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.

Position statement on the diagnosis and management of congenital pituitary deficiency in adults: The French National Diagnosis and Treatment Protocol (NDTP).

Pituitary deficiency, or hypopituitarism, is a rare chronic disease. It is defined by insufficient synthesis of one or more pituitary hormones (growth hormone, TSH, ACTH, LH-FSH, prolactin), whether or not associated with arginine vasopressin deficiency (formerly known as diabetes insipidus). In adult patients, it is usually acquired (notably during childhood), but can also be congenital, due to abnormal pituitary development. The present study focuses on congenital pituitary deficiency in adults, from diagnosis to follow-up, including special situations such as pregnancy or the elderly. The clinical presentation is highly variable, ranging from isolated deficit to multiple deficits, which may be part of a syndromic form or not. Diagnosis is based on a combination of clinical, biological (assessment of all hormonal axes), radiological (brain and hypothalamic-pituitary MRI) and genetic factors. Treatment consists in hormonal replacement therapy, adapted according to the period of life and the deficits, which may be progressive. Comorbidities, risk of complications and acute decompensation, and the impact on fertility and quality of life all require adaptative multidisciplinary care and long-term monitoring.

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.

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.

Decannulation in congenital central hypoventilation syndrome.

RATIONALE: Patients with congenital central hypoventilation syndrome (CCHS) require long-term ventilation to ensure gas exchange and to prevent deleterious consequences for neurocognitive development. Two ventilation modes may be used for these patients depending on their tolerance, one invasive by tracheostomy and the other noninvasive (NIV). For patients who have undergone a tracheostomy, transition to NIV is possible when they meet predefined criteria. Identifying the conditions favorable for weaning from a tracheostomy is critical for the success of the process. OBJECTIVE: The aim of the study was to share our experience of decannulation in a reference center; we hereby describe the modality of ventilation and its effect on nocturnal gas exchange before and after tracheostomy removal. METHODS: Retrospective observational study at Robert Debré Hospital over the past 10 years. The modalities of decannulation and transcutaneous carbon dioxide recordings or polysomnographies before and after decannulation were collected. RESULTS: Sixteen patients underwent decannulation following a specific procedure for transition from invasive to NIV. All decannulations were successful. The median age at decannulation was 12.6 [9.4; 14.1] years. Nocturnal gas exchange was not significantly different before and after decannulation, while expiratory positive airway pressure and inspiratory time increased significantly. An oronasal interface was chosen in two out of three patients. The median duration of hospital stay for decannulation was 4.0 [3.8; 6.0] days. CONCLUSION: Our study underlines that decannulation and transition to NIV are achievable in CCHS children using a well-defined procedure. Patient preparation is crucial to the success of the process.

Functional specialization of short-lived and long-lived macrophage subsets in human tonsils.

Macrophages play a central role in tissue homeostasis and host defense. However, the properties of human macrophages in non-diseased tissues remain poorly understood. Here, we characterized human tonsil macrophages and identified three subsets with distinct phenotype, transcriptome, life cycle, and function. CD36hi macrophages were related to monocytes, while CD36lo macrophages showed features of embryonic origin and CD36int macrophages had a mixed profile. scRNA-seq on non-human primate tonsils showed that monocyte recruitment did not pre-exist an immune challenge. Functionally, CD36hi macrophages were specialized for stimulating T follicular helper cells, by producing Activin A. Combining reconstruction of ligand-receptor interactions and functional assays, we identified stromal cell-derived TNF-α as an inducer of Activin A secretion. However, only CD36hi macrophages were primed for Activin A expression, via the activity of IRF1. Our results provide insight into the heterogeneity of human lymphoid organ macrophages and show that tonsil CD36hi macrophage specialization is the result of both intrinsic features and interaction with stromal cells.

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.

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.

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.

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.

Prevalence of mouth breathing, with or without nasal obstruction, in children with moderate to severe obstructive sleep apnea.

BACKGROUND: Mouth breathing (MB) is a symptom of obstructive sleep apnea (OSA) in children, but its diagnosis remains challenging. The main objectives of our study were to evaluate whether parents' and physician's diagnose of MB were concordant and to evaluate the prevalence of nasal obstruction in children with OSA and MB. METHODS: Ninety-three children (median age: 10.6 years, range 3-18) with moderate to severe OSA prospectively underwent otorhinolaryngologist (endoscopy, acoustic rhinometry and pharyngometry allowing calculation of pharyngeal compliance) and orthodontist (clinical exam and cephalometry) assessments together with parental interview (daytime MB: never, sometimes, often, always). MB was also assessed by the otorhinolaryngologist (nasal obstruction on endoscopy) and the orthodontist (incompetent lips or anterior open bite or low tongue position). RESULTS: Thirty-eight children (41%) were mouth (parental criterion: MB often or always, median age 8.2 years) and 55 nasal (11.4 years, p = 0.016) breathers. The agreement of parental and physician diagnosis of MB was slight (orthodontist) to moderate (otorhinolaryngologist). Parental diagnosis of MB was associated with nasal obstruction on acoustic rhinometry and endoscopy (hypertrophy of inferior turbinate, n = 18 or adenoids, n = 15) and with an adenoid facies (increased Frankfort's mandibular plane angle on cephalometry). Eleven children had MB by habit and were characterized by more severe OSA and higher pharyngeal compliance than mouth breathers with nasal obstruction. CONCLUSION: MB diagnosis by parents is acceptable and is mainly related to nasal obstruction. A subset of children had MB by habit associated with worst OSA and increased pharyngeal compliance that could benefit from myofunctional therapy.

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.

Step-by-step development and evaluation of a 3D printed home-made low-cost pediatric tracheobronchial tree for foreign body aspiration extractions.

OBJECTIVES: The management of foreign body aspirations (FBA) is dreaded by pediatric physicians due to the high risk of respiratory distress and a potential fatal outcome, favored by a lack of experience of young specialists. Furthermore, there has been an increasing requirement for low-cost simulation. The aim was to describe the step-by-step manufacturing process and to validate a low-cost, easily home-made training model of pediatric tracheo-bronchial tree (pTBT) for simulation-based training in order to teach young physicians to practice foreign body (FBA) extractions. METHODS: A simulator was designed in order to reproduce the physical and esthetic properties of a pTBT. The production cost of a single simulator was estimated. The simulator was then tested by experienced physicians using a rigid bronchoscope. A manufacturing manual of the simulator is hereby presented. A group of 7 experienced pediatric otolaryngologists performed a FBA extraction in the conditions of installation of an operating room. RESULTS: The result of the survey showed a high fidelity of the simulator in mimicking the biological esthetics and physical properties of a pTBT during a FBA extraction (mean 4.3 ± 0.8). The total cost of the custom-made simulator is about 20.5 € ($23.4) for the production of the first simulator. CONCLUSIONS: A highly realistic and easily reproducible pediatric tracheo-bronchial tree simulator is presented and can therefore be used during simulation-based training.

Histological Severity Risk Factors Identification in Juvenile-Onset Recurrent Respiratory Papillomatosis: How Immunohistochemistry and AI Algorithms Can Help?

Juvenile-onset recurrent respiratory papillomatosis (JoRRP) is a condition characterized by the repeated growth of benign exophytic papilloma in the respiratory tract. The course of the disease remains unpredictable: some children experience minor symptoms, while others require multiple interventions due to florid growth. Our study aimed to identify histologic severity risk factors in patients with JoRRP. Forty-eight children from two French pediatric centers were included retrospectively. Criteria for a severe disease were: annual rate of surgical endoscopy ≥ 5, spread to the lung, carcinomatous transformation or death. We conducted a multi-stage study with image analysis. First, with Hematoxylin and eosin (HE) digital slides of papilloma, we searched for morphological patterns associated with a severe JoRRP using a deep-learning algorithm. Then, immunohistochemistry with antibody against p53 and p63 was performed on sections of FFPE samples of laryngeal papilloma obtained between 2008 and 2018. Immunostainings were quantified according to the staining intensity through two automated workflows: one using machine learning, the other using deep learning. Twenty-four patients had severe disease. For the HE analysis, no significative results were obtained with cross-validation. For immunostaining with anti-p63 antibody, we found similar results between the two image analysis methods. Using machine learning, we found 23.98% of stained nuclei for medium intensity for mild JoRRP vs. 36.1% for severe JoRRP (p = 0.041); and for medium and strong intensity together, 24.14% for mild JoRRP vs. 36.9% for severe JoRRP (p = 0.048). Using deep learning, we found 58.32% for mild JoRRP vs. 67.45% for severe JoRRP (p = 0.045) for medium and strong intensity together. Regarding p53, we did not find any significant difference in the number of nuclei stained between the two groups of patients. In conclusion, we highlighted that immunochemistry with the anti-p63 antibody is a potential biomarker to predict the severity of the JoRRP.

IVORY Guidelines (Instructional Videos in Otorhinolaryngology by YO-IFOS): A Consensus on Surgical Videos in Ear, Nose, and Throat.

OBJECTIVES/HYPOTHESIS: Otolaryngology instructional videos available online are often of poor quality. The objective of this article was to establish international consensus recommendations for the production of educational surgical videos in otolaryngology. STUDY DESIGN: DELPHI survey. METHODS: Twenty-seven international respondents participated in this study from 12 countries. Consensus was reached after three rounds of questionnaires following the Delphi methodology. The proposals having reached the 80% agreement threshold in the third round were retained. RESULTS: The main recommendations are as follows: 1) Ethics: patients must be anonymized and unrecognizable (apart from plastic surgery if necessary). A signed authorization must be obtained if the person is recognizable. 2) Technical aspects: videos should be edited and in high-definition (HD) quality if possible. Narration or subtitles and didactic illustrations are recommended. 3) Case presentation: name of pathology and procedure must be specified; the case should be presented with relevant workup. 4) Surgery: surgical procedures should be divided into several distinct stages and include tips and pitfalls. Pathology should be shown if relevant. Key points should be detailed at the end of the procedure. 5) Organ-specific: type of approach and bilateral audiometry should be specified in otology. Coronal plane computed tomography scans should be shown in endonasal surgery. It is recommended to show pre- and postoperative videos in voice surgery and preoperative drawings and photos of scars in plastic surgery, as well as the ventilation method in airway surgery. CONCLUSIONS: International recommendations have been determined to assist in the creation and standardization of educational surgical videos in otolaryngology and head and neck surgery. LEVEL OF EVIDENCE: 5 Laryngoscope, 131:E732-E737, 2021.

YO-IFOS Guidelines for Pediatric ENT Surgery during COVID-19: An Overview of Recommendations.

OBJECTIVE/HYPOTHESIS: To review the literature on pediatric ENT COVID-19 guidelines worldwide, in particular, surgical practice during the pandemic, and to establish a comprehensive set of recommendations. STUDY DESIGN: Review. METHODS: A comprehensive literature review through an independent electronic search of the COVID-19 pandemic in PubMed, Medline, Google, and Google Scholar was performed on April 26-30, 2020. Resources identified comprised of published papers, national and international pediatric ENT society guidelines. RESULTS: Fourteen guidelines fit the inclusion criteria. Key statements were formulated and graded: 1) Strong recommendation (reported by 9 or more/14); 2) Fair recommendation (7-8/14); 3) Weak recommendation (5-6/14); and 4) Expert opinion (2-4/14). Any single source suggestion was included as a comment. Highly scored recommendations included definition of urgent/emergent cases that required surgery; surgery for acute airway obstruction; prompt diagnosis of suspected cancer; and surgical intervention for sepsis following initial first-line medical management. Other well scored recommendations included senior faculty to perform the surgery; the use of open approaches rather than endoscopic ones; and avoidance of powered instruments that would aerosolize virus-loaded tissue. A tracheostomy should be performed on a case by case basis where key technical modifications become necessary. CONCLUSIONS: The COVID-19 pandemic will have a profound short and long-term impact on pediatric ENT practice. During this rapidly evolving climate, guidelines have been based on local practice and expert opinion. Until evidence-based practice in the COVID era is established, a comprehensive set of recommendations for pediatric ENT surgical practice based on a review of currently available literature and guidelines, is therefore, appropriate. Laryngoscope, 131:1876-1883, 2021.

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.