Background
Long‐term home noninvasive ventilation (NIV) is increasingly employed in children with sleep‐disordered breathing and chronic respiratory failure. While studies suggest its successful ...implementation in tertiary care centers, little is known about the situation in a general care setting. Hence, we aim to evaluate the clinical profiles of these children in a general pediatric unit over the past two decades.
Methods
Data collected retrospectively on patients younger than 18 years old receiving long‐term home NIV from January 1, 1997 to December 31, 2017 in a Hong Kong regional general pediatric unit were reviewed.
Results
The number of children on home NIV increased more than 10‐fold over the past two decades. In total, 114 children were commenced on NIV during the 21‐year period. Upper airway obstruction was the most common cause (77%), followed by neuromuscular diseases (16%), pulmonary disorders (4%), and abnormal ventilatory control (3%). Continuous positive airway pressure was the most common NIV type (59%). To date, 46% of the children remained in our NIV program, while 18% discontinued NIV support. NIV adherence increased significantly with follow‐up (median of 78.6% and 82.5% at baseline and last follow‐up, respectively). Sixty‐five percent of the children used NIV for at least 4 h on 70% of the days monitored. Higher body mass index was associated with lower adherence.
Conclusion
Pediatric home NIV is feasible in the general care setting with good outcomes and adherence. As the demand for NIV service grows, input from local hospitals will be of increasing importance and should be considered upon healthcare planning.
Neurite outgrowth is a fundamental process in neurons that produces extensions and, consequently, neural connectivity. Neurite damage and atrophy are observed in various brain injuries and disorders. ...Understanding the intrinsic pathways of neurite outgrowth is essential for developing strategies to stimulate neurite regeneration. Insulin is a pivotal hormone in the regulation of glucose homeostasis. There is increasing evidence for the neurotrophic functions of insulin, including the induction of neurite outgrowth. However, the associated mechanism remains elusive. Here, we demonstrate that insulin potentiates neurite outgrowth mediated by the small GTPases ADP‐ribosylation factor 6 (ARF6) and Ras‐related C3 botulinum toxin substrate 1 (Rac1) through the neuronal adaptor FE65. Moreover, insulin enhances atypical protein kinase Cι/λ (PKCι/λ) activation and FE65 phosphorylation at serine 459 (S459) in neurons and mouse brains. In vitro and cellular assays show that PKCι/λ phosphorylated FE65 at S459. Consistently, insulin potentiates FE65 S459 phosphorylation only in the presence of PKCι/λ. Phosphomimetic studies show that an FE65 S459E mutant potently activates ARF6, Rac1, and neurite outgrowth. Notably, this phosphomimetic mutation enhances the FE65‐ARF6 interaction, a process that promotes ARF6‐Rac1‐mediated neurite outgrowth. Likewise, insulin treatment and PKCι/λ overexpression potentiate the FE65–ARF6 interaction. Conversely, PKCι/λ knockdown suppresses the stimulatory effect of FE65 on ARF6‐Rac1‐mediated neurite outgrowth. The effect of insulin on neurite outgrowth is also markedly attenuated in PKCι/λ knockdown neurons, in the presence and absence of FE65. Our findings reveal a novel mechanism linking insulin with ARF6‐Rac1‐dependent neurite extension through the PKCι/λ‐mediated phosphorylation of FE65.
Omicron generally causes milder disease than previous strains of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), especially in fully vaccinated individuals. However, incompletely ...vaccinated children may develop Omicron‐related complications such as those affecting the central nervous system. To characterize the spectrum of clinical manifestations of neuro‐COVID and to identify potential biomarkers associated with clinical outcomes, we recruited 15 children hospitalized for Omicron‐related neurological manifestations in three hospitals in Hong Kong (9 boys and 6 girls aged 1–13 years). All were unvaccinated or incompletely vaccinated. Fourteen (93.3%) were admitted for convulsion, including benign febrile seizure (n = 7), complex febrile seizure (n = 2), seizure with fever (n = 3), and recurrent breakthrough seizure (n = 2), and the remaining nonconvulsive patient developed encephalopathic state with impaired consciousness. None of the seven children with benign febrile seizure and six of eight children with other neurological manifestations had residual deficits at 9‐month follow‐up. SARS‐CoV‐2 RNA was undetectable in the cerebrospinal fluid (CSF) specimens of seven patients who underwent lumbar puncture. Spike‐and‐wave/sharp waves affecting the frontal lobes were detected in four of seven (57.1%) patients who underwent electroencephalogram. Children with Omicron‐related neurological manifestations had significantly higher blood levels of IL‐6 (p < 0.001) and CHI3L1 (p = 0.022) than healthy controls, and higher CSF levels of IL‐6 (p = 0.002) than children with non‐COVID‐19‐related febrile illnesses. Higher CSF‐to‐blood ratios of IL‐8 and CHI3L1 were associated with longer length of stay, whereas higher ratios of IL‐6 and IL‐8 were associated with higher blood tau level. The role of CSF:blood ratio of IL‐6, IL‐8, and CHI3L1 as prognostic markers for neuro–COVID should be further evaluated.
Heated humidified high flow nasal cannula (HHHFNC) has gained popularity in the treatment of children with respiratory distress and bronchiolitis in the past decade. Its efficacy as a mode of ...non-invasive respiratory support has been demonstrated in both adults and children. However, reports on its use in the treatment of obstructive sleep apnea (OSA) in infants are limited. We aimed to evaluate the efficacy of HHHFNC therapy as treatment in infants with OSA.
A retrospective analysis of OSA infants who had undergone polysomnographic titration between 2015 and 2017 was undertaken. Data about the age, gender, AHI, co-morbid conditions and flow used for each patient were retrieved.
Ten infants were included in this study (median age 34 weeks; IQR 27–38 weeks). The median optimal HHHFNC flow rate was 8.0 L/min (IQR 6.7–8.0 L/min). HHHFNC significantly reduced median obstructive apnea–hypopnea index (OAHI) from 9.1 (IQR 5.1–19.3) to 0.9 (IQR 0–1.6; P = 0.005) events/h; median obstructive apnea index (OAI) from 5.8 (IQR 1.1–13.4) to 0 (IQR 0–0.9; P = 0.021) events/h; median obstructive hypopnea index (OHI) from 4.1 (IQR 0.9–6.8) to 0.1 (0–0.9; P = 0.017) events/h; and median oxygen saturation (SpO2) nadir increased from 88% (IQR 83–94%) to 94% (IQR 93–96%; P = 0.040).
HHHFNC significantly reduced respiratory events and improved oxygenation in infants with OSA.
•Heated humidified high flow can be used to treat obstructive sleep apnea in infants.•HHHFNC is an alternative to CPAP in treating OSA in infants.•Malacic airway is a cause of OSA in both preterm and term infants.
Summary Given that miR-124 is preferentially expressed in differentiating and mature neurons and external granule cells of cerebellum are thought to be cells-of-origins of medulloblastomas, we ...investigated if miR-124 played a role in the development of medulloblastomas. Quantitative expression analysis of 29 medulloblastomas demonstrated significant down-regulation of miR-124 in 21 (72%) tumors by at least 2-fold, with 11 of them exhibiting greater than 10-fold reduced level compared to normal cerebella ( P < .01). Ectopic expression of miR-124 in medulloblastoma cell lines, ONS-76 and DAOY, inhibited cell proliferation. Using computational and expression analyses, solute carrier family 16, member 1 (SLC16A1) was identified as a candidate target of miR-124. Transfection of miR-124 resulted in down-regulation of SLC16A1 at both transcript and protein levels. Reporter assay with 3′ untranslated region of SLC16A1 cloned downstream of the luciferase gene showed reduced luciferase activity in the presence of miR-124, providing strong evidence that miR-124 is a direct regulator of SLC16A1. Expression analysis further revealed that SLC16A1 transcript was elevated in 26 (90%) of 29 tumors examined. Knockdown of SLC16A1 by siRNA induced cell death in medulloblastoma cells. SLC16A1 functions to efflux lactic acid during aerobic glycolysis. We speculated that inhibition of SLC16A1 function resulted in a decrease of intracellular pH to a lethal level. In conclusion, our study demonstrates that miR-124 deregulation is common in medulloblastomas, and restoration of its function inhibits cell proliferation, suggesting that miR-124 may act as a growth suppressor. Our findings also raise the possibility that the miR-124/SLC16A1 pathway may represent a novel therapeutic target for treatment of malignant medulloblastomas.
Evidence about the association between the level of sports activities participation post-diagnosis and quality of life (QoL) among Chinese women with early-stage breast cancer is limited. A validated ...modified Chinese Baecke questionnaire was used to prospectively measure sports activities among a breast cancer cohort at four time-points: baseline and 18, 36, and 60 months after diagnosis (sports activities during the previous 12 months before each interview); QoL was measured at the same time. In total, 1289, 1125, and 1116 patients were included in the analyses at 18-, 36- and 60-month follow-up, respectively. The percentages of patients who belonged to no (0 metabolic equivalent of task (MET)-hours per week), low-level (<10 MET-hours/week), and high-level (≥10 MET-hours/week) sports activities group were 20.7%, 45.5%, and 33.8% at 18-month follow-up, respectively; the corresponding figures at 36 and 60 months differed slightly. Using data from the three follow-ups, generalized estimating equation (GEE) analyses showed that higher levels of sports activities participation were associated with better QoL in several items as well as fewer symptoms. The present findings in Chinese women with breast cancer provide important evidence on the beneficial effect of regular participation in sports activities following cancer diagnosis on patients’ QoL.
DNA damage plays a central role in the cellular pathogenesis of polyglutamine (polyQ) diseases, including Huntington's disease (HD). In this study, we showed that the expression of untranslatable ...expanded CAG RNA per se induced the cellular DNA damage response pathway. By means of RNA sequencing (RNA-seq), we found that expression of the
(
) gene was down-regulated in mutant CAG RNA-expressing cells. The loss of NUDT16 function results in a misincorporation of damaging nucleotides into DNAs and leads to DNA damage. We showed that small CAG (sCAG) RNAs, species generated from expanded CAG transcripts, hybridize with CUG-containing
mRNA and form a CAG-CUG RNA heteroduplex, resulting in gene silencing of
and leading to the DNA damage and cellular apoptosis. These results were further validated using expanded CAG RNA-expressing mouse primary neurons and in vivo R6/2 HD transgenic mice. Moreover, we identified a bisamidinium compound, DB213, that interacts specifically with the major groove of the CAG RNA homoduplex and disfavors the CAG-CUG heteroduplex formation. This action subsequently mitigated RNA-induced silencing complex (RISC)-dependent
silencing in both in vitro cell and in vivo mouse disease models. After DB213 treatment, DNA damage, apoptosis, and locomotor defects were rescued in HD mice. This work establishes NUDT16 deficiency by CAG repeat RNAs as a pathogenic mechanism of polyQ diseases and as a potential therapeutic direction for HD and other polyQ diseases.
The proportionality between anatomical characteristics and disease severity in children and adolescents with obstructive sleep apnea (OSA) has not been well characterized. The present study ...investigated the relationship between the dentoskeletal and oropharyngeal features of young patients with OSA and either the apnea-hypopnea index (AHI) or the amount of upper airway obstruction.
MRI of 25 patients (8- to 18-year-old) with OSA (mean AHI = 4.3 events/h) was retrospectively analyzed. Sleep kinetic MRI (kMRI) was used to assess airway obstruction, and static MRI (sMRI) was used to assess dentoskeletal, soft tissue, and airway parameters. Factors related to AHI and obstruction severity were identified with multiple linear regression (significance level
= 0.05).
As evidenced by kMRI, circumferential obstruction was present in 44% of patients, while laterolateral and anteroposterior was present in 28%; as evidenced by kMRI, obstructions were retropalatal in 64% of cases and retroglossal in 36% (no nasopharyngeal obstructions); kMRI showed a higher prevalence of retroglossal obstructions compared to sMRI(
= 0.037); the main obstruction airway area was not related to AHI; the maxillary skeletal width was related to AHI (
= -0.512,
= 0.007) and obstruction severity (
= 0.625,
= 0.002); and the retropalatal width was related to AHI (
= -0.384,
= 0.024) and obstruction severity (
= 0.519,
= 0.006).
In children and adolescents, the severity of OSA and obstruction were inversely proportional to the maxillary basal width and retropalatal airway width. Further studies are needed to assess the benefits of targeted clinical treatments widening the transverse dimension of these structures.
To investigate the effect of surgical intervention on 24-h ABP in children with OSA. It was hypothesized that blood pressure would improve following adenotonsillectomy.
This was a two-centered ...investigator-blinded randomized controlled trial. Non-obese pre-pubertal children aged 6–11 years with OSA (obstructive apnea-hypopnea index, OAHI >3/h) underwent 24-h ABP monitoring at baseline and 9 months after the randomly assigned intervention, i.e. Early Surgery (ES) or Watchful Waiting (WW). Intention-to-treat analysis was performed.
137 subjects were randomized. Sixty-two (Age: 7.9y ± 1.3, 71% boys) and 47 (Age: 8.5y ± 1.6, 77% boys) participants from the ES and WW groups, respectively completed the study. Changes in ABP parameters were similar in the ES and WW groups (nighttime systolic BP z-scores: +0.03 ± 0.93 vs. −0.06 ± 1.04, p = 0.65; nighttime diastolic BP z-scores: −0.20 ± 0.95 vs. −0.02 ± 1.00, p = 0.35) despite a greater improvement in OSA in the ES group. However, a reduction in nighttime diastolic BP z-score correlated with improvements in OSA severity indexes (r = 0.21–0.22, p < 0.05), and a significant improvement in nighttime diastolic BP z-score -0.43 ± 1.01, p = 0.027 following surgery was observed in participants with severe preoperative OSA (OAHI ≥10/h). The ES group had a significant increase in body mass index z-score after surgery +0.27 ± 0.57, p < 0.001, which correlated with the increase in daytime systolic BP z-score (r = 0.2, p < 0.05).
Surgical treatment did not lead to significant improvements in ABP in OSA children except in those with more severe disease. The improvement in BP was partially masked by the weight gain following surgery.
The trial was registered with the Chinese Clinical Trial Registry (http://www.chictr.org.cn. Registration number: ChiCTR-TRC-14004131).
•No significant treatment effect of adenotonsillectomy on BP was observed in OSA children.•The improvement on BP after the surgery was more prominent in children with severe OSA.•Weight gain after the surgery was associated with the increase in BP.
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