Pediatrics

Sialoblastoma of the submandibular gland: a distinct entity? Abstract Sialoblastoma is a rare congenital malignant tumor of the salivary glands. A case of a submandibular sialoblastoma in a 1.5-year-old child is presented. A comparative analysis on 79 pediatric cases reported in the literature suggests a less aggressive behavior for submandibular sialoblastoma in comparison with other sites. Classically, diagnosis is confirmed by open biopsy, but fine-needle aspiration may offer an alternative with reduced morbidity. Expression of AFP and high levels of Ki-67 have been associated with poor prognosis. Whilst early surgical resection with negative margins is widely accepted as first-line treatment, there is no consensus on therapy of recurrence and follow-up. MRI and sonography represent valid tools for the follow-up, which is usually restricted to 3–5 years. Conclusion: Submandibular sialoblastomas may have a different biological profile in comparison with parotid tumors with the absence of metastasis and much lower rate of recurrence. Comprehensive diagnostics should include additional options such as fine-needle aspiration and markers to assess cell proliferation and AFP. Literature suggests that surgery alone is sufficient for the treatment of tumors with low malignancy. Follow-up should be tailored according to the tumor site and might be limited to 3–5 years. What is Known: • Sialoblastoma is a rare congenital malignant tumor with an unpredictable clinical outcome. What is New: • Sialoblastoma of submandibular origin seems to have a less aggressive behavior in comparison with other sites. • Fine-needle aspiration and markers to assess proliferation index (i.e., suggestive of potential more aggressive course/malignancy) should be strongly considered in the diagnostic work-up. • Radical surgery as first-line therapy and a 3–5-year follow-up are acceptable for tumors with a low malignancy.

Somatic symptom disorder should be suspected in children with alleged chronic Lyme disease Abstract We report a case series of seven children admitted to a tertiary level pediatric ward for long-lasting physical symptoms with a previous diagnosis of chronic Lyme disease. In these children, medical history and clinical features were strongly suggestive of a psychopathological disorder, mainly a somatic symptom disorder. What is Known: • There is an increasing number of diagnoses of chronic Lyme disease both in North America and in Europe. Adults receive this diagnosis to explain chronic physical complaints often with negative history and serology. What is New: • Somatic symptom disorder should be suspected in children and adolescents with non-specific symptoms diagnosed with chronic Lyme disease.

Ten-year trend in prevalence and outcome of Down syndrome with congenital heart disease in a middle-income country Abstract Limited data are available on the survival of patients with Down syndrome and congenital heart disease (CHD) from middle-income countries. This retrospective cohort study was performed to determine the trends in the prevalence and survival of such patients born from January 2006 to December 2015 in Malaysia. Among 754 patients with Down syndrome, 414 (55%) had CHD, and no significant trend was observed during the 10 years. Of these 414 patients, 30% had lesions that closed spontaneously, 35% underwent surgery/intervention, 9% died before surgery/intervention, and 10% were treated with comfort care. The overall mortality rate was 23%, the median age at death was 7.6 months, and no significant changes occurred over time. The early and late post-surgery/intervention mortality rates were 0.7% and 9.0%, respectively. Most deaths were of non-cardiac causes. The overall 1-, 5-, and 10-year survival rates were 85.5%, 74.6%, and 72.9%, respectively. Patients with severe lesions, persistent pulmonary hypertension of the newborn, atrioventricular septal defect, and pulmonary hypertension had low survival at 1 year of age. Conclusion: The prevalence of CHD in patients with Down syndrome is similar between Malaysia and high-income countries. The lower survival rate is attributed to limited expertise and resources which limit timely surgery. What is Known: • The survival of patients with Down syndrome with congenital heart disease (CHD) has improved in high-income countries. However, little is known about the survival of patients with Down syndrome with CHD from middle-income countries. • In the Caucasian population, atrioventricular septal defect is the most common type of CHD associated with Down syndrome. What is New: • In middle-income countries, the prevalence of CHD is the same as in high-income countries, but with a lower survival rate. • In the Asian population, ventricular septal defect is the most common type of CHD in patients with Down syndrome.

Genotype and phenotype analysis of a cohort of patients with congenital hyperinsulinism based on DOPA-PET CT scanning Abstract Congenital hyperinsulinism (CHI) is a clinically, genetically, and morphologically heterogeneous disorder. 18F DOPA-PET CT scanning greatly improves its clinical outcome. Here, we presented the first Chinese 18F DOPA-PET CT scanning–based CHI cohort highlighting the variable ethic clinical phenotypes and genotypes. Fifty CHI patients were recruited. Median age at presentation was 2 days. Median fasting time was 2 h. Mean insulin level was 25.6 μIU/ml. Fifty-two percent of patients were diazoxide-unresponsive with significantly shorter fasting tolerance time and higher serum insulin level compared with the responsive patients. Seventy-four percent of patients experienced at least one adverse drug reaction. Tremendously increased focal lesions (32%) were detected and 75% of them were cured through surgery. Thirty-one nucleotide sequence changes were identified in 48% patients. Four novel variants (Q608X, Q1347X, Q289X, F1489S) in ABCC8 gene and 2 novel variants (G132A, V138E) in KCNJ11 gene were detected. Of the variants, 87.1% harbored in ABCC and KCNJ11 genes. T1042Qfs*75 in ABCC8 gene was the most common mutation. Conclusion: Highly increased portion of focal lesion was presented in Chinese CHI patients compared with that of the previous reports. Intolerance to diazoxide was much more evident in Chinese or East Asian than other populations. Certain hotspot mutations harbored in Chinese CHI patients. What is Known: • 18F DOPA-PET CT scanning can provide informative guidance for surgical procedure when medical therapy is not well responded in CHI patients. What is New: • Intolerance to diazoxide is much more evident in Chinese and East Asian CHI patients compared with the other ethnic populations. • Novel mutations were detected in ABCC8 and KCNJ11 gene. Hotspot mutations such as T1042Qfs*75, I1511K, E501K, G111R in ABCC8 gene, and R34H in KCNJ11 gene are predominantly responsible for Chinese CHI patients.

A new simple formula built on the American Academy of Pediatrics criteria for the screening of hypertension in overweight/obese children Abstract We evaluated the performance of a new simple formula (NSF) for the screening of hypertension by American Academy of Pediatrics Guidelines 2017 (AAPG2017) in children with overweight/obesity (OW/OB). The performance of the NSF and the modified blood pressure to height ratio (MBPHR3) thresholds against AAPG2017 was evaluated; both methods were also compared to assess the association with concentric left ventricular hypertrophy (cLVH). The study included 3259 OW/OB children (5–13 years). Two centers served as learning sample (LS) (n = 1428), four centers served as validation sample (VS) (n = 1831), and the echocardiographic evaluation was available in 409 children in VS. The NSF was [1.5 × systolic blood pressure (mmHg) + diastolic blood pressure (mmHg)] − [(26 × height (m)] − age (years). A cut-off of the NSF ≥ 193 mmHg showed sensitivity, specificity, positive, and negative predictive values of 0.92, 0.93, 0.83, and 0.97, respectively, versus the standard procedure. Against AAPG2017, the NSF showed higher specificity and positive predictive values than the MBPHR3 thresholds. Among hypertensive children defined by AAPG2017, NSF, or MBPHR3, the odds ratio (95%CI) for cLVH was respectively 1.73 (1.06–2.83), 1.69 (1.05–2.75), and 1.18 (0.75–1.85). Conclusions: The NSF shows a very high performance for the screening of OW/OB children at risk of hypertension and cLVH. What is Known: • The American Academy of Pediatrics released updated guidelines (AAPG 2017) to classify hypertension (HTN) in children. • The process needs categorization of height percentiles and comparison of blood pressure versus gender and age-adjusted values. What is New: • A user-friendly formula built on the AAPG 2017 was validated for the categorization of HTN in children with overweight/obesity. • The formula showed high performance in identifying children with HTN versus the standard procedure (sensitivity 0.92, specificity 0.93) and similar ability in identifying hypertensive children with concentric left ventricular hypertrophy versus the standard procedure (40% and 39% respectively).

Benefits of medical clowning in the treatment of young children with autism spectrum disorder Abstract We investigated the contribution of group therapy delivered by a medical clown to young children diagnosed with autism spectrum disorder (ASD). So far, scientific publications regarding medical clowning focus on general health advantages. The current study is the first controlled research examining the use of medical clowning in the therapy for children with ASD. Twenty-four children aged 2–6 years old with ASD enrolled in our special education intensive program were examined before and after group sessions with clown intervention (CI) and other intervention (OI). We tested stereotypic behaviors, verbal expression, play reciprocity, and social smiles. Data was collected during 12 weeks of intervention, and the trajectory of change was evaluated in addition to the pre-/post-intervention. Conclusion: improvement over time in all measures: Significant increase in word production, play reciprocity, and amount of social smiles during CI as compared with OI. We also found a reduction in frequency of stereotypic behaviors during and following CI as compared with before CI. These preliminary results indicate that medical clowning may be beneficial for young children with ASD, since it promotes communication and social reciprocity in a fun and lively interventional setting. What is Known: • Many therapies are used and proven as efficacious interventions for children with ASD. • So far, medical clowning was not tested as an intervention or therapy for ASD. What is New: • Medical clowning sessions with children with ASD elicited enhanced communication during the interventions as compared with other interventions. • Medical clowning sessions contributed to a decrease in frequency of stereotypic movements over time, in children with ASD.

RAPIDOMICS: rapid genome-wide sequencing in a neonatal intensive care unit—successes and challenges Abstract Genetic disorders are one of the leading causes of infant mortality and are frequent in neonatal intensive care units (NICUs). Rapid genome-wide sequencing (GWS; whole genome or exome sequencing (ES)), due to its diagnostic capabilities and immediate impacts on medical management, is becoming an appealing testing option in the NICU setting. RAPIDOMICS was a trio-based rapid ES pilot study of 25 babies with suspected genetic disorders in the BC Women's Hospital NICU. ES and bioinformatic analysis were performed after careful patient ascertainment. Trio analysis was performed using an in-house pipeline reporting variants in known disease-causing genes. Variants interpreted by the research team as definitely or possibly causal of the infant's phenotype were Sanger validated in a clinical laboratory. The average time to preliminary diagnosis was 7.2 days. Sanger validation was pursued in 15 patients for 13 autosomal dominant and 2 autosomal recessive disorders, with an overall diagnostic rate (partial or complete) of 60%. Conclusion: In total, 72% of patients enrolled had a genomic diagnosis achieved through ES, multi-gene panel testing or chromosomal microarray analysis. Among these, there was an 83% rate of significant and immediate impact on medical decision-making directly related to new knowledge of the diagnosis. Health service implementation challenges and successes are discussed. What is Known: • Rapid genome-wide sequencing in the neonatal intensive care setting has a greater diagnostic hit rate and impact on medical management than conventional genetic testing. However, the impact of consultation with genetics and patient ascertainment requires further investigation. What is New: • This study demonstrates the importance of genetic consultation and careful patient selection prior to pursuing exome sequencing (ES). • In total, 15/25 (60%) patients achieved a diagnosis through ES and 18/25 (72%) through ES, multi-gene panel testing or chromosomal microarray analysis with 83% of those having immediate effects on medical management.

Influence of chronic diseases on the olfactory function in children Abstract The association between smell impairment and chronic diseases has been reported in some studies in adults. Such information is not available for chronic diseases in children. The aim of this study was to examine olfactory function of children with chronic diseases such as diabetes mellitus type 1, hypothyroidism, and bronchial asthma in combination with allergic rhinitis in comparison to healthy controls. The data were obtained from n = 205 participants (104 boys, 101 girls) between the age of 6 and 17 years. Seventy-eight of the participants were healthy controls, n = 43 had diabetes mellitus type 1, n = 50 suffer from allergic rhinitis or bronchial asthma, and 34 presented a reduced function of their thyroid in medical history. All participants underwent olfactory testing including olfactory threshold using "Sniffin' Sticks" and odor identification using the "U-Sniff" test. In addition, a depression inventory and cognitive testing using the Ravens Progressive Matrices was performed. No significant difference in olfactory function was observed for any of the chronic diseases in children in comparison to healthy controls. Further analysis showed a trend in significance for a subpopulation of children with bronchial asthma and comorbidities performed worse on the olfactory threshold test compared to patients with bronchial asthma without comorbidities. Pediatric patients suffering from chronic diseases scored higher on the depression inventory compared to healthy controls. Conclusion: In conclusion, this study demonstrates that the influence of chronic diseases (bronchial asthma, diabetes mellitus type 1 and hypothyroidism) on olfactory function in childhood, if any, seems to be insignificant. This is partly in contrast to adult patients. Further research should be conducted in a subgroup of patients with bronchial asthma, allergic rhinitis, and atopic dermatitis or other comorbidities to better understand the association of allergic diathesis and olfactory function and the putative pathogenesis of olfactory dysfunction. What is known: • The association between smell impairment and chronic diseases has been reported in some studies in adults. • Such information is not available for chronic diseases in children. What is new: • The influence of chronic diseases (bronchial asthma, diabetes mellitus type 1, and hypothyroidism) on olfactory function in childhood, if any, seems to be insignificant. • In patients with bronchial asthma and allergic rhinitis, only a subgroup of patients with additional comorbidity (atopic dermatitis) showed a tendency to a reduced sense of smell.

Diaphragm electromyography results at different high flow nasal cannula flow rates Abstract Heated, humidified, high-flow nasal cannula (HHHFNC) is increasingly being used, but there is a paucity of evidence as to the optimum flow rates in prematurely born infants. We have determined the impact of three flow rates on the work of breathing (WOB) assessed by transcutaneous diaphragm electromyography (EMG) amplitude in infants with respiratory distress or bronchopulmonary dysplasia (BPD). Flow rates of 4, 6 and 8 L/min were delivered in random order. The mean amplitude of the EMG trace and mean area under the EMG curve (AEMGC) were calculated and the occurrence of bradycardias and desaturations recorded. Eighteen infants were studied with a median gestational age of 27.8 (range 23.9–33.5) weeks and postnatal age of 54 (range 3–122) days. The median flow rate prior to the study was 5 (range 3–8) L/min and the fraction of inspired oxygen (FiO2) was 0.29 (range 0.21–0.50). There were no significant differences between the mean amplitude of the diaphragm EMG and the AEGMC and the number of bradycardias or desaturations between the three flow rates. Conclusions: In infants with respiratory distress or BPD, there was no advantage of using high (8 L/min) compared with lower flow rates (4 or 6 L/min) during support by HHHFNC. What is known: • Humidified high flow nasal cannulae (HHHFNC) is increasingly being used as a non-invasive form of respiratory support for prematurely born infants. • There is a paucity of evidence regarding the optimum flow rate with 1 to 8 L/min being used. What is new: • We have assessed the work of breathing using the amplitude of the electromyogram of the diaphragm at three HHHFNC flow rates in infants with respiratory distress or BPD. • No significant differences were found in the EMG amplitude results or the numbers of bradycardias or desaturations at 4, 6 and 8 L/min.

The role of sleep-related cognitive functions in the spectrum of benign epilepsy with centro-temporal spikes Abstract Heterogeneous cognitive deficits have been described in the spectrum of benign epilepsy with centro-temporal spikes, which strongly correlate with the intensity of interictal epileptiform discharges and its spreading, in particular during sleep, mostly within the perisylvian cognitive network. The aim of this review is to discuss current findings regarding the connection between sleep alterations and cognitive function in the spectrum of benign epilepsy with centro-temporal spikes. A longer sleep onset latency is the only evident sleep macrostructure alteration reported in the spectrum of benign epilepsy with centro-temporal spikes. On a microstructural level, a higher spike count of descending compared to ascending slopes of sleep cycles, an impairment of slow wave downscaling, and amplitude and slope of slow waves were found in the spectrum of benign epilepsy with centro-temporal spikes. Moreover, children with benign epilepsy with centro-temporal spikes had a reduced non-rapid eye movement sleep instability, in terms of cyclic alternating pattern, similar to that found in children with attention-deficit hyperactivity disorders and in children with obstructive sleep apnea and centro-temporal spike during sleep. Children with benign epilepsy with centro-temporal spikes have a known comorbidity with attention-deficit hyperactivity disorders and obstructive sleep apnea. Conclusion: Considering the common sleep microstructure alterations, the presence of attention deficit and hyperactivity and/or sleep apnea may be a considered warning sign in the case of benign epilepsy with centro-temporal spikes. What is Known: • Sleep related-cognitive deficits have been described in the spectrum of benign epilepsy with centro-temporal spikes. The degree of sleep alterations may predict the neurocognitive outcome, and help clinicians to choose the right treatment. What is New: • Considering the common sleep microstructure alterations, attention deficit and sleep apnea, may be a considered warning signs.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com