Post-operative anterior diaphragmatic hernias in children with Trisomy 21 after cardiac surgery.

Morgagni hernias account for less than 5% of congenital diaphragmatic hernias. They are characteristically retrosternal and bilateral, with right-sided predominance. An association between Trisomy 21 and diaphragmatic hernias resembling Morgagni hernia has been reported, but the effect of cardiac surgery on its formation has not been investigated. The purpose of this study was to determine whether there is a higher incidence of anterior diaphragmatic hernias in children with Trisomy 21 after cardiac surgery. We compared the prevalence of anterior diaphragmatic hernias in 92 patients with Trisomy 21 who underwent cardiac surgery with its prevalence in 100 children without Trisomy 21 who underwent cardiac surgery. All available CXRs of all children underwent revision for the presence of an anterior diaphragmatic hernia by a pediatric radiologist. Within the study group, four cases of an anterior diaphragmatic hernia were detected, all upon presentation to the emergency room due to breathing difficulties. No cases of an anterior diaphragmatic hernia were found in the control group (P = 0.0094). CONCLUSIONS: A high index of suspicion for an anterior diaphragmatic hernia should be maintained in children with Trisomy 21 who have undergone cardiac surgery and present with breathing difficulty. If CXR findings are uncertain, UGI series and\or CT should be performed. In light of our findings, the surgical technique has been modified in patients with DS in our medical center. WHAT IS KNOWN: • Several studies reported an association between Trisomy 21 and diaphragmatic hernia resembling Morgagni hernia, but the effect of cardiac surgery on its formation has not been investigated. WHAT IS NEW: • There is a higher incidence of anterior diaphragmatic hernia resembling a Morgagni hernia in children with Trisomy 21 after cardiac surgery. • A high index of suspicion for an anterior diaphragmatic hernia should be maintained in children with Trisomy 21 who have undergone cardiac surgery and present with breathing difficulty. If CXR findings are uncertain, UGI series and\or CT should be performed.

Optic pathway glioma and endocrine disorders in patients with and without NF1.

BACKGROUND: Optic pathway gliomas (OPGs) are classified by anatomic location and the association with neurofibromatosis type 1 (NF1). Children with OPGs face sequelae related to tumor location and treatment modalities. We assessed the prevalence of endocrine dysfunction in children with OPGs and compared outcomes between those with and without NF1. METHODS: We performed a retrospective medical record review of medical history, and clinical and laboratory data, of children diagnosed with OPGs (n = 59, 61% with NF1) during 1990-2020, followed at a tertiary endocrine clinic. Growth and puberty parameters and occurrence of endocrine dysfunction were evaluated. RESULTS: Isolated optic nerve involvement was higher among patients with than without NF1. Patients without NF1 were younger at OPG diagnosis and more often treated with debulking surgery or chemotherapy. At the last endocrine evaluation, patients without NF1 had comparable height SDS, higher BMI SDS, and a higher rate of endocrine complications (78.3% vs. 41.7%, p = 0.006). Younger age at diagnosis, older age at last evaluation, and certain OPG locations were associated with increased endocrine disorder incidence. CONCLUSIONS: Endocrine dysfunction was more common in patients without NF1; this may be related to younger age at presentation, tumor locations, a greater progressive rate, and more aggressive treatments. IMPACT: The literature is sparse regarding sporadic OPGs, and the mean duration of follow-up is shorter than at our study. Our data show a higher rate of endocrine dysfunction in patients with OPGs than previously described. We also found a higher prevalence of endocrine dysfunctions among patients without compared to those with NF-1. A better understanding of the true prevalence of endocrine disabilities that may evolve along time can help in guiding physicians in the surveillance needed in patients with OPG.

Diagnosing Growth Hormone Deficiency: Can a Combined Arginine and Clonidine Stimulation Test Replace 2 Separate Tests?

OBJECTIVE: Given the large number of false-positive growth hormone deficiency (GHD) diagnoses from a single growth hormone (GH) stimulation test in children, 2 different pharmacologic tests, performed on separate days or sequentially, are required. This study aimed to assess the reliability and safety of a combined arginine-clonidine stimulation test (CACST). METHODS: This was a retrospective, single-center, observational study. During 2017-2019, 515 children aged >8 years underwent GH stimulation tests (CACST: n = 362 or clonidine stimulation test [CST]: n = 153). The main outcome measures used to compare the tests were GH response (sufficiency/deficiency) and amplitude and timing of peak GH and safety parameters. RESULTS: Population characteristics were as follows: median age of 12.2 years (interquartile range [IQR]: 10.7, 13.4), 331 boys (64%), and 282 prepubertal children (54.8%). The GHD rate was comparable with 12.7% for CACST and 14.4% for CST followed by a confirmatory test (glucagon or arginine) (P = .609). Peak GH was higher and occurred later in response to CACST compared with CST (14.6 ng/mL [IQR: 10.6, 19.4] vs 11.4 ng/mL [IQR: 7.0, 15.8], respectively, P < .001; 90 minutes [IQR: 60, 90] vs 60 minutes [IQR: 60, 90], respectively, P < .001). No serious adverse events occurred following CACST. CONCLUSION: Our findings demonstrate the reliability and safety of CACST in detecting GHD in late childhood and adolescence, suggesting that it may replace separate or sequential GH stimulation tests. By diminishing the need for the second GH stimulation test, CACST saves time, is more cost-effective, and reduces discomfort for children, caregivers, and medical staff.

Pediatricians as Case Managers Reduce the Exposure to Computerized Tomography in Children Experiencing Minor Head Trauma.

BACKGROUND: Head trauma is one of the most common reasons for pediatric emergency medicine department (PED) visits. Computerized tomography (CT) scan is considered the criterion standard for the diagnosis of traumatic brain injury but was shown to increases the risk of malignancies. METHODS: We retrospectively analyzed collected data of all children (ages 0-16 years) experiencing mild head trauma who were admitted to a single center, from January 1, 2010, to December 31, 2015. Comparison between patients treated by pediatricians/pediatric emergency medicine physicians (PEMP) with those treated by surgeons regarding CT rates and prognosis was done. RESULTS: During the previously mentioned period, 4232 children presented to the PED after minor head trauma, the average age was 5.4 (±4) years and 67.1% were male. Head CT was done in 7.7%, of which 30.7% had positive findings. Younger children tended to have higher percentage of positive findings on CT scan (60%, 43.8%, 26.6%, P = 0.003, for children up to 5 months, 5-24 months, and older than 24 months, respectively). Pediatricians ordered less CT scans when compared with surgeons (5.4% vs 8.5%, P < 0.001). Moreover, they had higher rates of positive findings on CT scan (52.5% vs 25.8%, P < 0.001). When all other characteristics were similar, if the case manager was a pediatrician, the patient's chances to undergo a CT scan were 4.3 times lower than if the case manager was a surgeon (odds ratio, 4.277; confidence interval, 2.274-7.104). No difference in readmissions or other complications were found between the 2 groups. DISCUSSION: This study highlights that when the case manager of children with minor head trauma is a pediatrician/PEMP, CT scan rates and thus exposure to radiation are diminished without a failure to detect clinically important traumatic brain injury.In conclusion, our findings suggest that when possible, all children experiencing minor head trauma should be treated by a pediatrician/PEMP in the PED.

The Beneficial Effect of Combined GH/GnRHa Therapy in Increasing Adult Height Outcome in Children With ISS.

CONTEXT: Management of GH-treated children with idiopathic short stature (ISS) with early puberty and adolescents in midpuberty at initiation of treatment is challenging. OBJECTIVE: To assess the effect of combined GH/GnRHa therapy during puberty on achieved adult height (AHt) in these children with ISS and to determine whether outcome depended on sex and pubertal status at initiation of GH therapy. DESIGN: Retrospective, single-center observational study from 2003-2018. SETTING: Tertiary endocrine center. PATIENTS: One hundred ninety-two GH-treated children with ISS; 58 of 192 were treated by GH/GnRHa during puberty; 31 of 58 were prepubertal (19 girls) and 27 of 58 pubertal (19 girls) at initiation of GH. MAIN OUTCOME MEASURES: AHt, gain-in-height standard deviation score (SDS), AHt vs predicted adult height (PAHt), AHt vs target height (THt). RESULTS: Most boys and girls attained AHt SDS within the normal range (-0.73 ± 0.60 and -0.85 ± 0.65, respectively). Treatment modality, pubertal status, and sex were tested for their joint effect on growth outcome measures. Combined GH/GnRHa therapy increased AHt vs PAHt (P < 0.001) and AHt vs THt (P = 0.035). Prepubertal status at onset of GH treatment increased AHt (P = 0.049), gain-in-height SDS (P < 0.001), AHt vs PAHt (P < 0.001), and AHt vs THt (P = 0.042). Female sex increased AHt vs PAHt (P < 0.001). CONCLUSIONS: Our study demonstrated a beneficial effect of combined GH/GnRHa therapy in increasing AHt outcome in children with ISS with early/normal puberty and in adolescents naïve to GH treatment who are in midpuberty at initiation of therapy. This effect was more pronounced in the prepubertal group and in girls. Prospective randomized controlled trials are needed to assess whether GnRHa can increase AHt in GH-treated children with ISS.

Eradication failure of newly acquired Pseudomonas aeruginosa isolates in cystic fibrosis.

Eradication of Pseudomonas aeruginosa (PA) is critical in cystic fibrosis (CF) patients. OBJECTIVES: To determine eradication success rate of newly acquired PA and to identify characteristics associated with eradication failure. METHODS: In an observational study, data from patients with newly acquired PA infection from 2007 to 2013 were collected. Clinical variables were compared in patients with and without successful eradication for ≥1year. RESULTS: Of 183 patients out of 740 (25%) from 7 CF Centers that had newly acquired PA, eradication succeeded in 72%. Patients with the highest risk of failure had multi-resistant PA, fewer sputum cultures taken, were older, and were diagnosed at a later age. The risk of eradication failure increased by 1.3% with each year of delayed CF diagnosis; successful eradication increased by 17% with each additional sputum culture taken. CONCLUSIONS: Delayed detection of PA infection leading to delayed treatment and growth of multi-resistant organisms is associated with eradication failure.

Infections caused by Fusobacterium in children: a 14-year single-center experience.

PURPOSE: This study aimed at reviewing our experience with infections caused by Fusobacterium in children. METHODS: A retrospective analysis of medical records of children admitted to Hadassah-Hebrew University Medical Center from 2000 to 2013, in whom Fusobacterium spp. was identified in any specimen. RESULTS: A total of 22 patients (males = 12) at a mean ± SE age of 5 ± 1 (range 1-17) years, were identified. The most common complication was abscess formation (n = 11, 50 %). Eight children (36.4 %) had intracranial complications, including brain abscess (n = 4), meningitis (n = 4) and cerebral sinus vein thrombosis (CSVT, n = 5). Seventeen children (77 %) had bacteremia. Primary site of infection was otogenic (n = 9), oropharyngeal (n = 7), respiratory (n = 2), sinuses (n = 2), intra-abdominal (n = 1) and mucositis (n = 1). Fourteen cases were caused by Fusobacterium necrophorum, including four cases with CSVT, 7/8 cases of mastoiditis, four of them with subperiosteal abscess formation; all four cases with meningitis and two brain abscesses. Fifteen (68 %) patients required surgical intervention and 3 (14 %) received anti-coagulation therapy. Excluding one patient with overwhelming sepsis with fatal outcome, all patients recovered. CONCLUSIONS: Fusobacterium infections in children can cause a diverse spectrum of disease and is associated with high rates of abscess formation and intracranial complications. Although Fusobacterium nucleatum is abundant in the oral cavity, F. necrophorum is the main pathogen that causes severe infections in healthy children.

Hospitalization of children with down syndrome.

INTRODUCTION: Children with Down syndrome present with multiple medical problems in a higher prevalence compared with the general population, which may lead to hospitalizations. METHODS: Analysis of 560 hospitalizations of 162 children aged 0-16 years with Down syndrome at Hadassah Medical Center during the years 1988-2007 compared with data on children in the general population, hospitalized at the same period. Data was collected from patient files and statistical data from the Ministry of Health. RESULTS: Respiratory infections were the leading cause for hospitalization of children with Down syndrome. The number of hospitalizations of children with Down syndrome compared to the number of all children, who were hospitalized was surprisingly similar to their proportion in the general population. Eleven children died during their hospitalization (five heart failure, three sepsis, one respiratory tract infection, and one due to complication after surgery). Nine of the 11 had a congenital heart anomaly. CONCLUSION: Children with Down syndrome can present with complex medical issues and we support the concept of a multidisciplinary team that has experience and knowledge to serve as a "one stop shop" for these individuals and their families, with timely visits in which a comprehensive evaluation is performed, problems attended to and prevention plans applied. In this way, we may prevent morbidity, hospitalizations, and mortality.

Anemia and iron deficiency in children: association with red meat and poultry consumption.

OBJECTIVE: The aim of this study was to study the relative contribution of dietary sources of iron in children with high prevalence of anemia and iron deficiency (ID). METHODS: A cross-sectional study in 263 healthy, 1.5- to 6-year-old children in the Jewish sector of Jerusalem, Israel. Venous blood samples and a qualitative Food Frequency Questionnaire on iron-rich foods were obtained. Anemia was defined as hemoglobin <11 g/dL for children younger than 4 years and <11.5 g/dL for children older than 4 years; ID was defined as ferritin <12 µg/L. RESULTS: Anemia was found in 11.2%, ID in 22%, and iron-deficiency anemia in 3.7%. The prevalence of anemia was higher in toddlers ages 1.5 to 3 years compared with children ages 3 to 6 years (17.7% vs 7.3%, P = 0.01). Children with extremely low red meat consumption (seldom) had 4-fold higher rates of ID than those who consumed ≥2 times per week (odds ratio 3.98; 95% confidence interval 1.21-13.03; P = 0.023), whereas poultry consumption was not associated with ID. Soy consumption was inversely associated with ferritin (marginally significant, r = -0.134, P = 0.057). CONCLUSIONS: The high prevalence of anemia and ID found in this study, mainly in children 1.5 to 3 years old, is related to low red meat consumption. The characteristically high poultry consumption in the Israeli population was not protective. The shift toward reduced red meat consumption and higher poultry consumption in developed countries may result in increasing the risk of ID.

Mitochondrial OXPHOS function is unaffected by chronic azithromycin treatment.

BACKGROUND: Certain antibiotics may cause unwanted side effects due to the similarity of the mitochondrial translation system to the prokaryotic one. Children with cystic fibrosis (CF) are vulnerable to recurrent respiratory tract infections and azithromycin, a translation targeted antibiotic, is often used chronically to treat CF patients. No major clinical side effects were found with chronic treatment. However, mitochondrial function was not previously assessed. We evaluated oxidative phosphorylation (OXPHOS) in lymphocytes from children with CF receiving chronic azithromycin treatment using an improved ATP production assay. METHOD: Enzymatic activities of respiratory chain complexes II-IV and ATP production were measured in lymphocytes. RESULTS: Relative to controls and to CF patients without azithromycin treatment, no significant difference in mitochondrial respiratory chain complexes II-IV was detected, and ATP production with pyruvate, glutamate and succinate, did not disclose any differences between the groups. CONCLUSION: We suggest that chronic treatment with azithromycin does not significantly affect OXPHOS function.

The role of hematopoietic stem cell transplantation in SP110 associated veno-occlusive disease with immunodeficiency syndrome.

BACKGROUND: Veno-occlusive disease with immunodeficiency (VODI) is an autosomal recessive disorder of combined immunodeficiency (CID) and hepatic injury. Hematopoietic stem cell transplantation (HSCT) - the only definitive treatment for CID - appeared to have a high rate of complications in a previous report. In this study, we describe a new group of patients with VODI highlighting further clinical and immunologic aspects of this disease and re-evaluating the effectiveness of HSCT for the treatment of this disorder. PATIENTS AND METHODS: Review of clinical data, immunologic features, molecular studies, treatment, and final outcome of eight kindred members with VODI. RESULTS: The patients described had clinical and immunologic findings consistent with VODI. The molecular studies revealed a new mutation in the SP110 gene. HSCT was carried out in five patients and was successful in three. CONCLUSIONS: The diagnosis of VODI should be considered in all patients regardless of ethnicity with a severe combined immunodeficiency (SCID)-like presentation, especially with a normal mitogen response, or with signs of hepatic injury. VODI is a primary immune deficiency, which can be successfully corrected by bone marrow transplantation if applied early in the course of disease using appropriate conditioning.

Effect of eutectic mixture of local anesthetics (EMLA) for pain relief during suprapubic aspiration in young infants: a randomized, controlled trial.

OBJECTIVES: The purpose of this study was to determine whether a eutectic mixture of local anesthetics (EMLA) cream reduce the pain experienced by newborns and young infants undergoing suprapubic aspiration (SPA). METHODS: A single-center, randomized, placebo-controlled, double-blind, prospective study including 52 infants 1 to 60 days of age undergoing SPA to obtain urine for culture. Twenty-four infants were randomly assigned to receive 1-g EMLA cream 1 hour before the procedure, whereas 28 were randomly assigned to receive placebo cream 1 hour before the planned procedure. Pain symptoms were measured using the Premature Infant Pain Profile (PIPP). RESULTS: The mean PIPP scores were significantly lower in the EMLA group compared with the placebo group (8.90+/-3.04 vs. 10.46+/-2.29; P=0.038). There were significantly fewer patients in the EMLA group who were scored as having some degree of pain (defined as PIPP score >6) in comparison with the placebo group (70% vs. 96%; P=0.025). DISCUSSION: Newborns and infants undergoing SPA experience pain during the procedure. Application of EMLA cream 1 hour before SPA is effective in reducing the pain associated with SPA. In situations in which an SPA is not emergent, strong consideration should be given to the use of EMLA.

Angiogenesis induced by novel peptides selected from a phage display library by screening human vascular endothelial cells under different physiological conditions.

Angiogenesis is a process modulated by several endogenous vascular growth factors as well as by oxygen conditions. For example VEGF failed to induce useful therapeutic angiogenesis in clinical trials. We used a combinatory phage display peptide library screening on human umbilical endothelial cells under normoxia and hypoxia conditions in order to identify novel peptides that bind endothelial cells. The identified peptides induced angiogenesis as demonstrated by endothelial cell proliferation, migration and tube formation. Injection of peptides into the ears of mice resulted in increased numbers of blood vessels. Peptides did not induce VEGF receptor gene expression indicating a possible VEGF unrelated mechanism.