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Corona virus disease-19 (COVID-19) is the latest global pandemic. COVID-19 is mainly transmitted through respiratory droplets and, apart from respiratory symptoms, patients often present with gastrointestinal symptoms and liver involvement. Given the high percentage of COVID-19 patients that present with gastrointestinal symptoms (GIS), in this review, we report a practical up-to-date reference for the physician in their clinical practice with patients affected by chronic gastrointestinal (GI) diseases (inflammatory bowel disease, coeliac disease, chronic liver disease) at the time of COVID-19. First, we summarised data on the origin and pathogenetic mechanism of SARS-CoV-2. Then, we performed a literature search up to December 2020 examining clinical manifestations of GI involvement. Next, we illustrated and summarised the most recent guidelines on how to adhere to GI procedures (endoscopy, liver biopsy, faecal transplantation), maintaining social distance and how to deal with immunosuppressive treatment. Finally, we focussed on some special conditions such as faecal–oral transmission and gut microbiota. The rapid accumulation of information relating to this condition makes it particularly essential to revise the literature to take account of the most recent publications for medical consultation and patient care. Supplementary Information The online version contains supplementary material available at 10.1007/s10620-021-07158-0.

The association between eosinophilic esophagitis and celiac disease is still controversial and its prevalence is highly variable. We aimed to investigate the prevalence of esophageal eosinophilia and eosinophilic esophagitis in a large group of children with celiac disease, prospectively followed over 11 years. Methods: Prospective observational study performed between 2008 and 2019. Celiac disease diagnosis was based on ESPGHAN criteria. At least four esophageal biopsies were sampled in patients who underwent endoscopy. The presence of at least 15 eosinophils/HPF on esophageal biopsies was considered suggestive of esophageal eosinophilia, at the same time, eosinophilic esophagitis was diagnosed according to the International Consensus Diagnostic Criteria for Eosinophilic Esophagitis. Results: A total of 465 children (M 42% mean age 7.1 years (range: 1–16)) were diagnosed with celiac disease. Three hundred and seventy patients underwent endoscopy, and esophageal biopsies were available in 313. The prevalence of esophageal eosinophilia in children with celiac disease was 1.6% (95% CI: 0.54–2.9%). Only one child was diagnosed as eosinophilic esophagitis, we calculated a prevalence of 0.3% (95% CI: 0.2–0.5%). The odds ratio for an association between eosinophilic esophagitis and celiac disease was at least 6.5 times higher (95% CI: 0.89–47.7%, p = 0.06) than in the general population. Conclusion: The finding of an increased number of eosinophils (&gt, 15/HPF) in celiac patients does not have a clinical implication or warrant intervention, and therefore we do not recommend routine esophageal biopsies unless clinically indicated.

Goals:The goals of this study were to evaluate the efficacy and safety of a probiotic mixture in patients with celiac disease (CD) with irritable bowel syndrome (IBS)-type symptoms despite a strict gluten-free diet (GFD).Background:About 30% of patients with CD adherent to a GFD suffer from IBS-type

Background: non-autoimmune thyroid disorder is a common finding in celiac patients, more frequent than in the general population. An impairment of iodine absorption has been hypothesized, but it has never been investigated so far. We aimed to evaluate the iodine absorption in children and adolescents with newly diagnosed celiac disease. Methods: 36 consecutive celiac patients (age 7.4 years, range 2.4–14.5 years) before starting a gluten-free diet (GFD) were enrolled. We assayed the urinary iodine concentration (UIC) in a 24-h urine sample, at baseline (T0) after 3 (T1) and 12 months (T2) of GFD. Results: UIC at T0 was 64 μg/L (IQR 45–93.25 μg/L) with an iodine deficiency rate of 77.8%. UIC was not different according to histological damage, clinical presentation (typical vs atypical), we found no correlation with the thyroid function tests and auxological parameters. UIC was not statistically different at T1 (76 μg/L) and T2 (89 μg/L) vsT0. UIC at T2 was similar between patients with positive and negative anti-transglutaminase antibodies at T2. No patients presented overt hypothyroidism during the study. Conclusions: We found that iodine absorption in celiac children is impaired compared to the general population, it increases slightly, but not significantly, during the GFD. We should regularly reinforce the need for a proper iodine intake in celiac disease patients to reduce iodine deficiency risk.

Background. To date, there is no reliable marker for the diagnosis of non-celiac gluten sensitivity (NCGS), which benefits from a gluten-free diet (GFD). This condition is characterized by functional gastrointestinal symptoms similar to those occurring in the course of irritable bowel syndrome (IBS). However, IBS has a higher prevalence, and often benefits from the administration of a low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet. The overlap of symptoms between these two pathologies has led to an overestimation of self-made diagnosis NCGS. Aims. To better identify NCGS in subjects with a previous diagnosis of IBS. Methods. All subjects received a low FODMAP diet that was also gluten-free (low FODMAP-GFD), and those presenting an improvement of symptoms were exposed to gluten or placebo (double-blind challenge with wash-out and crossover). The response to dietary treatments was evaluated by visual analogue scale (VAS). Results. Of 30 patients (23 women, seven men, aged 42.2 &plusmn, 12.5 years, body mass index (BMI ) 24.7 &plusmn, 4.1 kg/m2), 26 benefited from the administration of low FODMAP-GFD and were exposed to the gluten/placebo challenge. After the challenge, using an increase of visual analogue scale VAS (&Delta, VAS) &ge, 30%, 46.1% of the patients were NCGS+. However, this percentage became only 19.2% using a different method (mean ∆-VAS score plus two standard deviations). Conclusions. FODMAP intolerance could hide the response to a challenge test with gluten for the identification of NCGS in IBS patients. A low FODMAP-GFD followed by gluten/placebo challenge is able to identify patients with NCGS better. ClinicalTrials.gov registration number NCT04017585.

Background/Aims Combined multichannel intraluminal impedance and pH monitoring (MII/pH) is considered the most accurate test to detect gastroesophageal reflux (GER), however lacking reference values. We aim to determine reference values for the pediatric population and to correlate these values with age and postprandial/fasting period. Methods We evaluated MII/pH traces from patients (newborns, infants, and children) admitted to 3 Italian hospitals and who underwent MII/ pH for suspected GER disease. Patients with MII/pH traces that showed significant symptom-reflux associations and/or a pathological reflux index (> 6% for newborns and infants, > 3% for children) were excluded. Traces were analysed in their entirety, and in the postprandial period (first hour after a meal) and the fasting period (the following hours before the next meal) separately. Results A total of 195 patients (46 newborns, 83 infants, and 66 children) were included. Age positively correlated with frequency of acidic GER events (r = 0.37, P < 0.05) and negatively associated with weakly acidic GER events (r = 0.46, P < 0.05). Conclusions This study describes the distribution of MII/pH values in a pediatric population with normally acidic GER exposure and no significant association between GER events and symptoms. These MII/pH values may be used as reference values in clinical practice for a corrected GER disease diagnosis in the pediatric population. (J Neurogastroenterol Motil 2020;26:370-377)

Multichannel intraluminal impedance pH (MII-pH) monitoring currently represents the gold standard diagnostic technique for the detection of gastro-esophageal reflux (GER), since it allows to quantify and characterize all reflux events and their possible relation with symptoms. Over the last ten years, thanks to its strengths and along with the publication of several clinical studies, its worldwide use has gradually increased, particularly in infants and children. Nevertheless, factors such as the limited pediatric reference values and limited therapeutic options still weaken its current clinical impact. Through an up-to-date review of the available scientific evidence, our aim was to produce a position paper on behalf of the working group on neurogastroenterology and acid-related disorders of the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP) on MII-pH monitoring technique, indications and interpretation in pediatric age, in order to standardise its use and to help clinicians in the diagnostic approach to children with GER symptoms.

OBJECTIVE: The clinical relevance of esophageal baseline impedance (BI) remains to be determined. In the present study, we explored the impact of gastroesophageal reflux disease (GERD) and esophageal dysmotility on BI. METHODS: A total of 18 children with esophageal atresia, 26 children with GERD, and 17 controls prospectively underwent esophagogastroduodenoscopy and pH-impedance monitoring. BI was measured in both proximal and distal esophagus. Gastroesophageal reflux (GER) and bolus transit indicators were defined according to published criteria. RESULTS: Patients with esophageal atresia showed significantly lower proximal and distal BI values (952 [716-1811] Ω; 895 [284-1189] Ω; respectively) compared with those with GERD (3015 [2368-3975] Ω; 2231 [1770-3032] Ω, P < 0.001 and

OBJECTIVE In children with type 1 diabetes mellitus (T1DM), elevated levels of antitissue transglutaminase (anti-tTG) antibody may spontaneously normalize, despite continued consumption of gluten. We aimed to investigate the prevalence of spontaneous normalization of anti-tTG levels and the existence of factors predictive for this outcome. RESEARCH DESIGN AND METHODS All children referred from 2002 to 2012 were screened for celiac disease (CD) at diabetes onset and at specific intervals. In the presence of a high anti-tTG titer or clinical symptoms, children were offered endoscopy, and asymptomatic patients with a low anti-tTG titer were invited to a second serological test after 6 months of eating a gluten-containing diet. RESULTS The study included 446 children. Of these, 65 (14.5%) became positive for celiac serology: 38 (58%) had a persistently elevated anti-tTG titer and 27 (41%) fluctuating anti-tTG titer; 18 (28%) became negative. The prevalence of positive CD autoimmunity and overt CD was 14.3% (95% CI 11–17) and 8.5% (95% CI 5–10), 15- and 8-times higher than the general pediatric population, respectively. Asymptomatic children older than 9.1 years at T1DM onset had the lowest risk to develop CD. CONCLUSIONS Serum anti-tTG levels decreased spontaneously in 40% of children with T1DM and became negative in 20%, despite gluten consumption. This finding supports the hypothesis of a state of temporary positivity of celiac serology in children with diabetes. In absence of clinical symptoms or signs of CD, histological confirmation of the disease and the gluten-free diet should be postponed to avoid unnecessary procedures and reduce an additional psychological burden.

Non-celiac gluten sensitivity (NCGS) is characterized by intestinal and extra-intestinal symptoms that are related to the ingestion of gluten in subjects who are not affected by either celiac disease (CD) or wheat allergy (WA). In this multicenter study, we aim for the first time to evaluate the prevalence of NCGS in pediatric subjects with chronic functional gastrointestinal symptoms associated with gluten ingestion using a double-blind placebo-controlled (DBPC) gluten challenge with crossover.Among 1,114 children with chronic gastrointestinal symptoms (negative CD and WA), those exhibiting a positive correlation between symptoms and gluten ingestion were eligible for a diagnostic challenge including the following phases: run-in, open gluten-free diet (GFD) and DBPC crossover gluten challenge. Patients were randomized to gluten (10 g/daily) and placebo (rice starch) for 2 weeks each, separated by a washout week. The gluten challenge was considered positive in the presence of a minimum 30% decrease of global visual analogue scale between gluten and placebo.Out of 1,114 children, 96.7% did not exhibit any correlation with gluten ingestion. Thirty-six children were eligible; after the run-in and open GFD, 28 patients entered the gluten challenge. Eleven children (39.2%; 95% CI: 23.6-53.6%) tested positive.This is the first demonstration of the existence of NCGS in children that reinforce the need for a DBPC for the diagnosis as the diagnosis is ruled out in60% of cases. The registration identifier in ClinicalsTrials.gov is NCT02431585.

Gastroesophageal reflux (GER) refers to retrograde movement of gastric contents out of the stomach with or without regurgitation and vomiting.

Achalasia is a rare esophageal motility disorder: its optimal treatment in children is still a matter of debate. Records of children treated for achalasia, over an 18-year period, were reviewed.Forty-eight children (median age at diagnosis 10 years; range 3-17 years) were identified. Twenty-eight patients were initially treated with Heller's myotomy (HM) and 20 with balloon dilatation (BD). At last follow-up (median 3 years; range 1-5.5 years), 43.8% (21/48) of children were symptom free. The number of asymptomatic children was significantly higher among those treated initially with HM compared to BD (HM 15/28, 53.6% BD 6/20, 30%, p 0.05). All children who underwent BD required HM due to symptom recurrence. The median (range) total number of procedures was significantly higher in the BD group (BD 3 (1-7); HM 1 (1-5); p 0.05) with a shorter time to the second intervention (BD 14 months, 95%CI 4-24; HM 58 months, 95%CI 38-79; p 0.05). Of 108 procedures, esophageal perforation occurred in two children after HM (two out of 48 HM procedures in total, 4%) and one child after BD (1/60, 1.7%).Less than half of children with achalasia are symptom free after initial treatment with either BD or HM. HM, however, when performed as first procedure, provided longer symptom-free period and reduced need for subsequent intervention. What is Known: • Balloon dilatation (BD) and Heller's myotomy (HM) are safe and effective treatment options for achalasia. • Controversy, however, exists regarding the most effective initial therapeutic approach. What is New: • HM with or without fundoplication may represent the initial therapeutic approach of choice. • Initial BD may negatively affect the outcome of a subsequent HM.

It has been suggested that sourdough fermented products have beneficial health effects. Fungal proteases and selected sourdough lactic acid bacteria were used to produce wheat bread and pasta with a reduced-gluten content (&lt, 50% of traditional products). Fermentable oligo-, di- and mono- saccharides and polyols and amylase/trypsin inhibitors were also evaluated. The sensorial features of new products were similar to traditional ones. The efficacy of these new products in reducing the severity of symptoms in Irritable Bowel Syndrome (IBS) patients were compared to traditional bread and pasta using a randomized, crossover-controlled trial. While on a strict gluten-free diet, patients were randomized to consume a reduced- or normal-gluten diet for 2weeks, then, patients from both arms started the wash-out period of one week, and subsequently started the final 2-week period on a normal or reduced-gluten diet. Compared to normal-gluten content, the administration of a reduced-gluten content diet resulted in a decrease of the Visual Analogue Scale score (p = 0.042), while no differences were found in the IBS-Severity Score, Hospital Anxiety and Depression Scale, and IBS-Quality of Life. Data herein reported are novel encouraging findings that should spur a new avenue of research aiming to develop products specifically designed for IBS patients.

Background Aprepitant (Emend, Merck Sharp & Dohme Ltd, Haarlem, the Netherlands), a neurokinin-1 receptor antagonist, prevents vomiting in a range of conditions. No data are available on its use in children with cyclical vomiting syndrome (CVS). Aim We investigated the efficacy of aprepitant as prophylactic treatment or acute intervention in CVS children refractory to conventional therapies. Methods Forty-one children (median age: 8 years) fulfilling NASPGHAN criteria treated acutely (RegA) or prophylactically (RegP) with aprepitant were retrospectively reviewed. Primary outcome was the clinical response (decrease in frequency and intensity of CVS episodes). Secondary outcomes were: number of CVS episodes/year, number of hospital admissions/year, CVS episode duration, number of vomits/h, symptom-free interval length (days), and school attendance percentage. The follow-up period was 18-60 months. Results Sixteen children received RegP and 25 RegA. One child on RegP stopped treatment due to severe migraine. At 12-months on intention-to-treat analysis, 13 children on RegP (81%) achieved either complete (3/16, 19%) or partial (10/16, 62%) clinical response. On RegA, 19 children (76%) had either complete (3/25, 12%) or partial (16/25, 64%) response (P = 0.8 vs. RegP). In both RegP and RegA, there was a significant decrease in CVS episodes/year, hospital admission number/year, CVS episode length, number of vomits/h, as well as an increase in symptom-free interval duration and school attendance percentage. Side effects were reported only in RegP (5/16, 31%) including hiccough (3/16, 19%), asthenia/fatigue (2/16, 12.5%), increased appetite (2/16, 12.5%), mild headache (1/16, 6%) and severe migraine (1/16, 6%). Conclusion Aprepitant appears effective for both acute and prophylactic management of paediatric cyclical vomiting syndrome refractory to conventional therapies.

The clinical presentation of celiac disease in children is very variable and differs with age. The prevalence of atypical presentations of celiac disease has increased over the past 2 decades. Several studies in adults and children with celiac disease indicate that obesity/overweight at disease onset is not unusual. In addition, there is a trend towards the development of overweight/obesity in celiac patients who strictly comply with a gluten-free diet. However, the pathogenesis and clinical implications of the coexistence of classic malabsorption (e.g., celiac disease) and overweight/obesity remain unclear. This review investigated the causes and main clinical factors associated with overweight/obesity at the diagnosis of celiac disease and clarified whether gluten withdrawal affects the current trends of the nutritional status of celiac disease patients.

Non Celiac Gluten sensitivity (NCGS) was originally described in the 1980s and recently a “re-discovered” disorder characterized by intestinal and extra-intestinal symptoms related to the ingestion of gluten-containing food, in subjects that are not affected with either celiac disease (CD) or wheat allergy (WA). Although NCGS frequency is still unclear, epidemiological data have been generated that can help establishing the magnitude of the problem. Clinical studies further defined the identity of NCGS and its implications in human disease. An overlap between the irritable bowel syndrome (IBS) and NCGS has been detected, requiring even more stringent diagnostic criteria. Several studies suggested a relationship between NCGS and neuropsychiatric disorders, particularly autism and schizophrenia. The first case reports of NCGS in children have been described. Lack of biomarkers is still a major limitation of clinical studies, making it difficult to differentiate NCGS from other gluten related disorders. Recent studies raised the possibility that, beside gluten, wheat amylase-trypsin inhibitors and low-fermentable, poorly-absorbed, short-chain carbohydrates can contribute to symptoms (at least those related to IBS) experienced by NCGS patients. In this paper we report the major advances and current trends on NCGS.

s / Digestive and Liver Disease 47S (2015) e237–e276 e269 Conclusions: An increased frequency of autoimmune diseases iswell described inCD, but few studies have analysed this immunological phenomena at diagnosis: is autoimmunity positivity only an epiphenomenon at this stage? Follow up studies are needed. http://dx.doi.org/10.1016/j.dld.2015.07.135