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Background: Variability in glucagon-like peptide (GLP)-1 and GLP-2 plasma concentrations has been suggested in Celiac disease (CD), with inconclusive results. We assessed the association between serum levels of GLP-1 and GLP-2 and their duodenal receptor expression in children with and without CD. Methods: This was a two-part, cross-sectional and prospective cohort study. Group assignment, performed after duodenal samples for mRNA expression of GLP-1 receptor (GLP1R) and GLP-2 receptor (GLP2R), were taken during esophagogastroduodenoscopy. The control group consisted of patients with normal endoscopy and negative serology. The CD group consisted of patients with positive serology and endoscopy suggestive of CD. All had an oral glucose-tolerance test (OGTT). CD patients underwent a second OGTT after 6 months of a gluten-free diet (GFD). Results: The CD group included 12 patients; 7 males with mean age 9.2 ± 2.5 years. The control group included 10 patients; 5 males with mean age 12 ± 4 years, (p = 0.14). No differences were detected in basal or peak levels of GLP-1 or GLP-2 between control, naïve CD (before GFD) and treated CD (after GFD) groups. Expression of GLP1R and GLP2R mRNA was similar. Significant positive correlations between glucose and C-peptide secretion (r = 0.9, p < 0.01) and GLP-1 and GLP-2 (r = 0.8, p = 0.01) were detected in the control group. Significant negative correlations were found in the naïve CD group between GLP2R expression and glucose secretion (r = −0.68, p = 0.015) and GLP1R expression and serum GLP-1 (r = −0.7, p = 0.016). Conclusions: Although no significant differences were detected in secretion patterns or gut receptor expression of GLP-1 and GLP-2 in healthy versus CD pediatric patients, the detected discrepancy between the ligand levels and their tissue receptors requires additional study.

Background The effect of the amount of transient cow's milk formula (CMF) consumed during the first days of life on IgE‐cow's milk allergy (IgE‐CMA) is unknown. Methods A cohort of 58 patients with IgE‐CMA was identified from a large scale population‐based study of 13,019 infants followed from birth. A group of 116 infants matched for sex and breastfeeding only duration (beyond the nursery period), and another random group of 259 healthy infants were used as controls. Parents were interviewed and the infants' medical records were searched to assess CMF consumption in the nursery. Results While 96% of the mothers of the 174 infants (58 with Cow's milk allergy and 116 controls) reported on exclusive breastfeeding during the stay in the nursery, CMF consumption was documented in 96 (55%) of the infants. Of those, most (57; 59%) received one to three feedings, 20 (21%) received four to nine feedings, and 19 (20%) received ≥10 feedings. Fewer formula feeds (1–3) were significantly more common in the allergic group than ≥4 feeds (p = 0.0003) and no feeds at all (p = 0.02) compared to controls (n = 116). Of those exclusively breastfed in the nursery, 13/23 allergic infants (57%) introduced CMF at age 105–194 days (the period with highest‐risk for IgE‐CMA) compared to 33/98 (34%) from the random control group (n = 259) (p = 0.04). Conclusions Most infants end up receiving few CMF feeds in the nursery. Transient CMF in the nursery is associated with increased risk of IgE‐CMA.

Objective. To assess the neuroradiological findings of children with congenital hypothyroidism (CHT) compared to healthy controls (HC). Patients and Methods. Thirty children with CHT, mean age 12.5 ± 1.6 years, 14 (44.8%) males, were compared with 38 HC mean age 11.7 ± 1.7 years, 16 (45.7%) males. Clinical data were collected from medical charts and questionnaires seeking information on family history, birth and perinatal period events, medications, and overall health history. Neurocognitive function was assessed for global intelligence, visual and verbal memory, and executive functioning using standardized tests. Neuroimaging was performed using 1.5 T magnetic resonance imaging and assessed by two pediatric radiologists. Results. Children with CHT had a similar proportion of incidental findings as did the children in the HC group, at 43.3% and 39.5%, respectively, P=0.69. Abnormalities of the sellar region were reported in 13.3% of CHT group and 7.9% of HC group, P=0.46. Other incidental findings included cerebellar ectopia, choroidal fissure and pineal cysts, and multiple increased signal intensity foci. Neuroradiological findings were not associated with clinical and neurocognitive abnormalities. Conclusion. Neuroimaging of children with CHT demonstrated a similar incidence of structural abnormalities as in the healthy population. There is no association between those findings and neurocognitive function.

BackgroundUse of a continuous glucose-monitoring system (CGMS) in the management of type 1 diabetes (T1D) may cause local skin irritation.ObjectiveTo examine the effects of fluticasone propionate aqueous nasal solution (nsFP), sprayed topically prior to CGMS insertion among youth with T1D.MethodsThis is a case series observational report, including real-life 6-month follow-up data from one pediatric diabetes center. All patients suffering from local skin irritation due to CGMS adhesives were offered prevention form skin irritation by spraying 2 puffs of nsFP on the skin area prior to adhesion of CGMS. Data were collected from their charts after 6 months. Outcome measures included the difference in degree of skin irritation, number of days of CGMS use, BMI SDS, mean glucose, and HbA1c, prior to use and during 6 months after use.ResultsTwelve patients used nsFP prior to CGMS insertion, mean age 8.6 ± 4.9 years and 66.7% males. Ten patients, median age 6.1 years (5.3–9.5) and 56% males, continued using nsFP for a mean of 0.56 ± 0.11 years, with no recurrence of local irritation nor dermatitis to same adhesive material. No differences were found before and after use of nsFP in CGMS mean glucose 180 mg/dl (153–202) versus 165 mg/dl (150–192). BMI SDS was slightly higher 0.44 (− 0.9–1.2) versus 0.25 (− 0.47–1.06), P = 0.05.ConclusionsThis small-scale, single-site description of a simple intervention by nsFP and favorable outcome provides valuable insight for a simple solution for skin irritation and dermatitis in the pediatric population with T1D.

AimsBillions of people have been under lockdown in an attempt to prevent COVID-19 spread. Lifestyle changes during lockdown could lead to deterioration of glycemic control in type 1 diabetes (T1D). We aimed to assess the impact of COVID-19 lockdown on the glycemic control of pediatric patients with T1D.MethodsThis observational real-life study from the AWeSoMe Group assessed continuous glucose monitoring (CGM) metrics of 102 T1D patients (52.9% males, mean age 11.2 ± 3.8 years, mean diabetes duration 4.2 ± 3.8 years) who used Dexcom G5. The data were accessed without any interface between patients, caregivers, and the diabetes team. Study variables from CGM metrics were: mean glucose level, time-in-range (TIR, 70–180 mg/dL; 3.9–10 mmol/L), hypoglycemia (< 54 mg/dL; < 3 mmol/L), hyperglycemia (> 250 mg/dL; > 13.3 mmol/L), coefficient of variation (CV), and time CGM active before and during lockdown. Delta-variable = lockdown variable minus before-lockdown variable.ResultsThe mean TIR was 60.9 ± 14.3% before lockdown, with no significant change during lockdown (delta-TIR was 0.9 ± 7.9%). TIR during lockdown was significantly correlated with TIR before lockdown (r = 0.855, P < 0.001). Patients with improved TIR (delta-TIR > 3%) were significantly older than patients with stable or worse TIR (P = 0.028). Children aged < 10 years had a significantly higher CV before lockdown and during lockdown than children aged ≥ 10 years (P = 0.02 and P = 0.005, respectively). Among children aged < 10 years, a multiple linear regression model revealed associations of age and lower socioeconomic cluster with delta-TIR (F = 4.416, P = 0.019) and with delta-mean glucose (F = 4.459, P = 0.018).ConclusionsCGM metrics in pediatric patients with T1D were relatively stable during a nationwide lockdown. Intervention plans should focus on younger patients with lower socioeconomic position.

The objective of this study was to assess the frequency of symptomatic urinary tract infections (UTIs) following voiding cystourethrography (VCUG) while using prophylactic antibiotics. Medical records of 421 patients who underwent a VCUG during a period of 4 years were reviewed. Three hundred forty-nine had a VCUG following a febrile UTI, and 72 had the test for evaluation of hydronephrosis. All received prophylactic antibiotics and were evaluated within 7-10 days following the VCUG. One hundred seventy-two children (41%) had an abnormal VCUG. Seven of 421 children (1.7%) had symptoms suggestive of UTI. Two had culture negative pyuria; one had Escherichia Coli UTI, and four had Pseudomonas aeruginosa UTI. On multivariate logistic regression analysis, the risk factors contributing to the development of UTI following VCUG were the presence of vesicoureteral reflux (VUR) and its severity (odds ratio [OR] 2.52; 95% confidence interval [CI] 2.24, 2.83, p =0.001; and OR 2.32; 95% CI 2.05,2.62, p =0.04, respectively). The incidence of VCUG-induced UTI in children receiving prophylactic antibiotic therapy is low. There is a relatively high rate of Pseudomonas UTI, especially in children with moderate to severe reflux. We recommend that children with symptoms suggesting a UTI following a VCUG should be treated for Pseudomonas aeruginosa pending culture results.

The aim of the study was to assess the epidemiology and risk factors of adrenal crises (AC) in children with adrenal insufficiency (AI). Children diagnosed with AI between 1990 and 2017 at four Israeli pediatric endocrinology units were studied. Demographic and clinical data were retrieved retrospectively from their files. The study population consisted of 120 children (73 boys, 47 girls) and comprised 904 patient years. Median age at diagnosis was 0.3 years (0–17.5). Thirty-one AC events in 26 children occurred during the study period, accounting for a frequency of 3.4 crises/100 patient years. Fifty-two percent of AC events occurred at presentation. The significant risk factors for developing AC were the following: younger age at diagnosis (P = 0.003), primary AI vs. secondary AI (P = 0.016), specific diagnosis of autoimmune AI, adrenal hypoplasia congenita and salt wasting congenital adrenal hyperplasia (P < 0.001), mineralocorticoid treatment (P < 0.001), and recurrent hospital admissions (P > 0.001). After applying a stepwise logistic regression model, only the group of diagnoses, including salt wasting CAH, AHC, and Addison’s disease, remained significant predictor of AC (OR 17.5, 95% CI 4.7–64.9, P < 0.001). There was no AC-associated mortality during the study period.Conclusions: Since significant percent of AC events occurred at presentation, measures to increase the awareness to signs and symptoms of AI among primary care physicians should be taken. Efforts to prevent AC should be focused on younger patients, especially those with primary AI.What Is Known:• Diagnosis and long-term management of pediatric patients with adrenal insufficiency (AI) remain a challenge.• Adrenal crises (AC) pose life-threatening emergencies in affected youngsters. Studies on the rate and risk factors of AC in children with AI are scarce, and they were done mainly on children with congenital adrenal hyperplasia (CAH).What Is New:• The rate of AC was relatively low and there was no AC-associated mortality during the study period.• Children with primary AI were at higher risk for AC than children with secondary AI. Specifically, children with salt wasting CAH, adrenal hypoplasia congenita, and Addison’s disease at the highest risk.

Purpose In recent years there has been a noticeable increase in the use of advanced hybrid closed-loop systems (AHCLs) for managing type 1 diabetes (T1D) among youth. However, there is a lack of comparison between the open-source automated insulin delivery (AID) system and the MiniMed™ 780 G system (780 G). Methods In this multi-center study, we retrospectively compared selected glycemic ranges of 26 individuals who used open-source AID and 20 individuals who used 780 G (age 11.3 years [IQR 9.3, 12.9] and 13.4 years [IQR 10.9, 16.5], respectively, p  = 0.069) from system initiation to the most recent visit. Results At baseline, the median HbA1c was significantly lower and the time below range (TBR) <54mg/dL was significantly higher in the open-source AID group compared to the 780 G group (6.8% [IQR 6.4, 7.1] vs. 7.4% [IQR 6.9, 8.6], p  = 0.006 and (1.0% [IQR 0.5, 2.8] vs. 0.0% [0.0, 1.0], p  = 0.014), respectively; the median time in range (TIR 70–180mg/dL ) was similar ( p  = 0.068). After a median duration of 10.9 months on AHCLs the reduction of HbA1c was similar ( ~ 0.3%). The time spent in the hypoglycemic ranges was longer among users of the open-source AID compared to 780 G (TBR 54–70mg/dL 4.2% [IQR 2.6, 7.3] vs. 2.0% [1.0, 4.0], p  = 0.005) and TBR <54mg/dL 1.1% [IQR 0.4, 2.3] vs. 0.0 [0.0, 1.0], p  = 0.001). Conclusions Both AHCLs similarly improved HbA1c and TIR 70–180mg/dL . The open-source AID youth had better glycemic control but spent longer time in the hypoglycemic range. These findings must be considered when choosing the use of AHCL technologies.

Purpose The use of open-source automated insulin delivery systems (OS-AIDs), for the management of type 1 diabetes (T1D), has increased over recent years in all age groups. Real-life data has demonstrated the safety and efficacy of these systems, however, studies in the pediatric population remain limited. In this study, we aimed to examine the effect of transition to an OS-AIDs on glycemic parameters, and on several aspects related to quality of life. In addition, we aimed to characterize the socioeconomic position of families who chose this treatment modality, assess their motivations to do so, and evaluate treatment satisfaction. Methods In this multi-center observational real-life study from the AWeSoMe Group, we compared glycemic parameters of 52 individuals with T1D (56% males, mean diabetes duration 4.2 ± 3.9 years), from the last clinic visit prior to OS-AIDs initiation to the most recent clinic visit while using the system. Socioeconomic position (SEP) index was retrieved from the Israel Central Bureau of Statistics. Caregivers completed questionnaires assessing reasons for system initiation and treatment satisfaction. Results Mean age at OS-AIDs initiation was 11.2 ± 4 years, range 3.3–20.7 years with a median usage duration of 11.1 months (range 3–45.7). Mean SEP Index was 1.033 ± 0.956 (value range: −2.797 to 2.590). Time in range (TIR) of 70 to 180 mg/dl increased from 69.0 ± 11.9 to 75.5 ± 11.7%, ( P  < 0.001), and HbA1c decreased from 6.9 ± 0.7 to 6.4 ± 0.6%, ( P  < 0.001). Time in tight range (TITR) of 70 to 140 mg/dl increased from 49.7 ± 12.9 to 58.8 ± 10.8% ( P  < 0.001). No episodes of severe hypoglycemia or DKA were reported. Reduction in diabetes burden and sleep quality improvement were the main reasons for OS-AID initiation. Conclusions In our cohort of youth with T1D, the transition to an OS-AID resulted in greater TIR and less severe hypoglycemia regardless of age, diabetes duration or SEP, which was found to be above average. The overall improvement in glycemic parameters in our study population with excellent baseline glycemic control, provides additional evidence of beneficence and efficacy of OS-AIDs in the pediatric population.

AimsChildren with chronic diseases were unable to receive their usual care during COVID-19 lockdown. We assessed the feasibility and impact of telehealth visits on the time-in-range (TIR) of paediatric individuals with type 1 diabetes (T1D).MethodsAn observational multicentre real-life study. Patients scheduled for an in-clinic visit during the lockdown were offered to participate in a telehealth visit. Sociodemographic, clinical, continuous glucose monitor and pump data were recorded 2 weeks prior and 2 weeks after telehealth visit. The primary endpoint was change in relative-TIR, i.e. change in TIR divided by the percent of possible change (∆TIR/(100-TIRbefore)*100).ResultsThe study group comprised 195 individuals with T1D (47.7% males), mean±SD age 14.6 ± 5.3 years, and diabetes duration 6.0 ± 4.6 years. Telehealth was accomplished with 121 patients and their parents (62.0%); 74 (38.0%) did not transfer complete data. Mean TIR was significantly higher for the two-week period after the telehealth visit than for the two-week period prior the visit (62.9 ± 16.0, p < 0.001 vs. 59.0 ± 17.2); the improvement in relative-TIR was 5.7±26.1%. Initial higher mean glucose level, lower TIR, less time spent at <54 mg/dl range, longer time spent at 180–250 mg/dl range, higher daily insulin dose, and single-parent household were associated with improved relative-TIR. Multiple regression logistic analysis demonstrated only initial lower TIR and single-parent household were significant, odds ratio: −0.506, (95%CI −0.99,−0.023), p=0.04 and 13.82, (95%CI 0.621, 27.016), p=0.04, respectively.ConclusionsPaediatric and young adult patients with T1D benefited from a telehealth visit during COVID-19. However, this modality is not yet suitable for a considerable proportion of patients.