Long term follow-up after haematopoietic stem cell transplantation for mucopolysaccharidosis type I-H: a retrospective study of 51 patients.

Mucopolysaccharidosis type I-H (MPS I-H) is a rare lysosomal storage disorder caused by α-L-Iduronidase deficiency. Early haematopoietic stem cell transplantation (HSCT) is the sole available therapeutic option to preserve neurocognitive functions. We report long-term follow-up (median 9 years, interquartile range 8-16.5) for 51 MPS I-H patients who underwent HSCT between 1986 and 2018 in France. 4 patients died from complications of HSCT and one from disease progression. Complete chimerism and normal α-L-Iduronidase activity were obtained in 84% and 71% of patients respectively. No difference of outcomes was observed between bone marrow and cord blood stem cell sources. All patients acquired independent walking and 91% and 78% acquired intelligible language or reading and writing. Intelligence Quotient evaluation (n = 23) showed that 69% had IQ ≥ 70 at last follow-up. 58% of patients had normal or remedial schooling and 62% of the 13 adults had good socio-professional insertion. Skeletal dysplasia as well as vision and hearing impairments progressed despite HSCT, with significant disability. These results provide a long-term assessment of HSCT efficacy in MPS I-H and could be useful in the evaluation of novel promising treatments such as gene therapy.

International Pediatric Otolaryngology Group (IPOG) consensus recommendations: Evaluation and management of congenital tracheal stenosis.

OBJECTIVES: To outline an expert-based consensus of recommendations for the diagnosis and management of pediatric patients with congenital tracheal stenosis. METHODS: Expert opinions were sought from members of the International Pediatric Otolaryngology Group (IPOG) via completion of an 18-item survey utilizing an iterative Delphi method and review of the literature. RESULTS: Forty-three members completed the survey providing recommendations regarding the initial history, clinical evaluation, diagnostic evaluation, temporizing measures, definitive repair, and post-repair care of children with congenital tracheal stenosis. CONCLUSION: These recommendations are intended to be used to support clinical decision-making regarding the evaluation and management of children with congenital tracheal stenosis. Responses highlight the diverse management strategies and the importance of a multidisciplinary approach to care of these patients.

Natural history of Myhre syndrome.

BACKGROUND: Myhre syndrome (MS) is a rare genetic disease characterized by skeletal disorders, facial features and joint limitation, caused by a gain of function mutation in SMAD4 gene. The natural history of MS remains incompletely understood. METHODS: We recruited in a longitudinal retrospective study patients with molecular confirmed MS from the French reference center for rare skeletal dysplasia. We described natural history by chaining data from medical reports, clinical data warehouse, medical imaging and photographies. RESULTS: We included 12 patients. The median age was 22 years old (y/o). Intrauterine and postnatal growth retardation were consistently reported. In preschool age, neurodevelopment disorders were reported in 80% of children. Specifics facial and skeletal features, thickened skin and joint limitation occured mainly in school age children. The adolescence was marked by the occurrence of pulmonary arterial hypertension (PAH) and vascular stenosis. We reported for the first time recurrent strokes from the age of 26 y/o, caused by a moyamoya syndrome in one patient. Two patients died at late adolescence and in their 20 s respectively from PAH crises and mesenteric ischemia. CONCLUSION: Myhre syndrome is a progressive disease with severe multisystemic impairement and life-threathning complication requiring multidisciplinary monitoring.

Noninvasive Respiratory Support as an Alternative to Tracheostomy in Severe Laryngomalacia.

OBJECTIVES/HYPOTHESIS: To analyze the role of noninvasive respiratory support (NRS) as an alternative to tracheostomy in the management of severe laryngomalacia. STUDY DESIGN: We conducted a monocentric retrospective study in a tertiary pediatric care center. METHODS: All children under the age of 3 years with severe laryngomalacia, treated between January 2014 and December 2019, were included. Patient demographics, medical history, nutrition, surgery, NRS, and outcome were reviewed. Predictors for NRS were analyzed. RESULTS: One hundred and eighty-eight patients were included. Mean age was 4 ± 5 months and mean weight was 4,925 ± 1,933 g. An endoscopic bilateral supraglottoplasty was performed in 183 (97%) patients and successful in 159 (87%). NRS was initiated in 29 (15%) patients at a mean age of 3 ± 2 months (1-11 months): 15 (52%) patients were treated with NRS after surgical failure, 9 (31%) were treated with NRS initiated prior to surgery because of abnormal overnight gas exchange, and 5 (17%) were treated exclusively with NRS due to comorbidities contraindicating an endoscopic procedure. NRS was successfully performed in all patients with a mean duration of 6 ± 11 months. No patient required a tracheostomy. Univariate analysis identified the following predictors of NRS: neonatal respiratory distress (P = .003), neurological comorbidity (P < .001), associated laryngeal abnormality (P < .001), cardiac surgery (P = .039), surgical endoscopic revision (P = .007), and nutritional support (P < .001). CONCLUSION: NRS is a safe procedure, which may avoid a tracheostomy in severe laryngomalacia, in particular, in case of endoscopic surgery failure, respiratory failure before surgery, and/or severe co-morbidity. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:1861-1868, 2022.

Impact of COVID-19 lockdown on a tertiary center pediatric otolaryngology emergency department.

To assess the quantitative and qualitative impact of the COVID-19 lockdown on pediatric otolaryngology emergency activity. A retrospective study was conducted in a pediatric otolaryngology tertiary care center. Emergency activity during the lockdown period from March 17 to May 11, 2020, was compared to the 2019 and 2018 averages for the same period. Study data included a number of emergency consultations and the number and type of surgical procedures: infection management, endoscopic airway procedure, and post-tonsillectomy hemorrhage. Only 350 children were referred to the pediatric otolaryngology emergencies in our center during the lockdown, compared to 761 on the same period the year before (- 54%); 62 emergency surgeries were performed, compared to 93 (- 33%). The ratio between emergency surgeries and consultations was 18% in 2020, versus 12% previously (p = 0.014). The number of surgical procedures for infectious diseases decreased (- 68%), at 16% of surgical emergencies in 2020 compared to 33% previously (p = 0.017). In 2020, 52 emergency endoscopies were performed, versus 59 previously (- 12%), 27% being performed for suspected tracheobronchial or esophageal foreign bodies, compared to 66% in previous years (p < 0.0001). No post-tonsillectomy hemorrhages were managed in 2020.Conclusion: The COVID-19 lockdown changed pediatric ENT emergency activity quantitatively and also qualitatively. What is Known: • SARS-CoV-2 pandemic impacted pediatric ENT emergency activity quantitatively and qualitatively. What is New: • here was a 54% decrease in pediatric ENT emergency consultation and 33% decrease in emergency ENT surgeries. • Rates of surgery for infection of whatever type decreased by 68%.

Geleophysic and acromicric dysplasias: natural history, genotype-phenotype correlations, and management guidelines from 38 cases.

PURPOSE: Geleophysic dysplasia (GD) and acromicric dysplasia (AD) are characterized by short stature, short extremities, and progressive joint limitation. In GD, cardiorespiratory involvement can result in poor prognosis. Dominant variants in the FBN1 and LTBP3 genes are responsible for AD or GD, whereas recessive variants in the ADAMTSL2 gene are responsible for GD only. The aim of this study was to define the natural history of these disorders and to establish genotype-phenotype correlations. METHODS: This monocentric retrospective study was conducted between January 2008 and December 2018 in a pediatric tertiary care center and included patients with AD or GD with identified variants (FBN1, LTBP3, or ADAMTSL2). RESULTS: Twenty-two patients with GD (12 ADAMTSL2, 8 FBN1, 2 LTBP3) and 16 patients with AD (15 FBN1, 1 LTBP3) were included. Early death occurred in eight GD and one AD. Among GD patients, 68% presented with heart valve disease and 25% developed upper airway obstruction. No AD patient developed life-threatening cardiorespiratory issues. A greater proportion of patients with either a FBN1 cysteine variant or ADAMTSL2 variants had a poor outcome. CONCLUSION: GD and AD are progressive multisystemic disorders with life-threatening complications associated with specific genotype. A careful multidisciplinary follow-up is needed.

Thulium LASER for endoscopic closure of tracheoesophageal fistula in esophageal atresia's spectrum: An appropriate tool?

PURPOSE: To report our experience with endoscopic Thulium LASER for treatment of recurrent TEF after EA surgery, and for H-Type fistulas. METHODS: A retrospective chart review of consecutive patients undergoing standardized endoscopic closure as first line therapy of recurrent tracheoesophageal fistula (RTEF) and H-type fistula using Thulium LASER, from 2013 to 2019, in a pediatric tertiary care center. Control endoscopic procedure was systematically performed. If persistence of the TEF was noted an external approach was performed. Patient demographics, medical history, symptoms, TEF type, treatment modalities, complications and outcomes were collected. RESULTS: Eleven patients with tracheoesophageal fistula were included: six RTEF after primary repair of esophageal atresia and five H-type fistulas. The average age at endoscopic treatment was 19 months (SD 23 months, range 13 days-63 months). Closure of the fistula after single endoscopic procedure with Thulium LASER was obtained in 3 RTEF (50%) and 1 H-type fistula (20%). Six patients with failure of endoscopic treatment were cured after a single external procedure without any complications. One child, treated for H-type fistula, presented a severe complication of Thulium LASER treatment. Median follow-up after last repair was 24 months (range: 14-72 months). All fistulas were successfully treated. CONCLUSIONS: In H-Type fistula, success rate of Thulium LASER is only 20% and thus should not be used. In contrast, in RTEF, success rate of 50% is achieved, avoiding as many open procedures, and Thulium LASER could be considered as first line treatment. In any case, open surgery is safe and efficient and can be considered as a first-line treatment for H-type fistulas, and as a salvage treatment for endoscopic treatment failures. LEVELS OF EVIDENCE: Level IV.

Respiratory polygraphy in subjects with bronchopulmonary dysplasia: a retrospective study.

BACKGROUND: Periodic assessment of the need for oxygen supplementation and/or mechanical ventilation in children with severe bronchopulmonary dysplasia (BPD) is crucial. The aim of the study was to analyze the indications and results of respiratory polygraphies (RP) performed in preterm infants with BPD followed at a tertiary university hospital. METHODS: All subjects < 5-year-old with BPD who had a RP between September and February 2018 were included. The indications and results of RP and consequent medical management were analyzed. RESULTS: Fourteen infants (9 females, mean gestational age 27.6±3.3 weeks) underwent a RP at mean age of 26.4±19.4 months. Five subjects were evaluated for the need of long-term respiratory support (RS), 3 started continuous positive airway pressure (CPAP), 2 were weaned from RS. Four subjects underwent RP for suspected obstructive sleep apnea (OSA), one started on CPAP. Central apnea syndrome (CSA) was confirmed in 2 subjects and one was started on non-invasive ventilation. RP allowed safe tracheostomy decannulation in 2 subjects. Finally, RP was normal in one patient who had a brief resolved unexplained event (BRUE). CONCLUSIONS: RP represents an important tool for the evaluation of children with BPD and leads to important therapeutic decisions.

Outcome measures for pediatric laryngotracheal reconstruction: International consensus statement.

OBJECTIVES: Develop multidisciplinary and international consensus on patient, disease, procedural, and perioperative factors, as well as key outcome measures and complications, to be reported for pediatric airway reconstruction studies. METHODS: Standard Delphi methods were applied. Participants proposed items in three categories: 1) patient/disease characteristics, 2) procedural/intraoperative/perioperative factors, and 3) outcome measures and complications. Both general and anatomic site-specific measures were elicited. Participants also suggested specific operations to be encompassed by this project. We then used iterative ranking and review to develop consensus lists via a priori Delphi consensus criteria. RESULTS: Thirty-three pediatric airway experts from eight countries in North and South America, Europe, and Australia participated, representing otolaryngology (including International Pediatric Otolaryngology Group members), pulmonology, general surgery, and cardiothoracic surgery. Consensus led to inclusion of 19 operations comprising open expansion, resection, and slide procedures of the larynx, trachea, and bronchi as well as three endoscopic procedures. Consensus was achieved on multiple patient/comorbidity (10), disease/stenosis (7), perioperative-/intraoperative-/procedure-related (16) factors. Consensus was reached on multiple outcome and complication measures, both general and site-specific (8 general, 13 supraglottic, 15 glottic, 17 subglottic, 8 cervical tracheal, 12 thoracic tracheal). The group was able to clarify how each outcome should be measured, with specific instruments defined where applicable. CONCLUSION: This consensus statement provides a framework to communicate results consistently and reproducibly, facilitating meta-analyses, quality improvement, transfer of information, and surgeon self-assessment. It also clarifies expert opinion on which patient, disease, procedural, and outcome measures may be important to consider in any pediatric airway reconstruction patient. LEVEL OF EVIDENCE: 5 Laryngoscope, 129:244-255, 2019.

A retrospective study on sleep-disordered breathing in Morquio-A syndrome.

Respiratory problems are common in Morquio-A syndrome (MPS IVA) but objective data on sleep-disordered breathing are scarce. The aim of our study was to review polygraphic (PG) findings and the need for noninvasive continuous positive airway pressure (CPAP) or noninvasive ventilation (NIV) in children with MPS IVA. A retrospective review of the clinical charts and PG of 16 consecutive children (7 boys, mean age 10.5 ± 4.2 years) with MPS IVA seen over a period of 3 years was performed. The prevalence of obstructive sleep apnea (OSA) was 69% with only five patients, all younger than 10 years old, having a normal PG. Four patients had mild OSA (apnea-hypopnea index [AHI] ≥1.5 and <5 events/hr), three patients had moderate OSA (AHI ≥5 and <10 events/hr), and three patients had severe OSA (AHI ≥ 10 events/hr). Among the 10 patients with OSA, 3 had prior adenoidectomy ± tonsillectomy and 6 were on enzyme replacement therapy. Only one patient had a central apnea index >5 events/hr despite prior cervico-occipital decompression. Six patients, all older than 11 years old, were started on CPAP or NIV because of severe OSA (n = 4), nocturnal hypoventilation (n = 1), or impossibility to be weaned from NIV after an acute respiratory failure (n = 1). Prevalence of OSA is high in patients with MPS IVA, underlying the importance of a systematic screening for sleep-disordered breathing. CPAP and NIV are efficient and well accepted for treating sleep-disordered breathing.

Obstructive sleep apnea in Down syndrome: Benefits of surgery and noninvasive respiratory support.

Children with Down syndrome are at increased risk of obstructive sleep apnea (OSA). The aim of the study was to describe the management of OSA in a large cohort of children with Down syndrome. A retrospective analysis of sleep studies and consequent management was performed for all consecutive Down syndrome patients evaluated between September 2013 and April 2016. The data of 57 patients were analyzed: 51/53 had an interpretable overnight polygraphy and 4 the recording of nocturnal gas exchange. Mean age at baseline sleep study was 6.2 ± 5.9 years. Eighteen patients (32%) had prior upper airway surgery. Mean apnea-hypopnea index (AHI) was 14 ± 16 events/hr with 41 of the 51 (80%) patients having OSA with an AHI >1 event/hr and 20 patients (39%) having an AHI ≥10 events/hr. Consequently, eight patients (14%) had upper airway surgery. OSA improved in all patients except two who needed noninvasive respiratory support. Nineteen (33%) patients required noninvasive respiratory support. Mean age at noninvasive respiratory support initiation was 7 ± 7 years. On 11 patients with objective adherence data available, mean compliance at 2 ± 1 years of treatment was excellent with an average use per night of 8 hr46 ± 3 hr59 and 9 patients using the noninvasive respiratory support >4 hr/night. Noninvasive respiratory support was associated with an improvement of nocturnal gas exchange. The prevalence of OSA is high in Down syndrome. Upper airway surgery is not always able to correct OSA. Noninvasive respiratory support represents then an effective treatment for OSA and good compliance may be achieved in a majority of patients.

Results of VSB implantation at the short process of the incus in children with ear atresia.

OBJECTIVE(S): To describe a new and more simple surgical procedure for implanting the Vibrant Soundbridge (VSB) on the short process of the incus in children with ear atresia and atretic plate and present the audiometric results. METHODS: Since 2014, pre- and post-operative audiometric tests with tonal and vocal audiometryat the maximal follow up, respectively 33, 22 and 12 months were performed after VSB implantation at the ENT department, Necker Enfants Malades Hospital, Paris, France. 3 children aged 11, 9 and 15 years with conductive hearing loss due to high grade ear atresia and absent ear canal were implanted. The malformed and fused malleus-incus complex was found to be immobile in two of the subjects, who then underwent a superior tympanotomy to carefully remobilize the malleus. Stapes were mobile in all cases. The FMT clip was customized and crimped on the short process, stabilized by the metallic wire. RESULTS: At the maximum follow-up time, the bone conduction was unchanged, and the mean aided ACPTA was 21 dB, 29 dB and 30 dB, compared to 66 dB, 63 dB and 68 dB unaided, respectively. The word recognition score (WRS) at 65 dB SPL increased from 10%, 10% and 70% (unaided) respectively to 100% (aided). CONCLUSIONS: The long process of the incus is usually very hypoplastic in patients with ear atresia with a fused malleus-incus complex lateral to the stapes. VSB coupling to the long process of the incus or the stapes may be challenging in small mastoids. Coupling to the short process of the incus is comparatively a simple procedure, since there is no need for posterior tympanotomy and has no proximity to the facial nerve. The results of this study are similar to other ear atresia cases in the literature with classic FMT placement on the stapes or long process of the incus. Outcomes should be confirmed in a larger number of patients.

Using a new otologic operating microscope: unexpected complications.

The present work report cases of auricular burns after routine otologic surgery possibly induced by the operating microscope. Single-center retrospective study. April 2013 to January 2014, eight children presented with auricular burns after otologic surgery. Median age was 10.1 years. Cheloid scar occurred in six cases. A small scar was present for the other two patients without any other sequelae. No patient had chondritis nor cartilage loss. There was no possibility of physical or electrical trauma in the pretragal or retroauricular cutaneous area during the operations. Therefore, the only remaining hypothesis to explain these burns was thermal damage induced by the operative microscope.

Pediatric cochlear implantation in residual hearing candidates.

OBJECTIVES: To propose categories for the various types of residual hearing in children and to review the outcomes of cochlear implantation (CI) in children with these different hearing conditions. METHODS: We identified 53 children with residual hearing who had received a cochlear implant. Five groups were arbitrarily defined based on auditory features: G1, characterized by low-frequency residual hearing (n=5); G2, characterized by severe sensorineural hearing loss (SNHL) and low speech discrimination (n=12); G3, characterized by asymmetric SNHL (n=9); G4, characterized by progressive SNHL (n=15); and G5, characterized by fluctuating SNHL (n=12). The main audiometric features and outcomes of the groups were analyzed. RESULTS: The mean age at implantation was 10.15 years (range, 2.5-21 years). The mean preoperative score for the discrimination of open-set words was 48%; this score increased to 74% at 12 months and 81% at 24 months after the CI procedure (G1 to G5, respectively: 79/62/77%, 50/81/88%, 59/75/86%, 35/74/67%, and 39/69/80%). Children who were implanted after 10 years of age did not improve as much as those who were implanted at a younger age (open-set word list speech perception [OSW] score at 12 months: 62% vs 83%; P=.0009). Shorter delays before surgery were predictive of better performance (P=.003). Inner ear malformation and SLC26A4 mutations were not predictive of the outcome. CONCLUSIONS: CIs provide better results compared with hearing aids in children with residual hearing. Factors that may impact the benefits of CIs in patients with residual hearing are age, delay in performing the CI procedure, which ear is implanted, and initial underestimation of the patient's hearing difficulties.

Hearing rehabilitation with the closed skin bone-anchored implant Sophono Alpha1: results of a prospective study in 15 children with ear atresia.

OBJECTIVE: To study gain and cutaneous tolerance of the Sophono Alpha1 implant, used for unilateral hearing rehabilitation in children with ear atresia, and to demonstrate non-inferiority compared to the referral closed skin device, BAHA® on a test-band. METHODS AND MATERIALS: Fifteen children included in a prospective clinical trial from September 2010 to November 2012. Tertiary care center. MAIN OUTCOMES: Pure tone and speech audiometry before surgery and at M6 and 12; Speech-in-noise tests with and without Alpha1 at M6. Quality of life questionnaire completed before surgery and at M6; children and parent's satisfaction assessed at M6. Cutaneous appearance assessed at M6, M12 and during the last clinical assessment. RESULTS: Patients' ages ranged from 61 to 129 months. They had a pure conductive deafness with a mean air conduction pure-tone average (ACPTA) of 69.02±9.31dB, and a mean SRT of 71.73±9.20dB. Follow-up was 12-32 months. At M6, the mean aided ACPTA was 33.49±4.89dB, the mean aided SRT 38.27±4.54dB and the mean aided SRT in noise was statistically improved (-7.80dB). Sophono Alpha1 demonstrated non-inferiority compared to BAHA® on a test-band. At M12, mean aided ACPTA was 2.94dB higher (p<0.001) but the mean SRT variation (+0.73dB) was not significantly different (p=0.35). At M12, all children used the implant 5 to 12h daily (mean: 10) without cutaneous complications. Both children and parents reported being satisfied or very satisfied. The score for 7/10 questions in silence or noisy environment was statistically improved when wearing the device. CONCLUSIONS: This prospective study demonstrate non inferiority, good cutaneous tolerance, satisfaction of children and parents and improvement of the quality of life with the Sophono Alpha1 compared to BAHA® on a test-band. In the light of this study and of the previously published series, the aided threshold is between that obtained with BAHA on a softband and percutaneous BAHA. The Sophono Alpha1 device needs to be part of the hearing solutions proposed for the hearing rehabilitation in children with ear atresia.

Cochlear implant failure and revision surgery in pediatric population.

OBJECTIVE: This study aimed to report pediatric cochlear reimplantation data focusing on failure of the device and to assess surgical challenges and functional outcomes. METHODS: Retrospective case review from 1990 to 2012. Tertiary referral academic center. A retrospective review of medical and surgical records, audiologic results, and report of the manufacturer's analysis was performed. The causes of revision cochlear implantation were divided into hard failure and soft failure. Results compared speech perception in open set or closed set words before and after revision surgery with cochlear implant only. RESULTS: During the study period, 877 cochlear implantations were performed. Our reimplantation rate for failure of the device is 5.7% (50 of 877). The main reasons for hard failure were loss of hermeticity and cracked casing following head trauma. Surgical difficulties might be due to neo-osteogenesis related to the use of bone dust. Initial atraumatic insertion is important to ensure that revision surgeries are less problematic. In postmeningitis deafness, initial choice of electrode array is of utmost importance. We would suggest a plain shape and a larger diameter array, to ensure sufficient subsequent insertion. Post-reimplantation audiologic results were the same or better than preoperative levels in 86% of cases. CONCLUSION: Failure might be difficult to diagnose in children with limited language skills. The surgical team and patients should be aware of the surgical difficulties that can be encountered, especially in cases of meningitis or initial traumatic insertion. Auditory performances after reimplantation are the same or better in most cases.

Idiopathic bilateral vocal cord paralysis in infants: Case series and literature review.

OBJECTIVES/HYPOTHESIS: Vocal fold paralysis is the second most common congenital laryngeal anomaly in newborns. Bilateral paralysis is a severe condition and often remains of unknown etiology. We report our experience of congenital idiopathic bilateral vocal fold paralysis in newborns and infants, and discuss the therapeutic options. STUDY DESIGN: Retrospective review. METHODS: A retrospective review was carried out at a single tertiary referral center over a 15-year period of children presenting with congenital idiopathic bilateral laryngeal paralysis (CIBP). RESULTS: Twenty-six patients were identified and managed over period of the study (mean follow-up, 6.7 years). A tracheostomy was eventually performed in 14 patients, 12 during the neonatal period. Endoscopic treatment was performed in 16 patients and an external approach in five patients after endoscopic failure. Three patients were managed by watchful waiting. Spontaneous recovery occurred in 16 patients (median age, 14.5 months), including nine with a tracheostomy. Decannulation was achieved in 12 patients (median age, 42 months), and noninvasive positive pressure ventilation (NPPV) was applied in six patients. CONCLUSIONS: Only inhomogeneous series of pediatric bilateral laryngeal palsies have been published so far, making it difficult to identify prognostic and predictive markers, as well as therapeutic guidelines. Focusing on CIBP, our data suggest that the management strategy must take into account the possibility of a delayed spontaneous recovery. NPPV is an interesting therapeutic tool in this situation. A systematic somatic assessment is mandatory to look for associated conditions.