Esophageal food bolus impaction in pediatric age.

OBJECTIVES: Esophageal food impaction (EFI) is the sudden onset of dysphagia that occurs when a food bolus becomes lodged in the esophagus, requiring endoscopic removal. Scientific data on the prevalence and causes of EFI in children is lacking. The aim of this study was to provide further insights into EFI episodes in children. METHODS: We have prospectively enrolled all children admitted for a first episode of EFI between March 2018 and March 2023. A fluoroscopic contrast study was performed in all patients to confirm the boluses and assess their position. Boluses were extracted by esophagogastroduodenoscopies, and esophageal biopsies were routinely obtained for histologic evaluation. RESULTS: Over the study period, 41 children were admitted for a first episode of food impaction. Drooling was the most commonly reported symptom. Half children experiencing a first episode of food bolus were diagnosed with EoE (20/41, 48.8%). Almost a fourth of the episodes subtended a different condition, such as esophageal anastomotic, peptic or congenital strictures, stricturing caustic esophagitis, esophageal duplication, and achalasia. In the last fourth of patients the cause of EFI was not identified and thus probably related to quick eating and inadequate chewing of food. DISCUSSION: Our study represents the largest known series of pediatric patients evaluated for food bolus impaction. Our main finding is the high frequency of EoE, which accounts for a half of EFI episodes in pediatric age, especially in older children. This finding highlights the importance of obtaining esophageal biopsies after the endoscopic bolus removal in children with EFI to provide a complete diagnostic evaluation.

Ocular endothelial dysfunction in pediatric inflammatory bowel disease.

OBJECTIVES: To assess ocular microvasculature changes using optical coherence tomography angiography (OCTA) in pediatric patients with inflammatory bowel disease (IBD). METHODS: Patients (aged 6-18 years) with IBD were recruited between September 2021 and May 2023. All eligible participants underwent comprehensive clinical assessment and laboratory investigation. Patients with functional gastrointestinal disorders served as the controls. This study assessed specific IBD phenotypes, disease duration, clinical and endoscopic activity indices, laboratory markers, and medication histories. OCTA was utilized to evaluate ocular microvasculature changes in both groups. RESULTS: A total of 63 children (mean age 12.9 ± 3.3 years) were enrolled, comprising 38 in the IBD group (16 ulcerative colitis, 22 Crohn's disease, and 25 in the control group). Most patients in the IBD group were in remission or had mild-to-moderate disease activity at enrollment. Analysis of the OCTA results revealed significant differences in the choroidal luminal area and total choroidal area between the IBD and control groups. CONCLUSIONS: The study identified distinct ocular microvasculature changes in pediatric IBD patients through OCTA, suggestive of potential systemic endothelial dysfunction. These findings underscore the utility of OCTA in evaluating microvascular alterations associated with pediatric IBD, offering insights into potential systemic complications linked to inflammation in IBD patients.

Palmitoylethanolamide and polydatin in pediatric irritable bowel syndrome: A multicentric randomized controlled trial.

OBJECTIVE: This study aimed to evaluate the efficacy and safety of co-micronized palmitoylethanolamide (PEA)/polydatin (PD) in the treatment of abdominal pain symptoms in pediatric patients with irritable bowel syndrome (IBS). METHODS: This was a multicenter trial conducted at three Italian pediatric gastroenterology centers, employing a double-blind, placebo-controlled, parallel-arm design. Participants were ages 10 to 17 y and met Rome IV criteria for pediatric IBS. They were randomly allocated to receive either co-micronized PEA/PD or placebo, administered three times daily in a 1:1 ratio, over a 12-wk period. The study assessed baseline severity using the IBS-Severity Scoring System (IBS-SSS) at enrollment and after 4, 8, and 12 wk of treatment. Abdominal pain frequency was assessed on a scale from 1 to 7 d/wk, while stool consistency was classified using the Bristol Stool Scale (BSS) to categorize various IBS subtypes. The primary outcome was the percentage of patients who achieved complete remission, defined as IBS-SSS score <75 points after 12 wk of therapy. RESULTS: The study involved 70 children with IBS. Of the participants, 34 received co-micronized PEA/PD, and 36 received a placebo. As compared with the placebo group, the co-micronized therapy group had significantly more patients achieving complete remission after 12 wk (P = 0.015), with particular benefit in the IBS-diarrhea subtype (P = 0.01). The treatment group also experienced a significant reduction in abdominal pain intensity and frequency compared with the placebo group. No adverse events were recorded during the study period. CONCLUSIONS: Co-micronized PEA/PD is a safe and effective treatment to treat abdominal pain symptoms in pediatric IBS.

Associations between immune biomarkers and symptoms of anxiety, depression, and insomnia in paediatric inflammatory bowel disease: A preliminary longitudinal analysis.

Innate immunity may influence the onset of affective symptoms and alter sleep patterns in chronic inflammatory conditions. Here, we tested the prospective associations between baseline serum C-reactive protein (CRP), albumin, and CRP/albumin ratio (CAR, i.e., an emerging biomarker of disease activity), and self-reported symptoms of anxiety, depression, and insomnia at 1-year follow up in paediatric inflammatory bowel disease (n = 17). After controlling for baseline values, CAR (ρ = 0.591, p = 0.026) predicted anxiety symptoms, while albumin predicted both anxiety (ρ = -0.687, p = 0.007) and insomnia symptoms (ρ = -0.648, p = 0.012). Current findings preliminarily suggest that inflammation may influence anxiety and sleep disturbance in paediatric IBD.

Mobile Health technology in pediatric esophagogastroduodenoscopy quality indicators assessment: results from a national program of the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition.

BACKGROUND AND AIMS: Upper endoscopy procedures (UEP, esophagogastroduodenoscopy [EGDS] and retrograde endoscopic retrograde cholangiography [ERCP]) are an established standard of care in pediatric gastroenterology. The Pediatric endoscopy quality improvement network (PEnQuIN) recently published its pediatric-specific endoscopy quality guidelines. This study, initiated by the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP), aims to evaluate the adherence of Italian Pediatric Endoscopy Centers to these established quality standards. METHODS: Conducted between April 2019 and March 2021, this nationwide study utilized a smartphone app-based approach. Data encompassing pediatric endoscopy facilities, patient profiles, endoscopy indications, 17 procedure-related PEnQuIN indicators, and a GHAA-9m patient satisfaction questionnaire were systematically collected. RESULTS: A comprehensive analysis of 3582 procedures from 24 PECs revealed that 2654 (76%) were UEP. The majority of centers (75%) involved more than one operator, with 9 PEC incorporating adult endoscopists, responsible for 5% of UEPs. Overall, adherence to quality standards was good; however, areas of improvement include sub-optimal reporting of sedation details, adherence to disease-specific guidelines, and patient satisfaction questionnaire completeness (56%). The complication rate aligned with literature standards (1%), and patient satisfaction was generally high. A noteworthy observation was a 30% decrease monthly reporting rate and a shift in disease-specific patterns following the COVID-19 outbreak. CONCLUSIONS: Pediatric UEP practices in Italy adhere well to established quality standards. Emphasizing the adoption of disease-specific guidelines is crucial for optimizing resources, enhancing diagnostic accuracy, and minimizing unnecessary procedures. Prioritizing patient satisfaction is important for immediate enhancements in practice as well as for future research endeavors.

Italian guidelines for the management of irritable bowel syndrome in children and adolescents : Joint Consensus from the Italian Societies of: Gastroenterology, Hepatology and Pediatric Nutrition (SIGENP), Pediatrics (SIP), Gastroenterology and Endoscopy (SIGE) and Neurogastroenterology and Motility (SINGEM).

The irritable bowel syndrome (IBS) is a functional gastrointestinal disorder (FGID), whose prevalence has widely increased in pediatric population during the past two decades. The exact pathophysiological mechanism underlying IBS is still uncertain, thus resulting in challenging diagnosis and management. Experts from 4 Italian Societies participated in a Delphi consensus, searching medical literature and voting process on 22 statements on both diagnosis and management of IBS in children. Recommendations and levels of evidence were evaluated according to the grading of recommendations, assessment, development, and evaluation (GRADE) criteria. Consensus was reached for all statements. These guidelines suggest a positive diagnostic strategy within a symptom-based approach, comprehensive of psychological comorbidities assessment, alarm signs and symptoms' exclusion, testing for celiac disease and, under specific circumstances, fecal calprotectin and C-reactive protein. Consensus also suggests to rule out constipation in case of therapeutic failure. Conversely, routine stool testing for enteric pathogens, testing for food allergy/intolerance or small intestinal bacterial overgrowth are not recommended. Colonoscopy is recommended only in patients with alarm features. Regarding treatment, the consensus strongly suggests a dietary approach, psychologically directed therapies and, in specific conditions, gut-brain neuromodulators, under specialist supervision. Conditional recommendation was provided for both probiotics and specific fibers supplementation. Polyethylene glycol achieved consensus recommendation for specific subtypes of IBS. Secretagogues and 5-HT4 agonists are not recommended in children with IBS-C. Certain complementary alternative therapies, antispasmodics and, in specific IBS subtypes, loperamide and rifaximin could be considered.

Chronic intestinal pseudo-obstruction: associations with gut microbiota and genes expression of intestinal serotonergic pathway.

BACKGROUND: Pediatric chronic intestinal pseudo-obstruction (PIPO) is a rare disease characterized by symptoms and radiological signs suggestive of intestinal obstruction, in the absence of lumen-occluding lesions. It results from an extremely severe impairment of propulsive motility. The intestinal endocrine system (IES) jointly with the enteric nervous system (ENS) regulates secreto-motor functions via different hormones and bioactive messengers/neurotransmitters. The neurotransmitter 5-hydroxytryptamine (5-HT) (or serotonin) is linked to intestinal peristalsis and secretory reflexes. Gut microbiota and its interplay with ENS affect 5-HT synthesis, release, and the subsequent serotonin receptor activation. To date, the interplay between 5-HT and gut microbiota in PIPO remains largely unclear. This study aimed to assess correlations between mucosa associated microbiota (MAM), intestinal serotonin-related genes expression in PIPO. To this purpose, biopsies of the colon, ileum and duodenum have been collected from 7 PIPO patients, and 7 age-/sex-matched healthy controls. After DNA extraction, the MAM was assessed by next generation sequencing (NGS) of the V3-V4 region of the bacterial RNA 16 S, on an Illumina Miseq platform. The expression of genes implicated in serotoninergic pathway (TPH1, SLC6A4, 5-HTR3 and 5-HTR4) was established by qPCR, and correlations with MAM and clinical parameters of PIPO have been evaluated. RESULTS: Our results revealed that PIPO patients exhibit a MAM with a different composition and with dysbiosis, i.e. with a lower biodiversity and fewer less connected species with a greater number of non-synergistic relationships, compared to controls. qPCR results revealed modifications in the expression of serotonin-related intestinal genes in PIPO patients, when compared to controls. Correlation analysis do not reveal any kind of connection. CONCLUSIONS: For the first time, we report in PIPO patients a specific MAM associated to underlying pathology and an altered intestinal serotonin pathway. A possible dysfunction of the serotonin pathway, possibly related to or triggered by an altered microbiota, may contribute to dysmotility in PIPO patients. The results of our pilot study provide the basis for new biomarkers and innovative therapies targeting the microbiota or serotonin pathways in PIPO patients.

IL-10-producing regulatory cells impact on celiac disease evolution.

Celiac Disease (CD) is a T-cell mediated disorder caused by immune response to gluten, although the mechanisms underlying CD progression are still elusive. We analyzed immune cell composition, plasma cytokines, and gliadin-specific T-cell responses in patients with positive serology and normal intestinal mucosa (potential-CD) or villous atrophy (acute-CD), and after gluten-free diet (GFD). We found: an inflammatory signature and the presence of circulating gliadin-specific IFN-γ+ T cells in CD patients regardless of mucosal damage; an increased frequency of IL-10-secreting dendritic cells (DC-10) in the gut and of circulating gliadin-specific IL-10-secreting T cells in potential-CD; IL-10 inhibition increased IFN-γ secretion by gliadin-specific intestinal T cells from acute- and potential-CD. On GFD, inflammatory cytokines normalized, while IL-10-producing T cells accumulated in the gut. We show that IL-10-producing cells are fundamental in controlling pathological T-cell responses to gluten: DC-10 protect the intestinal mucosa from damage and represent a marker of potential-CD.

Inflammation as an aetiological trigger for depressive symptoms in a prospective cohort of patients with inflammatory bowel disease.

OBJECTIVE: Inflammatory bowel disease (IBD) is often comorbid with mood disorders and depressive symptoms. The aetiology of depressive symptoms in IBD, however, remains largely unknown. Consistent with the inflammatory hypothesis of depression, the aim of this study was to explore the prospective associations between inflammatory biomarkers and depressive symptoms in a cohort of IBD patients with and without a previous clinical diagnosis of mood disorder. METHOD: IBD clinical activity was determined using the Harvey-Bradshaw Index for CD and the Partial Mayo score for UC; serum C-reactive protein (CRP) and faecal calprotectin (fCAL) were used as biomarkers of systemic and intestinal inflammation, respectively. Participants were administered the Hospital Anxiety and Depression Scale-depression (HADS-D) at baseline and 1-year follow-up. RESULTS: Eighty-four participants (50 ± 16 years; 75% UC and 25% CD) were included in the main analyses. Longitudinal moderated regression models showed that baseline CRP significantly predicted follow-up HADS-D scores among individuals with a previous mood disorder diagnosis (ß = 0.843, p < .001), but not among individuals without (ß = -0.013, p = .896), after controlling for baseline HADS-D scores, body mass index, IBD phenotype, sex, and perceived stress. Likely due to lower power, results on FCAL (n = 31) were not statistically significant. CONCLUSION: This study suggests that IBD patients with previous diagnosis of mood disorder may be at higher risk of inflammation-related depressive symptoms.

Gastrointestinal bleeding in children: diagnostic approach.

Different conditions may underlie gastrointestinal bleeding (GIB) in children. The estimated prevalence of GIB in children is 6.4%, with spontaneous resolution in approximately 80% of cases. Nonetheless, the initial approach plays a pivotal role in determining the prognosis. The priority is the stabilization of hemodynamic status, followed by a systematic diagnostic approach. GIB can originate from either upper or lower gastrointestinal tract, leading to a broad differential diagnosis in infants and children. This includes benign and self-limiting disorders, alongside serious conditions necessitating immediate treatment. We performed a nonsystematic review of the literature, in order to describe the variety of conditions responsible for GIB in pediatric patients and to outline diagnostic pathways according to patients' age, suspected site of bleeding and type of bleeding which can help pediatricians in clinical practice. Diagnostic modalities may include esophagogastroduodenoscopy and colonoscopy, abdominal ultrasonography or computed tomography and, when necessary, magnetic resonance imaging. In this review, we critically assess these procedures, emphasizing their respective advantages and limitations concerning specific clinical scenarios.

A possible unexpected link: Could wheat elimination trigger food protein-induced enterocolitis syndrome in a celiac disease patient?

Cases of association between celiac disease and wheat allergy have been described in the literature. However, to date, no reported cases have linked celiac disease with wheat food protein-induced enterocolitis syndrome (FPIES). We report a case of this association. A child diagnosed with celiac disease at the age of 2 years, following a gluten-free diet, experienced uncontrollable vomiting, and subsequent hypotension within 2 h of accidental ingestion of wheat flour. As a result, the child required hospitalization for fluid therapy. A similar episode occurred when the child turned 5 y, again resulting from accidental gluten ingestion. This time, the symptoms included vomiting, hypotension, and a loss of consciousness, leading to hospitalization for rehydration treatment. After this second episode, on suspicion of FPIES, the patient was referred to the pediatric allergists, who confirmed the diagnosis. To our knowledge, this is the first case of an association between celiac disease and FPIES. It has been hypothesized that exclusion diets in food-allergic children may lead to an increase in specific immunoglobulin E levels for those foods and, consequently, the risk of anaphylaxis. However, FPIES is not an immunoglobulin E-mediated condition. Hence, further investigations are warranted to elucidate the underlying mechanisms linking these 2 disorders.

Rectal Bleeding in Infants: Diagnostic Work-up and Management.

Lower gastrointestinal bleeding is an alarming symptom in pediatrics, especially in infancy. However, it is commonly secondary to benign and self-limiting conditions, such as anal fissures, infections, and allergies; more rarely it is caused by more serious disorders, such as necrotizing enterocolitis, very early onset inflammatory bowel diseases, and vascular malformations. The present review aims at summarizing the different clinical conditions presenting with rectal bleeding in infancy and provides an evidence-based diagnostic work-up for the clinical management of patients with this occurrence.

Oxidative stress and optical coherence tomography angiography evaluation of choriocapillaris and retinal vessel density in children with obstructive sleep apnea.

OBJECTIVES: To investigate the vascular networks of the retina and choroid using optical coherence tomography angiography (OCTA) to identify early biomarkers of obstructive sleep apnea (OSA) severity and to evaluate correlations with blood levels of oxidative stress. STUDY DESIGN: Patients with OSA were diagnosed based on video-polysomnography (PSG) and blood samples were collected to evaluate oxidative stress markers: total antioxidant status (TAS), biological antioxidant potential (BAP) test, Diacron reactive oxygen metabolites (d-ROMs) test. The eyes of children with OSA were evaluated and compared with eyes of healthy age-matched children. OCTA imaging was carried out to evaluate the choroidal and retinal vascular network density indices. RESULTS: A total of 31 children with OSA were recruited and compared with 10 healthy children. Choriocapillaris flow area decreased (p = 0.006) and superficial capillary plexus vessel density increased (p=0.01) with increasing severity of OSA. Children with OSA showed significant differences in TAS and d-ROMs test when compared to normal pediatric values (p<0.05). In calculating the correlations between PSG, oxidative stress, and OCTA variables, there was a negative correlation between choriocapillaris flow area and apnea hypopnea index (AHI) (p = 0.02, r2 -0.5) and between choriocapillaris flow area and the d-ROMs test (p 0.03; r2 0.5). CONCLUSIONS: The severity of OSA was associated with the choroidal and retinal capillary vascular networks. The correlation of the choriocapillaris flow area with AHI and the d-ROMs test indicates the connection of the choroidal microvasculature with the number of obstructive apnea and hypopnea events and oxidative stress.

Pediatric hypnic headache: a systematic review.

Introduction: Hypnic headache (HH) is a primary headache, and it is considered a rare condition in children. The underlying mechanisms of HH are not yet fully understood. This systematic review aims to provide a comprehensive description of the clinical features of all published cases of pediatric HH. It will also discuss the differences in headache features between children and adults, the increased diagnostic sensitivity of the new diagnostic criteria (ICHD-3), potential pathophysiological hypotheses explaining the higher incidence in adults, differential diagnoses, and therapeutic options for children. Methods: A systematic search was conducted to identify and analyze articles reporting cases of HH in patients under the age of 18. The search was performed in major medical databases including Cochrane Library, EBSCO, Embase, Medline, PubMed, Science Direct, Scopus, and Web of Science. The search covered the period from 1988 to April 2023. Relevant studies were screened for eligibility, and data extraction was performed using a standardized approach. Results: Seven children with HH were included in the analysis. The mean age of onset for headache attacks was 10 ± 4.3 years (range 3-15 years). The average time from the start of headaches to diagnosis was 15.8 ± 25.0 months (range 1-60 months). Headache features in children differed from those observed in adult HH patients. Children experienced throbbing/pulsating pain, while adults reported dull/pressure-like pain. Children also had lower frequency and shorter duration of attacks compared to adults. The use of ICHD-3 criteria appeared to be more sensitive and inclusive for diagnosing HH in children compared to the previous ICHD-2 criteria. The association of headache attacks with sleep suggests that HH may be a primary disorder with a chronobiological origin. Hypothalamic dysfunction and melatonin dysregulation, which are more prevalent in older individuals, could potentially explain the higher incidence of HH in adults. Other primary headaches and secondary causes should be ruled out. Melatonin prophylactic therapy may be considered for pediatric patients. Discussion: Further evaluation of the clinical features of HH in children is needed. The development of specific diagnostic criteria for pediatric cases could improve diagnostic rates and enhance the management of children with HH.

Children under 6 years with acute headache in Pediatric Emergency Departments. A 2-year retrospective exploratory multicenter Italian study.

BACKGROUND: Preschool age (i.e. children under six years of age) represents a red flag for requiring neuroimaging to exclude secondary potentially urgent intracranial conditions (PUIC) in patients with acute headache. We investigated the clinical characteristics of preschoolers with headache to identify the features associated with a greater risk of secondary "dangerous" headache. METHODS: We performed a multicenter exploratory retrospective study in Italy from January 2017 to December 2018. Preschoolers with new-onset non-traumatic headache admitted to emergency department were included and were subsequently divided into two groups: hospitalized and discharged. Among hospitalized patients, we investigated the characteristics linked to potentially urgent intracranial conditions. RESULTS: We included 1455 preschoolers with acute headache. Vomiting, ocular motility disorders, ataxia, presence of neurological symptoms and signs, torticollis and nocturnal awakening were significantly associated to hospitalization. Among the 95 hospitalized patients, 34 (2.3%) had potentially urgent intracranial conditions and more frequently they had neurological symptoms and signs, papilledema, ataxia, cranial nerves paralysis, nocturnal awakening and vomiting. Nevertheless, on multivariable logistic regression analysis, we found that only ataxia and vomiting were associated with potentially urgent intracranial conditions. CONCLUSION: Our study identified clinical features that should be carefully evaluated in the emergency department in order to obtain a prompt diagnosis and treatment of potentially urgent intracranial conditions. The prevalence of potentially urgent intracranial conditions was low in the emergency department, which may suggest that age under six should not be considered an important risk factor for malignant causes as previously thought.

Celiac crisis as the life-threatening onset of celiac disease in children: a case report.

Celiac disease (CD) is an immune-mediated enteropathy caused by a permanent sensitivity to gluten in genetically susceptible individuals. In rare cases, CD may occur with a severe potential life-threatening manifestation known as a celiac crisis (CC). This may be a consequence of a delayed diagnosis and expose patients to possible fatal complications. We report the case of a 22-month-old child admitted to our hospital for a CC characterized by weight loss, vomiting, and diarrhea associated with a malnutrition state. Early identification of symptoms of CC is essential to provide a prompt diagnosis and management.

Tolerogenic IL-10-engineered dendritic cell-based therapy to restore antigen-specific tolerance in T cell mediated diseases.

Tolerogenic dendritic cells play a critical role in promoting antigen-specific tolerance via dampening of T cell responses, induction of pathogenic T cell exhaustion and antigen-specific regulatory T cells. Here we efficiently generate tolerogenic dendritic cells by genetic engineering of monocytes with lentiviral vectors co-encoding for immunodominant antigen-derived peptides and IL-10. These transduced dendritic cells (designated DCIL-10/Ag) secrete IL-10 and efficiently downregulate antigen-specific CD4+ and CD8+ T cell responses from healthy subjects and celiac disease patients in vitro. In addition, DCIL-10/Ag induce antigen-specific CD49b+LAG-3+ T cells, which display the T regulatory type 1 (Tr1) cell gene signature. Administration of DCIL-10/Ag resulted in the induction of antigen-specific Tr1 cells in chimeric transplanted mice and the prevention of type 1 diabetes in pre-clinical disease models. Subsequent transfer of these antigen-specific T cells completely prevented type 1 diabetes development. Collectively these data indicate that DCIL-10/Ag represent a platform to induce stable antigen-specific tolerance to control T-cell mediated diseases.

Migraine, Allergy, and Histamine: Is There a Link?

The relationship between migraines and allergies is controversial. Though they are epidemiologically linked, the underlying pathophysiological connection between them remains unclear. Migraines and allergic disorders have various underlying genetic and biological causes. As per the literature, these conditions are epidemiologically linked, and some common pathophysiological pathways have been hypothesized. The histaminergic system may be the clue to understanding the correlation among these diseases. As a neurotransmitter in the central nervous system with a vasodilatory effect, histamine has a well-documented influence on the allergic response and could be involved in the pathophysiology of migraines. Histamine may influence hypothalamic activity, which may play a major role in migraines or may simply influence their severity. In both cases, antihistamine drugs could prove useful. This review examines whether the histaminergic system, particularly H3 and H4 receptors, may provide a mechanistic link between the pathophysiology of migraines and allergic disorders, two common and debilitating conditions. Identifying their connection could help identify novel therapeutic strategies.