Is the Pediatric Eosinophilic Esophagitis Symptom Score v2.0 reliable for telemedicine?

BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease. Telemedicine is a healthcare technology used when a patient is separated by distance. The reliability of the Pediatric Eosinophilic Esophagitis Symptom Score, version 2.0 (PEESS v2.0) for telemedicine applications, has not been studied yet. Therefore, we aimed to evaluate the reliability of PEESS v2.0 for telemedicine. METHODS: We sent a telesurvey using questionnaires via electronic telecommunication as the telemedicine method. Children with EoE and their parents were asked to complete PEESS v2.0 with the telesurvey method (unsynchronized with the physician) and attend in-person visits one week apart. Intraclass correlation (ICC), Wilcoxon, and Bland-Altman tests were used as reliability analyses. Reliability was defined as a strong agreement between the measurements in ICC ≥ 0.8 and a p-value of ≤0.05 and no statistically significant difference between the scores of the two methods in the Wilcoxon and Bland-Altman analyses, i.e. a p-value of >0.05. RESULTS: The total scores of children and parents were higher in in-person visits than in the telesurvey (Wilcoxon tests, p ≤ 0.05). Bland- Altman analysis showed that the mean difference in total scores between the two methods was significant for both children and parents (p ≤ 0.05). ICC levels for the children and parent scores for the entire group ranged from 0.595 to 0.763 (moderate agreement). DISCUSSION: Unsynchronized telesurvey use of PEESS v2.0 is unreliable both for children and parents. We suggest testing the reliability of chosen telemedicine methods before using them in clinical and research practice.

Portal Hypertension in Children: A Tertiary Center Experience in Turkey.

Purpose: Portal hypertension (PH) and its complications have a significant impact on morbidity and mortality. This study aimed to evaluate the etiology; clinical, laboratory, and endoscopic findings; treatment approaches; long-term outcomes; and prognosis of pediatric PH. Methods: This retrospective study included 222 pediatric patients diagnosed with PH between 1998 and 2016, and data encompassing clinical, laboratory, and radiological features; treatments; and complications were analyzed. Results: The most common causes of PH were portal vein thrombosis (20.3%), progressive familial intrahepatic cholestasis (18.9%), and biliary atresia (12.2%). Among the enrolled patients, 131 (59.0%) were included in the cirrhotic group and 91 (41.0%) in the non-cirrhotic group. Hepatomegaly and increased transaminase levels were more frequent in the cirrhotic group than in the non-cirrhotic group. Additionally, portal gastropathy, esophageal varices, and variceal bleeding were more frequent in the non-cirrhotic group, whereas ascites, hepatopulmonary syndrome and hepatic encephalopathy were more common in the cirrhotic group. The incidence of hepatomegaly was higher in the presinusoidal group than in the prehepatic group (p<0.001). Hyperbilirubinemia was more frequent in the prehepatic group (p=0.046). The frequency of esophageal varices was similar between the prehepatic and presinusoidal groups; however, variceal bleeding was more frequent in the prehepatic group (p=0.002). Conclusion: Extrahepatic portal vein obstruction, genetic-metabolic diseases, and biliary atresia were the most prevalent causes of PH in our country. In patients with PH, hepatomegaly, increased transaminase levels, and synthesis dysfunction were suggestive of cirrhotic PH. Notably, PH in patients without cirrhosis might be more severe than that in those with cirrhosis.

Food-induced immediate response of the esophagus in pediatric eosinophilic esophagitis.

BACKGROUND: Food-induced immediate response of the esophagus (FIRE) is a new phenomenon that has been described in eosinophilic esophagitis (EoE) patients. It is suspected when unpleasant symptoms occur suddenly on contact of the triggering food with the esophageal surface and recur with repeated exposures. It can often be mistaken for pollen-food allergy syndrome (PFAS) and solid food dysphagia. Data on FIRE is limited to one survey study and case reports, and there are no screening studies conducted on either adults or children with EoE. In this study, we aimed to screen children aged ≥7 years old with EoE for FIRE. METHODS: Demographic data were collected from medical records. A questionnaire about FIRE was applied to all participants. Skin prick tests were done on suspected patients to identify the triggering foods. FIRE is defined as suitable clinical symptoms with suspected food allergen exposure. RESULTS: A total of 78 patients (74.4% male, median age: 13.5 years) were included. Unpleasant and recurrent symptoms distinct from dysphagia with specific foods were reported in 16.7% of the patients, all of whom had concomitant allergic rhinitis (AR). The symptoms described by almost all patients were oropharyngeal itching and tingling (PFAS: 15.3%) excluding only one patient reporting retrosternal narrowing and pressure after specific food consumption (FIRE: 1.2%). CONCLUSIONS: Although definitive conclusions regarding the true prevalence of FIRE cannot be made, it does not seem to be common as PFAS. However, it deserves questioning particularly in the presence of concurrent AR and/or PFAS in children with EoE.

A novel pediatric Eosinophilic Esophagitis Symptoms and Adaptive Behavior Scale for different ages: GaziESAS v2.0.

BACKGROUND: High-quality scales (HQS) suitable that measure symptoms and adaptive behaviors (AB) with proven validity and reliability are needed for different age groups of children with eosinophilic esophagitis (EoE). OBJECTIVE: To develop a high-quality pediatric EoE symptoms and AB scale for different age groups. METHODS: Children (7-11 years), teens (12-18 years), and parents of 2-18-year-old children with EoE were included. A HQS should have encompassed: the identification of domain and item generation; content validity (CnV) and field test for construct validity (CsV) and reliability. Convergent validity (CgV) was examined for CsV. Correlations between the Pediatric Eosinophilic Esophagitis Symptom Score, version 2.0 (PEESS v2.0) and Gazi University Eosinophilic Esophagitis Symptoms and Adaptive Behavior Scale (GaziESAS) version 2.0 (v2.0) were examined for CgV. Reliability was determined through internal consistency (Cronbach-α) and test-retest reliability (intraclass correlation coefficients: ICC). RESULTS: Nineteen children, 42 teens, and 82 parents completed the study. GaziESAS v2.0 was composed of 20 items with two main domains: symptoms (subdomains: dysphagia and nondysphagia) and AB. CnV indexes were excellent for all items. The CgV varied from good to excellent correlation (r = 0.6 to r = 0.9). GaziESAS v2.0 showed good reliability (Cronbach-α >0.7 and ICC >0.6). CONCLUSION: GaziESAS v2.0 is the first pediatric HQS that measures the frequency of symptoms and AB in EoE within the last month with separate forms for children, teens, and parents.

Oropharyngeal Dysphagia in Children with Eosinophilic Esophagitis.

Dysphagia is the most troublesome symptom of eosinophilic esophagitis (EoE). This study aimed to investigate oropharyngeal dysphagia in children with EoE and possible related factors. Children with a definite diagnosis of EoE were included in the study. Medical and feeding histories were recorded. A disease control level was determined for each child. An oral structure examination, the Turkish version of the Mastication and Observation Evaluation (T-MOE), the Pediatric version of the Eating Assessment Tool-10 (PEDI-EAT-10) and the 3-oz water swallow test were applied in screening for oropharyngeal dysphagia. Fifty-two children participated in the study. Oropharyngeal dysphagia took the form of abnormal swallowing (PEDI-EAT-10 score ≥ 4) and increased aspiration risk (PEDI- EAT-10 score ≥ 13) in 51.9% and 25.0% of the children, respectively. Seven children failed the 3-oz water swallow test. Abnormal swallowing and aspiration risk were significantly higher in children with prolonged mealtimes, impaired chewing function, and uncontrolled disease (p < 0.05). Chewing function was the most important risk factor for abnormal swallowing and increased aspiration (R2 = 0.36, R2 = 0.52, p < 0.001, respectively). Oropharyngeal dysphagia is common in children with EoE and associated with increased aspiration risk in a subpopulation. Uncontrolled disease, prolonged mealtimes, and impaired chewing function may provide clues for oropharyngeal dysphagia in EoE.

Long-Term Outcomes of Patients With Progressive Familial Intrahepatic Cholestasis After Biliary Diversion.

OBJECTIVES: Progressive familial intrahepatic cholestasis is a heterogeneous group of genetic disorders characterized by disrupted bile homeostasis. Patients with this disease typically present with cholestasis and pruritus early in life and often progress to end-stage liver disease. The clinical symptoms that patients with progressive familial intrahepatic cholestasis encounter are usually refractory to medical treatment. Although the effects of biliary diversion surgery on native liver survival are not exactly known, this procedure may provide a positive impact on pruritus and laboratory parameters in these patients. MATERIALS AND METHODS: We retrospectively evaluated the clinical and laboratory characteristics of patients with progressive familial intrahepatic cholestasis who underwent partial external biliary diversion between 2002 and 2020 at our center. Diagnosis of progressive familial intrahepatic cholestasis was made by clinical, biochemical, and histopathological characteristics as well as genetic testing. RESULTS: Nine patients were included in the study. Five patients required liver transplant during follow-up, with 4 having liver transplant as a result of endstage liver disease (median interval of 5 years). In 1 patient, partial external biliary diversion was performed 1.5 years after liver transplant for severe diarrhea, metabolic acidosis, and hepatic steatosis. Four patients did not require liver transplant during follow-up (median follow-up time of 7.6 years). Pruritus responded well to partial external biliary diversion in all patients. Among laboratory values evaluated 6 months after biliary diversion, only albumin showed significant improvement. CONCLUSIONS: Partial external biliary diversion had favorable results on long-term follow-up. This procedure can provide the relief of pruritus and delay the requirement for liver transplant in patients with progressive familial intrahepatic cholestasis. In our view, partial external biliary diversion should be considered the first-line surgical management for patients with this disease.

Partial External Biliary Diversion for Severe Diarrhea After Liver Transplant in Patients with Progressive Familial Intrahepatic Cholestasis Type 1.

Progressive familial intrahepatic cholestasis is a heterogeneous group of autosomal recessive disorders, and liver transplant is the only curative treatment. A biliary diversion operation for disruption of enterohepatic circulation in patients with progressive familial intrahepatic cholestasis type 1 without cirrhosis is another option. We present a pediatric patient with progressive familial intrahepatic cholestasis type 1 who underwent liver transplant due to end-stage liver disease. After transplant, diarrhea and growth retardation complications resolved after partial external biliary diversion surgery.

Two Cases With Neonatal Cholestasis and Renal Disorders Due to DCDC2 Mutation.

Ciliopathies are a heterogeneous group of diseases that are observed after deterioration of the ciliary structures on the cell surface that facilitate communication with the environment. Both liver and kidney involvement are frequently observed in this disease. Recently, a doublecortin domain containing protein 2 (DCDC2) mutation in a ciliopathy disease group was identified. Here, we present 2 patients with this mutation and with neonatal cholestasis and renal involvement.

Nutritional characteristic of children with inflammatory bowel disease in the nationwide inflammatory bowel disease registry from the Mediterranean region.

BACKGROUND/OBJECTIVES: We analyzed the nationwide pediatric inflammatory bowel disease (PIBD) registry (1998-2016), to evaluate the nutritional status at the time of diagnosis. SUBJECTS/METHODS: Nine types of nutritional status by the combination of weight-for-length (<2 years)/body mass index (>2 years) and length/height-for-age with three categories (<-2, -2 to 2, and >2 SD) were described. Malnutrition was defined by WHO criteria. Univariate and multivariate regression analysis was used to identify risk factors for malnutrition. RESULTS: In total, 824 IBD patients (498 Ulcerative colitis (UC); 289 Crohn's Disease (CD); 37 Indeterminate Colitis (IC); 412 male; the median age 12.5 years) were eligible. The prevalence of eutrophy, wasting/thinness, stunting, overweight, tall stature, concurrent wasting/thinness and stunting, tall stature with overweight, tall stature with wasting/thinness, and short stature with overweight were 67.4%, 14.9%, 6.6%, 3.1%, 3.2%, 3.3%, 1.1%, 0.4%, and 0.1%, respectively. The prevalence of malnutrition was 32.7%, indicating a higher prevalence in CD (p < 0.001). Incidence of overweight was less common in the CD than UC and IC (p < 0.001). Multivariate analysis revealed that age of onset (>10 years), prepubertal stage, severe disease activity, perianal involvement, and high C reactive protein level were independently associated with malnutrition in pediatric IBD. CONCLUSION: We showed the frequency of nutritional impairment in PIBD. The percentage of overweight subjects was lower than the other studies. The age of onset, disease activity, CRP level, perianal involvement, and pubertal stage were associated with a higher risk for developing malnutrition. Our results also confirmed that CD patients are particularly vulnerable to nutritional impairment. CLINICAL TRIAL NUMBER: ClinicalTrials.gov Identifier: NCT04457518.

Expected or unexpected clinical findings in liver glycogen storage disease type IX: distinct clinical and molecular variability.

OBJECTIVES: To reveal the different clinical presentations of liver glycogen storage disease type IX (GSD IX), which is a clinically and genetically heterogeneous type of glycogenosis. METHODS: The data from the electronic hospital records of 25 patients diagnosed with liver GSD IX was reviewed. Symptoms, clinical findings, and laboratory and molecular analysis were assessed. RESULTS: Of the patients, 10 had complaints of short stature in the initial presentation additionally other clinical findings. Elevated serum transaminases were found in 20 patients, and hepatomegaly was found in 22 patients. Interestingly, three patients were referred due to neurodevelopmental delay and hypotonia, while one was referred for only autism. One patient who presented with neurodevelopmental delay developed hepatomegaly and elevated transaminases during the disease later on. Three of the patients had low hemoglobin A1C and fructosamine values that were near the lowest reference range. Two patients had left ventricular hypertrophy. Three patients developed osteopenia during follow-up, and one patient had osteoporosis after puberty. The most common gene variant, PHKA2, was observed in 16 patients, 10 variants were novel and six variants were defined before. Six patients had variants in PHKG2, two variants were not defined before and four variants were defined before. PHKB variants were found in three patients. One patient had two novel splice site mutations in trans position. It was revealed that one novel homozygous variant and one defined homozygous variant were found in PHKB. CONCLUSIONS: This study revealed that GSD IX may present with only hypotonia and neurodevelopmental delay without liver involvement in the early infantile period. It should be emphasized that although liver GSDIX is thought of as a benign disease, it might present with multisystemic involvement and patients should be screened with echocardiography, bone mineral densitometry, and psychometric evaluation.

Reliability and Validity Study of Turkish Version of Pediatric Eosinophilic Esophagitis Symptom Scores® (Tr-PEESS v2.0) Led to Development of a New Pediatric Eosinophilic Esophagitis Scale: GaziESAS.

BACKGROUND/AIMS: There has been no valid and reliable Turkish scale that measures symptoms in children with eosinohilic esophagitis (EoE). The aim of the study is test the validity and reliability of Turkish version of Pediatric Eosinophilic Esophagitis Symptom Scores® (Tr-PEESS v2.0) Materials and Methods: Relevant forms of Tr-PEESS v2.0 were applied to 2-18 years old children with EoE and to their parents. KINDL QoL patient and parent questionnaires and GaziESAS scale which was developed in this study were used to test convergent validity of Tr-PEESS v2.0. Discriminant validity was evaluated among three EoE treatment groups: under treatment, off treatment due to remission and uncompliant with treatment. Reliability was evaluated by internal consistency, test-retest reliability, and item analysis. RESULTS: Fiftytwo children/teens (mean age 130.2±60.3 months) and 84 parents were interviewed twice one week apart. Mean duration of EoE was 47.2±35.6 months. Tr-PEESS v2.0 reports correlated with GaziESAS (range,0.361-0.855) and KINDL QoL questionnaires (range,-0.316-0.413). Parent report of Tr-PESS v2.0 discriminated children uncompliant with treatment from the ones off treatment and undertreatment. Cronbach's α values and intraclass correlation coeffcients (ICC) values of Tr-PEESS v2.0 ranged from 0.614 to 0. 895 and 0.646 to 0.910, respectively. CONCLUSION: Tr-PEESS v2.0 is a valid and reliable tool to use in Turkish children. GaziESAS is a new parent-proxy pediatric EoE scale with additional adaptive behaviour domain that passed scale developmental stages successfully for Turkish children with EoE.

Familial Mediterranean Fever Mutation Analysis in Pediatric Patients With Inflammatory Bowel Disease: A Multicenter Study.

BACKGROUND: The aim of the study was to evaluate familial Mediterranean fever (FMF) mutation analysis in pediatric patients with inflammatory bowel disease (IBD). The relation between MEFV mutations and chronic inflammatory diseases has been reported previously. METHODS: Children with IBD (334 ulcerative colitis (UC), 224 Crohn's disease (CD), 39 indeterminate colitis (IC)) were tested for FMF mutations in this multicenter study. The distribution of mutations according to disease type, histopathological findings, and disease activity indexes was determined. RESULTS: A total of 597 children (mean age: 10.8 ± 4.6 years, M/F: 1.05) with IBD were included in the study. In this study, 41.9% of the patients had FMF mutations. E148Q was the most common mutation in UC and CD, and M694V in IC (30.5%, 34.5%, 47.1%, respectively). There was a significant difference in terms of endoscopic and histopathological findings according to mutation types (homozygous/ heterozygous) in patients with UC (P < .05). There was a statistically significant difference between colonoscopy findings in patients with or without mutations (P = .031, P = .045, respectively). The patients with UC who had mutations had lower Pediatric Ulcerative Colitis Activity Index (PUCAI) scores than the patients without mutations (P = .007). CONCLUSION: Although FMF mutations are unrelated to CD patients, but observed in UC patients with low PUCAI scores, it was established that mutations do not have a high impact on inflammatory response and clinical outcome of the disease.

GIMAP5 maintains liver endothelial cell homeostasis and prevents portal hypertension.

Portal hypertension is a major contributor to decompensation and death from liver disease, a global health problem. Here, we demonstrate homozygous damaging mutations in GIMAP5, a small organellar GTPase, in four families with unexplained portal hypertension. We show that GIMAP5 is expressed in hepatic endothelial cells and that its loss in both humans and mice results in capillarization of liver sinusoidal endothelial cells (LSECs); this effect is also seen when GIMAP5 is selectively deleted in endothelial cells. Single-cell RNA-sequencing analysis in a GIMAP5-deficient mouse model reveals replacement of LSECs with capillarized endothelial cells, a reduction of macrovascular hepatic endothelial cells, and places GIMAP5 upstream of GATA4, a transcription factor required for LSEC specification. Thus, GIMAP5 is a critical regulator of liver endothelial cell homeostasis and, when absent, produces portal hypertension. These findings provide new insight into the pathogenesis of portal hypertension, a major contributor to morbidity and mortality from liver disease.

Deep mining of oxysterols and cholestenoic acids in human plasma and cerebrospinal fluid: Quantification using isotope dilution mass spectrometry.

Both plasma and cerebrospinal fluid (CSF) are rich in cholesterol and its metabolites. Here we describe in detail a methodology for the identification and quantification of multiple sterols including oxysterols and sterol-acids found in these fluids. The method is translatable to any laboratory with access to liquid chromatography - tandem mass spectrometry. The method exploits isotope-dilution mass spectrometry for absolute quantification of target metabolites. The method is applicable for semi-quantification of other sterols for which isotope labelled surrogates are not available and approximate quantification of partially identified sterols. Values are reported for non-esterified sterols in the absence of saponification and total sterols following saponification. In this way absolute quantification data is reported for 17 sterols in the NIST SRM 1950 plasma along with semi-quantitative data for 8 additional sterols and approximate quantification for one further sterol. In a pooled (CSF) sample used for internal quality control, absolute quantification was performed on 10 sterols, semi-quantification on 9 sterols and approximate quantification on a further three partially identified sterols. The value of the method is illustrated by confirming the sterol phenotype of a patient suffering from ACOX2 deficiency, a rare disorder of bile acid biosynthesis, and in a plasma sample from a patient suffering from cerebrotendinous xanthomatosis, where cholesterol 27-hydroxylase is deficient.

Broadly effective metabolic and immune recovery with C5 inhibition in CHAPLE disease.

Complement hyperactivation, angiopathic thrombosis and protein-losing enteropathy (CHAPLE disease) is a lethal disease caused by genetic loss of the complement regulatory protein CD55, leading to overactivation of complement and innate immunity together with immunodeficiency due to immunoglobulin wasting in the intestine. We report in vivo human data accumulated using the complement C5 inhibitor eculizumab for the medical treatment of patients with CHAPLE disease. We observed cessation of gastrointestinal pathology together with restoration of normal immunity and metabolism. We found that patients rapidly renormalized immunoglobulin concentrations and other serum proteins as revealed by aptamer profiling, re-established a healthy gut microbiome, discontinued immunoglobulin replacement and other treatments and exhibited catch-up growth. Thus, we show that blockade of C5 by eculizumab effectively re-establishes regulation of the innate immune complement system to substantially reduce the pathophysiological manifestations of CD55 deficiency in humans.

Primary Eosinophilic Gastrointestinal Diseases Beyond Eosinophilic Esophagitis in Children.

OBJECTIVES: There are many unknowns about primary eosinophilic gastrointestinal disease (EGID) in childhood. The aim of this study is to provide data about the frequency, management, control level, and prognosis of well documented primary EGID in childhood. METHODS: This study was conducted in children who underwent endoscopy and/or colonoscopy at a single center over 10-year period up to August 2018. Primary EGID was diagnosed after exclusion of secondary EGID and classified as eosinophilic gastritis (EG), eosinophilic enteritis (EE), eosinophilic gastroenteritis (EGE: eosinophilic gastritis with eosinophilic enteritis) and eosinophilic colitis (EC) according to histopathological evaluation. The pathological number of eosinophil counts were accepted as >30 hpf for gastric mucosa in 5 hpf area, ≥20/hpf for duodenal, jejunal, and ileal mucosa, >50/hpf for right colonic mucosa, >35/hpf for transverse colonic mucosa, and >25/hpf for left colonic mucosa. Presenting symptoms, signs, management, follow-up, disease control level, and remission were analyzed. Remission is defined if the patient is controlled with all clinical, endoscopic/colonoscopic, and histopathologic parameters without any treatments or diet for at least a year. RESULTS: During the study period, 7457 biopsies were taken in 8262 endoscopy and/or colonoscopy procedures. Primary and secondary EGID frequencies were found 0.23% (n = 17 patients) and 0.1% (n =8 patients) per procedure with biopsy in children, respectively. Endoscopy/colonoscopy procedures were not able to performed in 9 patients because of short follow-up period (n = 6) or patients leaving follow-up (n = 3). Nine of the primary EGID patients had esophageal eosinophilia (EsE) at the time of diagnosis, 5 of them were previously managed as EoE. The median follow-up period of primary EGID patients excluding the ones without a control endoscopy/colonoscopy procedure was 3.35 years (min-max: 1.1-9.0 years). Proton pump inhibitors (PPI) were the most frequently used treatment alone or in combination with diet, systemic and/or topical corticosteroids. Disease control was evaluated in 8 of 17 patients and it was uncontrolled in 4, partially controlled in 1, and controlled in 3 patients. Remission was achieved in 2 patients. CONCLUSIONS: The frequency of primary EGID beyond eosinophilic esophagitis (EoE) in children is low. It may be difficult to achieve control in children with primary EGID in the long-term follow-up.

Obstructive jaundice and severe pancreatitis due to the foramen of Winslow hernia with multiple anomalies.

Internal hernia through the foramen of Winslow is a very rare condition, especially in children. Here we report a 16-month-old girl who presented with obstructive jaundice and elevation of pancreatic enzymes and was ultimately diagnosed with internal hernia and malrotation by radiologic investigation and open approach surgery. To the best of our knowledge, obstructive jaundice with pancreatitis and other congenital abnormalities in children with the foramen of Winslow hernia have not been reported previously in the literature.

Portal Hypertensive Biliopathy as a Cause of Severe Cholestasis in Children With Congenital Hepatic Fibrosis.

Portal hypertensive biliopathy may occur in patients with noncirrhotic hepatic fibrosis. Portal hypertensive biliopathy treatment should be focused on management of portal hypertension and relief of biliary obstruction. In patients with noncirrhotic portal fibrosis and symptomatic portal hypertensive biliopathy, portal decompression surgery by proximal splenorenal shunt is one successful treatment option.