Immunoproteomics of cow's milk allergy in Mexican pediatric patients.

Immunological mechanisms of non-IgE-mediated cow's milk protein allergy (CMPA) are not well understood. Such a circumstance requires attention with the aim of discovering new biomarkers that could lead to better diagnostic assays for early treatment. Here, we sought both to investigate the mechanism that underlies non-IgE-mediated CMPA and to identify cow's milk immunoreactive proteins in a Mexican pediatric patient group (n = 34). Hence, we determined the IgE and IgG1-4 subclass antibody levels against cow's milk proteins (CMP) by ELISA. Then, we performed 2D-Immunoblots using as first antibody immunoglobulins in the patients'serum that bound specifically against CMP together with CMP enrichment by ion-exchange chromatography. Immunoreactive proteins were identified by mass spectrometry-based proteomics. The serological test confirmed absence of specific IgE in the CMPA patients but showed significant increase in antigen-specific IgG1. Additionally, we identified 11 proteins that specifically bound to IgG1. We conclude that the detection of specific IgG1 together with an immunoproteomics approach is highly relevant to the understanding of CMPA's physiopathology and as a possible aid in making a prognosis since current evidence indicates IgG1 occurrence as an early signal of potential risk toward development of IgE-mediated food allergy. SIGNIFICANCE: Allergies are one of the most studied topics in the field of public health and novel protein allergens are found each year. Discovery of new principal and regional allergens has remarkable repercussions in precise molecular diagnostics, prognostics, and more specific immunotherapies. In this context, specific IgE is widely known to mediate physiopathology; however, allergies whose mechanism does not involve this immunoglobulin are poorly understood although their incidence has increased. Therefore, accurate diagnosis and adequate treatment are delayed with significant consequences on the health of pediatric patients. The study of type and subtypes of immunoglobulins associated with the immunoreactivity of cow's milk proteins together with an immunoproteomics approach allows better comprehension of physiopathology, brings the opportunity to discover new potential cow's milk protein allergens and may help in prognosis prediction (IgG1 occurrence as an early signal of possible risk toward development of IgE-mediated food allergy).

Treatment Approaches for Swallowing Disorders in Children.

A swallowing disorder or dysphagia is defined as a disorder in the sequence of swallowing, during the oral or pharyngeal phase, which compromises the safety and/or efficiency of transit of the food bolus to the esophagus. The evaluation of neurodevelopment, nutrition, and preventive medicine actions are as important as the clinical evaluation of dysphagia, so they must be included and systematized in all pediatric evaluations; This evaluation can be divided into different parts: bedside swallowing evaluation, instrumental swallowing evaluation, and additional studies. The management of swallowing disorders requires a multidisciplinary team approach, depending on the child's age, cognitive and physical abilities, and the specific swallowing and feeding disorder, ensuring adequate and safe nutrition and improving the patient's quality of life.

Alterations in the Rectal Sensitivity of Children With Chronic Constipation Evaluated by High-Resolution Anorectal Manometry.

Introduction Constipation is one of the most frequent chronic disorders in children and is almost always of functional etiology. Manometric alterations in anorectal sensitivity in children with chronic constipation are described in the literature; nevertheless, the impact of the duration of constipation on the parameters of anorectal manometry sensitivity is unknown. Objective To compare the parameters of sensitivity of high-resolution anorectal manometry (first sensation, threshold volume for urgency, and maximal tolerability) in children with chronic constipation, related to the time of evolution from the beginning of the symptoms. Methods This was a retrospective observational analytic study. The data of 39 children with functional constipation who were subjected to high-resolution anorectal manometry were included to evaluate constipation. The patients were divided into three groups according to the duration of constipation: <1 year; from 1 to 2 years; and >2 years. The parameters of sensitivity of the anorectal manometry were compared between the three groups and correlation tests were performed with the duration in months from the beginning of the symptoms of constipation. Results There was no difference between the sensitivity parameters of high-resolution anorectal manometry of the three groups; no correlation of these parameters with the time of evolution of the symptoms was found. Conclusions Alterations in the anorectal distensibility could develop early in the course of the disease, even from the first year of the beginning of the symptoms.

[Liver and colonic manifestation of active chronic infection by Epstein Barr virus]. / Manifestación hepática y colónica de la infección crónica activa por virus de Epstein Barr.

INTRODUCTION: Chronic active Epstein Barr virus infection (CAEBV) is a rare condition, where the body is unable to counteract Epstein Barr viral replication (EBV), leading the patient to a chronic state with variable symptoms. Early recognition of infrequent or atypical clinical manifestations is relevant due to the particularities of their management and prognosis. OBJECTIVE: to describe a case of CAEBV manifes ted with colitis and hepatitis, summarizing the clinical-pathological and endoscopic characteristics and their evolution. CLINICAL CASE: A 6-year-old girl, previously healthy, presented recurrent episodes of jaundice, hepatosplenomegaly, and fever. EBV hepatitis was diagnosed with a blood viral load of 328,000 copies / mL. Her liver biopsy revealed Epstein-Barr virus-encoded small RNAs (EBER). She evolved with mucosanguineous diarrhea and weight loss; the colonoscopy showed loss of the haustral pattern, multiple aphthous ulcers covered with fibrin, and 7 million copies of EBV / gram of tissue were found in the colon. T-cell lineage infection was identified, therefore Rituximab was started, with a decrease in viral load, complete resolution of diarrhea, and improvement in liver function tests. The definitive treatment was bone marrow transplantation. CONCLUSIONS: CAEBV is a serious disor der, little documented, and should be considered in the face of a prolonged or intermittent course of hepatitis, accompanied by general and gastrointestinal manifestations such as chronic diarrhea, hematochezia, and weight loss, since its outcome without treatment can be fatal.

Nutritional benefits in pediatric patients with percutaneous endoscopic gastrostomy placement.

Gastrostomy is an enteral nutrition option. Indications for its placement are diverse, among them, the alteration in the mechanics of swallowing, frequently present in patients with neurological diseases. Nutritional recovery is the objective in these patients evaluating the nutritional status after the placement of a PEG in the pediatric population. This is a retrospective cohort conducted to evaluate nutritional recovery in pediatric patients with PEG placement. It was performed using anthropometric and biochemical parameters before and after placement. Forty-seven subjects were included, from which weight, height, and upper arm circumference were obtained, to evaluate nutritional recovery using BMI or W/L according to age. Significant nutritional improvement was demonstrated in a population of 39 patients, who had a mean follow-up of 7 months. In our population, PEG is an enteral nutrition strategy that has a significant positive impact on nutritional status in a mean of 7 months after its placement. Therefore, considering the evolution time of these patients will guide the clinician in making decisions regarding surveillance and monitoring parameters of the nutritional status.

Low Mean Nocturnal Baseline Impedance is Associated With a Pathological Acid Exposure Time in Children.

BACKGROUND: The baseline impedance (BI) and the mean nocturnal baseline impedance (MNBI) serve as markers of mucosal integrity in patients with pathologic acid exposure time (AET). This work aims to investigate the association between the BI and MNBI with the AET in children. METHODOLOGY: A retrospective study was performed in children ≤18 years old with suspicion of gastroesophageal reflux disease who underwent both endoscopy and pH-impedance monitoring (pH-MII). Esophagitis was graded according to the Los Angeles classification. The pathological AET was determined depending on the age (≥5% in patients >1 year and ≥10% in those ages ≤1 year). For the BI, 60 s measurements were taken every 4 h, and for the MNBI, 3 10 min measurements were taken between 1.00 and 3:00 am; then, they were averaged. The means of BI and MNBI were compared with each other, with the AET, and other variables. RESULTS: Sixty-eight patients were included, 25% of patients presented pathological AET. The mean of the MNBI was higher than BI in channels 6 (2195 vs 1997 Ω, P = 0.011) and 5 (2393 vs 2228 Ω, P = 0.013). BI and MNBI at channel 6 were lower in patients with pathological AET than in those with normal AET (1573 vs 2138 Ω, P = 0.007) and (1592 vs 2396 Ω, P = 0.004), respectively. CONCLUSIONS: Children with pathological AET had lower impedance values than those with normal AET. BI and MNBI measurements should be part of the routine MII-pH assessment in children.

[Hyponatremia in children with liver cirrhosis: Treatment strategies]. / Hiponatremia en niños con cirrosis hepática: Estrategias de tratamiento.

Hyponatremia is a common hydroelectrolytic disorder in pediatric patients with advanced cirrhosis. This complication is related to the alteration in the renal capacity to eliminate free water with solutes such as sodium, which leads to disproportionate water retention, a condition known as dilutional hyponatremia. The main pathogenic factors are the non-osmotic secretion of antidiuretic hormone and the activation of the renin-angiotensin-aldosterone axis and the sympathetic nervous system. Given that hyponatremia in cirrhosis is associated with an increase in morbidity and mortality, the objective of this review is to propose a systematic approach, based on the level of serum sodium, assessment of hemodynamic status and diuresis, which allows precise modifications that minimize negative impacts on survival and neurological sequelae.

Validez del hallazgo de nódulos en la colonoscopia para el diagnóstico de hiperplasia nodular linfoide en niños / Validity of nodules detected at colonoscopy for the diagnosis of nodular lymphoid hyperplasia in children

Resumen Introducción: la hiperplasia nodular linfoide del colon se define como > 10 nódulos linfoides visibles en colonoscopia. No existen estudios de su validez al compararlo con la histopatología. Objetivos: determinar la validez del hallazgo de nódulos en colonoscopia para el diagnóstico de hiperplasia nodular linfoide. Material y métodos: estudio prospectivo de prueba diagnóstica. Se incluyeron colonoscopias realizadas consecutivamente de 2014 al 2018 con equipos Olympus PCFQ150AI y GIFXP150N con obtención de biopsias. El criterio endoscópico fue la presencia de > 10 nódulos de 2 a 10 mm y el criterio histológico fue hiperplasia de folículos linfoides y mantos de linfocitos en lámina propia o submucosa. Los datos se analizaron en Epidat3.1. Se obtuvo la sensibilidad (S), especificidad (E), valor predictivo positivo (VPP) y negativo (VPN), y coeficientes de probabilidad positivo (LR+) y negativo (LR-) con sus intervalos de confianza. Resultados: se incluyeron 327 colonoscopias, la mediana de edad fue de 84 meses. La principal indicación para la colonoscopia fue sangrado digestivo bajo (38,8%). El hallazgo de nódulos se encontró en el 21% y el sitio de mayor frecuencia fue el colon total (46%), mientras que por histopatología se encontró hiperplasia nodular linfoide en el 38%. El hallazgo de nódulos obtuvo una S de 32% (intervalo de confianza [IC] del 95%: 24-140), E de 84% (IC 95%: 79-89), VPP de 56% (IC 95%: 44-68), VPN de 67% (IC 95%: 61-72), LR+ de 2,04 (IC 95%: 1,4-3) y LR- de 0,8 (IC 95%: 0,8-0,9). Conclusiones: la validez diagnóstica del hallazgo de nódulos en colonoscopia para hiperplasia nodular linfoide es pobre, por lo que la toma de biopsia debe recomendarse siempre.

Abstract Introduction: Nodular lymphoid hyperplasia of the colon is characterized by the presence of >10 lymphoid nodules visible in colonoscopy. There are no studies that confirm their validity when compared with histopathology. Objective: To determine the validity of nodules detected at colonoscopy for the diagnosis of nodular lymphoid hyperplasia in children. Materials and methods: Prospective study of diagnostic test accuracy. Colonoscopies performed consecutively from 2014 to 2018 using Olympus PCFQ150AI and GIFXP150N biopsy machines were included. The endoscopic criterion was the presence of >10 nodules from 2 to 10mm of diameter, while the histological criterion was presence of follicular lymphoid hyperplasia and lymphocyte mantles in lamina propia or submucosa. Data were analyzed in Epidat3.1. Sensitivity (SE), specificity (SP), positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR+) and negative likelihood ratio (LR-) were obtained with their corresponding confidence intervals. Results: 327 colonoscopies were included; the median age was 84 months. The main indication for colonoscopy was lower gastrointestinal bleeding (38.8%). Nodules were found in 21% of the patients, predominantly throughout the whole colon (46%), whereas histopathology found nodular lymphoid hyperplasia in 38%. SE for the finding of nodules was 32% (95% confidence interval [CI]: 24-140), SP was 84% (95% CI: 79-89), PPV was 56% (95% CI: 44-68), NPV was 67% (95% CI: 61-72), LR+ was 2.04 (95% CI: 1.4-3) and LR- was 0.8 (95% CI: 0.8-0.9). Conclusions: The validity of the presence of nodules on colonoscopy for the diagnosis of nodular lymphoid hyperplasia is poor, so biopsy should always be performed.

Differential Cytokine Expression in the Duodenum and Rectum of Children with Non-Immunoglobulin E-Mediated Cow's Milk Protein Allergy.

BACKGROUND: Cow's milk protein allergy (CMPA) is the most prevalent food allergy in children, and its pathogenesis remains poorly understood. It has been shown that the combination of genetic predisposition, perinatal factors, and intestinal imbalance of the immune response mediated by cytokines may play an essential role in CMPA pathogenesis. AIM: To characterize the gene expression of Th1, Th2, and Th17 cytokines in the duodenum and rectum in patients with CMPA. METHODS: This is an observational, descriptive, cross-sectional, prospective study. We used specific IgE (ImmunoCAP®) in serum and biopsies from the rectum and duodenum for the detection of cytokine messenger RNA levels by real-time PCR in patients with a positive oral food challenge for CMPA. We analyzed the relative quantification of the gene expression of cytokines by real-time PCR, and we used the housekeeping gene GAPDH for normalization purposes. RESULTS: Thirty children (13 male and 17 female) were evaluated. All patients had an open challenge for CMPA. IgE specific to casein, alfa-lactalbumin, and beta-lactoglobulin was negative in all patients. In terms of cytokine levels, the levels of TNFα, IL-6, IL-12 (Th1), IL-4, IL-10, IL-13 (Th2), and IL-17 were found to be higher in the rectum than in the duodenum (p < 0.05). IL-15 was found to be higher in the duodenum than in the rectum (p < 0.05). CONCLUSIONS: In the present study we observed that the immune response in CMPA seems to be mediated by a Th1, Th2, and Th17 cytokine profile, with the rectum being the main affected site.

Dyspepsia in children: organic or functional? Experience in a tertiary care hospital.

INTRODUCTION: Dyspepsia comprises a group of symptoms that can have organic or functional origin. The purpose of this study was to describe the main causes of dyspepsia and its clinical evolution in children cared for in a tertiary care hospital. MATERIAL AND METHODS: Retrospective study in children with dyspepsia. Patients underwent endoscopy with biopsy and rapid urease test to detect the presence of Helicobacter pylori. In case of normal endoscopy and biopsy, hydrogen breath test was performed. In all cases, follow-up was provided in order to evaluate symptom improvement. RESULTS: One hundred children were included, out of whom 52 were girls; mean age was 8.59 years. Esophagitis or erosive gastropathy were found in 54% of the cases (n = 54), H. pylori infection in 12% (n = 12), small intestinal bacterial overgrowth in 12% (n = 12), and functional dyspepsia in 20% (n = 20). CONCLUSION: In children with dyspepsia, organic causes should first be ruled out before dyspepsia being characterized as functional. In general terms, we consider that a stepped approach that includes endoscopy with biopsy, search for H. pylori and hydrogen breath test is necessary.

INTRODUCCIÓN: La dispepsia consiste en un conjunto de síntomas que pueden tener origen orgánico o funcional. El objetivo de este estudio fue describir las principales causas de la dispepsia y su evolución clínica en niños en un hospital de tercer nivel. MATERIAL Y MÉTODOS: Estudio retrospectivo en niños con dispepsia. Los pacientes fueron sometidos a endoscopia con toma de biopsia y prueba de urea rápida para Helicobacter pylori. En caso de endoscopia y biopsia normal, se tomó prueba de hidrogeniones en aliento. En todos los casos se dio seguimiento para evaluar la mejoría de síntomas. RESULTADOS: Se incluyeron 100 niños, de los cuales 52 eran niñas; la edad media fue de 8.59 años. Se encontró esofagitis y gastropatía erosiva en el 54% de los casos (n = 54), infección por H. pylori en el 12% (n = 12), sobrecrecimiento bacteriano del intestino delgado en el 12% (n = 12) y dispepsia funcional en el 20% (n = 20). CONCLUSIÓN: En niños con dispepsia se deben de descartar primero causas orgánicas antes de diagnosticar dispepsia funcional. En términos generales consideramos que es necesario un abordaje escalonado que incluya endoscopia con toma de biopsia, búsqueda de H. pylori y una prueba de hidrogeniones.

Lactobacillus acidophilus LB: a useful pharmabiotic for the treatment of digestive disorders.

Dysbiosis, a loss of balance between resident bacterial communities and their host, is associated with multiple diseases, including inflammatory bowel diseases (nonspecific chronic ulcerative colitis and Crohn's disease), and digestive functional disorders. Probiotics, prebiotics, synbiotic organisms and, more recently, pharmabiotics, have been shown to modulate the human microbiota. In this review, we provide an overview of the key concepts relating to probiotics, prebiotics, synbiotic organisms, and pharmabiotics, with a focus on available clinical evidence regarding the specific use of a unique pharmabiotic, the strain Lactobacillus acidophilus LB (Lactobacillus boucardii), for the management of gastrointestinal disorders. Since it does not contain living organisms, the administration of L. acidophilus LB is effective and safe as an adjuvant in the treatment of acute diarrhea, chronic diarrhea, and antibiotic-associated diarrhea, even in the presence of immunosuppression.

Esophageal motility disorders in children with dysphagia: the utility of the Chicago classification

BACKGROUND: esophageal manometry is the standard criterion for the evaluation of dysphagia and the diagnosis of a primary motor disorder of the esophagus in adults and children. AIMS: to describe the diagnosis according to the Chicago classification (CC) v3.0 in children with dysphagia, in whom an esophageal motility disorder was documented. The associated comorbidities were also determined. METHODS: an observational retrospective study was performed of 54 patients evaluated for dysphagia, who had undergone a high-resolution manometry (HREM). RESULTS: a normal HREM was found in 52 % (n = 28) of the children, whereas 48 % (n = 26) had some esophageal motility disorder. The most frequent diagnosis was ineffective esophageal motility and achalasia. Excluding previously healthy children, most children had a history of autoimmune disease and intellectual disability. CONCLUSIONS: an esophageal motor disorder can be diagnosed in nearly half of infants and children with dysphagia. In this study, all esophageal diseases could be classified according to the CC v3.0. HREM should be considered for the evaluation of children with dysphagia, in addition to other studies

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Esophageal motility disorders in children with dysphagia: the utility of the Chicago classification.

BACKGROUND: esophageal manometry is the standard criterion for the evaluation of dysphagia and the diagnosis of a primary motor disorder of the esophagus in adults and children. AIMS: to describe the diagnosis according to the Chicago classification (CC) v3.0 in children with dysphagia, in whom an esophageal motility disorder was documented. The associated comorbidities were also determined. METHODS: an observational retrospective study was performed of 54 patients evaluated for dysphagia, who had undergone a high-resolution manometry (HREM). RESULTS: a normal HREM was found in 52 % (n = 28) of the children, whereas 48 % (n = 26) had some esophageal motility disorder. The most frequent diagnosis was ineffective esophageal motility and achalasia. Excluding previously healthy children, most children had a history of autoimmune disease and intellectual disability. CONCLUSIONS: an esophageal motor disorder can be diagnosed in nearly half of infants and children with dysphagia. In this study, all esophageal diseases could be classified according to the CC v3.0. HREM should be considered for the evaluation of children with dysphagia, in addition to other studies.

Small intestinal bacterial overgrowth: could it be associated with chronic abdominal pain in children with allergic diseases?

Background and aims: small intestinal bacterial overgrowth (SIBO) is a well-known cause of chronic abdominal pain (CAP) during the pediatric age. On the other hand, children with a history of some allergic disorder present CAP more frequently. The aim of this study was to determine the association between the presence of allergic diseases and SIBO in patients diagnosed with CAP. Materials and methods: this was an observational, analytical, retrospective study. Children with CAP who had undergone a lactulose hydrogen breath test to determine the presence of SIBO were included in the study. All patients underwent an evaluation for allergies by means of a skin prick test or the determination of specific IgE, according to clinical diagnosis. The study groups were established according to the presence of SIBO and the results of the allergic evaluation were statistically compared between the groups. Results: seventy patients were included (41 females and 29 males) and SIBO was diagnosed in 35 patients. In addition, 71.4% of children with SIBO were found to have an allergic disease, in contrast with 28.6% of children without SIBO (p = 0.001). The odds ratio for having any type of allergy in patients with SIBO was 5.45 (95% CI, 1.96-15.17; p = 0.001). Conclusions: we found an association between SIBO and allergic disease, especially allergic rhinitis, cow's milk protein allergy and asthma. Thus, SIBO should be ruled out in pediatric patients with CAP and allergic disease

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Small intestinal bacterial overgrowth: could it be associated with chronic abdominal pain in children with allergic diseases?

BACKGROUND AND AIMS: small intestinal bacterial overgrowth (SIBO) is a well-known cause of chronic abdominal pain (CAP) during the pediatric age. On the other hand, children with a history of some allergic disorder present CAP more frequently. The aim of this study was to determine the association between the presence of allergic diseases and SIBO in patients diagnosed with CAP. MATERIALS AND METHODS: this was an observational, analytical, retrospective study. Children with CAP who had undergone a lactulose hydrogen breath test to determine the presence of SIBO were included in the study. All patients underwent an evaluation for allergies by means of a skin prick test or the determination of specific IgE, according to clinical diagnosis. The study groups were established according to the presence of SIBO and the results of the allergic evaluation were statistically compared between the groups. RESULTS: seventy patients were included (41 females and 29 males) and SIBO was diagnosed in 35 patients. In addition, 71.4% of children with SIBO were found to have an allergic disease, in contrast with 28.6% of children without SIBO (p = 0.001). The odds ratio for having any type of allergy in patients with SIBO was 5.45 (95% CI, 1.96-15.17; p = 0.001). CONCLUSIONS: we found an association between SIBO and allergic disease, especially allergic rhinitis, cow's milk protein allergy and asthma. Thus, SIBO should be ruled out in pediatric patients with CAP and allergic disease.

Blastocystis Hominis and Chronic Abdominal Pain in Children: Is there an Association between Them?

Chronic abdominal pain has many etiologies, one of them being parasites. The aim of this study was to find an association between chronic abdominal pain in children and Blastocystis hominis (Bh). Clinical files of patients with Bh and functional abdominal pain were reviewed. A comparison was made between patients who showed an improvement of their symptoms and those who did not. Out of the 138 patients who had functional abdominal pain and Bh, 37 patients did not receive any treatment (26.8%), while 101 received it and were treated with different antimicrobial agents (73.2%); regarding the improvement of symptoms, a statistically significant difference (p < 0.001) was observed. Chronic abdominal pain in children has different etiologies; however, we have documented through this work that it is appropriate to provide antimicrobial treatment for patients with Bh and chronic abdominal pain.

Cirrosis biliar secundaria a obstrucción de la vía biliar por pólipos hamartomatosos en una paciente con síndrome de Peutz-Jeghers. Reporte de Caso / Biliary cirrhosis secondary to bile duct obstruction by hamartomatous polyps in a patient with Peutz-Jeghers syndrome. Case Report

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