Children's Hospital Foundation

In school-age children, the myelination of the auditory radiation thalamocortical pathway is associated with the latency of auditory evoked responses, with the myelination of thalamocortical axons facilitating the rapid propagation of acoustic information. Little is known regarding this auditory system function-structure association in infants and toddlers. The present study tested the hypothesis that maturation of auditory radiation white-matter microstructure (e.g., fractional anisotropy (FA); measured using diffusion-weighted MRI) is associated with the latency of the infant auditory response (P2m measured using magnetoencephalography, MEG) in a cross-sectional (2 to 24 months) as well as longitudinal cohort (2 to 29 months) of typically developing infants and toddlers. In the cross-sectional sample, non-linear maturation of P2m latency and auditory radiation diffusion measures were observed. After removing the variance associated with age in both P2m latency and auditory radiation diffusion measures, auditory radiation still accounted for significant variance in P2m latency. In the longitudinal sample, latency and FA associations could be observed at the level of a single child. Findings provide strong support for a contribution of auditory radiation white matter to rapid cortical auditory encoding processes in infants.

A subset of individuals with COVID-19 can suffer from a severe form of the disease requiring breathing support for respiratory failure and even death due to disease complications. COVID-19 disease severity can be attributed to numerous factors, where several studies have associated changes in the expression of serum pro-inflammatory cytokines with disease severity. However, very few studies have associated the changes in expression of pro-inflammatory changes in the nasopharyngeal milieu with disease severity. Therefore, in the current study, we performed differential gene expression analysis of various pro-inflammatory cytokines in the nasopharyngeal milieu of mild & severe COVID-19 cases. For this retrospective, cross-sectional study, a total of 118 nasopharyngeal swab samples, previously collected from mild and severe (based on the WHO criteria) COVID-19 patients were used. A real-time qPCR was performed to determine the viral loads and also evaluate the mRNA expression of eight cytokines (IL-1, IL-2, IL-4, IL-6, IL-10, IFN-γ, TGF-β1, and TNF-α). Subsequently, an unpaired T-test was applied to compare the statistical difference in mean expression of viral loads and each cytokine between the mild and severe groups, while the Pearson correlation test was applied to establish a correlation between disease severity, viral load, and cytokines expression. Similarly, a multivariable logistic regression analysis was performed to assess the relationship between different variables from the data and disease severity. Out of 118 samples, 71 were mild, while 47 were severe. The mean viral load between the mild and severe groups was comparable (mild group: 27.07± 5.22; severe group: 26.37 ±7.89). The mRNA expression of cytokines IL-2, IL-6, IFN- γ, and TNF-α was significantly different in the two groups (p<0.05), where the Log2 normalized expression of IL-2, IL-6, IFN- γ, and TNF-α was found to be 2.2-, 16-, 2.3-, and 1.73-fold less in the severe group as compared to the mild group. Furthermore, we also observed a significant positive correlation between all the cytokines in the severe group. The multivariate analysis showed a significant relationship between age, IL-6, and disease severity. This decreased expression of certain cytokines (IL-2, IL-6, TNF-α, and IFN-γ) in the nasopharyngeal milieu may be considered early biomarkers for disease severity in COVID-19 patients.

Abstract Background Glaucoma is increasing as a significant global health problem being the major cause of irreversible blindness worldwide. Early detection and timely management of glaucoma can decrease the burden of blindness worldwide.Methods This was a retrospective hospital -based study conducted at Glaucoma unit in CHEERS Hospital, Bhaktapur from August 2015 to July 2019. Patients demographic profile, along with a comprehensive examination, reviewed from the records. Collected data included: age, sex, race/ethnicity, intraocular pressure, cup/disc ratio, different types of glaucoma, visual field. Data analysis dome with IBM SPSS version 24 and was presented in mean (±SD), frequency and proportions and chi- square test was applied. P value &lt; 0.05 was considered statistically significant.Results Total of 312 glaucoma cases were reviewed and included in this study. The mean age presentation was 61.89±14.4 years, and maximum number (52.6%) was between ages 60-79 years. The majority of patients were primary open angle glaucoma (173, 55.4%) followed by primary angle closure (92, 29.5%). The association between all types of glaucoma and increasing age was statistically significant (P&lt;0.001). Similarly, the association between all types of glaucoma with positive family history and caste/ ethnicity was statistically significant (P&lt;0.001).Conclusion This study showed primary open angle glaucoma as the most common glaucoma. There was a positive association seen between all types of glaucoma with increasing age (beyond age of 40 years) and family history of glaucoma. Screening programs in population with risk factors and opportunistic eye examinations should be conducted for early detection of glaucoma.Trial registration: retrospective registered

To assess the diagnostic accuracy and prognostic value of functional MRI (fMRI) in determining lateralization and predicting postsurgical language and memory outcomes. An 11-member panel evaluated and rated available evidence according to the 2004 American Academy of Neurology process. At least 2 panelists reviewed the full text of 172 articles and selected 37 for data extraction. Case reports, reports with <15 cases, meta-analyses, and editorials were excluded. The use of fMRI may be considered an option for lateralizing language functions in place of intracarotid amobarbital procedure (IAP) in patients with medial temporal lobe epilepsy (MTLE; Level C), temporal epilepsy in general (Level C), or extratemporal epilepsy (Level C). For patients with temporal neocortical epilepsy or temporal tumors, the evidence is insufficient (Level U). fMRI may be considered to predict postsurgical language deficits after anterior temporal lobe resection (Level C). The use of fMRI may be considered for lateralizing memory functions in place of IAP in patients with MTLE (Level C) but is of unclear utility in other epilepsy types (Level U). fMRI of verbal memory or language encoding should be considered for predicting verbal memory outcome (Level B). fMRI using nonverbal memory encoding may be considered for predicting visuospatial memory outcomes (Level C). Presurgical fMRI could be an adequate alternative to IAP memory testing for predicting verbal memory outcome (Level C). Clinicians should carefully advise patients of the risks and benefits of fMRI vs IAP during discussions concerning choice of specific modality in each case.

Many findings support a possible association between gastroesophageal reflux disease (GERD) and asthma in children, but there is not enough evidence to support the causality of this association. Longitudinal studies with long-term follow-up are urgently required to cover the many gaps that persist in this area. Treatment of GERD with proton pump inhibitors (PPIs) in children with uncontrolled asthma does not substantively improve asthma outcomes but large, controlled trials in children symptomatic of both asthma and GERD are lacking. Since there are significant safety concerns for long-term PPIs use in children, physicians should carefully balance their therapeutic decisions in individual cases.

Technological advances have added considerable complexity to newer generations of mechanical ventilators. But it is unclear that the addition of this complexity has led to improved ventilation and presumably improved outcomes. And in some situations neonatal/pediatric clinicians are forced to use ventilators on low birth weight babies that are primarily designed for adults. It is well known that some very widely used neonatal and pediatric ventilators cannot not accurately measure tidal volumes in neonatal and pediatric applications. Also, ventilator-patient dyssynchrony is a major concern of ventilator performance and affects clinical outcomes. Yet, some ventilators are known to have more dyssynchrony than others in neonates. Newer ventilators have been equipped with increasing numbers of modes and features, few if any of which have been proven to improve ventilation related outcomes. Thus, selection of ventilators to use in pediatrics and neonates has become more complex. The well informed decision maker should do bench testing of ventilators being considered for purchase, in order to evaluate the claims of the manufacturers and determine the devices suitability for infants and children. This chapter reviews the features and modes that should be included in a neonatal-pediatric ventilator and describes a systematic approach to evaluating performance of these devices and making a capital budget purchasing decision.

12 September 2011 Dear Editor, Although bisphosphonate therapy is effective in severe childhood osteoporosis, both short and long term side effects occur.1 We have treated a total of 124 children including those with severe Osteogenesis Imperfecta (OI) since 1998, and more recently, patients with other forms of osteoporosis (e.g. juvenile idiopathic osteoporosis or steroid induced) with serious fractures (e.g. vertebral crush fractures). All patients received intravenous pamidronate therapy. The protocols (Table 1) were those used at the Children's Hospital at Westmead at that time. Our protocol included a dietary calcium assessment to ensure a dietary calcium intake of ≥1200 mg/day for at least 1 week after the initial infusion to prevent hypocalcaemia, a known complication of bisphosphonate therapy. Patients were prescribed calcitriol 0.25 mcg twice daily at the time of each pamidronate infusion and for 7 days post-infusion. We present four patients who developed nephrocalcinosis during intravenous pamidronate therapy. None of these patients had nephrocalcinosis prior to commencement of therapy. An 8-year-old boy with severe OI Type 1B and multiple long-bone fractures was treated with intravenous pamidronate and vitamin D as per protocol. His dietary intake of calcium was adequate and baseline vitamin D levels were normal. Early medullary nephrocalcinosis was noted on ultrasound after 3.5 years of pamidronate therapy. Calcitriol therapy was ceased and pamidronate continued. Repeat renal ultrasound after 6 months showed complete resolution of the nephrocalcinosis. A 7-year-old boy with Juvenile Idiopathic Osteoporosis and multiple vertebral compression fractures was referred for continuation of bisphosphonate therapy. He was treated with calcitriol 0.25 mcg (as per protocol) and given supplemental calcium. Mild medullary nephrocalcinosis was identified on renal ultrasound after 2 years of pamidronate therapy. Vitamin D therapy was ceased. Pamidronate therapy was ceased after 3 years of treatment. Renal ultrasound showed complete resolution of nephrocalcinosis after 6 years. A 2-year-old girl with OI Type 1A was commenced on IV pamidronate therapy (total duration 2.5 years) following a history of multiple, atraumatic hip and vertebral fractures. Dietary calcium intake was adequate and baseline vitamin D levels were normal. She was commenced on pamidronate and calcitriol, as per protocol. After 12 months of therapy, she was advised to cease Calcitriol because of concerns arising from Cases 1 and 2 above. Early nephrocalcinosis was noted after 22 months of intravenous bisphosphonate therapy. Follow-up ultrasound after 3 years was normal. A 15-year-old boy with severe ulcerative colitis and steroid induced osteoporosis presented with painful crush fractures of the thoracic spine. Calcium supplementation was commenced. Baseline vitamin D level was normal and vitamin D supplementation was not prescribed. After 12 months of pamidronate therapy ultrasound demonstrated a small area of nephrocalcinosis of the mid pole of the left kidney. The patient admitted taking a natural supplement which contained 320 IU (8 mcg) vitamin D3 per day. Advice was given to cease this supplement and pamidronate therapy was continued. An ultrasound 12 months later was normal. Serum calcium and alkaline phosphatase levels remained normal in all four patients whilst on bisphosphonate therapy. Urinary calcium: creatinine ratio was normal in the four cases presented. Bone turnover markers (urinary pyridinoline and deoxypyridinoline) were measured yearly in all patients on bisphosphonate therapy and remained within the normal range in the four cases. Nephrocalcinosis is defined as a generalised increased solute content (in particular, calcium) within the kidney. Medullary nephrocalcinosis is the typical pattern seen in 98% of cases in humans.2 The diagnosis of nephrocalcinosis is usually made radiologically, using ultrasound, computed tomography or intravenous pyelogram. Risk factors for the development of nephrocalcinosis include; hypercalciuria, vitamin D intoxication, distal renal tubular acidosis, hyperparathyroidism, hyperoxaluria and prematurity.3 The mechanism of development of nephrocalcinosis is likely related to hypercalcaemia and subsequent hypercalciuria. Nephrocalcinosis has not been previously reported following bisphosphonate therapy in children, but has been seen in pamidronate-treated rabbits.4 Vitamin D excess or intoxication can cause severe hypercalcaemia resulting in calcium deposition in the tissues, including nephrocalcinosis.3,5 All of the cases described above were taking vitamin D supplementation in addition to bisphosphonate therapy, either as part of a treatment protocol to prevent hypocalcaemia (Cases 1–3) or as self medication (Case 4). Interestingly, three of the four cases presented were treated with bisphosphonate prior to 2001, when vitamin D supplementation was routine. Since cessation of routine supplementation, only one case has developed nephrocalcinosis and he was found to be inadvertently taking a supplement containing vitamin D. Nephrocalcinosis has been observed in four children treated with both intravenous pamidronate and vitamin D supplementation. Excess Vitamin D has been shown to be a cause of nephrocalcinosis. We suggest that vitamin D supplementation during bisphosphonate therapy may have contributed to the development of nephrocalcinosis. In the presence of normal vitamin D levels, vitamin D supplementation on bisphosphonate therapy may be unnecessary and may be associated with the development of nephrocalcinosis.