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Objectives: We present an adolescent in whom olfactory neuroblastoma (ONB) was detected on follow-up magnetic resonance imaging (MRI) 2.5 years after SIADH diagnosis. Our case contrasts prior pediatric reports in which ONB and SIADH were diagnosed concurrently. Case presentation: A previously healthy 13-year-old girl was found to have SIADH during evaluation for restrictive eating. Work-up ruled out adrenal, thyroid and paraneoplastic causes, diuretic use, and vasopressin receptor and aquaporin channel mutations. Brain MRI was normal except for paranasal sinus (PNS) inflammatory changes to the left fronto-maxillary sinuses and frontoethmoidal recess. The sodium levels normalized with fluid restriction (800-900 ml/m2 /day). Multiple repeated attempts to liberalize fluid intake resulted in recurrent hyponatremia. Follow-up brain MRIs 4 and 11 months after the initial presentation showed persistent PNS inflammatory changes. A subsequent brain MRI 31 months after initial presentation demonstrated a lesion in the left frontoethmoidal recess extending into the left nasal cavity and biopsy showed low grade ONB. The patient underwent surgery with normalization of serum sodium on liberalized fluid intake. Seven days after surgery, she had recurrence of SIADH, and brain MRI showed remnant of the ONB at the fovea ethmoidalis. She completed adjuvant radiotherapy though her SIADH persisted. Conclusions: Our case highlights the importance of considering ONB in the evaluation of children with SIADH. Idiopathic SIADH is rare in children and if no cause is identified, computed tomography of sinuses and nasal endoscopy should be considered earlier in the work-up of these patients, particularly in the absence of sinus symptoms. [ABSTRACT FROM AUTHOR]

Rural children are more at risk for childhood obesity but may have difficulty participating in pediatric weight management clinical trials if in-person visits are required. Remote assessment of height and weight observed via videoconferencing may provide a solution by improving the accuracy of self-reported data. This study aims to validate a low-cost, scalable video-assisted protocol for remote height and weight measurements in children and caregivers. Families were provided with low-cost digital scales and tape measures and a standardized protocol for remote measurements. Thirty-three caregiver and child (6–11 years old) dyads completed remote (at home) height and weight measurements while being observed by research staff via videoconferencing, as well as in-person measurements with research staff. We compared the overall and absolute mean differences in child and caregiver weight, height, body mass index (BMI), and child BMI adjusted Z-score (BMIaz) between remote and in-person measurements using paired samples t-tests and one sample t-tests, respectively. Bland–Altman plots were used to estimate the limits of agreement (LOA) and assess systematic bias. Simple regression models were used to examine associations between measurement discrepancies and sociodemographic factors and number of days between measurements. Overall mean differences in child and caregiver weight, height, BMI, and child BMIaz were not significantly different between remote and in-person measurements. LOAs were − 2.1 and 1.7 kg for child weight, − 5.2 and 4.0 cm for child height, − 1.5 and 1.7 kg/m2 for child BMI, − 0.4 and 0.5 SD for child BMIaz, − 3.0 and 2.8 kg for caregiver weight, − 2.9 and 3.9 cm for caregiver height, and − 2.1 and 1.6 kg/m2 for caregiver BMI. Absolute mean differences were significantly different between the two approaches for all measurements. Child and caregiver age were each significantly associated with differences between remote and in-person caregiver height measurements; there were no significant associations with other measurement discrepancies. Remotely observed weight and height measurements using non-research grade equipment may be a feasible and valid approach for pediatric clinical trials in rural communities. However, researchers should carefully evaluate their measurement precision requirements and intervention effect size to determine whether remote height and weight measurements suit their studies. Trial registration: ClinicalTrials.gov NCT04142034 (29/10/2019). [ABSTRACT FROM AUTHOR]

Hypercalcemia has been reported as an uncommon complication of the ketogenic diet (KD). Here we present a toddler whose hypercalcemia persisted for 2 months after stopping the KD. A 2 year 11-month-old child with global developmental delay, infantile spasms, neuromuscular weakness with limited mobility, tracheostomy and ventilator dependence, and oropharyngeal dysphagia with G-tube dependence presented with hypercalcemia in the setting of recurrent vomiting. At presentation, the patient was adherent to a KD and taking topiramate since infancy for intractable seizures. His laboratory parameters at presentation showed hypercalcemia (11.9 mg/dL), hypercalciuria, acute renal failure, low alkaline phosphatase (76 IU/L [110–302 IU/L]), parathyroid hormone (PTH) <6 pg/mL (18–80 pg/mL), normal thyroid function, cortisol and vitamin D level. The patient's hypercalcemia persisted post-discontinuation of the KD and topiramate. PTH-related protein was mildly elevated at 15.3 pmol/L. Follow-up laboratory and imaging studies ruled out malignancy. He was managed with calcitonin 4 u/kg/dose Q12H × 1 day and 8 u/kg/dose Q8H × 1 day, hydration and low-calcium formula. Post-discontinuation of the KD, normalization of alkaline phosphatase levels preceded the normalization of calcium on day 55 and PTH on day 85. Hypercalcemia may persist for an extended period after weaning from a KD; lab parameters may mimic that of hypophosphatasia as previously described in the literature. Normalization of alkaline phosphatase, a marker of bone turnover, indicates recovery from the adynamic state induced by the KD and typically precedes the normalization of calcium and PTH. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To describe the evolving impact of the coronavirus disease 2019 pandemic on the incidence and presentation of new-onset pediatric type 2 diabetes. RESEARCH DESIGN AND METHODS: Retrospective medical record review of youth with new-onset type 2 diabetes comparing the prepandemic period (1 January 2017–29 February 2020) with the first (1 March 2020–31 December 2020) and second pandemic year (1 January 2021–31 December 2021). RESULTS: The annualized incidence of type 2 diabetes increased nearly threefold during the pandemic versus prior, with a 61% increase in the 2nd versus 1st year. BMI increased during the pandemic versus prior (129% of 95th percentile vs. 141%, P = 0.02). In the 1st year, patients were younger (12.9 years vs. 14.8, P < 0.001), with higher incidence of diabetic ketoacidosis and/or hyperglycemic hyperosmolar syndrome (20% vs. 3.5%, P = 0.02) versus prior. CONCLUSIONS: Providers should be aware of the escalating incidence of youth-onset type 2 diabetes to avoid delays in diagnosis and inform educational programs to combat the continued impact of the pandemic on health outcomes. [ABSTRACT FROM AUTHOR]

Acquired hypothyroidism due to iodine deficiency is extremely rare in the United States due to the introduction of table salt iodization in the 1920s (Leung et al., 2012). We present the case of an adolescent male with a history of mild autism spectrum disorder and an extremely restrictive diet who was found to have iodine deficiency as the etiology for his rapidly enlarging goiter and antibody-negative hypothyroidism. Thyroid-stimulating hormone (TSH) was 416 μIU/mL (0.350–5.500 μIU/mL), free thyroxine (T4) was <0.1 ng/dL (0.80–1.80 ng/dL), and triiodothyronine (T3) was 41 ng/dL (82–213 mg/dL) at diagnosis. The patient's 24-hour urinary iodine was undetectable. He was started on iodine supplementation with rapid visible improvement of goiter within two weeks and normalization of thyroid function tests within four weeks. Thorough dietary history and nutritional screening are important in cases of acquired hypothyroidism and/or goiter. Alternatively, diets that are low in iodized salt, dairy, bread, and seafood should raise concern for iodine deficiency, and patients with suspected or proven iodine deficiency should be screened for hypothyroidism. [ABSTRACT FROM AUTHOR]

Context: Youth with classical congenital adrenal hyperplasia (CAH) exhibit abnormal adrenomedullary function with decreased epinephrine levels noted in newborns and young infants. Little is known about how this relates to morbidity during the first year of life. Objective: This work aimed to study plasma epinephrine levels in infants with classical CAH and examine the clinical significance of epinephrine deficiency in the first year of life. Methods: This prospective cohort study comprised participants recruited from a pediatric tertiary care center: 36 infants with classical CAH due to 21-hydroxylase deficiency and 27 age-matched unaffected controls with congenital hypothyroidism. Main outcome measures included plasma epinephrine levels (N = 27), CYP21A2 genotype (N = 15), and incidence of acute illnesses from birth to age 1 year (N = 28). Results: Epinephrine levels in CAH infants independently predicted illness incidence in the first year of life (ß = -0.018, R = -0.45, P = .02) and were negatively correlated with 17-hydroxyprogesterone at diagnosis (R = -0.51, P = .007). Infants with salt-wasting CAH exhibited lower epinephrine levels as newborns than simple-virilizing infants (P = .02). CAH patients had lower epinephrine as newborns than did controls (P = .007) and showed decreases in epinephrine from birth to age 1 year (P = .04). Null genotype was associated with lower newborn epinephrine and more illness in the first year of life, compared to less severe mutation categories. Conclusion: Lower epinephrine levels are associated with increased risk of illness among CAH infants. While not currently part of clinical standard of care, measuring epinephrine levels and assessing genotype may help predict acute illness in the first year of life. [ABSTRACT FROM AUTHOR]

Food choices are a key determinant of dietary intake, with brain regions, such as the mesolimbic and prefrontal cortex maturing at differential rates into adulthood. More needs to be understood about developmental changes in healthy and unhealthy food perceptions and preference. We investigated how food perceptions and preference vary as a function of age and how food attributes (taste and health) impact age-related changes. One hundred thirty-nine participants (8–23 years, 60 females) completed computerized tasks to rate high-calorie and low-calorie food cues for taste, health, and liking (preference), followed by 100 binary food choices based on each participant's ratings. Dietary self-control was considered successful when the healthier (vs. tastier) food was chosen. Self-control success ratio was the proportion of success trials over total number of choices. Beta-weights for health (β-health) and taste (β-taste) were calculated as each attribute's influence on food preference. Adiposity measurements included BMI z-score and waist-to-height ratio (WHtR). High-calorie foods were rated more tasty and less healthy with increasing age. Older participants liked high-calorie foods more (vs. younger participants), and β-taste was associated with age. Significant age-by-WHtR interactions were observed for health and taste ratings of high-calorie foods, β-taste, and marginally for preference of high-calorie foods. Stratifying by WHtR (high, low), we found age-related increases in taste and preference ratings of high-calorie foods in the high WHtR group alone. In contrast, age-related decreases in health ratings of high-calorie foods were significant in the low WHtR group alone. Age and β-taste were significantly associated in the high WHtR group and only marginally significant with low WHtR. Although participants rated low-calorie foods as less tasty and less healthy with increasing age, there was no association between age and preference for low-calorie foods. Participants made faster food choices with increasing age regardless of WHtR, with a significant age-by-WHtR interaction on reaction time (RT). There were no age-related effects in self-control success ratio and β-health. These results suggest that individual differences in age and central adiposity play an important role in preference for high-calorie foods, and a higher importance of food tastiness in food choice may contribute to greater preference for high-calorie foods with increasing age. [ABSTRACT FROM AUTHOR]

A prefrontal control system that is less mature than the limbic reward system in adolescence is thought to impede self-regulatory abilities, which could contribute to poor dietary choices and obesity. We, therefore, aimed to examine whether structural morphology of the prefrontal cortex (PFC; involved in cognitive control) and the amygdala (a key brain region for reward-related processing) are associated with dietary decisions and obesity in children and adolescents. Seventy-one individuals between the ages of 8–22 years (17.35 ± 4.76 years, 51% female, 56% were overweight or obese) participated in this study; each participant completed a computer-based food choice task and a T1- and T2-weighted structural brain scans. Two indices of obesity were assessed, including age- and sex-specific body mass index (BMIz) and waist-to-height ratio (WHtR). The behavioral task included rating 60 food stimuli for tastiness, healthiness, and liking. Based on each participant's self-ratings, 100 binary food choices were then made utilizing a computer mouse. Dietary "self-control" was calculated as the proportion of trials where the individual chose the healthier food item (vs. the tastier food item) over the total number of trials. Cortical thickness and amygdala subnuclei volumes were quantified using FreeSurfer 6.0 and CIT168 atlas, respectively. We found that WHtR was negatively associated with the thickness of bilateral superior frontal, left superior temporal, right insula, and right inferior temporal regions (p < 0.05, corrected for multiple comparisons). We also found WHtR to be positively associated with the volume of the central nucleus (CEN) region of the amygdala (p = 0.006), after adjusting for the hemisphere, age, sex, and intracranial volumes. A similar data pattern was observed when BMIz was used. Moreover, we found that across all participants, thinner right superior frontal cortex and larger left CEN volumes predicted lower dietary self-control. These results suggest that differential development of the PFC and amygdala relate to obesity and dietary self-control. Further longitudinal studies are merited to determine causal relationships among altered PFC to amygdala neural circuitry, dietary self-control, and obesity. [ABSTRACT FROM AUTHOR]

Parathyroid carcinoma is a rare cause of primary hyperparathyroidism amongst children, with only nine previously reported cases. The objective of the study was to present the first pediatric case with a germline CDC73 (formerly known as HRPT2) mutation, and to review the literature. A 14-year-old girl presented with pathologic slipped capital femoral epiphysis (SCFE). The patient was noted to have an elevated calcium level of 3.4 mmol/L (13.4 mg/dL), a parathyroid hormone (PTH) level of 1013 ng/L (1013 pg/mL), and a 3-cm palpable neck mass. Ultrasound and 99mTc-Sestamibi confirmed the suspicion of a parathyroid mass. Intraoperative findings and pathology confirmed the diagnosis of parathyroid carcinoma. Postoperative PTH decreased to 14 ng/L (14 pg/mL). Genetic testing showed a germline 70 G > T HRPT2/CDC73 mutation. This is the first case documenting a germline 70 G > T HRPT2/CDC73 gene mutation in a pediatric parathyroid carcinoma. Patients with sporadic parathyroid carcinoma may benefit from HRPT2/CDC73 gene mutation screening. [ABSTRACT FROM AUTHOR]

The DNA damage response (DDR) is critical for the maintenance of genetic stability and serves as an anti-cancer barrier during early tumorigenesis. However, the role of the DDR in tumor progression and metastasis is less known. Here, we demonstrate that the ATM kinase, one of the critical DDR elements, is hyperactive in late stage breast tumor tissues with lymph-node metastasis and this hyperactivity correlates with elevated expression of the epithelial–mesenchymal transition marker, Snail. At the molecular level, we demonstrate that ATM regulates Snail stabilization by phosphorylation on Serine-100. Using mass spectrometry, we identified HSP90 as a critical binding protein of Snail in response to DNA damage. HSP90 binds to and stabilizes phosphorylated Snail. We further provide in vitro and in vivo evidence that activation of ATM-mediated Snail phosphorylation promotes tumor invasion and metastasis. Finally, we demonstrate that Snail Serine-100 phosphorylation is elevated in breast cancer tissues with lymph-node metastasis, indicating clinical significance of the ATM-Snail pathway. Together, our findings provide strong evidence that the ATM-Snail pathway promotes tumor metastasis, highlighting a previously undescribed role of the DDR in tumor invasion and metastasis. [ABSTRACT FROM PUBLISHER]

Group A Streptococcus (GAS) is a human-adapted pathogen that causes a variety of diseases, including pharyngitis and invasive infections. GAS strains are categorized by variation in the nucleotide sequence of the gene (emm) that encodes the M protein. To identify the emm types of GAS strains causing pharyngitis in Ontario, Canada, we sequenced the hypervariable region of the emm gene in 4,635 pharyngeal GAS isolates collected during 2002-2010. The most prevalent emm types varied little from year to year. In contrast, fine-scale geographic analysis identified inter-site variability in the most common emm types. Additionally, we observed fluctuations in yearly frequency of emm3 strains from pharyngitis patients that coincided with peaks of emm3 invasive infections. We also discovered a striking increase in frequency of emm89 strains among isolates from patients with pharyngitis and invasive disease. These findings about the epidemiology of GAS are potentially useful for vaccine research. [ABSTRACT FROM AUTHOR]

Group A Streptococcus (GAS) is a human-adapted pathogen that causes a variety of diseases, including pharyngitis and invasive infections. GAS strains are categorized by variation in the nucleotide sequence of the gene (emm) that encodes the M protein. To identify the emm types of GAS strains causing pharyngitis in Ontario, Canada, we sequenced the hypervariable region of the emm gene in 4,635 pharyngeal GAS isolates collected during 2002-2010. The most prevalent emm types varied little from year to year. In contrast, fine-scale geographic analysis identified inter-site variability in the most common emm types. Additionally, we observed fluctuations in yearly frequency of emm3 strains from pharyngitis patients that coincided with peaks of emm3 invasive infections. We also discovered a striking increase in frequency of emm89 strains among isolates from patients with pharyngitis and invasive disease. These findings about the epidemiology of GAS are potentially useful for vaccine research. [ABSTRACT FROM AUTHOR]

Many pathogens colonize different anatomical sites, but the selective pressures contributing to survival in the diverse niches are poorly understood. Group A Streptococcus (GAS) is a human-adapted bacterium that causes a range of infections. Much effort has been expended to dissect the molecular basis of invasive (sterile-site) infections, but little is known about the genomes of strains causing pharyngitis (streptococcal "sore throat"). Additionally, there is essentially nothing known about the genetic relationships between populations of invasive and pharyngitis strains. In particular, it is unclear if invasive strains represent a distinct genetic subpopulation of strains that cause pharyngitis. We compared the genomes of 86 serotype M3 GAS pharyngitis strains with those of 215 invasive M3 strains from the same geographical location. The pharyngitis and invasive groups were highly related to each other and had virtually identical phylogenetic structures, indicating they belong to the same genetic pool. Despite the overall high degree of genetic similarity, we discovered that strains from different host environments (i.e., throat, normally sterile sites) have distinct patterns of diversifying selection at the nucleotide level. In particular, the pattern of polymorphisms in the hyaluronic acid capsule synthesis operon was especially different between the two strain populations. This finding was mirrored by data obtained from full-genome analysis of strains sequentially cultured from nonhuman primates. Our results answer the long-standing question of the genetic relationship between GAS pharyngitis and invasive strains. The data provide previously undescribed information about the evolutionary history of pathogenic microbes that cause disease in different anatomical sites. [ABSTRACT FROM AUTHOR]