A Five-year Surveillance of Carbapenemase-producing Klebsiella pneumoniae in a Pediatric Hospital in China Reveals Increased Predominance of NDM-1

Objective To characterize carbapenem （CPM）-non-susceptible Klebsiella pneumoniae （K. pneumoniae） and carbape-nemase produced by these strains isolated from Beijing Children＇s Hospital based on a five-year surveillance. Methods The Minimal Inhibition Concentration values for 15 antibiotics were assessed using the Phonixl00 compact system. PCR amplification and DNA sequencing were used to detect genes encoding carbapenemases. WHONET 5.6 was finally used for resistance analysis. Results In total, 179 strains of CPM-non-susceptible K. pneumoniae were isolated from January, 2010 to December, 2014. The rates of non-susceptible to imipenem and meropenem were 95.0% and 95.6%, respectively. In the 179 strains, 95 （53.1%） strains carried the blalMP gene, and IMP-4 and IMP-8 were detected in 92 （96.8%） and 3 （3.2%） IMP-producing isolates, respectively. 65 （36.3%） strains carried the blaNDM_1 gene. 6 （3.4%） strains carried the blaKpc gene, and KPC-2 were detected in 6 KPC-producing isolates. In addition, New Delhi-Metallo-1 （NDM-1） producing isolates increased from 7.1% to 63.0% in five years and IMP-4 producing isolates decreased from 75.0% to 28.3%. Conclusion High frequencies of multiple resistances to antibiotics were observed in the CPM-non-susceptible K. pneumoniae strains isolated from Beijing Children＇s Hospital. The production of IMP-4 and NDM-1 metallo-13-1actamases appears to be an important mechanism for CPM-non- susceptible in K. pneumoniae.

Pediatric otolaryngology-head and neck surgery in China: Present situation and future prospects

Evolution Pediatric otolaryngology–head and neck surgery (OHNS) is a young discipline in the 21st century. During its development, the discipline and its sub-areas were increasingly enriched and refined, and its name evolved from 'ear, nose and throat' to 'otorhinolaryngology' and then to 'otolaryngology–head and neck surgery' In the United States, the American Laryngological Association was established in 1878, and the American Academy of Ophthalmology and Otolaryngology was founded in 1903. However, no doctors specialized in pediatric OHNS until the 1940s.

The putative NAD(P)H Nitroreductase,Rv3131,is the Probable Activating Enzyme for Metronidazole in Mycobacterium Tuberculosis

Tuberculosis(TB),which is caused by the intracellular pathogen,Mycobacterium tuberculosis(Mtb),remains one of the deadliest infectious diseases worldwide,accounting for 1.45 million deaths in 2018[1].Thus,there is an increasing need to develop new antibiotics or to repurpose old drugs that have the potential to shorten the current duration of therapy.Metronidazole(MTZ)is a 5-nitroimidazole antibiotic that is mainly used in the treatment of anaerobic and protozoal infections[2].The action of mechanism for metronidazole has not been fully established.As a prodrug,MTZ is inactive until taken up and reduced by anaerobic bacteria and protozoa.It is possible that the reduction of Mtz leads to the production of toxic metabolites,which bind to deoxyribonucleic acid and electron-transport proteins of microbial pathogens,thus blocking nucleic acid synthesis[3].The impressive potency of MTZ against anaerobic bacteria indicates the potential for killing Mtb under anaerobic conditions.A previous in vitro study demonstrated that MTZ has potent activity against tubercle bacilli under anaerobic conditions[4].In a non-human primate model,MTZ has been shown to prevent reactivation of latent Mtb infection,indicating the in vivo role in targeting Mtb within an anaerobic environment[5].Although there is strong evidence for the role of MTZ in affecting anaerobic bacilli,the mechanism of action has not been elucidated in Mtb considering that MTZ must be catalyzed to a nitro-free radical form with endogenous nitroreductase.To provide insight=into how MTZ is activated in anaerobic Mtb bacilli,we first characterized the nitroreductase gene,Rv3131,and identified the key residue conferring the activation of MTZ in Mtb.

Application of genome analysis strategies in the clinical testing for pediatric diseases

Next-generation sequencing (NGS) is being used in clinical testing.Government authorities in both China and the United States are overseeing the clinical application of NGS instruments and reagents.In addition,the US Association for Molecular Pathology and the College of American Pathologists have jointly released a guidance to standardize the analysis and interpretation of NGS data involved in clinical testing.At present,the analysis strategies and pipelines for NGS data related to the clinical detection of pediatric disease are similar to those used for adult diseases.However,for rare pediatric diseases without linkage to known genetic variants,it is currently difficult to detect the relevant pathogenic genes using NGS technology.Additionally,it is challenging to identify novel pathogenic genes of familial pediatric tumors.Therefore,characterization of the pathogenic genes associated with above diseases is important for the diagnosis and treatment of rare diseases in children.This article introduces the general pipelines for NGS data analyses of diseases and elucidates data analysis strategies for the pathogenic genes of rare pediatric diseases and familial pediatric tumors.

Long-term follow-up of auditory performance and speech perception and effects of age on cochlear implantation in children with pre-lingual deafness

Background: The development of auditory and speech perception ability of children with hearing loss is affected by many factors after they undergo cochlear implantation (CI). Age at CI (CI age) appears to play an important role among these factors. This study aimed to evaluate the development of auditory and speech perception ability and explore the impact of CI age on children with pre-lingual deafness present before 3 years of age. Methods: Two hundred and seventy-eight children with pre-lingual deafness (176 boys and 102 girls) were included in this study, and the CI age ranged from 6 to 36 months (mean age, 19 months). Categorical auditory performance (CAP) was assessed to evaluate auditory ability, and the speech intelligibility rating was used to evaluate speech intelligibility. The evaluations were performed before CI and 1, 3, 6, 12, 18, 24, 36, 48, and 60 months after CI. Results: The auditory ability of the pre-lingually hearing-impaired children showed the fastest development within 6 months after CI (k = 0.524, t = 30.992, P < 0.05);then, the progress started to decelerate (k = 0.14, t = 3.704, P < 0.05) and entered a plateau at the 24th month (k = 0.03, t = 1.908, P < 0.05). Speech intelligibility showed the fastest improvement between the 12th and 24th months after CI (k = 0.138, t = 5.365, P < 0.05);then, the progress started to decelerate (k = 0.026, t = 1.465, P < 0.05) and entered a plateau at the 48th month (k = 0.012, t = 1.542, P < 0.05). The CI age had no statistical significant effect on the auditory and speech abilities starting at 2 years after CI (P > 0.05). The optimal cutoff age for CI was 15 months. Conclusions: Within 5 years after CI, the auditory and speech ability of young hearing-impaired children continuously improved, although speech development lagged behind that of hearing. An earlier CI age is recommended;the optimal cutoff age for CI is at 15 months.

Better design leads to better results-Importance of virological outcome design in clinical trials for antiviral treatment of coronavirus disease 2019

Since the outbreak of the pandemic coronavirus disease 2019(COVID-19),various articles on different fields of the disease published in medical and related journals increased in a way of explosion.A recent literature search at PubMed using the term“COVID-19”only displayed more than 314000 articles.

Vestibular function of pediatric patients with sudden sensorineural hearing loss:based on vertigo symptom and vestibular function testing

Background This study aimed to evaluate the relationship between vestibular and auditory functions in pediatric patients with sudden sensorineural hearing loss(SSHL).Methods A total of 30 pediatric patients experiencing unilateral SSHL between 5.9 and 13.0 years of age were enrolled in this study.Pure tone audiometry was evaluated prior to treatment initiation and again after one month of treatment.Prior to treatment initiation,vertigo symptoms were noted;then several vestibular function tests were conducted including caloric testing,ocular vestibular evoked myogenic potentials(o-VEMPs)and cervical vestibular evoked myogenic potentials(c-VEMPs).Associations between pre and post-treatment vestibular function and hearing threshold levels were analyzed.Results Initial hearing thresholds of children with vertigo were higher than thresholds of children without vertigo(92 dB vs 79 dB,F=0.033),while initial hearing thresholds of children with abnormal caloric test findings were higher than thresholds of children with normal caloric test findings(93 dB vs 67 dB.P=0.014).Cutoff values of hearing thresholds for those with vertigo symptoms and abnormal vestibular test results were 86.000-and 89.583-dB HL.respectively.Regarding prognosis,children with vertigo exhibited lower recovery rates than children without vertigo(33%vs 75%,P=0.025);recovery rates of children with abnormal caloric test results were lower than the overall recovery rate(25%vs 73%,respectively,P=0.039).Conclusion Assessments of vertigo symptoms and vestibular function are useful tools in predicting pediatric SwSHL patient disease severity and prognosis.

Progresses in clinical studies on antiviral therapies for COVID-19—Experience and lessons in design of clinical trials

Antiviral therapy with antiviral agents is a very important component of treatment for the 2019 novel coronavirus disease(COVID-19)caused by the severe acute respiratory syndrome coronavirus-2(SARS-CoV-2).It is important to clarify how to evaluate efficacy and safety of antiviral agents in treatment of COVID-19 during the pandemic of this disease.We need to answer the following questions:do we still need to use rigorously designed randomized controlled clinical trials(RCTs)?Or,will it be enough if we use loosened criteria,observational studies or even retrospective case series and case reports?The answer is"No,we still need to use the strictly designed preferably blinded multicenter RCTs to evaluate the antiviral agents."In this article,we reviewed almost all the RCT reports on monotherapies and combined therapies with antiviral agents for COVID-19,and found that among the reports on monotherapies,only remdesivir,and among combined antiviral agents,only the combined regimen with interferon-β1b,lopinavir-ritonavir and ribavirin were effective and safe based on evidences from RCTs.The results of five RCTs for chloroquine or hydroxychloroquine consistently showed that they were ineffective and unsafe in the treatment of COVID-19,especially at larger doses.Many aspects in the design of the clinical trials may be related to success or failure of a trial and the relevant factors need to be analyzed,discussed and emphasized from the specific requirements and considerations of antiviral therapies.We hope such discussions be of certain use in designing clinical trials for pediatric antiviral therapies.

DCX and CRABP2 are candidate genes for differential diagnosis between pre-chemotherapy embryonic and alveolar rhabdomyosarcoma in pediatric patients

Importance Rhabdomyosarcoma(RMS)is the most common soft tissue sarcoma in children.More than 90%of cases are classified as embryonic RMS(ERMS)or alveolar RMS(ARMS).ERMS has a worse prognosis than ARMS.Early differential diagnosis is of paramount importance for optimization of treatment.Objective To identify genes that are differentially expressed between ARMS and ERMS,which can be used for accurate rhabdomyosarcoma classification.Methods Three Gene Expression Omnibus datasets composed of ARMS and ERMS samples were screened and 35 differentially expressed genes(DEGs)were identified.Receiver operating characteristic curve analysis and area under the curve analysis was performed for these 35 DEGs and seven candidate genes with the best differential expression scores between ARMS and ERMS were determined.The expression of these seven candidate genes was validated by immunohistochemical analysis of pre-chemotherapy ARMS and ERMS specimens.Results The levels of DCX and CRABP2 were confirmed to be remarkably different between paraffin-embedded ARMS and ERMS tissues,while EGFR abundance was only marginally different between these two RMS subtypes.Interpretation DCX and CRABP2 are potential biomarkers for distinguishing ARMS from ERMS in pre-chemotherapy pediatric patients.

Correlation between BRAF^(V600E) mutation and clinicopathological features in pediatric papillary thyroid carcinoma

In adults, the presence of the BRAF^(V600E) mutation in papillary thyroid cancer(PTC) has been demonstrated to be strongly associated with aggressive cancer-cell characteristics and poor patient prognosis. In contrast, the frequency of this mutation in pediatric PTC has undergone limited study, and the few available estimates range from 0 to 63%. Furthermore, the role of the BRAF^(V600E) mutation in pediatric PTC is controversial; thus, the present study aimed to investigate the prevalence and role of the BRAF^(V600E) mutation in48 pediatric patients with PTC, aged 3–13 years. Of these patients, 41 were diagnosed with classic PTC, five were found to have a follicular variant of PTC, and two to exhibit a diffuse sclerosing PTC variant. The BRAF^(V600E) mutation was identified to be present in 35.4% of the 48 analyzed patients, and in 41.5% of the patients diagnosed with classical PTC. Furthermore, the presence of the BRAF^(V600E) mutation was found to be associated with a patient age at diagnosis of less than ten years(P=0.011), the performance of a thyroidectomy(P=0.03), exhibited tumor multifocality(P=0.02) and/or extra-thyroidal invasion(P=0.003), and both a low MACIS(Metastases, Age, Completeness of resection, Invasion, Size)(P=0.036) and AMES(Age, Metastasis, Extent of tumor,Size)(P=0.001)score. Together, these data suggest that the presence of the BRAF^(V600E) mutation may be negatively correlated with partial aggressive clinicopathological features of pediatric PTC.

The Challenge and promise of rare disease diagnosis in China

Rare diseases are chronic and serious,featuring early onset at birth or in childhood,rapid deterioration and high mortality rate,which creates a burden on society and public health systems.Of the known rare diseases,80 percent are genetic in origin,and half of those affected worldwide are children.In China,the rare disease patients are over 10 million,and70 percent of the patients are children(Song et al.,2012;Liu et al.,2010).

Correlation between TERT C228T and clinic-pathological features in pediatric papillary thyroid carcinoma

The aims of the present study were to reveal the prevalence of the TERT C228 T mutation in pediatric papillary thyroid carcinoma(PPTC) and to further investigate the role of the TERT C228 T mutation in PPTC. We also tested another TERT mutation, TERT C250 T, although this was not detected in PPTC patients. In this study, 48 patients with PPTC(41 with classic PPTC) were enrolled. DNA was extracted from PPTC tissues and TERT C228 T mutation analysis was performed. Chi-squared analysis,Fisher’s exact test, and a t-test were applied to test the significance of differences. The TERT C228 T mutation presented in 13(27.1%) of the 48 PPTC patients and 10(24.4%) of the 41 classical PPTC patients. There were significant differences between PPTC patients with the TERT C228 T mutation and those without in terms of modified radical neck dissection, multifocality,capsular invasion, extrathyroidal invasion, and American Joint Committee on Cancer(AJCC) tumor stage(P<0.05). In classical PPTC, there were additional significant differences in other clinic-pathological features, such as AJCC nodal stage(P=0.009)and American Thyroid Association(ATA) PPTC stage(P=0.021) between patients with and without the TERT C228 T mutation.These findings indicate that the TERT C228 T mutation is significantly correlated with certain aggressive clinic-pathological features of PPTC.

A review of the risk factors associated with juvenile-onset recurrent respiratory papillomatosis:genetic,immune and clinical aspects

Background Juvenile-onset recurrent respiratory papillomatosis(JoRRP)is one of the most common benign lesions of hyperplastic respiratory epithelial tissue in children and is predominantly caused by human papillomaviruses(HPVs)6 and 11.The clinical course of the disease is variable,and some patients even develop a malignancy.The purpose of this review was to summarize the related factors affecting the disease course in patients with JoRRP.Data sources We used databases,including PubMed and Google Scholar,to search for publications on factors associated with the genetic,immune,and clinical aspects of JoRRP.The most relevant articles to the scope of this review were chosen for analysis.Results Mother-to-child transmission is the most important mode of disease transmission;other factors,such as immune condition or genetic susceptibility,may be important determinants of JoRRP occurrence.Genetically,the presence of DRBI*0301 and HFV 6/11 E6/E7 is associated with a more severe disease.Immunewise,patients have an enhanced T helper 2-like response.In addition,regulatory T cells are enriched in tumors and may become one of the effective prognostic indicators.For clinical characteristics,patients infected with HPV-11 have more aggressive disease.However,compared with HPV type,age at first onset is a more important factor related to the aggressiveness of JoRRP.Furthermore,socioeconomic status may also affect the course.Conclusions Genetic,immune,and some clinical factors have been noted to play an important role in the course of JoRRP.Exploring definite influencing factors will be an important direction of research in the future.

Sleep Duration and Factors Related to Sleep Loss in 3-14-Year-Old Children in Beijing： A Cross-Sectional Survey

Background： It is known that short sleep duration adversely affects children＇s behavior and physical development. This study aimed to investigate the status of sleep duration in 3-14-year-old children in Beijing and explore the related factors of sleep loss with them. Methods： In this study, a cross-sectional study of random stratified cluster sampling was conducted on 3-14-year-old children and adolescents in Beijing. According to the proportion of children in each district and school, the final cohort included a total of 11 kindergartens, 7 primary schools, and 8 junior high schools from 7 districts of Beijing. Children of sampled classes were included, and their parents were invited to fill a series of questionnaires including the simplified Chinese version of Pediatric Sleep Questionnaire, Sleep Questionnaire Scale, and Hong Kong-Children Sleep Questionnaire about the performance of the last 6 months. Results： Out of the total 11,420 questionnaires, 9198 questionnaires were valid and effective with the response rate of 80.54%. The age of the investigated children was 8.8 ± 3.8 years, including 4736 males and 4462 females. The daily sleep duration of children in Beijing was 9.7 ± 0.7 h. The prevalence of sleep loss （〈9 h/day） of children in Beijing was 11.8%. The daily sleep duration of children aged 〈6, 6 ≤ age 〈11, and ≥11 years was 9.7 ± 0.6 h, 9.6 ± 0.6 h, and 9.5 ± 0.8 h, respectively. The sleep duration reduced significantly in children aged ≥11 years as compared to younger children in Beijing which was mainly contributed by the variation tendency of sleep duration on weekdays. The multivariate logistic regression analysis identified factors associated with sleep loss （P 〈 0.05）： male （odds ratio [OR] = 1.32, 95% confidence interval [CI ]： 1.15-1.51 ）, age ≥11 years （OR = 2.37, 95% CI： 1.92-2.93）, overweight （OR = 1.34, 95% CI： 1.17-1.54）, family history of snoring （OR - 1.35, 95% CI： 1.13-1.61 ） and activities before bedtime with watching TV （OR = 1.24, 95% CI： 1.08 1.43）, sports （OR = 1.22, 95% C/： 1.01-1.48）, playing cellphone （OR = 1.91,95% CI： 1.31-2.73） and surfing the Internet （OR = 1.27, 95% CI： 1.06-1.52） and among them age 〉11 years and playing cellphone betbre bedtime had greater impact on children＇s short sleep duration than that of other factors. Conclusions： Sleep loss was common among 3-14-year-old children in Beijing. Sleep duration decreased with age, especially among children over 11 years old. Factors associated with sleep loss covered sociodemographic characteristics, family sleep habits and routine activities before bedtime, and among those variables, age ≥11 years and playing with cellphones before bedtime had a greater impact on sleep duration, indicating that existing sleep loss in 3-14-year-old children could be, at least partly, improved by paying more attention to children aged of l I years or entering Grade 5 and Grade 6 and to children with a family history of snoring; by reducing the use of electronic products betbre bedtime, especially cellphones; by managing weight and keeping fit; and by improving the bedtime routine.

effective treatment of post-intubation subglottic stenosis in children with holmium laser therapy and cryotherapy via flexible bronchoscopy

Importance:Post-intubation subglottic stenosis(SGS)in children can be life threatening.Definitive treatment varies and lacks a universally accepted approach.Objective:We performed a prospective study to assess the safety and feasibility of holmium laser combined with cryotherapy delivered via flexible bronchoscopy for the treatment of post-intubation SGS in children.Methods:This study involved all patients with post-intubation SGS seen at the Interventional Pulmonology Department of Beijing Children's Hospital between July 2014 and December 2016.Holmium laser treatment and cryotherapy was then performed under flexible bronchoscopy,whose parents refused to accept the alternative standard treatment of tracheotomy and balloon dilation under direct laryngoscopy.results:Sixteen patients with post-intubation SGS were included in this study.Ages ranged from 2 months to 12.25 years old.According to the Cotton-Myer grading system,three cases were Grade II,12 cases were Grade III,and one case was Grade IV.According to the McCaffrey system,eight cases were Stage 1,two cases were Stage 2,and six cases were Stage 3.The average number of procedures was 4.88.Fifteen of the 16 patients achieved clinical cure.One patient achieved clinical improvement.The average treatment course duration was 55.31 days.No severe complications were seen.Post-treatment clinical symptoms,endoscopic findings and quality of life showed marked improvement.Interpretation:Our study supports the conclusion that holmium laser treatment combined with cryotherapy via flexible bronchoscopy appears to be a safe and feasible treatment for post-intubation SGS in children.

Application of topical gentamicin ointment in the treatment of Nagashima-type palmoplantar keratosis in children with a nonsense mutation

Importance:Nagashima-type palmoplantar keratosis(NPPK)is a hereditary dermatosis mostly caused by a nonsense mutation in SERPINB7.Despite the increasing interest in readthrough gentamicin treatment of NPPK,clinical evidence for this treatment is limited.Objective:This study aimed to provide further evidence for the use of topical gentamicin in the treatment of NPPK in children with nonsense mutations.Methods:We designed a bilaterally controlled study of topical gentamicin ointment.Children diagnosed with NPPK carrying nonsense mutations were enrolled in this study.A 0.1%gentamicin ointment was applied to one hand and an emollient to the other for 3 months.A bilateral comparison of the visual analog scale scores for clinical manifestations and safety was performed.Results:Ten children with NPPK were included in this study.In comparison with the emollient side,the topical gentamicin side showed significant improvements in hyperkeratosis,erythema,maceration,and desquamation after 1 and 3 months of treatment(P<0.05).However,hyperhidrosis and odor did not improve significantly.No adverse events were observed during the systemic safety monitoring examinations.Interpretation:Topical gentamicin ointment showed good safety in the treatment of NPPK with nonsense mutations,indicating that it is a promising therapeutic choice in children with NPPK.

Validity of web-based self-assessment of pubertal development against pediatrician assessments

Importance:A web-based instrument for self-assessment of puberty could be convenient and feasible for large-scale multicenter populationbased epidemiological studies for Tanner stages evaluation.Objective:To validate web-based self-assessment of pubertal development against assessment by a pediatrician.Methods:Outpatients aged 8-18 years were consecutively recruited in the endocrinology department of Beijing Children's Hospital from October 2016 to August 2017.A web-based self-assessment instrument for pubertal development was introduced to participants by an appointed pediatrician.Tanner stage of puberty was self-assessed by participants in a private environment.Participants were then examined by a senior pediatrician underwent blinded assessment.Weighted kappa and Spearman correlation analyses were conducted to evaluate agreement.The accuracy of the web-based instrument for self-assessment of pubertal onset was evaluated according to sensitivity,specificity,positive predictive value and negative predictive value.Results:A total of 174 participants (including 82 girls and 92 boys)were assessed consecutively.Correlation coefficients were 0.872 for pubic hair and 0.933 for testicular volume (P<0.001) among boys;a similar result was obtained for the weighted kappa value (0.825).For girls,the correlation coefficient and weighted kappa for pubic hair was 0.785 and 0.878,respectively.However,breast self-assessment had a medium level of agreement with pediatrician assessment (weighted kappa,0.495;correlation coefficient,0.643).Moreover,the accuracy of self-assessment in children aged 10 years or above was better than that in children aged less than 10 years.Interpretation:Assessment of pubertal development using a webbased self-assessment instrument could be less accurate among children aged less than 10 years,especially for girls' breast assessment.Therefore,self-assessment of pubertal development,especially for breast development,should be interpreted cautiously.

Sequencing XMET genes to promote genotype-guided risk assessment and precision medicine

High-throughput next generation sequencing (NGS) is a shotgun approach applied in a parallel fashion by which the genome is fragmented and sequenced through small pieces and then analyzed either by aligning to a known reference genome or by de novo assembly without reference genome.This technology has led researchers to conduct an explosion of sequencing related projects in multidisciplinary fields of science.However,due to the limitations of sequencing-based chemistry,length of sequencing reads and the complexity of genes,it is difficult to determine the sequences of some portions of the human genome,leaving gaps in genomic data that frustrate further analysis.Particularly,some complex genes are difficult to be accurately sequenced or mapped because they contain high GC-content and/or low complexity regions,and complicated pseudogenes,such as the genes encoding xenobiotic metabolizing enzymes and transporters (XMETs).The genetic variants in XMET genes are critical to predicate interindividual variability in drug efficacy,drug safety and susceptibility to environmental toxicity.We summarized and discussed challenges,wet-lab methods,and bioinformatics algorithms in sequencing "complex" XMET genes,which may provide insightful information in the application of NGS technology for implementation in toxicogenomics and pharmacogenomics.

Disease characteristics and neuropathological changes associated with cognitive dysfunction in obstructive sleep apnea

Obstructive sleep apnea(OSA)is a common sleep-disordered breathing disease that often leads to many comorbidities(e.g.,cognitive dysfunction),which adversely affect the quality of life for patients with OSA.Thus far,the underlying mechanisms of this dysfunction remain unclear.Many studies have focused on OSA-related characteristics,including intermittent hypoxemia and sleep fragmentation.There is increasing emphasis on neuroimaging studies to explore underlying relationships between neuropathological changes and cognitive dysfunction.This article reviews recent research progress concerning cognitive dysfunction associated with OSA to reveal potential mechanisms that contribute to this dysfunction.

Clinical evaluation of cochlear implantation in children younger than 12 months of age

Importance Cochlear implantation(CI)is an effective therapy for patients with severe to profound sensorineural hearing loss.It remains controversial whether children younger than 12 months of age should undergo CI.Objective To evaluate the safety and effectiveness of CI in children younger than 12 months of age.Methods We performed a retrospective study of clinical data of pediatric patients younger than 12 months of age who underwent CI and were followed up for 1 to 2 years.Patients’developmental levels were evaluated by the Gesell score before CI.Intraoperative and postoperative complications were recorded to evaluate the safety of CI.Auditory and speech abilities were scored by the LittlEARS®auditory questionnaire(LEAQ),categories of auditory performance(CAP),speech intelligibility rating(SIR),infant‐toddler meaningful auditory integration scale(IT‐MAIS),and meaningful use of speech scale(MUSS)at 1,2,3,6,9,and 12 months after CI.The associations between clinical characteristics before CI and postoperative scores at 1 year after CI were analyzed by the linear mixed‐effects model.Results Eighty‐nine children(47 boys and 42 girls)were included in this study(mean age at CI,9.2±1.6 months).Sixteen patients were diagnosed with cochlear malformation and 16 underwent bilateral CI.No severe complications occurred in any patients.The mean developmental quotient of the Gesell score was 78.00±10.03.The median LEAQ scores were 0,5,10,16,22,26 and 30 before and at 1,2,3,6,9,and 12 months after CI,respectively.These findings implied that the LEAQ score greatly improved in the first year after CI.The overall CAP,SIR,IT‐MAIS,and MUSS scores also increased with increasing duration after CI.No significant associations were detected between clinical characteristics(age,sex,implant number,pre‐CI Gesell score,and inner ear malformation)and LEAQ outcomes at 12 months after CI.Interpretation With increasing duration after CI,auditory and speech behavior dramatically improve in young children.Our findings indicate that CI is feasible for children younger than 12 months of age.