Tracheal Resection for Critical Airway Obstruction in Morquio A Syndrome.

Introduction: The primary cause of death in Morquio A syndrome (mucopolysaccharidosis (MPS) IVA) is airway obstruction, brought about by an inexorable and pathognomonic multilevel airway tortuosity, buckling, and obstruction. The relative pathophysiological contributions of an inherent cartilage processing defect versus a mismatch in longitudinal growth between the trachea and the thoracic cage are currently a subject of debate. Enzyme replacement therapy (ERT) and multidisciplinary management continue to improve life expectancy for Morquio A patients by slowing many of the multisystem pathological consequences of the disease but are not as effective at reversing established pathology. An urgent need has developed to consider alternatives to palliation of progressive tracheal obstruction to preserve and maintain these patients' hard-won good quality of life, as well as to facilitate spinal and other required surgery. Case Report. Following multidisciplinary discussion, transcervical tracheal resection with limited manubriectomy was successfully performed, without the need for cardiopulmonary bypass, in an adolescent male on ERT with the severe airway manifestations of Morquio A syndrome. His trachea was found to be under significant compressive forces at surgery. On histology, chondrocyte lacunae appeared enlarged, but intracellular lysosomal staining and extracellular glycosaminoglycan staining was comparable to control trachea. At 12 months, this has resulted in a significant improvement in respiratory and functional status, with corresponding enhancement to his quality of life. Conclusion: This addressing of tracheal/thoracic cage dimension mismatch represents a novel surgical treatment approach to an existing clinical paradigm and may be useful for other carefully selected individuals with MPS IVA. Further work is needed to better understand the role and optimal timing of tracheal resection within this patient cohort so as to individually balance considerable surgical and anaesthetic risks against the potential symptomatic and life expectancy benefits.

Laryngeal reinnervation for paediatric vocal cord palsy: a systematic review.

OBJECTIVE: This systematic review aims to provide an overview of the current evidence-base for paediatric surgical reinnervation in unilateral and bilateral vocal fold palsies in clinical practice. We aim to assess patient demographics, surgical technique and pre- and post-operative outcome measures. METHODS: A systematic literature review was performed and reported according to international PRISMA recommendations. A comprehensive search of PubMed, Embase, and Cochrane CENTRAL databases for relevant publications for all available dates with appropriate MESH search criteria was performed. Articles were categorised by four authors independently. A pooled summative analysis was carried out to allow review of demographic and outcome data. RESULTS: Our systematic PRISMA approach resulted in 19 papers being selected for inclusion and analysis with 179 patients undergoing reinnervation (153 unilateral, 26 bilateral). The youngest patient was 1.9 years. Iatrogenic injury to recurrent laryngeal nerve most common aetiology (65.4% and 19.2% of unilateral and bilateral vocal fold palsies, respectively). Patent ductus arteriosus ligation was the single most common procedure resulting in unilateral vocal fold palsies (43.1% of cases). Statistically significant improvements in subjective and objective outcomes for both voice and swallowing were seen. Meta-analysis was able to be performed on the particularly evident improvements in GRBAS score and Maximum Phonation Time (MPT). GRBAS scores improved by 3.64 (p < 0.01, 95% CI 2.65 to 4.63). MPT showed a statistically significant improvement of 5.26 s (p < 0.05, 95% CI 4.28 to 6.24). No major complications were reported. CONCLUSION: The current published evidence on one-hundred and seventy-nine paediatric surgical reinnervation procedures demonstrates its role as a safe and effective treatment for both unilateral and bilateral vocal fold palsies. Anatomically it has been shown to improve vocal fold tone, bulk and position. Both post-operative voice and swallowing outcomes show improvement as well as associated quality of life measures.

Evolution of viral variants in remdesivir-treated and untreated SARS-CoV-2-infected pediatrics patients.

Detailed information on intrahost viral evolution in SARS-CoV-2 with and without treatment is limited. Sequential viral loads and deep sequencing of SARS-CoV-2 from the upper respiratory tract of nine hospitalized children, three of whom were treated with remdesivir, revealed that remdesivir treatment suppressed viral load in one patient but not in a second infected with an identical strain without any evidence of drug resistance found. Reduced levels of subgenomic RNA during treatment of the second patient, suggest an additional effect of remdesivir on viral replication. Haplotype reconstruction uncovered persistent SARS-CoV-2 variant genotypes in four patients. These likely arose from within-host evolution, although superinfection cannot be excluded in one case. Although our dataset is small, observed sample-to-sample heterogeneity in variant frequencies across four of nine patients suggests the presence of discrete viral populations in the lung with incomplete population sampling in diagnostic swabs. Such compartmentalization could compromise the penetration of remdesivir into the lung, limiting the drugs in vivo efficacy, as has been observed in other lung infections.

Use of Simulation to Visualize Healthcare Worker Exposure to Aerosol in the Operating Room.

SUMMARY STATEMENT: Simulation resources offer an opportunity to highlight aerosol dispersion within the operating room environment. We demonstrate our methodology with a supporting video that can offer operating room teams support in their practical understanding of aerosol exposure and the importance of personal protective equipment.

Micro-CT Imaging of Pediatric Thyroglossal Duct Cysts: A Prospective Case Series.

Objectives: To determine the feasibility of micro-CT as a high-resolution 3D imaging tool for thyroglossal duct cysts and to evaluate its role augmenting traditional histopathological examination of resected specimens. Methods: A single centre, prospective case series of consecutive children undergoing excision of a thyroglossal duct cyst was performed at a quaternary paediatric referral hospital in the United Kingdom. Consecutive children listed for excision of a thyroglossal duct cyst whose parents agreed to participate were included and there were no exclusion criteria. Results: Surgically excised thyroglossal duct cyst or remnant specimens from five patients (two males, three females) were examined using micro-CT alongside traditional histopathological examination. In all cases, micro-CT imaging was able to demonstrate 3D imaging datasets of the specimens successfully and direct radio-pathological comparisons were made (Figures 1-5, Supplementary Video 1). Conclusions: The study has shown the feasibility and utility of post-operative micro-CT imaging of thyroglossal duct cysts specimens as a visual aid to traditional histopathological examination. It better informs the pathological specimen sectioning using multi-planar reconstruction and volume rendering tools without tissue destruction. In the complex, often arborised relationship between a thyroglossal duct cyst and the hyoid, micro-CT provides valuable image plane orientation and indicates proximity of the duct to the surgical margins. This is the first case series to explore the use of micro-CT imaging for pediatric thyroglossal duct specimens and it informs future work investigating the generalizability of micro-CT imaging methods for other lesions, particularly those from the head and neck region where precisely defining margins of excision may be challenging.

Subglottic ectopic thymus mimicking airway haemangioma.

Subglottic haemangioma presents as progressive obstruction in the neonatal and infantile airway, with a soft lesion seen during endoscopy. Diagnosis is based on macroscopic findings, biopsy is not usually performed and propranolol is first-line treatment. In contrast, ectopic thymus is a rare differential diagnosis for subglottic mass made by histopathological examination after excision or autopsy. In this article, we present a case of an infant with a subglottic lesion with endoscopic features consistent with haemangioma. After initial clinical response to propranolol, the patient represented with progressive stridor no longer responding to therapy. Open excision of the lesion was performed, and histopathology revealed ectopic thymus tissue. In this case, ectopic thymus tissue mimicked the presentation of subglottic haemangioma, and confirmation bias persisted due to an apparent initial clinical response to treatment with propranolol. In cases of subglottic mass refractory to medical treatment, excision of the lesion should be considered.

Bilobed tongue base associated with multiple branchial anomalies.

A bilobed tongue base was identified in an infant with multiple other head, neck and cardiac congenital anomalies. This anatomical variation of the posterior tongue is rare, with only two other cases identified in the literature. We report a case of a 5-month-old boy with a bilobed posterior tongue incidentally identified during workup for cardiac surgery.

Infant With SARS-CoV-2 Infection Causing Severe Lung Disease Treated With Remdesivir.

We describe an ex-premature infant presenting with severe acute respiratory syndrome coronavirus 2 infection in the fifth week of life. In current reports, researchers indicate that acute symptomatic severe acute respiratory syndrome coronavirus 2 infection is relatively rare and much less severe than in adults. This case highlights that infection can be associated with life-threatening pulmonary disease in young infants and that infection can follow a similar disease course to that described in adults. We provide first data on the use of the novel antiviral remdesivir in a young child and an innovative approach to expedited approval from a multidisciplinary clinical team and bioethics committee for compassionate access to the drug.

Practical insights for paediatric otolaryngology surgical cases and performing microlaryngobronchoscopy during the COVID-19 pandemic.

Paediatric otolaryngology practice involves examining and operating in anatomical locations with high levels of aerosol generation and transmission of COVID-19 to treating clinicians, especially from the asymptomatic patient populations including children. During the COVID-19 pandemic all emergent otolaryngological conditions affecting the airway, oral, and nasal cavities should be managed medically where possible and any operating deferred. We present guidelines for operating on paediatric otolaryngological patients when necessary during the COVID-19 pandemic, and incorporate experience gathered during microlaryngobronchoscopy on a COVID-19 positive infant at our institution.

National Surgical Quality Improvement Program risk calculator validity in South Australian laryngectomy patients.

BACKGROUND: Assessing an individual patient's post-operative risk profile prior to laryngectomy for cancer is difficult. The American College of Surgeons' National Surgical Quality Improvement Program (ACS-NSQIP) risk calculator was developed to better inform preoperative decision-making. The calculator uses patient-specific characteristics to estimate the risk of experiencing post-operative complications within 30 days of surgery. We investigated the ACS-NSQIP risk calculator's performance for Australian laryngectomy patients. METHODS: The ACS-NSQIP risk calculator was used to retrospectively calculate the 30-day post-operative predicted outcomes in patients who underwent laryngectomy for laryngeal, hypopharyngeal and thyroid cancers (with laryngeal involvement) in two institutions in South Australia. These data were compared against the actual mortality, morbidity, complications and length of stay (LOS) collected from a retrospective chart review. RESULTS: A total of 144 patients underwent surgical intervention for malignancies with laryngeal involvement. The median LOS was 25 days (range 13-197) compared to the predicted LOS of 6.5 days (range 3.5-12.5). Overall mortality was 2.78% with post-operative complications occurring in 63% of patients. The most common complication was wound infection, occurring in 33% of patients. Hosmer-Lemeshow plots demonstrated good agreement between predicted and observed rates for complications. CONCLUSION: The ACS-NSQIP risk calculator effectively predicted post-operative complication rates in South Australian laryngeal cancer patients undergoing laryngectomy. However, differences in predicted and actual LOS may limit the usefulness of the calculator's LOS predictions for Australian patients.

Examining the Evidence for an Adult Healthy Middle Ear Microbiome.

Otitis media (OM) is a cluster of diseases of the middle ear that commonly result from bacterial infection. OM subtypes in which the tympanic membrane is intact (acute otitis media and otitis media with effusion) are presumed to result from pathogen translocation through the eustachian tube. Recent molecular-based studies have suggested that a diverse middle ear microbiome exists in the absence of disease. These have been largely unsupported by culture and feature species that commonly contaminate low-biomass sequencing data. Combining culture-based and molecular techniques, we undertook a detailed investigation of the evidence for bacterial colonization of the healthy middle ear. Middle ear (ME), nasopharynx (NP), and external ear canal (EC) swabs were collected from a total of 25 adult patients undergoing cochlear implant, stapedotomy, or translabyrinthine vestibular schwannoma resection. Diagnostic culture, microscopy, quantitative PCR, and 16S rRNA gene amplicon sequencing were used to assess sample bacterial content. EC and NP microbiota were consistent with previous reports. In contrast, bacterial levels in ME samples were not significantly above those in unused control swabs. Commonly detected taxa were among recognized sequencing contaminants (Methylobacterium, Pseudomonas, and Acinetobacter). Linear regression of dominant ME taxa confirmed a negative relationship between relative abundance and bacterial load, consistent with contamination. No bacteria were detected by microscopy or diagnostic culture in any middle ear sample. Our findings cast substantial doubt on previous reports identifying a healthy middle ear microbiome using 16S amplicon sequencing.IMPORTANCE Recent molecular-based studies have suggested that a diverse middle ear microbiome in adults and children can exist in the absence of disease. These studies have been largely unsupported by culture and feature species that commonly contaminate low-biomass sequencing data. While 16S rRNA gene amplicon sequencing has proven to be a highly informative technique in many clinical contexts, it is susceptible to spurious signal arising from sequencing reagent contaminants where sample biomass is low. Combining culture-based and molecular techniques, we undertook a detailed investigation of the evidence for bacterial colonization of the healthy middle ear. In finding no evidence of viable bacterial cells in middle ear samples, our study further underlines the importance of careful consideration of amplicon sequence data derived from very-low-biomass contexts and the value of analytical approaches that combine culture and molecular techniques.

Benchmarking the value of ultrasound for acute appendicitis in children.

BACKGROUND: This study appraises the diagnostic quality of ultrasound for acute appendicitis in children and consequently challenges the perception of inferior accuracy and suitability compared to computed tomography (CT). METHODS: Radiologist reports for consecutive "query appendicitis" ultrasound studies were retrieved from a hospital database for the study period 2009-2014. Children who subsequently underwent appendicectomy were identified. Corresponding operative and histopathology findings were evaluated. Diagnostic accuracy of ultrasound was determined by analyzing overall accuracy, sensitivity, specificity, predictivity, and likelihood ratios. RESULTS: A total of 3799 ultrasound examinations were evaluated. Mean age was 11.5±3.8years. The proportion of patients investigated with preoperative ultrasound was 59.9% (1103/1840). Appendix visualization rate was 91.7%. Overall diagnostic accuracy was 95.5%. Sensitivity and specificity values were 97.1% (95.9-98.1; 95% CI) and 94.8% (93.9-95.6; 95% CI), respectively. Separate analysis of only ultrasound positive and negative examinations (i.e., excluding nondiagnostic examinations) confirmed sensitivity and specificity values of 98.8% and 98.3%. CONCLUSION: In this largest reported single institution series of ultrasound examinations for appendicitis, we report benchmark standard quality of diagnostic accuracy and visualization rates. Given the radiation and cost implications of CT, there is a strong argument to recommend ultrasound as the primary imaging modality. Diagnostic Study-Level II.

The effect of nasal irrigation formulation on the antimicrobial activity of nasal secretions.

BACKGROUND: Saline-based irrigation solutions are evidence-based rhinological treatments; however, the formulation of these solutions could theoretically alter the function of innate antimicrobial peptides. The aim of this study was to determine if the antimicrobial activity of normal human nasal secretions in vivo is altered by commercially available large volume irrigation solutions. METHODS: Minimally manipulated sinonasal secretions were collected from patients with chronic rhinosinusitis (CRS; n = 10) and normal healthy volunteers (n = 20). In a subset of control patients (n = 10) secretions were collected prior to, and at 1 hour, 6 hours, and 24 hours after nasal irrigation with 4 commercial irrigation solutions. Lysozyme and lactoferrin levels were analyzed and the antimicrobial activity of secretions determined using a radial diffusion assay. RESULTS: The antimicrobial activity of nasal secretions was reduced in CRS patients compared to healthy volunteers (p < 0.01), but there was no significant difference in antimicrobial peptide concentrations. Isotonic nasal irrigation reduced lysozyme and lactoferrin levels, which returned to baseline levels by 6 hours; in addition to a sustained decrease in antimicrobial activity before returning to baseline at 24 hours. Low-salt solution stimulated peptide secretion by approximately 40% at 6 hours and 24 hours, but produced a transient decrease in antimicrobial activity, returning to baseline levels by 6 hours. Hypertonic solution initially decreased lysozyme and lactoferrin levels but maintained baseline levels of antimicrobial activity and increased peptide secretion by approximately 30% at 24 hours. CONCLUSION: The formulation of nasal irrigation solutions significantly affects the measured levels and functionality of sinonasal antimicrobial peptides.

Aquaporin expression profiles in normal sinonasal mucosa and chronic rhinosinusitis.

BACKGROUND: Thickened secretions, mucosal edema, and polyp formation are pathological features in chronic rhinosinusitis (CRS) that could theoretically be caused by aberrant water flow through sinonasal mucosa. Aquaporins (AQPs) are a family of proteins with roles in water transport, with tissue-specific expression profiles. This study aims to determine if AQP expression in sinonasal mucosa is different between normal controls and patients with CRS, either with (CRSwNP) or without (CRSsNP) nasal polyps. METHODS: During endoscopic sinus surgery or transsphenoidal surgery, sinonasal tissue was collected and classified as CRSwNP (n = 13), CRSsNP (n = 10), or normal (n = 10). Messenger RNA (mRNA) expression of human AQP0 to AQP12b was determined using quantitative real-time polymerase chain reaction (qRT-PCR). Cellular localization of AQP1, AQP3, AQP4, AQP5, AQP7, and AQP11 was determined by immunohistochemistry. RESULTS: mRNA of AQP0 to AQP11 was identified in all samples. AQP12b mRNA was not detected. Significant differences in the mRNA expression levels of AQP4 and AQP11 were identified between normal and CRSwNP patients (p < 0.05). Differences in the cellular localization of AQPs were observed in both CRSsNP and CRSwNP patients vs normal controls. More intense localization to the cell cytoplasm was observed for AQP5 in glandular epithelium (CRSwNP; p < 0.05) and surface epithelium (CRSsNP; p < 0.05), and AQP4 in glandular epithelium (CRSsNP; p < 0.05). CONCLUSION: This study characterized AQP mRNA expression and protein localization in normal human sinonasal tissue. Significant differences in mRNA expression were found for AQP4 and AQP11 in CRSwNP and differences in protein localization patterns of AQP4 and AQP5 were identified in both types of CRS.