, stimulating the search for non-invasive diagnostic tests., Aims: In this study the efficacy of a new enzyme immunoassay designed to detect H. pylori antigens in stools (HpSA) was evaluated before and after eradication therapy., Methods: HpSA was performed on stool samples collected from 268 patients whose H. pylori status was defined on the basis of concordant results for the (13)C-urea breath test, rapid urease test and histology. The H. pylori-positive patients were treated with a 1-week triple therapy to eradicate the infection. One (T30) and 3 months (T90) after the end of therapy, (13)C-urea breath test and HpSA were repeated in the treated patients., Results: The overall diagnostic accuracy of HpSA at T30 (83%, 95% confidence interval (CI) 77--89%) was significantly lower in comparison to the values obtained at baseline (94%, 95% CI: 91--97%) and at T90 (97%, 95% CI: 94--99%). No significant difference was found between the diagnostic accuracy of HpSA at baseline and at T90 (P=0.253)., Conclusions: The present data suggest that HpSA provides a low diagnostic accuracy when used shortly after treatment. It needs a longer period of follow-up (8--12 weeks) to reach a reliability comparable to the (13)C-urea breath test.