Dietary profile of pediatric obstructive sleep apnea patients, effects of routine educational counseling, and predictors for outcomes.

Background: Dietary behavior is a main contributing yet modifiable factor to the body weight status of children and may be involved in the pathophysiology of childhood obstructive sleep apnea (OSA). This study aimed to investigate the dietary profile of pediatric OSA patients, effects of educational counseling after adenotonsillectomy, and predictor for disease resolution. Methods: This observational study included 50 pediatric OSA patients undergoing adenotonsillectomy with routine educational counseling (Group 1), 50 pediatric OSA patients undergoing adenotonsillectomy without formal educational counseling (Group 2), and 303 healthy children without OSA (Control). The three groups were matched by age. The consumption frequency of 25 food items/groups was assessed by the Short Food Frequency Questionnaire. Quality of life was evaluated by the OSA-18 questionnaire. Sleep architecture and OSA severity were measured by standard polysomnography. Between- and within-group comparisons were analyzed by non-parametric approaches and generalized estimating equations. Prediction of disease recovery was performed by multivariable logistic regression models. Results: Group 1 children consumed fruit drinks with sugar, vegetables, sweets, chocolate, rice, and noodles more frequently than Control Group children. At baseline, the distributions of sex, weight status, OSA-18 scores, and polysomnographic variables were comparable between Group 1 and Group 2. After a 12-month follow-up, Group 1 had better improvements in physical suffering, caregiver concerns, sleep architecture, and mean peripheral oxygen saturation compared to Group 2. Furthermore, Group 1 no longer had excessive consumption of fruit drinks with sugar, chocolate, and noodles; however, food consumption frequencies did not change significantly. Notably, younger age and reduced intake of butter/margarine on bread and noodles were independent predictors of cured OSA in Group 1. Conclusion: The present study preliminarily characterized an unhealthy dietary profile among pediatric OSA patients and suggested that routine educational counseling in addition to adenotonsillectomy yielded some clinical benefits. Certain items/groups of food frequencies may be associated with disease recovery and further investigations are warranted.

Effect of Preoperative Weight Status and Disease Presentation on Postoperative Elevated Blood Pressure After Childhood Adenotonsillectomy.

OBJECTIVE: To investigate the risk factors of postoperative elevated blood pressure (BP) in children with childhood obstructive sleep apnea syndrome (OSAS) after adenotonsillectomy (AT). STUDY DESIGN: Case series with planned data collection. SETTING: Tertiary referral center. METHODS: Two hundred forty-five consecutive children (180 boys and 65 girls, median age 6.6 years) with polysomnography-diagnosed OSAS who underwent AT between January 2010 and August 2019. Clinical, polysomnographic, and evening BP data were assessed preoperatively and postoperatively (≥3 months after AT). Changes in the variables before and after AT and between individuals with and without hypertension were compared. RESULTS: Postoperatively, the median (interquartile range) apnea-hypopnea index significantly decreased from 10.4 (5.3-22.6) to 2.2 (1.0-3.8) events/h. In addition, the mean (standard deviation) evening diastolic BP z-score significantly decreased from 0.7 (0.94) to 0.5 (0.81) in the overall cohort, and both systolic (2.1 [0.94]-1.0 [1.31]) and diastolic BP z-scores (1.6 [0.98]-0.7 [0.85]) significantly decreased in the preoperative elevated BP subgroup. Multivariate logistic regression analysis showed that preoperative obesity (adjusted odds ratio = 4.36, 95% confidence interval = 2.24-8.49) and mean peripheral oxygen saturation <95% during sleep (adjusted odds ratio = 2.73, 95% confidence interval = 1.29-5.79) were independently associated with postoperative elevated BP. CONCLUSION: Preoperative obesity and mean peripheral oxygen saturation <95% during sleep were significantly associated with postoperative elevated BP in the children with OSAS, further indicating the importance of careful BP monitoring in this subgroup despite AT treatment.

Adenotonsillectomy-related changes in systemic inflammation among children with obstructive sleep apnea.

BACKGROUND: Adenotonsillar hypertrophy is the most common cause of pediatric obstructive sleep apnea (OSA). Although adenotonsillectomy considerably reduces OSA and systemic inflammation, whether and how systemic inflammation influences the effects of adenotonsillectomy on OSA has yet to be determined. METHODS: This study investigated the associations between changes in anatomical variables, % changes in subjective OSA-18 questionnaire scores, % changes in 11 polysomnographic parameters, and % changes in 27 systemic inflammatory biomarkers in 74 children with OSA. RESULTS: Fifty-six (75.6%) boys and 18 (24.4%) girls with the mean age of 7.4 ± 2.2 years and apnea-hypopnea index (AHI) of 14.2 ± 15.9 events/h were included in the statistical analysis. The mean period between before and after adenotonsillectomy was 5.6 ± 2.6 months. After adenotonsillectomy, the OSA-18 score, eight of 11 polysomnographic parameters, and 20 of 27 inflammatory biomarkers significantly improved (all p < 0.005). Notably, there were significant associations between change in tonsil size and % change in AHI ( r = 0.23), change in tonsil size and % changes in interleukin-8 (IL-8) ( r = 0.34), change in tonsil size and % change in and IL-10 ( r = -0.36), % change in IL-8 and % change in C-C chemokine ligand 5 (CCL5) ( r = 0.30), and % change in CCL5 and % change in AHI ( r = 0.38) (all p < 0.005). Interestingly, % change in IL-8 and % change in CCL5 serially mediated the relationship between change in tonsil size and % change in AHI (total effect: ß = 16.672, standard error = 8.274, p = 0.048). CONCLUSION: These preliminary findings suggest that systemic inflammation is not only a complication of OSA but also that it mediates the surgical effects, which may open avenues for potential interventions to reduce tonsil size and OSA severity through the regulation of IL-8 and CCL5.

Using sleep heart rate variability to investigate the sleep quality in children with obstructive sleep apnea.

Background: Obstructive sleep apnea (OSA) is associated with impaired sleep quality and autonomic dysfunction. Adenotonsillectomy significantly improves subjective and objective sleep quality in children with OSA. However, the postoperative changes in heart rate variability (HRV) indices (indicators of cardiac autonomic function) and their importance remain inconclusive in childhood OSA. This retrospective case series aimed to investigate the association of sleep HRV indices, total OSA-18 questionnaire score (a subjective indicator of sleep quality) and polysomnographic parameters (objective indicators of sleep quality), and effects of adenotonsillectomy on HRV indices, total OSA-18 questionnaire score and polysomnographic parameters in children with OSA. Methods: Seventy-six children with OSA were included in baseline analysis, of whom 64 (84%) completed at least 3 months follow-up examinations after adenotonsillectomy and were included in outcome analysis. Associations between baseline variables, and relationships with treatment-related changes were examined. Results: Multivariable linear regression models in the baseline analysis revealed independent relationships between tonsil size and obstructive apnea-hypopnea index (OAHI), adenoidal-nasopharyngeal ratio and very low frequency (VLF) power of HRV (an indicator of sympathetic activity), and normalized low frequency power (an indicator of sympathetic activity) and OAHI. The outcome analysis showed that adenotonsillectomy significantly improved standard deviation of all normal-to-normal intervals, and high frequency power, QoL (in terms of reduced total OSA-18 questionnaire score), OAHI and hypoxemia. Using a conceptual serial multiple mediation model, % change in OSA-18 questionnaire score and % change in VLF power serially mediated the relationships between change in tonsil size and % change in OAHI. Conclusions: The improvement in OAHI after adenotonsillectomy was serially mediated by reductions in total OSA-18 questionnaire score and VLF power. These preliminary findings are novel and provide a direction for future research to investigate the effects of VLF power-guided interventions on childhood OSA.

Cognitive Outcomes Following Intravitreal Bevacizumab for Retinopathy of Prematurity: 4- to 6-Year Outcomes in a Prospective Cohort.

PURPOSE: To determine the long-term cognitive outcomes in children who underwent intravitreal bevacizumab (IVB) for retinopathy of prematurity (ROP). DESIGN: Prospective cohort study. METHODS: This single-center study enrolled 186 children between 3 and 6 years of age and included 101 children in the final analysis: premature without ROP (group 1), ROP not needing treatment (group 2), IVB monotherapy (group 3), IVB plus laser therapy (group 4), and laser monotherapy (group 5). The Full-Scale Intelligence Quotient (FSIQ) was evaluated by the Wechsler Preschool and Primary Scale of Intelligence Test at baseline and then annually for 1-2 years and compared among groups. RESULTS: The age at cognitive evaluation was 4.5-4.9 years at baseline and 6.1-7.0 years at the last follow-up. The FSIQ was comparable among the groups at both time points (P = .08 and .50, respectively). Severe cognitive impairment (FSIQ < 70) was more common in group 4 at baseline (4%, 22%, 13%, 33%, and 0% in groups 1-5, respectively; P = .03) but did not differ among the groups at the last follow-up (6%, 0%, 4%, 22%, and 0%; P = .22). After adjusting for sex, Apgar score, neonatal adverse events, and days on mechanical ventilation, IVB was not associated with FSIQ either at baseline or at the last follow-up. CONCLUSIONS: At 4.5 to beyond 6 years of age, children who underwent IVB monotherapy had comparable cognitive outcomes compared to the other premature children without prior IVB. Children who underwent IVB plus laser showed higher severe cognitive impairment at 4.5 years of age.

Short-term and long-term psychological impact and quality of life of patients undergoing orthognathic surgery.

BACKGROUND: Orthognathic Surgery (OGS) is a surgery for patients with dento-facial deformity but not all patients are satisfied with its outcome. The purpose of this study is to find out the short-term and long-term psychological impact and quality-of-life of OGS. METHODS: 77 participants receiving OGS and 32 age and gender-matched controls were enrolled. The data of questionnaires were collected before OGS, one month and 9 months after OGS, including short form of the Derriford-Appearance-Scale (DAS-24), Big-Five-Inventory (BFI), Hospital-Anxiety-and-Depression-Scale (HADS), Pittsburgh-sleep-quality-index (PSQI), and 36-Item Short-Form-Health-Survey (SF-36). Variables were presented as mean ± standard deviation or frequency. Paired t-test, ANOVA and MANOVA were used to evaluate the pre-and post-surgery data. RESULTS: Short-term and long-term satisfaction of OGS was high. Before OGS, BFI showed the extraversion had significant difference between the male and female OGS subgroups. Several domains of DAS-24 were significantly different between the OGS and the control groups. Both groups had no significant difference in PSQI, HADS and SF-36, except sleep-efficiency. After OGS, many domains of DAS-24 were significantly improved and the improvement persisted to 9 months later. Sleep-latency, physical-function, role-limitations-due-to-physical-health and social-functioning exacerbated after OGS. Sleep-latency, physical-function, and social-functioning were improved 9 months after OGS, but sleep-efficiency and role-limitations-due-to-physical-health were still significantly worse than controls. CONCLUSION: People received OGS for unfavorable appearance and the surgery could decrease their distress of appearance and impact to their daily living. Through long-term assessment, we should pay attention to sleep problems and role-limitations-due-to-physical-health after OGS.

Involvement of Rare Mutations of SCN9A, DPP4, ABCA13, and SYT14 in Schizophrenia and Bipolar Disorder.

Rare mutations associated with schizophrenia (SZ) and bipolar disorder (BD) usually have high clinical penetrance; however, they are highly heterogeneous and personalized. Identifying rare mutations is instrumental in making the molecular diagnosis, understanding the pathogenesis, and providing genetic counseling for the affected individuals and families. We conducted whole-genome sequencing analysis in two multiplex families with the dominant inheritance of SZ and BD. We detected a G327E mutation of SCN9A and an A654V mutation of DPP4 cosegregating with SZ and BD in one three-generation multiplex family. We also identified three mutations cosegregating with SZ and BD in another two-generation multiplex family, including L711S of SCN9A, M4554I of ABCA13, and P159L of SYT14. These five missense mutations were rare and deleterious. Mutations of SCN9A have initially been reported to cause congenital insensitivity to pain and neuropathic pain syndromes. Further studies showed that rare mutations of SCN9A were associated with seizure and autism spectrum disorders. Our findings suggest that SZ and BD might also be part of the clinical phenotype spectra of SCN9A mutations. Our study also indicates the oligogenic involvement in SZ and BD and supports the multiple-hit model of SZ and BD.

Sleep, Distressed Appearance, and Quality of Life Relate to Satisfaction with Orthognathic Surgery.

BACKGROUND: In this study, we aimed to identify factors correlating with satisfaction with orthognathic surgery in order to improve its outcome. METHODS: We recruited 77 participants who had received orthognathic surgery and 32 age- and gender-matched normal-controls. Questionnaires that included devised questions for family support, Big Five Inventory, Derriford Appearance Score, Pittsburgh Sleep Quality Index, Hospital Anxiety and Depression Scale, 36-Item Short-Form Health Survey, and a visual analogy scale for satisfaction, were completed before and one month and nine months after the surgery. The statistical analysis methods included descriptive statistics, t-test, and Pearson correlation. RESULTS: All participants received the preoperative and one-month follow-up, while 28 also completed the nine-month follow-up. Satisfaction was not significantly related to demographic data, but long-term satisfaction was related to an extraverted personality. The preoperative and postoperative results of the Derriford Appearance Scale were related to short-term and long-term satisfaction. Furthermore, both the preoperative and one-month postoperative Pittsburgh Sleep Quality Index findings were significantly related to short-term satisfaction. The postoperative 36-Item Short-Form Health Survey was significantly related to short-term and long-term satisfaction. CONCLUSIONS: Not only subjective distress and dysfunction of appearance but also sleep problems and quality of life were correlated to satisfaction with orthognathic surgery. In the future, relevant interventions can be developed to further improve patient's satisfaction and their physical and mental health.

Screening Severe Obstructive Sleep Apnea in Children with Snoring.

Efficient screening for severe obstructive sleep apnea (OSA) is important for children with snoring before time-consuming standard polysomnography. This retrospective cross-sectional study aimed to compare clinical variables, home snoring sound analysis, and home sleep pulse oximetry on their predictive performance in screening severe OSA among children who habitually snored. Study 1 included 9 (23%) girls and 30 (77%) boys (median age of 9 years). Using univariate logistic regression models, 3% oxygen desaturation index (ODI3) ≥ 6.0 events/h, adenoidal-nasopharyngeal ratio (ANR) ≥ 0.78, tonsil size = 4, and snoring sound energy of 801-1000 Hz ≥ 22.0 dB significantly predicted severe OSA in descending order of odds ratio. Multivariate analysis showed that ODI3 ≥ 6.0 events/h independently predicted severe pediatric OSA. Among several predictive models, the combination of ODI3, tonsil size, and ANR more optimally screened for severe OSA with a sensitivity of 91% and a specificity of 94%. In Study 2 (27 (27%) girls and 73 (73%) boys; median age, 7 years), this model was externally validated to predict severe OSA with an accuracy of 76%. Our results suggested that home sleep pulse oximetry, combined with ANR, can screen for severe OSA more optimally than ANR and tonsil size among children with snoring.

Objective and subjective long term outcome of maxillomandibular advancement in obstructive sleep apnea.

STUDY OBJECTIVES: To evaluate the objective and subjective long-term outcome of maxillomandibular advancement (MMA) in Far-East Asian patients with moderate to severe obstructive sleep apnea (OSA). METHODS: This is a long-term follow-up study to evaluate the treatment outcome of MMA in OSA patients by objective polysomnography (PSG) and subjective questionnaires (Pittsburgh Sleep Quality Index-PSQI, Insomnia Severity Index-ISI, Beck Anxiety Inventory-BAI, Beck Depression Inventory-BDI, Epworth Sleepiness scale-ESS, and Short Form-36 Quality of Life-SF-36). Evaluation was done before surgery and we followed these patients one and two years after surgery. We also assessed the neurocognitive function by Continuous performance test (CPT) and Wisconsin Card Sorting Test (WCST) before and after MMA. RESULTS: A total of 82 patients with OSA (female = 19) were enrolled and 53 participants (75.7% men, age 35.66 ± 11.66 years [mean ± SD], BMI = 24.80 ± 3.29) completed the two-year follow-up. The apnea-hypopnea index (AHI) decreased from a mean of 34.78 ± 26.01 to 3.61 ± 2.79 and 7.43 ± 6.70 events/hour (p = 0.007) at the first and second year evaluation. There was significant improvement in PSG (especially respiratory profile), questionnaires (PSQI and ISI total score), and neurocognitive testing (attention and executive function) after MMA. Meanwhile, no major complication such as avascular necrosis of bonny segments, facial nerve injury, blindness or compromise of airway was found after surgery. CONCLUSIONS: MMA is a clinically effective treatment for patients with moderate-to-severe OSA as demonstrated by significant long-term decrease in AHI and improvement in neurocognitive testing.

Differences in Anthropometric and Clinical Features among Preschoolers, School-Age Children, and Adolescents with Obstructive Sleep Apnea-A Hospital-Based Study in Taiwan.

Pediatric obstructive sleep apnea (OSA) is associated with adverse health outcomes; however, little is known about the diversity of this population. This retrospective study aims to investigate age-related differences in the anthropometric and clinical features of this population. A total of 253 Taiwanese children (70 (27.7%) girls and 183 (72.3%) boys) with OSA were reviewed. Their median age, body mass index (BMI) z-score, and apnea-hypopnea index were 6.9 years, 0.87, and 9.5 events/h, respectively. The cohort was divided into three subgroups: 'preschoolers' (≥2 and <6 years), 'school-age children' (≥6 and <10 years), and 'adolescents (≥10 and <18 years)'. The percentage of the male sex, BMI z-score, neck circumference, systolic blood pressure z-score, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio tended to increase with age. Adenoid grades tended to decrease with age. Overall, disease severity was independently correlated with neck circumference, tonsil size, and adenoid grade. Increased neck circumference and tonsillar hypertrophy were the most influential factors for younger children, whereas adenoidal hypertrophy became more important at an older age. In conclusion, gender prevalence ratio, anthropometric measures, and clinical features varied with age, and the pathogenic drivers were not necessarily the same as the aggravating ones.

Inflammatory Factors: Nonobese Pediatric Obstructive Sleep Apnea and Adenotonsillectomy.

BACKGROUND: Inflammation is often considered relating to pediatric obstructive sleep apnea (OSA). We conducted a study investigating cytokines, including Il-17 and Il-23, in children with OSA before and after adenotonsillectomy (T&A), compared with controls. METHODS: Children with OSA between age 4 and 12 receiving T&A were prospectively followed. Evaluation before and reevaluation six months after the treatment were done, including polysomnography (PSG), blood tests, and questionnaires. Blood samples were obtained to determine the values of high-sensitivity-C-reactive-protein (HS-CRP); tumor-necrosis-factor-alpha (TNF-α); and interleukin (IL)-1, 6, 10, 12, 17, and 23. We compared the results with an age-matched control group. RESULTS: We included 55 OSA children and 32 controls. Children with OSA presented significant improvement after T&A in complaints, signs, apnea hypopnea index (AHI) (p < 0.001), mean oxygen desaturation index (p < 0.001), and mean oxygen saturation (p = 0.010). Upon entering this study, children with OSA had significantly higher cytokine levels than the controls and significant changes in HS-CRP (p = 0.013), TNF-α (p = 0.057), IL-1ß (p = 0.022), IL-10 (p = 0.035), and IL-17 (p = 0.010) after T&A. Children with improved but persistently abnormal AHI did not have all cytokine levels normalized, particularly IL-23 and HS-CRP. CONCLUSION: Sleep-disordered breathing can persist after T&A and can continue to have a negative inflammatory effect. HS-CRP and IL-23 may serve as blood markers for the persistence of sleep-disordered breathing after T&A.

Relationships Among and Predictive Values of Obesity, Inflammation Markers, and Disease Severity in Pediatric Patients with Obstructive Sleep Apnea Before and After Adenotonsillectomy.

Both obstructive sleep apnea (OSA) and obesity are major health issues that contribute to increased systemic inflammation in children. To date, adenotonsillectomy (AT) is still the first-line treatment for childhood OSA. However, the relationships among and predictive values of obesity, inflammation, and OSA severity have not been comprehensively investigated. This prospective study investigated body mass index (BMI), serum inflammatory markers, and OSA severity before and after AT in 60 pediatric patients with OSA. At baseline, differences in levels of interleukin-6, interleukin-9, basic fibroblast growth factor, platelet-derived growth factor-BB, as well as regulated on activation, normal T cell expressed and secreted (RANTES) were significant among the various weight status and OSA severity subgroups. After 3 months postoperatively, the differences in these inflammatory markers diminished along with a decrease in OSA severity while obesity persisted. The rate of surgical cure (defined as postoperative obstructive apnea-hypopnea index < 2.0 and obstructive apnea index < 1.0) was 62%. Multivariate analysis revealed that age, BMI z-score, granulocyte-macrophage colony-stimulating factor, monocyte chemotactic protein-1, and RANTES independently predicted surgical cure. Despite the significant reductions in inflammatory markers and OSA severity after AT, an inter-dependent relationship between obesity and OSA persisted. In addition to age and BMI, several inflammatory markers helped to precisely predict surgical cure.

Neurodevelopmental Outcomes after Intravitreal Bevacizumab Therapy for Retinopathy of Prematurity: A Prospective Case-Control Study.

PURPOSE: To evaluate the neurodevelopmental and ocular developmental outcomes in premature children who have undergone intravitreal bevacizumab injection (IVB) for treatment of type 1 retinopathy of prematurity (ROP). DESIGN: Prospective case-control study. PARTICIPANTS: We enrolled 3 groups of premature patients: premature children who had no history of ROP (group 0), premature children with history of ROP without treatment (group 1), and premature children with ROP who had received a single IVB (0.625 mg; group 2). METHODS: Ocular developmental assessment, including cycloplegic refractometry, axial length, Cardiff acuity, and neurodevelopmental assessment via the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley III), were performed at 1 to 3 years of age and were compared between groups. MAIN OUTCOME MEASURES: Ocular developmental outcomes and Bayley III scores. RESULTS: A total of 148 patients (85 boys and 63 girls) were included. The mean age at assessment was 1.49±0.59 years. Group 0 patients demonstrated significantly higher gestational age (GA), birth weight, and Apgar scores compared with group 1 and 2 patients. There were no significant differences between groups 1 and 2 in demographics or systemic risk factors except for lower GA in group 2. The cylindrical power was significantly larger in groups 1 and 2 compared with group 0. The spherical equivalent was significantly more myopic and the Cardiff acuity was significantly poorer in group 2 than in group 0. There were no significant differences between groups 1 and 2 in refractive status, axial length, or Cardiff acuity. Neurodevelopmental assessment using Bayley III showed no significant difference among the 3 groups in any aspect after adjusting for GA and other systemic risk factors. The risks for poor neurodevelopmental outcomes also were not significantly different. CONCLUSIONS: At the mean age of 1.5 years, children with prior history of IVB (group 2) showed similar refractive and visual outcomes and similar neurodevelopmental outcomes compared with premature patients with ROP without requirement of treatment (group 1), although there is a possibility that a small but clinically significant difference may not have been detected in the current study.

Snoring sound energy as a potential biomarker for disease severity and surgical response in childhood obstructive sleep apnoea: A pilot study.

OBJECTIVE: To investigate the relationship between baseline snoring sound energy (SSE) and disease severity, changes in SSE after adenotonsillectomy, and the predictors of surgical success in children with obstructive sleep apnoea (OSA). DESIGN: Prospective cohort study. SETTING: Tertiary referral medical centre. PARTICIPANTS: Thirty-two children with OSA whose apnoea-hypopnoea index ≥5 or apnoea-hypopnoea index ≥1.5 with OSA comorbidities were recruited. Patients with complicated OSA were excluded. All participants underwent snoring sound analysis, polysomnography, and adenotonsillectomy. MAIN OUTCOME MEASURES: Snoring sound energy and apnoea-hypopnoea index were assessed at baseline and 6 months after adenotonsillectomy. Surgical success was defined as a postoperative apnoea-hypopnoea index <1.5. RESULTS: The median age, body mass index, and apnoea-hypopnoea index was 9 years, 19.0 kg/m2 , and 13.2 events/h, respectively. Multivariate logistic regression showed that a baseline tonsil size of IV (odds ratio 15.7 [95% CI: 1.5-166.3]) and SSE of 801-1000 Hz > 21.9 dB (odds ratio 32.3 [95% CI: 2.6-396.6]) were significantly related to severe OSA. Following adenotonsillectomy, apnoea-hypopnoea index decreased significantly (P < 0.001). SSE of 41-200 Hz, 201-400 Hz and 801-1000 Hz also decreased significantly (P = 0.04, 0.01 and 0.006, respectively). Baseline SSE of 801-1000 Hz < 8.5 dB significantly predicted surgical success (odds ratio 11.0 [95% CI: 1.4-85.2]). CONCLUSIONS: Our findings suggest the potential utility of SSE of 801-1000 Hz to screen for severe OSA, predict surgical success and assess therapeutic outcomes. Specific baseline SSE may represent a potential biomarker for childhood OSA.

HCBP6 Is Involved in the Development of Hepatic Steatosis Induced by High-Fat Diet and CCL4 in Rats.

INTRODUCTION AND AIM: Hepatitis C virus core-binding protein 6 (HCBP6) was previously found to be an hepatitis C virus corebinding protein, its biological function remains unclear. Our research aims to investigate the role of HCBP6 in the development of hepatic steatosis induced by high-fat diet and carbon tetrachloride (CCL4) in rats. MATERIAL AND METHODS: Eighteen Wistar rats were randomly allocated into 3 groups: control group, model group 1, and model group 2. The control group was treated with a standard diet for 5 weeks. Model groups were treated with high-fat diet and CCL4 injection twice a week for 3 weeks in Group 1 and 5 weeks in Group 2, respectively. After the intervention, hepatic steatosis was observed by histological staining with hematoxylin and eosin (H&E) and Oil Red O staining. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total colesterol (TC), and triglycerides (TGs) were measured. The TG content in liver homogenates was evaluated. Expressions of HCBP6 and SREBP-1c were determined by immunofluorescence, quantitative real-time PCR, and Western blot analysis. RESULTS: Hepatic steatosis was successfully induced in model groups. ALT, AST, TC, and TGs elevated in model groups compared with those in control group (P < 0.05). Hepatic steatosis induced by high-fat diet and CCL4 resulted in low expression of HCBP6 and high expression of SREBP-1c in the liver of rats (P < 0.05). CONCLUSION: HCBP6 is involved in the development of high-fat diet- and CCL4-induced hepatic steatosis and related negatively with SREBP-1c.

Nocturnal Oximetry-based Evaluation of Habitually Snoring Children.

RATIONALE: The vast majority of children around the world undergoing adenotonsillectomy for obstructive sleep apnea-hypopnea syndrome (OSA) are not objectively diagnosed by nocturnal polysomnography because of access availability and cost issues. Automated analysis of nocturnal oximetry (nSpO2), which is readily and globally available, could potentially provide a reliable and convenient diagnostic approach for pediatric OSA. METHODS: Deidentified nSpO2 recordings from a total of 4,191 children originating from 13 pediatric sleep laboratories around the world were prospectively evaluated after developing and validating an automated neural network algorithm using an initial set of single-channel nSpO2 recordings from 589 patients referred for suspected OSA. MEASUREMENTS AND MAIN RESULTS: The automatically estimated apnea-hypopnea index (AHI) showed high agreement with AHI from conventional polysomnography (intraclass correlation coefficient, 0.785) when tested in 3,602 additional subjects. Further assessment on the widely used AHI cutoff points of 1, 5, and 10 events/h revealed an incremental diagnostic ability (75.2, 81.7, and 90.2% accuracy; 0.788, 0.854, and 0.913 area under the receiver operating characteristic curve, respectively). CONCLUSIONS: Neural network-based automated analyses of nSpO2 recordings provide accurate identification of OSA severity among habitually snoring children with a high pretest probability of OSA. Thus, nocturnal oximetry may enable a simple and effective diagnostic alternative to nocturnal polysomnography, leading to more timely interventions and potentially improved outcomes.

Pediatric Obstructive Sleep Apnea: Where Do We Stand?

Pediatric obstructive sleep apnea (OSA) was initially described in 1976. In 1981, Dr. Guilleminault emphasized that pediatric OSA was different from the clinical presentation reported in adults. It was characterized by more disturbed nocturnal sleep than excessive daytime sleepiness, and presented more behavioral problems, particularly school problems, hyperactivity, nocturnal enuresis, sleep terrors, depression, insomnia, and psychiatric problems. The underlying causes of pediatric OSA are complex. Such factors as adenotonsillar hypertrophy, obesity, anatomical and neuromuscular factors, and hypotonic neuromuscular disease are also involved. Adenotonsillectomy (T&A) has been the recommended treatment for pediatric OSA, but in the recent past this practice has been placed very much in question. Therefore, we will discuss the mechanism of pediatric OSA and investigate obese and nonobese pediatric sleep-disordered breathing. Moreover, the important concept that dysfunction leads to the dysmorphism that impacts on the size of the upper airway has been advanced recently. Finally, the treatments of pediatric OSA, such as T&A, medication, the orthodontic approaches (rapid maxillary expansion, or mandibular advancement with functional appliances), positive airway pressure, and noninvasive treatment, such as myofunctional therapy (MFT), will be investigated. A "passive MFT" has been tried recently, but very few results exist. In conclusion, we have made progress in our understanding of pediatric OSA, and we can even recognize factors leading to its development or worsening. However, pediatricians and pediatric subspecialists are often unaware of the advances and the remedies available.

Inflammatory cytokines in pediatric obstructive sleep apnea.

Pediatric obstructive sleep apnea (OSA) is associated with chronic systemic inflammation and with cognitive impairments. This study aimed to investigate the status of proinflammatory cytokines, particularly interleukin 17 (IL-17) and interleukin 23 (IL-23) and cognition in pediatric OSA.Controls and OSA children participated in the study. Exclusion criteria were adenotonsillectomy, heart, neurological and severe psychiatric diseases, craniofacial syndromes, and obesity. Polysomnogram was followed by serum testing for inflammatory markers and neurocognitive tests such as continuous performance task (CPT) and Wisconsin card sorting test, questionnaires, analyses of plasma high-sensitivity C-reactive protein (HS-CRP), tumor necrosis factor alpha (TNF-α), interleukin 1 (IL-1), interleukin 6 (IL-6), IL-17, and IL-23.Seventy-nine, 4 to 12-year-old subjects in 2 groups ended the study: 47 nonobese OSA children (mean age = 7.84 ±â€Š0.56 years, body mass index [BMI] = 16.95 ±â€Š0.47 kg/m, BMI z-score = 0.15 ±â€Š0.21, and mean apnea-hypopnea index [AHI] = 9.13 ±â€Š1.67 events/h) and 32 healthy control children (mean age = 7.02 ±â€Š0.65 years, with BMI = 16.55 ±â€Š0.58 kg/m, BMI z-score = -0.12 ±â€Š0.27, and mean AHI = 0.41 ±â€Š0.07 event/h) were enrolled. Serum cytokine analyses showed significantly higher levels of HS-CRP, IL-17, and IL-23 in OSA children (P = 0.002, P = 0.024, and P = 0.047). Regression test showed significant influence of HS-CRP, TNF-α, IL-6, IL-17, and specifically IL-23, with the continuous performance test and Wisconsin card sorting test.OSA children have abnormal levels of IL-17, an interleukin related to T helper 17 cells, a T helper cell involved in development of autoimmunity and inflammation. This high expression level may contribute to the complications of pediatric OSA; we also found a significant influence of inflammatory cytokines, particularly IL-23, on abnormal neurocognitive testing.

Clinical manifestations of pediatric obstructive sleep apnea syndrome: Clinical utility of the Chinese-version Obstructive Sleep Apnea Questionaire-18.

AIMS: Childhood obstructive sleep apnea syndrome (OSA) affects not only the children's physical health, but also their mental development, behavioral problems and learning difficulties. Therefore, an early diagnosis is important. However, the assessment tools of polysomnography are demanding. The Obstructive Sleep Apnea Questionnaire-18 (OSA-18) is designed to screen OSA and has good reliability and validity. The goal of this study was to validate the Chinese version of the OSA-18, to analyze the frequency of symptoms and find the most common symptoms of OSA in Taiwanese children. METHODS: We validated the OSA-18 in an ethnic Chinese group and compared the treatment outcomes to show the sensitivity of the questionnaire. The caregivers completed the questionnaire twice at an interval of 4 weeks to test reliability. In the validation study, we included 88 OSA children. The OSA-18 and follow-up polysomnography were performed before and 6 months after adenotonsillectomy. RESULTS: Results showed the excellent test-retest reliability (r = 0.84**) of the OSA-18. There was a statistically significant correlation between the OSA-18 and, respectively, the Apnea-Hypopnea Index (r = 0.29*), and the Hypopnea Index (r = 0.29*). Quality of life showed a significant correlation with the Apnea Index (r = 0.43**), central apnea count (r = 0.50***), and mixed apnea count (r = 0.36*). The cut-off point of the OSA-18 total scores for detecting pediatric OSA in children aged 6-12 years was 66. The common symptoms of pediatric OSA were poor attention span, loud snoring, caregiver worried about child's health, difficulty awakening, and mouth breathing. CONCLUSIONS: Our results show that the Chinese version of the OSA-18 is a reliable and valid instrument. The questionnaire also showed improvement in the quality of life of OSA children post-adenotonsillectomy.