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1.
Nat Immunol ; 24(1): 186-199, 2023 01.
Article in English | MEDLINE | ID: mdl-36536106

ABSTRACT

Most studies of adaptive immunity to SARS-CoV-2 infection focus on peripheral blood, which may not fully reflect immune responses at the site of infection. Using samples from 110 children undergoing tonsillectomy and adenoidectomy during the COVID-19 pandemic, we identified 24 samples with evidence of previous SARS-CoV-2 infection, including neutralizing antibodies in serum and SARS-CoV-2-specific germinal center and memory B cells in the tonsils and adenoids. Single-cell B cell receptor (BCR) sequencing indicated virus-specific BCRs were class-switched and somatically hypermutated, with overlapping clones in the two tissues. Expanded T cell clonotypes were found in tonsils, adenoids and blood post-COVID-19, some with CDR3 sequences identical to previously reported SARS-CoV-2-reactive T cell receptors (TCRs). Pharyngeal tissues from COVID-19-convalescent children showed persistent expansion of germinal center and antiviral lymphocyte populations associated with interferon (IFN)-γ-type responses, particularly in the adenoids, and viral RNA in both tissues. Our results provide evidence for persistent tissue-specific immunity to SARS-CoV-2 in the upper respiratory tract of children after infection.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Child , Pandemics , Adaptive Immunity , Palatine Tonsil , Antibodies, Viral
2.
N Engl J Med ; 384(19): 1789-1799, 2021 05 13.
Article in English | MEDLINE | ID: mdl-33979487

ABSTRACT

BACKGROUND: Official recommendations differ regarding tympanostomy-tube placement for children with recurrent acute otitis media. METHODS: We randomly assigned children 6 to 35 months of age who had had at least three episodes of acute otitis media within 6 months, or at least four episodes within 12 months with at least one episode within the preceding 6 months, to either undergo tympanostomy-tube placement or receive medical management involving episodic antimicrobial treatment. The primary outcome was the mean number of episodes of acute otitis media per child-year (rate) during a 2-year period. RESULTS: In our main, intention-to-treat analysis, the rate (±SE) of episodes of acute otitis media per child-year during a 2-year period was 1.48±0.08 in the tympanostomy-tube group and 1.56±0.08 in the medical-management group (P = 0.66). Because 10% of the children in the tympanostomy-tube group did not undergo tympanostomy-tube placement and 16% of the children in the medical-management group underwent tympanostomy-tube placement at parental request, we conducted a per-protocol analysis, which gave corresponding episode rates of 1.47±0.08 and 1.72±0.11, respectively. Among secondary outcomes in the main analysis, results were mixed. Favoring tympanostomy-tube placement were the time to a first episode of acute otitis media, various episode-related clinical findings, and the percentage of children meeting specified criteria for treatment failure. Favoring medical management was children's cumulative number of days with otorrhea. Outcomes that did not show substantial differences included the frequency distribution of episodes of acute otitis media, the percentage of episodes considered to be severe, and antimicrobial resistance among respiratory isolates. Trial-related adverse events were limited to those included among the secondary outcomes of the trial. CONCLUSIONS: Among children 6 to 35 months of age with recurrent acute otitis media, the rate of episodes of acute otitis media during a 2-year period was not significantly lower with tympanostomy-tube placement than with medical management. (Funded by the National Institute on Deafness and Other Communication Disorders and others; ClinicalTrials.gov number, NCT02567825.).


Subject(s)
Anti-Bacterial Agents/therapeutic use , Middle Ear Ventilation , Otitis Media/drug therapy , Otitis Media/surgery , Acute Disease , Anti-Bacterial Agents/adverse effects , Child, Preschool , Drug Resistance, Bacterial , Female , Humans , Infant , Intention to Treat Analysis , Kaplan-Meier Estimate , Male , Otitis Media with Effusion , Quality of Life , Recurrence
3.
Am J Med Genet A ; 191(1): 90-99, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36263470

ABSTRACT

Aldehyde Dehydrogenase 1, Family Member A2 (ALDH1A2) is essential for the synthesis of retinoic acid from vitamin A. Studies in model organisms demonstrate a critical role for ALDH1A2 in embryonic development, yet few pathogenic variants are linked to congenital anomalies in humans. We present three siblings with multiple congenital anomaly syndrome linked to biallelic sequence variants in ALDH1A2. The major congenital malformations affecting these children include tetralogy of Fallot, absent thymus, diaphragmatic eventration, and talipes equinovarus. Upper airway anomalies, hypocalcemia, and dysmorphic features are newly reported in this manuscript. In vitro functional validation of variants indicated that substitutions reduced the expression of the enzyme. Our clinical and functional data adds to a recent report of biallelic ALDH1A2 pathogenic variants in two families with a similar constellation of congenital malformations. These findings provide further evidence for an autosomal recessive ALDH1A2-deficient recognizable malformation syndrome involving the diaphragm, cardiac and musculoskeletal systems.


Subject(s)
Tretinoin , Child , Humans , Aldehyde Dehydrogenase 1 Family/genetics , Aldehyde Dehydrogenase 1 Family/metabolism , Tretinoin/metabolism , Retinal Dehydrogenase/genetics
4.
Am J Otolaryngol ; 44(6): 103991, 2023.
Article in English | MEDLINE | ID: mdl-37487464

ABSTRACT

PURPOSE: MPOX has numerous otolaryngologic presentations that have been recognized as clinically important, especially with the onset of the 2022 outbreak. However, how these features vary across region and outbreak have yet to be elucidated or supported by meta-analysis. The objective of this study is to identify the otolaryngologic manifestations of MPOX across previous and current outbreaks and among endemic and non-endemic regions. BASIC PROCEDURES: Data sources of MEDLINE (PubMed), the Cochrane Library, Scopus, Embase, Web of Science, Google Scholar, and OpenGrey were searched through August 2022. All observational studies reporting data on laboratory-confirmed MPOX patients with otolaryngologic symptoms were included. Two authors independently performed the screening process while a third resolved disagreements. Data were extracted into a structured form by two authors independently. We performed a meta-analysis of the prevalence of otorhinolaryngologic symptoms using MetaXL software (version 5.3) under a random-effects model. MAIN FINDINGS: 38 studies with 5952 patients were included. The four most prevalent manifestations were headache at 31 % (95 % CI [0.16-0.49], I 2  = 99 %), sore throat at 22 % (95 % CI [0.09-0.37], I 2  = 99 %), cough at 16 % (95 % CI [0.05-0.30], I 2  = 99 %), and cervical lymphadenopathy at 10 % (95 % CI [0.01-0.26], I 2  = 100 %). Otolaryngologic features were more prevalent in previous outbreaks as compared to the 2022 outbreak including 37 % prevalence of headache (95 % CI [0.11-0.66], I 2  = 100 %), 33 % prevalence of cough (95 % CI [0.21-0.47], I 2  = 98 %), 27 % prevalence of sore throat (95 % CI [0.07-0.53], I 2  = 99 %), 15 % prevalence of cervical lymphadenopathy (95 % CI [0.00-0.428], I 2  = 100 %), 13 % prevalence of oral ulcers (95 % CI [0.02-0.30], I 2  = 99 %), 6 % prevalence of oral exanthem (95 % CI [0.00-0.17], I 2  = 99 %), 5 % prevalence of dysphagia (95 % CI [0.00-0.18], I 2  = 99 %), and 5 % prevalence of tonsillar signs (95 % CI [0.00-0.13], I 2  = 99 %). Features that were more prevalent in endemic areas versus non-endemic areas include 27 % prevalence of cough (95 % CI [0.14-0.41], I 2  = 99 %), 15 % prevalence of oral ulcers (95 % CI [0.02-0.36], I 2  = 99 %), 6 % prevalence of tonsillar signs (95 % CI [0.00-0.18], I 2  = 99 %), and 19 % prevalence of cervical lymphadenopathy (95 % CI [0.00-0.48], I 2  = 100 %), while the only feature more prevalent in non-endemic areas was headache with a prevalence of 36 % (95 % CI [0.24-0.47], I 2  = 96 %). PRINCIPAL CONCLUSIONS: In this systematic review and meta-analysis, four symptoms - headache, sore throat, cough, and cervical lymphadenopathy - were found to be the most prevalent otolaryngologic features of MPOX. Otolaryngologic manifestations of MPOX were more pronounced in prior outbreaks and in endemic areas as compared to the 2022 outbreak and non-endemic areas. These findings may aid MPOX recognition in an otolaryngology setting.


Subject(s)
Lymphadenopathy , Mpox (monkeypox) , Oral Ulcer , Otolaryngology , Pharyngitis , Humans , Cough , Headache/epidemiology , Headache/etiology , Pain , Pharyngitis/epidemiology , Mpox (monkeypox)/complications
7.
FASEB J ; 32(4): 1855-1867, 2018 04.
Article in English | MEDLINE | ID: mdl-29191962

ABSTRACT

Nontypeable Haemophilus influenzae (NTHi), one of the most common acute otitis media (OM) pathogens, is postulated to promote middle-ear epithelial remodeling in the progression of OM from acute to chronic. The goal of this study was to examine early quantitative proteomic secretome effects of NTHi lysate exposure in a human middle-ear epithelial cell (HMEEC) line. NTHi lysates were used to stimulate HMEEC, and conditional quantitative stable isotope labeling with amino acids in cell culture of cell secretions was performed. Mass spectrometry analysis identified 766 proteins across samples. Of interest, several heterogeneous nuclear ribonucleoproteins (hnRNPs) were regulated by NTHi lysate treatment, especially hnRNP A2B1 and hnRNP Q, known to be implicated in microRNA (miRNA) packaging in exosomes. After purification, the presence of exosomes in HMEEC secretions was characterized by dynamic light scattering (<100 nm), transmission electron microscopy, and CD63/heat shock protein 70 positivity. hnRNP A2B1 and hnRNP Q were confirmed to be found in exosomes by Western blot and proteomic analysis. Finally, exosomal miRNA content comprised 110 unique miRNAs, with 5 found to be statistically induced by NTHi lysate (miR-378a-3p + miR-378i, miR-200a-3p, miR-378g, miR30d-5p, and miR-222-3p), all known to target innate immunity genes. This study demonstrates that NTHi lysates promote release of miRNA-laden exosomes from middle-ear epithelium in vitro. -Val, S., Krueger, A., Poley, M., Cohen, A., Brown, K., Panigrahi, A., Preciado, D. Nontypeable Haemophilus influenzae lysates increase heterogeneous nuclear ribonucleoprotein secretion and exosome release in human middle-ear epithelial cells.


Subject(s)
Ear, Middle/cytology , Epithelial Cells/metabolism , Exosomes/metabolism , Haemophilus influenzae/pathogenicity , Ribonucleoproteins/metabolism , Cell Extracts/pharmacology , Cell Line , Epithelial Cells/drug effects , Epithelial Cells/microbiology , Exocytosis , Haemophilus influenzae/chemistry , Humans , MicroRNAs/genetics , MicroRNAs/metabolism
8.
Pediatr Res ; 84(2): 296-305, 2018 08.
Article in English | MEDLINE | ID: mdl-29915406

ABSTRACT

BACKGROUND: Chronic otitis media with effusion (COME) is characterized by persistent middle ear effusions that are in most cases highly viscous, but some patients present with serous fluid. This study aimed at comprehensively characterizing the macromolecular composition of mucoid vs. serous middle ear effusions (MEEs). METHODS: MEEs from patients with COME were analyzed for proteins by mass spectrometry (MS) and western blot techniques, total DNA quantity, bacterial DNA (16S sequencing), and cytokine content. Proteomics datasets were studied in Ingenuity Pathway Analysis (IPA). RESULTS: Mucoid samples showed a global tendency of increased pro-inflammatory mediators. Interleukin-1ß (IL-1ß) and IL-10 were significantly more abundant in serous samples (p < 0.01). Mucoid samples had higher DNA quantity (p = 0.04), more likely to be positive in MUC5B protein (p = 0.008) and higher peptide counts (12,786 vs. 2225), as well as an overall larger number of identified proteins (331 vs. 177), compared to serous. IPA found the mucoid sample dataset to be related to immune cell function and epithelial remodeling, whereas the serous sample dataset showed acute responses and blood-related proteins. Interestingly, serous samples showed more bacterial DNA than mucoid ones, with less bacterial genera variability. CONCLUSION: This study demonstrates divergent immune responses in children with COME by effusion quality.


Subject(s)
Ear, Middle/pathology , Mucus/metabolism , Otitis Media with Effusion/immunology , Otitis Media with Effusion/metabolism , Blood Proteins/chemistry , Child , Child, Preschool , Chronic Disease , Complement System Proteins/chemistry , DNA, Bacterial/genetics , Female , Humans , Immune System , Immunoglobulins/chemistry , Infant , Inflammation , Interleukin-10/metabolism , Interleukin-1beta/metabolism , Male , Mass Spectrometry , Mucin-5B/metabolism , Proteomics , RNA, Ribosomal, 16S/genetics
9.
Pediatr Res ; 81(6): 911-918, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28157838

ABSTRACT

BACKGROUND: Otitis media (OM) is characterized by acute infection progressing to chronic middle ear effusion (MEE). Extracellular secretion of microRNAs (miRNAs) in exosomes is a newly discovered mechanism for cells exerting distant cell genetic regulation. Whether MEE contains exosomes with specific miRNAs is unknown. This study aimed to purify and characterize the exosomal and miRNA content of MEE. METHOD: MEEs were subjected to Exoquick exosomal purification and EXOCET exosomal quantification. Extracted vesicles were analyzed by dynamic light scattering (DLS), transmission electron microscopy (TEM), and immunoblotting of HSP-70. NanoString hybridization was performed to profile miRNAs. Exosomal protein content was profiled by Liquid chromatography tandem mass spectrometry (LC-MS/MS). RESULTS: EXOCET assays showed presence of exosomes (0-0.5 × 107/ml) in MEEs. DLS confirmed exosomal size between 10 and 200 nm. Western blot analysis showed presence of HSP-70. Twenty-nine miRNAs were found to be unique to MEEs. The most abundant miRNA was miR-223, a miRNA typically secreted by neutrophils. Proteomics demonstrated typical neutrophil markers as well as common innate immune molecules. CONCLUSION: To our knowledge, this the first report demonstrating the presence of exosomes transporting miRNAs in MEEs. These findings open a broad and novel area of research in OM pathophysiology as driven by miRNA cell communication.


Subject(s)
Exosomes/metabolism , MicroRNAs/isolation & purification , Otitis Media/metabolism , Blotting, Western , Chromatography, Liquid , Exosomes/ultrastructure , Humans , Mass Spectrometry , MicroRNAs/metabolism , Microscopy, Electron, Transmission , Otitis Media/physiopathology , Polymerase Chain Reaction , Proteomics
10.
Pediatr Radiol ; 46(7): 1059-67, 2016 Jun.
Article in English | MEDLINE | ID: mdl-26637999

ABSTRACT

Peritonsillar infections are one of the most common deep neck space infections, particularly in adolescents. Inaccurate diagnosis can lead to delay in management and potentially life-threatening complications. Contrast-enhanced computed tomography (CT) scan of the neck traditionally has been used to diagnose suspected peritonsillar abscess. With growing concern over radiation exposure, there has been increasing utilization of ultrasound (US) using intraoral and transcutaneous approaches. We chose the transcutaneous US technique due to its ease of performance in children. The purpose of this article is twofold: a) to describe our technique of performing transcutaneous US of the tonsil showing sonographic appearance of normal tonsil, highlighting pertinent anatomy and unique considerations for this modality in children, and b) to illustrate the sonographic findings in the spectrum of pediatric peritonsillar infections, which includes uncomplicated tonsillitis, peritonsillar cellulitis, small intratonsillar abscess and frank peritonsillar abscess. Parapharyngeal abscess can sometimes be detected.


Subject(s)
Peritonsillar Abscess/diagnostic imaging , Ultrasonography/methods , Child , Contrast Media , Diagnosis, Differential , Humans
11.
Pediatr Res ; 77(2): 356-62, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25420179

ABSTRACT

BACKGROUND: Chronic rhinosinusitis (CRS) is characterized by mucous overproduction and submucosal gland hyperplasia. The global protein profile of sinonasal secretions in pediatric CRS has not been studied. We hypothesized that MUC5B, a glandular mucin, would be relatively increased in CRS secretions compared to other mucins. METHODS: Secretions were collected at Children's National Health System (Children's National) from CRS patients undergoing sinus surgery and from control patients without CRS undergoing craniofacial procedures. Proteins were extracted, digested to peptides, and analyzed by mass spectometry. Fold change significance was calculated using the QSpec algorithm. Western blot analysis was performed to validate proteomic findings. RESULTS: In total, 294 proteins were identified. Although both MUC5B and MUC5AC were identified in a majority of samples, the relative abundance of MUC5B was found to be significantly higher (P < 0.05). Western blot data validated these findings. Other proteins with the highest significant positive-fold change in CRS samples were BP1 fold-containing family A member 1, chitinase-3-like protein 1, plastin-2, serpin 10, and BP1 fold-containing family B member 1. CONCLUSION: Overall, our data demonstrate an increase of MUC5B abundance in the sinus secretions of pediatric patients with CRS.


Subject(s)
Mucin-5B/metabolism , Mucous Membrane/metabolism , Paranasal Sinuses/metabolism , Rhinitis/metabolism , Sinusitis/metabolism , Adolescent , Blotting, Western , Child , Child, Preschool , Electrophoresis, Polyacrylamide Gel , Gene Ontology , Humans , Proteomics
12.
Pediatr Res ; 78(4): 389-94, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26086642

ABSTRACT

BACKGROUND: It is unknown why human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) cause severe respiratory infection in children, particularly in premature infants. Our aim was to investigate if there are defective airway antiviral responses to these viruses in young children with history of prematurity. METHODS: Nasal airway secretions were collected from 140 children ≤ 3 y old without detectable virus (n = 80) or with PCR-confirmed HMPV or RSV infection (n = 60). Nasal protein levels of IFNγ, CCL5/RANTES, IL-10, IL-4, and IL-17 were determined using a multiplex magnetic bead immunoassay. RESULTS: Full-term children with HMPV and RSV infection had increased levels of nasal airway IFNγ, CCL5, and IL-10 along with an elevation in Th1 (IFNγ)/Th2 (IL-4) ratios, which is expected during antiviral responses. In contrast, HMPV-infected premature children (< 32 wk gestation) did not exhibit increased Th1/Th2 ratios or elevated nasal airway secretion of IFNγ, CCL5, and IL-10 relative to uninfected controls. CONCLUSION: Our study is the first to demonstrate that premature infants have defective IFNγ, CCL5/RANTES, and IL-10 airway responses during HMPV infection and provides novel insights about the potential reason why HMPV causes severe respiratory disease in children with history of prematurity.


Subject(s)
Infant, Premature , Interferon-gamma/immunology , Lung/immunology , Metapneumovirus/immunology , Paramyxoviridae Infections/immunology , Respiratory Syncytial Virus Infections/immunology , Respiratory Syncytial Viruses/immunology , Chemokine CCL5/immunology , Chemokine CCL5/metabolism , Child, Preschool , Cross-Sectional Studies , DNA, Viral/genetics , Female , Gestational Age , Host-Pathogen Interactions , Humans , Infant , Interferon-gamma/metabolism , Interleukin-10/immunology , Interleukin-10/metabolism , Interleukin-4/immunology , Interleukin-4/metabolism , Lung/metabolism , Lung/virology , Male , Metapneumovirus/genetics , Metapneumovirus/isolation & purification , Paramyxoviridae Infections/diagnosis , Paramyxoviridae Infections/metabolism , Paramyxoviridae Infections/virology , Prospective Studies , Respiratory Syncytial Virus Infections/diagnosis , Respiratory Syncytial Virus Infections/metabolism , Respiratory Syncytial Virus Infections/virology , Respiratory Syncytial Viruses/genetics , Respiratory Syncytial Viruses/isolation & purification , Th1 Cells/immunology , Th1 Cells/metabolism , Th1 Cells/virology , Th17 Cells/immunology , Th17 Cells/metabolism , Th17 Cells/virology , Th2 Cells/immunology , Th2 Cells/metabolism , Th2 Cells/virology , Up-Regulation
13.
Pediatr Allergy Immunol ; 26(2): 145-52, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25640734

ABSTRACT

BACKGROUND: Rhinovirus (RV) has been linked to the pathogenesis of asthma. Prematurity is a risk factor for severe RV infection in early life, but is unknown if RV elicits enhanced pro-asthmatic airway cytokine responses in premature infants. This study investigated whether young children born severely premature (<32 wks gestation) exhibit airway secretion of Th2 and Th17 cytokines during natural RV infections and whether RV-induced Th2-Th17 responses are linked to more respiratory morbidity in premature children during the first 2 yrs of life. METHODS: We measured Th2 and Th17 nasal airway cytokines in a retrospective cohort of young children aged 0-2 yrs with PCR-confirmed RV infection or non-detectable virus. Protein levels of IL-4, IL-13, TSLP, and IL-17 were determined with multiplex immunoassays. Demographic and clinical variables were obtained by electronic medical record (EMR) review. RESULTS: The study comprised 214 children born full term (n = 108), preterm (n = 44) or severely premature (n = 62). Natural RV infection in severely premature children was associated with elevated airway secretion of Th2 (IL-4 and IL-13) and Th17 (IL-17) cytokines, particularly in subjects with history of bronchopulmonary dysplasia. Severely premature children with high RV-induced airway IL-4 had recurrent respiratory hospitalizations (median 3.65 hosp/yr; IQR 2.8-4.8) and were more likely to have at least one pediatric intensive care unit admission during the first 2 yrs of life (OR 8.72; 95% CI 1.3-58.7; p = 0.02). CONCLUSIONS: Severely premature children have increased airway secretion of Th2 and Th17 cytokines during RV infections, which is associated with more respiratory morbidity in the first 2 yrs of life.


Subject(s)
Common Cold/immunology , Cytokines/immunology , Infant, Extremely Premature/immunology , Respiratory System/immunology , Respiratory System/virology , Asthma/immunology , Asthma/virology , Bronchopulmonary Dysplasia/immunology , Bronchopulmonary Dysplasia/virology , Cohort Studies , Common Cold/complications , Cytokines/biosynthesis , Female , Humans , Infant, Newborn , Infant, Premature , Male , Multiplex Polymerase Chain Reaction , Retrospective Studies , Rhinovirus
14.
Int J Pediatr Otorhinolaryngol ; 177: 111867, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38290273

ABSTRACT

OBJECTIVES: Pediatric cochlear implantation (CI) provides sound perception to children with significant sensorineural hearing loss and, despite its challenging process, early implantation can enhance children's speech/language outcomes and potentially improve parental quality of life (PQoL). This study aims to examine parental perspectives on quality of life and parenting children with CI. METHODS: This study combined retrospective chart review and parent reported outcomes. Data were abstracted from medical charts of 85 children who underwent CI between 2016 and 2022 at a tertiary pediatric hospital. Parents were administered the Acceptance and Action Questionnaire (AAQ-MCHL), an 8-item self-report assessment of quality of life for parents of children with CI. Multivariate linear regression analyses examined clinical factors associated with PQoL scores. RESULTS: Parents whose children were implanted at less than two years of age reported significantly higher PQoL, indicated by lower AAQ scores, with a mean AAQ-MCHL of 7.6 + 5.7. In contrast, implantation at age >2 years yielded a mean AAQ-MCHL of 16.2 + 9.6. Parents interviewed within one year post-surgery reported lower PQoL, with a mean AAQ-MCHL of 12.3 + 8.8 compared to those interviewed after one year, with 20.5 + 10.4. CONCLUSION: Early identification of profound hearing loss in children, coupled with early surgical CI, may be associated with higher parental quality of life. The beneficial outcomes appear to be potentiated over time. Further research is essential to fully comprehend the impact of CI on the quality of life of children and their parents.


Subject(s)
Cochlear Implantation , Cochlear Implants , Deafness , Hearing Loss, Sensorineural , Speech Perception , Child , Humans , Child, Preschool , Quality of Life , Retrospective Studies , Hearing Loss, Sensorineural/diagnosis , Hearing Loss, Sensorineural/surgery , Parents , Deafness/surgery
15.
Otolaryngol Head Neck Surg ; 171(1): 247-253, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38482949

ABSTRACT

OBJECTIVES: Laryngotracheal reconstruction (LTR) has revolutionized the management of pediatric subglottic stenosis (SGS). However, postoperative stenosis remains a difficult hurdle to overcome. Our goal is to determine the clinical impact of recalcitrant stenosis after LTR and the factors contributing to postoperative stenosis. STUDY DESIGN: Retrospective review of 181 open LTR patients between 2008 and 2021. SETTING: Stand-alone tertiary children's hospital. METHODS: Recalcitrant stenosis was defined as new or worsening stenosis despite open LTR. Fisher's exact and Mann-Whitney tests were used to detect differences in categorical and continuous clinical data between patients with and without treatment-resistant stenosis. Time-to-decannulation analysis of both groups was performed using Kaplan-Meier analysis and evaluated with log-rank and Cox proportional hazards regression. Multivariate logistical regression was used to assess the validity of associations found in univariate analysis. RESULTS: As expected, the 27 patients with postoperative stenosis were less likely to be decannulated (P < .001, Fisher's Exact), more likely to require a postoperative tracheostomy (P < .001, Fisher's Exact) or revision LTR (P < .001, Fisher's Exact) and had prolonged time to decannulation (P < .001, Log-rank). Children with Grade IV SGS (P = .004, Fisher's Exact), and those with longer suprastomal stent duration (P = .03, Fisher's Exact) were more likely to suffer from recalcitrant stenosis. Stent duration longer than 4 weeks (P = .01) contributed to refractory stenosis when controlling for all aforementioned variables using multivariable logistic regression. Interposition grafts had a protective effect (P = .005). CONCLUSION: Maintaining suprastomal stents over 4 weeks after LTR increases the risk for postoperative stenosis and its sequelae.


Subject(s)
Laryngostenosis , Postoperative Complications , Humans , Retrospective Studies , Male , Female , Laryngostenosis/surgery , Laryngostenosis/etiology , Child, Preschool , Infant , Child , Tracheal Stenosis/surgery , Tracheal Stenosis/etiology , Plastic Surgery Procedures/methods , Risk Factors , Tracheostomy
16.
Laryngoscope ; 134(4): 1926-1932, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37658702

ABSTRACT

OBJECTIVES: To evaluate how patient characteristics and surgical techniques influence the rate of and time to decannulation after pediatric revision laryngotracheal reconstruction. METHODS: The study was a retrospective cohort investigation of children with a history of laryngotracheal stenosis treated between 2008 and 2021 with revision open airway surgery. The primary outcome evaluated was decannulation. The secondary outcome analyzed was time to decannulation. RESULTS: Thirty-nine children were included in the study with median age 49 months; 61.5% were male. Children undergoing single stage revision surgery were far more likely to be decannulated (OR 6.25, 95% CI 1.33-45.97, p = 0.0343). Rolling logistic regression of the probability of decannulation stratified by time between open surgeries demonstrated significantly decreased chance of decannulation with reoperation within 6 months. Children managed with anterior/posterior grafting compared with a single graft were observed to have an increased time to decannulation, (HR 0.365, 95% CI 0.148-0.899, p = 0.005, Log-Rank). CONCLUSION: We observe that in the case of revision pediatric open airway surgery, chance of decannulation is improved when surgery is performed in a single stage as well as 6 months after the most recent procedure. Patients and families should be counseled that complex stenosis requiring double stage procedures or anterior/posterior grafting is associated with a decreased probability of decannulation and increased postoperative time with a tracheostomy, respectively. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:1926-1932, 2024.


Subject(s)
Laryngostenosis , Plastic Surgery Procedures , Humans , Child , Male , Child, Preschool , Female , Retrospective Studies , Constriction, Pathologic/surgery , Treatment Outcome , Laryngostenosis/surgery
17.
Int J Pediatr Otorhinolaryngol ; 176: 111814, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38101097

ABSTRACT

OBJECTIVE: To review and summarize recently published key articles on the topics of animal models, cell culture studies, tissue biomedical engineering and regeneration, and new models in relation to otitis media (OM). DATA SOURCE: Electronic databases: PubMed, National Library of Medicine, Ovid Medline. REVIEW METHODS: Key topics were assigned to the panel participants for identification and detailed evaluation. The PubMed reviews were focused on the period from June 2019 to June 2023, in any of the objective subject(s) or keywords listed above, noting the relevant references relating to these advances with a global overview and noting areas of recommendation(s). The final manuscript was prepared with input from all panel members. CONCLUSIONS: In conclusion, ex vivo and in vivo OM research models have seen great advancements in the past 4 years. From the usage of novel genetic and molecular tools to the refinement of in vivo inducible and spontaneous mouse models, to the introduction of a wide array of reliable middle ear epithelium (MEE) cell culture systems, the next five years are likely to experience exponential growth in OM pathophysiology discoveries. Moreover, advances in these systems will predictably facilitate rapid means for novel molecular therapeutic studies.


Subject(s)
Otitis Media , Animals , Mice , Humans , Otitis Media/drug therapy , Ear, Middle , Disease Models, Animal , Biomedical Engineering , Cell Culture Techniques
18.
Article in English | MEDLINE | ID: mdl-38769854

ABSTRACT

OBJECTIVE: To identify associations between cochleovestibular anatomy findings and hearing outcomes found in children with imaging evidence of an absent or hypoplastic cochlear nerve treated with cochlear implantation (CI). STUDY DESIGN: retrospective review. SETTING: Cochlear implant program at tertiary care center. METHODS: A retrospective review was performed to identify children with imaging evidence of cochlear nerve absence or deficiency who underwent CI evaluation. High-resolution 3-dimensional T2-weighted magnetic resonance imaging in the oblique sagittal and axial planes were reviewed by a neuroradiologist to identify cochleovestibular anatomy. Hearing was assessed pre and postoperatively with Speech Perception Category scores. RESULTS: Seven CI recipients were identified (n = 10 ears) who had bilateral severe to profound sensorineural hearing loss with lack of auditory development with binaural hearing aid trial and imaging evidence of cochlear nerve aplasia/hypoplasia. All ears had 2 nerves in the cerebellopontine angle (100%, n = 10), half of the ears had evidence of 2 or less nerves in the internal auditory canal (IAC). All children showed large improvement in speech perception after CI. CONCLUSION: Our experience with CIs for children with absent or hypoplastic cochlear nerves demonstrates that CI can be a viable option in select patients who satisfy preoperative audiological criteria. Radiological identification of a hypoplastic or aplastic cochlear nerve does not preclude auditory innervation of the cochlea. CI recipients in this subgroup must be counseled on difficulty in predicting postimplantation language and speech outcomes, and cautioned about facial nerve stimulation.

19.
Int J Pediatr Otorhinolaryngol ; 164: 111398, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36455431

ABSTRACT

BACKGROUND: Interviews for Pediatric Otolaryngology fellowship rapidly transitioned to virtual interviews mid-cycle in March 2020 due to the COVID-19 pandemic. OBJECTIVE: This study aims to describe perspectives on virtual versus in-person interviews for both applicants and program directors. METHODS: Cross-sectional study. Surveys were conducted of all Pediatric Otolaryngology fellowship applicants participating in the San Francisco Match and program directors in 2020 and 2021. RESULTS: Out of 32 U.S. trained fellowship applicants, 24 completed the survey in 2020 and 18 in 2021. While 70% of applicants felt they did not get the same experience with virtual interviews, 75% did not feel it changed how they ranked programs. Applicant perception of virtual interviews improved in 2021, with the majority (56%) preferring virtual interviews if provided an option. Twenty out of 36 fellowship directors completed the survey in 2020, and eighteen in 2021. While fellowship directors continued to prefer in-person in 2021, an increased number (10% in 2020, 30% in 2021) felt continuing with virtual interviews may increase the number of applicants in the future. CONCLUSION: Based on the survey, both applicants and fellowship directors had a less favorable perception of virtual interviews compared to in-person interviews initially; however, applicant perception favored virtual interviews in 2021, while Program Directors continued to prefer in-person.


Subject(s)
COVID-19 , Internship and Residency , Otolaryngology , Child , Humans , Cross-Sectional Studies , Fellowships and Scholarships , Pandemics , COVID-19/epidemiology , Attitude , Surveys and Questionnaires
20.
Ann Otol Rhinol Laryngol ; 132(5): 558-565, 2023 May.
Article in English | MEDLINE | ID: mdl-35723210

ABSTRACT

OBJECTIVE: To identify factors predicting success in slide tracheoplasty surgery at a regional children's hospital and compare with available published literature. MEASURES: Retrospective chart review comparing demographics (age, weight) and clinical (operative and hospital course, need for additional airway intervention) factors experienced with slide tracheoplasty. Findings were compared with a systematic review of published literature. RESULTS: Of the 16 tracheal stenosis patients in our cohort, 13 (81.3%) presented with an additional congenital or cardiovascular anomaly. When adjusted for cardiovascular anomalies, congenital tracheal stenosis patients had a mean age of 5.2 months (range 6 days-17 months), mean weight of 5.04 kg, and average ICU and hospital length of stay of 31.5 and 36.0 days, respectively. Tracheostomy was required for 4 patients and no early deaths were recorded. Of the 391 children in the grouped cohort, mean age and weight was older at 7.67 months and larger at 5.70 kg. Length of stay in both ICU and overall hospital course was 31.6 and 43.5 days, respectively. Mortality etiology for 44 patients was reported: 17 (38.6%) cardiac-related and 28 (63.6%) late mortalities. Our overall calculated mortality risk of 1.26 (P < .05) was lower than reported ratios of 2.0+. CONCLUSION: Despite the numerous institutional studies involving tracheal stenosis, mortality and surgical challenges remain high. Future studies with the inclusion of specific perioperative data can prove to further evaluate correlations between presentation characteristics and mortality.


Subject(s)
Tracheal Stenosis , Child , Humans , Infant , Infant, Newborn , Tracheal Stenosis/surgery , Retrospective Studies , Treatment Outcome , Trachea/surgery
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