Nap polysomnography in infants with laryngomalacia as a tool to predict treatment strategy.

PURPOSE: This study aimed to investigate the role of nap polysomnography (NPSG) in predicting treatment strategies for infants with moderate to severe laryngomalacia and to explore the association between obstructive sleep apnea (OSA) severity, weight gain, and laryngomalacia severity. METHODS: A retrospective analysis was conducted on infants diagnosed with moderate to severe laryngomalacia who underwent NPSG between January 2019 and June 2023. Clinical variables, NPSG parameters, and treatment decisions were collected. Weight gain rate and its correlation with NPSG indices were assessed. Logistic regression analyses were performed to predict treatment strategies based on NPSG findings. RESULTS: Of the 39 infants included (median age: 3.3 months), 77% exhibited OSA, with 69% having moderate to severe OSA [apnea-hypopnea index (AHI) > 5/h]. Weight gain rate correlated negatively with indices of OSA severity, including the hypopnea index (HI) and the AHI. In a multiple logistic regression analysis incorporating the severity of OSA (AHI), weight gain rate, and laryngomalacia severity, only AHI predicted the decision for surgical or non-invasive ventilation treatment (OR = 2.1, CI95 [1.6; 2.8], p ≤ 10-4). The weight gain rate was predicted (r2 = 0.28) by the AHI and the presence of retractions of auxiliary inspiratory muscles. CONCLUSION: This study underscores the importance of NPSG in assessing infants with moderate to severe laryngomalacia. The AHI from NPSG emerged as a potential predictor for treatment decisions and weight gain rate, emphasizing its clinical relevance. These findings advocate incorporating NPSG into the diagnostic and management process for infants with laryngomalacia.

PEANUTS: a national survey on the management of pediatric tracheobronchial foreign bodies.

To assess the different types of management of pediatric foreign body aspirations in order to help define guidelines, depending on clinical presentation. A national survey in France was emailed to all 30 university-affiliated departments of otolaryngology-head and neck surgery and pediatric pulmonologists in France. Data concerning the center and the experience of each participant were collected in order to define an "senior expert" group with experience of extracting more than 10 foreign bodies and a "junior/non-expert" group. Both groups answered questions concerning five clinical cases of foreign body aspiration of different severities. Ninety-eight participants answered this survey (75 otolaryngologists and 23 pulmonologists), representing 28 of the 30 university-affiliated departments in France with a completion rate of 89%. Responses of the senior expert group were similar for clear-cut situations, such as an asymptomatic child with a low probability of foreign body aspiration and for a symptomatic child with respiratory distress. However, for intermediate situations, management varied significantly according to the physician when considering clinical, radiological, and surgical management. In comparison to the senior expert group, the junior non-expert group seemed more precautious in the management of foreign body aspiration for intermediate cases, in particular, concerning the time at which extraction was performed.  Conclusion: The management of foreign body aspiration depends on the physician's experience and the center's habits. In order to optimize patient care for foreign body aspiration, we suggested a management algorithm based on the senior expert group responses. What is Known: • Foreign body aspirations (FBA) are dreaded by pediatricians, pediatric otolaryngologists, and pulmonologists particularly because of the potential fatal outcome. • However, consensus concerning their management is not clearly defined in the literature. What is New: • This study is the first to evaluate the management of foreign body aspirations (FBA) from the clinical assessment by the emergency medicine physician to the extraction of the foreign body. • A management algorithm was designed and secondarily validated by the SE group to help to emergency medicine physician and specialist to manage FBA.

Is CMV PCR of inner ear fluid during cochlear implantation a way to diagnose CMV-related hearing loss?

To evaluate the diagnostic performance of cytomegalovirus (CMV) polymerase chain reaction (PCR) on inner ear fluid collected during cochlear implantation and to assess its interest in current practice. This monocentric prospective study included consecutive children presenting with severe to profound sensorineural hearing loss (SNHL) who were candidates for unilateral and/or bilateral cochlear implantation. The etiology of the SNHL was determined before cochlear implantation when possible. During the surgery, drop-like samples of inner ear fluid and blood were collected. CMV PCR was then performed on both samples. Between January 2017 and September 2021, 113 children with severe to profound SNHL underwent cochlear implantation with inner ear fluid collection. Among these children, 77 of them presented with a known cause of SNHL (68%) and 36 of them had an unknown cause of SNHL at the time of surgery (32%). Sensitivity and specificity of the CMV PCR on inner ear fluid were 60% (95% CI: [49-71]) and 98% (95% CI: [96-100]), respectively. Positive and negative predictive values were 90% (95% CI: [83-97]) and 92% (95% CI: [86-98]), respectively. A sensitivity analysis according to age at cochlear implantation showed a decrease with age. CONCLUSION: Sampling of inner ear fluid during cochlear implant surgery is an interesting, simple and safe way to diagnose CMV-related hearing loss, especially when the diagnosis of congenital infection can no longer be confirmed. However, the sensitivity decreases with age. TRIAL REGISTRATION: NCT04724265 What is Known: • Congenital cytomegalovirus infection is the leading infectious cause of neurological disabilities and sensorineural hearing loss in children. In the absence of systematic screening at birth, many cCMV infections go undetected and are often undiagnosed despite the development of sensorineural sequelae.  • Nearly 40% of indications for cochlear implantation are of unknown etiology. WHAT IS NEW: • Performing CMV PCR on inner ear fluid at the time of cochlear implantation is a safe way with high diagnostic performance (PPV = 90%, NPV = 92%) to detect a CMV-related hearing loss. • This sample may be interesting in cases of unknown cause of hearing loss in order to identify undiagnosed cCMV infections.

New surgical frontiers for 4K 3D-exoscope in paediatric head and neck surgery.

PURPOSE: To define the interest, advantages, and disadvantages of the use of a 3D-exoscope in paediatric ENT surgery. METHODS: Four surgeons with experience in paediatric surgery completed a questionnaire following each surgery performed under 3D-exoscope to evaluate the contribution of the tool compared to the usual practice (microscope or magnifying loupes). Surgeries were separated into three groups: otology, transoral and cleft palate surgery, and open head and neck surgery. RESULTS: Between June 2021 and June 2022, 151 paediatric surgeries were included in this study. Among them, 93 (62%) otologic surgeries, 35 (23%) transoral surgeries, and 23 (15%) head and neck surgeries were performed. The median age at surgery was 68 months (interquartile range 19-135 months). For otologic surgeries, the mean scores (/100) for the contribution of the exoscope compared to the microscope were 68.4(± 23.2). For transoral and cleft palate surgery, the mean score (/100) for the contribution of the use of the exoscope compared to the magnifying loupes was 92.9 (± 8.6), whereas for open head and neck surgeries, the mean score (/100) was 89.5 (± 7.2). CONCLUSION: 3D-exoscopy appears to be a relevant tool for paediatric head and neck surgery, applicable in otologic, transoral, and cervical fields. It presents educational and ergonomic advantages and improves surgical team communication.

CCL2 recruits fetal microchimeric cells and dampens maternal brain damage in post-partum mice.

Preventing brain cell loss and enhancing tissue repair are crucial objectives to improve the outcome of stroke. Fetal microchimerism has been implicated in brain repair following ischemic stroke in mice. CCL2/CCR2 signaling pathway triggers fetal progenitors trafficking to cutaneous wounds. Therefore, we sought to evaluate whether CCL2 could dampen brain damage in a model of excitotoxic lesion in post-partum mice. Virgin or post-partum mice were subjected to an intracerebral injection of ibotenate to induce excitotoxic lesions. Low doses of CCL2 or its vehicle were concomitantly injected. Morphological and molecular analyses were performed 1 and 5 days following the procedure. Intracerebral treatment with low doses of CCL2 was able to limit brain excitotoxic damage induced by ibotenate in post-partum mice, through an enhanced recruitment of fetal microchimeric cells to the damaged hemisphere. At day 1 post-injection, we observed a decreased cortical apoptosis associated with a reduced reactive astrocytosis. At day 5, we found an increased proportion of mature neurons and oligodendrocytes correlating with an increase in GAP43 growth cones. At this stage, immune microglial cells were reduced, while angiogenesis was enhanced. Importantly, CCL2 did not have beneficial effects in virgin mice therefore ruling out a specific role of CCL2 independently from fetal microchimeric cells mobilization. CCL2 treatment efficiently enhances fetal cell mobilization to improve the outcome of a brain excitotoxic challenge in post-partum mice. This study paves the way for a "natural stem cell therapy" based on the selective recruitment of fetal progenitors to repair maternal brain injury.

Human Cytomegalovirus Interactions with the Basement Membrane Protein Nidogen 1.

In 2000, we reported that human cytomegalovirus (HCMV) induced specific damage on chromosome 1. The capacity of the virus to induce DNA breaks indicated potent interaction between viral proteins and these loci. We have fine mapped the 1q42 breaksite. Transcriptional analysis of genes encoded in close proximity revealed virus-induced downregulation of a single gene, nidogen 1 (NID1). Beginning between 12 and 24 hours postinfection (hpi) and continuing throughout infection, steady-state (ss) NID1 protein levels were decreased in whole-cell lysates and secreted supernatants of human foreskin fibroblasts. Addition of the proteasomal inhibitor MG132 to culture medium stabilized NID1 in virus-infected cells, implicating infection-activated proteasomal degradation of NID1. Targeting of NID1 via two separate pathways highlighted the virus' emphasis on NID1 elimination. NID1 is an important basement membrane protein secreted by many cell types, including the endothelial cells (ECs) lining the vasculature. We found that ss NID1 was also reduced in infected ECs and hypothesized that virus-induced removal of NID1 might offer HCMV a means of increased distribution throughout the host. Supporting this idea, transmigration assays of THP-1 cells seeded onto NID1-knockout (KO) EC monolayers demonstrated increased transmigration. NID1 is expressed widely in the developing fetal central and peripheral nervous systems (CNS and PNS) and is important for neuronal migration and neural network excitability and plasticity and regulates Schwann cell proliferation, migration, and myelin production. We found that NID1 expression was dramatically decreased in clinical samples of infected temporal bones. While potentially beneficial for virus dissemination, HCMV-induced elimination of NID1 may underlie negative ramifications to the infected fetus.IMPORTANCE We have found that HCMV infection promotes the elimination of the developmentally important basement membrane protein nidogen 1 (NID1) from its host. The virus both decreased transcription and induced degradation of expressed protein. Endothelial cell (EC) secretion of basement membrane proteins is critical for vascular wall integrity, and infection equivalently affected NID1 protein levels in these cells. We found that the absence of NID1 in an EC monolayer allowed increased transmigration of monocytes equivalent to that observed after infection of ECs. The importance of NID1 in development has been well documented. We found that NID1 protein was dramatically reduced in infected inner ear clinical samples. We believe that HCMV's attack on host NID1 favors viral dissemination at the cost of negative developmental ramifications in the infected fetus.

Audiovestibular Consequences of Congenital Cytomegalovirus Infection: Greater Vulnerability of the Vestibular Part of the Inner Ear.

OBJECTIVES: To investigate the impact of congenital cytomegalovirus infection on cochlear and vestibular function. DESIGN: This retrospective study conducted between March 2014 and March 2020 included children with confirmed congenital cytomegalovirus infection who underwent a complete audio-vestibular evaluation. It included a bithermal caloric test, a video head impulse test and a cervical vestibular evoked myogenic potential associated with a complete hearing assessment. RESULTS: The cohort of 130 children included in the study had a median age of 21 months (interquartile range: 12 to 37 months). Eighty-three children (64%) showed an inner ear impairment (both cochlear and vestibular). The vestibular part of the inner ear was significantly more frequently impaired than the cochlear part (ρ = 0.003). Sixty-two children (48%) showed confirmed hearing impairment. The severity of hearing loss was variable, with a high proportion of profound hearing loss (30/62, 48%), which was often bilateral (47/62, 76%). The vestibular assessment showed a canal function disorder in 67 children (88%) and an otolith function disorder in 63 children (83%; ρ = 0.36). The video head impulse test was significantly less altered (64%) compared with the bithermal caloric test (80%; ρ = 0.02) and the cervical vestibular evoked myogenic potential (83%; ρ = 0.009). Only seven out of 83 children (8%) showed hearing loss without vestibular dysfunction, of which only one had a normal hearing screening test at birth. For the children who passed the hearing screening test at birth and presented an inner ear impairment [n = 36, median age: 16 (11 to 34) months], vestibular disorders were later found in 35 children (97%) and 17 of them (47%) developed hearing loss secondarily. This underlines the importance of assessing both vestibular and auditory parts of the inner ear. When comparing the agreement of cochlear and vestibular impairment, the severity and the laterality of the impairment were low [Cohen's kappa 0.31 (0.22 to 0.40) and 0.43 (0.32 to 0.55), respectively]. CONCLUSION: In our study, we demonstrated that although both cochlear and vestibular parts of the inner ear can be impaired by congenital cytomegalovirus infection, the vestibular part seems more often impaired compared with the cochlear part. This underlines the importance of vestibular evaluation in the follow-up of cytomegalovirus-infected children associated with hearing assessment.

Predictors of cochleovestibular dysfunction in children with congenital cytomegalovirus infection.

The purpose of this study is to assess the predictive factors of both hearing and vestibular impairment in congenitally cytomegalovirus-infected children (cCMV) through a multivariate analysis of clinical and imaging characteristics collected during pregnancy and at birth. This retrospective study was conducted between March 2014 and March 2020, including confirmed congenitally CMV-infected children with a complete vestibular and hearing assessment. Data concerning pregnancy, date of infection, clinical characteristics, and symptomatology at birth were collected. In total, 130 children were included, with a median age of 21 months. Eighty-three children (64%) presented with an inner ear impairment (both cochlear and vestibular impairment). Sex, modality of maternal infection (seroconversion or reactivation), pregnancy term, weight and head circumference at birth, neonatal clinical signs of infection, and treatment were not significantly correlated with inner ear impairment. However, multivariate analysis confirmed that there are two independent predictive factors of inner ear impairment: antenatal imaging lesions (ORa = 8.02 [1.74; 60.27], p-value = 0.01) and infection during the first trimester (ORa = 4.47 [1.21; 19.22], p-value = 0.03). Conversely, infections occurring during the second trimester were rarely associated with inner ear impairment: 4/13 (31%) in our series, with vestibular impairment alone (4/4) and no hearing loss. None of the children infected during the third trimester developed inner ear dysfunction. CONCLUSION: Besides the symptomatic status of the CMV infection at birth, we found that antenatal imaging brain damage and early infection (mainly during the first trimester) constitute the two best independent predictive factors of inner ear involvement in congenitally CMV-infected children. WHAT IS KNOWN: • Congenital cytomegalovirus infection is the leading infectious cause of neurological disabilities and sensorineural hearing loss in children and responsible of vestibular disorders, which are probably underestimated. • No articles have yet defined the predictive factors of the entire inner ear impairment (vestibule and cochlea). WHAT IS NEW: • The timing of the infection during pregnancy (first and second trimester, ORa=4.47) and antenatal imaging lesions (ORa=8.02) are independently predictive (in a multivariate analysis) of inner ear involvement. • The symptomatic status at birth is a poor predictor of inner ear impairment.

Olfactory function in congenital cytomegalovirus infection: a prospective study.

Congenital cytomegalovirus (CMV) infection leads to olfactory bulb lesions in the fetus, yet little is known about its impact on olfaction after birth. Here, we have assessed in a prospective study conducted on children in two French hospitals from 2016 to 2019, infection severity and olfactory performance after congenital CMV infection. Children with congenital CMV infection aged 3 to 10 years and healthy controls (CTL) matched for age and sex to CMV children symptomatic at birth (sCMV) were enrolled. Olfactory discrimination was assessed using mono-odorants and binary mixtures. Data were analyzed for 54 children with PCR-confirmed congenital CMV infection, including 34 sCMV (median [IQR] age, 6 [5-8] years; 19 [55.9%] male), and 20 CMV asymptomatic at birth (aCMV, median [IQR] age, 4 [3-6] years; 12 [60.0%] male). sCMV were compared to 34 CTL children. Olfactory scores in CMV-infected children were independent from vestibular deficit and hearing loss. The olfactory score was efficient to discriminate between CTL and sCMV for children > 6 years (area under the receiver-operating characteristic curve (AUC, 0.85; P = 0.0006), but not for children < 7 years. For children > 6 years, the proportion of children with total olfactory score < 4 differed between sCMV and CTL groups (91.2% and 18.7%, P < 0.001), but not between aCMV and age-matched healthy control groups.   Conclusion: Congenital CMV infection is associated with reduced olfactory performance in children with infection symptoms at birth.   Clinical trial registration: NCT02782988 (registration date: May 26, 2016). What is Known: •Congenital cytomegalovirus infection leads to olfactory bulb lesions in the fetus, yet little is known about its impact on olfaction after birth. •Depending on neonatal clinical presentation, children are either categorized as having a symptomatic or asymptomatic infection at birth. What is New: •Congenital cytomegalovirus infection is associated with reduced olfactory performance in children with infection symptoms at birth.

CDK5RAP2 primary microcephaly is associated with hypothalamic, retinal and cochlear developmental defects.

BACKGROUND: Primary hereditary microcephaly (MCPH) comprises a large group of autosomal recessive disorders mainly affecting cortical development and resulting in a congenital impairment of brain growth. Despite the identification of >25 causal genes so far, it remains a challenge to distinguish between different MCPH forms at the clinical level. METHODS: 7 patients with newly identified mutations in CDK5RAP2 (MCPH3) were investigated by performing prospective, extensive and systematic clinical, MRI, psychomotor, neurosensory and cognitive examinations under similar conditions. RESULTS: All patients displayed neurosensory defects in addition to microcephaly. Small cochlea with incomplete partition type II was found in all cases and was associated with progressive deafness in 4 of them. Furthermore, the CDK5RAP2 protein was specifically identified in the developing cochlea from human fetal tissues. Microphthalmia was also present in all patients along with retinal pigmentation changes and lipofuscin deposits. Finally, hypothalamic anomalies consisting of interhypothalamic adhesions, a congenital midline defect usually associated with holoprosencephaly, was detected in 5 cases. CONCLUSION: This is the first report indicating that CDK5RAP2 not only governs brain size but also plays a role in ocular and cochlear development and is necessary for hypothalamic nuclear separation at the midline. Our data indicate that CDK5RAP2 should be considered as a potential gene associated with deafness and forme fruste of holoprosencephaly. These children should be given neurosensory follow-up to prevent additional comorbidities and allow them reaching their full educational potential. TRIAL REGISTRATION NUMBER: NCT01565005.

Congenital Cytomegalovirus Infection Alters Olfaction Before Hearing Deterioration In Mice.

In developed countries, cytomegalovirus (CMV)-infected newborns are at high risk of developing sensorineural handicaps such as hearing loss, requiring extensive follow-up. However, early prognostic tools for auditory damage in children are not yet available. In the fetus, CMV infection leads to early olfactory bulb (OB) damage, suggesting that olfaction might represent a valuable prognosis for neurological outcome of this viral infection. Here, we demonstrate that in utero CMV inoculation causes fetal infection and growth retardation in mice of both sexes. It disrupts OB normal development, leading to disproportionate OB cell layers and rapid major olfactory deficits. Olfaction is impaired as early as day 6 after birth in both sexes, long before the emergence of auditory deficits. Olfactometry in males reveals a long-lasting alteration in olfactory perception and discrimination, particularly in binary mixtures of monomolecular odorants. Although sensory inputs to the OB remain unchanged, hallmarks of autophagy are increased in the OB of 3-postnatal week-old mice, leading to local neuroinflammation and loss of neurons expressing tyrosine hydroxylase and calbindin. At the cellular level, we found CMV-infected cells and an increased number of apoptotic cells scattered throughout the OB layers, whereas cell proliferation in the neurogenic subventricular zone was decreased. These cellular observations were long-lasting, persisting up to 16 weeks after birth in both males and females and thus providing a mechanism supporting olfactory loss. Despite obvious differences in neurogenesis between human and mouse, these findings offer new strategies aimed at early detection of neurological dysfunctions caused by congenital infections.SIGNIFICANCE STATEMENT In developed countries, congenital cytomegalovirus (CMV)-infected newborns are at high risk of developing sensory handicaps such as hearing loss, thus requiring prolonged follow-up. In this study, we describe for the first time the functional impact of congenital CMV infection on the olfactory system and its associated sense of smell. We demonstrate that a mouse model of congenital CMV infection shows defects in olfactory bulb (OB) normal development and pronounced olfactory deficits affecting acuity and discrimination of odorants. These major olfactory deficits occur long before the emergence of auditory deficits through the upregulation of OB autophagy inducing local neuroinflammation and altered neuron content. Our findings provide new opportunities for designing olfactory means to monitor the possible neurological outcome during congenital CMV infection.

Multimodal techniques failed to detect cytomegalovirus in human glioblastoma samples.

The role of the human cytomegalovirus (HCMV) in gliomagenesis is largely debated. Contradictory data exist regarding the sensitivity and specificity of HCMV detection techniques, including immunohistochemistry (IHC), in situ hybridization (ISH), and RNA and DNA sequencing. The aim of this study is to detect HCMV in glioblastoma (GBM) tumor samples using IHC, ISH, and real-time PCR (qPCR), as well as to correlate the findings with serological status and HCMV DNA load in blood. Forty-seven patients with histopathological diagnosis of GBM and HCMV serological status were retrospectively reviewed. HCMV DNA quantification in whole blood was performed in 31 patients. The detection of HCMV in tumor samples was performed using IHC in 42 cases, ISH in 10 cases, and qPCR in 29 cases. All but two patients were taking high steroid doses at the time of biological testing. HCMV seroprevalence was 68%. Active infection with HCMV DNA detected in blood was diagnosed in 6 out of 21 (28%) seropositive patients. HCMV was not detected in GBM samples using IHC or ISH, while qPCR was positive in one case (also positive for blood HCMV DNA). These data do not support a crucial role of HCMV in GBM tumorigenesis. HCMV might be reactivated in GBM patients, due to steroid treatment.

Hearing loss in children with sickle cell disease: A prospective French cohort study.

BACKGROUND: Sickle cell disease (SCD) is the most common genetic disease in France. In developing countries, it is associated with a high incidence of hearing loss. The aim of this study was to determine the prevalence of hearing loss in French children with SCD in order to determine if they need a close audiological follow-up. METHODS: We performed a single-center prospective cross-sectional study of children with SCD. The children, without specific hearing symptom, underwent an ear, nose and throat examination with a hearing assessment between 2015 and 2016. RESULTS: Eighty-nine children were included, aged from 5 to 19 years, with 73% of SS or Sß0 genotype and 27% of SC or Sß+ genotype. Ten children (11.2%) had hearing thresholds higher than 20 dB in at least one ear: one child with subnormal hearing, six otitis media with effusion (OME), and three sensorineural hearing loss. Late age at diagnosis of SCD, a high platelet count and a low hematocrit level were significantly associated with OME; moreover, children with OME had more severe clinical and biological characteristics than children with normal hearing. Furthermore, 12.4% of the children complained of tinnitus. The rate of sudden hearing loss was 2.2%. Finally, 7.1% of patients with normal hearing showed a speech discrimination disorder. CONCLUSIONS: Several causes were identified for hearing loss in children with SCD. They therefore need a close audiological follow-up in order to avoid complications due to curable phenomena and to enable appropriate management for progressive complications.

Routine multi detector computed tomography evaluation of tracheal impairment compared to laryngo-tracheal endoscopy in children with vascular ring.

PURPOSE: The aim of this study is to compare free-breathing routine multi detector computed tomography (MDCT) and laryngo-tracheal (LT) flexible endoscopy in the evaluation of tracheal impairment in children with vascular ring (VR). MATERIALS AND METHODS: We performed a retrospective and monocentric study of all patients with VR from 1997 to 2014. Clinical data included: initial symptoms, type of surgery and clinical outcome. MDCT were blindly reviewed by two radiologists in consensus, independently of LT endoscopy results. Radiologic and endoscopic results were reviewed according to four criteria: percentage of tracheal narrowing, distance of the compression from carina, presence of bronchial compression and signs of tracheomalacia (TM). Concordance was evaluated for each criterion with a Spearman coefficient. RESULTS: From 1997 to 2016, 21 patients with a vascular ring were operated on, among which 57% by thoracoscopy: double aortic arch (n = 14), Neuhauser anomaly (n = 4) and Right aorta + aberrant right subclavian artery (n = 3). 90% of them presented with respiratory symptoms among which 43% of stridor. Chest X-ray was suggestive of VR in 87% of the cases. MDCT images and LT endoscopy results were available and analyzed for nine patients. Concordance (Spearman correlation coefficient) was excellent for percentage and level of tracheal narrowing (1) and good for TM (0.79). CONCLUSION: Free breathing routine MDCT is a reliable exam compared to LT endoscopy in the evaluation of tracheal impairment in children with VR. In case of respiratory symptoms (except stridor) and suggestive chest X-ray of VR, endoscopy could be avoided and routine MDCT alone performed.

[Diagnostic approach to child deafness]. / Démarche diagnostique devant une surdité de l'enfant.

Diagnostic approach to child deafness. The identification of a hearing loss in a child must lead the practitioner to take two initiatives: first, he must characterize it as a conductive or perceptive hearing loss, and assess its severity; secondly, he must try to establish its origin because the management can depend on it. The etiological search relies on a careful physical examination and complementary tests oriented on the findings of the latter, the clinical history and not only personal but also prenatal medical history. Admittedly, genetic causes are majoritarian among perception deafness, but acquired causes should not be underestimated, especially those due to bacterial or viral infections. Etiological assessments should not, however, slow down the management of the hearing loss, which is often based on hearing aids or surgery and speech therapy when necessary.

Démarche diagnostique devant une surdité de l'enfant. La découverte d'une surdité chez un enfant doit amener le praticien à entreprendre deux démarches : d'une part, il doit caractériser celle-ci en tant que surdité de transmission ou de perception, et en apprécier sa sévérité ; d'autre part, il doit essayer d'en établir l'origine, car la prise en charge peut en dépendre. La recherche étiologique repose sur un examen clinique minutieux et des examens complémentaires orientés en fonction de celui-ci, de l'histoire clinique et des antécédents non seulement personnels mais aussi anténataux. Certes, les causes génétiques sont majoritaires parmi les surdités de perception, mais il ne faut pas sous-estimer les causes acquises, en particulier la suite d'une infection bactérienne ou virale. Les bilans étiologiques ne doivent cependant pas ralentir la prise en charge qui repose le plus souvent sur un appareillage ou une chirurgie et un accompagnement orthophonique si nécessaire.

Congenital middle ear anomalies: anatomical and functional results of surgery.

The aim of this study was to describe the audiometric results following surgery in a consecutive series of pediatric patients with a congenital middle ear disorder. Retrospective chart review was performed for 29 consecutive children who underwent 33 middle ear surgeries for congenital ossicular chain anomaly between 1990 and 2012. Anomalies were classified into four groups according to the Teunissen and Cremers classification. Audiological parameters using four frequency averages (0.5, 1, 2 and 4 kHz) were assessed pre- and postoperatively. Clinical and audiometric follow-up times were, respectively, 49 ± 8 and 35 ± 5 months (mean ± SEM). Fifty-eight percent of all patients achieved an air-bone gap (ABG) ≤20 dB, 62.5% in class I, 50% in class II and 57.9% in class III. The improvement of the mean ABG was 13.6 dB, 19.2 dB for class I, 0.2 dB in class II and 15.4 dB in class III. Overall mean pure-tone averages improved 14.8 dB with 13.9 dB for class I; there was no improvement for class II and 20.2 dB for class III. The sensorineural hearing loss rate was 9%. This pediatric series showed that hearing results depend on type of anomaly. Class I and class III showed better hearing improvement than class II.

G protein-coupled receptor kinase 2 and group I metabotropic glutamate receptors mediate inflammation-induced sensitization to excitotoxic neurodegeneration.

OBJECTIVE: The concept of inflammation-induced sensitization is emerging in the field of perinatal brain injury, stroke, Alzheimer disease, and multiple sclerosis. However, mechanisms underpinning this process remain unidentified. METHODS: We combined in vivo systemic lipopolysaccharide-induced or interleukin (IL)-1ß-induced sensitization of neonatal and adult rodent cortical neurons to excitotoxic neurodegeneration with in vitro IL-1ß sensitization of human and rodent neurons to excitotoxic neurodegeneration. Within these inflammation-induced sensitization models, we assessed metabotropic glutamate receptors (mGluR) signaling and regulation. RESULTS: We demonstrate for the first time that group I mGluRs mediate inflammation-induced sensitization to neuronal excitotoxicity in neonatal and adult neurons across species. Inflammation-induced G protein-coupled receptor kinase 2 (GRK2) downregulation and genetic deletion of GRK2 mimicked the sensitizing effect of inflammation on excitotoxic neurodegeneration. Thus, we identify GRK2 as a potential molecular link between inflammation and mGluR-mediated sensitization. INTERPRETATION: Collectively, our findings indicate that inflammation-induced sensitization is universal across species and ages and that group I mGluRs and GRK2 represent new avenues for neuroprotection in perinatal and adult neurological disorders.

Child-TRACH: Management of tracheostomy in children, a Yo-IFOS survey.

OBJECTIVES: The number of tracheostomies in children has increased the last twenty years thanks to neonatal and pediatric intensive care improvement. As it is often a difficult situation to deal with for children and their caregivers, we wished to draw up the inventory of the management protocols of pediatric tracheostomies around the world. METHODS: We performed an online international survey for ENTs managing children with tracheostomies. The survey was in English and diffused through ENT national and international societies (International Federation of Otorhinolaryngologists Societies, IFOS and French Society of Otorhinolaryngologists, SFORL). Answers were anonymized and collected online between September 2021 and January 2022. All data were analyzed as a whole and according to the continent. RESULTS: 119 ENTs from the different continents responded to the survey: Europe (45.4 %), Asia (16 %), North America (14.3 %), South America (10.9 %), Africa (6.7 %) and Oceania (6.7 %). The most common indication for tracheostomy was laryngeal obstruction (77.3 %). Once initial management and surgical procedure performed, the majority of children returned home with their tracheostomy; tracheostomy was a contraindication for only 1.7 % of the responders. Concerning patient autonomy on daily care of the cannula at home, it was acquired in only 27.7 % of the cases, no difference was observed between countries (p = 0.22). Therapeutic patient education (TPE) was offered for 86.9 % of the patients taken care by the responders: it was dedicated to training the parents (96.8 %), with no differences between countries; however, in some countries, TPE for could also be offered to other caregivers. The mean delay between surgery and first change of cannula was 27.3 days (1-100) but varied depending on the country (4 days in Nigeria, 20 days in north America, 40 days in Europe, Asia and south America). CONCLUSION: Although tracheostomies in children can encompass several indications, practices across the world are similar and aim to offer a life as normal as possible for these children.

Diagnosis and management of congenital hypopituitarism in children.

Hypopituitarism (or pituitary deficiency) is a rare disease with an estimated prevalence of between 1/16,000 and 1/26,000 individuals, defined by insufficient production of one or several anterior pituitary hormones (growth hormone [GH], thyroid-stimulating hormone [TSH], adrenocorticotropic hormone [ACTH], luteinizing hormone [LH], follicle-stimulating hormone [FSH], prolactin), in association or not with diabetes insipidus (antidiuretic hormone [ADH] deficiency). While in adults hypopituitarism is mostly an acquired disease (tumors, irradiation), in children it is most often a congenital condition, due to abnormal pituitary development. Clinical symptoms vary considerably from isolated to combined deficiencies and between syndromic and non-syndromic forms. Early signs are non-specific but should not be overlooked. Diagnosis is based on a combination of clinical, laboratory (testing of all hormonal axes), imaging (brain magnetic resonance imaging [MRI] with thin slices centered on the hypothalamic-pituitary region), and genetic (next-generation sequencing of genes involved in pituitary development, array-based comparative genomic hybridization, and/or genomic analysis) findings. Early brain MRI is crucial in neonates or in cases of severe hormone deficiency for differential diagnosis and to inform syndrome workup. This article presents recommendations for hormone replacement therapy for each of the respective deficient axes. Lifelong follow-up with an endocrinologist is required, including in adulthood, with multidisciplinary management for patients with syndromic forms or comorbidities. Treatment objectives include alleviating symptoms, preventing comorbidities and acute complications, and optimal social and educational integration.